Treatment with a combination of alendronate and calcitriol, starting preoperatively, can improve cancellous bone mineral density and the stability of hydroxyapatite-coated implants in an osteoporotic rat.

The reduced stability of hydroxyapatite (HA)-coated implants in osteopenic conditions is considered to be a major problem. We therefore developed a model of a boosted cementless implantation in osteopenic rats.Twelve-week-old rats were either ovariectomised (OVX) or sham-operated (SO), and after 24 weeks plain or HA-coated implants were inserted. They were treated with either a prostaglandin EP4 receptor agonist (ONO-4819) or saline for one month. The EP4 agonist considerably improved the osteoporosis in the OVX group. Ultrastructural analysis and mechanical testing showed an improvement in the implant-bone attachment in the HA-coated implants, which was further enhanced by the EP4 agonist. Although the stability of the HA-coated implants in the saline-treated OVX rats was less than in the SO normal rats, the administration of the EP4 agonist significantly compensated for this shortage. Our results showed that the osteogenic effect of the EP4 agonist augmented the osteoconductivity of HA and significantly improved the stability of the implant-bone attachment in the osteoporotic rat model.

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.

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The agonist of the prostaglandin EP4 receptor can increase bone density in osteoporosis. Using ovariectomized (OVX) and sham-operated (SO) rats, the effects of the EP4 receptor agonist, ONO-4819, and hydroxyapatite (HA) on implant-bone fixation in implants with a rough surface were investigated. Female Wistar rats (12 weeks old) were divided into either SO or bilateral OVX groups. Twenty four weeks later, either hydroxyapatite/titanium (HA/Ti) composite-coated or Ti-coated implants were implanted into the femora, and the animals were treated with either ONO-4819 or saline for 4 weeks. The fixation strength of the HA/Ti-coated implants was higher than that of the Ti-coated implants in the saline-treated OVX rats. In the OVX rats, ONO-4819 enhanced fixation of the rough Ti-coated implants to levels similar to that of HA/Ti-coated implants. These data suggest that a combination of treatment with an EP4 receptor agonist and a rough-surfaced implant might be useful in increasing the early fixation of cement-less arthroplasty, particularly in elderly patients with osteoporosis.