Exploring the relationship between bone mineral density and bone biomarkers with the duration of childhood-onset type 1 diabetes in Kuwait

Introduction The significance of the human skeleton as an endocrine organ has been emphasized in recent literature where it may have the ability to regulate metabolic pathways including insulin signaling and glucose homeostasis. Therefore, the consequences of T1D can significantly impact bone health and structural formation, leading to osteoporosis later in life. This study aimed to evaluate lumbar spine size adjusted bone mineral density (BMD) and bone turnover biomarkers in Kuwaiti youth with childhood-onset T1D, and to examine its association with diabetes duration and glycemic control. Methods In this cross-sectional study, 132 Kuwaiti participants aged 5 to 18 years with T1D were recruited from a pediatric diabetes clinic. Anthropometric measurements, pubertal status, and clinical histories were recorded. Dual-energy X-ray absorptiometry (DXA; Hologic Discovery W, Hologic APEX Software version 5.6.0.5) was used to assess lumbar spine bone mineral apparent density (BMAD). Bone formation (osteocalcin, P1NP, P1CP) and resorption (urine CTX) biomarkers were measured. Multivariable linear regression models adjusted for age at diagnosis, sex, pubertal status, height, and HbA1c were used to assess associations between (i) diabetes duration and BMAD Z-score and (ii) diabetes duration and each bone biomarker. Results Median diabetes duration was 3.5 years (LQ-UQ: 1.01-6.98 years). Each additional year of diabetes duration was associated with a non-significant decrease in BMAD Z - score after adjustment for age at diagnosis, sex, Tanner pubertal status, average HbA1c, and height (effect size: –0.11, 95% CI: –0.22 to 0.01). Higher average HbA1c was significantly associated with lower BMAD Z - score (–0.18 per unit increase, p=0.005). Each additional year of diabetes duration was associated with lower osteocalcin levels by 30.6% (95%CI: 37.5-22.9%) amongst females and 14.5% (95% CI: 24.7-2.8%) amongst males, and lower Urine CTX levels by 14.3% amongst females (95% CI: 8.5-19.7%), but not amongst males. Conclusion Higher mean HbA1c was associated with a lower lumbar-spine BMAD Z-score, whereas diabetes duration was not significantly associated with BMAD Z-score. Sex-specific associations were observed between diabetes duration and selected bone-turnover markers. These cross-sectional findings require confirmation in longitudinal studies incorporating appropriately matched controls and population-appropriate DXA reference data.