Profiling bone status indices reveals evidence of a low-turnover bone phenotype in type 2 diabetes: findings from the DiaFALL cohort

People with type 2 diabetes have increased fracture risk despite preserved bone density. In this matched cross-sectional study, suppressed Bone Status Indices and exploratory sex-related hormonal associations were observed in T2D, indicating altered bone remodeling that is not captured by aBMD alone. These findings support the need for fracture risk assessment approaches that incorporate biochemical markers and potential sex-related differences. INTRODUCTION/AIM: People with type 2 diabetes (T2D) experience increased fracture risk despite preserved or higher areal bone mineral density (aBMD). We evaluated Bone Status Indices (BSIs) and their relationships with aBMD in T2D, with exploratory evaluation of sex-related hormonal influences. METHODS: In this matched cross-sectional study from the DiaFALL cohort, 105 adults with T2D were compared 1:1 with age- and sex-matched controls. aBMD was assessed at lumbar spine, femoral neck, arms, and legs using DXA. BSIs included intact PINP (i-PINP), β-CTX-I, osteocalcin (OCN), sclerostin, TRACP5b, IGF-1, OPN, PTH, and vitamin-D metabolites. Group differences and associations with aBMD were evaluated using multivariable regression and Spearman correlations, with exploratory sex-stratified analyses. RESULTS: , 95%CI + 0.072 to + 0.202, p < 0.001). In contrast, multiple BSIs were suppressed in T2D, including i-PINP (men: Δ-12.8 µg/L, 95%CI -19.4 to -6.2, p = 0.002; women: Δ-13.6 µg/L, 95%CI -25.9 to -1.3, p = 0.002), osteocalcin (men: Δ-6.36 µg/L, 95%CI -9.15 to -3.57, p < 0.001; women: Δ-6.66 µg/L, 95%CI -11.0 to -2.20, p < 0.001), and β-CTX-I (men: Δ-40.5 ng/L, 95%CI -62 to -18, p = 0.012; women: Δ-110 ng/L, 95%CI -180 to -44, p = 0.014). Sclerostin was higher in men with T2D (Δ + 24.6 pmol/L, 95%CI + 1.5 to + 47.7, p = 0.019) and correlated positively with lumbar-spine aBMD (r = 0.411; p = 0.007). Furthermore, 1,25(OH)₂D (men p = 0.013; women p = 0.001) and magnesium (p = 0.002 both sexes) were lower in T2D despite similar PTH. No significant T2D-sex interactions were observed for any BSI (all p > 0.05). CONCLUSION: T2D was characterized by higher aBMD together with broadly suppressed BSIs, consistent with a low-turnover skeletal phenotype not captured by DXA alone. Osteocalcin og sclerostin appeared most informative. These findings support longitudinal studies to determine whether BSIs can enhance identification of skeletal fragility in T2D.