Effects of Simvastatin and Combination of Simvastatin and Nylestriol on Bone Metabolism in Ovariectomized Rats

Abstract

We aim to compare the effects of simvastatin and combination of simvastatin and nylestriol on bone metabolism in ovariectomized (OVX) rats. Fifty healthy Wistar female rats were randomly allocated into 5 groups: sham + saline group (group A), OVX + saline group (group B), OVX + simvastatin (5 mg·kg·d) (group C), OVX + nylestriol (0.01 mg·kg·d) (group D), and OVX + simvastatin (3 mg·kg·d) + nylestriol (0.005 mg·kg·d) (group E). All mice were orally administrated with saline or medicine dissolved in saline for 10 weeks. Body weight of rats before and after the experiment was measured. Twenty-four hours after the experiment, calcium (Ca), creatinine (Cr), and hydroxyproline in urine were detected. Serum levels of osteocalcin (bone Gla-protein, BGP) and alkaline phosphatase (ALP) were measured. Bone mineral density was detected and trabecular bone was observed after the isolation of femur and tibia. Remarkably decreased serum BGP and increased serum ALP levels were detected in group B compared with those in group A. However, notably increased serum BGP and decreased serum ALP levels were found in groups C, D, and E compared with those in group B; femoral and tibial bone mineral density decreased in group B compared with that in group A, but increased in groups C, D, and E compared with that in group B. Simvastatin and combination of simvastatin and nylestriol promote formation of new bone, increase bone density, and improve bone microstructure damage in OVX rats.

Experimental study on the effects of simvastatin in reversing the femoral metaphyseal defects induced by sodium valproate in normal and ovariectomized rats

“…The calculated doses of SVP and SIM were also in conformity with previous reports [ 37 , 38 ]. Body weight was measured weekly and the drug doses were adjusted accordingly ( Figure 1 ).…”

Role of Simvastatin on fracture healing and osteoporosis: a systematic review onin vivoinvestigations

“…2,3,[9][10][11][12][13]16, Of these, 24.75% used calvarial and parietal models (skull surgery), 23.63% used maxillofacial surgery models (alveolar-, nasal-, and mandibular bone), 37.64% used orthopaedic models (a variety of tibial, femoral, radial and ulnar fractures, defects, and holes and also other modalities) and 13.98% used osteoporosis models. Rat was the most popular animal model possibly because of its low cost, thus the researchers can include a higher number of animals in their studies.…”

“…1 Although Simvastatin is not a new generation of the statin family, it is the most investigated statin family member in the field of bone research, particularly in animal models. [5][6][7][8][9][10][11][12][13] However, the mechanisms, route of administration, dose and dosages, and effectiveness of Simvastatin have not been clearly defined in different in vivo studies on bone repair and osteoporosis. 1 In addition, some controversial results regarding the role of Simvastatin on bone metabolism are seen in the literature.…”