*10.1.5 Anti-diabetes medications*

Thiazolidinediones (TZDs, glitazones) enhance insulin sensitivity and beta cell response to a glucose load by acting as agonists of nuclear peroxisome proliferator-activated receptor gamma (PPAR-Ƴ). The differentiation of precursor cells into osteoblasts depends heavily on PPAR-Ƴ, which is expressed in osteoblasts, osteoclasts, and stromal cells of the bone marrow. Adipogenesis is enhanced by PPAR-Ƴ activation, which also inhibits osteoblastogenesis [130]. The ADOPT trial was the first to report a link between TZDs and an elevated risk of fracture [130, 131]. When compared to metformin and glyburide treatment arms, the incidence of fracture in the lower and upper limbs was roughly twice as high in women using rosiglitazone [132]. The RECORD study displayed that rosiglitazone was associated with an increased risk of fractures (10.7%) as compared to the combination of metformin/ sulfonylurea (6.8%) [130]. Both rosiglitazone and pioglitazone were associated with a significantly increased risk of fractures [133]. In men with type 2 diabetes, rosiglitazone has been linked to a higher risk of vertebral fractures [134, 135]. In the ACCORD bone research, female patients who stopped taking TZD had a reduced incidence of fracture after 1–2 years [136].
