Anabolic effects of human biosynthetic parathyroid hormone fragment (1-34), LY333334, on remodeling and mechanical properties of cortical bone in rabbits

Intermittent administration of parathyroid hormone (PTH) has an anabolic ef fect in cancellous bone of osteoporotic humans. However, the effect of PTH on cortical bone with Haversian remodeling remains controversial. The aim o f this study was to determine the effects of biosynthetic human PTH(1-34) o n the histology and mechanical properties of cortical bone in rabbits, whic h exhibit Haversian remodeling. Mature New Zealand white rabbits were treat ed with once daily injections of vehicle, or PTH(1-34), LY333334, at 10 mu g/kg/day or 40 mu g/kg/day for 140 days. Bodyweight in rabbits treated with PTH did not change significantly over the experimental period. Serum calci um and phosphate were within the normal range, but a 1 mg/ml increase in se rum calcium was observed in rabbits given the higher dose of PTH. Histomorp hometry of cortical bone in the midshaft of the tibia showed significant in creases in periosteal and endocortical bone formation in these rabbits, Int racortical bone remodeling in the tibia was activated and cortical porosity increased by PTH. Cross-sectional bone area and bone mass of the midshaft of the femur increased significantly after PTH treatment. Ultimate force, s tiffness, and work to failure of the midshaft of the femur of rabbits given the 40 mu g dose of PTH were significantly greater than those in the contr ol group, whereas elastic modulus was as significantly tower than that in t he rabbits given the 10 pg dose of PTH, but not different from controls. In the third lumbar vertebra, PTH increased both formation and resorption wit hout increasing cancellous bone volume. The increases in bone turnover and cortical porosity were accompanied hy concurrent increases in bone at the p eriosteal and endocortical surfaces. The combination of these phenomena res ulted in an enhancement of the ultimate stress, stiffness, and work to fail ure of the femur.