What to do about postmenopausal fracture risk

Diet, exercise, calcium, and vitamin D are always important, but women at high risk for fractures may need drug therapy, too.

If you're over age 50, you have an even lifetime chance of breaking a bone because of osteoporosis. This disorder weakens bones, leaving them vulnerable to fracture even without a serious fall or other trauma. The risk increases with age in both sexes, but postmenopausal women are at special risk because bone loss is accelerated by the decline in estrogen at menopause.

In 1994, the World Health Organization (WHO) developed criteria for diagnosing osteoporosis based on a measurement of bone mineral density (BMD) called a T-score. These scores are best determined by dual-energy x-ray absorptiometry (DXA). A T-score of –2.5 or lower marks the threshold for osteoporosis and the point at which treatment is clearly indicated.

But BMD measurements alone can't predict who's most likely to break a bone — the main reason for concern about osteoporosis. Among postmenopausal women, as many as half of all fractures occur in those whose T-scores don't meet the criteria for full-blown osteoporosis. Moreover, women with the same T-scores don't necessarily have the same fracture risk. For example, one study concluded that an 80-year-old woman with a T-score of –2.5 was almost five times more likely to break a bone than a 50-year-old woman with the same T-score.

In 2008, a WHO task force introduced FRAX, a risk assessment tool that incorporates a number of risk factors besides BMD. (See "Risk factors used in FRAX.") FRAX provides an estimate of the likelihood that you will suffer a hip or other major fracture in the next 10 years. Using this tool, the National Osteoporosis Foundation has issued new guidelines that are helping to clarify who should be tested and treated.

Who needs treatment?

Most experts recommend DXA screening for all women ages 65 and over, as well as younger women who have risk factors associated with bone loss. That includes women over 50 who have a low body mass index, a history of low-trauma fracture as an adult, or a condition associated with bone loss, such as celiac disease, Crohn's disease, rheumatoid arthritis, or anorexia nervosa. A woman who is taking certain medications, including glucocorticoids, chemotherapy drugs, immunosuppressants, or certain anticonvulsants is also at increased risk of bone loss and may benefit from DXA testing before age 65. Women who discontinue estrogen therapy lose bone rapidly, just like those in the first few years of menopause.

The FRAX tool (available online at www.shef.ac.uk/FRAX) is designed to assess postmenopausal women's fracture risk even without BMD measurement. (In the United States, where DXA is widely available, the FRAX formula may soon be added to DXA software, providing results that incorporate both T-scores and FRAX risk estimates.) The National Osteoporosis Foundation guidelines suggest that clinicians consider treatment with an FDA-approved drug for women (and men) ages 50 and over who meet one or more of the following criteria:

• a history of hip or spine fracture

• a T-score of less than –2.5 at the hip or spine

• a T-score of –1.0 to –2.5 at the hip or spine (indicating low bone mass short of osteoporosis) together with a 10-year, FRAX-estimated risk of more than 20% for any major osteoporosis related fracture or more than 3% for hip fracture.

Keep in mind that falls are one of the biggest risks for fractures. There are many strategies for preventing falls and the resulting broken bones, including home safety precautions and exercises to improve strength and balance. (Fall prevention resources are available at www.stopfalls.org.)

Anyone taking an osteoporosis medication should also get adequate calcium and vitamin D. Aim for a calcium intake of 1,200 to 1,500 milligrams daily, mostly through foods, which have many important nutrients in addition to calcium. The National Osteoporosis Foundation currently recommends 800 to 1,000 international units (IU) of vitamin D per day, but some experts think that isn't enough. Up to 2,000 IU per day is considered safe.

Medication options

The main goal of treatment is to prevent fractures by slowing bone loss or strengthening bone. Several medications are now available for this purpose, and more are under development. Bone continually undergoes remodeling, or bone turnover, in two distinct phases — resorption (breakdown) and formation. Different osteoporosis medications target different phases of the remodeling process. Most approved drugs are antiresorptive — that is, they protect existing bone from being broken down, or resorbed. Only one, teriparatide (Forteo), directly stimulates new bone formation. As with many drugs, it's unclear whether a particular medication works best, because of the lack of head-to-head trials comparing the effectiveness of these various drugs in reducing fractures. (Most of what we know comes from trials comparing individual drugs to a placebo.)

Currently available drugs (see "Medications for prevention or treatment of postmenopausal osteoporosis" above) fall into three main classes:

Bisphosphonates. These drugs, the first-line medications for osteoporosis, slow bone resorption by sticking to the surface of bone and interfering with osteoclasts (the cells that break down bone). When resorption drops, so does new bone formation, which is closely linked to resorption. Consequently, antiresorptive drugs don't produce a big increase in BMD. But that doesn't mean the drug isn't doing its job, says Dr. Steven Harris, an osteoporosis expert at the University of California at San Francisco. Speaking at the annual meeting of the North American Menopause Society in October 2009, Harris noted, "Antiresorptive therapy decreases fracture risk more rapidly and to a larger extent than one would predict from the small changes in BMD."

In women with osteoporosis, the oral bisphosphonates alendronate (Fosamax) and risedronate (Actonel) reduce the risk of vertebral (spine), hip, and nonvertebral (arm or wrist) fractures. Ibandronate (Boniva) reduces vertebral fractures but has little effect on nonvertebral or hip fractures. A key trial of zoledronic acid (Reclast), which is given intravenously, found that it reduced vertebral, hip, and nonvertebral fractures.

The biggest complaint about oral bisphosphonates is upper gastrointestinal distress, including acid reflux, trouble swallowing, heartburn, and nausea. (To help prevent these problems, take the drug on an empty stomach first thing in the morning with a large glass of water, and don't eat or lie down for 30 to 60 minutes afterward.) A less common complaint is muscle, bone, and joint pain. One potential side effect is very serious but also very rare: osteonecrosis (bone death) of the jaw. This problem has occurred mostly among cancer patients taking high intravenous doses of bisphosphonates. The rare cases among people taking lower doses for osteoporosis have generally been in those undergoing invasive dental procedures. As a precaution, women are advised not to have major dental work performed while they're taking bisphosphonates. There are also scattered reports of nontraumatic fractures of the thighbone in people on long-term bisphosphonate therapy.

Selective estrogen receptor modulators (SERMs). These are estrogen-like compounds that act on estrogen receptors to slow osteoclast activity in postmenopausal women. Raloxifene (Evista) is the only SERM approved so far for osteoporosis prevention and treatment. In women with low BMD, raloxifene helps reduce vertebral fractures but has little effect on nonvertebral or hip fractures. It's also approved for the prevention of breast cancer. Side effects include exacerbation of hot flashes and increased risk of blood clots and stroke. Raloxifene is preferable mainly for women who can't tolerate the side effects of bisphosphonates or are at increased risk for breast cancer.

Hormones. Medications in this category include estrogen with or without a progestin (hormone therapy), calcitonin (Miacalcin, Fortical), and Forteo.

Many randomized trials have shown that hormone therapy reduces the risk of vertebral, hip, and nonvertebral fractures. Before the Women's Health Initiative found that its risks outweighed its benefits, hormone therapy was routinely prescribed for long-term prevention and treatment of osteoporosis. The National Osteoporosis Foundation and the North American Menopause Society say that other medications should be considered first, but that hormone therapy may be an option if alternative therapies aren't suitable or cause intolerable side effects. Currently, it is approved only for osteoporosis prevention.

Calcitonin, a thyroid-derived peptide, slows bone resorption and can reduce the risk of new vertebral fractures. It may also help reduce pain caused by vertebral fracture. However, calcitonin is not first-line therapy. It's expensive and has frequent and annoying side effects, including nausea, flushing, and (when taken in a nasal spray) nasal irritation. It also doesn't reduce hip or nonvertebral fractures.

Forteo, a synthetic preparation of human parathyroid hormone given by daily injection, is the only approved osteoporosis drug that works by boosting the formation of bone rather than slowing its breakdown. In women with severe osteoporosis, Forteo significantly reduces the risk of vertebral and nonvertebral fractures. It has relatively few short-term side effects, but its long-term safety hasn't been established. It's also expensive and burdensome to administer, so it's usually reserved for women at very high risk for fracture. Other versions of human parathyroid hormone are under investigation.

On the horizon

Several drugs that target bone resorption are in development or awaiting FDA approval. Two, bazedoxifene and lasofoxifene, are orally administered SERMs. In clinical trials, bazedoxifene reduced vertebral but not nonvertebral fracture risk; lasofoxifene lowered the risk of vertebral and nonvertebral fracture, as well as heart disease, stroke, and breast cancer. Another antiresorptive drug, denosumab, targets a protein required for making osteoclasts. Clinical trials indicate that it reduces vertebral, hip, and nonvertebral fractures.