Bone disease in diabetes.

The relationship between diabetes and bone disease is complex. While low bone mineral density (BMD) is consistently observed in type 1 diabetes (T1DM), in type 2 diabetes (T2DM) bone mineral density is similar to or higher than in non diabetic subjects. Yet, for both types of diabetes bone appears to be more fragile for a given density. Recent meta-analyses and cohort studies confirm that T1DM and T2DM are associated with higher fracture risk. Many factors influence the probability of fractures. Diabetes can affect bone through multiple pathways including obesity, changes in insulin levels, higher concentrations of advanced glycation end products in collagen, increased urinary excretion coupled with lower intestinal absorption of calcium, inappropriate homeostatic response of parathyroid hormone secretion, complex alterations of vitamin D regulation, reduced renal function, lower insulin-like growth factor-I, microangiopathy, and inflammation. Data on cellular mechanisms and experimental models are extensive, but the relevance of each one of these factors to the clinical situation is unclear. In this article we review the pathophysiological mechanisms potentially involved in the altered BMD found in diabetic patients, show data on the increased risk of fractures, and speculate on the potential causes of the increased risk of fractures in this context. Finally, we comment on the prevention and treatment of osteoporosis in diabetes, although the lack of trials testing the use of pharmacotherapy on preventing fractures in this context is emphasized.

Biochemical effects of calcifediol supplementation in mild, asymptomatic, hyperparathyroidism with concomitant vitamin D deficiency.

It has been proposed to cautiously supplement with vitamin D to any patient with asymptomatic primary hyperparathyroidism (PHTP) and a plasma 25-hydroxyvitamin D [25(OH)D] concentration <50 nmol/l. Evidence about the safeness of this intervention is limited to two studies. Our aim was to prospectively assess the biochemical effects of one-year 25(OH)D supplementation in this context. Twenty-seven patients were included in this study. Calcifediol was started at a dose of 480-960 IU/24 h (8-16 microg/24 h) and adjusted up to a maximum of 960 IU/24 h (16 microg/24 h). Basal calcium, phosphate, albumin, total alkaline phosphatase (ALP), creatinine, 24 h calcium urinary excretion, intact PTH (iPTH) and 25(OH)D were measured before and during vitamin D supplementation. The mean basal 25(OH)D was 28.7 +/- 8.0 nmol/l, and at 12 months was 71.5 +/- 32.5 nmol/l (P = 0.00 vs. baseline). After 3, 6 and 12 months iPTH levels were 141.7 +/- 108.4 ng/l (P = 0.00 vs. baseline), 131.1 +/- 95.7 ng/l (P = 0.03 vs. baseline) and 162.2 +/- 139.3 ng/l (P = ns vs. baseline). Mean calcium did not change. Mean urinary calcium excretion increased significantly (basal: 5.7 +/- 2.9 mmol/24 h, 12 months: 7.9 +/- 4.9 mmol/24 h, P = 0.02). Cautious calcifediol supplementation significantly increased mean 25(OH)D and temporarily reduced mean iPTH. It did not change mean serum calcium, but urinary calcium excretion increased significantly. We suggest that serum calcium and 24 h calciuria be measured at regular intervals in patients with PHTP, while on calcifediol supplementation.