The effects of strontium ranelate on BMD in osteoporotic men were similar to those in postmenopausal osteoporotic women, supporting its use in the treatment of osteoporosis in men.

Calcium malabsorption is common in the elderly and may contribute to the development of age-related bone loss. To investigate its cause, we have measured radio-calcium absorption, plasma 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone in forty-eight elderly women with a normal plasma creatinine. Calcium malabsorption was associated with low 25-hydroxyvitamin D concentrations and was corrected by increasing these into the normal range by treatment with oral 25-hydroxyvitamin D,. Treatment also increased 1 ,X-dihydroxyvitamin D, and decreased parathyroid hormone concentrations.Before treatment, plasma parathyroid hormone was related to plasma creatinine but not to 25-hydroxyvitamin D, and the change in absorption on treatment correlated inversely with plasma creatinine. "Cr EDTA clearance was measured in sixteen elderly women and confirmed that renal impairment was common even with a plasma creatinine in the normal range. Our results suggest that calcium malabsorption in the elderly is predominantly due to vitamin D deficiency; renal impairment is also common and contributes to the malabsorption by increasing the requirements for vitamin D.

Background-Primary biliary cirrhosis (PBC) is increasingly being diagnosed in the earlier non-cholestatic stages of disease. Accepted wisdom has been that PBC is frequently complicated by osteoporosis. Whether this association holds true for the broader spectrum of PBC patients now recognised has not as yet been studied. Aims-To examine the extent to which osteoporosis occurs more commonly in PBC patients than in normal individuals of the same age and sex. Design-Retrospective review of a large cohort of well characterised PBC patients. Patients-A total of 272 PBC patients with definite or probable PBC followed up for a mean of 10.1 years (total follow up 2726 patient years) who had at least one bone mineral density measurement (BMD). Results-In this unselected group of PBC patients, mean Z scores (number of SDs from age and sex matched normal mean values) at the neck of femur (NOF) and lumbar spine (LS) at first BMD measurement (7 (6) years after PBC diagnosis) were −0.1 (1.4) and 0.1 (1.4), respectively. At first BMD measurement, 18 PBC patients had Z scores less than −2.0 and 85 had T scores less than −2.5. No factors predictive of osteoporosis were found in aVected patients. A total of 957 BMD measurements were performed (0.35 per patient year of follow up); 220 patients had two or more measurements. No patient went on to develop de novo osteoporosis during follow up. In the 51 patients (who were clinically representative of the whole group) who received no PBC or bone related treatment during follow up, %BMD changes per year at the NOF and LS were −1.6 (3.2) and 0.1 (2.2), respectively. No variance in this "natural" rate of BMD measurement was seen in patients receiving PBC modulating agents (including prednisolone and UDCA) or osteoporosis prophylaxis/therapy. Significant improvement at the LS was seen in patients undergoing liver transplantation. Conclusions-Osteoporosis is not a specific complication of PBC. (Gut 2001;49:282-287)

Radio-calcium absorption, plasma 25-hydroxyvitamin D [25-(OH)D] and 1,25-dihydroxyvitamin D [1,25-(OH)2D] concentrations were measured in 19 elderly women with, and 21 without, vertebral fractures, before and after treatment with 25-hydroxyvitamin D3 [25-(OH)D3], to establish whether malabsorption of calcium in elderly women with vertebral fractures has a cause different from that in elderly women without vertebral fractures. Malabsorption of calcium and low plasma 25-(OH)D and 1,25-(OH)2D concentrations were common in both groups of women but there was no significant difference in these variables between the two groups. After treatment with 40 micrograms of 25-(OH)D3 daily for 7 days, there was a significant increase in plasma 25-(OH)D and 1,25-(OH)2D in both groups of women, but radio-calcium absorption increased significantly only in the group without vertebral fractures. Elderly women with vertebral fractures have malabsorption of calcium which is resistant to the action of vitamin D metabolites at concentrations which correct calcium malabsorption in elderly women without vertebral fractures.

We have screened the mitochondrial genome of 15 men with symptomatic vertebral fractures (median age 62 years, range 27-72 years) and 17 male control subjects (median age 61 years, range 40-73 years) for the presence of mitochondrial DNA (mtDNA) deletions in peripheral monocyte DNA. Polymerase chain reaction analysis provided evidence of a common age-related (4.9 kb) mtDNA deletion situated between nucleotides 8470 and 13.460 of the genomic sequence in 5 of the 17 controls (29%) and 9 of the 15 patients (60%) investigated. Southern blotting and polymerase chain reaction revealed a novel 3.7 kb deletion in 2 patients. One of the affected patients, a 27-year-old man with severe osteoporosis (lumbar spine bone mineral density (BMD) 0.381 g/cm(2); Z-score -6.45) was found to harbor deletion in almost 50% of the mitochondria. The patient had a blood lactic acid level (4.6 nM) that was over 3 times the upper reference range (0-1.3 mM), thus confirming the presence of systemic oxidative stress. Further analysis by modified primer shift polymerase chain reaction showed the 5' breakpoint to be between the nucleotides 10.63 kb and 10.80 kb of the mtDNA. The second patient harboring the 3.7 kb deletion was older (62 years) with less severe osteoporosis (lumbar spine BMD 0.727/cm(2); Z-score -2.58) and the proportion of affected mitochondria was lower (25%). The significance of these findings is discussed and the possible relation between oxidative stress and accelerated bone loss is examined.