Type 2 diabetes mellitus (T2DM) is common in patients with chronic kidney disease (CKD). Both conditions associate with an increased fracture risk, with proposed etiology including impaired bone quantity and quality. This cross-sectional study examined the bone phenotype in patients with T2DM and kidney failure and explored the role of glycemic control on the bone phenotype. To do so laboratory parameters of mineral metabolism (including sclerostin) and bone turnover markers (BTM) (bone-specific alkaline phosphatase (BALP), trimeric pro-collagen type I N-terminal propeptide (intact PINP) and tartrate-resistant acid phosphatase isoform 5b (TRACP5b)) were assessed in 647 patients with kidney failure, of which 102 had T2DM (median hemoglobin A1c (HbA1c) of 6.2%), at time of kidney transplantation. Patients with type 1 DM were excluded. Bone mineral density (BMD, n = 555) by densitometry, and bone histomorphometry (n = 188) were available for subsets, and correlations between HbA1c and both BTM and BMD were examined. This study found that intact PINP was lower (68 vs. 82 μg/L, p = .03) while sclerostin was higher (2.1 vs. 1.8 ng/mL, p = .04) in T2DM versus non-T2DM in unadjusted analysis. BMD at the lumbar spine (Z-score - 0.066 vs. -0.760, p < .001) and femoral neck (Z-score - 0.680 vs. -0.965, p = .04) were higher in T2DM, and T2DM was in multivariable regression analysis identified as a significant determinant of lumbar spine BMD, independent of age, sex, and BMI. Bone histomorphometric parameters did not differ between groups. A correlation between HbA1c and BTM and BMD was present, but only in non-T2DM (BALP (ρ = -0.12, p = .007), intact PINP (ρ = 0.14, p = .002), TRACP5b (ρ = -0.13, p = .003), BMD at lumbar spine (ρ = 0.12, p = .008), femoral neck (ρ = 0.11, p = .02), and total hip (ρ = 0.17, p < .001)). In conclusion, patients with kidney failure and T2DM have preserved BMD compared to patients without diabetes. Our findings suggest a role for hyperglycemia as a determinant of the bone phenotype.
Hauge et al. (Wed,) studied this question.