PARATHYROID-HORMONE MONOTHERAPY AND COTHERAPY WITH ANTIRESORPTIVE AGENTS RESTORE VERTEBRAL BONE MASS AND STRENGTH IN AGED OVARIECTOMIZED RATS

Previous studies have shown that parathyroid hormone (PTH) monotherapy and cotherapy with estrogen or risedronate augment vertebral bone mas s and bone strength in young, ovariectomized (OVX) rats, The current s tudy was designed to determine whether PTH has similar bone anabolic e ffects in aged OVX rats at a much later stage of estrogen depletion, F emale Sprague Dawley rats were subjected to sham surgery or bilateral ovariectomy at three months of age and maintained untreated for one ye ar after surgery to allow for the development of vertebral osteopenia in OVX rats, Groups of baseline control and OVX rats were sacrificed a t the end of this pretreatment period, The remaining OVX rats were the n treated for ten weeks with vehicle, antiresorptive agents alone (est rogen, risedronate, or calcitonin), or PTH alone, Other groups of OVX rats were treated concurrently with PTH and each of the antiresorptive agents, The first and fourth lumbar vertebral bodies were processed u ndecalcified for quantitative bone histomorphometry and biomechanical testing, respectively, As expected, bone mass and compressive strength were decreased in the lumbar vertebral body of baseline OVX rats comp ared to baseline control rats, This bone loss was associated with decr eases in trabecular number and width and an increase in trabecular sep aration, Treatment with estrogen, risedronate, or calcitonin alone fai led to reverse the changes in bone mass, structure, and strength induc ed by ovariectomy, In contrast, treatment of OVX rats with PTH alone r estored vertebral cancellous bone volume and ash density to the level of vehicle-treated control rats and increased vertebral maximum load, stress, and normalized load to well above this level, The hormone sign ificantly increased trabecular width, but not number, in the lumbar ve rtebral body of OVX rats, Concurrent treatments with PTH and the antir esorptive agents did not augment cancellous bone and biomechanical com petence to a greater, or lesser, extent than treatment with PTH alone, Compressive strength correlated significantly with bone mass and trab ecular width in the lumbar vertebral body, These results indicate that PTH completely restores lost bone mass and improves bone strength in the vertebral body of aged OVX rats with established osteopenia. With our previous study in younger OVX rats, the current study demonstrates that the anabolic effect of PTH is independent of age and the stage o f estrogen depletion in the rat skeleton.