RESEARCH ARTICLE


Long Term Cyclic Pamidronate Reduces Bone Growth by Inhibiting Osteoclast Mediated Cartilage-to-Bone Turnover in the Mouse



K.D Evans1, L.E Sheppard1, D.I Grossman1, S.H Rao2, R.B Martin2, A.M Oberbauer*, 1
1 Department of Animal Science, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA
2 Ellison Musculoskeletal Research Center, UC Davis Medical Center 4635 Second Avenue, Sacramento, CA 95817, USA


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Creative Commons License
© Evans et al.; Licensee Bentham Open.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.

* Address correspondence to this author at the Department of Animal Science, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA; E-mail: amoberbauer@ucdavis.edu


Abstract

Bisphosphonates, used to treat diseases exhibiting increased osteoclast activity, reduce longitudinal bone growth through an as yet undefined mechanism. Pamidronate, an aminobisphosphonate, was given weekly to mice at 0, 1.25, or 2.50 mg/kg/wk beginning at 4 weeks of age. At 12 weeks of age, humeral length, growth plate area, regional chondrocyte cell numbers, chondrocyte apoptosis, TRAP stained osteoclast number, and osteoclast function assessed by cathepsin K immunohistochemistry were quantified. Humeral length was decreased in pamidronate treated mice compared to vehicle control mice, and correlated with greater growth plate areas reflecting greater proliferative and hypertrophic chondrocyte cell numbers with fewer hypertrophic cells undergoing apoptosis. Pamidronate treatment increased TRAP stained osteoclast numbers yet decreased cathepsin K indicating that pamidronate repressed osteoclast maturation and function. The data suggest that long term cyclic pamidronate treatment impairs bone growth by inhibition of osteoclast maturation thereby reducing cartilage-to-bone turnover within the growth plate.

Keywords: Pamidronate, growth plate, bisphosphonates.