Abstract
Bone loss with aging and menopause may be linked to vascular endothelial dysfunction. The purpose of the study was to determine whether putative modifications in endothelium-dependent vasodilation of the principal nutrient artery (PNA) of the femur are associated with changes in trabecular bone volume (BV/TV) with altered estrogen status in young (6 mon) and old (24 mon) female Fischer-344 rats. Animals were divided into 6 groups: 1) young intact, 2) old intact, 3) young ovariectomized (OVX), 4) old OVX, 5) young OVX plus estrogen replacement (OVX+E2), and 6) old OVX+E2. PNA endothelium-dependent vasodilation was assessed in vitro using acetylcholine. Trabecular bone volume of the distal femoral metaphysis was determined by microCT. In young rats, vasodilation was diminished by OVX and restored with estrogen replacement (intact, 82±7; OVX, 61±9; OVX+E2, 90±4%), which corresponded with similar modifications in BV/TV (intact, 28.7±1.6; OVX, 16.3±0.9; OVX+E2, 25.7±1.4%). In old animals, vasodilation was unaffected by OVX but enhanced with estrogen replacement (intact, 55±8; OVX, 59±7; OVX+E2, 92±4%). Likewise, modifications in BV/TV followed the same pattern (intact, 33.1±1.6; OVX, 34.4±3.7; OVX+E2, 42.4±2.1%). Furthermore, in old animals with low endogenous estrogen (i.e., intact and old OVX), vasodilation was correlated with BV/TV (R2 = 0.630; P<0.001). These data demonstrate parallel effects of estrogen on vascular endothelial function and BV/TV, and provide for a possible coupling mechanism linking endothelium-dependent vasodilation to bone remodeling.
Highlights
Postmenopausal osteoporosis is characterized by pronounced bone resorption
The purpose of this study was to determine whether estrogen status affects endothelium-dependent vasodilation in the femoral diaphyseal principal nutrient artery, and whether these putative changes in vascular endothelial function are associated with alterations in trabecular bone volume
The results demonstrate that lowering circulating estrogen through ovariectomy impairs endothelium-dependent vasodilation (Fig. 2A) and diminishes trabecular bone volume in the femur (Fig. 2B), whereas replacement of estrogen following ovariectomy maintains both endothelium-mediated vasodilation and trabecular bone volume
Summary
Postmenopausal osteoporosis is characterized by pronounced bone resorption. A clear link between estrogen deficiency and reduced bone mass is evident by the increased prevalence of osteoporosis in women vs. men [1] and the direct association between circulating estrogen levels and rates of bone loss [2,3,4,5]. There is increasing evidence in the literature that the osseous vasculature influences bone remodeling. The osseous resistance vasculature regulates skeletal perfusion and, fluid filtration and interstitial fluid flow, which can affect bone cell activity through release of autocrine/paracine factors [12,13,14,15,16,17]. Dysfunction of these vascular mechanisms could contribute to postmenopausal and old age-related osteoporosis. Aging and estrogen loss may contribute to enhanced bone turnover in females through impairment of endothelial responsiveness in the skeletal circulation
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