Failure of bone union remains a major complication in orthopedic reconstruction using massive intercalary allografts. Recombinant parathyroid hormone (rPTH1-34, teriparatide) has shown strong anabolic effects on bone in small-animal studies, prompting investigation of its translational potential in larger, clinically relevant models.
In this study, 20 adult mongrel hounds underwent a standardized 5-cm mid-diaphyseal femoral osteotomy reconstructed with a plated massive allograft. Dogs were randomized to receive placebo, continuous high-dose rPTH1-34, or delayed high-dose rPTH1-34. Treatment efficacy and safety were monitored over an eight-week postoperative period.
Radiographic and cone beam CT analyses revealed that continuous rPTH1-34 treatment significantly increased callus volume and cortical union as early as four weeks, with sustained improvements at eight weeks compared with placebo. Delayed treatment also enhanced callus volume and mineral apposition rates by the end of the study period.
Dynamic histomorphometry confirmed these findings, showing significantly increased mineral apposition rates at host bone and graft–host junctions in treated dogs. These results demonstrate a clear anabolic response to rPTH1-34 at sites critical for graft incorporation.
However, the high-dose regimen was poorly tolerated. Most treated dogs required intravenous fluid therapy to manage hypercalcemia, and one animal died as a direct consequence of calcium imbalance. These adverse events highlight a narrow therapeutic window for systemic anabolic stimulation of bone.
Biomechanical testing did not yet show significant differences in torsional strength, which was expected given the early stage of healing. Notably, radiographic healing scores were significantly correlated with biomechanical performance, supporting their validity as early indicators of functional recovery.
The authors conclude that while high-dose intermittent rPTH1-34 accelerates bone healing and graft union in a large-animal model, the associated systemic risks severely limit its clinical applicability at these doses. Future work must focus on optimizing dosing strategies or localized delivery methods to preserve efficacy while minimizing adverse effects.
Source: Nishitani, K., Mietus, Z., Schwarz, E. M., et al. (2017). High dose teriparatide (rPTH1-34) therapy increases callus volume and enhances radiographic healing at 8-weeks in a massive canine femoral allograft model. PLoS ONE, published October 11, 2017.
