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 to normal bone (left image), osteoporotic bone (right image) shows thinning and loss of trabeculi resulting in bone that is very fragile. There is an increased risk for fractures, even after minimal trauma.

Image courtesy of Wikimedia Commons.

According to the National Osteoporosis Foundation (NOF), 9.9 million Americans have osteoporosis and an additional 43.1 million have low bone density. In the United States, two million fractures are attributed to osteoporosis annually, with 432,000 hospital admissions, 2.5 million medical office visits and approximately 180,000 nursing home admissions.^[2] About 1 out of every 2 white women will experience an osteoporosis-related fracture in her lifetime, as will approximately 1 out of 5 men.^[3]

The estimated cost of osteoporosis and related fractures is approximately $16 billion each year.^[4] With an increasingly aged population, these numbers are predicted to steadily increase in the future.

Image from U.S. Department of Health and Human Services. The Frequency of Bone Disease. In: Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD: U.S. Department of Health and Human Services, Office of the Surgeon General; 2004.

Adult bone undergoes constant remodeling to maintain strength. Bone mineral density and bone architecture are the result of a balance between osteoclastic resorption and osteoblastic formation. Osteoblasts (top image) produce new bone over a period of months. Numerous hormonal and dietary factors influence the balance of bone production. Calcium, vitamin D, estrogen, and parathyroid hormone help maintain bone homeostasis.

Osteoclasts (bottom image) resorb bone over a period of weeks, and are especially active during periods of rapid remodeling (eg, after menopause). 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]

Images courtesy of Wikimedia Commons/ Robert M. Hunt.

Woven bone is the primitive bone first laid down during fracture repair or new bone formation. It consists of a higher percentage of osteocytes than normal. The gross structure is highly disorganized and thus much weaker. It is eventually replaced by concentrically organized lamellar bone with much lower proportions of osteocytes. The image on the left demonstrates woven bone arising directly from surrounding mesenchymal tissue.

Bony remodeling is a chronic process of replacement with minimal change in the gross shape of the bone structure. Osteoblasts and osteoclasts together are referred to as bone remodeling units. They work in concert together, coordinated via paracrine signaling by the osteoblasts. The constant remodeling allows for calcium homeostasis and the repair of microscopic daily stressors.

The image on the right depicts bone remodeling with osteoclasts resorbing one side of a bony trabecula and osteoblasts depositing new bone on the other side.

Images courtesy of Medscape.

Osteoporosis is typically asymptomatic until a fracture occurs. 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, 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 (as shown) over time, and the characteristic hunched-over posture of severe osteoporosis develops eventually.

Images courtesy of Medscape.

The two major spinal fracture patterns in osteoporotic bone are wedge fractures and burst fractures. In wedge fractures (left image), the anterior column of the vertebral body is compressed leading to kyphotic changes, but usually with preservation of the spinal cord. In burst fractures (right image), an axial load disrupts some combination of the anterior, middle, and posterior columns, which frequently leads to disruption of the spinal cord.

Although hip and spinal fractures are the most commonly associated osteoporosis-related fractures,^[6] low bone mineral density places all bones at risk for fracture.

Images courtesy of Medscape/ JP Kochan.

The National Osteoporosis Foundation has categorized the risk factors for osteoporosis as uncontrollable and controllable risk factors (shown).^[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 40 years of age and older, a patient's signs of vertebral fracture, a patient's risk factors for falls, and a patient's co-existing medical conditions that are associated with bone loss (e.g., celiac disease). In addition, it is important to assess whether the patient is taking medications that are associated with bone loss.

Image data from the National Osteoporosis Foundation and the International Osteoporosis Foundation.

Osteoporosis can be primary from hereditary factors or secondary from environmental factors. A whole host of medical conditions are risk factors for the development of secondary osteoporosis.^[8] 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 evnironmental factors likely contribute to development of osteoporosis.

Image from U.S. Department of Health and Human Services. Diseases of Bone. In: Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD: U.S. Department of Health and Human Services, Office of the Surgeon General; 2004.

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. Failure to identify at-risk patients, educate them, and implement preventive measures may lead to tragic consequences.

Indications for bone mineral density (BMD) testing are shown ^[2]. BMD is expressed as grams of mineral per area or volume. In any given individual, BMD is determined by peak bone mass and amount of bone loss. Bone quality refers to architecture, turnover, damage accumulation (e.g., microfractures), and mineralization. Bone strength depends on both the BMD and the bone quality.

Image courtesy of the International Society for Clinical Densitometry.

Workup for osteoporosis consists of laboratory studies to establish baselines and look for potential secondary causes of osteoporosis, along with bone mineral density (BMD) measurement to assess bone loss and estimate fracture risk.^[9] Densitometry techniques include single-photon absorptiometry (SPA), dual-photon absorptiometry (DPA), dual-energy x-ray absorptiometry (DXA), and quantitative computed tomography (QCT). Examination time, cost, and sites scanned vary among the techniques (shown). Other techniques include quantitative ultrasound, magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), and bone scanning. Bone biopsy is reserved for patients with unusual forms of osteoporosis. Methods that measure hip and spine osteoporosis are generally considered better predictors of fracture risk.

Image data from Nayak S, Roberts MS, Greenspan SL. Cost-effectiveness of different screening strategies for osteoporosis in postmenopausal women. Ann Intern Med. 2011; 155(11):751-761.

The primary imaging modalities used to measure BMD are DXA, QCT, and quantitative ultrasound. Currently, DXA^[10] is the most accurate and recommended method for BMD measurement. It is able to detect changes in bone density only 6-12 months after a previous BMD measurement. A DXA scanner is shown. In the United States, current diagnostic and treatment criteria for osteoporosis are based solely on DXA measurements. Conventional radiography is used for the qualitative and semiquantitative evaluation of osteoporosis. Areas for future imaging development include high-resolution CT scanning (HRCT) and high-resolution MRI (HRMRI), which will provide a better assessment of bone structure.

Image courtesy of Wikimedia Commons.

DXA scanners act like a modified radiography unit. They produce 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. Measurements are typically made in both the hip and lumbar spine (shown). The forearm may be substituted in some patients if the hip or spine cannot be measured.

Image from Germain DP. Fabry Disease. Orphanet J Rare Dis. 2010; 5(30)./ Courtesy of Dr Caroline LEBRETON, CHU Raymond Poincaré, Garches, France.

DXA of the hip (left image) requires the standardized placement of multiple regions of interest. Four regions of interest are measured (shown): the femoral neck (red box), Ward's triangle (blue box), the trochanter (yellow region), and the intertrochanter (green region). False measurements may be produced by improper placement of the regions of interest due to patient rotation, overlying calcifications such as in dermatomyositis, benign or malignant bone tumors, or congenital or acquired hip deformities. Degenerative changes to the femoral head are usually excluded from the area of interest.

DXA of the lumbar spine (right image) involves placement of regions of interest over the L1 through L4 vertebral bodies (shown). As in the hip, correct positioning is very important, in particular the appropriate labeling of vertebral bodies. In general, vertebral body area and BMD increase with increasing vertebral body number. In some cases, a radiograph may be needed for correlation, especially in cases of variant anatomy such as with the 13th paired ribs or in sacralized L5 vertebral bodies.

Images courtesy of Medscape.

More potential etiologies underlie false measurements in the spine than in the hip, including body jewelry, vertebral body fractures (shown), 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 DXA 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.

Images courtesy of Medscape.

Upon measurement completion, a report is generated. The T-score is the number of standard deviations that a patient's BMD is above or below the mean BMD of young, healthy person of the same sex. The Z-score is the number of standard deviations that a patient's BMD is above or below the mean BMD of others of the same age and sex. According to the WHO, a T-score between -1.0 and -2.5 is a sign of osteopenia, and a T-score of -2.5 or below indicates osteoporosis.^[11] The report scores of an 80-year-old woman are shown. The Z-score instead of the T-score should be used for healthy premenopausal women, men under age 50, and children. A Z-score less than -2.0 is below the expected range.

Images courtesy of Medscape.

DXA BMD measurements have multiple limitations. Measurements from different machines cannot be compared due to different dual-energy methods, calibrations, detectors, and regions of interest. T-scores are based on white women and may not apply to 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. The web-based tool (shown) asks for input on factors including an individual's age, sex, smoking history, and alcohol use. The tool is available for European, Asian, Middle Eastern, African, North American, and Latin American populations. It is available at http://www.shef.ac.uk/FRAX/.

Image courtesy of World Health Organization Collaborating Centre for Metabolic Bone Diseases, University of Sheffield, UK.

Quantitative CT^[12] is an alternative to DXA that is useful in patients with a very small or very large body size, older patients with advanced degenerative disease or morphological abnormalities, and patients treated with parathyroid hormone or corticosteroids. It allows for measurement of trabecular and cortical bone mineral density. Patients are first scouted, and the lumbar vertebral bodies are marked.

A region of interest is then placed under the vertebra and is used to convert Hounsfield units into milligrams per cubic centimeter of calcium hydroxyapatite. The advantages of quantitative CT over DXA are that it allows true volumetric measurements independent of body size and better discrimination in patients with fragility fractures. The disadvantages of quantitative CT are that it involves a higher radiation dose, fewer studies exist to validate the datasets, and T-scores cannot be used to define osteoporosis. Potential pitfalls of quantitative CT include streak artifact from adjacent metallic objects and beam hardening artifact.

The image shows an anteroposterior lumbar radiograph with advanced syndesmophytes (left) and a quantitative CT scan of L5 vertebral body showing the region of interest containing trabecular bone (right).

Image from Korkosz M, Gąsowski J, Grzanka P, et al. Baseline new bone formation does not predict bone loss in ankylosing spondylitis as assessed by quantitative computed tomography (QCT) - 10-year follow-up. BMC Musculoskelet Disord. 2011 May 31;12:121.

Nuclear medicine does not have an established role in bone density screening; however, it is an important tool in evaluating occult fractures, as the whole body may be scanned. The radionuclide bone scan (shown) demonstrates insufficiency fractures in the pelvis (arrows) in the so-called Honda pattern due to its similarity to the Honda H-shaped logo. Quantitative ultrasonography of the calcaneus is an alternative to general screening. It relies on the principal of sound wave attenuation, which is dependent on both bone mineral density and bone macroscopic architecture. The patient simply places his or her foot into the machine and an index measurement is produced without ionizing radiation, at a low cost, and with a mobile device. Unfortunately, because the index measurement does not directly correlate with BMD, some studies have shown a poor correlation with measurements obtained from DXA scans.

Images courtesy of Medscape.

Treatment and prevention begins with adequate nutritional support. Foods rich in calcium are important for all individuals, but especially those at risk for osteoporosis. Dairy products are the most well-known high calcium foods, but for vegans or those with lactose intolerance, numerous other greens, nuts, and fruits contain significant quantities of calcium. 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 total of 1200-1500 mg of calcium daily.

Vitamin D is also necessary to maintain adequate bone density. It is naturally produced by the human body when exposed to direct sunlight, but supplementation is frequently necessary. Dairy products and fatty fish are good sources of dietary vitamin D. Adults younger than 50 years of age should receive 400-800 IU of vitamin D 3 daily. All adults older than 50 years should receive 800-1000 IU of vitamin D 3 daily. Since smoking and alcohol intake increase calcium loss, smoking should be discontinued and excessive alcohol intake avoided in those with osteopenia.

Images courtesy of Medscape.

Long-term care of osteoporosis focuses on cigarette cessation, alcohol moderation,^[13] weight loss, nutritional support, medication, frequent exercise, and control of secondary disease processes. Imaging should be repeated every 1-2 years for patients undergoing osteoporosis treatment, and every 2-3 years for at-risk patients with normal bone mineral density.

Weight-bearing exercises positively affect bone mineral density by increasing cortical bone mass and load-bearing strength^[14]; 45 minutes 4 times per week is the recommended schedule. Specialty training regimens, such as the tai chi chuan exercises, are also helpful in improving agility and balance, thereby reducing the risk for falls and subsequent fractures.

Image courtesy Dreamstime | Katarzyna Bialasiewicz.

Medical management of osteoporosis focuses on manipulating the resorption-production balance in bones to restore normal bone mineral density. Bisphosphonates,^[15] denosumab, selective estrogen-receptor modulators, calcitonin, and parathyroid analogues are currently used for osteoporosis treatment in combination with calcium and vitamin D supplementation.

Bisphosphonates (shown) are recommended as initial treatment for most patients. Given their high cost and long-term toxicity, parathyroid analogues should only be used in patients at very high fracture risk. The other agents are used when bisphosphonates are contraindicated or poorly tolerated. Although hormone replacement therapy was once used, due to the increased risk for breast cancer, myocardial infarction, stroke, and venous thromboembolic events, it is no longer recommended for osteoporosis treatment in postmenopausal women.

A number of different complementary and alternative medicine remedies are used; however, as with many nontraditional treatment modalities, the evidence is lacking from large scale trials. Red clover and soy extracts are common over-the-counter remedies that patients may be ingesting.

Images courtesy of Wikimedia Commons.

Patients with spinal compression fractures that do not compromise the spinal canal may be treated with a percutaneous kyphoplasty. A percutaneous needle is inserted into the vertebral body under fluoroscopic guidance and a balloon is inflated to expand the compressed vertebrae (top image). The void created by the balloon is then filled with bone cement in an attempt to replace the osteoporotic height loss.

Before and during kyphoplasty images are shown (bottom image) with superior endplate elevation and height restoration. The bone cement shows up as radiopaque compared to 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 only be used on a case-by-case basis, generally for persistent severe focal back pain related to vertebral collapse.

Images courtesy of Medscape.

Insufficiency fractures can develop in patients with osteoporosis; if not properly treated, they can lead to complete femoral neck fractures with displacement. Prompt orthopaedic surgery intervention is needed to stabilize the hip with the exact type of fixation to be determined by the area of injury, quality of bone, and patient age. Percutaneous screws are the preferred method, but in the elderly or those with poor healing states, then hemiarthroplasty is the operation of choice.

Images courtesy of Medscape.

This image reveals osteoporosis of the spine, with a reduction in overall vertebral bone density. Routine osteoporosis screening is not as widespread in men as in women. However, the U.S. Preventive Services Task Force indicates that bone measurement tests may help detect this disease in men and prevent its burden.^[16] The American College of Physicians recommends periodic evaluation of osteoporosis risk factors in older men before age 65.^[17] Risk factors include: age >70, body mass index <20 to 25 kg/m2, weight loss >10% (relative to usual weight or weight loss in recent years), physical inactivity, corticosteroid use, androgen deprivation therapy, and previous fragility fracture.^[17]

Images courtesy of Medscape.