Vertebral fracture assessment (VFA) for monitoring vertebral reshaping in children and adolescents with osteogenesis imperfecta treated with intravenous neridronate.

PURPOSE: The study was aimed at monitoring vertebral bodies changes with the use of Vertebral Fracture Assessment (VFA) in children and adolescents affected by osteogenesis imperfecta (OI) during treatment with intravenous neridronate. METHODS: 60 children and adolescents (35 males and 25 females; age 1-16 years) with OI type I, III and IV were included in the study. Intravenous neridronate was administered at the dose of 2 mg/kg every 3 months in all patients. Lumbar spine (LS) bone mineral density (BMD) and VFA by dual X-ray absorptiometry (DXA) were assessed every 6 months up to 24 months during treatment. VFA with vertebral morphometry (MXA) was used to calculate the three indices of vertebral deformity: wedging, concavity and crushing. Serum calcium, phosphate, parathyroid hormone (PTH), 25-hydroxy-vitamin D [25(OH)D], total alkaline phosphatase (ALP), bone alkaline phosphatase (BALP) and urinary C-terminal telopeptide of type 1 collagen (CTx) were measured at any time point. RESULTS: Mean LS BMD values significantly increased at 24 months compared to baseline (p < 0.0001); the corresponding Z-score values were -1.28 ± 1.23 at 24 months vs -2.46 ± 1.25 at baseline; corresponding mean Bone Mineral Apparent Density (BMAD) values were 0.335 ± 0.206 vs 0.464 ± 0.216. Mean serum levels of ALP, BALP and CTx significantly decreased from baseline to 24 months. By MXA, we observed a significant 19.1% reduction of the mean wedging index of vertebral reshaping at 12 months, and 38.4% at 24 months (p < 0.0001) and of the mean concavity index (16.3% at 12 months and 35.9% at 24 months; p < 0.0001). Vertebral reshaping was achieved for 66/88 (75%) wedge fractures and 59/70 (84%) concave fractures, but there were 4 incident mild fractures. Finally, VF rate was reduced at 24 months compared to baseline: 37/710 (5.2%) vs 158/710 (22.2%). CONCLUSION: Our study demonstrates the utility of VFA as a safe and alternative methodology in the follow-up of children and adolescents with OI.

Circulating endothelin-1 in non-insulin-dependent diabetic patients with retinopathy.

Endothelin-1 (ET-1), a novel 21-amino acid vasoconstrictive peptide secreted by endothelial cells, has been thought to play a role in various forms of vascular disease. Diabetes mellitus is well known for its association with microvascular damage. To investigate whether ET-1 levels may be related to microangiopathy in diabetes mellitus, plasma ET-1 levels were measured in two groups of diabetic patients: A) 47 patients with non-insulin dependent diabetes mellitus (NIDDM) and retinopathy (28 M, 19 F; mean age 60.7+/-8.5 yrs) but without nephropathy (microalbuminuria < 30 mg/day) and hypertension (SBP < 140, DBP < 90 mmHg); group A was divided in three subgroups based on the severity of retinopathy: a) 16 with background retinopathy; b) 21 with pre-proliferative retinopathy; c) 10 with proliferative retinopathy. B) 8 patients with insulin-dependent diabetes mellitus (IDDM) recently diagnosed (6 M, 2 F; 16.4+/-3.8 yrs) without complications. C) 28 healthy subjects (HS) (16 M, 12 F; 47.8+/-11.8 yrs) as controls. In the NIDDM group the ET-1 concentration was significantly higher (17.3+/-2.4 pg/ml) than both in the HS (8+/-4.7 pg/ml) and IDDM patients (10.2+/-3.7 pg/ml) (p < 0.0001). In the subgroups with retinopathy the ET-1 levels were a) 15.1+/-4.3 pg/ml; b) 22.2+/-6.8 pg/ml and c) 16.6+/-5.1 pg/ml. These values were significantly elevated as compared to HS (p<0.001; p < 0.0001; p < 0.002, respectively), being the highest levels of ET-1 observed in the NIDDM patients with pre-proliferative retinopathy. In conclusion our study revealed that the ET-1 concentrations are elevated in NIDDM patients with retinopathy especially in those patients with pre-proliferative retinopathy.