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Sunday, October 17, 2010

Reduced bone density: to treat or not to treat?

Osteoporosis is a condition that is sure to become increasingly diagnosed as our population ages. Osteoporosis is significant because it is associated with an increased risk of bone fracture, including fracture of the hip and vertebra, which are the cause of significant morbidity, mortality, loss of independence and medical expense in the elderly. In current clinical practice, osteoporosis is diagnosed on the basis of either the occurrence of a low-impact or fragility fracture, or on the basis of measured low bone mineral density (BMD). A low-impact fracture is one that occurs after a fall from standing height or less; a fragility fracture occurs spontaneously or with no trauma (cough, sneeze, sudden movement).

Bone strength is determined by bone density, bone “quality,” and bone microarchitecture. Of these features, bone density, or mass,  is what we are able to measure. Osteoporosis is defined by World Health Organization criteria based on a person’s bone density by dual energy x-ray absorptiometry (DXA). Osteoporosis occurs when bone density is below 2.5 standard deviations from the mean for non-Hispanic white women between ages 20 and 29 (T score < -2.5). Osteopenia is defined by bone density of between 1 and 2.5 standard deviations below the mean for non-Hispanic white women in their twenties (T score of -1 to -2.5).

In recent years a variety of effective medications have been developed and approved for treatment of low bone density. Nonetheless, there are still significant gaps in our knowledge. Last week the FDA issued a warning about an increased risk of “atypical fractures” that has been observed amongst women who take bisphosphonates, the most commonly prescribed drugs for osteoporosis. A few years ago these drugs were also linked to another rare problem, osteonecrosis of the jaw. This was primarily described in cancer patients and those on cancer medications, but the finding got patients, dentists, and oral surgeons quite worked up over the potential risks.

In clinical practice there is significant variation in the practice of screening for and treating osteoporosis and its precursor, osteopenia. According to national epidemiological data from NHANES III over 56% of women over age 50 have reduced bone density, of these 16% have osteoporosis.  In their 80s 87% of women have reduced bone density and 44% of have osteoporosis. The key to prevention and treatment is trying to figure out who and when to treat aggressively to best prevent fractures. Current guidelines by the US Preventive Services Task Force support screening women at age 65. However, many post-menopausal women under age 65 are also at risk and the conservative evidence-based USPSTF guidelines do not comment on which of these women should also be screened. Other professional guidelines, such as those issued by the National Osteoporosis Foundation, support screening younger women who are post-menopausal and who have risk factors.

A variety of clinical tools exist to help women quantify their osteoporosis risk.

Osteoporosis risk factors include:

• Low body weight (<57 kg)
• Asian or Caucasian ethnicity
• Personal history of fragility fracture
• Family history of osteoporosis
• Smoking
• Drinking > 2 glasses of alcohol per day
• Excessive caffeine intake
• Certain medications (glucocorticoids)
• Sedentary lifestyle
• Amenorrhea (lapses in menstruation prior to menopause)
• Eating disorders
• Marathon running
• Dietary deficiencies of calcium and vitamin D
• Chronic health conditions (chronic liver and kidney disease, rheumatoid arthritis)

Many women fall into these increased risk categories and thus are screened before age 65 leaving them with a diagnosis of osteopenia or osteoporosis and creating the conundrum of what to do for the remainder of a woman’s life.

In general, most women with osteopenia should not receive pharmacologic therapy unless they are higher risk, or have already suffered a fracture. Instead, they should be counseled to institute behavioral measures, such as increased weight-bearing exercise and increases in calcium and vitamin D supplementation. When these women should be rescreened is not clear, but probably no more often than every two years. Tracking the rate of bone density decline may help identify women who subsequently should receive drug therapy.

Effective pharmacologic treatments for osteoporosis are available and are, in general, well tolerated. Medication options include the bisphosphonates: alendronate, residronate, ibandronate and zoledronic acid, hormonal treatments (estrogen and selective estrogen receptor modulators), and recombinant parathyroid hormone (teriparatide). Of these options, the oral bisphosphonates, alendronate (Fosamax) and residronate (Actonel), have the most evidence supporting their efficacy in fracture prevention, and are considered first line. These drugs, however, can be somewhat inconvenient to administer because of their poor bioavailability that requires them to be taken on an empty stomach for best absorption. In addition, they are associated with gastrointestinal side effects—specifically esophagitis, and for this reason are contraindicated in patients with precancerous changes of the espophagus, “Barrett’s Esophagus.” For patients who experience gastrointestinal side effects the intravenous bisphosphonate, zoledronic acid may be administered every one to two years.

Hormonal therapies, such as estrogen, are effective treatment for low bone density. However, as indicated by the results of the Women’s Health Initiate, their use has been associated with an increased risk of breast cancer and cardiovascular disease. Raloxifene, a selective estrogen receptor modulator (SERM), is approved for both prevention and treatment of osteoporosis. Its use, while associated with a reduction in breast cancer risk, is also associated with an increased risk of thomboembolism. Its effect on cardiovascular disease appears to be neutral.

The appropriate duration of therapy and frequency of monitoring patients who are on pharmaceutical treatment are areas that remain ill-defined. Studies have indicated that 5 years of alendronate may be adequate for many average risk women. However, my experience in clinical practice is that many women are left on these drugs for years and years. Some have advocated drug “holidays” after five years of therapy. The largest randomized controlled trial looking at alendronate use and fracture outcomes was 10 years in duration, which in my view calls into question the safety of prolonged use.

Many questions remain about how to approach the treatment of aging bones to prevent the debilitating outcome of bone fracture. Seasoned clinicians have seen the problems that may occur in some cases with treating large populations of well patients for normal life processes (postmenopausal estrogen replacement therapy). Let’s hope that future research will address the question of when to treat with medication and for how long with further precision. Until then let’s use appropriate caution when prescribing medicine for normal senior bones.