Sections

Osteoporosis

Presentation

History

Keep in mind that osteoporosis occurs in many people who have few or no risk factors for this condition. Often, patients who have not sustained a fracture do not report symptoms that would alert the clinician to suspect a diagnosis of osteoporosis; thus, this disease is a "silent thief" that generally does not become clinically apparent until a fracture occurs.

Screening at-risk populations is, therefore, essential; unfortunately, many women do not receive proper screening or treatment for osteoporosis, which, in turn, may result in improper management of this disease and its related complications.^[105]For example, the presence of a disorder known to cause secondary osteoporosis—such as rheumatoid arthritis, celiac disease, or Crohn disease—should increase a clinician’s suspicion that the patient may have osteoporosis and that screening may be indicated.

Multiple risk factors exist for osteoporosis. The National Osteoporosis Foundation (NOF) has categorized these risk factors into two categories: nonmodifiable and modifiable. Nonmodifiable risk factors include the following:

Personal history of fracture as an adult
History of fracture in a first-degree relative
White race
Advanced age
Female sex
Dementia
Poor health or fragility

Potentially modifiable risk factors include the following:

Current cigarette smoking
Low body weight (< 127 lb)
Estrogen deficiency such as that caused by early menopause (age < 45 years) or bilateral ovariectomy and prolonged premenopausal amenorrhea (>1 year)
Low lifelong calcium intake
Alcoholism ^[74]
Impaired eyesight despite adequate correction
Recurrent falls
Inadequate physical activity
Poor health or frailty

Assessment of fracture risk

A thorough history should be obtained to screen for and identify the presence of known risk factors for osteoporosis and osteoporotic fracture. Specifically, the history should focus on the following^{[106, 107]}:

Age (> 50 years), sex (female), and race (white or Asian)^[106]; the US Preventive Services Task Force (USPSTF) recommendations include screening for osteoporosis in women aged 65 years or older and in younger women with a fracture risk that is the same or greater than that of a 65-year-old white woman who has no additional risk factors^[107]
Family history of osteoporosis, particularly maternal history of fractures
Reproductive factors, especially regarding early menopause and estrogen replacement therapy: postmenopausal women are at high risk, as are women who have undergone hysterectomy and oophorectomy
Hypogonadal states: men with hypogonadism secondary to any genetic or other conditions are at higher risk^[106]; the USPSTF notes that there is insufficient current evidence to assess the risk versus benefit of screening for osteoporosis in men^[107]
Smoking: smokers are at higher risk
Alcohol consumption
Low levels of physical activity: immobility increases the risk^[65]; spinal cord injury and stroke cause physical impairment and are common causes of immobility
Strenuous exercise that results in amenorrhea (such as that which occurs in marathon runners)
Calcium and vitamin D intake
History of low-trauma "fragility" fracture in patients aged 40 years or older: a fragility fracture is defined as a fracture due to trauma that would not normally cause fracture (a force equal to or less than that resulting from a fall from standing height)
Signs of vertebral fracture (see below)
Coexisting medical conditions associated with bone loss: examples are hyperparathyroidism, hypogonadism, leukemia, rheumatoid arthritis, celiac disease, and Cushing syndrome^[108]
Medications associated with bone loss: examples are glucocorticoids, cyclosporine, anticonvulsants, heparin, lithium, and tacrolimus^[108]
Risk factors for falls in older patients: these include poor balance, orthostatic hypotension, weakness of the lower extremity muscles and deconditioning, use of medications with sedative effects, poor vision or hearing, and cognitive impairment

FRAX tool

The USPSTF did not find any studies that assessed whether patient outcomes are affected by the use of risk prediction instruments, either alone or in combination with bone measurement tests. Nevertheless, there are many validated instruments for predicting the risk for low bone mineral density (BMD) in postmenopausal women; few of these, however, have been validated for use in men.^[107]

The Fracture Risk Assessment (FRAX) tool, accessible to healthcare providers and patients, is a validated instrument used to estimate 10-year risks for fractures, including those for black, Asian, and Hispanic women.^[95]A 65-year-old white woman with no other risk factors has a 9.3% 10-year risk for any osteoporotic fracture. Generally, estimated fracture risks in nonwhite women are lower than those for white women of the same age.

Examples of white women aged 50 to 64 years with ≥10-year fracture risks, based on specific risk factors, include the following^[107]:

A 50-year-old current smoker with a body mass index (BMI) less than 21 kg/m ², daily alcohol use, and parental fracture history
A 55-year-old woman with a parental fracture history
A 60-year-old woman with a BMI less than 21 kg/m ² and daily alcohol use
A 60-year-old current smoker with daily alcohol use

Differentiating fracture types by history

Patients with acute insufficiency fractures may report a history of minimal or no trauma resulting in pain. They may report a fall from a standing or sitting position. Patients with compression fractures resulting in thoracic kyphosis may report iliocostal friction with associated abdominal protrusion, decreased tolerance for oral intake, and breathing difficulties. Patients with hip, pelvic, or sacral fractures may report pain that is worsened with weight-bearing.

Patients who have sustained a vertebral compression fracture may note progressive kyphosis with loss of height. They may also present with an episode of acute back pain after bending, lifting, or coughing. It should be noted, however, that two thirds of vertebral fractures are asymptomatic.

With respect to those vertebral fractures that are painful, typical subjective information may include the following:

The episode of acute pain may follow a fall or minor trauma.
Pain is localized to a specific, identifiable, vertebral level in the midthoracic to lower thoracic or upper lumbar spine.
The pain is described variably as sharp, nagging, or dull; movement may exacerbate pain; in some cases, pain radiates to the abdomen.
Pain is often accompanied by paravertebral muscle spasms exacerbated by activity and decreased by lying supine.
Patients often remain motionless in bed because they are afraid of exacerbating the pain.
Acute pain usually resolves after 4-6 weeks; in the setting of multiple fractures with severe kyphosis, the pain may become chronic.

Patients who have sustained a hip fracture may experience the following:

Pain in the groin, posterior buttock, anterior thigh, medial thigh, and/or medial knee during weight-bearing or attempted weight-bearing of the involved extremity
Diminished hip range of motion (ROM), particularly internal rotation and flexion
External rotation of the involved hip while in the resting position

Patients with osteoporosis may report lactose intolerance or celiac sprue. Celiac sprue has been shown to be associated with osteoporosis in approximately 5% of cases.

Physical Examination

Patients with suspected osteoporosis should undergo a comprehensive physical examination. The physical examination should begin with an inspection of the patient. Height measurement with a stadiometer at each visit may be useful. Examination of active and passive range of motion (ROM) assists in determining whether spine, hip, wrist, or other osseous pathology may be present. A thorough neurologic examination is essential to rule out spinal cord and/or peripheral nerve compromise.

The examination may elicit pain, or the patient may be pain free. Thoracic kyphosis may be present secondary to vertebral compression fractures, a dowager hump, and a history of loss of height. Patients may have an associated scoliosis.

Areas of concern include the following:

A history of loss of height
Low body weight (body mass index < 19 kg/m ²)
Signs that might indicate existing osteoporosis (eg, kyphosis or dowager hump; point tenderness over a vertebra or other suspected fracture site)
Signs suggestive of secondary osteoporosis
Signs in older patients that may indicate increased fall risk (eg, difficulty with balance or gait, orthostatic hypotension, lower-extremity weakness, poor vision or hearing, cognitive impairment)

A 10-year longitudinal study assessed the Timed Up and Go (TUG) test performance (a validated predictor of falling) and hip area BMD (bone mineral density calculated using bone area as opposed to bone volume). Using data from 1126 women (mean age, 75 years), the study noted that risks of nonvertebral fracture and hip fracture were significantly higher in those who had slow TUG test performance and normal hip BMD or both slow TUG test performance and low hip BMD. These results suggest that the TUG test is an independent risk factor for incident nonvertebral fracture; this inexpensive physical assessment may be beneficial in screening patients at increased risk of fracture.^[109]

Signs of fracture

Patients with vertebral compression fractures may demonstrate a thoracic kyphosis with an exaggerated cervical lordosis (dowager hump). This is followed by a loss of lumbar lordosis. After each episode of vertebral compression fracture and progressive kyphosis, the patient's height may decrease by 2-3 cm.

Patients with acute vertebral fractures may have point tenderness over the involved vertebrae. Palpation of the spinous processes often does not aid the examiner in localizing point tenderness, but percussion may be helpful in acute or subacute vertebral compression fractures.

Patients with hip fractures may have severe pain with ambulation. A FABER (flexion in abduction and external rotation) hip joint test may reveal limited ROM with end-range pain. Patients with hip fractures may show decreased weight-bearing on the fractured side or an antalgic gait pattern.

Patients with pubic and sacral fractures may report marked pain with ambulation and tenderness to palpation, percussion, or both. Furthermore, patients with sacral fractures may have pain with physical examination techniques used to assess the sacroiliac joint, such as the FABER, Gaenslen, or squish test.

Fractures in other parts of the body, including the distal radius and humerus, are typically painful and result in limited range of motion of the involved joint.

Signs of collagen defects

Patients with osteoporosis may have physical findings consistent with subtle collagen defects. These include a short fifth digit, dentinogenesis imperfecta, hyperlaxity, hearing loss, pes planus, bunions, and blue sclerae.

Balance difficulties

Patients with osteoporosis are known to have decreased balance, possibly secondary to differences in balance control strategies and sway amplitude. Patients may have difficulty performing tandem gait and performing single limb stance. Poor balance may be noted particularly in patients with severe kyphosis resulting from vertebral compression fractures because their altered center of gravity makes ambulation with a stable base of support difficult for them.^[3]

Fractures are the most common and serious complication of osteoporosis. Patients with osteoporosis are at high risk for recurrent fractures of the hips, vertebrae, ribs, and wrists.

Screening in Men

Although routinely screening men for osteoporosis is not as widespread a practice as that of screening in women, the US Preventive Services Task Force (USPSTF) indicates that using bone measurement tests in men may not only help to detect this disease but also prevent its associated burden of fractures and fracture-related illness.^[110] Approximately 30% of all hip fractures occur in men and the mortality is higher in men than in women.

In weighing the risk versus benefit of screening men, clinicians should consider that osteoporosis is a preventable condition and that the potential harm in screening is likely to be small and mostly due to cost, such as that required to increase the number of dual-energy x-ray absorptiometry (DXA) scanners available for screening.^[110]In addition, assuming that the risk versus benefit of therapy for osteoporosis is similar for men and women, the men who are most likely to benefit from screening would be those with a 10-year risk for osteoporotic fracture that is equal to or greater than that for 65-year-old white women who have no additional risk factors.^[110]It is important to note, however, that there is insufficient current evidence for assessing the risk versus benefit of screening for osteoporosis in men.

The American College of Physicians (ACP) has similar recommendations for screening of osteoporosis in men, including periodic evaluation of risk factors in older men before age 65 years (particularly men who do not choose to be screened) and obtaining DXA for men at increased risk for the disease who are candidates for drug therapy.^[111]Risk factors for osteoporosis in men include the following^[111]:

Age older than 70 years
Low body weight (body mass index [BMI] < 20 to 25 kg/m ²)
Greater than 10% weight loss (relative to the usual young or adult weight or weight loss in recent years)
Physical inactivity
Corticosteroid use
Androgen deprivation therapy
Previous fragility fracture

Like the USPSTF, the ACP recommends further research to assess osteoporosis screening tests in men, to determine whether risk factors for osteoporosis in women also apply to men.^[111]

Osteoporosis in men should be treated. However, there has been less drug study for osteoporosis in men compared with that of women.^[112]Only zoledronic acid has been studied and has shown a risk reduction of new fractures. In a study of 1199 men with osteoporosis, treatment with zoledronic acid resulted in a 67% reduction in the risk of new vertebral fractures.^[112] Other medications use in the treatment of osteoporosis in men include risedronate, strontium ranelate, teriparatide, and denosumab.^[112]

Complications

Vertebral fractures from osteoporosis may lead to prolonged immobilization and medication use, which carry a range of complications.^[113]

Complications of prolonged immobilization include the following:

Deep venous thrombosis/pulmonary embolism
Infections
Pressure sores
Decreased muscle strength, 10-15% per week
Decreased bone mass
Cardiac effects - postural hypotension, decreased cardiac function
Gastrointestinal effects - constipation, fecal impaction
Neurosensory side effects - restlessness, anxiety, depression, fear, rapid mood changes, insomnia, hostility, pain intolerance, impaired intellectual and perceptual functioning

Complications of the medications used to relieve symptoms of vertebral fractures include the following:

Narcotics - constipation, somnolence, dependence
Nonsteroidal anti-inflammatory drugs (NSAIDs) - peptic ulcer disease, cardiovascular effects, kidney and liver effects, aspirin-exacerbated respiratory effects
Muscle relaxants - somnolence, dizziness, anticholinergic effects, weakness

Differential Diagnoses

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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.

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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. [Medline].

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^[118]; 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^[119]
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^[119]
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

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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, Georgia Regents 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