Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020438 (hypercalciuria)
 2,502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Decreased bone mass has been reported in patients with idiopathic hypercalciuria. Previous studies, using bioassays, have suggested a role of interleukin-1 (IL-1), in the decreased bone mineral density (BMD) of fasting hypercalciuria. The present study was designed to determine which IL-1 fraction (alpha or beta) correlates with bone resorption and whether other known bone resorting cytokines like interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) may play a role in this process. Cytokines production was determined by quantitative and specific analysis, enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase polymerase chain reaction (RT-PCR). Dual-energy X-ray absorptiometry and cytokine production by unstimulated and lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) were determined in a group of 29 patients with recurrent nephrolithiasis (17 hypercalciurics and 12 normocalciurics), and 12 healthy controls. The hypercalciuric subjects showed lower vertebral BMD than the normocalciuric or normal controls. There was no difference in spinal or femoral BMD between absorptive or fasting hypercalciurics. A significant negative correlation existed between urinary calcium excretion and vertebral BMD (r = -0.55, P < 0.01). Basal IL-1 alpha production correlated with vertebral BMD (r = -0.45, P < 0.02). This correlation was not seen with IL-1 beta, IL-6 or TNF-alpha production. LPS-induced IL-6 and TNF-alpha production were enhanced in the hypercalciuric patients, when compared to normocalciurics or controls. Control and normocalciuric subjects showed minimal amounts of IL-1 alpha mRNA. In contrast, hypercalciuric patients showed a significant increase of spontaneous IL-1 alpha mRNA transcription. These results suggest that different cytokines could be involved in the bone resorption process observed in hypercalciuria.
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PMID:Possible role of cytokines on the bone mineral loss in idiopathic hypercalciuria. 877 Sep 75

Calcium stone formers (CaSF) with idiopathic hypercalciuria (IH) have been shown to have decreased bone mineral density (BMD). The mechanism of their bone loss remains obscure. Monokines like interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor-alpha (TNF-alpha), and granulocyte macrophage stimulating factor (GM-CSF) are involved in bone remodeling, but only IL-1 excess has been incriminated in the bone loss of CaSF with IH. Therefore, to more precisely delineate the role of monocyte activation in the pathogenesis of bone loss in these patients, we studied the production of IL-1 beta, IL-6, TNF-alpha, and GM-CSF by unstimulated or lipopolysaccharide (LPS)-stimulated cultured peripheral blood monocytes in 15 CaSF with IH, in 10 CaSF with dietary calcium-dependent hypercalciuria (DH), and in 10 healthy controls (C). Cytokines were measured in the culture medium by sensitive enzyme-linked immunosorbent assay and vertebral BMD by single energy computed tomography. The decrease of vertebral BMD in IH compared with DH, was confirmed (Z score: -1.2 +/- 0.2 vs. -0.5 +/- 0.2; P = 0.04; Mann-Whitney). In the supernatant of unstimulated peripheral blood monocytes, IL-1 beta and TNF-alpha levels were higher in IH than in C (respectively, 40 +/- 21 vs. 7 +/- 1 pg/mL, P = 0.008 and 236 +/- 136 vs. 39 +/- 23 pg/mL, P = 0.03); those of GM-CSF were greater in IH than in DH and C (respectively, 52 +/- 27 vs. 6 +/- 2, P = 0.04 and 6 +/- 2 pg/mL, P = 0.01) and those of IL-6 were not significantly different among the groups. After in vitro stimulation by LPS (10 micrograms/mL), the levels of the various monokines were not significantly different. In IH patients, the post-LPS levels of IL-6 were negatively correlated to vertebral BMD (n = 15, Z = -1.97, P = 0.04; Spearman), whereas those of GM-CSF were positively related to vertebral BMD (n = 15, Z = 2.01, P = 0.04). In this study, calcium stone formers with IH have bone mineral decrease and a particular profile of peripheral blood monocytes activation. This latter is characterized by a spontaneously increased synthesis of IL-1 beta, TNF-alpha, and GM-CSF. Furthermore, post-LPS levels of IL-6 and GM-CSF are correlated with vertebral BMD. These results suggest that monocyte activation may be involved in the bone loss of calcium stone formers with IH.
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PMID:Low bone mineral density and peripheral blood monocyte activation profile in calcium stone formers with idiopathic hypercalciuria. 954 80

Previous studies from our laboratory demonstrated that bone mineral content is affected in patients with idiopathic hypercalciuria and that there is a correlation between bone mineral loss and in-vitro cytokine production. At the same time we found that short term treatment with alendronate decreased urinary calcium in these subjects. In the present study we have examined the long-term effects of alendronate treatment (10 mg/day for one year) on urinary calcium, urinary hydroxyproline and bone mineral content in 18 idiopathic hypercalciuric and 8 normocalciuric stone formers. Clinical characteristics, as well as gender and age distribution were similar in both groups. Urinary calcium and hydroxyproline, were measured monthly. Calcium excretion decreased significantly at the end of the first month, and remained lower thereafter (277 +/- 28, before vs. 202 +/- 26 mg/g creatinine, after 12 months on alendronate, p < 0.01). Urinary hydroxyproline decreased significantly during the study (125.5 +/- 32.1 vs. 39.66 +/- 17.5 mg/g creatinine, p < 0.05). Serum calcium, glomerular filtration rate, and urinary sodium, did not change during the study. Lumbar spine bone density (trabecular bone) obtained with X ray absorptiometry revealed a significant increase from 1.162 +/- 0.231 to 1.197 +/- 0.248 g/cm2 (p < 0.01). These changes were associated with a significant decrease in IL-1 alpha mRNA transcription by unstimulated and lipopolysaccharide stimulated blood mononuclear cells, as tested by the reverse transcriptase polymerase chain reaction. No changes were observed in bone cortical sites (femoral neck). Normocalciuric subjects showed no significant changes in urinary calcium. In summary, the changes observed in urinary calcium excretion and different bone metabolic parameters, suggest a role of bone in the pathophysiology of idiopathic hypercalciuria.
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PMID:[Role of bones in the physiopathology of idiopathic hypercalciuria: effect of amino-bisphosphonate alendronate]. 956 54