Paola Portillo-Sanchez1,2, Fernando Bril1,2, Romina Lomonaco1,2, Diana Barb1,2, Beverly Orsak3, Jan Marie Bruder4, Kenneth Cusi1,2. 1. Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida, USA. 2. Division of Endocrinology, Diabetes and Metabolism, Malcom Randall Veterans Administration Medical Center (VAMC), Gainesville, Florida, USA. 3. Diabetes Division, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA. 4. Division of Radiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Abstract
BACKGROUND: The effects of pioglitazone on bone metabolism are unclear. This study evaluated the long-term effects of pioglitazone on bone mineral density (BMD) and bone metabolism in patients with prediabetes or type 2 diabetes mellitus (T2DM) and non-alcoholic steatohepatitis (NASH). METHODS:Ninety-two patients with prediabetes or T2DM and biopsy-proven NASH with BMD and baseline biochemical bone measurements were included. Patients (mean [±SEM] age 51 ±1 years, 71% male, mean body mass index 34.5 ± 0.5 kg/m2 ) were randomly assigned to pioglitazone (45 mg/day) or placebo for 18 months, followed by an 18-month open-label pioglitazone treatment phase. Baseline, 18- and 36-month evaluations included plasma vitamin D and bone turnover biomarker levels, and BMD measurements at the spine, femoral neck, total hip, and one-third radius. RESULTS: After 18 months of pioglitazone treatment, there were no differences in BMD versus placebo at either the femoral neck (P =0.87), total hip (P =0.78), or one-third radius (P =0.44); however, bone density decreased at the level of the spine with pioglitazone (-3.5%; P =0.002). During the extension phase (18-36 months), patients had no further decreases in BMD or plasma biomarkers of bone turnover during pioglitazone treatment. No patient experienced a low-energy bone fracture. CONCLUSIONS: Treatment of patients with prediabetes or T2DM withpioglitazone for up to 3 years was associated with decreased BMD at the level of the lumbar spine. This reduction in BMD at the lumbar spine at 18 months versus placebo suggests an early deleterious effect of pioglitazone on bone metabolism.
RCT Entities:
BACKGROUND: The effects of pioglitazone on bone metabolism are unclear. This study evaluated the long-term effects of pioglitazone on bone mineral density (BMD) and bone metabolism in patients with prediabetes or type 2 diabetes mellitus (T2DM) and non-alcoholic steatohepatitis (NASH). METHODS: Ninety-two patients with prediabetes or T2DM and biopsy-proven NASH with BMD and baseline biochemical bone measurements were included. Patients (mean [±SEM] age 51 ± 1 years, 71% male, mean body mass index 34.5 ± 0.5 kg/m2 ) were randomly assigned to pioglitazone (45 mg/day) or placebo for 18 months, followed by an 18-month open-label pioglitazone treatment phase. Baseline, 18- and 36-month evaluations included plasma vitamin D and bone turnover biomarker levels, and BMD measurements at the spine, femoral neck, total hip, and one-third radius. RESULTS: After 18 months of pioglitazone treatment, there were no differences in BMD versus placebo at either the femoral neck (P =0.87), total hip (P =0.78), or one-third radius (P =0.44); however, bone density decreased at the level of the spine with pioglitazone (-3.5%; P =0.002). During the extension phase (18-36 months), patients had no further decreases in BMD or plasma biomarkers of bone turnover during pioglitazone treatment. No patient experienced a low-energy bone fracture. CONCLUSIONS: Treatment of patients with prediabetes or T2DM with pioglitazone for up to 3 years was associated with decreased BMD at the level of the lumbar spine. This reduction in BMD at the lumbar spine at 18 months versus placebo suggests an early deleterious effect of pioglitazone on bone metabolism.
Authors: Mohammed Eslam; Shiv K Sarin; Vincent Wai-Sun Wong; Jian-Gao Fan; Takumi Kawaguchi; Sang Hoon Ahn; Ming-Hua Zheng; Gamal Shiha; Yusuf Yilmaz; Rino Gani; Shahinul Alam; Yock Young Dan; Jia-Horng Kao; Saeed Hamid; Ian Homer Cua; Wah-Kheong Chan; Diana Payawal; Soek-Siam Tan; Tawesak Tanwandee; Leon A Adams; Manoj Kumar; Masao Omata; Jacob George Journal: Hepatol Int Date: 2020-10-01 Impact factor: 6.047