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Mice lacking beta-adrenergic receptors have increased bone mass but are not protected from deleterious skeletal effects of ovariectomy.

Abstract：

:Activation of beta2-adrenergic receptors inhibits osteoblastic bone formation and enhances osteoclastic bone resorption. Whether beta-blockers inhibit ovariectomy-induced bone loss and decrease fracture risk remains controversial. To further explore the role of beta-adrenergic signaling in skeletal acquisition and response to estrogen deficiency, we evaluated mice lacking the three known beta-adrenergic receptors (beta-less). Body weight, percent fat, and bone mineral density were significantly higher in male beta-less than wild-type (WT) mice, more so with increasing age. Consistent with their greater fat mass, serum leptin was significantly higher in beta-less than WT mice. Mid-femoral cross-sectional area and cortical thickness were significantly higher in adult beta-less than WT mice, as were femoral biomechanical properties (+28 to +49%, P < 0.01). Young male beta-less had higher vertebral (1.3-fold) and distal femoral (3.5-fold) trabecular bone volume than WT (P < 0.001 for both) and lower osteoclast surface. With aging, these differences lessened, with histological evidence of increased osteoclast surface and decreased bone formation rate at the distal femur in beta-less vs. WT mice. Serum tartrate-resistance alkaline phosphatase-5B was elevated in beta-less compared with WT mice from 8-16 wk of age (P < 0.01). Ovariectomy inhibited bone mass gain and decreased trabecular bone volume/total volume similarly in beta-less and WT mice. Altogether, these data indicate that absence of beta-adrenergic signaling results in obesity and increased cortical bone mass in males but does not prevent deleterious effects of estrogen deficiency on trabecular bone microarchitecture. Our findings also suggest direct positive effects of weight and/or leptin on bone turnover and cortical bone structure, independent of adrenergic signaling.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Bouxsein ML,Devlin MJ,Glatt V,Dhillon H,Pierroz DD,Ferrari SL

doi

10.1210/en.2008-0843

subject

Has Abstract

pub_date

2009-01-01 00:00:00

pages

144-52

issue

eissn

0013-7227

issn

1945-7170

pii

en.2008-0843

journal_volume

150

pub_type

杂志文章

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Mice lacking beta-adrenergic receptors have increased bone mass but are not protected from deleterious skeletal effects of ovariectomy.