Teriparatide (recombinant parathyroid hormone 1–34) enhances bone allograft integration in a clinically relevant pig model of segmental mandibulectomy

Abstract

Massive craniofacial bone loss poses a clinical challenge to maxillofacial surgeons.Structural bone allografts are readily available at tissue banks but are rarely used due to a high failure rate. Previous studies showed that intermittent administration of recombinant parathyroid hormone (rPTH) enhanced integration of allografts in a murine model of calvarial bone defect. To evaluate its translational potential, the hypothesis that rPTH would enhance healing of a mandibular allograft in a clinically relevant large animal model of mandibulectomy was tested. Porcine bone allografts were implanted into a 5-cm-long continuous mandible bone defect in six adult Yucatan minipigs, which were randomized to daily intramuscular injections of rPTH (1.75 μg/kg) and placebo (n = 3). Blood tests were performed on Day 56 preoperation, Day 0 and on Day 56 postoperation. Eight weeks after the surgery, bone healing was analyzed using high-resolution X-ray imaging (Faxitron and micro computed tomography [CT]) and three-point bending biomechanical testing. The results showed a significant 2.6-fold rPTH-induced increase in bone formation (p = 0.02). Biomechanically, the yield failure properties of the healed mandibles were significantly higher in the rPTH group (yield load: p < 0.05; energy to yield: p < 0.01), and the post-yield displacement and energy were higher in the placebo group (p < 0.05), suggesting increased mineralized integration of the allograft in the rPTH group. In contrast to similar rPTH therapy studies in dogs, no signs of hypercalcemia, hyperphosphatemia, or inflammation were detected. Taken together, we provide initial evidence that rPTH treatment enhances mandibular allograft healing in a clinically relevant large animal model.

Parathyroid Hormone 1 Receptor Signaling in Dental Mesenchymal Stem Cells: Basic and Clinical Implications

“…Allografts face the challenge of integrating with the host bone. However, PTH is reported to stimulate osteoprogenitor differentiation and enhance bone formation and bone mineralization in calvaria or mandible defects ( Sheyn et al, 2013 ; Pelled et al, 2020 ). It promotes neovascularization in the graft surroundings ( Cohn Yakubovich et al, 2017a ), resulting in less fibrosis and scar tissue formation as well as superior allograft integration.…”

A parathyroid hormone related supramolecular peptide for multi-functionalized osteoregeneration

“…It has been approved by the Food and Drug Administration (FDA) to treat postmenopausal osteoporosis as an anabolic drug [ 11 , 12 ]. Intermittent subcutaneous injection of PTH1-34 has also been used to promote bone repair in preclinical trials [ 13 ]. However, daily injection of PTH1-34 is generally related to low patient compliance, high care costs and systemic adverse effects.…”