Results of bisphosphonate withdrawal: duration of antiresorptive activity, fractures, changes in BMD and bone turnover markers

Abstract

The review discusses the possibility of discontinuation of bisphosphonates (BPs), based on the mechanism of action of the drugs, the duration of their antiresorptive activity, criteria for discontinuation and return to therapy. BPs have a unique feature – maintaining the clinical effect for a long time after their withdrawal. Since BPs therapy is carried out for a long time, their accumulation in bone tissue, on the one hand, and the risk of developing severe adverse events, on the other hand, gave rise to discussion on the concept of temporary withdrawal of drugs and the organization of «drug holidays». The main criteria that are relied upon in the question of discontinuation of BPs and re-prescription at present are: 1) the risk of developing new fractures, 2) changes in bone mineral density (BMD), 3) dynamics of markers of bone metabolism. The conducted studies suggest that the suspension of treatment after 3-5 years of continuous therapy with BPs is possible in women who do not have low BMD indicators at the end of the course of therapy, while with continuing low levels of BMD, additional benefits from continuing therapy are likely. The loss of bone mass in the proximal femur and its preservation in the spine 2 years after discontinuation of BPs treatment is explained by their different localization and longer-term effect on bone metabolism in the spongy bone, i.e. in the spine. Delivery and absorption of BPs in the spine may be more intense than in other parts of the skeleton. Tracking the level of markers during a break in the treatment of BPs can be useful to determine the time of resumption of therapy: if their concentration approaches the baseline (before treatment), the patient’s condition should be reassessed and the issue of resuming therapy should be discussed. It should be noted that the optimal duration of «drug holidays» has not been established and should be selected individually depending on clinical circumstances, taking into account the presence of fractures, a significant decrease in BMD or an increase in markers of bone metabolism, as well as the presence and/or appearance of new clinically significant risk factors.