Effect of ovariectomy on intraosseous vascularization and bone remodelling in rats: Action of tiludronate

Abstract

In order to study the action of tiludronate on the changes in intraosseous vascularization induced by ovariectomy, and to link these effects to those observed in bone remodelling, 30 female Sprague-Dawley rats (age 40 weeks) were studied. Ten rats were shamoperated and treated by vehicle, 10 rats were ovariectomized and treated by vehicle, and 10 rats were ovariectomized and treated orally with tiludronate, 0.16 mmol/kg/per day, 3 days a week for 16 weeks, from the day following ovariectomy. The rats were killed after 4 months, and a histomorphometric study and quantification of intraosseous vessels carried out on the sixth lumbar vertebra. The area of the intraosseous sinusoidal capillaries increased after ovariectomy, which also induced a moderate increase in resorption surfaces and osteoid surfaces leading to a decrease of 40% in the trabecular bone volume at the lumbar spine level. This bone mineral loss was completely prevented by tiludronate, which normalized the bone turnover. However, tiludronate was without any effect on intraosseous vascularization. These results indicate that the surface area of the intraosseous sinusoidal capillaries was correlated positively with resorption surfaces and negatively with trabecular bone volume and the number of bone trabeculae. In these experimental conditions, an inhibitor of bone resorption can exert its positive effect on bone mass without normalization of vascularization.

Mechanical, hormonal and metabolic influences on blood vessels, blood flow and bone

“…Bone loss with estrogen deficiency has been examined by several investigators who sought to determine the associated bone vascular consequences; however, the data have provided mixed results. In some investigations, estrogen deficiency via ovariectomy (OVX) served to 1) diminished trabecular bone volume and area, bone mineral density, bone biomechanical properties, erythropoietic marrow area, vascular density, vascular volume, immunohistochemical expression of vascular endothelial cell growth factor (VEGF) in bone, and bone perfusion, and 2) increased the area of sinusoidal capillaries and marrow fat cell area (Laroche et al 1996; Griffith et al 2010; Ding et al 2011). The area of sinusoids in the marrow coincided with bone resorption (r = +0.46), trabecular bone volume (r = −0.54) and trabecular number (r = −0.60) (Laroche et al 1996).…”

“…In some investigations, estrogen deficiency via ovariectomy (OVX) served to 1) diminished trabecular bone volume and area, bone mineral density, bone biomechanical properties, erythropoietic marrow area, vascular density, vascular volume, immunohistochemical expression of vascular endothelial cell growth factor (VEGF) in bone, and bone perfusion, and 2) increased the area of sinusoidal capillaries and marrow fat cell area (Laroche et al 1996; Griffith et al 2010; Ding et al 2011). The area of sinusoids in the marrow coincided with bone resorption (r = +0.46), trabecular bone volume (r = −0.54) and trabecular number (r = −0.60) (Laroche et al 1996). Interestingly, 15 days following OVX in mice, trabecular bone volume was not diminished but tibial bone perfusion and vascular density and volume in the marrow were reduced (Roche et al 2014).…”

“…Interestingly, 15 days following OVX in mice, trabecular bone volume was not diminished but tibial bone perfusion and vascular density and volume in the marrow were reduced (Roche et al 2014). Treatment with bisphosphonates prevented bone loss (Laroche et al 1996) and attenuated the declines in bone perfusion (Roche et al 2014) with OVX, but did not alter bone vascular density, volume, and blood vessel size (Laroche et al 1996; Roche et al 2014). In contrast, OVX and orchidectomy (i.e., castration) in rats demonstrated increased bone blood flow (Kapitola & Kubícková 1990; Egrise et al 1992; Kapitola et al 1994) with enhanced bone turnover and bone loss (Kapitola & Kubícková 1990; Egrise et al 1992; Kapitola et al 1994) and diminished bone density and ash weight (Kapitola & Kubícková 1990; Kapitola et al 1994) in young rats.…”

A Physical Mechanism for Coupling Bone Resorption and Formation in Adult Human Bone

“…Chemoattractants are believed to play a role in this process, but the mechanism supporting their spatial organization has not been investigated. 12,13 Nearby capillaries were also proposed to contribute to the guidance mechanism, [13][14][15] based on the histological analysis of the remodeling areas. Furthermore, a study conducted on bone sections of hyperparathyroid patients led to the proposal that OCs and OBs exert their activities in so-called bone-remodeling compartments (BRC), separated from the bone marrow cavity by a monolayer of flat cells that show OB-like cell markers.…”