Combination therapy: the Holy Grail for the treatment of postmenopausal osteoporosis?

Agents for the treatment of osteoporosis are divided into broad categories according to whether the predominant effect is to inhibit bone resorption (antiresorptive drugs) or stimulate bone formation (osteo-anabolic drugs). However, due to the coupling of these two components of bone remodeling, drugs that inhibit bone resorption generally also reduce bone formation, and those that stimulate bone formation also increase bone resorption. Since these synchronous changes may limit the beneficial effects of treatment, researchers have undertaken a search for combinations of antiresorptive and osteo-anabolic drugs given concurrently, sequentially, intermittently, or cyclically that could partially or totally uncouple bone resorption and bone formation. This offers the potential for greater increases in bone mineral density (BMD), restoration of lost structural elements, and perhaps greater reduction in fracture risk than monotherapy with currently approved drugs. While some methods of combining drugs have been shown to enhance BMD response and perhaps extend the duration of osteo-anabolic effects compared to monotherapy, none have been proven to provide greater reduction of fracture risk. Upon completion of a course of osteo-anabolic therapy with daily subcutaneous parathyroid hormone, antiresorptive therapy must be started in order to prevent subsequent loss of BMD.