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Low turnover osteoporosis in sheep induced by hypothalamic‐pituitary disconnection
Author(s) -
Beil Frank Timo,
Oheim Ralf,
Barvencik Florian,
Hissnauer Tim N.,
Pestka Jan M.,
Ignatius Anita,
Rueger Johannes M.,
Schinke Thorsten,
Clarke Iain J.,
Amling Michael,
Pogoda Pia
Publication year - 2012
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.22066
Subject(s) - bone remodeling , osteoporosis , osteoclast , medicine , endocrinology , osteopenia , leptin , osteoblast , hypothalamus , cortical bone , reduction (mathematics) , bone mineral , chemistry , receptor , anatomy , in vitro , geometry , mathematics , obesity , biochemistry
The hypothalamus is of critical importance in regulating bone remodeling. This is underscored by the fact that intracerebroventricular‐application of leptin in ewe leads to osteopenia. As a large animal model of osteoporosis, this approach has some limitations, such as high technical expenditure and running costs. Therefore we asked if a surgical ablation of the leptin signaling axis would have the same effects and would thereby be a more useful model. We analyzed the bone phenotype of ewe after surgical hypothalamo‐pituitary disconnection (HPD + OVX) as compared to control ewe (OVX) after 3 and 12 months. Analyses included histomorphometric characterization, micro‐CT and measurement of bone turnover parameters. Already 3 months after HPD we found osteopenic ewe with a significantly decreased bone formation (69%) and osteoclast activity (49%). After a period of 12 months the HPD group additionally developed an (preclinical) osteoporosis with significant reduction (33%) of femoral cortical thickness, as compared to controls (OVX). Taken together, HPD leads after 12 month to osteoporosis with a reduction in both trabecular and cortical bone caused by a low bone turnover situation, with reduced osteoblast and osteoclast activity, as compared to controls (OVX). The HPD‐sheep is a suitable large animal model of osteoporosis. Furthermore our results indicate that an intact hypothalamo‐pituitary axis is required for activation of bone turnover. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1254–1262, 2012