Hypothalamic Leptin Gene Therapy Does Not Prevent Ovariectomy-Induced Bone Loss in Rats

Post-menopausal women are at an increased risk for osteoporosis due to increased\ud bone resorption associated with estrogen deficiency. Subcutaneous administration of leptin, a\ud hormone produced primarily by adipocytes, attenuates bone loss in the ovariectomized (ovx)\ud rat, an animal model for post-menopausal bone loss. Leptin has both direct peripheral and\ud indirect central nervous system-mediated effects on bone. In the present study we evaluated\ud the efficacy of increased central leptin, via hypothalamic leptin gene therapy, in preventing\ud bone loss in ovx Sprague Dawley rats. Ovx rats were injected in the hypothalamus with either\ud rAAV-lep (recombinant adeno-associated virus encoding leptin) or rAAV-GFP (control vector\ud encoding green fluorescent protein) and maintained for ten weeks. As expected, bone\ud volume/tissue volume in the lumbar vertebra and bone area/tissue area in the proximal tibia\ud were lower in ovx compared to intact rats. Differences in osteoclast perimeter, an index of\ud bone resorption, were not detected with treatment. Osteoblast perimeter, an index of bone\ud formation, was higher in ovx rAAV-lep rats compared to intact rats. Differences between\ud rAAV-lep and rAAV-GFP-treated rats were not detected for any endpoints evaluated. The\ud results suggest that increasing central leptin has no positive or negative effect on bone mass or\ud architecture in ovx rats