# Relationship between bone turnover markers and diabetic kidney disease in patients with type 2 diabetes

**Authors:** Xueyan Men, Peipei Yue, Weiwei Hao, Lei Zhang, En Chen, Jing Liu

PMC · DOI: 10.3389/fendo.2025.1646690 · 2025-09-30

## TL;DR

This study finds that lower levels of a bone turnover marker called β-CTX are linked to a higher risk of diabetic kidney disease in type 2 diabetes patients.

## Contribution

The study identifies β-CTX as a potential independent marker for diabetic kidney disease risk in type 2 diabetes patients.

## Key findings

- DKD patients had significantly lower levels of N-MID, β-CTX, and PINP compared to non-DKD patients.
- Lower β-CTX levels were independently associated with a higher risk of DKD after adjusting for confounders.
- β-CTX showed weak positive correlations with eGFR and ALP levels.

## Abstract

Diabetic kidney disease (DKD) is one of the most serious complications of type 2 diabetes mellitus (T2DM), and bone metabolism disorders show a close linkage to DKD. Thus, this study aimed to explore the association between bone turnover markers (BTMs) and DKD.

In present cross-sectional study, serum BTMs were detected in 1433 hospitalized patients with T2DM. Logistic regression analysis was used to investigate the associations between osteocalcin (N-MID), β-cross-linked C-telopeptide (β-CTX), total type I collagen N-terminal propeptide (PINP), and the risk of DKD.

The circulation N-MID, β-CTX, and PINP levels were significantly lower in the DKD group compared with the non-DKD group (all P < 0.05), especially in male and aged < 60 subgroups. Serum BTM levels showed a weak correlations with certain glucose metabolism parameters–such as glycated hemoglobin, fasting blood glucose, C peptide, and fasting insulin−as well as alkaline phosphatase (ALP) levels and low-density lipoprotein (all P < 0.001). A weak negative correlation was also observed with the duration of diabetes (all P < 0.0001). In addition, β-CTX levels showed a minimal positive correlation with eGFR (r = 0.057, P=0.036) and a modest correlation with ALP (r = 0.31, P < 0.0001). After adjusting for potential confounders, higher serum β-CTX levels were independently associated with a lower risk of DKD. However, no significant associations were found among serum N-MID, PINP, and the risk of DKD.

BTM levels were significantly decreased in patients with DKD. Lower β-CTX levels were independently associated with a larger prevalence of DKD after adjusting for potential confounders, suggesting that serum β-CTX may be an independent marker associated with the risk of DKD.

## Linked entities

- **Proteins:** bglap2 (bone gamma-carboxyglutamate (gla) protein (osteocalcin) 2), ALPP (alkaline phosphatase, placental)
- **Diseases:** diabetic kidney disease (MONDO:0005016), DKD (MONDO:0005016), type 2 diabetes mellitus (MONDO:0005148), T2DM (MONDO:0005148)

## Full-text entities

- **Genes:** BGLAP (bone gamma-carboxyglutamate protein) [NCBI Gene 632] {aka BGP, OC, OCN}, ALPP (alkaline phosphatase, placental) [NCBI Gene 250] {aka ALP, PALP, PLAP, PLAP-1}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}
- **Diseases:** DKD (MESH:D003928), T2DM (MESH:D003924), diabetes (MESH:D003920), bone metabolism disorders (MESH:D001851)
- **Chemicals:** C peptide (MESH:D002096), glucose (MESH:D005947), N-MID (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

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Source: https://tomesphere.com/paper/PMC12518059