Bone safety of long-term bisphosphonate treatment.

Bisphosphonates (BPs) are widely used in osteoporosis and other bone diseases. Treatment of osteoporosis would, in many instances, involve continued use of BP for a number of years, so it is pertinent to examine skeletal consequences of long-term BP use. Through a non-systematic review of the literature, this commentary considers the reduction in bone turnover and retention in the skeleton with regard to the long-term safety of BP use. BPs normalize bone turnover rates within weeks and no further suppression is seen during long term use, documented up to 10 years. This indicates that the BP retained in bone does not augment or contribute to the pharmacological activity of newly administered BP. Therefore, pharmacologically, long term treatment is not different from short term treatment. Multiple studies have shown that reductions in bone turnover are associated with increased bone density, more homogeneous mineralization, and reduced fracture risk. The amount of BP retained in bone after 10 years of alendronate treatment was estimated at 75 mg per 2 kg mineral, using a pharmacokinetic model for a dose of 10 mg per day. This small fraction, which is unevenly distributed between cancellous and cortical bone, seems unlikely to change bone mechanical properties. Taken together, the known mechanism of action of potent BPs and the experience accrued from treating a large number of patients, including up to 10 years follow-up in controlled trials, have identified only beneficial BP effects on bone.