The effect of a single dose of osteoprotegerin in postmenopausal women

Osteoprotegerin (OPG), a tumor necrosis factor (TNF) receptor family member , is a critical regulator of bone resorption. It is an important inhibitor of the terminal differentiation and activation of osteoclasts. This randomi zed, double-blind, placebo-controlled, sequential dose escalation study was conducted in postmenopausal women to determine the effect of a single subc utaneous (sc) dose of OPG on bone resorption as indicated by the biochemica l markers, urinary N-telopeptide (NTS) and deoxypyridinoline (DPD), which a re stable collagen degradation products. NTS levels decreased within 12 h a fter OPG administration. At the highest dose administered (3.0 mg/kg), a me an percent decrease in NTS of approximately 80% was observed 4 days after d osing, Six weeks after dosing a mean decrease of 14% in NTX was observed. T he levels of bone-specific alkaline phosphatase (BSAP), a marker of bone fo rmation, did not change for approximately 3 weeks after dosing. Thereafter, a modest decrease, reaching approximately 30% at 6 weeks, was observed in the 3.0-mg/kg dose group. The rapid decrease from baseline in NTS and delay ed decrease in BSAP indicated that OPG acted primarily on osteoclasts to de crease bone resorption, OPG injections are well tolerated. This study, for the first time, indicates that a single sc injection of OPC is effective in rapidly and profoundly reducing bone turnover for a sustained period and t hat OPG therefore may be effective in treatment of bone diseases characteri zed by increased bone resorption such as osteoporosis.