Decreased Lumbar Spine Bone Mass and Low Bone Turnover in Children and Adolescents with Insulin Dependent Diabetes Mellitus Followed Longitudinally

Abstract

The effects of insulin dependent diabetes mellitus (IDDM) on bone metabolism are still not well defined. We evaluated total bone mineral content (TBMC) and bone mineral density (BMD) at the lumbar spine and femoral neck using dual X-ray absorptiometry in 26 IDDM children (15 M, 11 F) with a mean chronological age of 12.1+/-3.1 yr (range 7.1-14.2 yr). Duration of diabetes was 4.3+/-2.9 yr, with a mean glycosylated hemoglobin of 9.2+/-0.4%. BMD and TBMC standard deviation scores (Z-scores) were determined by comparing our results to controls matched for age, sex and pubertal status. BMD and bone formation and resorption markers were determined at the beginning of the study and after one year of follow up. Mean lumbar spine Z-score was -1.06+/-0.2, with negative values in 24 of 26 children (92.6%); 14/26 patients (53.8%) had a lumbar spine Z-score >1.0 SD below the mean. Mean lumbar spine Z-score remained unchanged after one year of follow up (-1.02+/-0.3). No significant differences were obtained in femoral neck BMD or TBMC between groups. No correlation was observed between lumbar spine BMD Z-scores and duration of IDDM or degree of diabetes control, as assessed by the mean glycosylated hemoglobin. Daily urinary calcium excretion was elevated in our patients initially and after one year of follow up; however, no correlation was obtained between lumbar spine BMD and 24 h urinary calcium excretion. Carboxy-terminal propeptide of type 1 collagen values and levels of urinary cross-linked N-telopeptides of type 1 collagen in the diabetic children were significantly lower than those of the matched controls. Osteoblastic activity as assessed by serum osteocalcin and by the carboxy-terminal propeptide of type I collagen and bone resorption as measured by cross-linked N-telopeptides of type 1 collagen did not correlate with the lumbar spine Z-scores. When IDDM patients were subdivided into males and females and into children with more than or less than 2 yr duration of diabetes since diagnosis, no differences between groups were found. These results suggest that insulin dependent diabetes in children is associated with low bone turnover resulting in a deficit in bone mass which may be manifested as osteopenia in the growing bone. This defect is already present in trabecular bone early on in the disease and seems not to be related to glycemic control.

MECHANISMS IN ENDOCRINOLOGY: Mechanisms and evaluation of bone fragility in type 1 diabetes mellitus

“…Some studies, however, documented the presence of osteopenia at diagnosis of diabetes (35). As depicted in Table 1, BMD correlated poorly with glycaemic control in most (29,33,34,35,36,37), but not all (28,31,32), studies. However many studies reported an association between the presence of microvascular complications of diabetes and the presence and/or progression of a decreased BMD (27,28,38,40,42,50).…”

“…Although the decreased BMD reported in subjects with T1DM (27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,50,58) may largely explain the higher fracture risk observed in these patients (17,18,19,20,21,22,26), alterations in bone quality, as described below, may also contribute and actually confer its specific nature to diabetic bone disease.…”

“…Most (27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44), although not all (45,46,47,48,49), studies report a significant decrease in BMD at either the spine, hip or total body. The magnitude of the decrease in BMD varied quite markedly from 8 to 67%, and large gender differences appear to be present, with many studies documenting changes in BMD in either males or females only.…”

“…A recent meta-analysis (17) reported an average decrease in spine BMD of K22% and a hip Z-score of K37% compared to that of age-and gender-matched controls. Many (27,30,36,43), but not all (29,35), studies suggested that a decrease in BMD occurred more frequently in those with longstanding diabetes. Some studies, however, documented the presence of osteopenia at diagnosis of diabetes (35).…”

Bone Size Normalizes With Age in Children and Adolescents With Type 1 Diabetes

“…In pediatric patients, in particular, this method has l i m i t a t i o n s b e c a u s e o f t h e t w odimensional measurement and therefore height dependency. Longitudinal data on relatively small numbers of patients over 2-4 years revealed disturbed or normal bone development (7,8). A recently published study over a wide time range from 12 to 84 months showed slightly reduced mineralization of the spine independent of metabolic control or microvascular complications (9).…”