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.

01 Mar 2000·Journal of Bone and Mineral ResearchQ1 · MEDICINE

The Discrepancy Between the Binding Affinity of PTH (1–34) and RS 66271 is Explained by Interaction of the PTH/PTHrP Receptor With G-Protein

Q1 · MEDICINE

Letter

Author: Sam R. J. Hoare ; Ted B. Usdin

A polemic in response to C. Frolick et al (ibid., 1999, 14:163-172) attributing the discrepancy in the binding affinities of human parathormone-1-34 and RS 66271 to cells expressing the cloned human PTH/PTHrP receptor to different receptor states that arise from receptor-G protein coupling.

01 Nov 1999·Clinical pharmacology and therapeuticsQ2 · MEDICINE

USAN Council. List No.421. New names. Semparatide acetate.

Q2 · MEDICINE

Article

100 Deals associated with Semparatide

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