Effect of combined treatment with alendronate and calcitriol on femoral neck strength in osteopenic rats

Abstract

BackgroundHip fracture is associated with pronounced morbidity and excess mortality in elderly women with postmenopausal osteoporosis. Many drugs have been developed to treat osteoporosis and to reduce the risk of osteoporotic fractures. We investigated the effects of combined alendronate and vitamin D3 treatment on bone mass and fracture load at the femoral neck in ovariectomized (OVX) rats, and evaluated the relationship between bone mass parameters and femoral neck strength.MethodsThirty 12-week-old female rats underwent either a sham-operation (n = 6) or OVX (n = 24). Twenty weeks later, OVX rats were further divided into four groups and received daily doses of either saline alone, 0.1 mg/kg alendronate, 0.1 μg/kg calcitriol, or a combination of both two drugs by continuous infusion via Alzet mini-osmotic pumps. The sham-control group received saline alone. After 12 weeks of treatment, femoral necks were examined using peripheral quantitative computed tomography (pQCT) densitometry and mechanical testing.ResultsSaline-treated OVX rats showed significant decreases in total bone mineral content (BMC) (by 28.1%), total bone mineral density (BMD) (by 9.5%), cortical BMC (by 26.3%), cancellous BMC (by 66.3%), cancellous BMD (by 29.0%) and total cross-sectional bone area (by 30.4%) compared with the sham-control group. The combined alendronate and calcitriol treatments improved bone loss owing to estrogen deficiency. On mechanical testing, although OVX significantly reduced bone strength of the femoral neck (by 29.3%) compared with the sham-control group, only the combined treatment significantly improved the fracture load at the femoral neck in OVX rats to the level of the sham-controls. The correlation of total BMC to fracture load was significant, but that of total BMD was not.ConclusionOur results showed that the combined treatment with alendronate and calcitriol significantly improved bone fragility of the femoral neck in OVX osteopenic rats.

The influence of long-term treadmill exercise on bone mass and articular cartilage in ovariectomized rats

“…They demonstrated bone loss of about 13.8% in the distal femur and 12.1% in the proximal tibia of ovariectomized rats compared to control ones. In addition, one recent study showed a 9.5% decrease of BMD in rats after receiving ovariectomy 32 weeks later compared to rats in control group [19]. Our results of decreased BMD in ovariectomized rats were consistent with these findings.…”

Alteration of RhoA Prenylation Ameliorates Cardiac and Vascular Remodeling in Spontaneously Hypertensive Rats

“…The adequacy of anaesthesia was monitored by the lack of the pedal withdrawal reflex, slow constant breathing, and no response to surgical manipulation. The osmotic mini-pump was changed every 4 weeks for 12 weeks, and the dose of alendronate (0.1 mg/kg/day) was chosen according to the results of previous studies [18,19].…”

Osteoblast Response to Ovariectomy Is Enhanced in Intrinsically High Aerobic-Capacity Rats

“…4g–i). At 12 weeks post-OVX, Nakamura et al [28] reported a significantly lower maximal fracture load (−29.3%), relative to the sham-control group, which was likely related to a decrease in cortical width that is typically statistically significant by approximately 90 days post-OVX [12]. …”