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)

This review describes the supposed mechanisms leading to idiopathic hypercalciuria (IHU) in childhood, further the diagnostic criteria and the proposed treatment modalities are discussed. IHU is not only one of the main causes of renal stone disease in children but it's also at the origin of the postglomerular haematuria and the frequency-dysuria syndrome. Its role in the development of osteoporosis in adults is also documented. The diagnosis of raised calcium excretion is based on age specific values during early infancy. In older children and adults a urinary calcium/creatinine ratio exceeding 0.6 mmol/mmol is regarded as elevated. Dietary calcium restriction can no longer be recommended for the treatment of IHU because it results in secondary hyperoxaluria and on the long-term causes decreased bone mineral density. Patients should be kept on dietary sodium restriction and high fluid intake. In cases IHU associated with recurrent episodes of macroscopic haematuria or recurrent stone disease a therapeutic trial with hydrochlorothiazide in the dose of 0.5-1 mg/kg/day with potassium-citrate supplementation and possibly magnesium citrate should be started. In some special forms of hypercalciuria such as the X-linked recessive nephrolithiasis syndrome or Bartter syndrome the localization and in some cases even the molecular mechanism of the events leading to increased calcium excretion are elucidated. In IHU enhanced Ca(++)-ATPase, and Na-Li countertransport activity and decreased Na+/K+ ATPase activity were described in the erythrocyte membrane model. It is expected that with the molecular genetic development the clinical classification of the hypercalciuric syndromes will become a rational genome-based one.
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PMID:[Idiopathic hypercalciuria in childhood]. 987

Osteoporosis is increasingly recognised in men. Low bone mass, risk factors for falling and factors causing fractures in women are likely to cause fractures in men. Bone mass is largely genetically determined, but environmental factors also contribute. Greater muscle strength and physical activity are associated with higher bone mass, while radial bone loss is greater in cigarette smokers or those with a moderate alcohol intake. Sex hormones have important effects on bone physiology. In men, there is no abrupt cessation of testicular function or 'andropause' comparable with the menopause in women; however, both total and free testosterone levels decline with age. A common secondary cause of osteoporosis in men is hypogonadism. There is increasing evidence that estrogens are important in skeletal maintenance in men as well as women. Peripheral aromatisation of androgens to estrogens occurs and osteoblast-like cells can aromatise androgens into estrogens. Human models exist for the effects of estrogens on the male skeleton. In men aged > 65 years, there is a positive association between bone mineral density (BMD) and greater serum estradiol levels at all skeletal sites and a negative association between BMD and testosterone at some sites. It is crucial to exclude pathological causes of osteoporosis, because 30 to 60% of men with vertebral fractures have another illness contributing to bone disease. Glucocorticoid excess (predominantly exogenous) is common. Gastrointestinal disease predisposes patients to bone disease as a result of intestinal malabsorption of calcium and colecalciferol (vitamin D). Hypercalciuria and nephrolithiasis, anticonvulsant drug use, thyrotoxicosis, immobilisation, liver and renal disease, multiple myeloma and systemic mastocytosis have all been associated with osteoporosis in men. It is possible that low-dose estrogen therapy or specific estrogen receptor-modulating drugs might increase BMD in men as well as in women. In the future, parathyroid hormone peptides may be an effective treatment for osteoporosis, particularly in patients in whom other treatments, such as bisphosphonates, have failed. Men with idiopathic osteoporosis have low circulating insulin-like growth factor-1 (IGF-1; somatomedin-1) concentrations, and IGF-1 administration to these men increases bone formation markers more than resorption markers. Studies of changes in BMD with IGF-1 treatment in osteoporotic men and women are underway. Osteoporosis in men will become an increasing worldwide public health problem over the next 20 years, so it is vital that safe and effective therapies for this disabling condition become available. Effective public health measures also need to be established and targeted to men at risk of developing the disease.
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PMID:Osteoporosis in men. New insights into aetiology, pathogenesis, prevention and management. 988 98

We performed a retrospective study of 237 patients attending a specialty osteoporosis practice. Secondary causes for reduced bone mineral density (BMD) were evaluated in 196 postmenopausal women and 41 premenopausal women; mean age was 56 +/- 13.8 years (mean +/- SD). BMD was measured by dual-energy X-ray absorptiometry (DXA) (QDR 1000W/2000 Hologic). Levels of intact parathyroid hormone (iPTH), calcidiol [25(OH)D], thyroid-stimulating hormone, and 24-hour urinary calcium were measured, and serum and urine protein (SPEP and UPEP) electrophoresis were performed. Overall, 16% of our patients had 25(OH)D levels <15 ng/ml, the lowest acceptable vitamin D level without a concomitant rise in iPTH levels. Among the osteoporotic patients (T score <-2.5 SD), 17% had 25(OH)D levels <15 ng/ml and 7% <10 ng/ml. Among the osteopenic patients (-2.5 < T < -1.0 SD), 11% had 25(OH)D levels <15 ng/ml. Seventeen percent of patients with Z score </=-1.0 SD (low range normal value) had 25(OH)D levels <15 ng/ml. Low 25(OH)D levels were inversely related to high iPTH values (r = 0.30, P < 0.0001). Hypercalciuria was present in 15% of our patients, elevations of PTH levels (>65 pg/ml, upper normal limit of assay) were present in 11.5%, and hyperthyroidism in 4%. A 25(OH)D level of <25 ng/ml in women (n = 86) with no known secondary causes of low BMD was associated with an iPTH level above 49 pg/ml. The measurement of 25(OH)D levels is recommended in the evaluation of secondary causes for reduced BMD. Supplementation with vitamin D appears needed to keep 25(OH)D above 25 ng/ml, the level required to prevent increments in iPTH levels.
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PMID:Calcidiol and PTH levels in women attending an osteoporosis program. 1008 17

We have shown that Walker 256/S mammary carcinoma caused osteoporosis-like changes in young female rats, accompanied by low serum estradiol and hypercalciuria without changes in the serum levels of calcium, phosphorus, and parathyroid hormone-related peptide. In this study, we investigated the cause of bone loss after Walker 256/S inoculation into female 6-week-old Wistar Imamichi rats, focusing on the sex hormone balance in the host animal. Walker 256/S-bearing rats showed characteristic osteoporosis, with a significant increase in spleen weight and a significant decrease in uterine weight by 14 days after s.c. tumor inoculation. In the in vitro bone marrow culture, mineralized nodule formation ability decreased according to the time after tumor inoculation, and tartrate-resistant acid phosphatase-positive multinucleated cell formation increased at 7 days after tumor inoculation, but it began to decrease at 14 days after tumor inoculation. This indicates that after inoculation with Walker 256/S tumor, the progenitors of osteoblasts and ostroclasts lost their balance in the bone turnover, resulting in bone resorption. On the other hand, Walker 256/S carcinoma expressed luteinizing hormone-releasing hormone (LH-RH) mRNA, and in Walker 256/S-bearing rats, the serum LH-RH level increased significantly from 3 days after tumor inoculation, whereas in the healthy control rats, this level was very low. Consequently, the serum levels of follicle-stimulating hormone, luteinizing hormone, estradiol, and progesterone were significantly lower in the tumor-bearing rats than in the healthy control rats. Because the LH-RH gene is located in the long prolactin release-inhibiting factor (PIF) gene and mRNA amplified by reverse transcription-PCR in this study contained whole LH-RH and a part of PIF, the Walker 256/S tumor is thought to express PIF. Indeed, the serum prolactin level decreased in tumor-bearing rats. The serum level of growth hormone, one of the other pituitary hormones, was not changed. Moreover, the level of an osteolytic cytokine, tumor necrosis factor alpha, increased in the serum of Walker 256/S-bearing rats, although this may be a result of the immune response of the host animal to tumor growth as well as an enlarged spleen. In conclusion, the Walker 256/S tumor lowers estrogen secretion through ectopical oversecretion of LH-RH, and then osteolytic cytokines, such as tumor necrosis factor alpha, increase in tumor-bearing rats, escape the control of estrogen, and activate osteoclasts, resulting in bone loss in a short period.
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PMID:Walker 256/S carcinosarcoma causes osteoporosis-like changes through ectopical secretion of luteinizing hormone-releasing hormone. 1009 51

There is a consensus that adequate calcium intake during bone development, and possibly in adulthood and senescence, helps to prevent bone resorption and osteoporosis. The uptake of dietary calcium should be sufficient to maintain both normal serum calcium concentrations and parathyroid hormone levels in the low normal range throughout the day, otherwise, increased bone resorption occurs. Calcium intake varies with race and with environmental and dietary conditions. Estimating the appropriate amount of calcium to be added to dietary sources for an optimal supplementation regimen is therefore difficult. Few intervention studies have evaluated the dose-effect relationship for calcium supplementation conclusively. The mechanisms regulating fractional calcium absorption as a function of intake suggest that very high daily doses are probably useless. They may be unsafe in the long term because of the risks of hypercalciuria and kidney stones, and of an imbalance in the ratio of calcium to magnesium. Concomitant supplementation with limited amounts of magnesium may reduce this risk and improve mineralization. Dietary intake is 500-600 mg/day in most studies, making 400 mg/day an appropriate supplementary dose for most premenopausal women (RDA 1000 mg/day). After the menopause and during lactation (RDA 1200-1500 mg/day), 800 mg/day is probably appropriate, particularly if low doses of vitamin D are taken concomitantly.
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PMID:Dietary calcium and mineral/vitamin supplementation: a controversial problem. 1041 56

Corticosteroid-induced osteoporosis (CIO) is a serious disorder that results in significant long-term morbidity. Increased bone resorption is caused by decreased Ca absorption and increased urinary Ca excretion leading to secondary hyperparathyroidsim. Calcium prophylaxis alone, when patients start corticosteroids, is associated with rapid rates of spinal bone loss and offers only partial protection from corticosteroid-induced spinal bone loss. Though calcium supplementation may have some benefit, it clearly cannot completely prevent corticosteroid-induced bone loss. At most, Ca therapy should only be considered adjunctive therapy in the treatment or prevention of corticosteroid-induced bone loss and should be administered in combination with other treatments. Earlier work demonstrated increases in forearm bone mineral density (BMD) with the use of Ca and vitamin D in patients with established CIO. However, caution should be taken when interpreting these results, since bone loss generally tapers or plateaus after the first 12 months of corticosteroid treatment; as such, any therapy might show benefit. In addition, bone density was only taken at the radius and not the spine where most of the bone loss takes place. Nonetheless, in recent trials of at least 2-year duration in which calcium and vitamin D therapy served as placebos, the result indicated that bone mass was maintained at the spine and hip throughout treatment in patients who had used chronic corticosteroids. In primary prevention trials, the amount of bone loss observed in the spine after therapy with Ca and vitamin D combinations is similar to that observed in other prevention studies in the Ca alone-treated control groups. Furthermore, Ca and vitamin D therapy appears to be less effective than other agents in the prevention of corticosteroid-induce bone loss. Although several studies do not report side effects that may be associated with Ca and vitamin D therapy, the few that do frequently report hypercalciuria. In the absence of other studies that support the use of Ca and vitamin D in the prevention of CIO, the data are too limited to generally recommend them alone as a preventative therapy. Activated vitamin D may be of greater benefit.
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PMID:Calcium and vitamin D therapy in corticosteroid-induced bone loss: what is the evidence? 1048 87

The first episode of nephrolithiasis provides an opportunity to advise patients about measures for preventing future stones. Low fluid intake and excessive intake of protein, salt and oxalate are important modifiable risk factors for kidney stones. Calcium restriction is not useful and may potentiate osteoporosis. Diseases such as hyperparathyroidism, sarcoidosis and renal tubular acidosis should be considered in patients with nephrolithiasis. A 24-hour urine collection with measurement of the important analytes is usually reserved for use in patients with recurrent stone formation. In these patients, the major urinary risk factors include hypercalciuria, hyperoxaluria, hypocitraturia and hyperuricosuria. Effective preventive and treatment measures include thiazide therapy to lower the urinary calcium level, citrate supplementation to increase the urinary citrate level and, sometimes, allopurinol therapy to lower uric acid excretion. Uric acid stones are most often treated with citrate supplementation. Data now support the cost-effectiveness of evaluation and treatment of patients with recurrent stones.
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PMID:Prevention of recurrent nephrolithiasis. 1059 18

This study was performed to analyze the relative and combined effects of ethanol and protein deficiency on bone histology and mineral metabolism in 4 groups of 7 animals each which were pair-fed during 8 weeks with 1) a nutritionally adequate diet; 2) a 36% (as energy) ethanol containing isocaloric diet; 3) a 2% protein, isocaloric diet; and 4) a 36% ethanol 2% protein isocaloric diet, respectively, following the Lieber-DeCarli model. Another group of five rats were fed ad libitum the control diet. The first and second lumbar vertebrae were removed after sacrifice, and processed for histomorphometrical analysis of undecalcified bone samples. Blood and 24-h urine were also collected. Protein malnutrition, but not ethanol, leads to osteoporosis and reduced osteoid synthesis, whereas ethanol and protein malnutrition both lead to impaired bone mineral apposition and increased urinary hydroxyproline excretion. These changes are accompanied by an increase in serum parathormone and serum 1,25 dihydroxy vitamin D3, a slight hypomagnesemia, hypercalciuria and hyperphosphaturia; protein deficiency plays an independent role in these alterations, whereas both ethanol and protein deficiency exert independent effects on decreasing serum testosterone levels; this last alteration may contribute to the bone changes mentioned before.
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PMID:Relative and combined effects of ethanol and protein deficiency on bone histology and mineral metabolism. 1068 Jul 11

Endogenous cortisol excess and glucocorticoid (GC) treatment have a profound effect on bone metabolism, acting at many sites. The mechanism of GC action on bone turnover is complex and has not been elucidated completely. GCs increase bone resorption, inhibit bone formation and have an indirect action on bone by decreasing intestinal Ca2+ absorption, modifying vitamin D metabolism, and sustaining a marked hypercalciuria, with variable changes in plasma PTH levels; finally, GCs inhibit the gonadotropic and somatotropic axis. GC-induced osteoporosis is preventable, treatable and potentially reversible. The prevention and treatment of GC-induced osteoporosis include some general measures (as well as the use of the minimal effective dose of GC), Ca2+ and vitamin D supplementation and treatment with bone anabolic and antiresorptive agents. Recent trials suggest that bisphosphonates are an effective therapeutic tool in the treatment of GC-induced bone damage. Recent data on GC receptor-selective modulators indicate that these new molecules might induce only minimal bone loss while maintaining the typical anti-inflammatory properties of GC. Another new line of study for the prevention of GC-induced osteoporosis is the characterization of the individual's susceptibility to GC-induced bone damage.
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PMID:Glucocorticoid-induced osteoporosis. 1070 47

Laboratory animal, clinical and epidemiological studies in the published literature have been reviewed in order to establish whether excessive salt intake is an important risk factor for the development of osteoporosis and whether an intervention strategy based on salt restriction would be beneficial in the prevention of osteoporosis. Genetic factors appear to be far more important than the combination of nutritional, hormonal, environmental and lifestyle factors in the pathogenesis of osteoporosis. The most important single non-genetic factor is oestrogen deficiency in postmenopausal women. Preventive measures should be aimed at maximizing peak bone mass at skeletal maturity and retarding bone loss thereafter. Apart from postmenopausal oestrogen deficiency, various factors have been incriminated as risk factors for osteoporosis, and these include age at menarche, age at and years since menopause, insufficient physical exercise, alcohol, smoking, low calcium intake, low or high protein intake and high intake of phosphorus, sodium or caffeine. Many of the risk factors are considered to be weak, although when combined they could impact significantly on bone health. Increased intakes of various nutritional factors (potassium, magnesium, zinc, vitamin C), fibre and alkaline-producing fruit and vegetables favour adult bone health. Calcium homeostasis is normally well regulated such that increased calcium loss via the urine leads to increased calcium absorption from the gut. However, the duration of this adaptive process may be greater than that of many of the studies demonstrating that increased salt intake leads to both increased sodium and calcium in the urine. In any case, higher urinary calcium output appears to be seen only in a minority of humans in response to increased salt intake. As numerous factors-genetic, nutritional, hormonal and lifestyle-are involved in the maintenance of calcium homeostasis, it is difficult to devise human studies which adequately take into account all the important factors. Another difficulty is that many past studies have relied on imprecise methods for the measurement of bone resorption. Nor have studies based on the use of the laboratory rat produced clear answers to the problem because the rat, as a species, is uniquely deficient in its ability to handle the relevant minerals. Limited studies to date indicate that increased sodium intake neither exerts a consistent effect on various biomarkers of bone health nor leads to irreversible changes in the bone modelling process in men or in pre- or postmenopausal women. We conclude from the available evidence that increased sodium (or salt) intake is not an important risk factor for osteoporosis and that a reduction of salt intake from 9 to 6g/day in the diet would not be beneficial as an intervention measure in the prevention of osteoporosis. More research is needed to (i) assess the effects (especially long-term) of various nutrients including sodium on bone health, (ii) assess the long-term value of any intervention strategy involving reduced intake of a particular nutrient such as sodium; and (iii) determine whether subpopulations exist particularly in the elderly (e.g. sodium-responsive subjects) in which adaptation to sodium-induced hypercalciuria may be compromised. General prudence dictates that excessively high levels of dietary salt should be eschewed by those persons with raised blood pressure or a limited range of genetic disorders. However, for the generally healthy person there is no sound evidence that the consumption of salt at the present average level of 9g/day constitutes a risk factor for osteoporosis.
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PMID:Review of risk factors for osteoporosis with particular reference to a possible aetiological role of dietary salt. 1071 63


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