Potential role of fibroblast growth factor 21 in the deterioration of bone quality in impaired glucose tolerance

Purpose Findings on trabecular bone score (TBS), an index of bone quality, have been reported in prediabetes defined by impaired fasting glucose or HbA1c. Here, we assessed the bone mineral density (BMD) and TBS in prediabetes individuals with impaired glucose tolerance (IGT), and investigated the association of these bone parameters with serum levels of fibroblast growth factor 21 (FGF21), a hormone implicated in bone metabolism and with higher levels in IGT. Methods Chinese postmenopausal women aged 55-80 years, without diabetes, were recruited from the Hong Kong Cardiovascular Risk Factor Prevalence Study in 2016-2018. Normal glucose tolerance (NGT) was defined by fasting glucose < 5.6 mmol/L and 2-h plasma glucose (2hG) < 7.8 mmol/L, and IGT by 2hG 7.8-11 mmol/L. Serum levels of FGF21 and other bone metabolism regulators were measured. Insulin sensitivity was assessed by the Matsuda index. Independent determinants of TBS were evaluated using multivariable stepwise linear regression. Results 173 individuals with NGT and 73 with IGT were included. TBS was lower in those with IGT compared to those with NGT, while BMD was comparable. Individuals with IGT had significantly higher serum FGF21 levels, which in turn showed an independent inverse relationship with TBS, attenuated after inclusion of the Matsuda index. Serum FGF21 levels, however, did not correlate with BMD. Conclusion Among Chinese postmenopausal women, bone quality was worse in IGT, despite comparable bone density. FGF21 levels showed a significant independent inverse relationship with TBS, partly attributed to insulin resistance. Whether FGF21 contributes to the impaired bone quality in IGT remains speculative.