Bone Metabolic Abnormalities Associated with Well-Controlled Type 1 Diabetes (IDDM) in Young Adult Women: A Disease Complication Often Ignored or Neglected

Objectives: This investigation on a homogenous cohort of young adult Caucasian type 1 diabetic (IDDM) patients (1) aimed at studying the occurrence of low bone mineral density (BMD) at an early stage prior to menopause (i.e., during the first decade after peak bone mass) and (2) elucidating the possible mechanisms underlying IDDM-induced bone complication.

Methods: Twenty-seven female patients with insulin-treated and well-controlled diabetes, without renal complications, and 32 well-matched healthy controls, aged between 30 and 40 years and fulfilling rigorous inclusion criteria to minimize bone-confounding factors, were enrolled. Areal BMD was evaluated by dual energy X-ray absorptiometry at axial (lumbar spine) and appendicular (femur) sites, using diagnostic WHO reference (T-scores). Osteoblast functions, bone metabolism, related key minerals, and 2 osteoclast-stimulating calciotropic hormones regulating their serum levels were assessed biochemically.

Results: The number of cases with low BMD (T-score below ?1.1 SD) was almost 2-fold greater (p < 0.01) in the IDDM group. BMD was significantly lower in this group for 3 lumbar sites (p < 0.01) and femur Ward's triangle (p < 0.05). Bone formation was reduced, as evidenced by the suppressions of osteocalcin (OC; p < 0.01) and IGF-I (p < 0.001). However, bone alkaline phosphatase (bALP) was induced (p < 0.01), in contrast to what is usually observed in cases of reduced bone formation. Correlated total ALP activity was also significantly increased. There was no change in the specific marker of bone resorption (urinary deoxypyridinoline). Serum calcium was significantly elevated, particularly after adjustment for albumin (p < 0.001), despite lower 1,25(OH)₂D₃ (p < 0.001) and no elevation of PTH. All significant bone-related biochemical changes were significantly correlated with glycosylated hemoglobin, a clinical indicator of long-term glycemic control, indicating a direct effect of the disease.

Conclusions: Bone loss in the IDDM group results from a decrease in bone formation rather than an increase of bone resorption. The induction of bALP is indicative of impaired osteoblast differentiation and maturation, which delayed (down-regulated) later stages of matrix mineralization, as evidenced by lower OC and BMD.