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17 September 2018 : Animal Research  

Strontium Ranelate Combined with Insulin Is as Beneficial as Insulin Alone in Treatment of Fracture Healing in Ovariectomized Diabetic Rats

Guo-Long Cao1ABCEF, Fa-Ming Tian23ADEFG, Guang-Yuan Liu1ABCF, Hui-Ping Song4DEF, Lei-Liang Yuan4BEF, Lin-Dan Geng4BF, Ming-Jian Bei4BE, Zhi-Yuan Zheng4BE, Liu Zhang15ADFG*

DOI: 10.12659/MSM.911573

Med Sci Monit 2018; 24: ANS6525-6536


BACKGROUND: Type 2 diabetes mellitus (T2DM) and estrogen deficiency both predispose fracture patients to increased risk of delayed union or nonunion. The present study investigated the effects of strontium ranelate (SR) on fracture healing in ovariectomized (OVX) diabetic rats.

MATERIAL AND METHODS: A mid-shaft fracture was established in female normal control (CF), diabetic (DF), and OVX diabetic (DOF) rats. Treated DOF rats received either insulin alone (DOFI) or combined with SR (DOFIS). All rats were euthanized at 2 or 3 weeks after fracture. Fracture healing was evaluated using radiological, histological, immunohistochemical, and micro-computed tomography analyses.

RESULTS: At 3 weeks after fracture, radiological and histological evaluations demonstrated delayed fracture healing in the DF group compared with the CF group, which was exacerbated by OVX, as indicated by the significantly lower X-ray score, BMD, BV/TV, and Md.Ar/Ps.Cl.Ar, and the markedly decreased OCN and Col I expression in the DOF group. All these changes were prevented by insulin alone or combined with SR treatment. In comparison with the DOFI group, DOFIS rats displayed markedly higher OCN expression at 2 weeks after fracture and Col I expression at 2 and 3 weeks after fracture.

CONCLUSIONS: These results demonstrated delayed fracture healing with preexisting estrogen deficiency and T2DM. While insulin alone and combined with SR were both effective in promoting bone fracture healing in this model, their combined treatment showed significant improvement in promoting osteogenic marker expression, but not of the radiological appearance, compared with insulin alone.

Keywords: Diabetes Mellitus, Type 2, Fracture Healing, Insulin, Osteoporosis, Strontium

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750