Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003873 (rheumatoid arthritis)
 53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

When correction was made for hypoalbuminaemia, 23 of 50 ambulant patients with definite or classical rheumatoid arthritis were found to have hypercalcaemia. When these 23 patients were studied 6 months later, 7 had hypercalcaemia as defined by the correction factor for a low serum albumin level, and 6 of these patients had raised serum ionised calcium concentrations. Biochemical studies in the 23 patients indicated evidence of hyperparathyroidism, namely, hypophosphataemia, increased serum alkaline phosphatase, hyperchloraemia, and reduced tubular reabsorption of calcium. However, serum immunoreactive parathyroid hormone concentrations were normal. Only one patient had an abnormally low serum 25-hydroxy-vitamin D result: this patient had a high level of urinary D-glucaric acid and was receiving phenobarbitone for treatment of epilepsy. The biochemical features suggestive of parathyroid overactivity were particularly found in patients with raised serum calcium levels. The cause of hypercalcaemia in rheumatoid arthritis remains to be explained.
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PMID:Hypercalcaemia in rheumatoid arthritis: investigation of its causes and implications. 51 39

The effect of 1alpha-hydroxyvitamin D3 (1alpha-OHD3) and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on the intestinal calcium absorption was studied in twenty patients with rheumatoid arthritis treated with prednisone at daily doses of 5--15 mg for 1/2--20 years. The fractional calcium absorption, measured before and after the treatment with the vitamin D compounds, increased in nineteen of the twenty patients. This was, however, accompanied by marked rises in the urinary calcium excretion. There was no correlation between the fractional calcium absorption and the duration of the prednisone treatment or the doses given.
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PMID:Effect of 1alpha-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 on intestine and bone in glucocorticoid-treated patients. 60 15

Bone remodeling is controlled by systemic factors such as parathyroid hormone (PTH), calcitonin (CT), and 1,25(OH)2 vitamin D and by local factors including cytokines and growth factors such as IL-1, IL-2, TNF alpha, TGF beta, IFN alpha, and IFN gamma. Derangement of such control mechanisms leading to an imbalance between osteoclastic bone resorption and osteoblastic bone formation could cause osteoporosis. Conditions associated with immune dysfunction such as aging, corticosteroid therapy, and rheumatoid arthritis are associated with osteoporosis, which is also more common in females than in males, like most of the autoimmune-collagen diseases. Peripheral lymphocyte subsets CD4/CD8 were higher in patients with senile osteoporosis than in the age-matched controls, and returned to normal after 1 month of 1 alpha(OH)vitamin D3 treatment. On multiple regression analysis of histomorphometric data and lymphocyte subsets, a negative correlation was found between CD4 lymphocytes and bone resorption. High CD4 is thus associated with a low level of osteoclastic bone resorption or low turnover osteoporosis. Plasma interferon reflecting macrophage function decreased with advance in age and increased in response to 1 alpha(OH)D3 treatment. As one of the immunoregulators, vitamin D tends to stimulate the macrophage-natural killer system and suppress the lymphocyte system, stimulating TGF beta and TNF alpha activity. Senile osteoporosis of low turnover thus appears to be associated with vitamin D deficiency, low macrophage function, high CD4 lymphocyte proportion, low IL-1 and high IL-2 activity, low IFN alpha and high IFN gamma activity, and low TGF beta and TNF alpha activity. Treatment with vitamin D derivatives tends to reverse these changes.
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PMID:Cytokines and osteoporosis. 197 74

Iliac crest bone histomorphometry, plasma and urine biochemistry and clinical history were examined in 78 unselected patients (68 women, 10 men) at the time of femoral fracture. Histological abnormalities occurred in 56 of the 78 biopsies. The commonest of these was a low bone volume of less than 15% which, irrespective of other abnormal histological features, was present in 37 of the biopsies. On the basis of the histomorphometry, patients could be classified into four main groups. Normal histomorphometry (bone volume greater than 15%, osteoid surfaces less than 24%, mineralising surface greater than 60%) was present in 22 patients, 23 had osteoporosis as the only abnormality (bone volume less than 15%, osteoid surface less than 24%, mineralising surface greater than 60%), nine had osteomalacia (osteoid surfaces greater than 24%, mineralising surface less than 60%, osteoid width greater than 13 microns) and 13 had decreased mineralising surfaces. Of the remainder, five had increased osteoid surface and six had insufficient osteoid to assess mineralising surface. Plasma and urine biochemistry in the four groups showed that, compared to age-matched controls, all groups had reduced plasma albumin. In comparison to the group with normal histomorphometry, patients with osteoporosis had a higher plasma calcium (P less than 0.01), tubular reabsorption of calcium (P less than 0.05) and plasma vitamin D binding protein (P less than 0.01); patients with osteomalacia had a higher plasma creatinine (P less than 0.02) and parathyroid hormone (P less than 0.02) and lower plasma 24,25-dihydroxyvitamin D (P less than 0.02), urinary calcium/creatinine ratio (P less than 0.02) and tubular reabsorption of phosphate (P less than 0.02). The biochemistry in patients with decreased mineralising surface was no different from patients with a normal biopsy. The prevalence of both osteoporosis and osteomalacia increased with age and, in subjects over the age of 90, osteoporosis occurred in 71% of patients and osteomalacia occurred in 29% of patients. The osteomalacic group were significantly older than the other three groups (P less than 0.05). The histomorphometry did not relate to the site of fracture (subcapital or intertrochanteric). A history of stroke, gastrectomy, rheumatoid arthritis, steroid treatment, thyroid disease, alcohol abuse and anti-convulsant therapy was present in patients with femoral fracture but did not relate to any particular histomorphometric classification.
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PMID:Osteomalacia and osteoporosis in femoral neck fracture. 226 50

Adjuvant-induced arthritis in rats shares many of the features of humans with rheumatoid arthritis, including the development of osteopenia in areas distal to erosive joint disease. We established adjuvant arthritis in male and female Sherman strain rats and then studied external calcium balances and vitamin D metabolism during the period of acute active clinical, serologic, and pathologic arthritis and osteopenia and in the preclinical period. While ingesting a calcium-sufficient vitamin D-replete diet (0.6% calcium, 0.65% phosphorus, and 2.2 IU D3 per g food), female rats with arthritis demonstrated reduced calcium balance (arthritic, 36 +/- 8 versus control, 169 +/- 13 mg per 6 days, p less than 0.02) because of inefficient gastrointestinal absorption of calcium (arthritic 9.7% versus control 37%). This was associated with calcitriol deficiency (arthritic 52 +/- 7 versus control 70 +/- 10 pg/ml) and reduced osteocalcin levels. Male rats with arthritis demonstrated an inability to raise serum calcitriol levels to the same degree as control rats (200 +/- 30 versus 440 +/- 70, respectively) while ingesting a calcium-deficient diet (0.002% calcium, 0.34% phosphorus, and 2.2 IU D3 per g food) and also had reduced balance (59 +/- 7 versus 85 +/- 10 mg per 6 days, respectively) due in part to decreased efficiency of absorption (55 versus 67%). No abnormalities in calcium balance or in serum calcitriol levels on the sufficient diet were present in the preclinical period. Physiologic calcitriol replacement to arthritic female rats increased osteoid available for mineralization and increased mineral apposition rates.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vitamin D metabolism in rats with adjuvant-induced arthritis. 228 22

The prevalence and mechanisms of hypercalcaemia were studied in a series of patients attending a regional referral centre for rheumatic diseases. In a prospective study one case of hypercalcaemia due to primary hyperparathyroidism was found in 251 consecutive patients who were screened over a three month period. In a retrospective study of 39 patients who had been discovered to be hypercalcaemic during the preceding 12 months known cases of hypercalcaemia were found in 38 (97%) cases. Primary hyperparathyroidism was the most common cause (n = 24; 62%), followed by thiazide treatment in five (13%), cancer in three (8%), immobility in three (8%), vitamin D toxicity in two (5%), and chronic liver disease in one (3%). In one case the diagnosis remained unclear after full investigation. This study shows that the causes of hypercalcaemia in rheumatological patients are similar to those in the general population. These observations contrast with previous reports, which suggested that hypercalcaemia may be a complication of rheumatoid arthritis itself.
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PMID:Hypercalcaemia in rheumatoid arthritis revisited. 231 Feb 23

To determine whether the osteopenia of rheumatoid arthritis (RA) is due to reduction of trabecular bone mass (TBV) and/or cortical width (CW), we evaluated these parameters by bone histomorphometry; we also measured the calciotropic hormones parathormone(PTH) and calcitonin (CT), vitamin D [25(OH)D] and the biological markers of bone remodeling in a group of patients with RA. Study subjects were divided into Group C - premenopausal patients, and Group A - menopausal patients and men of the same ages. These groups were compared to two age-matched control groups, B and D. In both A vs. B and C vs. D, TBV and CW were significantly lower in patients. There were no differences in PTH or CT, but 25(OH)D was significantly reduced, and BGP, OHP/Cr and AP were raised in patients. Patients also exhibited TBV loss in more than 55% and CW loss in more than 98%. These changes suggest that the decline in bone mass, mainly cortical, but also trabecular, is due to increased bone turnover and enhanced resorption and seem to reflect intrinsic alterations of RA.
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PMID:Osteopenia in rheumatoid arthritis: a biochemical, hormonal and histomorphometric study. 233 52

To further elucidate the pathogenesis of calcium regulating hormones and bone Gla-protein (BGP) on the deteriorated bone changes in rheumatoid arthritis (RA), the degree of the appendicular bone atrophy, using microdensitometry method in patients with RA, and the concentrations of midchain mainly recognized parathyroid hormone (p-PTH1-84, intact parathyroid hormone (in-PTH1-84) and BGP in sera of patients with RA were measured. With concomitant progression in X-ray stage in RA, the levels of p-PTH1-84, in-PTH1-84, BGP, 25 (OH) D, and 24, 25 (OH)2D were significantly increased in sera of RA patients. The levels of 1,25 (OH)2D were not shown significant differences among RA patients classified by bone stage. These results might be concluded that the pathogenesis of the deteriorated bone change in RA seemed to be implicated in hyper-turnover bone presumably caused by the actions of parathyroid hormone and abnormal vitamin D metabolism.
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PMID:[Calcium regulating hormone in the pathological changes of bone in rheumatoid arthritis]. 263 83

Many cells and their cytokines produce a significant effect on bone metabolism. Bone matrix synthesis is a function of the osteoblast (Fig 1), influenced directly by numerous local and systemic factors (Tables 1 and 2). Locally synthesized factors such as SGF, BMP, and BDGF may be particularly important in stimulating new bone formation at sites of bone resorption or following bony injury. Of the systemic factors, GH; somatomedin C (IGF-1); high concentrations of insulin, testosterone, PDGF and TGF beta; and low concentrations of PGE2 and IL-1 appear to stimulate bone formation in vitro. These latter factors may be more important in maintaining skeletal growth and bone mass. Bone resorption by osteoclasts (Figs 2 and 3) is also controlled by the osteoblast, as this cell produces a leukotriene-dependent polypeptide that stimulates osteoclastic bone resorption. Osteoblasts cover the periosteal and endosteal bone-surfaces and limit exposure of the underlying bone to osteoclasts. PTH, vitamin D, PGE2, and other systemic factors interact directly with the osteoblast, not the osteoclast. Surface receptor binding of PTH increases intracellular cAMP and calcium and results in release of the factor that stimulates osteoclastic bone resorption. PGE2 induces osteoblasts to activate osteoclasts and is a major controlling factor in bone metabolism; the osteoblast produces PGE2, which can then modify osteoblastic function by positive feedback. Although low concentrations of PGE2 stimulate bone formation, higher concentrations promote osteoblast-mediated bone resorption. Furthermore, many of the systemic factors stimulate bone resorption via a PGE2-associated mechanism. Immune cytokines also appear to exert a profound influence on bone metabolism. INF-gamma inhibits osteoclastic resorption, whereas IL-1, TNF, and LT strongly stimulate bone resorption. However, low concentrations of IL-1 paradoxically result in stimulation of bone formation. These cytokines, particularly in various combinations, may prove extremely important in understanding and treating the bone loss associated with malignancies, osteoporosis, and rheumatoid arthritis.
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PMID:The metabolism and immunology of bone. 267 41

The distribution of alpha-1-antitrypsin (PI) and vitamin D-binding globulin (GC) phenotypes and gene frequencies has been examined in a homogenous group of clinically well-defined patients (N = 81) with rheumatoid arthritis. The distribution pattern of the two markers was then compared with two control groups consisting of 40 individuals with osteoarthritis and 192 randomly selected normal individuals, drawn from the same geographical area as the rheumatoid arthritis patients. No association was observed between alpha-1-antitrypsin subtypes or deficient alleles and any of clinical variables observed in rheumatoid arthritis cases. Although a slightly high frequency of the GC*2 allele and a low frequency of the GC*1S allele were observed in rheumatoid arthritis and osteoarthritis compared to controls, the differences were not statistically significant. However, within the patients two clinical variables were found to be significantly associated with a particular GC phenotype. Periarticular bony erosions and antinuclear antibody were positively and negatively associated with GC 1S-2 phenotype, respectively.
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PMID:Alpha-1-antitrypsin (PI) and vitamin-D binding globulin (GC) phenotypes in rheumatoid arthritis: absence of an association. 278 61


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