COMPARISON OF THE ABILITY OF RECOMBINANT HUMAN PARATHYROID-HORMONE, RHPTH-(1-84), AND HPTH-(1-31)NH2 TO STIMULATE FEMORAL TRABECULAR BONE-GROWTH IN OVARIECTOMIZED RATS

A recombinant human parathyroid hormone, rhPTH-(1-84), which is curren tly in Phase II clinical trial, and hPTH-(131)NH2 (Ostabolin) are prom ising anabolic agents for treating osteoporosis because they can stimu late cortical and trabecular bone growth in osteopenic, ovariectomized (OVX) rats and in osteoporotic, postmenopausal women when injected su bcutaneously and intermittently at low doses. We have now found that, despite their different sizes and signaling properties (rhPTH-(1-84) s timulates adenylyl cyclase and phospholipase C; hPTH-(1-31)NH2 only st imulates adenylyl cyclase), they are equally osteogenic in OVX rats. T hus daily subcutaneous injections of 0.6 nmol/100 g of body weight of rhPTH-(1-84) or hPTH-(1-31)NH2 into 3-month-old OVX rats for 6 weeks s tarting 2 weeks after OVX equally reduced the otherwise large OVX-trig gered loss of femoral trabecular bone. Dairy subcutaneous injections o f 0.4 or 0.8 nmol/100 g of body weight of the two agents for 6 weeks a lso equally increased the mean thickness of the remaining femoral trab eculae in 3-month-old and 1-year-old OVX rats to 20 to 80% above the v alue in normal animals when started 9 weeks after ovariectomy.