Osteoporosis Treatment & Management

  • Author: Dana Jacobs-Kosmin, MD; Chief Editor: Herbert S Diamond, MD   more...
 
Updated: Apr 19, 2012
 

Approach Considerations

According to a clinical practice guideline by the American College of Physicians, because of the significant disability, morbidity, mortality, and expenses associated with osteoporotic fractures,[67] treatment is aimed at fracture prevention and includes modification of general lifestyle factors, such as increasing weight-bearing and muscle-strengthening exercise, which have been linked to fractures in epidemiologic studies and ensuring optimum calcium and vitamin D intake as adjunct to active antifracture therapy.[14]

Medical care includes the administration of adequate calcium, vitamin D, and anti-osteoporotic medication such as bisphosphonates,[78] parathyroid hormone (PTH), raloxifene, and estrogen.[66] In addition, potentially treatable underlying causes of osteoporosis such as hyperparathyroidism and hyperthyroidism should be ruled out or treated if detected.

Surgical care includes vertebroplasty and kyphoplasty. Vertebroplasty and kyphoplasty are minimally invasive spine procedures used for the management of painful osteoporotic vertebral compression fractures.

A 2008 literature review suggested that the use of "reminders plus education targeted to physicians and patients" can lead to increased bone mineral density (BMD) testing and greater use of osteoporosis medications.[79] In addition, a physician reminder in conjunction with a patient risk assessment strategy apparently 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.[2]

The first goal of rehabilitation in osteoporosis patients is to control pain if a fracture has occurred. Spinal compression fractures can be extremely painful and can cause short- and long-term morbidity. Oral analgesics on a regular schedule can be implemented. Pain-relieving modalities such as moist hot packs and transcutaneous electrical nerve stimulation should also be considered. During this period, monitoring the patient carefully for signs of constipation, urinary retention, and respiratory depression, which can occur with the use of narcotic analgesics, is essential.

A comfortable mechanical support for the spine and, in some cases, a thoracic orthosis may need to be prescribed. The primary reason for the application of a thoracic orthosis is to limit motion in the spine. The length of time a patient should wear a rigid spinal orthosis is undetermined. What is well known is that immobilization contributes to bone demineralization. During the early mobilization period, deep breathing exercises, pectoral and intercostal strengthening, and back conservation techniques need to be implemented.

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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.[66, 80]

Patients identified as at risk for osteoporosis (including children and adolescents) should undergo preventive measures, including adequate calcium intake, vitamin D intake, and exercise. It is recommended to counsel patients 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, discontinuing the drug as soon as possible, and supplementing with calcium and vitamin D.

Expert recommendations

The National Osteoporosis Foundation (NOF) recommends that pharmacologic therapy should be reserved for postmenopausal women and men aged 50 years or older who present with the following[35] :

  • A hip or vertebral fracture (vertebral fractures may be clinical or morphometric [ie, identified on a radiograph alone])
  • T-score of -2.5 or less at the femoral neck or spine after appropriate evaluation to exclude secondary causes
  • Low bone mass (T-score between -1.0 and -2.5 at the femoral neck or spine) and a 10-year probability of a hip fracture of 3% or greater or a 10-year probability of a major osteoporosis-related fracture of 20% or greater based on the US-adapted WHO algorithm

The American College of Physicians has reviewed the evidence and has proposed guidelines for pharmacologic treatments of osteoporosis.[67] The agents currently available for osteoporosis treatment include bisphosphonates, the selective estrogen-receptor modulator (SERM) raloxifene, calcitonin, denosumab, and an anabolic agent, teriparatide (human recombinant PTH [1-34]).[27, 81, 82] All therapies should be given with calcium and vitamin D supplementation.

Guidelines from the American Association of Clinical Endocrinologists (AACE), published in 2010, include the following recommendations for choosing drugs to treat osteoporosis[83] :

  • First-line agents: alendronate, risedronate, zoledronic acid, denosumab
  • Second-line agent: ibandronate
  • Second- or third-line agent: raloxifene
  • Last-line agent: calcitonin
  • Treatment for patients with very high fracture risk or in whom bisphosphonate therapy has failed: teriparatide

There are no studies that have shown that combination therapy with 2 or more agents have a greater effect on fracture reduction than single therapy. The AACE guidelines advise against the use of combination therapy, until the effect of combination therapy on fracture is better understood.

Bisphosphonates

Bisphosphonates are the most commonly used agents for osteoporosis. They have been employed for both treatment and prevention. Oral and intravenous options are available.

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 spinal and hip 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/wk, 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 alendronate/vitamin D3 (Fosamax Plus D) is indicated for the treatment of osteoporosis in men to increase bone mass.

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.[84]

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

Zoledronic acid

Zoledronic acid (Reclast) 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%. Zoledronic acid is a once-yearly intravenous infusion approved for the treatment of osteoporosis in men, in postmenopausal women, and in patients with glucocorticoid-induced osteoporosis.[85] 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.[86]

In September 2011, the FDA updated the prescribing information for zoledronic acid (Reclast) to provide improved information regarding the risk of kidney failure. Acute renal failure requiring dialysis and fatal outcomes have been reported to the FDA following the use of zoledronic acid. It is contraindicated with moderate to severe renal impairment (ie, CrCl < 35 mL/min) or in patients with evidence of acute renal impairment. Other risks for renal impairment include coadministration of zoledronic acid with nephrotoxic or diuretic medications, severe dehydration before or after administration, or advanced age.[87]

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.[88] Therefore, although the bisphosphonates are outstanding in their efficacy, bone turnover markers should be monitored. If these markers become profoundly suppressed, the patient should be taken off the bisphosphonates and given a rest period until return to therapeutic levels (N-telopeptide of collagen cross-links [NTx], 20-40).

Treatment interval and complications with bisphosphonate therapy

The limited trial data available regarding long-term treatment with bisphosphonates has raised questions about the optimal length of treatment with these medications.[89] This issue has become more important, given newly recognized complications of bisphosphonate use, including osteonecrosis of the jaw and atypical (subtrochanteric or femoral shaft) femur fractures (see the images below).

Normal femoral anatomy. Normal femoral anatomy. Stable intertrochanteric fracture of the femur. Stable intertrochanteric fracture of the femur.

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).[90] 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.[91]

The AACE recommends that if osteoporosis is mild, clinicians should consider a drug holiday after 4-5 years of bisphosphonate treatment; if fracture risk is high, a drug holiday of 1-2 years may be considered after 10 years of treatment.[83] BMD and bone turnover markers should be monitored during the drug holiday, and treatment should be restarted if density declines substantially, bone turnover markers increase, or a fracture occurs.[83]

Selective estrogen receptor modulator

Selective estrogen receptor modulators (SERMs) are considered to provide the beneficial effects of estrogen without the potentially adverse outcomes. Raloxifene (Evista) is 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. It has been shown to prevent bone loss, and data in females with osteoporosis have demonstrated that raloxifene causes a 35% reduction in the risk of vertebral fractures. It has also been shown to reduce the prevalence of invasive breast cancer.

Raloxifene may be most useful in younger postmenopausal women without severe osteoporosis. It has been shown to increase the incidence of deep vein thrombosis and hot flashes. 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.[92]

Parathyroid hormone

Teriparatide (Forteo) is a human recombinant parathyroid hormone (1-34) (PTH [1-34]) and is the only available 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, as well as 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.

When PTH is given continuously, it is associated with increased osteoclastic and osteoblastic turnover, leading to a net loss of bone. However, in an intermittent subcutaneous administration of 20 mcg/day, PTH has been demonstrated to lead to 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.[93, 94, 95]

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.[96]

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.[97]

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.[147] 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 by Deal et al and Ste-Marie et al on women have shown that the concurrent use of estrogen or raloxifene can enhance the bone-forming effects of teriparatide.[99, 98] Data on the use of PTH in men are much more limited, but they appear to have relatively comparable efficacy.

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.[100]

A study performed by the Austrian group using PTH 1-84 to treat pelvic fractures clearly demonstrated that the anabolic agent used in osteoporosis also has the ability to both increase the rate of union and enhance the speed of the process. Using CT evaluation of the fracture site, the authors not only proved their primary goal of improved fracture healing but also noted 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.[101]

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 should be reserved for patients who refuse or cannot tolerate estrogens or in whom estrogens 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 an analgesic property that makes it ideally suited for the treatment of acute vertebral fractures.

Calcitonin is an option for patients who are not candidates for other available osteoporosis treatments. 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.

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.[98] It decreases bone resorption by inhibiting osteoclast activity. Denosumab was approved by the US Food and Drug Administration in June 2010. It has been studied in cancer patients and in patients with postmenopausal osteoporosis.[102, 103]

It is indicated for the treatment of postmenopausal women with osteoporosis who are at high risk of fracture (defined as a history of osteoporotic fracture), have multiple risk factors for fracture, are intolerant to other available osteoporosis therapies, or in whom osteoporosis therapies have failed. In postmenopausal women with osteoporosis, denosumab reduces the incidence of vertebral, nonvertebral, and hip fractures.

Denosumab also increases bone mass in men at high risk for fracture who are receiving androgen deprivation therapy for nonmetastatic prostate cancer. In these patients, denosumab also reduces the incidence of vertebral fractures. It is also used to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer. Approved dosage is 60 mg given subcutaneously every 6 months.

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. Denosumab has been shown to increase BMD and decrease bone resorption in postmenopausal women with osteoporosis over a 12-month period.

In a randomized, placebo-controlled trial of 7868 women aged 60-90 years with osteoporosis who received either denosumab 60 mg SC or placebo every 6 months for 36 months, denosumab decreased the risk of vertebral, nonvertebral, and hip fractures.[104]

Smith et al reported a reduction in incident vertebral fractures when denosumab was used in 734 men receiving androgen-deprivation therapy for prostate cancer.[105] In this study, denosumab significantly increased lumbar spine, hip, femoral neck, and radial BMD.

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.[106]

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.

Data from the Women's Health Initiative confirmed that HRT can reduce fractures.[107] 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.[108, 109] Strontium is not approved for the treatment of osteoporosis in the United States.

Based on preliminary data that suggest women on nitrates have higher BMDs and lower fracture risk, Jamal et al conducted a randomized placebo-controlled trial of women who applied daily nitroglycerin ointment for 24 months.[110] The nitroglycerin ointment increased BMD and decreased bone resorption, although headaches were a limiting factor for many patients. Other nitrate preparations may be better tolerated and could show efficacy for fracture risk reduction.

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Vertebroplasty and Kyphoplasty

The goals of surgical treatment of osteoporotic fractures include rapid mobilization and return to normal function and activities. Traditional operative management of vertebral compression fractures is uncommon and is usually reserved for gross spinal deformity or for threatened or existing neurologic impairment.

Operative interventions include anterior and posterior decompression and stabilization with placement of such internal fixation devices as screws, plates, cages, or rods. Bone grafting is routinely performed to achieve bony union. The failure rate of spinal arthrodesis is significant because achieving adequate fixation of hardware in osteoporotic bone is difficult. Moreover, patients who are elderly have a reduced osteogenic potential.

Vertebroplasty and balloon kyphoplasty are indicated in patients with incapacitating and persistent severe focal back pain related to vertebral collapse (see the images below).

In kyphoplasty, a KyphX inflatable bone tamp is peIn 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). Reduction in kyphotic angulation after kyphoplastyReduction in kyphotic angulation after kyphoplasty. Osteoporosis. Lateral radiograph demonstrates multOsteoporosis. Lateral radiograph demonstrates multiple osteoporotic vertebral compression fractures. Kyphoplasty has been performed at one level. Osteoporosis. Lateral radiograph of the patient seOsteoporosis. Lateral radiograph of the patient seen in the previous image following kyphoplasty performed at 3 additional levels.

This procedure has been successful both in reducing the amount of kyphosis and in restoring vertebral body height. It also has successfully reduced pain. Studies have shown kyphoplasty to be a safe and minimally invasive spine procedure that results in improved function in elderly patients, allowing them to participate in increased activities, with resulting improvements in independence and quality of life.

For more information, see the Medscape Reference article Percutaneous Vertebroplasty and Kyphoplasty.

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Dietary Measures

Adequate calcium and vitamin D intake are important in persons of any age, particularly in childhood as the bones are maturing. Patients who ingest inadequate amounts of vitamin D and calcium should receive oral supplementation. Recommendations for patients with osteoporosis include daily dosages of 1200-1500 mg of calcium and 400-800 IU of vitamin D.

Adequate calcium intake is essential in the prevention and treatment of osteoporosis. Premenopausal women and men younger than 50 years without risk factors for osteoporosis should receive a total of 1000 mg of calcium daily. Postmenopausal women, men older than 50 years, and other persons at risk for osteoporosis should receive a daily calcium intake of 1200 mg. Good sources of calcium include dairy products, sardines, nuts, sunflower seeds, tofu, vegetables such as turnip greens, and fortified food such as orange juice. See the National Osteoporosis Foundation Website for further calcium recommendations.

Adults younger than 50 years should receive 400-800 IU of vitamin D3 daily. All adults older than 50 years should receive 800-1000 IU of vitamin D3 daily. Good 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 vitamin D recommendations.

A meta-analysis of 12 double-blind, randomized, controlled trials for nonvertebral fractures and 8 trials for hip fractures found that nonvertebral fracture prevention with vitamin D was dose dependent and that a higher dose reduced fractures by at least 20% for individuals aged 65 years or older.[111] 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.[112]

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,[113] 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

Calcium

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[83] :

  • 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
  • Age 50 years and older: 1200 mg/day
  • Pregnant and breastfeeding women age 18 years and younger: 1300 mg/day
  • Pregnant and breastfeeding women age 19 years and older: 1000 mg/day

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

Vitamin D is increasingly being recognized as a key element in overall bone health and muscle function. It plays a significant role in bone health, calcium absorption, balance (eg, reduction in risk of falls),[114] and muscle performance. The minimum daily requirement in patients with osteoporosis is 800 IU of vitamin D3, or 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 32 ng/mL.

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.

Calcium and vitamin D studies

Several large studies have demonstrated that supplementation with a combination of calcium and vitamin D can reduce fracture risk.[115] A meta-analysis showed that nonvertebral fracture prevention with vitamin D is dose-dependent and that a higher dose reduced fractures by at least 20% in individuals aged 65 years or older.[111]

Another meta-analysis concluded that vitamin D alone is not effective in preventing fractures, although, when administered with calcium, hip fractures and total fractures (and possibly vertebral fractures) were reduced.[116] The conclusions were based on 7 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. Bolland et al found that an increased risk for myocardial infarction was associated with calcium supplements.[117] This increased risk has not been associated with dietary calcium intake.

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Physical and Occupational Therapy

Physical therapy

Physical therapy focuses on improving a patient's strength, flexibility, posture, and balance to prevent falls and maximize physical function.[118, 119] 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.[120] In studies by Sinaki and colleagues, strengthening the back extensor muscles reduced kyphosis and decreased the risk of sustaining vertebral compression fractures.[121, 122]

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[32] 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.[119] 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, greatly improves home safety.

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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.[120]

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.[123]

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.[124]

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.[125]

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 a kyphosis.

The physical therapist must address balance training, because fall prevention is important in eliminating the complication of 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.[126, 127, 128, 129]

Tai chi chuan and specific physical therapy programs have been shown to be particularly 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%.[130]

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 improved their static balance, dynamic balance, and knee extension strength, although they did not benefit from a significant reduction in fall risk factors.[131]

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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 2 components: behavior modification and pharmacologic interventions.

The National Osteoporosis Foundation (NOF) specified that the following behaviors should be modified to reduce the risk of developing osteoporosis: cigarette smoking; physical inactivity; and intake of alcohol, caffeine, sodium, animal protein, and calcium.[35] Patients should be counseled on smoking cessation and moderated alcohol intake. Patients who have disorders or take medications that can cause or accelerate bone loss should receive calcium and vitamin D supplementation and, in some cases, pharmacologic treatment.[132]

Pharmacologic prevention methods include calcium supplementation and administration of raloxifene or bisphosphonates (alendronate or risedronate). Raloxifene and bisphosphonates should be considered as first-line agents for the prevention of osteoporosis.[133]

When alendronate or risedronate is used for prevention, the recommended dosage is the equivalent of 5 mg/d. In a study by Hosking et al, doses of 2.5 mg and 5 mg of alendronate were evaluated in postmenopausal women who did not have osteoporosis.[134] They found that the women who received placebo lost BMD at all measured sites, whereas the women treated with 5 mg/d of alendronate had a mean increase in BMD of 3.5% ± 0.2% at the lumbar spine, 1.9% ± 0.1% at the hip, and 0.7% ± 0.1% for the total body.

In 2010, the American College of Rheumatology published revised recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Recommendations included the categorization of patients by fracture risk (using the FRAX score) and initiation of treatment in appropriate patients including alendronate, risedronate, zoledronic acid, and teriparatide (in those patients at highest risk).[135]

Estrogen-progestin therapy is no longer considered a first-line approach for the treatment of osteoporosis in postmenopausal women, because it is associated with an increased risk for breast cancer, stroke, venous thromboembolism, and perhaps coronary disease. Estrogen is now only recommended 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 NOF, evaluating BMD on a periodic basis is the best way to monitor bone density and future fracture risk.[35] Bone density checks are recommended every 2 years in postmenopausal women. Regular weight-bearing exercises and back extensor strengthening help delay bone loss.

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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 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.[136, 137] Consult an orthopedist to assist with fracture management. Consultation with a spine surgeon is appropriate for patients with intractable, severe, function-limiting symptomatology 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.

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Long-Term Monitoring

Dual-energy x-ray absorptiometry (DXA) should be repeated every 2-3 years if the baseline test results are normal. DXA should be performed every 1-2 years in patients who are undergoing osteoporosis treatment.

The USPSTF 2011 recommendations, however, state that evidence is lacking regarding optimal intervals for repeated screening, as well as regarding whether a woman with normal BMD requires repeated screening.[66] “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.” According to a study funded by the National Institutes of Health, osteoporosis will develop in less than 10% of older, postmenopausal women during rescreening intervals of approximately 15 years for women with normal BMD or mild osteopenia; during rescreening intervals of approximately 5 years for women with moderate osteopenia; and during rescreening intervals of approximately 1 year for women with advanced osteopenia.”[138]

Orthotics are 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.[139, 140] Common orthotics used include the following:

  • Thoracolumbosacral orthosis (TLSO)
  • Cruciform anterior spinal hyperextension (CASH) brace
  • Jewett brace
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Contributor Information and Disclosures
Author

Dana Jacobs-Kosmin, MD  Attending Physician, Department of Medicine, Division of Rheumatology, Albert Einstein Medical Center; Clinical Assistant Professor of Medicine, Jefferson Medical College

Dana Jacobs-Kosmin, MD is a member of the following medical societies: American College of Physicians and American College of Rheumatology

Disclosure: Nothing to disclose.

Coauthor(s)

Sucharitha Shanmugam, MD  Consulting Physician, PMA Medical Specialists, Limerick, PA

Sucharitha Shanmugam, MD is a member of the following medical societies: American College of Rheumatology

Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD  Adjunct Professor of Medicine, Division of Rheumatology, University of Pittsburgh School of Medicine; 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, and Phi Beta Kappa

Disclosure: Merck Ownership interest Other; Smith Kline Ownership interest Other; Zimmer Ownership interest Other

Additional Contributors

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

Disclosure: Nothing to disclose.

Elliot Goldberg, MD Dean of the Western Pennsylvania Clinical Campus, Professor, Department of Medicine, Temple University School of Medicine

Elliot Goldberg, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, and American College of Rheumatology

Disclosure: Nothing to disclose.

Coburn Hobar, MD Clinician in Rheumatology, Hobar Health and Wellness, and Anti-Aging & Wellness Center of Sarasota

Coburn Hobar, MD is a member of the following medical societies: American Academy of Anti-Aging Medicine and American College of Rheumatology

Disclosure: Nothing to disclose.

Robert J Kaplan, MD James E Van Zandt VA Medical Center, Staff Physician, Department of Rehabilitation Medicine

Robert J Kaplan, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation

Disclosure: Nothing to disclose.

Joseph M Lane, MD  Professor of Orthopedic Surgery, Weill Medical College of Cornell University; Chief, Metabolic Bone Disease Service, Hospital for Special Surgery

Joseph M Lane, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American Association of University Professors, American Federation for Aging Research, American Orthopaedic Association, American Society for Bone and Mineral Research, Association of Bone and Joint Surgeons, Medical Society of the State of New York, Musculoskeletal Tumor Society, National Osteoporosis Foundation, North American Spine Society, and Orthopaedic Research Society

Disclosure: Lilly; Aventis; Novartis; Warner Chilcott; Biomimetics; Zimmer; DFine; Innovative Solutions; Honoraria Speaking and teaching; Graftys; Bone Technologies SA; CollPlant Consulting fee Consulting

David Lenrow, MD Vice Chair of Clinical Services, Medical Director, Erdman Clinic; Associate Professor, Department of Rehabilitation Medicine, University of Pennsylvania at Philadelphia

David Lenrow, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation and American Medical Assocation

Disclosure: Nothing to disclose.

Julie Lin, MD Assistant Professor, Department of Rehabilitation Medicine, Weill Medical College of Cornell University; Assistant Attending Physiatrist, Physiatry Department, Hospital for Special Surgery

Julie Lin, MD 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, North American Spine Society, and Physiatric Association of Spine, Sports and Occupational Rehabilitation

Disclosure: Nothing to disclose.

Elizabeth A Moberg-Wolff, MD Associate Professor, Department of Physical Medicine and Rehabilitation, Children's Hospital of Wisconsin, Medical College of Wisconsin

Elizabeth A Moberg-Wolff, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine and American Academy of Physical Medicine and Rehabilitation

Disclosure: Medtronic Neurological Grant/research funds Speaking and teaching

Srinivas R Nalamachu, MD Clinical Assistant Professor, Department of Internal Medicine, Kansas City University of Medicine and Biosciences; President and Medical Director, Internation Clinical Research Institute, Inc; Medical Director, Pain Management Institute

Srinivas R Nalamachu, MD is a member of the following medical societies: International Association for the Study of Pain

Disclosure: Nothing to disclose.

Richard Salcido, MD Chairman, Erdman Professor of Rehabilitation, Department of Physical Medicine and Rehabilitation, University of Pennsylvania School of Medicine

Richard Salcido, MD is a member of the following medical societies: American Academy of Pain Medicine, American Academy of Physical Medicine and Rehabilitation, American College of Physician Executives, American Medical Association, and American Paraplegia Society

Disclosure: Nothing to disclose.

Miguel A Schmitz, MD Consulting Surgeon, Department of Orthopedics, Klamath Orthopedic and Sports Medicine Clinic

Miguel A Schmitz, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American Orthopaedic Society for Sports Medicine, Arthroscopy Association of North America, and North American Spine Society

Disclosure: Nothing to disclose.

Alana C Serota, MD Fellow in Metabolic Bone Disease and Osteoporosis, Department of Orthopedics, Hospital for Special Surgery

Alana C Serota, MD is a member of the following medical societies: American Academy of Family Physicians

Disclosure: Nothing to disclose.

Curtis W Slipman, MD Director, University of Pennsylvania Spine Center; Associate Professor, Department of Physical Medicine and Rehabilitation, University of Pennsylvania Medical Center

Curtis W Slipman, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, Association of Academic Physiatrists, International Association for the Study of Pain, and North American Spine Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Shireesha Vuppalanchi, MD Consulting Staff, Methodist Hospital, Indianapolis; Hospitalist, Respiratory and Critical Care Consultants, PC

Disclosure: Nothing to disclose.

William S Whyte II, MD Director of Interventional Spine and Pain Management, Louisiana Pain Physicians

William S Whyte II, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Medical Association, Association of Academic Physiatrists, North American Spine Society, Physiatric Association of Spine, Sports and Occupational Rehabilitation, and Southern Medical Association

Disclosure: Nothing to disclose.

Jerome D Wiedel, MD Chair, Professor, Department of Orthopedics, University of Colorado Health Sciences Center

Disclosure: Nothing to disclose.

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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).
Reduction in kyphotic angulation after kyphoplasty.
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. http://www.imagingpathways.health.wa.gov.au/includes/dipmenu/osteo/image.html.
This radiograph of the spine shows a lateral wedge fracture of L3 (yellow asterisk) and compression fracture of L5 (red asterisk) in an osteoporotic patient who suffered a recent fall. More detailed imaging, usually with computed tomography (CT) scanning, is often needed to better evaluate compression fractures and to determine the urgency of surgical interventions.
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. http://www.imagingpathways.health.wa.gov.au/includes/dipmenu/osteo/image.html.
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. http://www.imagingpathways.health.wa.gov.au/includes/dipmenu/osteo/image.html.
Table 1. WHO Definition of Osteoporosis Based on BMD Measurements by DXA
Definition Bone Mass Density Measurement T-Score
NormalBMD within 1 SD of the mean bone density for young adult womenT-score ≥ –1
Low bone mass (osteopenia)BMD 1–2.5 SD below the mean for young-adult womenT-score between –1 and –2.5
OsteoporosisBMD ≥2.5 SD below the normal mean for young-adult womenT-score ≤ –2.5
Severe or “established” osteoporosisBMD ≥2.5 SD below the normal mean for young-adult women in a patient who has already experienced ≥1 fracturesT-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: http://www.who.int/chp/topics/Osteoporosis.pdf. Accessed February 6, 2012.[8]



(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.[7]



(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.[6]



BMD = bone mass 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.[9] .



Table 2. Types of Primary Osteoporosis
Type of Primary OsteoporosisCharacteristics
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 aged 50-65 years
  • 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 older than 70 years
  • Represents bone loss associated with aging
  • Fractures occur in cortical and trabecular bone
  • Wrist, vertebral, and hip fractures often seen in patients with type II osteoporosis
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
  • Hypophosphatasia
  • Idiopathic hypercalciuria
  • Porphyria
  • Hypogonadal states
Hypogonadal states
  • Androgen insensitivity
  • Anorexia nervosa/bulimia nervosa
  • Female athlete triad
  • Hyperprolactinemia
  • Panhypopituitarism
  • Premature menopause
  • Turner syndrome
  • Klinefelter syndrome
Endocrine disorders[24]
  • Cushing syndrome
  • Diabetes mellitus
  • Acromegaly
  • Adrenal insufficiency
  • Estrogen deficiency
  • Hyperparathyroidism
  • Hyperthyroidism
  • Hypogonadism
  • Pregnancy
  • Prolactinoma
Deficiency states
  • Calcium deficiency
  • Magnesium deficiency
  • Protein deficiency
  • Vitamin D deficiency[24, 25]
  • Bariatric surgery
  • Celiac disease
  • Gastrectomy
  • Malabsorption
  • Malnutrition
  • Parenteral nutrition
  • Primary biliary cirrhosis
Inflammatory diseases
  • Inflammatory bowel 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: phenytoin, barbiturates, carbamazepine (these agents are associated with treatment-induced vitamin D deficiency)
  • Antipsychotic drugs
  • Antiretroviral drugs
  • Aromatase inhibitors: exemestane, anastrozole
  • Chemotherapeutic/transplant drugs: cyclosporine, tacrolimus, platinum compounds, cyclophosphamide, ifosfamide, high-dose methotrexate[26]
  • Furosemide
  • Glucocorticoids and corticotropin[27] : prednisone (≥5 mg/day for ≥3 mo)[28]
  • Heparin (long term)
  • Hormonal/endocrine therapies: gonadotropin-releasing hormone (GnRH) agonists, luteinizing hormone-releasing hormone (LHRH) analogues, depomedroxyprogesterone, excessive thyroxine
  • Lithium
  • Selective serotonin reuptake inhibitors (SSRIs)
Miscellaneous
  • Alcoholism
  • Amyloidosis
  • Chronic metabolic acidosis
  • Congestive heart failure
  • Depression
  • Emphysema
  • Chronic or end-stage renal disease
  • Chronic liver disease
  • HIV/AIDS
  • Idiopathic scoliosis
  • Immobility
  • Multiple sclerosis
  • Ochronosis
  • Organ transplantation
  • Pregnancy/lactation
  • Sarcoidosis
  • Weightlessness
Sources:



(1) American Association of Clinical Endocrinologists medical guidelines for clinical practice for the prevention and treatment of postmenopausal osteoporosis: 2001 edition, with selected updates for 2003. Endocr Pract. Nov-Dec 2003;9(6):544-64.[21]



(2) Kelman A, Lane NE. The management of secondary osteoporosis. Best Pract Res Clin Rheumatol. Dec 2005;19(6):1021-37.[22]



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; AsianWomen2052
Men735
Non-Hispanic blackWomen5*
Men419
HispanicWomen1049
Men323
Source:  National Osteoporosis Foundation. Fast facts. Available at: http://www.nof.org/node/40. Accessed: February 16, 2012.[42]



* Low bone density is present in an additional 35% of black women, increasing their risk of developing osteoporosis.



Table 5. Comparison of Densitometry Techniques and Cost-Effectiveness
Single-photon absorptiometry Dual-photon absorptiometry Dual-energy x-ray absorptiometry Quantitative computed tomography
Time5-15 min20-30 min5-10 min10-30 min
Cost$50-150$150-300$100-200$150-300
Sites scannedRadius, forearm,



calcaneus



Spine, hip (anteroposterior)Spine (lateral), hip,



radius



Spine (lateral), hip,



radius



Source:  Nayak S, Roberts MS, Greenspan SL. Cost-effectiveness of different screening strategies for osteoporosis in postmenopausal women. Ann Intern Med. Dec 6 2011;155(11):751-61.[68]
Table 6. Baseline Studies for Baseline Conditions 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 levelsCalcium 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, alkaline phosphatase, and 25(OH) vitamin D 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[71] ; decreased levels of magnesium may affect calcium absorption and metabolism



Serum iron and ferritin levelsThese tests are helpful when malabsorption or hemochromatosis are suspected
Liver function testsIncreased levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), bilirubin, and alkaline phosphatase may indicate alcohol abuse
Thyroid-stimulating hormone (TSH) levelThyroid dysfunction has been associated with osteoporosis and should therefore be ruled out[72]
25-Hydroxyvitamin D levelThis test assesses for vitamin D insufficiency; inadequate vitamin D levels can predispose persons to osteoporosis
Table 7. Tests for Secondary Causes of Osteoporosis
Tests for Secondary Causes of Osteoporosis Disorder
24-Hour urine calcium levelThis study assesses for hypercalciuria to help rule out benign familial hypocalciuric hypercalcemia (FHH), in which urinary calcium levels are low
Parathyroid hormone (PTH) levelAn intact PTH result is essential in ruling out hyperparathyroidism; an elevated PTH level may be present in benign FHH
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[72]
Testosterone and gonadotropin levels in younger men with low bone densitiesThese tests may help evaluate a sex hormone deficiency as a secondary cause of osteoporosis
Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levelsSome practitioners include ESR and CRP values in the workup, although their utility in this setting has not been proven in an evidence-based manner
Urinary free cortisol level and tests for adrenal hypersecretionThese 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 and antiendomysial antibodiesThese tests can help identify celiac disease
Serum tryptase and urine N-methylhistamineThese tests help identify mastocytosis and are used to exclude the presence of multiple myeloma; serum tryptase may be performed to rule out plasma cell dyscrasias
Bone marrow biopsyThis study is obtained when a hematologic disorder is suspected
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