Is there Any Interest in Combining Treatments in Osteoporosis?

Combination therapy includes the concomitant or sequential use of compounds sharing the same mode of action (e.g. two or more inhibitors of bone resorption) or with distinct pathways of activity (e.g. an inhibitor of resorption plus an anabolic agent). Combinatorial use of anti-resorptive agents may generate concerns, due to the risk of inducing oversuppression of bone turnover. However, if low doses of estrogen, used for the management of climacteric symptoms, are insufficient to normalize bone turnover, an addition of a bisphosphonate to HRT can prove to be useful to achieve this objective. Patients pre-treated with inhibitors of resorption, who have no full therapeutic response, are good candidates for the treatment with anabolic agents. The increase in bone turnover that follows the introduction of parathyroid hormone in patients treated with an anti-resorptive agent is similar to that observed in treatment-naïve patients and the pattern of bone mineral density (BMD) increase is also identical, with the exception of a 6-month delay in the spine and hip BMD changes observed in prior alendronate-treated subjects. Current data discourage the concomitant use of alendronate and parathyroid hormone since the bisphosphonate appears to blunt, in men and women, the anabolic action of parathyroid hormone. Whether this also applies to other bisphosphonates or inhibitors of resorption remains unknown. The use of an inhibitor of bone resorption after completion of parathyroid hormone treatment seems an appropriate way to maintain the skeletal benefits gained during therapy. Longterm clinical studies, using fractures as an end-point should be initiated to better understand the clinical and pharmaco-economic interest of combination therapies in the management of osteoporosis.