Greater Urinary Calcium Excretion Is Associated With Diminished Bone Accrual in Youth With Type 1 Diabetes

Abstract

Context: The adverse skeletal effects of type 1 diabetes (T1D) include deficient bone accrual and lifelong increased fracture risk. The contributors to impaired bone accrual in people with T1D are incompletely understood.

Objective: To determine if urinary calcium excretion is associated with impaired bone accrual in youth with T1D and to characterize the contribution of glycemic control and markers of bone mineral metabolism to urinary calcium excretion.

Design: Observational study.

Participants: Fifty participants with T1D aged 6 to 20 years completed a 12-month longitudinal study of bone accrual. A second cohort of 99 similarly aged participants with T1D completed cross-sectional 24-hour urine and blood collections.

Main outcome measure: Whole body less head bone mineral content (WBLH BMC) velocity Z-score and fractional excretion of calcium (FeCa).

Results: Participants in the bone accrual cohort had lower WBLH BMC velocity compared to a healthy reference dataset (Z-score -0.3 ± 1.0, P = .03). FeCa was negatively associated with WBLH BMC velocity Z-score, ρ = -0.47, P = .001. In the urinary calcium excretion cohort, intact PTH (β = -0.4, P = .01), beta c-telopeptide (β = 0.35, P = .007), and either hemoglobin A1c (β = 0.08, P = .03) or urine fractional glucose excretion (β = 0.07, P = .03) were associated with FeCa in multivariable regression models that included known determinants of urinary calcium excretion.

Conclusion: Urinary calcium excretion was negatively associated with bone accrual in this cohort of youth with T1D. Mechanistic studies are needed to determine if interventions to reduce urinary calcium excretion could increase bone accrual and reduce skeletal fragility in people with T1D.

Keywords: DXA; disorders of calcium/phosphate metabolism; osteoporosis; type 1 diabetes.

Figure 1.

Study flow chart. Individuals with type 1 diabetes of at least 1 year and between the ages of 5 and 20 years were eligible to participate. Recruitment into the DXA study continued until 60 participants completed the first study visit; recruitment into the determinants for 24-hour urine calcium study continued until 100 participants returned complete urine collections. The final sample of urine collections for analysis included data from 44 subjects who completed the DXA study. ¹Adequacy of 24-hour urine collections based on age and sex-specific data for 24-hour urine creatinine excretion in children and young adults (18). Abbreviations: DXA, dual-energy X-ray absorptiometry.

Figure 2.

(A) WBLH BMC Z-score at baseline and 12-month follow-up in 50 youths with type 1 diabetes. WBLH BMC Z-score for age and sex adjusted for height Z-score at baseline (−0.2 ± 0.8) and 12-month follow-up (−0.2 ± 0.9) visit did not differ significantly from data for healthy children in the BMDCS from which the Z-scores were derived, P = .08 for both, or from baseline to 12 months, P = .56. Data presented as dot plots to illustrate all data points. Median represented by solid line; 25th and 75th percentile represented by dashed lines. (B) WBLH BMC velocity Z-score of −0.3 ± 1.0 was significantly lower than expected based upon BMDCS data for healthy children, P = .03. WBLH BMC velocity Z-score is sex and pubertal stage specific, adjusted for baseline BMC, age, height, height velocity, lean mass, and lean mass velocity. Data presented as dot plots to illustrate all data points. Median represented by solid line; 25th and 75th percentile represented by dashed lines. Abbreviations: BMC, bone mineral content; BMDCS, Bone Mineral Density in Childhood Study; WBLH, whole body less head.

Figure 3.

Urinary FeCa was significantly negatively associated with WBLH BMC velocity Z-score in 50 youths with type 1 diabetes. Spearman's rank coefficient of correlation (ρ) shown. FeCa is the average of baseline and 12 month; WBLH BMC velocity Z-score is sex and pubertal stage-specific, adjusted for baseline BMC, age, height, height velocity, lean mass, and lean mass velocity. Sensitivity analyses using baseline (ρ = −0.37, P = .01) or 12-month (ρ = −0.48, P = .001) FeCa, and excluding the subject in the upper left with very high FeCa (ρ = −0.44, P = .002), all confirm the statistically significant relationship between spot urinary FeCa and WBLH BMC velocity Z-score. FeCa calculated as [(urine calcium*serum creatinine) / (urine creatinine*serum calcium)] and expressed as a percentage. Dashed line represents liner trend between FeCa and WBLH BMC velocity Z-score. Abbreviations: BMC, bone mineral content; FeCa, fractional excretion of calcium; WBLH, whole body less head.