The search for the optimal anabolic osteoporosis therapy

Large increases in bone mineral density (BMD) and reductions in fracture risk, particularly vertebral fractures, have generated much enthusiasm for anabolic therapy in the osteoporosis community. Two forms of parathyroid hormone (PTH) (PTH[1‐34] or teriparatide, and PTH[1‐84]) have been used clinically for almost a decade (PTH[1‐84] has not been approved for use in the United States). They have been shown to be safe and effective in increasing BMD and reducing fracture risk. However, PTH increases bone resorption as well as formation, and an ideal anabolic treatment would be one that could optimize the impact on formation while producing lesser changes in resorption. The search for such a treatment has been a theme in many interesting clinical studies over the last 10 years. The report by Horwitz and colleagues(1) in this issue of the Journal of Bone and Mineral Research details a 3‐month trial of one such approach: PTH related protein (PTHrP[1‐36]). Earlier, preliminary data collected in short‐term and small human studies,(2, 3, 4) as well as preclinical studies,(5) had suggested that PTHrP might increase formation without increasing resorption and provided the rationale for the current randomized trial comparing two doses of PTHrP to teriparatide over 3 months.(1) The absence or near absence of hypercalcemia with comparable doses in those prior studies(2, 3, 4) also suggested that PTHrP might avoid that known potential side effect of PTH therapy.