Editors' ChoiceOsteoporosis

Nervous About Bone Fragility

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Science's STKE  12 Nov 2002:
Vol. 2002, Issue 158, pp. tw413
DOI: 10.1126/stke.2002.158.tw413

Takeda et al. discovered that leptin inhibits bone formation through an unexpected pathway entirely distinct from its regulation of body weight. The specter of falling and breaking a hip, an injury associated with significant morbidity and mortality, haunts many elderly individuals whose bones have become fragile because of osteoporosis, the most common degenerative disease in developed countries. The observation that gonadal failure increases the risk for osteoporosis, whereas obesity decreases the risk, led to the discovery that leptin, a hormone involved in regulating body weight and gonadal function, also inhibits bone formation. Takeda et al. used selective lesioning of hypothalamic regions, together with intraventricular infusion of leptin, in wild-type and various mutant mice to demonstrate that different neuronal pathways mediate leptin's regulation of body weight and bone mass. Cross-circulation experiments in leptin-deficient mice, as well as targeted expression of leptin in transgenic mice, indicated that, unlike its effects on appetite, leptin's effects on bone mass are not mediated humorally by circulating substances. Rather, they depend on adrenergic inhibition of osteoblast proliferation and function mediated through the sympathetic nervous system. Treatment with a β-adrenergic receptor antagonist increased bone mass in wild-type and ovariectomized mice, leading to the intriguing possibility that β-blockers could provide a new means of treating osteoporosis.

S. Takeda, F. Elefteriou, R. Levasseur, X. Liu, L. Zhao, K. L. Parker, D. Armstrong, P. Ducy, G. Karsenty, Leptin regulates bone formation via the sympathetic nervous system. Cell 111, 305-317 (2002). [Online Journal]

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