title: Prednisone-induced osteopenia in beagles: variable effects mediated by differential suppression of bone formation.
abstract: To examine the mechanism of glucocorticoid-induced osteopenia and the basis for variable bone loss after glucocorticoid administration, we gave prednisone (1.3 mg.kg-1.day-1) to normal male dogs (n = 15) for 29 wk to attempt induction of osteopenia. Compared with age-matched control dogs (n = 14), prednisone treatment rapidly decreased spinal bone density by 4.3%, as assessed by quantitative digital radiography, and reduced trabecular bone volume by 14.6%, as measured by quantitative histomorphology of iliac crest bone specimens. Bone loss was attenuated in prednisone-treated dogs after prolonged treatment (greater than 12 wk). Prednisone treatment resulted in diminished bone formation rates (15 +/- 3.4 vs. 47 +/- 4.5 microns/yr) and activation frequency (0.4 +/- 0.1 vs. 1.3 +/- 0.2/day). These findings indicate that suppression of osteoblastic function and recruitment is the primary histological abnormality mediating glucocorticoid-induced osteopenia in beagles. In contrast, prednisone administration had no effect on bone resorption or serum concentrations of parathyroid hormone and 1,25-dihydroxyvitamin D, which suggests that these factors are not essential for prednisone-induced bone loss. Moreover, 33% of beagles were totally resistant to glucocorticoid-induced osteopenia. Such heterogeneity of bone loss was associated with variable suppressive effects of prednisone on osteoblastic function, as evidenced by greater bone formation rates and activation frequency in prednisone-resistant animals. Collectively, these observations suggest that glucocorticoid-induced bone loss results from a dynamic interplay between steroid-mediated suppression of osteoblastic function and recruitment and undefined compensatory factors that ameliorate the effects of glucocorticoids on osteoblastic precursors.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: L D
authors.initials: LD
authors.lastname: Quarles
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001851:Bone Diseases, Metabolic / Q000139:chemically induced* / Q000473:pathology; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology; D004285:Dogs; D008297:Male; D010012:Osteogenesis / Q000187:drug effects*; D011241:Prednisone / Q000494:pharmacology*; D012044:Regression Analysis
chemical_list: D011241:Prednisone