Glucocorticoid-induced inhibition of osteolysis and the development of osteopetrosis, osteonecrosis and osteoporosis.
Changes in the developing femoral epiphysis, especially those concerning the osteocytes, were examined in pony foals systemically treated with daily intramuscular injections of either 0.5 or 5.0 mg of dexamethasone per 100 kg bodyweight for either 3, 8 or 11 months. Midsagittal sections of proximal femur from animals treated for 3 months contained significantly more bone tissue subchondrally and epiphyseally than did sections from untreated ponies. Large portions of the bone tissue appeared necrotic, although osteoblasts and patent capillaries were abundant. After 8 months the bone sections revealed marked osteoporosis. Abnormally dense bone was again observed after 11 months. There were significant increases in the severity of these changes in bone from the animals treated with the higher dosage. Calcium kinetics studies revealed an inhibition  of calcium deposition (bone formation) in the treated animals after 2 and 7 months. However, calcium removal (bone resorption) was inhibited to a greater extent. Osteopetrosis (radiographic sclerosis) resulted from the initial resorption/formation imbalance, and was accompanied by osteonecrosis and osteocyte death. Continued treatment resulted in osteopenia, caused by the removal of necrotic bone debris and the inhibition of new bone formation. The primary event in the development of glucocorticoid-induced bone disease was shown to be suppression of osteolysis with the development of osteonecrosis.
D000818:Animals; D001862:Bone Resorption / Q000662:veterinary*; D002118:Calcium / Q000378:metabolism; D003907:Dexamethasone / Q000009:adverse effects*; D004838:Epiphyses / Q000187:drug effects / Q000254:growth & development; D005269:Femur / Q000187:drug effects / Q000254:growth & development; D006734:Horse Diseases / Q000139:chemically induced*; D006736:Horses; D010011:Osteocytes / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D010014:Osteolysis / Q000662:veterinary*; D010020:Osteonecrosis / Q000139:chemically induced / Q000662:veterinary*; D010022:Osteopetrosis / Q000139:chemically induced / Q000662:veterinary*; D010024:Osteoporosis / Q000139:chemically induced / Q000662:veterinary*
D003907:Dexamethasone; D002118:Calcium