Objective: To assess the effect of intermittent subcutaneous injections of signal-selective parathyroid hormone (PTH) peptide analog on fracture healing in orchiectomized mouse models.
Methods: Thirty-six 7-week-old C57/BL male mice were orchiectomized and injected with hPTH(1-34), the signal-selective PTH peptide analog [Gly(1), Arg(19)]hPTH (1-34), or an identical volume of vehicle 1 week after induction of femoral fracture. At 14 and 28 days after the operation, the mice were sacrificed for measurement of bone mineral density (BMD) and bone mineral content (BMC) of the callus using by dual energy X-ray absorptiometry. The bone healing was evaluated by radiography, biomechanical testing, micro-computed tomography (Micro-CT) and histological examination.
Results: At 14 days after the operation, BMD in PTH peptide analog group was significantly increased (P<0.05). The mouse models treated with the PTH peptide analog showed significantly lower ultimate bending force and bending rigidity than those with hPTH(1-34) treatment. X-ray and Micro-CT scanning showed that callus transformation and remodeling was better in PTH peptide analog group than in the vehicle control group but poorer than in hPTH(1-34) group.
Conclusion: The signaling-selective PTH peptide analog G1, R19 (1-28) can accelerate fracture healing in orchiectomized mouse models, in which process cAMP/PKA pathway plays an important role.