Osteoporosis International

, Volume 18, Issue 8, pp 1073–1082

The RANKL inhibitor OPG-Fc increases cortical and trabecular bone mass in young gonad-intact cynomolgus monkeys

  • M. S. Ominsky
  • P. J. Kostenuik
  • P. Cranmer
  • S. Y. Smith
  • J. E. Atkinson
Original Article

DOI: 10.1007/s00198-007-0363-7

Cite this article as:
Ominsky, M.S., Kostenuik, P.J., Cranmer, P. et al. Osteoporos Int (2007) 18: 1073. doi:10.1007/s00198-007-0363-7

Abstract

Summary

Weekly treatment of gonad-intact cynomolgus monkeys (for up to 6 months) with the RANKL inhibitor OPG-Fc reduced bone turnover markers and increased volumetric cortical and trabecular BMD and BMC at radial and tibial metaphyses. OPG-Fc was well tolerated in this study without evidence of change in measured toxicologic parameters vs. control.

Introduction

RANKL is the primary mediator of osteoclast formation, function, and survival. The catabolic effects of RANKL are inhibited by OPG, a soluble decoy receptor for RANKL. We investigated the safety and pharmacology of OPG-Fc in gonad-intact cynomolgus monkeys.

Methods

Males and females were treated weekly with vehicle (n = 5/sex) or OPG-Fc (15 mg/kg) by s.c. (n = 5/sex) or i.v. (n = 3/sex) injection for 6 months.

Results

Routine toxicologic investigations, hematologic parameters, body and organ weights, and ophthalmologic and electrocardiographic findings were not affected by OPG-Fc treatment. Because s.c. and i.v. dosing of OPG-Fc caused similar effects, these groups were combined for analyses. The following endpoints were significantly different in males and/or females treated with OPG-Fc relative to sex-matched vehicle controls after 6 months (p < 0.05). Biochemical markers of bone turnover (urine N-telopeptide and serum osteocalcin) were significantly decreased with OPG-Fc treatment. Cortical and trabecular volumetric BMD and BMC, cortical thickness, and cross-sectional moment of inertia were significantly increased by OPG-Fc treatment at the proximal tibia and distal radius metaphyses. Increases in cortical thickness were associated with significantly greater periosteal circumference.

Conclusions

OPG-Fc increased cortical and trabecular BMD and BMC in young gonad-intact cynomolgus monkeys.

Keywords

Bone geometry Bone remodeling Cortical bone OPG Primate RANKL 

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2007

Authors and Affiliations

  • M. S. Ominsky
    • 1
  • P. J. Kostenuik
    • 1
    • 4
  • P. Cranmer
    • 2
  • S. Y. Smith
    • 3
  • J. E. Atkinson
    • 2
  1. 1.Department of Metabolic DisordersAmgen Inc.Thousand OaksUSA
  2. 2.Department of ToxicologyAmgen Inc.Thousand OaksUSA
  3. 3.Charles River Laboratories Preclinical Services Montreal, Inc.SennevilleCanada
  4. 4.Metabolic Disorders ResearchAmgen Inc.Thousand OaksUSA

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