Activin increases bone mass and mechanical strength of lumbar vertebrae inaged ovariectomized rats

Activin is a member of the transforming growth factor-beta superfamily and is thought to be involved in the regulation of bone formation due to its pr esence in bone tissue and its osteogenic activity both in vitro and in vivo . We recently found that systemic administration of activin increased both tibial bone mass and mechanical strength in young growing rats. The present study investigated the effects of activin in aged ovariectomized (ovx) rat s. Twelve-month-old Fischer rats were ovariectomized and maintained for 10 months. Recombinant human activin A (activin) or human parathyroid hormone 1-34 (PTH) was administered intramuscularly three times a week for 12 weeks . Activin (1 and 5 mu g/kg) markedly increased lumbar vertebral bone minera l content and bone mineral density. Activin also increased the mechanical s trength of the vertebral body, which was highly correlated to the bone mine ral density of the vertebral body. The maximal response in bone mass and st rength was observed at 1 mu g/kg of activin, which was approximately equal to that induced by PTH at 40 mu g/kg. Peripheral quantitative computed tomo graphy revealed that activin enlarged the cross-sectional size of the verte brae without changing the foramen area, indicating its effects on cortical shells. Histomorphometric analysis of cancellous bone of vertebral body in similar experiment showed that activin (3 mu g/kg) increased bone volume an d the mineralizing surface, although its effects were less than PTH, The pr esent results indicate that low doses of activin are effective against vert ebral bone loss in aged ovx rats. (Bone 27:91-96; 2000) (C) 2000 by Elsevie r Science Inc. All rights reserved.