ATYPICAL FRACTURES DUE TO LONG TREATMENT WITH BISPHOSPHONATES (CRITICAL REVIEW)

Abstract

This paper reviews the evidence for an association between atypical subtrochanteric fractures and long-term bisphosphonate use. A PubMed search of literature was performed. Estimation of scientific level of evidences, extraction of quantitative data about atypical fractures from publication were performed. Common clinical and X-ray features of ‘atypical’ fractures are described. Level IV publications contain assumptions of relationship between long term (more than 5 years) bisphosphonates’ (alendronate, ibandronate) treatment and atypical fractures. No data found about connection between zoledronic acid and atypical fractures. Data about relative risk of atypical fractures which is retrieved from meta-analysis’s and post-hock analysis’s of randomized clinical investigations is discrepant. No meta-analysis’s and randomized clinical investigations with statistically valid evidence of correlation between atypical fractures and long term bisphosphonates treatment have been found. Despite the relative rarity of atypical femoral fractures and doubtful evidences of their connection to bisphosphonates therapy, physicians and patients should be made aware of the possibility of such phenomenon. Principles of rational bisphosphonates therapy are being discussing. Because bisphosphonates accumulate in bone, they create a reservoir leading to continued release from bone for months or years after treatment is stopped. The feature described above is the base to recommendation for a drug holiday after 5-10 yr of bisphosphonate treatment. Clinical recommendations to reduce risks, rational diagnostic and surgical algorithm to treat atypical fractures are proposed for physicians dealing with osteoporosis, osteoporotic fractures and their consequences. Researches should be undertaken to get additional epidemiologic and clinical data to establish the true relationship between atypical fractures and long term bisphosphonates using. Bisphosphonates are effective and relatively safe remedies which reduce risk of osteoporotic fractures of any part of skeleton. Clinical advantages of bisphosphonates using exceed the doubtful and unproved risk of atypical fractures.