This cross-sectional study documented very low serum calcidiol and calcitriol concentrations and high urinary N-telopeptide excretion in institutionalized elderly people. There was no difference in serum iPTH concentrations between institutionalized and ambulatory elderly. This finding could not be explained by the differences in calcidiol and calcitriol concentration, nor urinary NTX excretion. These results suggest that other factors than vitamin D deficiency, such as lower mobility status and sedentary life style, might have an important role in the regulation of iPTH and mechanisms of bone loss in the elderly.

Highlights:• A LC-MS/MS method was developed and validated for simultaneous determination of aspirin and salicylic acid in human plasma.• The accuracy and the precision of the method with one-step liquid-liquid extraction were excellent for both analytes.• The method was highly robust and suitable for the analysis of > 2000 samples in a pharmacokinetic study.• The present method can contribute to the improvement of ASP/SAL determination in patients under antithrombotic therapy.• The method can contribute to the reduction of the risk for ASP resistance associated with bioavailability/exposure issues.

Objective: To investigate in¯uences of physical mobility and season on 25-hydroxyvitamin D±intact parathyroid hormone (iPTH) interaction in the elderly. Design: We examined 188 frail institutionalized elderly at the expected nadir of their serum vitamin D concentrations (winter). This group was compared with 309 healthy ambulatory elderly at the expected time of maximum vitamin D repletion (summer), to accentuate the in¯uences of season and physical activity. Methods: Serum concentrations of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, iPTH and urinary deoxypyridinoline (DPD) were measured. Results: Vitamin D metabolites were signi®cantly lower in the institutionalized elderly (P<0.0001), with an 82.5% prevalence of vitamin D de®ciency (25-hydroxyvitamin D <12 ng/ml) in institutionalized elderly in wintertime and 15.5% in ambulatory elderly in summertime. Overall, median iPTH did not differ between groups. However, median iPTH secretion in the presence of low vitamin D serum concentrations (5±30 ng/ml) was greater in ambulatory elderly. This could be explained by lower mobility status being correlated with greater serum calcium concentrations (r=0.24, P=0.02 in women; r=0.35, P=0.001 in men) and greater urinary excretion of DPD (r=0.41, P=0.0001 in women; r=0.42, P=0.0002 in men), independent of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and iPTH. Conclusions: These data support the hypothesis that immobility, even in the presence of vitamin D de®ciency, acts as an overriding in¯uence on bone metabolism by promoting bone resorption (measured as urinary DPD) and increasing serum calcium independent of iPTH. Therefore mobility status may substantially affect 25-hydroxyvitamin D threshold values and the degree to which patients bene®t from vitamin supplementation.

Bisphosphonates and fluoride salts are effective treatments for osteopomsis (OPt. Bisphosphonatas inhibit osteoclastic bone resorption, while fluoride salts increase bone formation by increasing the number of osteoblasts.In this open prospective study we evaluated combined treatment for 1-2 years with a bisphosphonate, (pamidronate, APD, 150 rag/day) and sodium monofluorophosphate (MFP, 2x76 mg/day), Extra calcium and vitamin D were supplemented. This study concerns 31 patients (9 men, 23 women) with a mean age of 65+11.5 years. Hyperthyroidism and hyperparathymidism were excluded in all patients by evaluating serum TSH and PTH values at study entry. Biannual dual energy X-ray absorptiometry (DEXA, QDR 1000, Hologic, Inc. Waltham, USA) was measured on the lumbar spine and left and right femoral neck. Serum calcium and alkaline phosphatase reactivity were determined. This treatment regimen was well tolereted. None of the patients experienced a non-vertebral fracture or the lower extremity pain syndrome, the major side effect of fluoride treatment. Moreover, significant increase in the BMD of the lumbar spine was induced, Lumbar spine BMD vs the values at study entry: 7.4+7.7% after 6 months, 11.3+t:8.2% after 12 months, 1g.3+12.3% after 18 months and 19.5:t:10.4% after 24 months. (p<0.05, after 12 months, Student's T-test) During this time period femoral BMDs remained unchanged, Serum calcium and alkaline phosphatase levels did not essentially change during treatment: 2.4:1:0.1 mmol/I and 70.2• U/I, respectively at study entry, 2.4i-O.1 and 69.6+34.2 after 12 months and 2.2+0.4 and 75.5:1:21.8 alter 24 months treatment. Only two patients with a significant increase in BMD presented additional spine fractures during the first treatment year. Another patient, who was not responding with increasing lumbar BMD values, developed one additional spine fracture.In conclusion combined treatment of APD and MFP for OP produced a significant increase in BMD of the lumbar spine progressively throughout the two years of therapy, without undesired side effects.

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