Combination antiresorptive and osteoanabolic therapy for osteoporosis: we are not there yet

Osteoanabolic therapy is theoretically and practically an appealing therapeutic option for men and postmenopausal women with osteoporosis because bone formation is directly stimulated, an action that is not shared by any antiresorptive agent. Parathyroid hormone (PTH), in the form of the full-length molecule (PTH[1-84]) and its fully active but truncated amino-terminal fragment teriparatide (PTH[1-34]), belong to this osteoanabolic class. Both formulations of PTH increase bone mineral density, increase biochemical markers of bone turnover, and reduce fracture incidence. They improve skeletal microstructure. While antiresorptive agents are considered by most to be first line for the treatment of osteoporosis, there are situations when anabolic therapy could be reasonably considered as first line. In most situations, however, treatment with PTH follows a course of antiresorptive therapy. Simultaneous combination therapy with PTH and an antiresorptive drug does not appear to provide any advantages over monotherapy. After the recommended 2-year period of PTH treatment, an antiresorptive should be used to maintain densitometric gains. The drugs are well tolerated. Early safety concerns about osteosarcoma in rats have not been borne out after almost 9 years experience with human subjects.