Clinical Review

Real-life risks and benefits of fracture-reducing drugs

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How do the high-profile studies of 2006 apply to our patients?


It is all too easy to focus on T-scores and lose sight of why we check bone mass: we want to prevent fragility fractures—not osteoporosis per se. Fracture incidence is greater in women with osteoporosis, but the absolute number of fragility fractures is far greater in the women who have not yet reached that threshold. That was my main message last year. It still is, although I had hoped we would by now have in our hands a fracture risk assessment tool due from the World Health Organization. It will use age, DXA score, history, and other factors to project 5- and 10-year risk of fracture. Then we will simply have to decide at what level of risk, for an individual patient, drug therapy is indicated. Watch this space!

What’s new in 2006

1 Osteonecrosis of the jaw: What clinicians need to know

2 Raloxifene: A bone drug that reduces new onset breast cancer

3 Estrogen for bone protection: Time for a comeback?

4 Risedronate: Not just for fracture prevention?

1 Osteonecrosis of the jaw: What clinicians need to know

Woo SB, Hellstein JW, Kalmar JR. Systematic review: bisphosphonates and osteonecrosis of the jaws. Ann Intern Med. 2006;144:753–761.

This was the year of massive media attention on bisphosphonate therapy and osteonecrosis of the jaw. A bone specialist I know said he got even more phone calls after this report was published than after the WHI blitz 4 years ago.

Patients started calling when the lay press limelight focused on a report by Woo et al, who reviewed all of the world’s literature published since 1966, and identified 368 reported cases of bisphosphonate-associated osteonecrosis of the jaw (ONJ).

Main findings

Of the 368 cases, 94% were being treated with intravenous bisphosphonate therapy; 85% of the patients had either multiple myeloma or metastatic cancer of the breast. More than half of all cases (60%) were preceded by tooth extraction or other dentoalveolar surgical procedure to treat infections, and the remaining 40% were related to infection, denture trauma, or other physical trauma.

The latter group of cases occurred spontaneously, although the patients affected often wore dentures. The mandible was more commonly affected than the maxilla by a ratio of 2:1.

Other studies have reported 75% of patients with ONJ were receiving chemotherapy at the time of diagnosis, and 38% were on corticosteroids.

Do these findings affect prescribing?

A small number of cases of ONJ in postmenopausal women taking oral bisphosphonates have occurred, though rarely—well under 1 per 100,000 patients treated. Realize that patients with myeloma or metastatic breast cancer are usually treated with high-dose, high-potency intravenous bisphosphonate.

There were no reports of ONJ in any of the controlled trials on use of bisphosphonates for osteoporosis; this represents more than 60,000 patients who in some cases were treated for more than 8 years.


The American Society for Bone and Mineral Research advises:

2 Raloxifene: An osteoporosis drug that reduces new onset breast cancer

Vogel VG, Costantino JP, Wickerham DL, et al. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes. The NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 Trial. JAMA 2006;295:2727–2741.

Barrett-Connor E, Mosca L, Collins P, et al. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med. 2006;355:125–137.

Two large trials cause me to believe that raloxifene significantly reduces new onset breast cancer in virtually every group of women in which it has been studied.

Why you didn’t hear about this until now

Raloxifene was FDA-approved for prevention of osteoporosis in 1997 and for treatment of osteoporosis in 1999. There was a statistically significant 76% reduction in new onset breast cancer in raloxifene-treated patients versus placebo through 4 years of the MORE (Multiple Outcomes of Raloxifene Evaluation) trial, and this persisted at a 66% reduction through the additional years of the CORE (Continued Observation of Raloxifene Evaluation) trial.

Findings effectively buried. However, because of the wording of the FDA label, and, as a result of a $36 million fine from the Department of Justice, for promotional activities in the early years after its release, these findings were effectively buried and not well promulgated.

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