Parathyroid hormone-related protein analog RS-66271 is an effective therapy for impaired bone healing in rabbits on corticosteroid therapy

Abstract

A new class of parathyroid hormone-related protein (PTHrP) analogs has been developed that causes a rapid gain in both trabecular and cortical bone in models of osteopenia. This study investigates the efficacy of the PTHrP analog, RS-66271 ([MAP 1–10] 22–31 hPTHrP(1-34)–NH 2), as systemic therapy for impaired bone healing in corticosteroid-treated rabbits. A 1 mm defect was created bilaterally in the ulnae of 30 rabbits. Delayed healing was induced by daily injections of prednisone (0.15 mg/kg) beginning 2 months prior to surgery and continuing until killing. Rabbits in the experimental group received daily subcutaneous injections of PTHrP analog RS-66271 (0.01 mg/kg) starting 1 day after surgery. Control animals received subcutaneous normal saline. At the 6 week timepoint, nine of ten ulnae from PTHrP-treated rabbits achieved radiographic union, whereas only two of ten limbs achieved union in control rabbits ( p < 0.01). In a separate part of the study, 20 animals (10 control, 10 RS-66271-treated) were killed when radiographic union was achieved bilaterally. In this portion of the study, all limbs in animals treated with PTHrP achieved union by 6 weeks. In the control animals that were allowed to heal for 10 weeks, only 20% of the limbs achieved radiographic union. In addition, ulnae in the PTHrP-analog-treated rabbits showed greater radiographic intensity (20%–40%), larger callus area (209% anteroposterior view, 417% lateral view) (mean area on AP radiographs: control, = 387 ± 276 mm 2; PTHrP analog, 1195 ± 408 mm 2), and greater stiffness (64%) and torque (87%) when compared with controls. RS-66271 was shown to be an effective therapy for preventing impaired bone healing caused by prednisone in a rabbit model.