Cancellous Bone Volume Is Restored By Intermittent PTH After Mechanical Unloading

Abstract

PURPOSE Skeletally mature rats subjected to 28 days of hindlimb unloading (HU) experience a significant loss of proximal tibia bone mineral density (BMD) and plantar flexor muscle strength. Although muscle strength recovers within 14 days of reambulation, there is no sign of BMD recovery through 28 days. The purpose of this study was to evaluate the effectiveness of daily PTH (1–34; 80μg/kg/day) administration on enhancing recovery of bone parameters following 28 days of HU to better match rate of muscle strength recovery. METHODS Six-month-old male Sprague Dawley rats were divided into 3 groups: 28 day HU (HU; n=4), 28 day HU + 28 day recovery with vehicle (VEH; n=8) and 28 day HU + 28 day recovery with PTH (PTH; n=8). Both recovery groups received daily subcutaneous injections for 28 days during recovery from HU. In vivo peripheral quantitative computed tomography (pQCT; Stratec, Research M) scans of the proximal tibia metaphysis were obtained at baseline, after 28 days of HU (R+0), and at recovery days 14 (R+14) and 28 (R+28). In vivo peak isometric torque (ISO) and mass of plantar flexor muscles were obtained at sacrifice. RESULTS After HU (R+0), there was a significant loss of volumetric bone mineral density (vBMD) for both total (cortical shell + cancellous core) and cancellous-only compartments (−7 and 9%, respectively). At R+14, total and cancellous BMD of VEH -treated animals (544± 14 and 223 ±10 mg/cm3, respectively) remained similar to R+0 values while PTH-treated animals significantly increased both total and cancellous BMD (635 ± 17 and 257 ± 6 mg/cm3, respectively), to baseline levels. By R+28, BMD of VEH animals remained at R+0 levels while values in PTH-treated animals exceeded baseline values (+11 and 21 % for total and cancellous BMD). Muscle mass was significantly greater in both VEH and PTH groups compared to HU (+37 and 29%, respectively) while ISO was non-significantly higher (+3 and 4%, respectively). A subset of bones (n=2/gp) were analyzed using microCT (GE Medical Systems, RS-9) at the same location as studied by pQCT. PTH-treated animals had significantly higher cancellous BV/TV (+ 141%), accounted for by higher trabecular thickness (+33%) and number (+ 83%), compared to VEH-treated animals; there was no difference between HU and VEH-treated values. CONCLUSIONS These data demonstrate that mechanical unloading of bone does not preclude a robust response to PTH during subsequent reloading, and that recovery of cancellous bone volume and architecture is significantly enhanced by intermittent PTH.