PREDNISONE INHIBITS FORMATION OF CORTICAL BONE IN SHAM-OPERATED AND OVARIECTOMIZED FEMALE RATS

Prednisone inhibits bone formation and causes bone loss. To investigat e possible mechanisms and sites, the effects of sham operation, ovarie ctomy, and prednisone were determined on bone and mineral metabolism i n 7-week-old growing female rats. Forty animals were divided into grou ps of 10 each. Sham operation and ovariectomy were performed. One week later, pellets containing 5 mg prednisone or drug free were implanted S.C. at the back of the neck. Four weeks later, animals were sacrific ed and tibiae were removed for histomorphometric analysis of the middi aphysis and proximal metaphysis. In both sham-operated and ovariectomi zed rats, prednisone (1) reduced weight gain (P < 0.02) and did not al ter uterine weight; (2) lowered serum magnesium (Mg) (P < 0.001) and d id not change serum calcium (Ca), phosphate (P), 25-hydroxyvitamin D ( 25OHD), or 1,25-dihydroxyvitamin D [1,25(OH)(2)D]; (3) produced striki ng increases in calcified cartilage, reduced cross-sectional area (P < 0.05) and cortical area (P < 0.01) and did not change medullary area of the tibial diaphysis; (4) lowered periosteal and endocortical bone formation and apposition rates; and (5) increased mean cancellous bone area (P < 0.05) and cancellous bone perimeter (P < 0.01) of the tibia l metaphysis. In both control and prednisone-treated rats, ovariectomy (1) reduced uterine weight (P < 0.001); (2) did not change serum Ca, P, Mg, 25OHD, or 1,25(OH)(2)D; (3) did not change mean cross-sectional , medullary, or cortical areas; (4) increased periosteal bone formatio n and apposition rates (P < 0.01) and did not alter endosteal bone for mation and apposition rates, and (5) decreased cancellous bone area (P < 0.01) and cancellous bone perimeter (P < 0.01). Thus, in short-term studies, prednisone increased calcified cartilage and inhibited the f ormation of cortical bone at periosteal and endosteal surfaces and red uced cortical bone of the tibia in both sham-operated and ovariectomiz ed, rapidly growing animals.