Effect of systemic parathyroid hormone (1-34) and a β-tricalcium phosphate biomaterial on local bone formation in a critical-size rat calvarial defect model

Objective: The objective of this study was to evaluate local bone formation following systemic administration of parathyroid hormone (1-34) (PTH), a surgically implanted synthetic β-tricalcium phosphate (β-TCP) bone biomaterial serving as a matrix to support new bone formation. Materials and Methods: Critical-size, 8 mm, calvarial through-and-through osteotomy defects were surgically created in 100 adult male Sprague-Dawley rats. The animals were randomized into five groups of 20 animals each to receive one of the following treatments: PTH (15 μg PTH/kg/day; subcutaneously), PTH/β-TCP, β-TCP, or particulate human demineralized freeze-dried bone (DFDB), and sham-surgery controls. Ten animals/group were euthanized at 4 and 8 weeks post-surgery for radiographic and histometric analysis. Results: The histometric analysis showed that systemic PTH significantly enhanced local bone formation, bone fill averaging (±SE) 32.2±4.0% compared with PTH/β-TCP (15.7±2.4%), β-TCP (12.5±2.3%), DFDB (14.5±2.3%), and sham-surgery control (10.0±1.5%) at 4 weeks (p<0.014). Systemic PTH showed significantly enhanced bone formation (41.5±4.0%) compared with PTH/β-TCP (22.4±3.0%), β-TCP (21.3±4.4%), and with the sham-surgery control (23.8±4.2%) at 8 weeks (p<0.025). The DFDB group showed significantly increased bone formation from 4 (14.5±2.3%) to 8 weeks (32.0±3.2%) (p<0.006). The PTH/β-TCP and β-TCP groups both showed limited biomaterials resorption. The radiographic analysis was not diagnostic to distinguish local bone formation from the radiopaque β-TCP biomaterial. Conclusions: Systemic administration of PTH significantly stimulates local bone formation. Bone formation was significantly limited by the β-TCP biomaterial.