Enhancing Bone Regeneration and Osseointegration using rhPTH(1-34) and Dimeric R25CPTH(1-34) in an Osteoporotic Beagle Model

Abstract

Despite continuous parathyroid hormone (PTH) exposure potentially accelerating bone resorption, intermittent PTH administration has shown anabolic effects on bone microarchitecture. This study investigates the therapeutic impacts of two PTH analogs, rhPTH(1-34) and dimeric R25C PTH(1-34) on bone regeneration and osseointegration in a postmenopausal osteoporosis animal model.Twelve female beagles, osteoporotic post-ovariectomy, underwent implant surgeries. Animals were divided into three groups: control, daily rhPTH(1-34) injection, and daily dimeric R25C PTH(1-34) injection. After 10 weeks, bone regeneration and implant osseointegration were evaluated using micro-CT, histological/histomorphometric analyses, and serum biochemical analysis.While the rhPTH(1-34) group demonstrated improved microarchitectural characteristics, such as BMD, BV, trabecular metrics, and osseointegration degree, the dimeric R25C PTH(1-34) group showed similarly enhanced anabolic effects around the titanium implants, albeit these were less pronounced than the rhPTH(1-34), yet significantly better than the control group. Histologic and TRAP assays revealed that both PTH analogs significantly promoted bone regeneration and remodeling, especially in artificially created bone defects.This study demonstrated the therapeutic effects of rhPTH(1-34) and dimeric R25C PTH(1-34) on bone regeneration and titanium osseointegration in a beagle model with osteoporosis.