Effect of the antidiabetic agent pioglitazone on bone metabolism in rats

Kanda, Junkichi; Izumo, Nobuo; Kobayashi, Yoshiko; Onodera, Kenji; Shimakura, Taketoshi; Yamamoto, Noriaki; Takahashi, Hideaki; Wakabayashi, Hiroyuki

doi:10.1016/j.jphs.2017.08.004

Cited by 17 publications

(15 citation statements)

References 42 publications

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“…The overall best combination therapy in controlling blood glucose without reducing calcium bone resorption has been shown in the animal group, which received Bifidobacterium longum and pioglitazone. A previous study showed that pioglitazone treatment did not affect serum calcium levels [37]. Similarly, no changes in serum calcium concentration in the pioglitazone group compared to the control group were found.…”

Section: Discussionmentioning

confidence: 78%

Probiotics ameliorate pioglitazone-associated bone loss in diabetic rats

Gholami

Dabbaghmanesh

Ghasemi

et al. 2020

Diabetol Metab Syndr

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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 × 10 9 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.

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Section: Discussionmentioning

confidence: 78%

Probiotics ameliorate pioglitazone-associated bone loss in diabetic rats

Gholami

Dabbaghmanesh

Ghasemi

et al. 2020

Diabetol Metab Syndr

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“…134 Studies in rodents exposed to pioglitazone have found either no adverse effects on bone 142,205 or negative effects. Several studies found that pioglitazone resulted in decreases in BMD, 199,202,206 decreased bone strength, 199,207 decreased osteoblast surface and mineralizing surface, and increased osteoclast surface and number, 199 supporting that pioglitazone suppresses bone formation and promotes bone resorption, 207 predisposing to bone fragility. These effects have been reversible in certain studies 206,207 with discontinuation of treatment.…”

Section: Skeletal Effects: In Vivomentioning

confidence: 99%

Diabetes pharmacotherapy and effects on the musculoskeletal system

Kalaitzoglou

Fowlkes

Popescu

et al. 2018

Diabetes Metabolism Res

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Summary Persons with type 1 or type 2 diabetes have a significantly higher fracture risk than age‐matched persons without diabetes, attributed to disease‐specific deficits in the microarchitecture and material properties of bone tissue. Therefore, independent effects of diabetes drugs on skeletal integrity are vitally important. Studies of incretin‐based therapies have shown divergent effects of different agents on fracture risk, including detrimental, beneficial, and neutral effects. The sulfonylurea class of drugs, owing to its hypoglycemic potential, is thought to amplify the risk of fall‐related fractures, particularly in the elderly. Other agents such as the biguanides may, in fact, be osteo‐anabolic. In contrast, despite similarly expected anabolic properties of insulin, data suggests that insulin pharmacotherapy itself, particularly in type 2 diabetes, may be a risk factor for fracture, negatively associated with determinants of bone quality and bone strength. Finally, sodium‐dependent glucose co‐transporter 2 inhibitors have been associated with an increased risk of atypical fractures in select populations, and possibly with an increase in lower extremity amputation with specific SGLT2I drugs. The role of skeletal muscle, as a potential mediator and determinant of bone quality, is also a relevant area of exploration. Currently, data regarding the impact of glucose lowering medications on diabetes‐related muscle atrophy is more limited, although preclinical studies suggest that various hypoglycemic agents may have either aggravating (sulfonylureas, glinides) or repairing (thiazolidinediones, biguanides, incretins) effects on skeletal muscle atrophy, thereby influencing bone quality. Hence, the therapeutic efficacy of each hypoglycemic agent must also be evaluated in light of its impact, alone or in combination, on musculoskeletal health, when determining an individualized treatment approach. Moreover, the effect of newer medications (potentially seeking expanded clinical indication into the pediatric age range) on the growing skeleton is largely unknown. Herein, we review the available literature regarding effects of diabetes pharmacotherapy, by drug class and/or by clinical indication, on the musculoskeletal health of persons with diabetes.

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“…Recently, several other drugs were also clearly shown to cause bone fragility. We have previously reported the effects of antidiabetic (11) and antiepileptic (12,13) agents on bone metabolism; these led to enhanced bone fragility. The present study investigates the effects of calcineurin inhibitors, which are immunosuppressants that have greatly contributed to the advancement of transplant therapy in recent years, on bone metabolism.…”

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confidence: 99%

<b>Effects of the calcineurin inhibitors cyclosporine and tacrolimus on bone metabolism in </b><b>rats </b>

et al. 2018

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Immunosuppressive therapy is considered as one of the factors inducing to the onset of osteoporosis after organ transplantation. Chronic immunosuppressive therapy after transplantation is required for organ transplant patients, and it is important to prevent the occurrence of osteoporotic fractures to maintain the quality of life in patients. In this study, we examined the effects of cyclosporine and tacrolimus on bone metabolism in rats. Five-week-old male Wistar rats were treated orally with 15 mg/kg cyclosporine or 1.5 mg/kg tacrolimus daily for 4 weeks. Each of cyclosporine and tacrolimus significantly reduced the bone strength of the femoral mid-diaphysis and bone mineral density of the tibia and femur. Bone histomorphometry showed that the administration of both drugs resulted in a decrease in bone volume, number and thickness of trabeculae, and an increase in trabecular separation. Bone formation parameters such as osteoid volume, osteoblast surface, mineralizing surface, mineral apposition rate, and bone formation rate significantly increased in the cyclosporine-treated group. Bone resorption parameters such as eroded surface, osteoclast surface, and osteoclast number significantly increased in both the cyclosporine- and the tacrolimus- treated groups. These results showed that cyclosporine increases both bone formation and bone resorption, leading to a high-turnover bone loss, and that tacrolimus increases bone resorption without affecting bone formation, leading to bone loss.

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Effect of the antidiabetic agent pioglitazone on bone metabolism in rats

Cited by 17 publications

References 42 publications

Probiotics ameliorate pioglitazone-associated bone loss in diabetic rats

Probiotics ameliorate pioglitazone-associated bone loss in diabetic rats

Diabetes pharmacotherapy and effects on the musculoskeletal system

<b>Effects of the calcineurin inhibitors cyclosporine and tacrolimus on bone metabolism in </b><b>rats </b>

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