Histamine mediates osteoclastic resorption only during the acute phase of bone loss in ovariectomized rats

Abstract

Short-term studies have shown that histamine is involved, via its H 2 receptors (H 2 R), 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 postOVX and treated daily with saline or famotidine (10 mg kg −1 ), an H 2 R antagonist. At the end of the experimental period, femur trabecular bone mass was markedly 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 tartrate-resistant acid phosphatase-positive preosteoclasts, whereas it had no influence on bone formation parameters. In vertebral bone marrow of OVX rats, the numbers of mast cells (MCs) and non-MC histamine-producing cells increased, while famotidine treatment significantly diminished both cell populations. These data show that H 2 R 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.

Antihistamine Therapy and Bone Mineral Density: Analysis in a Population-Based US Sample

“…Bone loss is known to be associated with mastocytosis, in which excess release of histamine enhances bone remodeling 19. Estrogen's effect on bone health may be partly related to histamine; estrogen depletion directly stimulates histamine release from mast cells and increases bone resorption through osteoclastogenesis 17, 20. Our observation of an increment in bone density in H1RA users suggests that histamine blockade by H1RA may protect against osteoporosis.…”

“…Animal studies suggested that histamine is involved in the early phase of bone destruction,18, 20 and that decreased osteoclastic activation by H1RA may not last long. 28 Along with the fact that the protective effect of histamine antagonists against femoral bone loss did not last more than 6 months after the beginning of the treatment, 20 our observation also suggests that the inhibitory effects of these medications on bone loss may not persist for over time.…”

The role of mast cells in parathyroid bone disease

“…(38,39) To date, studies have emphasized the role of mast cell–derived histamine in osteoclastogenesis and bone resorption. (40–44) The role of mast cells in osteoblast differentiation and HPT-induced bone marrow fibrosis has received less attention.…”

Famotidine, a H2 receptor antagonist, decreases the late phase of orthodontic tooth movement in rats

“…Famotidine decreased orthodontic tooth movement and the gene expression level of histamine H 2 receptors increased during the late stage of orthodontic tooth movement. Histamine H 2 antagonists have been shown to prevent osteoclastic bone resorption [2,7]. According to these results, histamine could play a role via the H 2 receptors during the late stage of orthodontic tooth movement in rats.…”

“…Many mediators are involved in that process [1], histamine is probably one of them. It is involved, via histamine H 2 receptors in regulating trabecular bone loss in long bones of ovariectomized rats [2]. The aim of the study was to determine the infl uence of famotidine, a histamine H 2 receptor antagonist, on orthodontic tooth movement in rats.…”