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

Prednisone inhibits bone formation and causes bone loss. To investigate possible mechanisms and sites, the effects of sham operation, ovariectomy, and prednisone were determined on bone and mineral metabolism in 7-week-old growing female rats. Forty animals were divided into groups 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 sacrificed and tibiae were removed for histomorphometric analysis of the middiaphysis and proximal metaphysis. In both sham-operated and ovariectomized rats, prednisone (1) reduced weight gain (P < 0.02) and did not alter uterine weight; (2) lowered serum magnesium (Mg) (P < 0.001) and did not change serum calcium (Ca), phosphate (P), 25-hydroxyvitamin D (25OHD), or 1,25-dihydroxyvitamin D [1,25(OH)(2)D]; (3) produced striking 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 tibial 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 formation and apposition rates (P < 0.01) and did not alter endosteal bone formation 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 formation of cortical bone at periosteal and endosteal surfaces and reduced cortical bone of the tibia in both sham-operated and ovariectomized, rapidly growing animals.