Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Coeliac disease (CD) is a disorder of the small intestine, characterized by villous atrophy, due to an intolerance to dietary gluten in genetically susceptible individuals, which responds to gluten withdrawal. The underlying immunological mechanisms causing the disorder are still being worked out. In recent years a wide range of clinical presentations has become increasingly apparent, as has a lengthening list of associated conditions. Severe malabsorption with steatorrhoea and profound weight loss is seen infrequently, perhaps as a result of earlier diagnosis and the recognition of 'silent' and 'latent' disease. The prevalence of CD as judged by population screening with, in particular, anti-endomysial antibodies, appears to be much higher than that found with clinically apparent cases. There are a variety of well recognized complications, the commonest probably being osteopenia and osteoporosis. The marked increased risk of lymphoma can be avoided by a strict gluten-free diet. Follow-up of patients needs to be lifelong with prompt investigation of new symptoms and blood test abnormalities.
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PMID:Review article: coeliac disease and its management. 989 74

Loss of bone is an almost universal accompaniment of aging that proceeds at an average rate of 0.5-1% per annum from midlife onwards. There are at least four nutrients involved in this process: calcium, salt, protein, and vitamin D, at least in women. The pathogenesis of osteoporosis in men is more obscure. Calcium is a positive risk factor because calcium requirement rises at the menopause due to an increase in obligatory calcium loss and a small reduction in calcium absorption that persist to the end of life. A metaanalysis of 20 calcium trials shows that this process can generally be arrested by calcium supplementation, although there is some doubt about its effectiveness in the first few years after menopause. Salt is a negative risk factor because it increases obligatory calcium loss; every 100 mmol of sodium takes 1 mmol of calcium out of the body. Restricting salt intake lowers the rate of bone resorption in postmenopausal women. Protein is another negative risk factor; increasing animal protein intake from 40 to 80 g daily increases urine calcium by about 1 mmol/day. Low protein intakes in third world countries may partially protect against osteoporosis. Vitamin D (sometimes called a nutrient and sometimes a hormone) is important because age-related vitamin D deficiency leads to malabsorption of calcium, accelerated bone loss, and increased risk of hip fracture. Vitamin D supplementation has been shown to retard bone loss and reduce hip fracture incidence in elderly women.
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PMID:Nutrition, osteoporosis, and aging. 992 42

Two experiments were carried out to examine whether the ovariectomized mouse is a potential in vivo model of intestinal calcium malabsorption as occurs in postmenopausal osteoporosis. In the first experiment, we compared the effects of ovariectomy and 17 beta-estradiol (E2) therapy on calcium absorption in C3H/HeJ (C3H) and C57BL/6J (C57BL) mice, which have high and low peak bone mass, respectively. For each strain of mice, three groups were studied: sham operated, ovariectomized, (OVX), and OVX + E2 (60 micrograms/kg of body weight [bw]/day). Therapy was continued for 35 days and calcium absorption measured. In the C3H mice, ovariectomy caused an increase in fecal calcium (17.6%), and a decrease in the amount (12.8%) and percentage (12.5%) of calcium absorbed. The decrease was prevented by E2 therapy, but the differences in the calcium absorption parameters among the groups were not statistically significant. In contrast, in the C57BL mice, ovariectomy caused a marked increase in fecal calcium (84.5%, p < 0.01), and a marked decrease in the amount (55%, p < 0.01) and percentage (34.8%, p < 0.001) of calcium absorbed, and the decrease in the percentage of calcium absorbed was partially prevented by E2 therapy (p < 0.05). In experiment 2, a dose-response study of the effects of E2 therapy on calcium absorption in OVX C57BL mice was carried out. Five groups of mice were studied: Group 1, sham operated; Group 2, OVX; Group 3, OVX + 60 micrograms of E2/kg of bw/day; Group 4, OVX + 120 micrograms of E2/kg of bw/day; Group 5, OVX + 240 micrograms of E2/kg of bw/day. Therapy was continued for 28 days and calcium absorption measured. Ovariectomy caused a marked increase in fecal calcium (50%, p < 0.0001) and urinary calcium (31%, p < 0.0001) and a marked decrease in calcium absorption (44.9%, p < 0.0001), and these changes were prevented by E2 therapy. The highest level of calcium absorption (109%, p < 0.0001, vs. OVX) was observed in the 120 micrograms of E2 group. Ovariectomy and E2 slightly increased plasma 1,25-dihydroxyvitamin D (1,25(OH)2D) levels but there was no significant correlation between 1,25(OH)2D levels and calcium absorption. The findings in the C57BL mice suggest that estrogen is a physiological regulator of calcium absorption in this strain of mice. Furthermore, these findings share many characteristics with intestinal calcium malabsorption and its reversal by estrogen therapy in hypoestrogenic women. We propose that the OVX C57BL mice warrants further characterization as a potential animal model for investigating issues related to calcium malabsorption in postmenopausal women.
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PMID:Ovariectomized murine model of postmenopausal calcium malabsorption. 1023 81

Normal intestinal calcium (Ca) absorption is an essential feature of bone homeostasis. As with many other organ systems, intestinal Ca absorption declines with aging, and this is one pathological factor that has been identified as a cause of senile osteoporosis in the elderly. This abnormality leads to secondary hyperparathyroidism, which is characterized by high serum parathyroid hormone (PTH) and an increase in bone resorption. Secondary hyperparathyroidism due to poor intestinal Ca absorption has been implicated not only in senile osteoporosis but also in age-related bone loss. Accordingly, in population-based studies, there is a gradual increase in serum PTH from about 20 years of age onward, which constitutes a maximum increase at 80 years of age of 50% of the basal value seen at 30 years of age. The cause of the increase in PTH is thought to be partly due to impaired intestinal Ca absorption that is associated with aging, a cause that is not entirely clear but at least in some instances is related to some form of vitamin D deficiency. There are three types of vitamin D deficiency: (1) primary vitamin D deficiency, which is due to a deficiency of vitamin D, the parent compound; (2) a deficiency of 1,25(OH)(2)D(3) resulting from decreased renal production of 1,25(OH)(2)D(3); and (3) resistance to 1,25(OH)(2)D(3) action owing to decreased responsiveness to 1, 25(OH)(2)D(3) of target tissues. The cause for the resistance to 1, 25(OH)(2)D(3) could be related to the finding that the vitamin D receptor level in the intestine tends to decrease with age. All three types of deficiencies can occur with aging, and each has been implicated as a potential cause of intestinal Ca malabsorption, secondary hyperparathyroidism, and senile osteoporosis. There are two forms of vitamin D replacement therapies: plain vitamin D therapy and active vitamin D analog (or D-hormone) therapy. Primary vitamin D deficiency can be corrected by vitamin supplements of 1000 U a day of plain vitamin D whereas 1,25(OH)(2)D(3) deficiency/resistance requires active vitamin D analog therapy [1, 25(OH)(2)D(3) or 1alpha(OH)D(3)] to correct the high serum PTH and the Ca malabsorption. In addition, in the elderly, there are patients with decreased intestinal Ca absorption but with apparently normal vitamin D metabolism. Although the cause of poor intestinal Ca absorption in these patients is unclear, these patients, as well as all other patients with secondary hyperparathyroidism (not due to decreased renal function), show a decrease in serum PTH and an increase in Ca absorption in response to therapy with 1, 25(OH)(2)D(3) or 1alpha(OH)D(3). In short, it is clear that some form of vitamin D therapy, either plain vitamin D or 1,25(OH)(2)D(3) or 1alpha(OH)D(3), can be used to correct all types of age-dependent impairments in intestinal Ca absorption and secondary hyperparathyroidism during aging. However, from a clinical standpoint, it is important to recognize the type of vitamin D deficiency in patients with senile osteoporosis so that primary vitamin D deficiency can be appropriately treated with plain vitamin D therapy, whereas 1,25(OH)(2)D(3) deficiency/resistance will be properly treated with 1,25(OH)(2)D(3) or 1alpha(OH)D(3) therapy. With respect to postmenopausal osteoporosis, there is strong evidence that active vitamin D analogs (but not plain vitamin D) may have bone-sparing actions. However, these effects appear to be results of their pharmacologic actions on bone formation and resorption rather than through replenishing a deficiency.
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PMID:Vitamin D therapy of osteoporosis: plain vitamin D therapy versus active vitamin D analog (D-hormone) therapy. 1048 82

Increased cytokine release and increased activity of osteoclasts (reduced osteoclast apoptosis) due to a fall in estrogen is of causal significance in postmenopausal bone loss as well as malfunction of the vitamin D activation and concomitant calcium (Ca) malabsorption. Alfacalcidol prevents rapid postmenopausal bone loss by elimination of Ca malabsorption and by blocking resorbing cytokines. Established osteoporosis in older patients of both sexes is characterized by decoupled bone remodeling induced by sex hormone deficits and by a so-called somatopause (insulin-like growth factor [IGF]-deficit), but also by lack of vitamin D and, very importantly, by reduced synthesis of D-hormone (Calcitriol) in kidneys and bone as well as by a lack of receptors or receptor affinity for D-hormone in the target organs. As a consequence of these facts, a rise in parathormone (PTH) frequently occurs. The lack of D-hormone and IGF-1 evidently causes a reduction in muscle strength as well and reinforces the risk of falling and, thus, the risk of a fracture. Alfacalcidol, a prodrug of D-hormone, is a specific antiosteoporotic therapy. In alfacalcidol therapy, D-hormone is provided to the body in circumvention of its own regulation, by means of which much higher hormone concentrations can be achieved in the target tissues than by administration of plain vitamin D. Chances have been significantly improved of reducing and frequently preventing the real osteoporosis complication for older male and female patients, i. e., bone fractures, by alfacalcidol. A clear distinction should be made between supplementation with low-dosed plain vitamin D and calcium as base supply in elderly housebound subjects or as adjuvant to antiosteoporotic drugs and the specific antiosteoporotic therapy with alfacalcidol in patients with osteoporosis. The expanded understanding of the pathogenesis of corticosteroid-induced osteoporosis with its disturbed Ca homeostasis and the pharmacological effects of alfacalcidol, counteracting such iatrogenic bone loss, explain the particularly good clinical efficacy in this most frequent form of secondary osteoporosis. Normalizing de-coupled bone remodeling due to cytokine modulation and the potential influence on deteriorated bone quality in patients with rheumatoid arthritis and Crohn's disease predestine this form of therapy for prevention and treatment of osteoporosis as a result of chronic inflammatory diseases as well as of transplantation osteoporosis cases in particular.
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PMID:Rationale for treatment of involutional osteoporosis in women and for prevention and treatment of corticosteroid-induced osteoporosis with alfacalcidol. 1048 85

In 20-60% of patients with Crohn's disease bone demineralization is found, usually osteoporosis, but also osteoporosis with malatic features. The cause is the reduced calcium intake (loss of appetite, lactose intolerance and malabsorption), reduced vitamin D intake and corticoid therapy. Nowadays the diagnosis is facilitated by the use of densitometers (ultrasonic and DEXA) and markers of osteoresorption and new bone formation. In treatment in addition to calcium and vitamin D used for a long time, fluorides are administered (only as monofluorophosphate), nasal thyrocalcitonin and bisphosphonates of the third series (alendronate). In postmenopausal women also hormonal treatment can be used unless contraindicated. However, burdening of the bones with regular exercise is a necessity. For prevention adequate calcium and vitamin D intake is important, non-smoking, and exercise.
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PMID:[Bone demineralization in Crohn's disease, its diagnosis, therapy and prevention]. 1056 30

In a randomized trial involving 71 postmenopausal osteoporotic women with vertebral compression fractures, radiocalcium absorption studies using the (45)Ca single isotope method (alpha) were performed at baseline and after 8 months of treatment with either continuous combined hormone replacement therapy (HRT, as piperazine estrone sulfate 0.625-0.937 mg daily +/- medroxyprogesterone acetate 2.5 mg daily depending on uterine status) or HRT plus calcitriol 0. 25 microg twice daily. A calcium supplement of 600 mg nocte was given to only those women who had a daily calcium intake of less than 1 g per day at baseline, as assessed by recalled dietary intake. There was a significant decrease [0.74 (+/- 0.35 SD) to 0.58 (+/- 0. 22), Dalpha = -0.17 (+/- 0.26), p<0.0005] in alpha at 8 months compared with baseline in the HRT-treated group, but a significant increase [0.68 (+/- 0.31) to 0.84 (+/- 0.27), Dalpha = +0.16 (+/- 0. 30), p<0.003] in the HRT-plus-calcitriol treated patients, resulting in alpha being significantly higher after 8 months in the latter group than in the HRT-only group. Although 72% of the patients had been supplemented with calcium between the first and second studies, separate analyses revealed that the change in calcium intake had not affected the result. Further breakdown of the groups into baseline 'normal' absorbers (alpha >/=0.55) and 'malabsorbers' (alpha <0.55) revealed that alpha decreased with HRT treatment only in the normal absorbers, and remained stable in the malabsorbers. Conversely, following HRT plus calcitriol treatment, alpha increased only in the malabsorbers, the normal absorbers in this group remaining unchanged. In conclusion, our data show that HRT, of the type and dose used in this study, did not produce an increase in absorption efficiency; it was in fact associated with a fall. Increased absorption efficiency cannot be achieved unless calcitriol is used concurrently, and then only in patients with malabsorption. Calcitriol also had a significant effect in normal absorbers in that it prevented the decline in alpha seen with HRT alone, and thus should be considered in all patients with postmenopausal osteoporosis treated with HRT.
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PMID:Calcium absorption in postmenopausal osteoporosis: benefit of HRT plus calcitriol, but not HRT alone, in both malabsorbers and normal absorbers. 1066 58

Gastrointestinal and hepatic diseases are frequently associated with metabolic bone disorders, especially osteoporosis and osteomalacia. Malabsorption of vitamin D and calcium are important aetiological factors, although other factors may contribute, like the use of glucocorticosteroids in the treatment of inflammatory bowel disease. Treatment is first of all focused on correction of calcium and vitamin D deficiency. In severe osteoporosis additional treatment with bisfosfonates needs serious consideration.
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PMID:[Disorders of bone metabolism in gastrointestinal and hepatic diseases]. 1072 54

Primary biliary cirrhosis (PBC) is a presumed autoimmune disease of the liver, which predominantly affects women once over the age of 20 years. Most cases are diagnosed when asymptomatic (60%). The antimitochondrial antibody is present in serum in most, but not in all, patients with PBC. The disease generally progresses slowly but survival is less than an age- and gender-matched general population. The symptomatic patient may have fatigue, generalized pruritus, portal hypertension, osteoporosis, skin xanthomata, fat soluble vitamin deficiencies, and/or recurrent asymptomatic urinary tract infections. Many nonhepatic autoimmune diseases are found in association with PBC and may prompt initial presentation. To date, immunosuppressive therapy has not been shown to prolong survival in PBC. The hydrophilic bile acid, ursodeoxycholic acid (UDCA), has been shown when given in a dose of 13 to 15 mg/kg daily for up to 4 years to delay the time to liver transplantation or death. This therapy also causes a significant improvement of all the biochemical markers of cholestasis but has no beneficial effects on any of the symptoms or associated disorders. Treatment with UDCA does not obviate the need for liver transplantation. Therapies to prevent complications arising from malabsorption, portal hypertension, and/or osteoporosis are required as well. Good control of pruritus can be achieved in most patients. PBC is diagnosed with increasing frequency, but the agent(s) responsible for this slowly progressive destruction of the interlobular bile ducts remains elusive and hence a specific therapy remains unavailable.
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PMID:Management of primary biliary cirrhosis. The American Association for the Study of Liver Diseases practice guidelines. 1073 59


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