Der Einfluss von Strontiumranelat auf die Frakturheilung osteopener Ratten

Abstract

Osteoporosis is a common bone disease that affects many people all over the world. Strontium ranelate (SR) is licensed for osteoporosis therapy since 2004. However, the effect of SR on fracture healing in osteoporotic bones especially in the metaphyseal region is still to be investigated. Furthermore, it is unknown, if an osteoporosis therapy with SR should be continued or interrupted when a fracture occurs? Therefore, three-month-old female rats were bilateral ovariectomized (OVX, n=48) or left intact (SHAM, n=12). After eight weeks, when the OVX rats develop severe osteoporosis, a bilateral osteotomy of the metaphyseal tibiae was performed in all rats. The 60 rats were arranged into five groups: two control groups (SHAM, OVX) and three SR-treated groups depending on the period of SR application (SR before osteotomy, SR after osteotomy, SR before and after osteotomy). SR was added to the rodent diet (10,5 g/kg of food). The average intake of SR was 654 mg/kg BW/day. After five weeks post-osteotomy, the study ends with the obduction of the rodents. Investigating the fracture healing mechanical and histomorphometric tests as well as micro-computed tomography (μCT) were performed. To advance the analysis of µCT scans, two different ways of analyzing were developed and compared. SR-treated groups showed higher biomechanical parameters, callus density and BV/TV in comparison to OVX-group. The highest increase in BMD and BV/TV was noted in the group SR before and after osteotomy.In conclusion, SR primarily has no negative effects on osteoporotic fracture healing, independently of SR application regimes. However, the application as fracture therapy (SR after osteotomy) shows no improvement in fracture healing. If a fracture occurred during SR therapy, the treatment should be continued because the application of SR as prophylaxis and therapy proved to be most effective for bone healing. That is a great advantage of SR versus bisphosphonates. Previously, it was shown, that the application of the bisphosphonate alendronate before and after osteotomy led to an impairment of fracture healing in osteoporotic animals.