Sections

Osteoporosis

Treatment

Approach Considerations

A clinical practice guideline from the American College of Physicians on treatment to prevent fractures in men and women with low bone density or osteoporosis includes six recommendations: two strong recommendations, based on high- or moderate-quality evidence, and four weak ones, based on low-quality evidence.^[144]The two strong recommendations are as follows:

Clinicians should offer pharmacologic treatment to women with known osteoporosis to reduce the risk for hip and vertebral fractures; alendronate, risedronate, zoledronic acid, or denosumab may be used.
In postmenopausal women, estrogen or estrogen plus progestogen or raloxifene should not be used for the treatment of osteoporosis.

The four weak recommendations are as follows:

In women with osteoporosis, pharmacologic treatment should last for 5 years; generic drugs should be used when possible.
Monitoring of bone mineral density (BMD) during the 5 years of treatment in women with osteoporosis is not advised, as evidence suggests that fracture risk may be reduced regardless of BMD changes.
For women aged 65 and older who have osteopenia and are at high fracture risk, decisions to treat should take into account patient preference, fracture-risk profile, benefits, harms, and price of medications.
In men with clinically recognized osteoporosis, clinicians should offer bisphosphonate therapy to reduce the risk of vertebral fracture; evidence is lacking on BMD monitoring in men.

Nonpharmacologic preventive measures include modification of general lifestyle factors, such as increasing weight-bearing and muscle-strengthening exercise, which epidemiologic studies have linked to lower fracture rates, and ensuring optimum calcium and vitamin D intake as adjunct to active antifracture therapy.^[11] In addition, potentially treatable underlying causes of osteoporosis such as hyperparathyroidism and hyperthyroidism should be ruled out or treated if detected.

There may be an increased risk of fractures involving adjacent vertebrae if therapies including vertebroplasty or kyphoplasty were used in the management of painful osteoporotic fractures^{[145, 146]}

A 2008 literature review suggested that the use of "reminders plus education targeted to physicians and patients" can lead to increased BMD testing and greater use of osteoporosis medications.^[147]In addition, a physician reminder in conjunction with a patient risk assessment strategy can result in a reduction in patient fractures and an increase in osteoporosis therapy. The authors concluded that multicomponent tools aimed at doctors and patients may support clinical decision making in the management of osteoporosis.

A 2009 study indicated that the use of a case manager for the treatment of patients with hip fractures can lead to more frequent use of appropriate osteoporosis treatment and may result in fewer fractures, increased life expectancy, and significant health-care cost savings.^[14]

In patients who have experienced an osteoporotic fracture, the first goal of rehabilitation is to control pain. Spinal compression fractures can be extremely painful and can cause short- and long-term morbidity. Oral analgesics can be implemented. Calcitonin may rarely help acute pain associated with acute osteoporotic vertebral compression fractures.^[148]Nonpharmacologic pain-relieving modalities such as moist hot packs and transcutaneous electrical nerve stimulation should also be considered. Patients receiving narcotic analgesics for acute pain control require careful monitoring for adverse effects of these agents: constipation, urinary retention, and respiratory depression. Orthotics may be used to decrease the flexion forces to prevent the worsening of kyphosis and to reduce the pressure on the fracture site in the acute phase of disease.^{[149, 150]}

Pharmacologic Therapy

Currently, no treatment can completely reverse established osteoporosis. Early intervention can prevent osteoporosis in most people. For patients with established osteoporosis, medical intervention can halt its progression. If secondary osteoporosis is present, treatment for the primary disorder should be provided. Therapy should be individualized based on each patient’s clinical scenario, with the risks and benefits of treatment discussed between the clinician and patient.^{[109, 151]}

Patients identified as at risk for osteoporosis (including children and adolescents) should undergo preventive measures, including adequate calcium intake, vitamin D intake, and exercise. Patients should be counseled to avoid tobacco and excessive alcohol use.

Protective measures should be taken in patients who must take glucocorticoids for other medical conditions. These include using the minimum effective dose of glucocorticoid and discontinuing the drug as soon as possible. The American College of Rheumatology provides recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis, which were updated in 2017. Recommendations include optimizing calcium and vitamin D supplementation, lifestyle modifications, and fracture risk stratification for all adults on long-term glucocorticoid treatment (≥2.5 mg/day prednisone for ≥3 months).^[12] Further recommendations regarding pharmacological therapy as dictated by fracture risk stratification for prevention of glucocorticoid-induced osteoporosis (GIOP) are discussed below in Prevention of Osteoporosis.

Bisphosphonates

Bisphosphonates are the most commonly used agents for osteoporosis. Oral and intravenous options are available.

Alendronate

Alendronate (Fosamax) is approved for the treatment of osteoporosis in men, in postmenopausal women, and in patients with glucocorticoid-induced osteoporosis. It has been shown to increase spine and hip bone mineral density in postmenopausal women. Well-conducted controlled clinical trials indicate that alendronate reduces the rate of fracture at the spine, hip, and wrist by 50% in patients with osteoporosis.

The treatment dose of alendronate is 70 mg/week, to be taken sitting upright with a large glass of water at least 30 minutes before eating in the morning. Alendronate is also available in combination with cholecalciferol (vitamin D3). The combination of alendronate with vitamin D3 (Fosamax Plus D) is indicated for the treatment of osteoporosis in men to increase bone mass.

The oral bioavailability of alendronate is drastically reduced when taken with food, even black coffee or orange juice alone.^[152] In addition, the results of a population-based, national register–based, open cohort study of 38,088 patients suggest that elderly patients who use proton pump inhibitors in conjunction with alendronate have a dose-dependent loss of protection against hip fracture.^[153]

Risedronate

Other oral bisphosphonates include risedronate (Actonel) or risedronate delayed-release (Atelvia), given daily, weekly, or monthly. It is also available as a combination product with calcium as risedronate/calcium carbonate (Actonel with Calcium). Risedronate reduced vertebral fractures by 41% and nonvertebral fractures by 39% over 3 years.^[154]

Ibandronate

Ibandronate (Boniva) is another bisphosphonate that can be given orally once a month and is also available as an intravenous formulation that is given every 3 months. Intravenous bisphosphonates are excellent choices for patients intolerant of oral bisphosphonates or for those in whom adherence is an issue. However, ibandronate has not shown efficacy in nonvertebral fractures in clinical trials.

Zoledronic Acid

Zoledronic acid (Reclast) is a once-yearly intravenous infusion approved for the treatment of osteoporosis in men, in postmenopausal women, and in patients with glucocorticoid-induced osteoporosis.^[155] Zoledronic acid is the most potent bisphosphonate available. It increases BMD at the spine by 4.3-5.1% and the hip by 3.1-3.5%, as compared with placebo. Over 3 years, it reduces the incidence of spine fractures by 70%, hip fractures by 41%, and nonvertebral fractures by 25% in postmenopausal women. A similar effect on vertebral fractures has been shown in men. A randomized, 2-year trial of men with osteoporosis found that once-yearly zoledronic acid infusions significantly decreased the risk of new morphometric vertebral fractures by 67%.^[156]

A randomized, placebo-controlled, double-blind trial suggested that a once-yearly 5-mg dose of IV zoledronic acid increases bone mass in men within 90 days of hip fracture repair; similar increases were noted in women.^[157]

Bisphosphonates and bone turnover

Over time, bisphosphonate therapy decreases bone turnover and, at very high levels in animals, decreases bone strength and resilience. Some limited reports, including that by Odvina et al, describe patients on long-term bisphosphonate therapy developing transverse stress fractures; biopsy specimens of these individuals have suggested extremely low turnover states in some of them.^[158]

Alendronate and risedronate inhibit bone resorption at doses 10-fold lower than those reducing osteoclast number. Thus, suppression of bone resorption with these agents is independent of their effects on apoptosis.^[159]

Complications of bisphosphonate therapy, treatment length, and drug holidays

In 2011, the US Food and Drug Administration (FDA) updated the prescribing information for zoledronic acid to provide improved information regarding the risk of kidney failure. Acute kidney injury requiring dialysis and fatal outcomes have been reported to the FDA following the use of zoledronic acid. The drug is contraindicated in patients with moderate to severe renal impairment (ie, creatinine clearance < 35 mL/min) or evidence of acute renal impairment. Risk for acute kidney injury is also increased by the following^[160]:

Coadministration of zoledronic acid with nephrotoxic or diuretic medications
Severe dehydration before or after administration
Advanced patient age

In 2012, the FDA made safety labeling changes for bisphosphonates, including zoledronic acid, to advise of the risk for atypical subtrochanteric and diaphyseal femoral fractures in patients who have received bisphosphonate therapy, including zoledronic acid. These fractures occur with minimal or no trauma and may present as groin pain weeks to months after fracture. The FDA also includes a safety warning for bisphosphonates, including zoledronic acid, regarding the risk for osteonecrosis of the jaw (ONJ).^[161] Atypical femur fractures and ONJ are rare events in patients on long- term antiresportive agents, including bisphosphonates or denosumab, when used in the treatment of osteoporosis.

The incidence of ONJ in patients on antiresportive therapy for osteoporosis is estimated to be between 1 in 10,000 and 1 in 100,000 per year of use; this risk is only very minimally, if at all, increased compared with the general population. In contrast, the use of IV bisphosphonates and denosumab in cancer patients to reduce complications of metastatic cancer results in the administration of substantially higher cumulative doses (due to the increased dosage used for these indications); therefore, atypical femoral fractures and ONJ are more commonly seen when IV bisphosphonates or denosumab are used as part of cancer treatment.^[162]

In 2012, the FDA made safety labeling changes for zoledronic acid to warn against the following adverse reactions^[161]:

Acute phase reaction within 3 days of zoledronic acid administration: symptoms include pyrexia, fatigue, bone pain and/or arthralgias, myalgias, chills, and influenza-like illness; symptoms usually resolve within 3 days of onset but can take 7-14 days to resolve, and some symptoms may persist for longer
Hypersensitivity reactions presenting as bronchospasms; interstitial lung disease (ILD) with positive re-challenge

The limited trial data available regarding long-term treatment with bisphosphonates has raised questions about the optimal length of treatment with these medications.^[163]This issue has become more important, given newly recognized complications of bisphosphonate use, including ONJ^[164]and atypical (subtrochanteric or femoral shaft) femur fractures.

Some studies have sought to clarify the true risks of complications in patients receiving bisphosphonates. A Canadian study by Park-Willie et al found the estimated absolute risk of a subtrochanteric or femoral shaft fracture to be low in 52,595 women with at least 5 years of bisphosphonate therapy (0.13% during the subsequent year and 0.22% within 2 years).^[165] Longer use of bisphosphonates has been shown to increase risk of atypical femoral fractures.^[166] Overall, a patient’s risk of fracture can be used to help guide length of treatment. Patients at high risk may be continued on bisphosphonates after 5 years; however, in some patients, especially those with a lower risk of fracture, bisphosphonate treatment may be stopped for a period with subsequent reassessment of fracture risk, often termed a "drug holiday."^[167]

The AACE recommends that if fracture risk is no longer high or the patient has remained fracture free, clinicians should consider a drug holiday after 5 years of bisphosphonate treatment; treatment should continue up to an additional 5 years if fracture risk remains high. For high fracture risk patients, a drug holiday may be considered after 6-10 years of treatment. For zoledronate, consider a bisphosphonate holiday after 3 years in high-risk patients or until fracture risk is no longer high, and continue for up to 6 years in very-high risk patients.^[11]

The ending of a bisphosphonate holiday should be based on individual patient circumstances. BMD and bone turnover markers should be monitored, and treatment should be restarted when the density declines substantially, bone turnover markers increase, or an increase in fracture risk or fracture occurs.^[11]

In 2016, the American Society for Bone and Mineral Research published guidelines on long-term bisphosphonate treatment that included the following recommendations^[168]:

After 5 years of oral bisphosphonates or 3 years of intravenous bisphosphonates, reassessment of risk should be considered.
In women at high risk (eg, older women, those with a low hip T-score or high fracture risk score, those with previous major osteoporotic fracture, or those who fracture on therapy), continuation of treatment for up to 10 years (oral) or 6 years (intravenous), with periodic evaluation, should be considered.
The risk of atypical femoral fracture, but not ONJ, clearly increases with the duration of bisphosphonate therapy, but such rare events are outweighed by vertebral fracture risk reduction in high-risk patients.
For women not at high fracture risk, a drug holiday of 2 to 3 years can be considered after 3 to 5 years of bisphosphonate treatment.

Selective estrogen receptor modulators

Selective estrogen receptor modulators (SERMs) are considered to provide the beneficial effects of estrogen while mitigating the potentially adverse outcomes.

Raloxifene

Raloxifene (Evista) is a SERM indicated for the treatment and prevention of osteoporosis in postmenopausal women. The usual dose is 60 mg given orally daily. It can also be given in combination with calcium and vitamin D. It is the first SERM studied for breast cancer prevention, and it decreases bone resorption through actions on estrogen receptors.

Raloxifene has been shown to prevent bone loss, and data in women with osteoporosis have demonstrated that this agent causes a 35% reduction in the risk of vertebral fractures. It has also been shown to reduce the prevalence of invasive breast cancer. However, raloxifene is not without risk; it has been shown to increase the incidence of deep vein thrombosis, stroke, and hot flashes.

Raloxifene may be most useful in younger postmenopausal women without severe osteoporosis. In 601 postmenopausal women who had daily therapy with raloxifene, BMD was increased, serum concentrations of total low-density lipoprotein cholesterol were lowered, and the endometrium was not stimulated.

Pooled mortality data from large clinical trials of raloxifene (60 mg/day) were analyzed by Grady et al in 2010. When compared with placebo, all-cause mortality was 10% lower in older postmenopausal women receiving raloxifene. The primary reduction was in noncardiovascular, noncancer deaths.^[169] However, in contrast, the FDA has advised a black box warning on raloxifene for increased risk of venous thromboembolism and death from stroke. Increased risk of deep vein thrombosis, pulmonary embolism, and death due to stroke have been seen in trials with raloxifene and this must be weighed against potential benefit to patient for osteoporosis when considering prescribing raloxifene or other SERMs.

Bazedoxifene/conjugated estrogens

The combination product of bazedoxifene, a SERM, and conjugated estrogens (CEs) is approved by the FDA for prevention of osteoporosis and treatment of vasomotor symptoms in postmenopausal women. Combining a SERM with CEs lowers the risk of uterine hyperplasia caused by estrogens. This eliminates the need for a progestin and its associated risks (eg, breast cancer, myocardial infarction, venous thromboembolism).

In clinical trials, this combination decreased bone turnover and bone loss in postmenopausal women at risk for osteoporosis. Bone mineral density increased significantly more with all bazedoxifene/CE doses compared with placebo at the lumbar spine and total hip and with most bazedoxifene/CE doses compared with raloxifene at the lumbar spine.^[170]

Parathyroid hormone analogues

Teriparatide

Teriparatide (Forteo) is a recombinant human parathyroid hormone (1-34) (PTH [1-34]) that acts as an anabolic agent for the treatment of osteoporosis. It is indicated for the treatment of women with postmenopausal osteoporosis who are at high risk of fracture, who have been intolerant of previous osteoporosis therapy, or in whom osteoporosis treatment has failed to increase bone mass. It is indicated in men with idiopathic or hypogonadal osteoporosis who are at high risk of fracture, who have been intolerant of previous osteoporosis therapy, or in whom osteoporosis therapy has failed. Teriparatide is also approved for the treatment of patients with glucocorticoid-induced osteoporosis.

Before treatment with teriparatide, levels of serum calcium, PTH, and 25(OH)D need to be monitored. Teriparatide cannot be given for more than 2 years total in a lifetime due to concerns for increased risk of osteosarcoma; higher incidence of osteosarcoma was seen with high doses in animal studies. However, evidence to show an increased risk of osteosarcoma in humans receiving therapeutic doses of teriparatide has not been obtained.^[171] Contraindications include the following:

Pre-existing hypercalcemia
Severe renal impairment
Pregnancy
Breast-feeding mothers
History of bone metastases or skeletal malignancies
Increased baseline risk for osteosarcoma, including but not limited to Paget disease, unexplained elevated alkaline phosphatase level, or prior external beam or implant radiation therapy
Children and young adults with open epiphyses or prior radiotherapy of the skeleton ^[172]
Monoclonal gammopathies of undetermined significance (MGUS) ^[173]

When PTH is given continuously, both osteoclastic and osteoblastic turnover increase, leading to a net loss of bone. However, intermittent subcutaneous administration of PTH in a dosage of 20 mcg/day has been demonstrated to induce a very active anabolic phase, with bone mass increasing up to 13% over 2 years in the spine and to a lesser degree in the hip.^{[174, 175, 176]}

Indications for PTH in men and women are a bone density decline while on bisphosphonate therapy, bone density stabilization while on extremely low-level bisphosphonate therapy, a fracture occurring while on bisphosphonate therapy, or a very low initial bone turnover rate for which an anabolic effect is clearly warranted. Teriparatide should be considered in younger and older postmenopausal women with severe osteoporosis.

Most studies with PTH have been performed on women. The medication decreases the risk of vertebral and nonvertebral fractures to the same extent as bisphosphonates. Teriparatide is given for a maximum of 2 years, after which time the gains in BMD achieved with PTH are secure and can even be augmented with bisphosphonate therapy; otherwise, the BMD slowly deteriorates to pretreatment levels.^[177]

According to Finkelstein et al, initial studies using a combination of concurrent PTH and bisphosphonate therapy showed decreased benefit compared with therapy with either agent alone; therefore, the general recommendation is that these drugs be given separately and in sequence.^[178]

A study by Cosman and colleagues challenged this conclusion by giving 3-month-on, 3-month-off pulses of teriparatide while the patients were on weekly alendronate; BMD in the spine increased above that of the alendronate-only arm.^[179]This pulsed regimen appears to take advantage of the 3- to 4-month so-called anabolic window, in which the markers of bone formation rise more quickly than the markers of bone resorption.

Studies in women by Deal et al and Ste-Marie et al have shown that the concurrent use of estrogen or raloxifene can enhance the bone-forming effects of teriparatide.^{[180, 181]}Data on the use of PTH in men are much more limited, but its efficacy appears to be relatively comparable.

In a randomized, controlled trial (DATA), 94 osteoporotic postmenopausal women were randomized to take 24 months of teriparatide or denosumab alone, or teriparatide and denosumab in combination. Those women taking teriparatide and denosumab in combination had increased BMD after 12 months. The 12-month changes in posterior-anterior lumbar spine, femoral neck, and total hip BMD in the combination-therapy group (9.1%, 4.2% and 4.9%, respectively) were greater than those in the groups receiving only teriparatide (6.2%, 0.8% and 0.7%, respectively) or only denosumab (5.5%, 2.1% and 2.5%, respectively).^[182]

As an extension to this study (DATA-Switch), women originally assigned to teriparatide received denosumab after 24 months and those originally assigned to denosumab received teriparatide. Switching from teriparatide to denosumab yielded progressive BMD increases, whereas switching from denosumab to teriparatide resulted in progressive or transient bone loss.^[183] Given those findings, using teriparatide early in the treatment course before instituting other therapies when severe osteoporosis is diagnosed is preferred.

In a retrospective analysis of the data from the Fracture Prevention Trial and the Multiple Outcomes of Raloxifene Evaluation trial, Bouxsein et al found that teriparatide reduced fracture risk to a greater extent than raloxifene in postmenopausal osteoporotic women. Compared with placebo, teriparatide reduced the risk of any new fractures by 72%, new adjacent fractures by 75%, and new nonadjacent vertebral fractures by 70%. Raloxifene reduced the risks by 54%, 54%, and 53%, respectively.^[184]

A double-blind, double-dummy trial by Kendler et al found that in postmenopausal women with severe osteoporosis, the risk of new vertebral and clinical fractures was significantly lower in patients receiving teriparatide than in those receiving risedronate. Study subjects had experienced at least two moderate or one severe vertebral fracture and had a BMD T-score of -1.50 or less. They were randomly assigned to receive teriparatide (daily injections of 20 μg) plus oral weekly placebo or risedronate (35 mg orally once weekly) plus daily injections of placebo for 24 months.^[185]

At 24 months, new vertebral fractures had occurred in 28 (5.4%) of 680 patients in the teriparatide group and 64 (12.0%) of 680 patients in the risedronate group (hazard ratio [HR] 0.44, 95% confidence index [CI] 0.29-0.68; P < 0·0001). Clinical fractures occurred in 30 (4.8%) of 680 patients in the teriparatide group compared with 61 (9.8%) of 680 in the risedronate group (hazard ratio 0.48, 95% CI 0.32-0.74; P=0.0009).^[185]

Use of teriparatide for atypical fractures has not been studied in large randomized controlled trials due to the small numbers of atypical fractures. Gomberg et al reported a case of successful healing of bilateral subtrochanteric stress fractures in a postmenopausal woman who had used a bisphosphonate for 13 years.^[186]A small case series showed that teriparatide may have potential in promoting healing of atypical fractures with radiolucent line in an incomplete fracture.^[187]

For ONJ, teriparatide may be a useful adjunctive therapy. Three cases have been reported in which teriparatide has been used successfully in patients with bisphosphonate-associated ONJ.^{[188, 189, 190]}

Abaloparatide

Another PTH analogue, abaloparatide (Tymlos), was approved by the FDA in 2017 for women and in 2022 for men. It is indicated for treatment of postmenopausal women with osteoporosis or to increase bone density in men at high risk for fracture, defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients with failure of or intolerance to other available osteoporosis therapy. Approval in women was based on results at 18 months from the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial^[191]and first 6 months of the ACTIVExtend trial.^[192] Approval in men was supported by the Abaloparatide Treatment of Men (ATOM phase 3 study).^[193]

In the ACTIVE trial of more than 2000 women, subcutaneous abaloparatide was associated with significant reductions in the relative risk for new vertebral fractures (86% reduction) and nonvertebral fractures (43% reduction) compared with placebo. The absolute risk reductions were 3.6% and 2.0%, respectively. The benefits were evident regardless of age, years since menopause, presence or absence of prior fracture (vertebral or nonvertebral), and BMD at baseline.^[191]

In the ACTIVExtend trial, roughly 1100 patients who had completed 18 months of abaloparatide or placebo in ACTIVE received open-label alendronate for up to 24 additional months. Data from the first 6 months of ACTIVExtend showed improved BMD and reduced fracture risk throughout the skeleton.^[192]

A study performed by an Austrian group using PTH 1-84 to treat pelvic fractures in postmenopausal women with osteoporosis demonstrated that this anabolic agent has the ability to both increase the rate of union and enhance the speed of the process. In addition to improved fracture healing, treatment with PTH 1-84 was also associated with a significant decrease of pain and improved function over the placebo arm. This clinical study supports the extensive animal data that predicted a clear role for PTH in fracture repair.^[194]

The ATOM study in men showed an increase from baseline in mineral density at 12 months of 8.5% and 1.2% in the abaloparatide and placebo groups, respectively (p < 0.0001).^[193]

Contraindications to abaloparatide are similar to those for teriparatide. A Black Box warning regarding increased risk of osteosarcoma, based on studies in rats, was removed in December 2021; however, use of abaloparatide should be avoided in patients with increased risk of osteosarcoma, and use of the drug for more than 2 years during a patient’s lifetime is not recommended.

Romosozumab

Romosozumab (Evenity) is a monoclonal antibody that binds with and inhibits sclerostin, and thus both increases bone formation and decreases bone resorption. It was approved by the FDA in 2019 for treatment of osteoporosis in postmenopausal women who are at high risk for fracture. It has been shown to reduce vertebral fracture rates in postmenopausal women with osteoporosis.^{[195, 196, 197]}

In the Fracture Study in Postmenopausal Women With Osteoporosis (FRAME), a phase 3 randomized trial in 7180 postmenopausal women who had a T score of -2.5 to -3.5 at the total hip or femoral neck, 1 year of treatment with romosozumab reduced vertebral fracture rates by 73% compared with placebo. A further reduction in vertebral fracture risk occurred in the second year following transition to denosumab.^{[195, 197]}

Romosozumab is also being investigated in men with osteoporosis. In the BRIDGE clinical trial, spine and hip BMD significantly improved following romosozumab for 12 months compared with placebo.^[198]

In a randomized, controlled trial of 4093 postmenopausal women with osteoporosis and a fragility fracture, a higher rate of adjudicated serious cardiovascular events (a composite endpoint including cardiac ischemic events, cerebrovascular events, heart failure, death, noncoronary revascularization, and peripheral vascular ischemic event not requiring revascularization) was seen in the romosozumab group (2.5%) compared with the alendronate group (1.9%), although the increased risk only reached statistical significance for cardiac ischemic events (0.8% versus 0.3%; odds ratio 2.65 with 95% CI 1.03 to 6.77).^[199]

Romosozumab carries a black box warning regarding increased risk of myocardial infarction, stroke, and cardiovascualr death. Romosozumab should not be initaited in patients who have had a myocardial infarction or stroke within the preceding year, and cardiovascular risk profile must be considered before initiating romosozumab. In patients who experience a myocardial infarction or stroke during therapy, romosozumab should be discontinued.

Denosumab

Denosumab (Prolia) is a humanized monoclonal antibody directed against the receptor activator of the nuclear factor–kappa B ligand (RANKL), which is a key mediator of the resorptive phase of bone remodeling.^[181]Denosumab decreases bone resorption by inhibiting osteoclast activity. Denosumab was approved by the FDA in 2010. It has shown benefit in cancer patients, patients with postmenopausal osteoporosis, and men with low BMD.^{[200, 201, 202]} The approved dosage is 60 mg given subcutaneously every 6 months.

Denosumab may be considered in certain patients with renal insufficiency, as impaired kidney function does not significantly affect the metabolism or excretion of the drug.^[203]

In 2018, denosumab was approved for treatment of glucocorticoid-induced osteoporosis (GIOP) in men and women at high risk of fracture who are either initiating or continuing systemic glucocorticoids in a daily dosage equivalent to 7.5 mg or greater of prednisone and who are expected to remain on glucocorticoids for at least 6 months. Patients are considered at high risk of fracture if they have a history of osteoporotic fracture, multiple risk factors for fracture, or failed or cannot tolerate other available osteoporosis therapy.

Approval for use in GIOP was based on an international phase 3 study in which denosumab proved more effective than the bisphosphonate risedronate for increasing BMD at the lumbar spine. In patients who had been on steroids for at least 3 months (n=505), the change from baseline in BMD at 12 months was 4.4% with denosumab versus 2.3% with risedronate (P < 0.0001); in those who had started steroids less than 3 months previously (n=290), the change was 3.8% vs 0.8% (P < 0.0001).^[204]

In postmenopausal women with osteoporosis, denosumab reduces the incidence of vertebral, nonvertebral, and hip fractures.^[205] Denosumab also increases bone mass in men at high risk for fracture who are receiving androgen deprivation therapy for nonmetastatic prostate cancer,^[206] and in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.

A meta-analysis of 10 randomized, controlled trials concluded that denosumab improved BMD significantly more than bisphosphonate treatment at the lumbar spine, total hip, and femoral neck at 12 and 24 months. However, only 1 of the 10 studies demonstrated greater osteoporotic fracture reduction with denosumab treatment.^[207]

In patients with multiple myeloma or bone metastases from breast cancer, a single subcutaneous dose of denosumab decreases bone turnover markers within 1 day, and this effect is sustained through 84 days at higher doses.^[200]Denosumab has been shown to increase BMD and decrease bone resorption in postmenopausal women with osteoporosis over a 12-month period. Because the overactivity of RANKL is a major factor in bone loss in patients with autoimmune and inflammatory disorders, such as ulcerative colitis, denosumab may become first-line therapy for these patients.^[208] Denosumab in combination with teriparatide has been shown to increase BMD more than either drug alone,^[209] although combination therapy with osteoporosis medications is not currently recommended in clinical practice.

Denosumab has uniquely been associated with rebound lumbar vertebral fractures after denosumab discontinuation. These vertebral fractures are often multiple and occur within months of the time that the next dose of denosumab would be due for administration.^[210] For this reason, denosumab should be continued indefinitely or followed by bisphosphonate therapy, if not contraindicated.

Calcitonin

Calcitonin salmon (Fortical, Miacalcin) is a hormone that decreases osteoclast activity, thereby impeding postmenopausal bone loss. It is indicated for the treatment of women who are more than 5 years post menopause and have low bone mass relative to healthy premenopausal women. Calcitonin salmon is not considered a first-line therapy for osteoporosis, and should be reserved for patients who refuse or cannot tolerate bisphosphonates or in whom bisphosphonates are contraindicated. It is recommended in conjunction with adequate calcium and vitamin D intake to prevent the progressive loss of bone mass. It is available as an injection and as an intranasal spray. The intranasal spray is delivered as a single daily spray that provides 200 IU of the drug. The drug can be delivered subcutaneously, but this route is rarely used.

Results from a single controlled clinical trial indicate that calcitonin may decrease osteoporotic vertebral fractures by approximately 30%. In the first 2 years, calcitonin has been found to increase spinal bone mineral density (BMD) by approximately 2%. Calcitonin also has analgesic properties. However, calcitonin lacks data showing a reduction in nonvertebral fracture rates.

In 2013, an FDA post-marketing review was prompted after studies showed increased risk of malignancies in calcitonin-treated patients. In a meta-analysis of 21 randomized, controlled clinical trials with calcitonin salmon (nasal spray or investigational oral formulations), the incidence of malignances in calcitonin-treated patients was 4.1%, versus 2.9% in placebo-treated patients. The data were not sufficient for further analysis by specific malignancies and a definitive causal relationship between calcitonin use and malignancies could not be established. The FDA has recommended that health care professionals assess a patient’s need for osteoporosis therapy as well as benefits and risk of available treatments.^[211]

Calcitonin is no longer widely used for treatment of osteoporosis.^[144] Common side effects of nasally administered calcitonin include nasal discomfort, rhinitis, irritation of nasal mucosa, and occasional epistaxis. Nausea, local inflammatory reactions at the injection site, sweating, and flushing are side effects noted with parenteral use.

Hormone replacement therapy

Hormone replacement therapy (HRT) was once considered a first-line therapy for the prevention and treatment of osteoporosis in women. Although HRT is not currently recommended for the treatment of osteoporosis, it is important to mention because many osteoporosis patients in a typical practice still use it for controlling postmenopausal symptoms.

The American College of Physicians concluded that moderate-quality evidence showed that estrogen treatment did not reduce fracture rates in postmenopausal women with established osteoporosis.^[144]Data from the Women's Health Initiative indicated that HRT can reduce fractures.^[212]However, the results of the Women's Health Initiative were distressing with respect to the adverse outcomes associated with combined estrogen and progesterone therapy (eg, risks for breast cancer, myocardial infarction, stroke, and venous thromboembolic events) and estrogen alone (eg, risks for stroke and venous thromboembolic events).

Other agents

Strontium ranelate is approved for the treatment of osteoporosis in some countries in Europe. It reduces the risk of both spine and nonvertebral fractures.^{[213, 214]}Strontium is not approved for the treatment of osteoporosis in the United States.

Dietary Measures

Adequate calcium and vitamin D intake are important in persons of any age, particularly in childhood as the bones are maturing, and are essential in the prevention and treatment of osteoporosis. Vitamin D is increasingly being recognized as a key element in overall bone health, calcium absorption, balance (eg, reduction in risk of falls),^[215]and muscle performance. Patients who ingest inadequate amounts of vitamin D and calcium in their diet should not receive additional oral supplements.

Good dietary sources of calcium include dairy products, sardines, nuts, sunflower seeds, tofu, vegetables such as turnip greens, and fortified food such as orange juice. Good dietary sources of vitamin D include eggs, liver, butter, fatty fish, and fortified food such as milk and orange juice. See the National Osteoporosis Foundation Website for further calcium and vitamin D recommendations.

The goal of the current recommendations for daily calcium intake is to ensure that individuals maintain an adequate calcium balance. Current recommendations from the American Association of Clinical Endocrinologists (AACE) for daily calcium intake are as follows^[11]:

Age 0-6 months: 200 mg/day
Age 6-12 months: 260 mg/day
Age 1-3 years: 700 mg/day
Age 4-8 years: 1000 mg/day
Age 9-18 years: 1300 mg /day
Age 19-50 years: 1000 mg/day
Females Age 51 years and older: 1200 mg/day
Males Age 51-70: 1000 mg/day
Males Age 71 and older: 1200 mg/day

The Institute of Medicine (IOM) has issued recommendations for calcium and vitamin D daily intake in older adults. For women older than 50 years, the IOM recommended 1200 mg/day of calcium. The IOM recommended 1000 mg/day of calcium for men 51-70 years of age and 1200 mg/day for men over 70. For both sexes, the recommended upper level was 2000 mg/day.^[216]

For both women and men, the recommended daily dietary allowance of vitamin D was 600 IU from age 51-70 and 800 IU for after age 70, with a recommended maximum of 4000 IU. Amid considerable controversy, the IOM also stated that the evidence supported a role for vitamin D and calcium in bone health, but not in other conditions.^[216]

The minimum daily requirement of vitamin D in patients with osteoporosis is 800 IU of cholecalciferol. Many patients require higher levels (continuously or for a short period) to be considered vitamin D replete, which is defined as a serum 25-hydroxyvitamin D level of at least 32 ng/mL.

Alcohol and anorexia nervosa can interfere with nutrition. Excessive alcohol intake can interfere with calcium balance by increasing PTH production and by inhibiting the enzymes that convert inactive vitamin D to its active form; in addition, alcohol can result in hormonal deficiencies and can increase the tendency for falls. Poor nutritional states, such as in anorexia nervosa,^[217]have been strongly associated with bone loss. Nutritional and endocrine factors contribute to bone loss; in particular, low estrogen states, which result from low body weight, result in significant bone loss.

Calcium and vitamin D supplementation

Commonly used calcium supplements include calcium carbonate and calcium citrate. Calcium carbonate is generally less expensive and is recommended as a first choice option. Calcium carbonate has better absorption with food, as opposed to calcium citrate, which is better absorbed in the fasting state. Also, fewer tablets are needed with calcium carbonate than with calcium citrate.

Vitamin D is available as ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3). Vitamin D is metabolized to active metabolites. These metabolites promote the active absorption of calcium and phosphorus by the small intestine, elevating serum calcium and phosphate levels sufficiently to permit bone mineralization. Ergocalciferol, the form mostly used in supplements and fortified foods, is absorbed with similar efficiency to cholecalciferol, the main dietary form, with similar effects on suppression of PTH.

Calcium and vitamin D studies

A meta-analysis suggested that supplementation with a combination of calcium and vitamin D can reduce fracture risk.^[218]Another meta-analysis of 12 double-blind, randomized, controlled trials for nonvertebral fractures and eight trials for hip fractures reported that nonvertebral fracture prevention with vitamin D was dose dependent and that a higher dose (> 400 IU/d) reduced fractures by at least 20% for individuals aged 65 years or older.^[219]However, a longitudinal and prospective cohort study concluded that gradual increases in dietary calcium intake did not further reduce fracture risk or osteoporosis in women.^[220]

Another meta-analysis concluded that vitamin D alone is not effective in preventing fractures, but vitamin D given together with calcium reduced hip fractures and total fractures, and possibly vertebral fractures.^[221]The conclusions were based on seven large studies that were randomized with at least one intervention arm in which vitamin D was given and included analysis of fractures as an outcome and at least 1000 participants.

More information is needed regarding risks associated with long-term calcium supplementation. Dietary calcium intake has not been associated with an increased risk of cardiovascular events.^[222]Additionally, some^[223]but not all^[224]studies suggest an increased risk of nephrolithiasis with calcium and vitamin D supplements, but not with calcium ingested in the diet.^[225]

Physical therapy

Physical therapy focuses on improving a patient's strength, flexibility, posture, and balance to prevent falls and maximize physical function.^{[226, 227]}Postural retraining is key in this population. Spinal bone mineral density (BMD) is directly correlated with the strength of the back extensors; therefore, maintaining and strengthening the back extensors should be emphasized.^[228]In studies by Sinaki and colleagues, strengthening the back extensor muscles reduced kyphosis and decreased the risk of sustaining vertebral compression fractures.^{[229, 230]}

As soon as the course of therapy allows, weight-bearing exercises should be initiated. Regular weight-bearing exercises are essential for the maintenance of bone mass^[65]and should be encouraged in all patients, including children and adolescents (to strengthen the skeleton during the maturation process). Exercise also improves agility and balance, thereby reducing the risk of falls.

Occupational therapy

Training in the performance of activities of daily living (ADLs) and in the proper use of adaptive equipment are essential to the prevention of future falls.^[227]Home modification focuses on reducing the risk of falling by installing handrails and grab bars in hallways, stairs, and bathrooms. The use of a shower chair, tub bench, and adaptive bathing devices also can be beneficial. The application of nonskid tape to steps (indoors and outdoors), as well as the removal of throw rugs, may improve home safety.

Exercise

Aerobic low-impact exercises, such as walking and bicycling, generally are recommended. During these activities, ensure that the patient maintains an upright spinal alignment. Sinaki and Mikkelsen showed that exercises that place flexion forces on the vertebrae tend to cause an increase in the number of vertebral fractures in patients.^[228]

Proper therapy for osteoporosis includes 3-5 sessions per week of weight-bearing exercises, such as walking or jogging, with each session lasting 45-60 minutes. The patient should be instructed in a home-exercise program that incorporates the necessary elements for improving posture and overall physical fitness.

In postmenopausal women, impact exercises can increase BMD in the hip and spine. Chien et al examined the efficacy of a 24-week aerobic exercise program consisting of treadmill walking followed by stepping exercises in osteopenic postmenopausal women aged 48-65 years. Women who exercised had increased bone mineral density in L2-L4 and the femoral neck, as well as improved quadriceps strength, muscular endurance, and peak exercise oxygen consumption (VO₂ max), whereas values in the control group declined.^[231]

Snow et al found increased BMD of the femoral neck, trochanter, and total hip in 18 postmenopausal women (average age, 64 years) who wore weighted vests and participated in jumping exercises 3 times per week for 32 weeks a year for 5 years.^[232]

The results of a Cochrane Database of Systematic Reviews study found that exercise may help prevent bone loss and fractures in postmenopausal women. The most effective type of exercise on BMD for the neck of the femur was found to be non–weight-bearing, high-force exercise, such as lower limb resistance strength training; combination exercise programs were most effective for BMD at the spine.^[233]

Although swimming is not a weight-bearing exercise that will improve BMD, it does provide chest expansion, spinal extension, and low-impact cardiopulmonary fitness. Isometric exercises should also be used to strengthen abdominal muscles, aiding in the prevention of kyphosis.

The physical therapist must address balance training, because fall prevention is important in reducing the risk of the clinically apparent manifestation of osteoporosis, fracture. Improving one's balance can significantly lower the risk of falling. Balance training incorporates the strengthening of various parts of the body (eg, trunk, legs), proprioception, and vestibular input. Several different exercises have been shown to be beneficial in patients with osteoporosis.^{[234, 235, 236, 237]}

Tai chi chuan and specific physical therapy programs may be effective in improving balance and reducing falls. Wolf et al monitored 200 elderly community dwellers who received tai chi and computerized balance training. After a 15-week intervention, the authors documented decreased fear of falling responses. In addition, tai chi was shown to reduce the risk of multiple falls by 47.5%.^[238]

Campbell et al monitored 233 elderly community dwellers randomized to an individually tailored physical therapy program in the home compared with usual care and an equal number of social visits. The authors found that after one year, the mean rate of falls was lower in the exercise group than in the control group (0.87 vs 1.34, respectively). In addition, after 6 months, persons in the exercise group had improved balance.

Other types of exercise training programs may also positively impact balance and strength. Carter et al demonstrated that osteoporotic women aged 65-75 years who underwent a 10-week community-based physical activity intervention program showed a trend toward improved static balance, dynamic balance, and knee extension strength, although the study failed to show a statistically significant reduction in these fall risk factors, likely due to limited power.^[239]

Prevention of Osteoporosis

Primary prevention of osteoporosis starts in childhood. Patients require adequate calcium intake, vitamin D intake, and weight-bearing exercise. Beyond this, prevention of osteoporosis has two components: behavior modification and pharmacologic interventions.

The National Osteoporosis Foundation specifies that the following behaviors should be modified to reduce the risk of developing osteoporosis^[4]:

Cigarette smoking
Physical inactivity
Intake of alcohol, caffeine, sodium, animal protein, and calcium

Patients should be counseled on smoking cessation and moderation of alcohol intake. Regular weight-bearing exercise and back extensor strengthening help delay bone loss. In a study that found osteopenia in over a quarter of men and women in early middle age, there was a negative correlation between exercise and BMD in the men despite relatively high levels of exercise—but the majority of men in the study reported cycling as their preferred exercise, rather than weight-bearing activities such as walking or running.^[76]

Patients who have disorders or take medications that can cause or accelerate bone loss should ensure adequate intakes of calcium and vitamin D and, in some cases, pharmacologic treatment.^[240] Pharmacologic prevention methods include calcium supplementation and administration of raloxifene or bisphosphonates (alendronate or risedronate). Bisphosphonates should be considered as first-line agents for the prevention of osteoporosis.^[241]

In 2017, the American College of Rheumatology published revised recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Recommendations include optimizing calcium and vitamin D supplementation and lifestyle modifications for all adults on long-term glucocorticoid treatment (≥2.5 mg/day prednisone for ≥3 months). Furthermore, categorization of patients by fracture risk (using the FRAX score adjusted for glucocorticoid use) is recommended. First-line pharmacotherapy for patients at moderate-to-high fracture risk is an oral bisphosphonate, which is preferred for safety, cost, and because of lack of evidence of superior antifracture benefits from alternative medications. Other pharmacologic treatments recommended, if oral bisphosphonates are not appropriate, include (in order of preference): IV bisphosphonates, teriparatide, denosumab, and raloxifene.^[12]

Estrogen-progestin therapy is no longer considered a first-line approach for the treatment of osteoporosis in postmenopausal women, because it has been linked to an increased risk for breast cancer, stroke, venous thromboembolism, and perhaps coronary disease. Estrogen is now recommended only if patients are also seeking relief of postmenopausal symptoms.

Regular monitoring may be helpful. Periodic bone densitometry helps in diagnosing osteoporosis in the early phase and aids in preventing fractures. According to the National Osteoporosis Foundation, evaluating BMD on a periodic basis is the best way to monitor bone density and future fracture risk.^[4]However, there is considerable controversy about how often to repeat BMD measurements, particularly in postmenopausal women with a normal baseline BMD.^[242]

Prevention of falls

Environmental measures to prevent falls/fractures include^[11]:

Remove or anchor rugs and use nonskid mats
Minimize clutter
Remove loose wires
Install handrails in bathrooms, halls, and long stairways
Ensure hallways, stairwells, and entrances are well lighted
Encourage patient to wear sturdy, low-heeled shoes

Consultations

For a patient with osteoporosis in the diagnostic and therapeutic phases, the most important consultation is with a rheumatologist or an endocrinologist. These specialists can help obtain the proper laboratory tests and imaging studies needed to rule out causes of secondary osteoporosis. In patients with uncontrolled pain that does not respond to conventional therapies, an invasive pain specialist may be consulted for proper interventional procedures.

A rheumatologist or endocrinologist may also provide useful assistance with management and determination of underlying etiologies in complex cases.

Consultations can include discussions of nonmedical/nonpharmacologic management of osteoporosis.^{[243, 244]}Consult an orthopedist to assist with fracture management. Consultation with a spine surgeon is appropriate for patients with intractable, severe, function-limiting symptomatology from vertebral fractures that has not been relieved by noninterventional techniques. Consultation with a nonsurgical spine specialist is appropriate for a patient who is not a surgical candidate or whose symptoms persist despite surgical fixation.

Long-Term Monitoring

The US Preventive Services Task Force (USPSTF) 2011 recommendations state that evidence is lacking regarding optimal intervals for repeated screening by dual-energy x-ray absorptiometry (DXA) for individuals with osteoporosis, as well as regarding whether a woman with a normal BMD requires repeated screening. The USPSTF noted that, “a minimum of 2 years may be needed to reliably measure a change in BMD; however, longer intervals may be necessary to improve fracture risk prediction.”^[109]

According to a study funded by the National Institutes of Health, osteoporosis will develop in fewer than 10% of older, postmenopausal women during the following rescreening intervals^[245]:

Women with normal BMD or mild osteopenia - Approximately 15 years
Women with moderate osteopenia - Approximately 5 years
Women with advanced osteopenia - Approximately 1 year

Guidelines

Porter JL, Varacallo M. Osteoporosis. 2022 Jan. [QxMD MEDLINE Link]. [Full Text].
Johnston CB, Dagar M. Osteoporosis in Older Adults. Med Clin North Am. 2020 Sep. 104 (5):873-884. [QxMD MEDLINE Link].
Lynn SG, Sinaki M, Westerlind KC. Balance characteristics of persons with osteoporosis. Arch Phys Med Rehabil. 1997 Mar. 78(3):273-7. [QxMD MEDLINE Link].
[Guideline] Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S, et al. Clinician's Guide to Prevention and Treatment of Osteoporosis. Osteoporos Int. 2014 Oct. 25 (10):2359-81. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Schousboe JT, Shepherd JA, Bilezikian JP, Baim S. Executive summary of the 2013 International Society for Clinical Densitometry Position Development Conference on bone densitometry. J Clin Densitom. 2013 Oct-Dec. 16(4):455-66. [QxMD MEDLINE Link].
Gosfield E 3rd, Bonner FJ Jr. Evaluating bone mineral density in osteoporosis. Am J Phys Med Rehabil. 2000 May-Jun. 79(3):283-91. [QxMD MEDLINE Link].
Kanis JA, McCloskey EV, Johansson H, Oden A, Melton LJ 3rd, Khaltaev N. A reference standard for the description of osteoporosis. Bone. 2008 Mar. 42(3):467-75. [QxMD MEDLINE Link].
Silverman SL. Selecting patients for osteoporosis therapy. Ann N Y Acad Sci. 2007 Nov. 1117:264-72. [QxMD MEDLINE Link].
Czerwinski E, Badurski JE, Marcinowska-Suchowierska E, Osieleniec J. Current understanding of osteoporosis according to the position of the World Health Organization (WHO) and International Osteoporosis Foundation. Ortop Traumatol Rehabil. 2007 Jul-Aug. 9(4):337-56. [QxMD MEDLINE Link].
Kanis JA. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int. 1994 Nov. 4(6):368-81. [QxMD MEDLINE Link].
[Guideline] Camacho PM, Petak SM, Binkley N, Diab DL, Eldeiry LS, Farooki A, et al. American Association of Clinical Endocrinologists/American College of Endocrinology Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis-2020 Update. Endocr Pract. 2020 May. 26 (Suppl 1):1-46. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Buckley L, Guyatt G, Fink HA, Cannon M, Grossman J, Hansen KE, et al. 2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis Care Res (Hoboken). 2017 Aug. 69 (8):1095-1110. [QxMD MEDLINE Link]. [Full Text].
Al Saedi A, Stupka N, Duque G. Pathogenesis of Osteoporosis. Handb Exp Pharmacol. 2020 Apr 16. 115(12):3318-25. [QxMD MEDLINE Link].
Majumdar SR, Lier DA, Beaupre LA, Hanley DA, Maksymowych WP, Juby AG, et al. Osteoporosis case manager for patients with hip fractures: results of a cost-effectiveness analysis conducted alongside a randomized trial. Arch Intern Med. 2009 Jan 12. 169(1):25-31. [QxMD MEDLINE Link].
Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S, et al. Clinician's Guide to Prevention and Treatment of Osteoporosis. Osteoporos Int. 2014 Oct. 25 (10):2359-81. [QxMD MEDLINE Link].
Maybury K. Strengthening Communication on Bone Health. Gallup. Available at http://www.gallup.com/poll/5851/Strengthening-Communication-Bone-Health.aspx?g_source=osteoporosis&g_medium=search&g_campaign=tiles. April 23, 2002; Accessed: December 20, 2022.
Haas AV, LeBoff MS. Osteoanabolic Agents for Osteoporosis. J Endocr Soc. 2018 Aug 1. 2 (8):922-932. [QxMD MEDLINE Link].
World Health Organization. WHO scientific group on the assessment of osteoporosis at primary health care level: summary meeting report. Available at http://www.who.int/chp/topics/Osteoporosis.pdf. 2007; Accessed: January 21, 2021.
Clarke B. Normal bone anatomy and physiology. Clin J Am Soc Nephrol. 2008 Nov. 3 Suppl 3:S131-9. [QxMD MEDLINE Link].
Bono CM, Einhorn TA. Overview of osteoporosis: pathophysiology and determinants of bone strength. Eur Spine J. 2003 Oct. 12 Suppl 2:S90-6. [QxMD MEDLINE Link].
Seeman E, Delmas PD. Bone quality--the material and structural basis of bone strength and fragility. N Engl J Med. 2006 May 25. 354(21):2250-61. [QxMD MEDLINE Link].
S Tanaka, K Nakamura, N Takahas. Role of RANKL in physiological and pathological bone resorption and therapeutics targeting the RANKL-RANK signaling system. Immunol Rev. 2005. 208:30-49. [Full Text].
Mora S, Gilsanz V. Establishment of peak bone mass. Endocrinol Metab Clin North Am. 2003 Mar. 32(1):39-63. [QxMD MEDLINE Link].
Föger-Samwald U, Dovjak P, Azizi-Semrad U, Kerschan-Schindl K, Pietschmann P. Osteoporosis: Pathophysiology and therapeutic options. EXCLI J. 2020. 19:1017-1037. [QxMD MEDLINE Link].
Raisz LG. Pathogenesis of osteoporosis: concepts, conflicts, and prospects. J Clin Invest. 2005 Dec. 115 (12):3318-25. [QxMD MEDLINE Link].
Jilka RL, Hangoc G, Girasole G, Passeri G, Williams DC, Abrams JS, et al. Increased osteoclast development after estrogen loss: mediation by interleukin-6. Science. 1992 Jul 3. 257(5066):88-91. [QxMD MEDLINE Link].
Föger-Samwald U, Dovjak P, Azizi-Semrad U, Kerschan-Schindl K, Pietschmann P. Osteoporosis: Pathophysiology and therapeutic options. EXCLI J. 2020. 19:1017-1037. [QxMD MEDLINE Link].
Cline-Smith A, Axelbaum A, Shashkova E, Chakraborty M, Sanford J, Panesar P, et al. Ovariectomy Activates Chronic Low-Grade Inflammation Mediated by Memory T Cells, Which Promotes Osteoporosis in Mice. J Bone Miner Res. 2020 Jun. 35 (6):1174-1187. [QxMD MEDLINE Link].
Demontiero O, Vidal C, Duque G. Aging and bone loss: new insights for the clinician. Ther Adv Musculoskelet Dis. 2012 Apr. 4 (2):61-76. [QxMD MEDLINE Link].
Warriner AH, Patkar NM, Curtis JR, Delzell E, Gary L, Kilgore M, et al. Which fractures are most attributable to osteoporosis?. J Clin Epidemiol. 2011 Jan. 64 (1):46-53. [QxMD MEDLINE Link].
Cummings SR, Melton LJ. Epidemiology and outcomes of osteoporotic fractures. Lancet. 2002 May 18. 359(9319):1761-7. [QxMD MEDLINE Link].
Rosen CJ, Tenenhouse A. Biochemical markers of bone turnover. A look at laboratory tests that reflect bone status. Postgrad Med. Oct 1998. 104(4):101-2, 107-10.
Nusse R. Wnt signaling in disease and in development. Cell Res. 2005 Jan. 15(1):28-32. [QxMD MEDLINE Link].
Ling L, Nurcombe V, Cool SM. Wnt signaling controls the fate of mesenchymal stem cells. Gene. 2009 Mar 15. 433(1-2):1-7. [QxMD MEDLINE Link].
Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999 Apr 2. 284(5411):143-7. [QxMD MEDLINE Link].
Rao TP, Kühl M. An updated overview on Wnt signaling pathways: a prelude for more. Circ Res. 2010 Jun 25. 106(12):1798-806. [QxMD MEDLINE Link].
Clevers H, Nusse R. Wnt/ß-catenin signaling and disease. Cell. 2012 Jun 8. 149(6):1192-205. [QxMD MEDLINE Link].
Krishnan V, Bryant HU, Macdougald OA. Regulation of bone mass by Wnt signaling. J Clin Invest. 2006 May. 116(5):1202-9. [QxMD MEDLINE Link]. [Full Text].
Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, et al. High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med. 2002 May 16. 346(20):1513-21. [QxMD MEDLINE Link].
Van Wesenbeeck L, Cleiren E, Gram J, Beals RK, Bénichou O, Scopelliti D, et al. Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density. Am J Hum Genet. 2003 Mar. 72(3):763-71. [QxMD MEDLINE Link]. [Full Text].
Levasseur R, Lacombe D, de Vernejoul MC. LRP5 mutations in osteoporosis-pseudoglioma syndrome and high-bone-mass disorders. Joint Bone Spine. 2005 May. 72(3):207-14. [QxMD MEDLINE Link].
Zhu Y, Sun Z, Han Q, Liao L, Wang J, Bian C, et al. Human mesenchymal stem cells inhibit cancer cell proliferation by secreting DKK-1. Leukemia. 2009 May. 23(5):925-33. [QxMD MEDLINE Link].
Kawano Y, Kypta R. Secreted antagonists of the Wnt signalling pathway. J Cell Sci. 2003 Jul 1. 116:2627-34. [QxMD MEDLINE Link].
Kaiser M, Mieth M, Liebisch P, Oberländer R, Rademacher J, Jakob C, et al. Serum concentrations of DKK-1 correlate with the extent of bone disease in patients with multiple myeloma. Eur J Haematol. 2008 Jun. 80(6):490-4. [QxMD MEDLINE Link].
Tai N, Inoue D. [Anti-Dickkopf1 (Dkk1) antibody as a bone anabolic agent for the treatment of osteoporosis]. Clin Calcium. 2014 Jan. 24 (1):75-83. [QxMD MEDLINE Link].
Bonewald LF. The amazing osteocyte. J Bone Miner Res. 2011 Feb. 26(2):229-38. [QxMD MEDLINE Link]. [Full Text].
Li X, Zhang Y, Kang H, Liu W, Liu P, Zhang J, et al. Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem. 2005 May 20. 280(20):19883-7. [QxMD MEDLINE Link].
FDA approves new treatment for osteoporosis in postmenopausal women at high risk of fracture. U.S. Food & Drug Administration. Available at https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-osteoporosis-postmenopausal-women-high-risk-fracture. April 09, 2019; Accessed: January 21, 2021.
Ringe JD, Farahmand P. Advances in the management of corticosteroid-induced osteoporosis with bisphosphonates. Clin Rheumatol. 2007 Apr. 26(4):474-84. [QxMD MEDLINE Link].
Dennison EM, Syddall HE, Sayer AA, Gilbody HJ, Cooper C. Birth weight and weight at 1 year are independent determinants of bone mass in the seventh decade: the Hertfordshire cohort study. Pediatr Res. 2005 Apr. 57(4):582-6. [QxMD MEDLINE Link].
Fall C, Hindmarsh P, Dennison E, Kellingray S, Barker D, Cooper C. Programming of growth hormone secretion and bone mineral density in elderly men: a hypothesis. J Clin Endocrinol Metab. 1998 Jan. 83(1):135-9. [QxMD MEDLINE Link].
Marini F, Cianferotti L, Brandi ML. Epigenetic Mechanisms in Bone Biology and Osteoporosis: Can They Drive Therapeutic Choices?. Int J Mol Sci. 2016 Aug 12. 17 (8):[QxMD MEDLINE Link].
Colangelo L, Biamonte F, Pepe J, Cipriani C, Minisola S. Understanding and managing secondary osteoporosis. Expert Rev Endocrinol Metab. 2019 Mar. 14 (2):111-122. [QxMD MEDLINE Link].
Kelman A, Lane NE. The management of secondary osteoporosis. Best Pract Res Clin Rheumatol. 2005 Dec. 19(6):1021-37. [QxMD MEDLINE Link].
Adams JS, Song CF, Kantorovich V. Rapid recovery of bone mass in hypercalciuric, osteoporotic men treated with hydrochlorothiazide. Ann Intern Med. 1999 Apr 20. 130(8):658-60. [QxMD MEDLINE Link].
Mann GB, Kang YC, Brand C, Ebeling PR, Miller JA. Secondary causes of low bone mass in patients with breast cancer: a need for greater vigilance. J Clin Oncol. 2009 Aug 1. 27(22):3605-10. [QxMD MEDLINE Link].
Holick MF. Vitamin D deficiency. N Engl J Med. 2007 Jul 19. 357(3):266-81. [QxMD MEDLINE Link].
di Munno O, Mazzantini M, Sinigaglia L, Bianchi G, Minisola G, Muratore M, et al. Effect of low dose methotrexate on bone density in women with rheumatoid arthritis: results from a multicenter cross-sectional study. J Rheumatol. 2004 Jul. 31(7):1305-9. [QxMD MEDLINE Link].
Migliaccio S, Brama M, Malavolta N. Management of glucocorticoids-induced osteoporosis: role of teriparatide. Ther Clin Risk Manag. 2009 Apr. 5(2):305-10. [QxMD MEDLINE Link]. [Full Text].
van Staa TP, Leufkens HG, Cooper C. The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int. 2002 Oct. 13(10):777-87. [QxMD MEDLINE Link].
Licata AA. Challenges of Estimating Fracture Risk with DXA: Changing Concepts About Bone Strength and Bone Density. Aerosp Med Hum Perform. 2015 Jul. 86 (7):628-32. [QxMD MEDLINE Link].
Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. World Health Organ Tech Rep Ser. 1994. 843:1-129. [QxMD MEDLINE Link].
Lyles KW, Schenck AP, Colón-Emeric CS. Hip and other osteoporotic fractures increase the risk of subsequent fractures in nursing home residents. Osteoporos Int. 2008 Aug. 19(8):1225-33. [QxMD MEDLINE Link]. [Full Text].
Fink HA, Kuskowski MA, Taylor BC, Schousboe JT, Orwoll ES, Ensrud KE. Association of Parkinson's disease with accelerated bone loss, fractures and mortality in older men: the Osteoporotic Fractures in Men (MrOS) study. Osteoporos Int. 2008 Sep. 19(9):1277-82. [QxMD MEDLINE Link].
Sinaki M. Exercise and osteoporosis. Arch Phys Med Rehabil. 1989 Mar. 70(3):220-9. [QxMD MEDLINE Link].
Yaturu S, DjeDjos S, Alferos G, Deprisco C. Bone mineral density changes on androgen deprivation therapy for prostate cancer and response to antiresorptive therapy. Prostate Cancer Prostatic Dis. 2006. 9(1):35-8. [QxMD MEDLINE Link].
Busko M. Chemical in Toothpaste Tied to Osteoporosis in Women. Medscape Medical News. Available at https://www.medscape.com/viewarticle/914888. June 26, 2019; Accessed: June 27, 2019.
Hansen D, Bazell C, Pelizzari P, Pyenson B. Medicare cost of osteoporotic fractures: The clinical and cost burden of an important consequence of osteoporosis. Available at https://static1.squarespace.com/static/5c0860aff793924efe2230f3/t/5d76b949deb7e9086ee3d7dd/1568061771769/Medicare+Cost+of+Osteoporotic+Fractures+20190827.pdf. August 2019; Accessed: January 21, 2021.
Cooper C, Campion G, Melton LJ 3rd. Hip fractures in the elderly: a world-wide projection. Osteoporos Int. 1992 Nov. 2(6):285-9. [QxMD MEDLINE Link].
Who are candidates for prevention and treatment for osteoporosis?. Osteoporos Int. 1997. 7(1):1-6. [QxMD MEDLINE Link].
Jensen GF, Christiansen C, Boesen J, Hegedüs V, Transbøl I. Epidemiology of postmenopausal spinal and long bone fractures. A unifying approach to postmenopausal osteoporosis. Clin Orthop Relat Res. 1982 Jun. 75-81. [QxMD MEDLINE Link].
Melton LJ 3rd, Kan SH, Frye MA, Wahner HW, O'Fallon WM, Riggs BL. Epidemiology of vertebral fractures in women. Am J Epidemiol. 1989 May. 129(5):1000-11. [QxMD MEDLINE Link].
Smith R, Wordsworth P. Osteoporosis. Clinical and Biochemical Disorders of the Skeleton. 2005. 123.
Chon KS, Sartoris DJ, Brown SA, Clopton P. Alcoholism-associated spinal and femoral bone loss in abstinent male alcoholics, as measured by dual X-ray absorptiometry. Skeletal Radiol. 1992. 21(7):431-6. [QxMD MEDLINE Link].
Robbins J, Aragaki AK, Kooperberg C, Watts N, Wactawski-Wende J, Jackson RD, et al. Factors associated with 5-year risk of hip fracture in postmenopausal women. JAMA. 2007 Nov 28. 298(20):2389-98. [QxMD MEDLINE Link].
Bass MA, Sharma A, Nahar VK, Chelf S, Zeller B, Pham L, et al. Bone Mineral Density Among Men and Women Aged 35 to 50 Years. J Am Osteopath Assoc. 2019 Jun 1. 119 (6):357-363. [QxMD MEDLINE Link]. [Full Text].
Woolf AD, Pfleger B. Burden of major musculoskeletal conditions. Bull World Health Organ. 2003. 81(9):646-56. [QxMD MEDLINE Link]. [Full Text].
Balfour F. China’s "Demographic Tsunami." Bloomberg Businessweek. January 5, 2012. Available at http://www.businessweek.com/magazine/chinas-demographic-tsunami-01052012.html. Accessed: February 16, 2012.
Morin SN, Lix LM, Majumdar SR, Leslie WD. Temporal trends in the incidence of osteoporotic fractures. Curr Osteoporos Rep. 2013 Dec. 11(4):263-9. [QxMD MEDLINE Link].
Melton LJ 3rd, Sampson JM, Morrey BF, Ilstrup DM. Epidemiologic features of pelvic fractures. Clin Orthop Relat Res. 1981 Mar-Apr. 43-7. [QxMD MEDLINE Link].
Cauley JA, Lui LY, Ensrud KE, Zmuda JM, Stone KL, Hochberg MC, et al. Bone mineral density and the risk of incident nonspinal fractures in black and white women. JAMA. 2005 May 4. 293(17):2102-8. [QxMD MEDLINE Link].
Bone Health and Osteoporosis: A Report of the Surgeon General. Washington, DC: Department of Health and Human Services; 2004. [Full Text].
Burge R, Dawson-Hughes B, Solomon DH, et al. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J Bone Miner Res. 2007 Mar. 22(3):465-75. [QxMD MEDLINE Link].
Ensrud KE, Kats AM, Boyd CM, Diem SJ, Schousboe JT, Taylor BC, et al. Association of Disease Definition, Comorbidity Burden, and Prognosis With Hip Fracture Probability Among Late-Life Women. JAMA Intern Med. 2019 Jun 17. [QxMD MEDLINE Link].
Sharon Chou, MD, Anjali Grover, MD, and Meryl S LeBoff, MD. New Osteoporotic/Vertebral Compression Fractures. Available at https://www.ncbi.nlm.nih.gov/books/NBK279035/. 09/19/18; Accessed: December 9 , 2022.
Cooper C, Atkinson EJ, Jacobsen SJ, et al. Population-based study of survival after osteoporotic fractures. Am J Epidemiol. 1993 May 1. 137(9):1001-5. [QxMD MEDLINE Link].
Kado DM, Browner WS, Palermo L, Nevitt MC, Genant HK, Cummings SR. Vertebral fractures and mortality in older women: a prospective study. Study of Osteoporotic Fractures Research Group. Arch Intern Med. 1999 Jun 14. 159(11):1215-20. [QxMD MEDLINE Link].
Vestergaard P, Rejnmark L, Mosekilde L. Increased mortality in patients with a hip fracture-effect of pre-morbid conditions and post-fracture complications. Osteoporos Int. 2007 Dec. 18(12):1583-93. [QxMD MEDLINE Link].
Trombetti A, Herrmann F, Hoffmeyer P, Schurch MA, Bonjour JP, Rizzoli R. Survival and potential years of life lost after hip fracture in men and age-matched women. Osteoporos Int. 2002 Sep. 13(9):731-7. [QxMD MEDLINE Link].
Michel JP, Hoffmeyer P, Klopfenstein C, et al. Prognosis of functional recovery 1 year after hip fracture: typical patient profiles through cluster analysis. J Gerontol A Biol Sci Med Sci. 2000 Sep. 55(9):M508-15. [QxMD MEDLINE Link].
Lindsay R, Silverman SL, Cooper C, et al. Risk of new vertebral fracture in the year following a fracture. JAMA. 2001 Jan 17. 285(3):320-3. [QxMD MEDLINE Link].
Klotzbuecher CM, Ross PD, Landsman PB, et al. Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis. J Bone Miner Res. 2000 Apr. 15(4):721-39. [QxMD MEDLINE Link].
Morin SN, Lix LM, Leslie WD. The importance of previous fracture site on osteoporosis diagnosis and incident fractures in women. J Bone Miner Res. 2014 Jul. 29(7):1675-80. [QxMD MEDLINE Link].
FRAX Fracture Risk Assessment Tool. Available at http://www.shef.ac.uk/FRAX/. Accessed: December 9, 2022.
Leslie WD, Morin S, Lix LM. Before-and-After Study of Fracture Risk Reporting and Osteoporosis Treatment Initiation. Ann Intern Med. Nov 2 2010. 153(9):580-6.
Schwartz AV, Vittinghoff E, Bauer DC, et al. Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes. JAMA. 2011 Jun 1. 305(21):2184-92. [QxMD MEDLINE Link].
Tremollieres FA, Pouilles JM, Drewniak N, Laparra J, Ribot CA, Dargent-Molina P. Fracture risk prediction using BMD and clinical risk factors in early postmenopausal women: sensitivity of the WHO FRAX tool. J Bone Miner Res. 2010 May. 25(5):1002-9. [QxMD MEDLINE Link]. [Full Text].
Grisso JA, Kelsey JL, Strom BL, Chiu GY, Maislin G, O'Brien LA, et al. Risk factors for falls as a cause of hip fracture in women. The Northeast Hip Fracture Study Group. N Engl J Med. 1991 May 9. 324(19):1326-31. [QxMD MEDLINE Link].
Nellans KW, Kowalski E, Chung KC. The epidemiology of distal radius fractures. Hand Clin. 2012 May. 28(2):113-25. [QxMD MEDLINE Link]. [Full Text].
Sandhu SK, Nguyen ND, Center JR, Pocock NA, Eisman JA, Nguyen TV. Prognosis of fracture: evaluation of predictive accuracy of the FRAX algorithm and Garvan nomogram. Osteoporos Int. 2010 May. 21(5):863-71. [QxMD MEDLINE Link].
Kanis JA, Harvey NC, Johansson H, Odén A, McCloskey EV, Leslie WD. Overview of Fracture Prediction Tools. J Clin Densitom. 2017 Jul - Sep. 20 (3):444-450. [QxMD MEDLINE Link].
Cooper C, Atkinson EJ, O'Fallon WM, et al. Incidence of clinically diagnosed vertebral fractures: a population-based study in Rochester, Minnesota, 1985-1989. J Bone Miner Res. 1992 Feb. 7(2):221-7. [QxMD MEDLINE Link].
Cook DJ, Guyatt GH, Adachi JD, Clifton J, Griffith LE, Epstein RS, et al. Quality of life issues in women with vertebral fractures due to osteoporosis. Arthritis Rheum. 1993 Jun. 36(6):750-6. [QxMD MEDLINE Link].
Schnatz PF, Marakovits KA, Dubois M, O'Sullivan DM. Osteoporosis screening and treatment guidelines: are they being followed?. Menopause. 2011 Oct. 18(10):1072-8. [QxMD MEDLINE Link].
Geusens P, Dumitrescu B, van Geel T, van Helden S, Vanhoof J, Dinant GJ. Impact of systematic implementation of a clinical case finding strategy on diagnosis and therapy of postmenopausal osteoporosis. J Bone Miner Res. 2008 Jun. 23(6):812-8. [QxMD MEDLINE Link].
[Guideline] Screening for osteoporosis: U.S. preventive services task force recommendation statement. Ann Intern Med. 2011 Mar 1. 154(5):356-64. [QxMD MEDLINE Link].
Bone Health and Osteoporosis: A Report of the Surgeon General. [Full Text].
Zhu K, Devine A, Lewis JR, Dhaliwal SS, Prince RL. Timed up and go test and bone mineral density measurement for fracture prediction. Arch Intern Med. 2011 Oct 10. 171(18):1655-61. [QxMD MEDLINE Link].
Nayak S, Roberts MS, Greenspan SL. Cost-effectiveness of different screening strategies for osteoporosis in postmenopausal women. Ann Intern Med. 2011 Dec 6. 155(11):751-61. [QxMD MEDLINE Link].
[Guideline] Liu H, Paige NM, Goldzweig CL, Wong E, Zhou A, Suttorp MJ, et al. Screening for osteoporosis in men: a systematic review for an American College of Physicians guideline. Ann Intern Med. 2008 May 6. 148(9):685-701. [QxMD MEDLINE Link]. [Full Text].
Spiegel R, Nawroth PP, Kasperk C. The effect of zoledronic acid on the fracture risk in men with osteoporosis. J Endocrinol Invest. 2014 Mar. 37 (3):229-32. [QxMD MEDLINE Link].
Dittmer DK, Teasell R. Complications of immobilization and bed rest. Part 1: Musculoskeletal and cardiovascular complications. Can Fam Physician. 1993 Jun. 39:1428-32, 1435-7. [QxMD MEDLINE Link].
Guglielmi G, Muscarella S, Bazzocchi A. Integrated imaging approach to osteoporosis: state-of-the-art review and update. Radiographics. 2011 Sep-Oct. 31(5):1343-64. [QxMD MEDLINE Link].
Khoo BC, Brown K, Cann C, et al. Comparison of QCT-derived and DXA-derived areal bone mineral density and T scores. Osteoporos Int. 2009 Sep. 20(9):1539-45. [QxMD MEDLINE Link].
Link TM. Axial and peripheral QCT. Guglielmi G, ed. Osteoporosis and Bone Densitometry Measurements. New York, NY: Springer Heidelberg; 2013. 123-32.
Beaudoin C, Moore L, Gagné M, Bessette L, Ste-Marie LG, Brown JP, et al. Performance of predictive tools to identify individuals at risk of non-traumatic fracture: a systematic review, meta-analysis, and meta-regression. Osteoporos Int. 2019 Apr. 30 (4):721-740. [QxMD MEDLINE Link].
Paunier L. Effect of magnesium on phosphorus and calcium metabolism. Monatsschr Kinderheilkd. 1992 Sep. 140(9 Suppl 1):S17-20. [QxMD MEDLINE Link].
Lee WY, Oh KW, Rhee EJ, Jung CH, Kim SW, Yun EJ, et al. Relationship between subclinical thyroid dysfunction and femoral neck bone mineral density in women. Arch Med Res. 2006 May. 37(4):511-6. [QxMD MEDLINE Link].
Tannenbaum C, Clark J, Schwartzman K, Wallenstein S, Lapinski R, Meier D. Yield of laboratory testing to identify secondary contributors to osteoporosis in otherwise healthy women. J Clin Endocrinol Metab. 2002 Oct. 87(10):4431-7. [QxMD MEDLINE Link].
Liu JM, Zhao HY, Ning G, Chen Y, Zhang LZ, Sun LH, et al. IGF-1 as an early marker for low bone mass or osteoporosis in premenopausal and postmenopausal women. J Bone Miner Metab. 2008. 26(2):159-64. [QxMD MEDLINE Link].
Vasikaran S, Cooper C, Eastell R, Griesmacher A, Morris HA, Trenti T, et al. International Osteoporosis Foundation and International Federation of Clinical Chemistry and Laboratory Medicine position on bone marker standards in osteoporosis. Clin Chem Lab Med. 2011 Aug. 49 (8):1271-4. [QxMD MEDLINE Link].
Resnick D, Kransdorf M. Osteoporosis. Bone and Joint Imaging. Third Edition. 2005. 551.
Hillier TA, Stone KL, Bauer DC, Rizzo JH, Pedula KL, Cauley JA, et al. Evaluating the value of repeat bone mineral density measurement and prediction of fractures in older women: the study of osteoporotic fractures. Arch Intern Med. 2007 Jan 22. 167(2):155-60. [QxMD MEDLINE Link].
Nayak S, Roberts MS, Greenspan SL. Cost-effectiveness of different screening strategies for osteoporosis in postmenopausal women. Ann Intern Med. 2011 Dec 6. 155(11):751-61. [QxMD MEDLINE Link]. [Full Text].
Lin JT, Lane JM. Bisphosphonates. J Am Acad Orthop Surg. 2003 Jan-Feb. 11(1):1-4. [QxMD MEDLINE Link].
Faulkner KG, Wacker WK, Barden HS, Simonelli C, Burke PK, Ragi S, et al. Femur strength index predicts hip fracture independent of bone density and hip axis length. Osteoporos Int. 2006. 17(4):593-9. [QxMD MEDLINE Link].
Prevrhal S, Shepherd JA, Faulkner KG, Gaither KW, Black DM, Lang TF. Comparison of DXA hip structural analysis with volumetric QCT. J Clin Densitom. 2008 Apr-Jun. 11(2):232-6. [QxMD MEDLINE Link].
Kaptoge S, Beck TJ, Reeve J, Stone KL, Hillier TA, Cauley JA, et al. Prediction of incident hip fracture risk by femur geometry variables measured by hip structural analysis in the study of osteoporotic fractures. J Bone Miner Res. 2008 Dec. 23(12):1892-904. [QxMD MEDLINE Link]. [Full Text].
Beck TJ. Extending DXA beyond bone mineral density: understanding hip structure analysis. Curr Osteoporos Rep. 2007 Jun. 5(2):49-55. [QxMD MEDLINE Link].
Hans D, Barthe N, Boutroy S, Pothuaud L, Winzenrieth R, Krieg MA. Correlations between trabecular bone score, measured using anteroposterior dual-energy X-ray absorptiometry acquisition, and 3-dimensional parameters of bone microarchitecture: an experimental study on human cadaver vertebrae. J Clin Densitom. 2011 Jul-Sep. 14(3):302-12. [QxMD MEDLINE Link].
Pothuaud L, Barthe N, Krieg MA, Mehsen N, Carceller P, Hans D. Evaluation of the potential use of trabecular bone score to complement bone mineral density in the diagnosis of osteoporosis: a preliminary spine BMD-matched, case-control study. J Clin Densitom. 2009 Apr-Jun. 12(2):170-6. [QxMD MEDLINE Link].
Silva BC, Leslie WD, Resch H, Lamy O, Lesnyak O, Binkley N, et al. Trabecular bone score: a noninvasive analytical method based upon the DXA image. J Bone Miner Res. 2014 Mar. 29(3):518-30. [QxMD MEDLINE Link].
Schuit SC, van der Klift M, Weel AE, de Laet CE, Burger H, Seeman E, et al. Fracture incidence and association with bone mineral density in elderly men and women: the Rotterdam Study. Bone. 2004 Jan. 34(1):195-202. [QxMD MEDLINE Link].
Imai K. Recent methods for assessing osteoporosis and fracture risk. Recent Pat Endocr Metab Immune Drug Discov. 2014 Jan. 8(1):48-59. [QxMD MEDLINE Link].
Yang L, Palermo L, Black DM, Eastell R. Prediction of incident hip fracture with the estimated femoral strength by finite element analysis of DXA Scans in the study of osteoporotic fractures. J Bone Miner Res. 2014 Dec. 29(12):2594-600. [QxMD MEDLINE Link].
Torres-del-Pliego E, Vilaplana L, Güerri-Fernández R, Diez-Pérez A. Measuring bone quality. Curr Rheumatol Rep. 2013 Nov. 15(11):373. [QxMD MEDLINE Link].
Kulkarni AG, Thonangi Y, Pathan S, Gunjotikar S, Goparaju P, Talwar I, et al. Should Q-CT Be the Gold Standard for Detecting Spinal Osteoporosis?. Spine (Phila Pa 1976). 2022 Mar 15. 47 (6):E258-E264. [QxMD MEDLINE Link].
Prior JC, Vigna YM, Wark JD, et al. Premenopausal ovariectomy-related bone loss: a randomized, double-blind, one-year trial of conjugated estrogen or medroxyprogesterone acetate. J Bone Miner Res. 1997 Nov. 12(11):1851-63. [QxMD MEDLINE Link].
Henzell S, Dhaliwal S, Pontifex R, et al. Precision error of fan-beam dual X-ray absorptiometry scans at the spine, hip, and forearm. J Clin Densitom. 2000 Winter. 3(4):359-64. [QxMD MEDLINE Link].
White J, Harris SS, Dallal GE, Dawson-Hughes B. Precision of single vs bilateral hip bone mineral density scans. J Clin Densitom. 2003 Summer. 6(2):159-62. [QxMD MEDLINE Link].
Bauer JS, Henning TD, Müeller D, Lu Y, Majumdar S, Link TM. Volumetric quantitative CT of the spine and hip derived from contrast-enhanced MDCT: conversion factors. AJR Am J Roentgenol. 2007 May. 188(5):1294-301. [QxMD MEDLINE Link].
Engelke K, Adams JE, Armbrecht G, et al. Clinical use of quantitative computed tomography and peripheral quantitative computed tomography in the management of osteoporosis in adults: the 2007 ISCD Official Positions. J Clin Densitom. 2008 Jan-Mar. 11(1):123-62. [QxMD MEDLINE Link].
Liu G, Peacock M, Eilam O, Dorulla G, Braunstein E, Johnston CC. Effect of osteoarthritis in the lumbar spine and hip on bone mineral density and diagnosis of osteoporosis in elderly men and women. Osteoporos Int. 1997. 7(6):564-9. [QxMD MEDLINE Link].
[Guideline] Qaseem A, Forciea MA, McLean RM, Denberg TD, for the Clinical Guidelines Committee of the American College of Physicians. Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update from the American College of Physicians. Ann Intern Med. 9 May 2017. [Full Text].
Fribourg D, Tang C, Sra P, Delamarter R, Bae H. Incidence of subsequent vertebral fracture after kyphoplasty. Spine (Phila Pa 1976). 2004 Oct 15. 29(20):2270-6; discussion 2277. [QxMD MEDLINE Link].
Movrin I, Vengust R, Komadina R. Adjacent vertebral fractures after percutaneous vertebral augmentation of osteoporotic vertebral compression fracture: a comparison of balloon kyphoplasty and vertebroplasty. Arch Orthop Trauma Surg. 2010 Sep. 130(9):1157-66. [QxMD MEDLINE Link].
Kastner M, Straus SE. Clinical decision support tools for osteoporosis disease management: a systematic review of randomized controlled trials. J Gen Intern Med. 2008 Dec. 23(12):2095-105. [QxMD MEDLINE Link]. [Full Text].
Knopp JA, Diner BM, Blitz M, Lyritis GP, Rowe BH. Calcitonin for treating acute pain of osteoporotic vertebral compression fractures: a systematic review of randomized, controlled trials. Osteoporos Int. 2005 Oct. 16 (10):1281-90. [QxMD MEDLINE Link].
Kirshblum SC. Rehabilitation Medicine: Principles and Practice. DeLisa JA, Gans BM. Spinal and upper extremity orthotics. 3rd. Philadelphia, Pa: Lippincott-Raven; 1998. 635-50.
Stillo JV. Low back orthoses. Phys Med Rehab Clin North Am. 1992. 3:57-94.
[Guideline] Eastell R, Rosen CJ, Black DM, Cheung AM, Murad MH, Shoback D. Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society* Clinical Practice Guideline. J Clin Endocrinol Metab. 2019 May 1. 104 (5):1595-1622. [QxMD MEDLINE Link].
Gertz BJ, Holland SD, Kline WF, Matuszewski BK, Freeman A, Quan H, et al. Studies of the oral bioavailability of alendronate. Clin Pharmacol Ther. 1995 Sep. 58 (3):288-98. [QxMD MEDLINE Link].
Abrahamsen B, Eiken P, Eastell R. Proton pump inhibitor use and the antifracture efficacy of alendronate. Arch Intern Med. 2011 Jun 13. 171(11):998-1004. [QxMD MEDLINE Link].
Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group. JAMA. 1999 Oct 13. 282 (14):1344-52. [QxMD MEDLINE Link]. [Full Text].
Black DM, Delmas PD, Eastell R, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007 May 3. 356(18):1809-22. [QxMD MEDLINE Link].
Boonen S, Reginster JY, Kaufman JM, Lippuner K, Zanchetta J, Langdahl B, et al. Fracture risk and zoledronic acid therapy in men with osteoporosis. N Engl J Med. 2012 Nov. 367(18):1714-23. [QxMD MEDLINE Link].
Boonen S, Orwoll E, Magaziner J, Colón-Emeric CS, Adachi JD, Bucci-Rechtweg C, et al. Once-yearly zoledronic acid in older men compared with women with recent hip fracture. J Am Geriatr Soc. 2011 Nov. 59(11):2084-90. [QxMD MEDLINE Link].
Odvina CV, Zerwekh JE, Rao DS, Maalouf N, Gottschalk FA, Pak CY. Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab. 2005 Mar. 90(3):1294-301. [QxMD MEDLINE Link].
Halasy-Nagy JM, Rodan GA, Reszka AA. Inhibition of bone resorption by alendronate and risedronate does not require osteoclast apoptosis. Bone. 2001 Dec. 29(6):553-9. [QxMD MEDLINE Link].
US Food and Drug Administration. FDA drug safety communication: New contraindication and updated warning on kidney impairment for Reclast (zoledronic acid). Available at http://www.fda.gov/Drugs/DrugSafety/ucm270199.htm. September 1, 2011; Accessed: June 19, 2019.
Safety Information: Zometa (zoledronic acid) for injection. U.S. Food and Drug Administration. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021817s022lbl.pdf. April 2016; Accessed: June 15, 2019.
Khan AA, Morrison A, Hanley DA, Felsenberg D, McCauley LK, et al, et al. Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus. J Bone Miner Res. 2015 Jan. 30 (1):3-23. [QxMD MEDLINE Link].
Strampel W, Emkey R, Civitelli R. Safety considerations with bisphosphonates for the treatment of osteoporosis. Drug Saf. 2007. 30(9):755-63. [QxMD MEDLINE Link].
Zebic L, Patel V. Preventing medication-related osteonecrosis of the jaw. BMJ. 2019 May 8. 365:l1733. [QxMD MEDLINE Link].
Park-Wyllie LY, Mamdani MM, Juurlink DN, Hawker GA, Gunraj N, Austin PC, et al. Bisphosphonate use and the risk of subtrochanteric or femoral shaft fractures in older women. JAMA. 2011 Feb 23. 305(8):783-9. [QxMD MEDLINE Link].
Lo JC, Neugebauer RS, Ettinger B, Chandra M, Hui RL, Ott SM, et al. Risk of complete atypical femur fracture with Oral bisphosphonate exposure beyond three years. BMC Musculoskelet Disord. 2020 Dec 3. 21 (1):801. [QxMD MEDLINE Link].
Geusens P. Bisphosphonates for postmenopausal osteoporosis: determining duration of treatment. Curr Osteoporos Rep. 2009 Mar. 7(1):12-7. [QxMD MEDLINE Link].
[Guideline] Adler RA, El-Hajj Fuleihan G, Bauer DC, Camacho PM, Clarke BL, Clines GA, et al. Managing Osteoporosis in Patients on Long-Term Bisphosphonate Treatment: Report of a Task Force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2016 Jan. 31 (1):16-35. [QxMD MEDLINE Link]. [Full Text].
Grady D, Cauley JA, Stock JL, Cox DA, Mitlak BH, Song J, et al. Effect of Raloxifene on all-cause mortality. Am J Med. 2010 May. 123(5):469.e1-7. [QxMD MEDLINE Link].
Lindsay R, Gallagher JC, Kagan R, Pickar JH, Constantine G. Efficacy of tissue-selective estrogen complex of bazedoxifene/conjugated estrogens for osteoporosis prevention in at-risk postmenopausal women. Fertil Steril. 2009 Sep. 92(3):1045-52. [QxMD MEDLINE Link].
Gilsenan A, Harris D, Reynolds M, McSorley D, Midkiff K, Jackson L, et al. Long-term cancer surveillance: results from the Forteo Patient Registry Surveillance Study. Osteoporos Int. 2020 Nov 5. [QxMD MEDLINE Link].
Quattrocchi E, Kourlas H. Teriparatide: a review. Clin Ther. 2004 Jun. 26(6):841-54. [QxMD MEDLINE Link].
Koski AM, Sikiö A, Forslund T. Teriparatide treatment complicated by malignant myeloma. BMJ Case Rep. 2010 Aug 13. 2010:[QxMD MEDLINE Link]. [Full Text].
Body JJ, Gaich GA, Scheele WH, Kulkarni PM, Miller PD, Peretz A. A randomized double-blind trial to compare the efficacy of teriparatide [recombinant human parathyroid hormone (1-34)] with alendronate in postmenopausal women with osteoporosis. J Clin Endocrinol Metab. 2002 Oct. 87(10):4528-35. [QxMD MEDLINE Link].
Dempster DW, Cosman F, Kurland ES, Zhou H, Nieves J, Woelfert L, et al. Effects of daily treatment with parathyroid hormone on bone microarchitecture and turnover in patients with osteoporosis: a paired biopsy study. J Bone Miner Res. 2001 Oct. 16(10):1846-53. [QxMD MEDLINE Link].
Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001 May 10. 344(19):1434-41. [QxMD MEDLINE Link].
Kurland ES, Heller SL, Diamond B, McMahon DJ, Cosman F, Bilezikian JP. The importance of bisphosphonate therapy in maintaining bone mass in men after therapy with teriparatide [human parathyroid hormone(1-34)]. Osteoporos Int. 2004 Dec. 15(12):992-7. [QxMD MEDLINE Link].
Finkelstein JS, Hayes A, Hunzelman JL, Wyland JJ, Lee H, Neer RM. The effects of parathyroid hormone, alendronate, or both in men with osteoporosis. N Engl J Med. 2003 Sep 25. 349(13):1216-26. [QxMD MEDLINE Link].
Cosman F, Nieves J, Zion M, Woelfert L, Luckey M, Lindsay R. Daily and cyclic parathyroid hormone in women receiving alendronate. N Engl J Med. 2005 Aug 11. 353(6):566-75. [QxMD MEDLINE Link].
Deal C, Omizo M, Schwartz EN, Eriksen EF, Cantor P, Wang J, et al. Combination teriparatide and raloxifene therapy for postmenopausal osteoporosis: results from a 6-month double-blind placebo-controlled trial. J Bone Miner Res. 2005 Nov. 20(11):1905-11. [QxMD MEDLINE Link].
Ste-Marie LG, Schwartz SL, Hossain A, Desaiah D, Gaich GA. Effect of teriparatide [rhPTH(1-34)] on BMD when given to postmenopausal women receiving hormone replacement therapy. J Bone Miner Res. 2006 Feb. 21(2):283-91. [QxMD MEDLINE Link].
Tsai JN, Uihlein AV, Lee H, Kumbhani R, Siwila-Sackman E, McKay EA, et al. Teriparatide and denosumab, alone or combined, in women with postmenopausal osteoporosis: the DATA study randomised trial. Lancet. 2013 Jul 6. 382(9886):50-6. [QxMD MEDLINE Link].
Leder BZ, Tsai JN, Uihlein AV, Wallace PM, Lee H, Neer RM, et al. Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-Switch study): extension of a randomised controlled trial. Lancet. 2015 Sep 19. 386 (9999):1147-55. [QxMD MEDLINE Link].
Bouxsein ML, Chen P, Glass EV, Kallmes DF, Delmas PD, Mitlak BH. Teriparatide and raloxifene reduce the risk of new adjacent vertebral fractures in postmenopausal women with osteoporosis. Results from two randomized controlled trials. J Bone Joint Surg Am. 2009 Jun. 91(6):1329-38. [QxMD MEDLINE Link].
Kendler DL, Marin F, Zerbini CAF, Russo LA, Greenspan SL, Zikan V, et al. Effects of teriparatide and risedronate on new fractures in post-menopausal women with severe osteoporosis (VERO): a multicentre, double-blind, double-dummy, randomised controlled trial. Lancet. 2017 Nov 9. [QxMD MEDLINE Link].
Gomberg SJ, Wustrack RL, Napoli N, Arnaud CD, Black DM. Teriparatide, vitamin D, and calcium healed bilateral subtrochanteric stress fractures in a postmenopausal woman with a 13-year history of continuous alendronate therapy. J Clin Endocrinol Metab. 2011 Jun. 96(6):1627-32. [QxMD MEDLINE Link].
Saleh A, Hegde VV, Potty AG, Schneider R, Cornell CN, Lane JM. Management strategy for symptomatic bisphosphonate-associated incomplete atypical femoral fractures. HSS J. 2012 Jul. 8(2):103-10. [QxMD MEDLINE Link]. [Full Text].
Lau AN, Adachi JD. Resolution of osteonecrosis of the jaw after teriparatide [recombinant human PTH-(1-34)] therapy. J Rheumatol. 2009 Aug. 36(8):1835-7. [QxMD MEDLINE Link].
Cheung A, Seeman E. Teriparatide therapy for alendronate-associated osteonecrosis of the jaw. N Engl J Med. 2010 Dec 16. 363(25):2473-4. [QxMD MEDLINE Link].
Narongroeknawin P, Danila MI, Humphreys LG Jr, Barasch A, Curtis JR. Bisphosphonate-associated osteonecrosis of the jaw, with healing after teriparatide: a review of the literature and a case report. Spec Care Dentist. 2010 Mar-Apr. 30(2):77-82. [QxMD MEDLINE Link]. [Full Text].
Miller PD, Hattersley G, Riis BJ, Williams GC, Lau E, Russo LA, et al. Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial. JAMA. 2016 Aug 16. 316 (7):722-33. [QxMD MEDLINE Link]. [Full Text].
Cosman F, Miller PD, Williams GC, Hattersley G, Hu MY, Valter I, et al. Eighteen Months of Treatment With Subcutaneous Abaloparatide Followed by 6 Months of Treatment With Alendronate in Postmenopausal Women With Osteoporosis: Results of the ACTIVExtend Trial. Mayo Clin Proc. 2017 Feb. 92 (2):200-210. [QxMD MEDLINE Link]. [Full Text].
Czerwinski E, Cardona J, Plebanski R, Recknor C, Vokes T, Saag KG, et al. The Efficacy and Safety of Abaloparatide-SC in Men With Osteoporosis: A Randomized Clinical Trial. J Bone Miner Res. 2022 Dec. 37 (12):2435-2442. [QxMD MEDLINE Link]. [Full Text].
Peichl P, Holzer LA, Maier R, Holzer G. Parathyroid hormone 1-84 accelerates fracture-healing in pubic bones of elderly osteoporotic women. J Bone Joint Surg Am. 2011 Sep 7. 93(17):1583-7. [QxMD MEDLINE Link].
Cosman F, Crittenden DB, Adachi JD, Binkley N, Czerwinski E, Ferrari S, et al. Romosozumab Treatment in Postmenopausal Women with Osteoporosis. N Engl J Med. 2016 Sep 18. [QxMD MEDLINE Link]. [Full Text].
Saag KG, Petersen J, Brandi ML, Karaplis AC, Lorentzon M, Thomas T, et al. Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis. N Engl J Med. 2017 Oct 12. 377 (15):1417-1427. [QxMD MEDLINE Link]. [Full Text].
Lewiecki EM, Dinavahi RV, Lazaretti-Castro M, Ebeling PR, Adachi JD, Miyauchi A, et al. One Year of Romosozumab Followed by Two Years of Denosumab Maintains Fracture Risk Reductions: Results of the FRAME Extension Study. J Bone Miner Res. 2019 Mar. 34 (3):419-428. [QxMD MEDLINE Link].
Lewiecki EM, Blicharski T, Goemaere S, Lippuner K, Meisner PD, Miller PD, et al. A Phase III Randomized Placebo-Controlled Trial to Evaluate Efficacy and Safety of Romosozumab in Men With Osteoporosis. J Clin Endocrinol Metab. 2018 Sep 1. 103 (9):3183-3193. [QxMD MEDLINE Link].
Saag KG, Petersen J, Brandi ML, Karaplis AC, Lorentzon M, Thomas T, et al. Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis. N Engl J Med. 2017 Oct 12. 377 (15):1417-1427. [QxMD MEDLINE Link].
Body JJ, Facon T, Coleman RE, Lipton A, Geurs F, Fan M, et al. A study of the biological receptor activator of nuclear factor-kappaB ligand inhibitor, denosumab, in patients with multiple myeloma or bone metastases from breast cancer. Clin Cancer Res. 2006 Feb 15. 12(4):1221-8. [QxMD MEDLINE Link].
McClung MR, Lewiecki EM, Cohen SB, Bolognese MA, Woodson GC, Moffett AH, et al. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med. 2006 Feb 23. 354(8):821-31. [QxMD MEDLINE Link].
Orwoll E, Teglbjærg CS, Langdahl BL, Chapurlat R, Czerwinski E, Kendler DL, et al. A randomized, placebo-controlled study of the effects of denosumab for the treatment of men with low bone mineral density. J Clin Endocrinol Metab. 2012 Sep. 97(9):3161-9. [QxMD MEDLINE Link].
Block GA, Bone HG, Fang L, Lee E, Padhi D. A single-dose study of denosumab in patients with various degrees of renal impairment. J Bone Miner Res. 2012 Jul. 27(7):1471-9. [QxMD MEDLINE Link]. [Full Text].
Saag KG, Wagman RB, Geusens P, Adachi JD, Messina OD, Emkey R, et al. Denosumab versus risedronate in glucocorticoid-induced osteoporosis: a multicentre, randomised, double-blind, active-controlled, double-dummy, non-inferiority study. Lancet Diabetes Endocrinol. 2018 Apr 6. [QxMD MEDLINE Link].
Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009 Aug 20. 361(8):756-65. [QxMD MEDLINE Link].
Smith MR, Egerdie B, Hernández Toriz N, Feldman R, Tammela TL, Saad F, et al. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med. 2009 Aug 20. 361(8):745-55. [QxMD MEDLINE Link].
Lyu H, Jundi B, Xu C, Tedeschi SK, Yoshida K, Zhao S, et al. Comparison of Denosumab and Bisphosphonates in Patients With Osteoporosis: A Meta-Analysis of Randomized Controlled Trials. J Clin Endocrinol Metab. 2019 May 1. 104 (5):1753-1765. [QxMD MEDLINE Link].
Schwarz EM, Ritchlin CT. Clinical development of anti-RANKL therapy. Arthritis Res Ther. 2007. 9 Suppl 1:S7. [QxMD MEDLINE Link]. [Full Text].
Tsai JN, Uihlein AV, Lee H, Kumbhani R, Siwila-Sackman E, McKay EA, et al. Teriparatide and denosumab, alone or combined, in women with postmenopausal osteoporosis: the DATA study randomised trial. Lancet. 2013 May 14. [QxMD MEDLINE Link].
Anastasilakis AD, Polyzos SA, Makras P, Aubry-Rozier B, Kaouri S, Lamy O. Clinical Features of 24 Patients With Rebound-Associated Vertebral Fractures After Denosumab Discontinuation: Systematic Review and Additional Cases. J Bone Miner Res. 2017 Jun. 32 (6):1291-1296. [QxMD MEDLINE Link].
Postmarket Drug Safety Information for Patients and Providers-Questions and Answers: Changes to the Indicated Population for Miacalcin (calcitonin-salmon). U.S. Food and Drug Administration. Available at http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm388641.htm. September 1, 2015; Accessed: January 21, 2021.
Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA. 2002 Jul 17. 288(3):321-33. [QxMD MEDLINE Link].
Blake GM, Fogelman I. Long-term effect of strontium ranelate treatment on BMD. J Bone Miner Res. 2005 Nov. 20(11):1901-4. [QxMD MEDLINE Link].
Burlet N, Reginster JY. Strontium ranelate: the first dual acting treatment for postmenopausal osteoporosis. Clin Orthop Relat Res. 2006 Feb. 443:55-60. [QxMD MEDLINE Link].
Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, Staehelin HB, Bazemore MG, Zee RY, et al. Effect of Vitamin D on falls: a meta-analysis. JAMA. 2004 Apr 28. 291(16):1999-2006. [QxMD MEDLINE Link].
Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011 Jan. 96(1):53-8. [QxMD MEDLINE Link]. [Full Text].
Bruni V, Dei M, Filicetti MF, Balzi D, Pasqua A. Predictors of bone loss in young women with restrictive eating disorders. Pediatr Endocrinol Rev. 2006 Jan. 3 Suppl 1:219-21. [QxMD MEDLINE Link].
Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet. 2007 Aug 25. 370(9588):657-66. [QxMD MEDLINE Link].
Bischoff-Ferrari HA, Willett WC, Wong JB, Stuck AE, Staehelin HB, Orav EJ, et al. Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch Intern Med. 2009 Mar 23. 169(6):551-61. [QxMD MEDLINE Link].
Warensjö E, Byberg L, Melhus H, et al. Dietary calcium intake and risk of fracture and osteoporosis: prospective longitudinal cohort study. BMJ. 2011 May 24. 342:d1473. [QxMD MEDLINE Link]. [Full Text].
DIPART (Vitamin D Individual Patient Analysis of Randomized Trials) Group. Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe. BMJ. 2010 Jan 12. 340:b5463. [QxMD MEDLINE Link]. [Full Text].
Li K, Kaaks R, Linseisen J, Rohrmann S. Associations of dietary calcium intake and calcium supplementation with myocardial infarction and stroke risk and overall cardiovascular mortality in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition study (EPIC-Heidelberg). Heart. 2012 Jun. 98(12):920-5. [QxMD MEDLINE Link].
Curhan GC, Willett WC, Speizer FE, Spiegelman D, Stampfer MJ. Comparison of dietary calcium with supplemental calcium and other nutrients as factors affecting the risk for kidney stones in women. Ann Intern Med. 1997 Apr 1. 126(7):497-504. [QxMD MEDLINE Link].
Candelas G, Martinez-Lopez JA, Rosario MP, Carmona L, Loza E. Calcium supplementation and kidney stone risk in osteoporosis: a systematic literature review. Clin Exp Rheumatol. 2012 Nov-Dec. 30(6):954-61. [QxMD MEDLINE Link].
Favus MJ. The risk of kidney stone formation: the form of calcium matters. Am J Clin Nutr. 2011 Jul. 94(1):5-6. [QxMD MEDLINE Link].
Sinaki M. Postmenopausal spinal osteoporosis: physical therapy and rehabilitation principles. Mayo Clin Proc. 1982 Nov. 57(11):699-703. [QxMD MEDLINE Link].
Tinetti ME, Speechley M. Prevention of falls among the elderly. N Engl J Med. 1989 Apr 20. 320(16):1055-9. [QxMD MEDLINE Link].
Sinaki M, Mikkelsen BA. Postmenopausal spinal osteoporosis: flexion versus extension exercises. Arch Phys Med Rehabil. 1984 Oct. 65(10):593-6. [QxMD MEDLINE Link].
Sinaki M, Itoi E, Wahner HW, Wollan P, Gelzcer R, Mullan BP, et al. Stronger back muscles reduce the incidence of vertebral fractures: a prospective 10 year follow-up of postmenopausal women. Bone. 2002 Jun. 30(6):836-41. [QxMD MEDLINE Link].
Sinaki M, Itoi E, Rogers JW, Bergstralh EJ, Wahner HW. Correlation of back extensor strength with thoracic kyphosis and lumbar lordosis in estrogen-deficient women. Am J Phys Med Rehabil. 1996 Sep-Oct. 75(5):370-4. [QxMD MEDLINE Link].
Chien MY, Wu YT, Hsu AT, Yang RS, Lai JS. Efficacy of a 24-week aerobic exercise program for osteopenic postmenopausal women. Calcif Tissue Int. 2000 Dec. 67(6):443-8. [QxMD MEDLINE Link].
Snow CM, Shaw JM, Winters KM, Witzke KA. Long-term exercise using weighted vests prevents hip bone loss in postmenopausal women. J Gerontol A Biol Sci Med Sci. 2000 Sep. 55(9):M489-91. [QxMD MEDLINE Link].
Howe TE, Shea B, Dawson LJ, et al. Exercise for preventing and treating osteoporosis in postmenopausal women. Cochrane Database Syst Rev. 2011 Jul 6. CD000333. [QxMD MEDLINE Link].
Iwamoto J, Takeda T, Ichimura S. Effect of exercise training and detraining on bone mineral density in postmenopausal women with osteoporosis. J Orthop Sci. 2001. 6(2):128-32. [QxMD MEDLINE Link].
Kerschan-Shindl K, Uher E, Kainberger F, Kaider A, Ghanem AH, Preisinger E. Long-term home exercise program: effect in women at high risk of fracture. Arch Phys Med Rehabil. 2000 Mar. 81(3):319-23. [QxMD MEDLINE Link].
Robertson MC, Devlin N, Gardner MM, Campbell AJ. Effectiveness and economic evaluation of a nurse delivered home exercise programme to prevent falls. 1: Randomised controlled trial. BMJ. 2001 Mar 24. 322(7288):697-701. [QxMD MEDLINE Link]. [Full Text].
Walker M, Klentrou P, Chow R, Plyley M. Longitudinal evaluation of supervised versus unsupervised exercise programs for the treatment of osteoporosis. Eur J Appl Physiol. 2000 Nov. 83(4 -5):349-55. [QxMD MEDLINE Link].
Wolf SL, Barnhart HX, Kutner NG, McNeely E, Coogler C, Xu T. Reducing frailty and falls in older persons: an investigation of Tai Chi and computerized balance training. Atlanta FICSIT Group. Frailty and Injuries: Cooperative Studies of Intervention Techniques. J Am Geriatr Soc. 1996 May. 44(5):489-97. [QxMD MEDLINE Link].
Carter ND, Khan KM, Petit MA, Heinonen A, Waterman C, Donaldson MG, et al. Results of a 10 week community based strength and balance training programme to reduce fall risk factors: a randomised controlled trial in 65-75 year old women with osteoporosis. Br J Sports Med. 2001 Oct. 35(5):348-51. [QxMD MEDLINE Link]. [Full Text].
Riggs BL, Melton LJ 3rd. The prevention and treatment of osteoporosis. N Engl J Med. 1992 Aug 27. 327(9):620-7. [QxMD MEDLINE Link].
Iwamoto J, Sato Y, Uzawa M, Takeda T, Matsumoto H. Comparison of effects of alendronate and raloxifene on lumbar bone mineral density, bone turnover, and lipid metabolism in elderly women with osteoporosis. Yonsei Med J. 2008 Feb 29. 49(1):119-28. [QxMD MEDLINE Link]. [Full Text].
Gourlay ML, Fine JP, Preisser JS, May RC, Li C, Lui LY, et al. Bone-density testing interval and transition to osteoporosis in older women. N Engl J Med. 2012 Jan 19. 366(3):225-33. [QxMD MEDLINE Link]. [Full Text].
Schwab P, Klein RF. Nonpharmacological approaches to improve bone health and reduce osteoporosis. Curr Opin Rheumatol. 2008 Mar. 20(2):213-7. [QxMD MEDLINE Link].
Lin JT, Lane JM. Nonmedical management of osteoporosis. Curr Opin Rheumatol. 2002 Jul. 14(4):441-6. [QxMD MEDLINE Link].
Gourlay ML, Fine JP, Preisser JS, May RC, Li C, Lui LY, et al. Bone-density testing interval and transition to osteoporosis in older women. N Engl J Med. 2012 Jan 19. 366(3):225-33. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Viswanathan M, Reddy S, Berkman N, Cullen K, Middleton JC, Nicholson WK, et al. Screening to Prevent Osteoporotic Fractures: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2018 Jun 26. 319 (24):2532-2551. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Updates to the Clinician’s Guide to the Prevention and Treatment of Osteoporosis. National Osteoporosis Foundation. Available at https://my.nof.org/bone-source/Incorporation-of-diagnostic-criteria-to-be-used-to-establish-a-clinical-diagnosis-of-osteoporosis. November 11, 2015; Accessed: January 21, 2021.
[Guideline] Eastell R, Rosen CJ, Black DM, Cheung AM, Murad MH, Shoback D. Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society* Clinical Practice Guideline. J Clin Endocrinol Metab. 2019 Mar 25. [QxMD MEDLINE Link]. [Full Text].
NIH Consensus conference. Optimal calcium intake. NIH Consensus Development Panel on Optimal Calcium Intake. JAMA. 1994 Dec 28. 272(24):1942-8. [QxMD MEDLINE Link].

Media Gallery

Osteoporosis. Lateral radiograph demonstrates multiple osteoporotic vertebral compression fractures. Kyphoplasty has been performed at one level.
Osteoporosis. Lateral radiograph of the patient seen in the previous image following kyphoplasty performed at 3 additional levels.
Osteoporosis of the spine. Observe the considerable reduction in overall vertebral bone density and note the lateral wedge fracture of L2.
Osteoporosis of the spine. Note the lateral wedge fracture in L3 and the central burst fracture in L5. The patient had suffered a recent fall.
Normal femoral anatomy.
Stable intertrochanteric fracture of the femur.
Percutaneous vertebroplasty, transpedicular approach.
Asymmetric loss in vertebral body height, without evidence of an acute fracture, can develop in patients with osteoporosis. These patients become progressively kyphotic (as shown) over time, and the characteristic hunched-over posture of severe osteoporosis develops eventually.
In kyphoplasty, a KyphX inflatable bone tamp is percutaneously advanced into the collapsed vertebral body (A). It is then inflated, (B) elevating the depressed endplate, creating a central cavity, and compacting the remaining trabeculae to the periphery. Once the balloon tamp is deflated and withdrawn, the cavity (C) is filled under low pressure with a viscous preparation of methylmethacrylate (D).
Osteoporosis is defined as a loss of bone mass below the threshold of fracture. This slide (methylmethacrylate embedded and stained with Masson's trichrome) demonstrates the loss of connected trabecular bone.
The bone loss of osteoporosis can be severe enough to create separate bone "buttons" with no connection to the surrounding bone. This easily leads to insufficiency fractures.
Inactive osteoporosis is the most common form and manifests itself without active osteoid formation.
Osteoporosis that is active contains osteoid seams (red here in the Masson's trichrome).
Woven bone arising directly from surrounding mesenchymal tissue.
This image depicts bone remodeling with osteoclasts resorbing one side of a bony trabecula and osteoblasts depositing new bone on the other side.
Osteoclast, with bone below it. This image shows typical distinguishing characteristics of an osteoclast: a large cell with multiple nuclei and a "foamy" cytosol.
In this image, several osteoblasts display a prominent Golgi apparatus and are actively synthesizing osteoid. Two osteocytes can also be seen.
Severe osteoporosis. This radiograph shows multiple vertebral crush fractures. Source: Government of Western Australia Department of Health.
Lateral spine radiograph depicting osteoporotic wedge fractures of L1-L2. Source: Wikimedia Commons.
Dual-energy computed tomography (CT) scan in a patient with involutional osteoporosis. Insufficiency fractures of the sacrum and the pubic rami are seen on an isotopic bone scan as a characteristic H, or Honda, sign (arrows), which appears as intense radiopharmaceutical uptake at the fracture sites.
Schematic example of an early bone densitometer: the QDR-1000 System (spine scan). (From: Third National Health and Nutrition Examination Survey Bone Densitometry Manual. Rockville, Md: Westat, Inc; 1989 [revised].)
Bone density scanner. This machine measures bone density to check for osteoporosis in the elderly and other vulnerable subjects. Source: Wikimedia Commons.
Example of a dual energy x-ray absorption (DXA) scan. This image is of the left hip bone. Source: Government of Western Australia Department of Health.
Example of a dual energy x-ray absorption (DXA) scan. This image is of the lumbar spine. Source: Government of Western Australia Department of Health.

of 24

Table 1. WHO Definition of Osteoporosis Based on BMD Measurements by DXA

Definition	Bone Mineral Density Measurement	T-Score
Normal	BMD within 1 SD of the mean bone density for young adult women	T-score ≥ –1
Low bone mass (osteopenia)	BMD 1–2.5 SD below the mean for young adult women	T-score between –1 and –2.5
Osteoporosis	BMD ≥2.5 SD below the normal mean for young-adult women	T-score ≤ –2.5
Severe or “established” osteoporosis	BMD ≥2.5 SD below the normal mean for young-adult women in a patient who has already experienced ≥1 fracture	T-score ≤ –2.5 (with fragility fracture[s])
Sources: (1) World Health Organization (WHO). WHO scientific group on the assessment of osteoporosis at primary health care level: summary meeting report. Available at: https://www.who.int/chp/topics/Osteoporosis.pdf. Accessed August 21, 2020^[18] (2) Kanis JA. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int. Nov 1994;4(6):368-81.^[10] (3) Czerwinski E, Badurski JE, Marcinowska-Suchowierska E, Osieleniec J. Current understanding of osteoporosis according to the position of the World Health Organization (WHO) and International Osteoporosis Foundation. Ortop Traumatol Rehabil. Jul-Aug 2007;9(4):337-56.^[9] BMD = bone mineral density; DXA = dual x-ray absorptiometry; SD = standard deviation; T-score = a measurement expressed in SD units from a given mean that is equal to a patient's BMD measured by DXA minus the value in a young healthy person, divided by the SD measurement in the population.

Table 2. Types of Primary Osteoporosis

Type of Primary Osteoporosis	Characteristics
Juvenile osteoporosis	Usually occurs in children or young adults of both sexes Normal gonadal function Age of onset: usually 8-14 years Hallmark characteristic: abrupt bone pain and/or a fracture following trauma
Idiopathic osteoporosis
Postmenopausal osteoporosis (type I osteoporosis)	Occurs in women with estrogen deficiency Characterized by a phase of accelerated bone loss, primarily from trabecular bone Fractures of the distal forearm and vertebral bodies common
Age-associated or senile osteoporosis (type II osteoporosis)	Occurs in women and men as BMD gradually declines with aging Represents bone loss associated with aging Fractures occur in cortical and trabecular bone Wrist, vertebral, and hip fractures often seen

Table 3. Causes of Secondary Osteoporosis in Adults

Cause	Examples
Genetic/congenital	Renal hypercalciuria – one of the most important secondary causes of osteoporosis; can be treated with thiazide diuretics Cystic fibrosis Ehlers-Danlos syndrome Glycogen storage disease Gaucher disease Marfan syndrome Menkes steely hair syndrome Riley-Day syndrome Osteogenesis imperfecta Hemochromatosis Homocystinuria Idiopathic hypercalciuria Hypogonadal states
Hypogonadal states	Androgen insensitivity Anorexia nervosa/bulimia nervosa Female athlete triad Hyperprolactinemia Panhypopituitarism Premature menopause Turner syndrome Klinefelter syndrome
Endocrine disorders^[56]	Cushing syndrome Diabetes mellitus Acromegaly Adrenal insufficiency Estrogen deficiency Growth hormone deficiency Hypercortisolism Hyperparathyroidism Hyperthyroidism Hypogonadism Hypophosphatasia Pregnancy Porphyria Prolactinoma
Deficiency states and malabsorption syndromes	Alcoholism Anorexia nervosa Calcium deficiency Magnesium deficiency Protein deficiency Vitamin D deficiency^{[56, 57]} Bariatric surgery Celiac disease Cystic fibrosis Gastrectomy Malnutrition Parenteral nutrition Chronic liver disease
Inflammatory diseases	Inflammatory bowel disease/Crohn disease Ankylosing spondylitis Rheumatoid arthritis Systemic lupus erythematosus
Hematologic and neoplastic disorders	Hemochromatosis Hemophilia Leukemia Lymphoma Multiple myeloma Sickle cell anemia Systemic mastocytosis Thalassemia Metastatic disease
Medications	Anticonvulsants Antipsychotic drugs Antiretroviral drugs Aromatase inhibitors Chemotherapeutic/transplant drugs: cyclosporine, tacrolimus, platinum compounds, cyclophosphamide, ifosfamide, high-dose methotrexate^[58] Furosemide Glucocorticoids and corticotropin^[59]: prednisone (≥5 mg/day for ≥3 mo)^[60] Heparin (long term) Hormonal/endocrine therapies: gonadotropin-releasing hormone (GnRH) agonists, luteinizing hormone-releasing hormone (LHRH) analogues, depomedroxyprogesterone, excessive thyroxine Lithium Proton pump inhibitors Selective serotonin reuptake inhibitors (SSRIs) SGLT2- inhibitors Thiazolidinediones
Miscellaneous	Amyloidosis Chronic metabolic acidosis Chronic heart failure Chronic obstructive pulmonary disease (COPD) Chronic or end-stage renal disease HIV/AIDS Idiopathic scoliosis Immobility Major Depression Multiple sclerosis Ochronosis Organ transplantation Renal insufficiency/ failure Renal tubular acidosis Sarcoidosis Weightlessness^[61]
Sources: (1) American Association of Clinical Endocrinologists medical guidelines for clinical practice for the prevention and treatment of postmenopausal osteoporosis: 2020 update. Endocr Pract. May2020; 26(Suppl 1):1-46.^[11] (2) Kelman A, Lane NE. The management of secondary osteoporosis. Best Pract Res Clin Rheumatol. Dec 2005;19(6):1021-37.^[54]

Table 4. Prevalence of Osteoporosis Among Racial and Ethnic Groups

Race/Ethnicity	Sex (age ≥50 y)	% Estimated to have osteoporosis	% Estimated to have low bone mass
Non-Hispanic white; Asian	Women	15.8	52.6
Non-Hispanic white; Asian	Men	3.9	36
Non-Hispanic black	Women	7.7	36.2
Non-Hispanic black	Men	1.3	21.3
Hispanic	Women	20.4	47.8
Hispanic	Men	5.9	38.3
Source: Wright NC, Looker AC, Saag KG, Curtis JR, Delzell ES, Randall S, et al. The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res. Nov 2014;29(11):2520-6. [QxMD MEDLINE Link].

Table 5. Baseline Laboratory Studies for Underlying Disorders in Osteoporosis

Baseline test	Disorder
Complete blood count (CBC)	CBC results may reveal anemia, as in sickle cell disease (patients with anemia, particularly those older than 60 years, should also be evaluated for multiple myeloma), and may raise the suspicion for alcohol abuse (in conjunction with results from serum chemistry tests and liver function tests)
Serum chemistry levels	Calcium levels can reflect underlying disease states (eg, severe hypercalcemia may reflect underlying malignancy or hyperparathyroidism; hypocalcemia can contribute to osteoporosis) Levels of serum calcium, phosphate, and alkaline phosphatase are usually normal in persons with primary osteoporosis, although alkaline phosphatase levels may be elevated for several months after a fracture Levels of serum calcium, phosphate, and alkaline phosphatase may be obtained to assess osteomalacia Creatinine levels may decrease with increasing parathyroid hormone (PTH) levels or may be elevated in patients with multiple myeloma Creatinine levels are also used to estimate creatinine clearance, which may indicate reduced renal function in elderly patients Magnesium is very important in calcium homeostasis^[117]; decreased levels of magnesium may affect calcium absorption and metabolism
Liver function tests	Increased levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), bilirubin, and alkaline phosphatase may indicate alcohol abuse An elevated level of alkaline phosphatase in combination with normal calcium, phosphate, and aminotransferase should prompt consideration of Paget disease
Thyroid-stimulating hormone (TSH) level	Thyroid dysfunction has been associated with osteoporosis and should therefore be ruled out^[118]
25-Hydroxyvitamin D level	This test assesses for vitamin D insufficiency; inadequate vitamin D levels can predispose persons to osteoporosis through a mechanism of secondary hyperparathyroidism If vitamin D insufficiency and bone pain are present, consider the alternative diagnosis of osteomalacia

Table 6. Tests for Secondary Causes of Osteoporosis

Tests for Secondary Causes of Osteoporosis	Disorder
24-Hour urine calcium level	This study assesses for hypercalciuria and hypocalciuria
Parathyroid hormone (PTH) level	An intact PTH result is essential in ruling out hyperparathyroidism; an elevated PTH level may be present in benign familial hypocalciuric hypercalcemia
Thyrotropin level (if on thyroid replacement)	Experts are divided on whether to include thyrotropin testing, regardless of a history of thyroid disease or replacement; however, one study showed reduced femoral neck bone mineral density (BMD) in women with subclinical hypothyroidism and hyperthyroidism^[118]
Testosterone and gonadotropin levels in younger men with low bone densities	These tests may help evaluate a sex hormone deficiency as a secondary cause of osteoporosis
Urinary free cortisol level and tests for adrenal hypersecretion	These tests are used to exclude Cushing syndrome, which, although uncommon, can lead to rapidly progressive osteoporosis when the condition is present; a urine free cortisol value or overnight dexamethasone suppression test should be ordered in suspected cases
Serum protein electrophoresis (SPEP) and urine protein electrophoresis (UPEP)	These are used to identify multiple myeloma
Antigliadin, antiendomysial, and anti-tissue transglutaminase (TTG) IgA antibodies	These tests can help identify celiac disease. A concomitant total IgA level is needed for interpretation, in case of IgA deficiency.
Serum tryptase and urine N-methylhistamine	These tests help identify mastocytosis
Bone marrow biopsy	This study is obtained when a hematologic disorder is suspected

Back to List

Author

Rachel Elizabeth Whitaker Elam, MD, MSc Fellow, Department of Rheumatology, Medical College of Georgia at Augusta University

Rachel Elizabeth Whitaker Elam, MD, MSc is a member of the following medical societies: Alpha Omega Alpha, American College of Rheumatology, Georgia Society of Rheumatology

Disclosure: Nothing to disclose.

Coauthor(s)

Nicola Natasha Jackson, MBBS Resident Physician, Department of Internal Medicine, Piedmont Athens Regional Medical Center

Disclosure: Nothing to disclose.

Wambui Machua, MD Rheumatologist, Piedmont Hospital

Wambui Machua, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology, Atlanta Medical Association, Georgia Society of Rheumatology, International Society for Clinical Densitometry, Medical Association of Atlanta, Medical Association of Georgia

Disclosure: Nothing to disclose.

Laura D Carbone, MD, MS, FACP Professor, Department of Internal Medicine, Section Chief of Rheumatology, Medical College of Georgia at Augusta University and Charlie Norwood Veterans Affairs Medical Center

Laura D Carbone, MD, MS, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Women's Association, American Society for Bone and Mineral Research, International Society for Clinical Densitometry, Society of General Internal Medicine

Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD Visiting Professor of Medicine, Division of Rheumatology, State University of New York Downstate Medical Center; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, Phi Beta Kappa

Disclosure: Nothing to disclose.

Additional Contributors

Kristine M Lohr, MD, MS Professor, Department of Internal Medicine, Interim Chief, Division of Rheumatology, Director, Rheumatology Training Program, University of Kentucky College of Medicine

Kristine M Lohr, MD, MS is a member of the following medical societies: American College of Physicians, American College of Rheumatology

Disclosure: Nothing to disclose.

Monique Bethel, MD Resident Physician, Department of Internal Medicine, Medical College of Georgia at Augusta University

Disclosure: Nothing to disclose.

Acknowledgements

Michael T Andary, MD, MS Professor, Residency Program Director, Department of Physical Medicine and Rehabilitation, Michigan State University College of Osteopathic Medicine

Michael T Andary, MD, MS is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Association of Neuromuscular and Electrodiagnostic Medicine, American Medical Association, and Association of Academic Physiatrists

Disclosure: Allergan Honoraria Speaking and teaching; Pfizer Honoraria Speaking and teaching

Harris Gellman, MD Consulting Surgeon, Broward Hand Center; Voluntary Clinical Professor of Orthopedic Surgery and Plastic Surgery, Departments of Orthopedic Surgery and Surgery, University of Miami, Leonard M Miller School of Medicine

Harris Gellman, MD is a member of the following medical societies: American Academy of Medical Acupuncture, American Academy of Orthopaedic Surgeons, American Orthopaedic Association, American Society for Surgery of the Hand, and Arkansas Medical Society