Parathyroid hormone induces formation of new cancellous bone with substantial mechanical strength at a site where it had disappeared in old rats

Objective: The present study addresses the question - can PTH induce formation of trabeculae in areas where cancellous bone has disappeared? Two-year-old male rats were chosen, because in this aged animal model the distal femurs have almost no cancellous bone, and the marrow cavity has reached a substantial dimension. Design: The rats were injected for 56 days with either PTH(1-34), 15 nmol/kg/day (62.5 mug/kg/day), or vehicle. Methods: Transverse specimens, 2-mm high, were cut from the distal femoral metaphysis. Marrow cavity diameters and cancellous bone trabeculae were analysed by a micro-computerized tomography scanner. The cancellous bone within the cortical and endocortical rim of each specimen was submitted to a biomechanical compression test. Furthermore, the cancellous bone was studied by dynamic tetracycline labelling and histomorphometry. Results: In the vehicle-injected group the trabecular bone volume was 0% (0-1.4), median (range). All PTH-injected rats had trabeculae in the distal metaphysis and the trabecular bone volume (6.7% (2.3-12.0)) was markedly increased (P < 0.003). The median trabecular thickness was increased (P < 0.003) in the PTH-injected rats (118 mum (104-125)) compared with the vehicle group (0 mum (0-71)). The compressive stress was increased (P < 0.003) in the PTH-injected group (0.7 MPa (0.1-2.1)) compared with the vehicle-injected group (0 MPa (0-0.4)). The histomorphometry revealed that only 3 animals of the 10 in the vehicle-injected group had trabeculae in the distal femoral metaphysis. All PTH-injected animals (12 of 12) had continuous trabecular bone network in the marrow cavity. Conclusion: Intermittent PTH treatment induced marked formation of new cancellous bone trabeculae with substantial mechanical strength, at a site where it had disappeared in old rats.