Recommendations vary, depending on which organization you consult. The American Academy of Clinical Endocrinologists (AACE) does not recommend therapy (primary prevention) for osteopenia, except in patients who have already suffered a fracture (secondary prevention). At the T-score threshold of -2.5 SD, where osteoporosis begins, according to the World Health Organization (WHO) definition, AACE recommends initiation of therapy. 

The National Osteoporosis Foundation recommends medications if the T score is below -2.5 SD and even for those merely osteopenic patients with T scores of <-1.0 to -2.5 SD if they have a preponderance of concomitant risk factors as calculated by the fracture risk assessment tool, FRAX, developed and endorsed by WHO.

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Concerns have arisen over the risk of side effects from bisphosphonates: osteonecrosis of the jaw, esophageal irritation, and even atypical femoral fractures. Also, prolonged therapy has unclear benefits and may accentuate problems with bone architecture. Do the potential risks outweigh the benefits for osteopenic patients, who are inherently at lower risk of fracture and possibly requiring longer treatment durations for prevention?

A study frequently invoked to support bisphosphonate therapy demonstrated a 50% reduction in risk of hip fracture with alendronate, but only in osteoporotic patients.18 Patients with T scores >-2.5 were not found to benefit in terms of fractures, but they did have enhanced bone density. In absolute terms, the risk reduction was 1.2% fewer hip fractures over three years in women with severe osteoporosis (2.2% of the placebo group had fractures and 1% in the alendronate group), for an NNT of 83. 

In another study of osteoporosis, actual adherence to a bisphosphonate regimen was found to be very low, with approximately half of patients discontinuing therapy within the first one to two years. This translates to a not very satisfactory NNT of 107 in sporadic users over four years. Moreover, the impact of even stringent compliance with bisphosphonate use was substantially less for fractures other than hip fractures and for younger women (<65 years of age).20

At this point, all we can say about drug intervention for osteopenia is that while it might not be very cost-effective, it may in certain select instances prevent fractures. Tools like the FRAX index, which applies a questionnaire-driven formula to enhance the predictive value of bone density scores, may help better identify a subset of osteopenic patients who deserve more aggressive therapy. The efficacy of lifestyle interventions, such as weight-bearing exercise or supplementation with bone-supportive nutrients like calcium and vitamin D, remains speculative in osteopenia but surely warrants investigation.


There are both advantages and disadvantages to medicine’s embrace of the concept of predisease. To counter the tendency toward unnecessary and harmful diagnostic creep, Viera has proposed that predisease as a category warranting preventive action makes sense only if three criteria are met: 

1. Individuals identified as having predisease must have a greater likelihood of developing disease than others not so identified.

2. An intervention must exist which, when used, effectively reduces the chance that the predisease will progress to actual disease.

3. The benefits of intervention in patients with predisease must outweigh any harms in the overall population.20

If these intelligent criteria are rigorously and consistently applied, while resisting commercial or policy imperatives that distort objectivity, predisease might well evolve into a valuable classification in a new preventive medical paradigm.

Ronald L. Hoffman is, MD, CNS, the founder and medical director of the Hoffman Center in New York City.


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