Probiotics ameliorate pioglitazone-associated bone loss in diabetic rats

Abstract

Background: Pioglitazone, as a PPAR gamma agonist, is used for the management of type 2 diabetes mellitus. Nevertheless, evidence showed that the therapeutic modulation of PPAR gamma activity using pioglitazone might be linked with bone mass reduction and fracture risk in type 2 diabetes mellitus patients. The objective of the current research was to inspect the preventive role of some types of probiotic strains, including (Lactobacillus acidophilus, Lactobacillus reuteri, Lactobacillus casei, Bifidobacterium longum, and Bacillus coagulans) against pioglitazone-induced bone loss. Methods: Streptozotocin (60 mg/kg) was administered for diabetes induction. Diabetic rats were fed orally with pioglitazone (300 mg/kg) and probiotics (1 × 109 CFU/ml/day) alone and in combination for four weeks. Dual-energy X-ray absorptiometry (DXA) was used to assess BMD, BMC, and area of the femur, spine, and tibia at the end of the experiment. Serum glucose, serum calcium (Ca), alkaline phosphatase (ALP), phosphorus (P), Blood urea nitrogen (BUN), creatinine, and urine calcium were also analyzed. Results: Administration of pioglitazone and probiotics alone and, in combination, significantly reduced elevated blood glucose. Pioglitazone treatment significantly increased urinary calcium and BUN and decreased ALP and creatinine. Co-treatment of probiotics with pioglitazone significantly decreased urinary calcium, creatinine, and ALP. Pioglitazone showed detrimental effects on femur-BMD, whereas treatment with probiotics remarkably ameliorated these effects. Among the tested probiotics, Bifidobacterium longum displayed the best protective effects on pioglitazone-induced bone loss in diabetic rats. Conclusion: This study suggests probiotic supplementation in diabetic patients on pioglitazone regime could be considering as an excellent strategy to ameliorate bone loss induced by pioglitazone.