Understanding Bone Health in Type 2 Diabetes

The link between type 2 diabetes mellitus (T2DM) and bone fragility is complex. While individuals with type 2 diabetes often have normal to elevated bone mineral density, their risk of fractures is up to three times higher (1, 2).

Understanding Bone Health in Type 2 Diabetes

Recent research has shed new light on the complex relationship between Type 2 diabetes mellitus (T2DM) and bone health. The study, titled “Profiling bone status indices reveals evidence of a low-turnover bone phenotype in type 2 diabetes: findings from the DiaFALL cohort. Rasmussen NH et al., Osteoporos Int. 2026, provides valuable insights into how diabetes affects bone metabolism and fracture risk.

In this matched cross-sectional study, the researchers profiled Bone Status Indices (BSIs), which are biochemical markers of bone remodeling, in individuals with type 2 diabetes (T2D).

The BIOMEDICA assays bioactive Sclerostin and intact FGF23 were included in the study.

Bioactive Sclerostin ELISA (cat. no. BI-20472)

• Characterized antibodies that target the Sclerostin receptor binding region
• The assay is  validated for clinical samples  (validation data file)
• Only  20µl sample /well (protocol booklet)
• Widely cited

 

 FGF23 intact ELISA (cat. no. BI-20700)

• Extensively validated according to international quality guidelines
• Correlates with existing methods (validation data file)
• One-step ELISA  (protocol booklet)
• Cited in top-tier journals

 

Key findings:

-Individuals with T2D have an increased risk of #fractures compared to those without diabetes.

-The elevated fracture risk persists even when bone mineral density (BMD) is normal or only slightly reduced.

-The researchers uncovered an altered bone remodeling processes in T2D, which could impact fracture risk and treatment strategies. 

Profiling bone status indices reveals evidence of a low-turnover bone phenotype in type 2 diabetes: findings from the DiaFALL cohort. Rasmussen NH, Kvist AV, Bech AA, Lykkeboe S, Starup-Linde J, Handberg A, van den Bergh JP, Vestergaard P. Osteoporos Int. 2026 Mar;37(3):703-716. doi: 10.1007/s00198-026-07850-9. Epub 2026 Jan 21. PMID: 41563408; PMCID: PMC13083425.

Abstract

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: Femoral-neck aBMD was higher in people with T2D (men: + 0.070 g/cm², 95%CI + 0.026 to + 0.114, p = 0.002; women: + 0.089, 95%CI + 0.039 to + 0.139, p = 0.001) and lumbar-spine aBMD was higher in women (+ 0.137 g/cm², 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.

 

Literature

1. Update on the impact of type 2 diabetes mellitus on bone metabolism and material properties. Picke AK, Campbell G, Napoli N, Hofbauer LC, Rauner M. Endocr Connect. 2019 Mar 1;8(3):R55-R70. doi: 10.1530/EC-18-0456. PMID: 30772871; PMCID: PMC6391903.
2. Bone Health in Patients With Type 2 Diabetes. Forner P, Sheu A. J Endocr Soc. 2024 Jun 6;8(7):bvae112. doi: 10.1210/jendso/bvae112. PMID: 38887632; PMCID: PMC11181004.

 

Related Reviews

Bone fragility in diabetes: novel concepts and clinical implications. Hofbauer LC, Busse B, Eastell R, Ferrari S, Frost M, Müller R, Burden AM, Rivadeneira F, Napoli N, Rauner M.Lancet Diabetes Endocrinol. 2022 Mar;10(3):207-220. doi: 10.1016/S2213-8587(21)00347-8. Epub 2022 Jan 31. PMID: 35101185.

Contributors to impaired bone health in type 2 diabetes. Sheu A, Greenfield JR, White CP, Center JR. Trends Endocrinol Metab. 2023 Jan;34(1):34-48. doi: 10.1016/j.tem.2022.11.003. Epub 2022 Nov 23. PMID: 36435679.