Wednesday , November 22 2017
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Bone Fracture Risk with Rosiglitazone Can Be Lowered with Exercise

Previous studies have shown that peroxisome proliferator-activated gamma (PPAR-gamma) agonists used for the treatment of type 2 diabetes have been shown to increase bone marrow adipose tissue leading to skeletal fragility, which causes increased bone fractures in diabetic patients. PPAR-gamma agonists such as rosiglitazone take glucose out of blood by packaging the glucose into lipid droplets to be stored in tissues such as belly fat and inside bone. Researchers from the University of North Carolina School of Medicine set out to find whether exercise could limit the bone marrow adipose tissue accrual and increase bone formation in patients receiving treatment with a PPAR-gamma agonist.

Eight-week-old female mice were treated with 20 mg/kg/day of rosiglitazone and compared with control mice. Exercise groups ran 12 km per day on running wheels. Femoral marrow adipose tissue volume and tibial bone morphology were evaluated by microcomputer tomography after 6 weeks. The results showed that the mice receiving rosiglitazone therapy had a 40% higher femur marrow adipose tissue volume compared to the control group (P < .0001). Exercise suppressed marrow adipose tissue volume by half in the control mice who exercised compared to the control mice who did not (P < .01) and 19% in the rosiglitazone-exercise group compared to rosiglitazone alone (P < .0001).

The results of the study indicate that despite the rosiglitazone-induction of marrow adipose tissue extending well into the femoral diaphysis, exercise was able to significantly suppress marrow adipose tissue volume and induce bone formation. In conclusion, impact of PPAR-gamma agonists on bone and marrow health can be partially mitigated by exercise.

The study’s author also noted that mice are natural runners and can run several miles at night, therefore their findings are not yet directly relatable to human activity. Whatever the case, exercise does aid in bone health and patients should still be advised on the risk of declining bone health and to find an exercise that suits them.

Practice Pearls:

  • The mice receiving rosiglitazone therapy had a 40% higher femur marrow adipose tissue volume compared to the control group (P < .0001).
  • Exercise suppressed marrow adipose tissue volume by half in the control mice who exercised compared to the control mice who did not (P < .01) and 19% in the rosiglitazone-exercise group compared to rosiglitazone alone (P < .0001).
  • The results of the study indicate that despite the rosiglitazone-induction of marrow adipose tissue extending well into the femoral diaphysis, exercise was able to significantly suppress marrow adipose tissue volume and induce bone formation.

Styner M, Pagnotti GM, Galior K, et al. Exercise Regulation of Marrow Fat in the Setting of PPARγ Agonist Treatment in Female C57BL/6 Mice. Endocrinology. 2015;156(8):2753-61.