Bone mineral density, collagen type 1 α 1 genotypes and bone turnover in premenopausal women with diabetes mellitus

Abstract

Diabetic osteopenia is a recognised but neglected complication of diabetes mellitus. Reduced bone mass and an overall twofold increase in fracture rate has been shown to occur in Type I (insulin-dependent) diabetes mellitus [1]. The situation in Type II (non-insulin-dependent) diabetes mellitus is less clear-cut, with reports of increased, decreased or unaltered bone mass reflecting the underlying heterogeneity of Type II diabetes [2]. The pathogenesis of diabetic osteopenia remains unclear. The reduction in bone mass could be due, in part, to a failure to reach peak bone mass especially in younger subjects with Type I diabetes [3] and partly to abnormal bone turnover [4]. In adults net bone loss has been found with a Diabetologia (1998) Summary Osteopenia is a recognised complication of diabetes mellitus which could be due to abnormal bone turnover or disturbances in the calcium/parathyroid hormone/vitamin D axis or both. Genetic factors also play an important part in determining bone mass although this has not been studied in diabetes.Recently a polymorphism of the collagen type 1 a 1 (COL1A1) gene has been shown to be associated with low bone mass in British women. To identify subjects with diabetes who may be at risk of developing osteoporosis and fractures, we analysed bone mineral density in relation to the biochemical markers of bone turnover, calcium homeostasis and the COL1A1 genotype in a group of premenopausal women with Type I (insulin-dependent) diabetes mellitus (n = 31), Type II (non-insulin dependent) diabetes mellitus (n = 21) and control subjects (n = 20). Bone mineral density was lower at the femoral neck in the subjects with Type I diabetes (p = 0.08) as were serum 25-hydroxyvitamin D compared with control subjects (p = 0.023) and this was negatively correlated with serum collagen type 1 C-terminal propeptide (r = ±0.56, p < 0.001). Bone mineral density in Type II diabetes was not different from control subjects, after correction for body mass index. Bone resorption was, however, raised in the Type II diabetic subjects as reflected by the higher urinary deoxypyridinoline values (p = 0.016) and lower collagen type 1 C-terminal propeptide:deoxypyridinoline ratio (p = 0.04). In the whole group studied, subjects with the COL1A1 s' genotype had lower bone mineral density at the femoral neck (p = 0.01) which was partly attributable to a lower body mass index. Following multiple regression analysis body mass index and collagen type 1 C-terminal propeptide concentrations remained determinants of bone mass at all three sites, whereas genotype appeared to be a predictor of bone mass at the femoral neck only. We conclude that measurement of these variables could prove useful in firstly identifying those diabetic women at risk of osteoporosis and secondly guiding therapeutic intervention. [Diabetologia (1998)

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

“…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 mineral density and its determinants in diabetes: the Fremantle Diabetes Study

“…Several mechanisms may contribute to type 1 diabetesassociated osteopenia, including impaired vitamin D-para-thyroid hormone (PTH) regulation [9,13] and altered bone mineral metabolism [14]. Increased bone resorption and decreased formation have been observed in young poorly controlled patients with type 1 diabetes of long duration [15,16].…”

Association between serum leptin level and osteoporosis in patients with type 2 diabetes mellitus

“…Although it has not been proven yet by community-based screenings, determining risk groups and following them closely is a logical approach in preventing osteoporosis (3). Recent findings strongly support direct or indirect role of leptin.…”