Deficits in Trabecular Bone Microarchitecture in Young Women With Type 1 Diabetes Mellitus

Abstract

The pathophysiological mechanism of increased fractures in young adults with type 1 diabetes mellitus (T1DM) is unclear. We conducted a case-control study of trabecular bone microarchitecture and vertebral marrow adiposity in young women with T1DM. Thirty women with T1DM with a median age (range) age of 22.0 years (16.9, 36.1) attending one outpatient clinic with a median age at diagnosis of 9.7 years (0.46, 14.8) were compared with 28 age-matched healthy women who acted as controls. Measurements included MRI-based assessment of proximal tibial bone volume/total volume (appBV/TV), trabecular separation (appTb.Sp), vertebral bone marrow adiposity (BMA), and abdominal adipose tissue and biochemical markers of GH/IGF-1 axis (IGF-1, IGFBP3, ALS) and bone turnover. Median appBV/TV in cases and controls was 0.3 (0.22, 0.37) and 0.33 (0.26, 0.4), respectively (p ¼ 0.018) and median appTb.Sp in T1DM was 2.59 (2.24, 3.38) and 2.32 (2.03, 2.97), respectively (p ¼ 0.012). The median appBV/TV was 0.28 (0.22, 0.33) in those cases with retinopathy (n ¼ 15) compared with 0.33 (0.25, 0.37) in those without retinopathy (p ¼ 0.02). Although median visceral adipose tissue in cases was higher than in controls at 5733 mm 3 (2030,11,144) and 3460 mm 3 (1808, 6832), respectively (p ¼ 0.012), there was no difference in median BMA, which was 31.1% (9.9, 59.9) and 26.3% (8.5, 49.8) in cases and controls, respectively (p ¼ 0.2). Serum IGF-1 and ALS were also lower in cases, and the latter showed an inverse association to appTbSp (r ¼ -0.30, p ¼ 0.04). Detailed MRI studies in young women with childhood-onset T1DM have shown clear deficits in trabecular microarchitecture of the tibia. Underlying pathophysiological mechanisms may include a microvasculopathy.

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

“…In some human studies, bone resorption in T1DM is either decreased or unaltered and does not explain the low BMD observed in this disease (80). In children and young adults, T1DM patients had lower PINP and CTX levels compared to controls (67,81). However enzymatic cross-linking of collagen is reduced in diabetes (82).…”

“…These data suggest that MVD may be an independent risk factor of fractures. By magnetic resonance imaging (MRI), Adbalrahaman confirmed trabecular deficits with reduced bone volume and trabecular number at the proximal tibia of young adults with childhood onset of T1DM, as well as increased medullary fat in the vertebrae (67).…”

MANAGEMENT OF ENDOCRINE DISEASE: Diabetes and osteoporosis: cause for concern?

“…The decrease was especially prominent in patients with signs of microangiopathy (expressed as retinopathy) (38). However, this may reflect some of the growth issues related to T1D in young persons.…”

“…A recent study using MRI (38) in young women with T1D (median age 22 years, median age at diagnosis 9.7 years) reported reduced bone volume and increased trabecular spacing. The decrease was especially prominent in patients with signs of microangiopathy (expressed as retinopathy) (38).…”

Growth in patients with type 1 diabetes

“…Clinically, in one small study of girls ages 12-15 with T1DM, serum IGF1 concentrations positively correlated with estimates of bone strength as measured by peripheral quantitative computed tomography 75 . Intriguingly, 2 recent studies of skeletal microarchitecture in adults with childhood onset T1DM have demonstrated decreased trabecular bone density at the distal radius and tibia 76,77 ; in both, effects on bone density were limited to those subjects who had clinical evidence of diabetic microvascular disease. These findings again point to the intimate relationship of compromised growth and bone accrual with classic microvascular disease.…”