title: 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.
authors.affiliation: Hospital for Special Surgery, New York, NY 10021, USA. Bostromm@hss.edu
authors.forename: M P
authors.initials: MP
authors.lastname: Bostrom
authors.forename: S C
authors.initials: SC
authors.lastname: Gamradt
authors.forename: P
authors.initials: P
authors.lastname: Asnis
authors.forename: B H
authors.initials: BH
authors.lastname: Vickery
authors.forename: E
authors.initials: E
authors.lastname: Hill
authors.forename: Z
authors.initials: Z
authors.lastname: Avnur
authors.forename: R V
authors.initials: RV
authors.lastname: Waters
mesh_terms: D000818:Animals; D017102:Fracture Healing / Q000187:drug effects*; D008297:Male; D011241:Prednisone / Q000627:therapeutic use*; D011817:Rabbits; D019379:Teriparatide / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D019379:Teriparatide; C104917:RS 66271; D011241:Prednisone