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Intermittent administration of parathyroid hormone (PTH) is known to stimulate bone formation in many skeletal sites and is being investigated as a possible therapeutic agent for the treatment of osteopenic conditions, including post-menopausal osteoporosis. The purpose of this study was to determine the ability of PTH to stimulate bone formation in the mandibles of aged ovariectomized (Ovx) rats, and the results are compared with a site in the appendicular skeleton (humerus). The Ovx rat is a useful model of estrogen deficiency, replicating many aspects of post-menopausal osteoporosis. Female rats were ovariectomized or sham-operated, and one year later a group of the ovariectomized rats was treated with the 1-34 fragment of human PTH daily, five days a week for 10 weeks. During the experiment, the animals were given fluorochrome bone markers for histomorphometry. More than one year after ovariectomy or sham surgery, there were few differences in the histomorphometric indices of bone formation in the humerus or mandible. PTH treatment had no effect on dentin formation, measured in the mandibular incisor; however, most indices of bone formation-including the double-labeled surface, mineralizing surface, mineral appositional rate, new bone area, and surface-referent bone formation rates-were substantially greater in the PTH-treated group compared with both the Ovx and the Sham controls measured at the periosteal and endocortical surfaces of the humerus and the periosteal and cancellous bone surfaces of the mandible. In addition, bone formation at the alveolar crest, particularly on the buccal side, was greater in the PTH-treated group. The results from this study demonstrate that systemic intermittent PTH treatment stimulates bone formation in the mandibles in aged, estrogen-deficient animals.
Anti-resorptive agents--including estrogen (E), calcitonin (CT), and bisphosphonates--are established in the treatment of osteoporosis. Intermittent administration of parathyroid hormone (PTH) stimulates bone formation and is a possible therapeutic agent for the restoration of bone mass. The purpose was to determine the effects of the anti-resorptive agents alone and in combination with intermittent PTH on bone formation in the mandible and a long bone in the aged ovariectomized (Ovx) rat. Female rats were ovariectomized or sham-operated. One year later, groups of Ovx rats were treated with E, CT, or the bisphosphonate, Risedronate (NE). Additional groups of Ovx rats were treated with each of these agents in combination with human PTH for 10 weeks. Estrogen treatment suppressed most indices of bone formation in the humerus and mandible, while NE decreased some indices of formation at the endocortical and endosteal surfaces of the mandible and humerus. Increased double-labeled surface and mineral apposition rates were observed only on the mandibular endosteal surfaces following CT treatment. When the anti-resorptive agents were combined with intermittent PTH, most indices of bone formation at all skeletal sites were substantially greater than those of the untreated Ovx controls as well as the E-, CT-, and NE-treated groups, respectively. These results provide additional evidence that established and emerging therapies for osteoporosis affect osseous tissues in the oral cavity, and this may influence the progression of diseases and/or aging changes at this site.
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