Sicurezza a lungo termine dei Farmaci anti riassorbitivi: chi, quando e per quanto tempo trattare?


Year: 2014



Sicurezza a lungo termine dei Farmaci anti riassorbitivi: chi, quando e per quanto tempo trattare?

The last 15 years has seen remarkable advances in predicting and reducing fracture risk; extremely good news for patients with osteoporosis and their clinicians. Therapies for osteoporosis have been developed and are now available that are highly effective in reducing fracture risk by as much as 40-50% for hip fractures and 50 to70% for spine fractures. Bisphosphonates in particular have been studied in large randomized trials and have become the mainstay of osteoporosis therapy. More good news: bisphosphonates are now generic, their cost is low and there are numerous convenient dosing options.

However, recent safety concerns have arisen which threaten widespread use of bisphosphonates and other antiresorptives. Particularly impactful have been concerns about atypical fractures (AFF) which have been studied in the last 2-3 years in a number of large case-control, cohort and randomized studies. These epidemiologic studies are characterized by varying methods which are reflected in greatly varying results from an bisphosphonate/AFF relative risk of 1 to a staggering RR=66. Importantly, overall this metaanalysis showed a modest relative risk of 1.7.

Two recent studies (by Schilcher and Feldstein) found that upon careful x-ray review, fractures meeting AFF criteria are vanishing rare, representing less that 0.5% of all hip fractures. A recently-published meta-analysis of bisphosphonates and AFF (Gedmintas) calculated that the RR for bisphosphonate/AFF was 1.7 (95%CI:1.2,2.4), although the authors emphasized the variation between studies. These analyses strongly suggest that benefits far outweigh risks. Using these recent studies, I will examine the potential benefits vs risk for bisphosphonate therapy for 3 to 5 years. Using the recent meta analysis results and others, we can calculate that for 10,000 osteoporotic women using bisphosphonates, we can expect to prevent 1000 fractures but cause only 1 or 2 AFF cases. Clearly the benefits of 3-5 years use strongly outweigh any possible risks. Therefore, the clinical community needs to consider strategies varying from research studies to public relations initiatives that could help put concerns into perspective for patients.

However, when considering longer term therapy beyond 5 years, fracture benefits from long term therapy may be less and concerns about AFF and ONJ, whether real or perception, become more important. Results suggest that continuation beyond 5 years will result in lower risk of vertebral fractures and that patients at highest risk of spine fracture will therefore receive the largest benefits. This is an important result that can help us select patients who are likely to benefit from continuation vs. those who might benefit from a drug holiday. Based on these results, I will discuss algorithms for selecting patients and treatment strategies beyond 5 years of therapy.