Effect Of Strontium Ranelate On Bone Loss And Microachitecture Of Localized Muscle Paralysis Rats

Objective To evaluate the effect of strontium ranelate on bone loss and microachitectural deterioration of localized muscle paralysis rats.Methods Twenty-one 3.5-month-old female Sprague-Dawley rats were randomly assigned to three groups:BTX group, localized muscle paralysis-disuse established by injecting of Clostridium botulinum toxin in the quadriceps femoris of the right hindlimb; BTX+SR group, each rat received BTX and treated with strontium ranelate at dose level of 625 mg/kg/day; and the control group.9 weeks after treatment, all the rats were anaesthetized by intraperitoneal injection of Pelltobarbitalum Natricum. BMD and body composition were measured in vivo, under general anesthesia, before the rats were sacrificed. Then both femurs of each rat were selected for micro CT analysis. A thickness of 5 mm of mid-diaphysis and the regions involving 0.7mm slice thickness and 0.8mm distance far from femur growth plate were selected as the regions of interest. After three dimension reconstruction, the cortical bone mass, cortical BMD, cortical thickness, inner or outer perimeter of cortical, and volumetric bone mineral density, tissue bone mineral density, bone volume fraction, bone surface fraction, trabecular thickness, trabecular separation, trabecular number, structure model index of spongy bone were auto-analysised by Micro View 2.0+ABA of Micro CT. Pictures of 3D micro-architecture were also obtained.Results The mean weight of BTX group and BTX+SR group lower than control group (P＜0.05). Compared with control group, mean Lean Mass and Total Bone Area of BTX group and BTX+SR group were significantly higher. In contrast to the control group, the cortical bone mass, cortical BMD, cortical area, and total cross-sectional area of the middle shaft of the disuse femur and trabecular bone volume fraction (BV/TV), tabecular thickness (Tr.Th), tabecular number (Tr.N) and connectivity density (Conn.D) significantly diminished; while trabecular bone surface fraction (BS/BV), trabecular separation (Tr.Sp) and structure model index (SMI) were significantly increased in the BTX group (P<0.05). In the BTX group treated with strontium ranelate, the cortical BMD, cortical area, and total cross-sectional area of the middle shaft of the disuse femur and trabecular BV/TV, Tr.Th, Tr.N and Conn.D were greatly improved;while BS/BV, Tr.Sp and SMI significantly diminished(P<0.05). Strontium ranelate also improved bone parameters, compared with BTX group and control group, aBMD, tBMD, BV/TV, Tr.Th in the intact femur of BTX+SR group were greatly increased. The results of four-point bending test on the disuse tibia showed that ultimate load, yield load and elastic modulus were significantly higher in BTX+SR group than BTX group; and there is no statistic difference between BTX+SR group and control group.Conclusion Strontium ranelate could prevent bone loss and microstructural degradation in localized muscle paralysis rats.