Osteoporosis: A Bare-Bones Guide to Diagnosis and Management
Osteoporosis is a progressive systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture.[1] It is a chronic condition of multifactorial etiology that is usually clinically silent for many years. Compared with normal bone (left), osteoporotic bone (right) shows thinning and loss of trabeculae; the result is very fragile bone. There is an increased risk for fractures, even after minimal trauma.
According to the Bone Health & Osteoporosis Foundation (formerly the National Osteoporosis Foundation), approximately 54 million Americans have osteoporosis or low bone mass,[2] and it is estimated that 12.3 million Americans have osteoporosis.[3] About 1 of every 2 White women will experience an osteoporosis-related fracture in her lifetime, as will approximately 1 of 5 men older than 50 years.[3] Two million fractures are attributed to osteoporosis annually in the United States, and this number is projected to rise to 3.2 million annually by 2040.[3]
The estimated annual cost of osteoporosis and related fractures was approximately $16 billion in 2011.[4] With an increasingly aged population, this number rose to $25 billion in 2025.[2] The image above shows the characteristic hunched-over posture of an individual with severe osteoporosis.
Adult bone undergoes constant remodeling to maintain strength. Bone mineral density (BMD) and bone architecture are the result of a balance between osteoclastic resorption and osteoblastic formation. Osteoblasts (top) produce new bone over a period of months. Hormonal and dietary factors influence the balance of bone production. Calcium, vitamin D, estrogen, and parathyroid hormone help maintain bone homeostasis.
Osteoclasts (bottom) resorb bone over a period of weeks and are especially active during periods of rapid remodeling (eg, after menopause). Osteoclasts and osteoblasts work in sequence to constantly replace and repair bone. Because osteoclasts work faster than osteoblasts, the rate of bone loss may outpace the rate of bone production. During these periods, the newly produced bone is at increased risk for fracture because it is less densely mineralized, collagen has not matured, and resorption sites are temporarily unfilled.[5]
Osteoporosis is typically asymptomatic until a fracture occurs. Spine and hip fractures are the two most common osteoporotic fractures, though osteoporotic fractures can occur in any bone.[6] Diagnosis should begin with a thorough review of risk factors, including family history, lifestyle factors, calcium and vitamin D intake, low-trauma fractures, signs of vertebral fractures, coexisting medical conditions, medications, and fall risk factors. Lifestyle factors associated with decreased bone density include smoking, excessive alcohol consumption, and limited physical activity. Asymmetric loss in vertebral body height, without evidence of an acute fracture, can develop in patients with osteoporosis. These patients become progressively kyphotic over time (a severe case is shown above), and the characteristic hunched-over posture of severe osteoporosis developed (see slide 2).
The Bone Health & Osteoporosis Foundation has categorized risk factors for osteoporosis and/or fracture as uncontrollable and controllable (shown above).[7] In osteoporosis screening, it is important to take a detailed patient history. It is essential to consider the history of a low-trauma "fragility" fracture (a fracture due to trauma that would not normally cause fracture) in patients aged 40 years or older, a patient's signs of vertebral fracture, a patient's risk factors for falls, and a patient's coexisting medical conditions that are associated with bone loss (eg, celiac disease). In addition, it is important to assess whether the patient is taking medications that are associated with bone loss.[7]
Image data from US Department of Health and Human Services. Diseases of bone. In: Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD: US Department of Health and Human Services, Office of the Surgeon General; 2004
Osteoporosis can be a result of hereditary or environmental factors. Many medical conditions are risk factors for the development of secondary osteoporosis. In addition, a number of medications are well known to cause or accelerate bone loss, including corticosteroids, anticonvulsants, heparin, chemotherapeutics, hormonal/endocrine therapies, lithium, and aromatase inhibitors. In most patients, both genetic and environmental factors probably contribute to development of osteoporosis.[8]
Osteoporosis is a preventable disease that can result in devastating physical, psychosocial, and economic consequences. However, it is often overlooked and undertreated, in large part because it is so often clinically silent before manifesting in the form of a fracture.[7] Osteoporosis occurs in many individuals who have no risk factors, or only a few risk factors, for the condition. It is essential to identify at-risk patients, educate them, and implement preventive measures to avoid the complications of osteoporosis.
Workup for osteoporosis includes BMD measurement to assess bone loss and help estimate fracture risk.[9] BMD measurements at the hip and spine are the best predictors of fracture risk. Indications for BMD testing are shown above.[8] In any given individual, BMD is expressed as fraction of peak adult bone mass. Bone quality includes architecture, turnover, damage accumulation (eg, microfractures), and mineralization. Bone strength depends on both BMD and bone quality.
Radiography is used for recognizing fractures. DEXA is the recommended method for BMD measurement. A DEXA scanner (shown above) produces x-ray beams with two different photon energies that can be manipulated to determine the BMD. The total scan time is usually less than 5 minutes, with a precision error of less than 1% and very little resulting radiation to the patient.[10]
In the United States, diagnostic and treatment criteria for osteoporosis are based primarily on DEXA measurements. Measurements are typically made in both hips and the lumbar spine. The forearm may be substituted in some patients if the hip or spine cannot be measured, but predictive accuracy is diminished. Accurate measurement requires proper placement of the patient. Rotation, degenerative changes, cysts, or other bone deformities can cause erroneous results.[10]
There are more potential etiologies for false measurements in the spine than in the hip. These include body jewelry, vertebral body fractures (shown above), benign or malignant sclerotic lesions, degenerative disease, aortic atherosclerotic calcifications, barium in the gastrointestinal tract, rotation from scoliosis, and prior vertebroplasty. It is important to note that DEXA is a two-dimensional measurement that measures density/area. Real BMD is susceptible to bone size and will therefore overestimate fracture risk in individuals with a small body frame.[10]
Once measurement is complete, a report is generated that includes a T-score and a Z-score (shown above). The T-score is the number of standard deviations by which a patient's BMD either exceeds or falls below the mean BMD of a young, healthy person of the same sex. The Z-score is the number of standard deviations by which a patient's BMD either exceeds or falls below the mean BMD of others of the same age and sex.
According to the World Health Organization (WHO), a T-score between -1.0 and -2.5 is a sign of osteopenia, and a T-score of -2.5 or lower indicates osteoporosis.[11] The Z-score instead of the T-score should be used for healthy premenopausal women, men younger than 50 years, and children. A Z-score lower than -2.0 is below the expected range.
The use of DEXA for BMD measurement has multiple limitations. Measurements from different machines are difficult to compare because of different dual-energy methods, calibrations, detectors, and regions of interest. T-scores are also based on data from White women and may not apply to women of other ethnicities. To compensate, the WHO has introduced the Fracture Risk Assessment Tool (FRAX) to calculate an individual's 10-year probability of a fracture. This web-based tool asks for input on multiple patient factors, including age, sex, smoking history, and alcohol use. The tool is available for European, Asian, Middle Eastern, African, North American, and Latin American populations and is country-specific. It is available at http://www.shef.ac.uk/FRAX/. The image above shows a hand-held FRAX calculator.
Treatment and prevention begin with adequate nutritional support. Foods rich in calcium are important for all individuals, but especially for those at risk for osteoporosis. Dairy products are the best-known high-calcium foods; however, vegans and individuals with lactose intolerance can obtain significant quantities of calcium from a variety of greens, nuts, and fruits. Premenopausal women and men younger than 50 years who have no risk factors for osteoporosis should receive 1000 mg of calcium daily.
Postmenopausal women, men older than 50 years, and other persons at risk for osteoporosis should receive at least 1200 mg of calcium daily.[12]
Vitamin D is also necessary for maintaining bone density. It is naturally produced by the human body with exposure to direct sunlight, but dietary supplementation is often necessary. Dairy products and fatty fish are good dietary sources of vitamin D. 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. Because smoking and excessive alcohol intake increase calcium loss, smoking should be discontinued, and excessive alcohol intake should be avoided in those with osteopenia.
For treatment of osteoporosis, daily intake of 1200 IU of vitamin D3 or more may be required to maintain vitamin D levels above 30 ng/mL.[12]
Long-term care of osteoporosis should include smoking cessation, alcohol moderation, weight loss, nutritional support, adequate calcium and vitamin D3 intake, regular exercise, fall prevention, and control of secondary disease processes. Imaging should be repeated every two years for patients undergoing osteoporosis treatment and every 2-3 years for at-risk patients with normal BMD.[13]
Weight-bearing exercises positively affect BMD by increasing cortical bone mass and load-bearing strength; 45 minutes four times per week is the recommended schedule. Specialty training regimens, such as tai chi chuan exercises, are also helpful in improving agility and balance, thereby reducing the risk for falls and subsequent fractures.[14]
Medical management of osteoporosis focuses on altering the resorption-production balance in bones to restore normal BMD. Bisphosphonates, which inhibit bone resorption, are recommended as initial treatment. In the United States, four bisphosphonates have been approved by the FDA for treatment of osteoporosis: oral alendronate, oral risedronate, oral ibandronate, and intravenous zoledronate. Denosumab, a potent but expensive resorption inhibitor, should be reserved for patients who cannot tolerate or have contraindications for bisphosphonates. To reduce rapid bone loss after discontinuance, denosumab must be followed by another resorption inhibitor.[15]
Long-term treatment with these agents has been associated with rare cases of jaw necrosis and atypical fractures. Given the rarity of such adverse occurrences and the greater frequency of and harm from osteoporotic fractures, necessary long-term treatment should not be avoided because of these complications.[16] In osteopenic women older than 65 years, an individualized approach to bisphosphonate administration is recommended.[15]
Three injectable anabolic drugs have been approved by the FDA: recombinant human parathyroid hormone (PTH; teriparatide), sclerostin inhibitor (romosozumab), and PTH-related protein (abaloparatide). Teriparatide and romosozumab are recommended by the American College of Physicians (ACP) for women who have a very high risk for fracture or who have sustained fractures despite antiresorptive therapy; the data are insufficient to permit a definite recommendation for men. The use of these agents should be limited to 12-36 months and must be followed by antiresorptive bisphosphonate therapy to prevent rapid bone loss after discontinuance.[15]
Patients with spinal compression fractures that do not compromise the spinal canal may be treated using percutaneous kyphoplasty. A needle is inserted into the vertebral body under fluoroscopic guidance, and a balloon is inflated to expand the compressed vertebrae. The void created by the balloon is then filled with bone cement to restore the lost vertebral height.
The image above shows radiographs before (left) and after (right) kyphoplasty. The bone cement shows up as radiopaque in comparison with the native bone. Although kyphoplasty provides rapid pain relief, long-term studies validating the risk-benefit ratio are lacking. Until more thorough studies have been performed, kyphoplasty should be used only on a case-by-case basis, generally for persistent severe focal back pain related to vertebral collapse.[17]
This image shows osteoporosis of the spine, with osteoporotic compression fractures of the T12 and L1 vertebrae.
Routine osteoporosis screening is not as widespread in men as in women. However, the US Preventive Services Task Force has indicated that bone measurement tests may help detect this disease in men and prevent its burden.[18] The ACP has recommended periodic evaluation of osteoporosis risk factors in older men after age 65.[15] Risk factors include[18]:
- Age > 70 years
- BMI < 20 to 25
- Weight loss > 10% (relative to usual weight or weight loss in recent years)
- Physical inactivity
- Corticosteroid use
- Androgen deprivation therapy
- Previous fragility fracture
