Mandibular Bone Formation Rates in Aged Ovariectomized Rats Treated with Anti-resorptive Agents Alone and in Combination with Intermittent Parathyroid Hormone

Abstract

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.

PTH Increases Jaw Mineral Density in a Rabbit Model of Osteoporosis

“…Consequently, analysis of our data has indeed shown significant positive PTH effects on BMD/BMC and calcium content of peri-alveolar bone. Thus, these results and those of others (Miller et al, 1997;Hunziker et al, 2000) support a beneficial effect of intermittent PTH administration in osteoporosis patients with periodontal disease, either alone or in combination with anti-resorptive agents. Moreover, an additional PTH benefit is that it might abrogate the risk of developing jaw osteonecrosis associated with bisphosphonates (Hess et al, 2008).…”

Distinctive anabolic roles of 1,25-dihydroxyvitamin D3 and parathyroid hormone in teeth and mandible versus long bones

“…One previous report showed that PTH stimulated dentin apposition in the thyroparathyroidectomized rat in a dose-dependent manner (Turnbull et al 1983), but another study showed that intermittent PTH treatment had no effect on dentin formation in aged ovariectomized rats . Although intermittent PTH treatment was shown to stimulate mandibular and alveolar crest bone formation in aged ovariectomized rats , the increased mineral apposition rate was much less in mandibles than in long bones (Hunziker et al 2000). Therefore, these findings suggest that the sensitivity of skeletal tissues to PTH may vary according to their embryological origin (Yonaga 1978).…”

Administration of Parathyroid Hormone, Prostaglandin E2, or 1-alpha,25-Dihydroxyvitamin D3 Restores the Bone Inductive Activity of rhBMP-2 in Aged Rats

“…Sustained elevated levels of PTH, such as occur in hyperparathyroidism, can be detrimental to skeletal metabolism; however, when given intermittently, PTH can be extremely anabolic (17). Intermittent administration of PTH increases both cortical and cancellous bone content (15,(18)(19)(20). Hunziker et al have demonstrated that intermittent PTH administration stimulates bone formation in the mandibles of aged ovariectomized rats (15,19).…”

“…Intermittent administration of PTH increases both cortical and cancellous bone content (15,(18)(19)(20). Hunziker et al have demonstrated that intermittent PTH administration stimulates bone formation in the mandibles of aged ovariectomized rats (15,19). Hence, it is possible that the response to the local bone-forming stimulus of rhBMP-2 was enhanced by the elevated bone metabolism caused by the daily injection of PTH.…”

“…The discrepancy between these studies may be partially due to the dose of PTH used. Hunziker et al (15) treated animals with PTH for 10 weeks (5 days per week) at a dose of 80 mg/kg BW and caused a substantial increase in BMD, but we used PTH at the low dose of (20 mg/kg) over a shorter period (2 weeks). PGE 2 and 1,25(OH) 2 D 3 had similar effects to PTH on local bone induction by rhBMP-2.…”