Clinical Review

Preventing fragility fractures: Effective drugs and doses

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The latest data from well-designed trials, including FACT, CORE, and MOBILE, have enlightened us on efficacy, tolerability, and patient-friendly dosing of antiresorptive drugs


It is all too easy to focus on T-scores and lose sight of why we are measuring women’s bone density. We are not trying to prevent osteoporosis; we are trying to prevent the fractures that result from osteoporosis.

The numbers tell why. The total number of fragility fractures in American women in a single year—1 million—out-numbers all heart attacks, strokes, breast cancers, and gynecologic cancers combined. A quality-of-life study by Toteson and Hammond found that 4 out of 10 Caucasian women over 50 will fracture a hip, spine, or wrist, sooner or later. One of every 5 who fracture a hip ends up in a nursing home. The direct care cost of osteoporotic fractures was $17 billion in 2001 dollars.

Now, we have more treatment options than ever. And 2005 has been a banner year for discoveries we can put into practice immediately, in our efforts to prevent fragility fractures.

Why so confusing?

McClung MR. The relationship between bone mineral density and fracture risk. Curr Osteoporos Rep. 2005;3:57–63.

  • The terms osteopenia and osteoporosis are arbitrary cutoffs. Fracture risk is a continuum and involves multiple factors in addition to bone mass.
Osteoporosis: A skeletal disease characterized by low bone mass and disruption of bone tissue architecture that results in a reduction in the mechanical strength of the skeleton, increasing the risk of fragility fractures.”

The clinically crucial part of that definition is…“increasing the risk of fragility fractures.” Certainly, low bone mass on DEXA is a risk factor. And guidelines from the World Health Organization (WHO), the National Osteoporosis Foundation, and the North American Menopause Society are based on T-scores. However, treatment that bases intervention on absolute fracture risk would be much more appropriate; in fact, the WHO is expected to shortly issue a method to calculate fracture risk. Factors are likely to include age, previous fracture, family history, body mass index, ever use of steroids, propensity for falling, eyesight, overall health, and bone mass (ie, BMD determinations).

We need to realize that WHO definitions of T-score categories are meant for postmenopausal women. Inappropriate use of DEXA scanning in a premenopausal patient may identify a woman with low bone mass, but her bone quality and risk of fragility fracture differ greatly from that of a distantly postmenopausal woman with the same T-score. It may seem counterintuitive, but a 50-year-old woman with a T-score of –3.0 has the same absolute fracture risk, going forward, as an 80-year-old woman with a T-score of –1.

Although the risk of fracture is greatest in women with osteoporosis, there are many more women with osteopenia who will have a fracture. But that doesn’t mean we should prescribe pharmacotherapy for every osteopenic woman in an attempt to prevent fractures. As the US Surgeon General’s report last October estimated, 34 million women have osteopenia and “only” 10 million have osteoporosis. Not every woman with osteopenia should be a candidate for pharmacotherapy, but these facts do underscore the need for a better way to assess absolute fracture risk.


  • Miller PD, Barlas S, Brenneman SK, et al. An approach to identifying osteopenic women at increased short-term risk of fracture. Arch Intern Med. 2004;164:1113–1120.
  • Salkeld G, Cameron ID, Cumming RG, et al. Quality of life related to fear of falling and hip fracture in older women: a time trade off study. BMJ. 2000;320:341–346.
  • Schuit SC, van der Klift M, Weel AE, et al. Fracture incidence and association with bone mineral density in elderly men and women: the Rotterdam Study. Bone. 2004;34:195–202.
  • Tosteson AN, Hammond CS. Quality-of-life assessment in osteoporosis: health-status and preference-based measures. PharmacoEconomics. 2002;20:289–303.

Are all bisphosphonates created equal?

Rosen CJ, Hochberg MC, Bonnick SL, et al. Postmenopausal osteoporosis: a randomized double-blind study. J Bone Miner Res. 2005;20:141–151.

  • Antifracture efficacy at the spine appears to be indistinguishable among antiresorptive agents, despite differences in BMD and bone turnover. Gastrointestinal tolerability was similar in the FACT study.
The FACT study (Fosamax Actonel Comparison Trial) found wide variations in 2 surrogate endpoints—BMD and bone turnover markers—but unfortunately was not powered to compare fracture reduction, which is the clinically relevant endpoint. This head-to-head trial comparing once-weekly risedronate (Actonel) and alendronate (Fosamax) in postmenopausal women with low BMD was designed to evaluate changes in BMD and bone turnover markers. Upper GI tolerability was also compared, and was found to be similar for both drugs. The double-blind, randomized, active-controlled study was conducted at 78 US sites and involved 1,053 patients. Postmenopausal women with a bone density T-score more than 2.0 standard deviations below the young normal mean bone mass were given 70 mg once-weekly alendronate or 35 mg once-weekly risedronate. The only exclusion criterion regarding previous GI symptoms was any abnormality of the esophagus that might delay esophageal emptying.


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