Background: Pioglitazone is mainly used for the management of type 2 diabetes and other insulinassociated
diseases. However, the molecular mechanism of pioglitazone can lead to an imbalance in bone metabolism,
thus decreasing bone mass density (BMD) and increasing the risk for fractures.
Objective: To demonstrate the effect of pioglitazone therapy on bone metabolism and fat mass.
Methods: A comprehensive search of the PubMed, EMBASE, Web of Science and Cochrane Central databases
for randomized controlled trials (RCTs) on the effect of pioglitazone therapy on BMD and fat mass was performed.
The primary outcome measures were the measured values of BMD, percentage changes in BMD, measured
values of bone turnover markers and bone metabolic hormones, changes in BMI, body and leg fat mass, and
fracture rates. The final search was performed in May 2019.
Results: Six RCTs were included. A total of 749 patients met the inclusion criteria. Pioglitazone therapy was
shown to significantly reduce the BMD of the whole body, lumbar spine, and total hip and serum PTH levels and
increase BMI, total body fat mass and leg fat mass. In addition, 30 mg/d and 30 mg/d initially for one month
followed by 45 mg/d pioglitazone could reduce the BMD of the lumbar spine. Pioglitazone therapy exerted no
significant influence on the BMD of the femoral neck, serum BSAP or 25-OHD levels, or fracture rates.
Conclusion: Compared with placebo, pioglitazone therapy reduced BMD and serum PTH levels and increased fat
mass and BMI with no difference in serum BSAP or 25-OHD levels or fracture rates; 30 mg/d pioglitazone was
sufficient to reduce the BMD of the lumbar spine.