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Current Pharmaceutical Design

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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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General Research Article

Pioglitazone Therapy Decreases Bone Mass Density and Increases Fat Mass: A Meta-Analysis

Author(s): Liyun Zuo*, Jianbin Wang, Nianping Zhang and Junjie Wang

Volume 25, Issue 33, 2019

Page: [3590 - 3596] Pages: 7

DOI: 10.2174/1381612825666190920123129

Price: $65

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Abstract

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.

Keywords: Pioglitazone, bone mass density, fat mass, meta-analysis, randomized controlled trials, type 2 diabetes.

« Previous
[1]
Yki-Järvinen H. Thiazolidinediones N Engl J Med 2004; 351(11): 1106-18.
[http://dx.doi.org/10.1056/NEJMra041001] [PMID: 15356308]
[2]
Lord JM, Flight IH, Norman RJ. Insulin-sensitising drugs (metformin, troglitazone, rosiglitazone, pioglitazone, D-chiro-inositol) for polycystic ovary syndrome. Cochrane Database Syst Rev 2003; (3): CD003053
[PMID: 12917943]
[3]
Gerstein HC, Yusuf S, Bosch J, et al. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet 2006; 368(9541): 1096-105.
[http://dx.doi.org/10.1016/S0140-6736(06)69420-8] [PMID: 16997664]
[4]
Liao HW, Saver JL, Wu YL, Chen TH, Lee M, Ovbiagele B. Pioglitazone and cardiovascular outcomes in patients with insulin resistance, pre-diabetes and type 2 diabetes: a systematic review and meta-analysis. BMJ Open 2017; 7(1)e013927
[http://dx.doi.org/10.1136/bmjopen-2016-013927] [PMID: 28057658]
[5]
Olefsky JM. Treatment of insulin resistance with peroxisome proliferator-activated receptor gamma agonists. J Clin Invest 2000; 106(4): 467-72.
[http://dx.doi.org/10.1172/JCI10843] [PMID: 10953021]
[6]
McGavock JM, Lingvay I, Zib I, et al. Cardiac steatosis in diabetes mellitus: A 1H-magnetic resonance spectroscopy study. Circulation 2007; 116(10): 1170-5.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.106.645614] [PMID: 17698735]
[7]
Bajaj M, Suraamornkul S, Hardies LJ, Pratipanawatr T, DeFronzo RA. Plasma resistin concentration, hepatic fat content, and hepatic and peripheral insulin resistance in pioglitazone-treated type II diabetic patients. Int J Obes Relat Metab Disord 2004; 28(6): 783-9.
[http://dx.doi.org/10.1038/sj.ijo.0802625] [PMID: 15024400]
[8]
McDonough AK, Rosenthal RS, Cao X, Saag KG. The effect of thiazolidinediones on BMD and osteoporosis. Nat Clin Pract Endocrinol Metab 2008; 4(9): 507-13.
[http://dx.doi.org/10.1038/ncpendmet0920] [PMID: 18695700]
[9]
Wang L, Li L, Gao H, Li Y. Effect of pioglitazone on transdifferentiation of preosteoblasts from rat bone mesenchymal stem cells into adipocytes. J Huazhong Univ Sci Technolog Med Sci 2012; 32(4): 530-3.
[http://dx.doi.org/10.1007/s11596-012-0091-x] [PMID: 22886965]
[10]
Grey A. Thiazolidinedione-induced skeletal fragility-mechanisms and implications. Diabetes Obes Metab 2009; 11(4): 275-84.
[http://dx.doi.org/10.1111/j.1463-1326.2008.00931.x] [PMID: 18671797]
[11]
Douglas IJ, Evans SJ, Pocock S, Smeeth L. The risk of fractures associated with thiazolidinediones: A self-controlled case-series study. PLoS Med 2009; 6(9)e1000154
[http://dx.doi.org/10.1371/journal.pmed.1000154] [PMID: 19787025]
[12]
Pavlova V, Filipova E, Uzunova K, Kalinov K, Vekov T. Pioglitazone therapy and fractures: Systematic review and meta- analysis. Endocr Metab Immune Disord Drug Targets 2018; 18(5): 502-7.
[http://dx.doi.org/10.2174/1871530318666180423121833] [PMID: 29683100]
[13]
Glintborg D, Andersen M, Hagen C, Heickendorff L, Hermann AP. Association of pioglitazone treatment with decreased bone mineral density in obese premenopausal patients with polycystic ovary syndrome: A randomized, placebo-controlled trial. J Clin Endocrinol Metab 2008; 93(5): 1696-701.
[http://dx.doi.org/10.1210/jc.2007-2249] [PMID: 18285411]
[14]
Pop LM, Lingvay I, Yuan Q, Li X, Adams-Huet B, Maalouf NM. Impact of pioglitazone on bone mineral density and bone marrow fat content. Osteoporos Int 2017; 28(11): 3261-9.
[http://dx.doi.org/10.1007/s00198-017-4164-3] [PMID: 28735463]
[15]
Billington EO, Grey A, Bolland MJ. The effect of thiazolidinediones on bone mineral density and bone turnover: systematic review and meta-analysis. Diabetologia 2015; 58(10): 2238-46.
[http://dx.doi.org/10.1007/s00125-015-3660-2] [PMID: 26109213]
[16]
Sears DD, Hsiao A, Ofrecio JM, Chapman J, He W, Olefsky JM. Selective modulation of promoter recruitment and transcriptional activity of PPARgamma. Biochem Biophys Res Commun 2007; 364(3): 515-21.
[http://dx.doi.org/10.1016/j.bbrc.2007.10.057] [PMID: 17963725]
[17]
Henriksen K, Byrjalsen I, Qvist P, et al. Efficacy and safety of the PPARγ partial agonist balaglitazone compared with pioglitazone and placebo: a phase III, randomized, parallel-group study in patients with type 2 diabetes on stable insulin therapy. Diabetes Metab Res Rev 2011; 27(4): 392-401.
[http://dx.doi.org/10.1002/dmrr.1187] [PMID: 21328517]
[18]
Bone HG, Lindsay R, McClung MR, Perez AT, Raanan MG, Spanheimer RG. Effects of pioglitazone on bone in postmenopausal women with impaired fasting glucose or impaired glucose tolerance: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab 2013; 98(12): 4691-701.
[http://dx.doi.org/10.1210/jc.2012-4096] [PMID: 24057294]
[19]
Bray GA, Smith SR, Banerji MA, et al. Effect of pioglitazone on body composition and bone density in subjects with prediabetes in the ACT NOW trial. Diabetes Obes Metab 2013; 15(10): 931-7.
[http://dx.doi.org/10.1111/dom.12099] [PMID: 23551856]
[20]
Grey A, Beckley V, Doyle A, et al. Pioglitazone increases bone marrow fat in type 2 diabetes: Results from a randomized controlled trial. Eur J Endocrinol 2012; 166(6): 1087-91.
[http://dx.doi.org/10.1530/EJE-11-1075] [PMID: 22408124]
[21]
Adams JE. Quantitative computed tomography. Eur J Radiol 2009; 71(3): 415-24.
[http://dx.doi.org/10.1016/j.ejrad.2009.04.074] [PMID: 19682815]
[22]
He L, Liu X, Wang L, Yang Z. Thiazolidinediones for nonalcoholic steatohepatitis: A meta-analysis of randomized clinical trials. Medicine (Baltimore) 2016; 95(42)e4947
[http://dx.doi.org/10.1097/MD.0000000000004947] [PMID: 27759627]

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