Clinical Review


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Dr. Goldstein serves on the advisory boards of Eli Lilly, Pfizer, GlaxoSmithKline, Novo Nordisk, Novartis, Procter & Gamble, Upsher Smith, and Wyeth; is a consultant for Cook ObGyn and Ackrad Labs (a Cooper Co.); and is a speaker for Eli Lilly, Novo Nordisk, Procter & Gamble, and Wyeth.

Among developments of the past year:
  • release of the long-awaited fracture risk-assessment tool, FRAX, from the World Health Organization
  • release of updated guidelines on osteoporosis treatment from the National Osteoporosis Foundation—the first revision since 2003
  • investigations of a possible association between atrial fibrillation and oral bisphosphonates
  • release of guidelines on diagnosis, risk identification, prevention, and management of bisphosphonate-associated osteonecrosis of the jaw
  • reports of low-energy femoral-shaft fractures associated with long-term use of alendronate
  • report of data from a comparison of alendronate and denosumab, a new antiresorptive agent.

Each of these is explored in detail in this review.

FRAX tool makes it possible to direct therapy to women who need it most

The World Health Organization (WHO) has finally released the FRAX risk-assessment tool, which enables clinicians to calculate a woman’s 10-year risk of developing a hip fracture or any major osteoporotic fracture. The tool (at should, ultimately, be available as part of all dual-energy x-ray absorptiometry (DXA) software so that, when bone mass is measured, the patient’s 10-year risk of hip fracture and overall osteoporotic fracture is reported along with bone density.

FRAX has different thresholds for treatment from country to country, depending on resources available. The tool uses age, weight, height, fracture history, parental fracture history, smoking status, glucocorticoid use, history of rheumatoid arthritis, alcohol consumption, and bone mineral density (BMD) of the femoral neck to determine a woman’s risk of fracture.

In many respects, this tool is a welcome change from the use of BMD measurements alone. I have long been concerned that many clinicians base treatment decisions solely on T-scores. Compare, for example, a 51-year-old newly menopausal woman who has a T-score of -2.0 at the hip with a 67-year-old woman who has the same T-score but who entered menopause at age 48 with a T-score of 0. These women have the same bone mass but very different degrees of bone quality and fracture risk.

Nevertheless, use of an arbitrary threshold (i.e., 3% risk of hip fracture and 20% risk of any osteoporotic fracture over the next 10 years) to determine who gets treatment has limitations. Virtually all bone experts would agree that a pharmacotherapeutic agent that reduces hip fracture by 50% is a “home run.” However, if we deny treatment until a woman’s 10-year risk of hip fracture reaches 3%, that is the same as saying that, for every 100 women who are treated, only 1.5 will fracture a hip instead of three. The health establishment may call that cost-effective, but it will not be acceptable to all patients.

Moreover, patients do not always understand the difference between risk reduction and prevention. It pays to remember these facts when counseling women.

NOF uses new risk-assessment tool to refine treatment guidelines

National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Available at: Accessed October 8, 2008.

Dawson-Hughes B, Tosteson ANA, Melton LJ 3rd, et al, for the National Osteoporosis Foundation Guide Committee. Implications of absolute fracture risk assessment for osteoporosis practice guidelines in the USA. Osteoporos Int. 2008;19:449–458.

Siris E, Delmas PD. Assessment of 10-year absolute fracture risk: a new paradigm with worldwide application [editorial]. Osteoporos Int. 2008;19:383–384.

In February, the National Osteoporosis Foundation (NOF) updated its Clinician’s Guide to Prevention and Treatment of Osteoporosis, first published in 1999 and last revised (with minor changes) in 2003. The guidelines are available at, along with a link to the WHO fracture risk-assessment tool, FRAX (

The previous NOF guidelines applied only to postmenopausal white women and based recommendations for intervention entirely on a patient’s T-score, with some modification of the level of intervention with the presence of clinical risk factors. The new guidelines make use of FRAX to focus recommendations on those at highest risk of fracture.


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