Advantages of concurrent use of anabolic and antiresorptive agents over single use of these agents in increasing trabecular bone volume, connectivity, and biomechanical competence of rat vertebrae

The purpose of this study was to evaluate the usefulness of a combination r egimen of anabolic and antiresorptive agents in increasing skeletal quantit y and quality in comparison to a single-drug regimen with these agents. We examined histomorphometrically and biomechanically the effects of separate and combined administration of intermittent parathyroid hormone (PTH) and e strogen or bisphosphonate on both axial and appendicular skeletons of male Wistar rats, which were 4 months old and weighed approximately 300 g at the beginning of the treatment, The animals were untreated or injected with ve hicle, recombinant human PTH(1-84) (PTH; 100 mu g/kg daily), 17 beta-estrad iol (E-2, 500 mu g/kg every other day), incadronate disodium (YM175, 80 mu g/kg every other day), combined PTH and E-2 (PTH + E-2), or a combination o f PTH and YM175 (PTH + YM175). After 1 month of treatment, the three groups in which PTH was administered (PTH, PTH + E-2, and PTH + YM175) had signif icantly higher trabecular bone volume and connectivity in the proximal tibi al metaphyses (PTMs) compared with the untreated and vehicle-treated groups , whereas only combination groups (PTH + E-2 and PTH + YM175) showed signif icant increases in these indices in the lumbar vertebrae. This site-related discrepancy was attributed to the fact that PTH significantly elevated bon e resorption not in the PTMs but in the vertebrae. This increased bone reso rption in the vertebrae was suppressed by the addition of an antiresorptive agent, As a result, trabecular bone mass, connectivity, and mechanical str ength of the vertebrae were significantly increased from control levels onl y in the concurrent treatment groups (PTH + E-2 and PTH + YM175), The super ior skeletal effects of PTH cotherapy over PTH monotherapy were not seen wi th regard to bone mass, but with increased connectivity and mechanical stre ngth. The concurrent use of PTH and an antiresorptive agent has been shown to be superior to the single use of PTH for enhancing these properties of r at vertebrae, which encourages future research, especially in larger animal s. (C) 1999 by Elsevier Science Inc. All rights reserved.