A randomized, parallel group, double-blind, multicentre study comparing the efficacy and safety of Avandamet (rosiglitazone/metformin) and metformin on long-term glycaemic control and bone mineral density after 80 weeks of treatment in drug-naïve type 2 d

Abstract

Superior glycaemic control was achieved with AVM compared with MET monotherapy. The superior glycaemic effects were shown to be durable over 18 months of treatment. AVM was associated with a significantly reduced BMD in comparison with MET at week 80 in the lumbar spine and total hip.

The effect of thiazolidinediones on bone mineral density and bone turnover: systematic review and meta-analysis

“…While bone loss appeared to be similar in studies of ≤6 months and >6 months duration, the meta-analyses did not have sufficient power to detect small differences in BMD changes between these subgroups of trials as only three studies extended beyond 1 year [13,16,26]. In one of these extended studies, BMD loss at the lumbar spine was greater after 80 weeks than after 56 weeks, arguing against a plateau [13]. Results of an observational cohort study by Schwartz and colleagues suggest that long-term treatment with TZDs may result in progressive bone loss [37].…”

“…10 studies reporting on CTX, five reported significant increases with TZDs [12,17,18,28,33] and five showed no effect [13-15, 25, 31]. Of the five studies reporting on bsALP, one reported a significant increase with TZDs [12] and no effect was seen in four [13,17,25,28]. Of the 11 studies reporting on PINP, three reported significant increases with TZDs [12,18,33], two showed significant decreases [27,31] and six found no effect [13-15, 17, 25, 28].…”

“…Where data were presented in figures, we used digital calipers to extract the data. For studies that presented absolute data rather than percentage change from baseline [13,16,[20][21][22][23], we calculated the mean percentage change from the raw data and calculated the SD of the percentage change using the approaches described in the Cochrane review handbook [24]. Data were pooled using random effects meta-analysis and heterogeneity was assessed using the I 2 statistic (I 2 >50% was considered significant heterogeneity).…”

“…Eight studies were of ≤6 months duration and 12 were of >6 months duration. Three studies extended beyond 12 months, but none were longer than 25 months [13,16,26]. Five studies included follow-up periods after withdrawal of TZD treatment, ranging 24-52 weeks [12,14,15,25,28].…”

“…At a cellular level, PPAR-γ acts on mesenchymal stem cells to preferentially promote differentiation into adipogenic cell lineages at the expense of osteoblastogenesis [11]. Some clinical studies report increased loss of bone mineral density (BMD) with TZDs [12][13][14][15], but the effects on bone turnover markers have been inconsistent, with evidence for both reduced bone formation [14,16,17] and increased bone resorption [12,17,18]. It is possible to detect biologically significant effects in surrogate endpoints for fracture, such as BMD and bone turnover, in much smaller cohorts than are required for investigation of effects on fracture incidence.…”