Received January 9, 2006
Revised January 23, 2006
Accepted after revision February 13, 2006
Neuroendocrinology/Endocrinology [270]
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Histamine mediates osteoclastic resorption only during the acute phase of bone loss in ovariectomized rats
Philippe Lesclous 1,
Frederic Schramm 1,
Sebastien Gallina 2,
Brigitte Baroukh 2,
Dominique Guez 2,
Jean-Louis Saffar 2*
1 Univ Paris-5 Faculte de Chirurgie Dentaire
2 Univ Paris-5 Faculte de Chirurgie Dentaire
* To whom correspondence should be addressed. E-mail: jean-louis.saffar{at}univ-paris5.fr.
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Abstract |
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Short-term studies have shown that histamine is involved, via its H2 receptors (H2R), in the mediator network regulating trabecular bone loss in long bones of ovariectomized (ovx) rats. It is not known whether this effect of histamine persists over time or involves other skeletal sites. In this study rats were maintained for 6 months post-ovx and treated daily with saline or famotidine (10 mg/kg), an H2R antagonist. At the end of the experimental period femur trabecular bone mass was strongly decreased in ovx rats, whether or not they were treated with famotidine. In contrast, in the fourth lumbar vertebra, where bone loss starts later than in the femur, famotidine treatment attenuated the decline in trabecular bone volume, protected the trabecular architecture, maintained the thickness of the cortices and reduced the numbers of osteoclasts and TRAP+ preosteoclasts, whereas it had no influence on formation parameters. In vertebral bone marrow of ovx rats, the numbers of mast cells (MC) and non-MC histamine-producing cells increased while famotidine treatment significantly diminished both cell populations. These data show that H2R antagonism does not protect trabecular bone mass in the long term, and that short term protection involves all bones. Histamine is involved during the early phase of strong osteoclastic resorption but not during the late phase of slower resorption, suggesting that different mediator networks control the two phases of destruction. Histamine would be part of the network mediating the early phase.
Key Words:
Bone, Histamine, Oestrogen