STIMULATION OF THE GROWTH OF FEMORAL TRABECULAR BONE IN OVARIECTOMIZED RATS BY THE NOVEL PARATHYROID-HORMONE FRAGMENT, HPTH-(1-31)NH2 (OSTABOLIN)

The human parathyroid hormone, hPTH-(1-84), and its hPTH-(1-34) fragme nt are promising anabolic agents for treating osteoporosis because the y can strongly stimulate the production of biomechanically effective c ortical and trabecular bone in osteopenic ovariectomized (OVX) rats an d trabecular bone in osteoporotic postmenopausal humans. The ideal PTH fragment for treating osteoporosis would be the smallest and function ally simplest fragment that activates only one signal mechanism and st ill strongly stimulates trabecular bone growth. A new PTH fragment, hP TH-(1-31)NH2, which only stimulates adenylyl cyclase instead Of stimul ating both adenylyl cyclase and phospholipase-C as do hPTH-(1-84) and hPTH-(1-34), is this minimum, high-potency anabolic fragment. hPTH-(1- 31)NH2 (which we have named Ostabolin) can greatly thicken trabeculae and increase the dry weight and calcium content of trabecular bone in the distal femurs of osteopenic, young, sexually mature OVX Sprague-Da wley rats when injected subcutaneously each day for 6 weeks at doses b etween 0.4 and 1.6 nmole/100 g of body weight.