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)

Serum testosterone and estradiol decline with advancing age in men, but the contribution of these changes to age-related bone loss remains unclear. Most studies show a closer relationship between bone density and serum estradiol than with serum testosterone. Nevertheless, hypogonadism is widely considered to be an important cause of male osteoporosis, occurring in up to 20% of men with vertebral fractures and 50% with hip fractures. Bone loss in hypogonadal men has been attributed to androgen and estrogen deficiency, low 1,25 dihydroxyvitamin D concentrations, malabsorption of calcium, and reduced circulating calcitonin. These abnormalities are corrected by testosterone replacement, which also decreases bone resorption and stimulates bone mineralization. Long-term testosterone replacement increases spine bone density by over 25%, although much of the improvement occurs in the first few years of treatment. There appears to be an inverse relationship between the basal serum testosterone and the increase in bone density observed with testosterone treatment, such that little change is seen in men with normal basal concentration. In contrast, an observational study in eugonadal men with vertebral fractures showed an increase in spine bone density of 5% after 6 months' treatment with testosterone, probably mediated by an increase in serum estradiol and a reduction in bone resorption. Although testosterone has beneficial effects on the skeleton, there may be adverse effects on the prostate and cardiovascular risk factors. Further studies are required to confirm the safety and efficacy of testosterone replacement in hypogonadal and eugonadal men with osteoporosis.
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PMID:Androgen replacement in aging men. 1173 Feb 58

There is no one cause of bone fragility; genetic and environmental factors play a part in development of smaller bones, fewer or thinner trabeculae, and thin cortices, all of which result in low peak bone density. Material and structural strength is maintained in early adulthood by remodelling; the focal replacement of old with new bone. However, as age advances less new bone is formed than resorbed in each site remodelled, producing bone loss and structural damage. In women, menopause-related oestrogen deficiency increases remodelling, and at each remodelled site more bone is resorbed and less is formed, accelerating bone loss and causing trabecular thinning and disconnection, cortical thinning and porosity. There is no equivalent midlife event in men, though reduced bone formation and subsequent trabecular and cortical thinning do result in bone loss. Hypogonadism contributes to bone loss in 20-30% of elderly men, and in both sexes hyperparathyroidism secondary to calcium malabsorption increases remodelling, worsening the cortical thinning and porosity and predisposing to hip fractures. Concurrent bone formation on the outer (periosteal) cortical bone surface during ageing partly compensates for bone loss and is greater in men than in women, so internal bone loss is better offset in men. More women than men sustain fractures because their smaller skeleton incurs greater architectural damage and adapts less effectively by periosteal bone formation. The structural basis of bone fragility is determined before birth, takes root during growth, and gains full expression during ageing in both sexes.
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PMID:Pathogenesis of bone fragility in women and men. 1204 92

Coeliac disease (CD) is one of the most frequent chronic diseases in childhood. The clinical spectrum has changed; in addition to the classical gastrointestinal form, other clinical manifestations have been described, such as hypogonadism and the consequent delay in onset of puberty. Recent studies reported not only a significantly retarded menarche in untreated CD girls as compared with girls following a gluten-free diet, but also in treated CD a negative effect on pregnancy, resulting in lower birth weight and shorter duration of pregnancy. In boys, there is a reduced serum level of dihydrotestosterone and an increased serum level of luteinizing hormone, an abnormality pattern suggesting androgen resistance. The pathogenesis of CD-related reproductive disorders is still unclear. Some hypotheses may be tried; for example, in CD there is a high level of autoantibodies directed against self-antigens, so there could be antibodies directed against hormones or organs critical for pubertal development. Moreover, in CD there could be a selective malabsorption of micronutrients essential for the metabolism of carrier or receptor proteins for sex hormones.
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PMID:Mechanisms of abnormal puberty in coeliac disease. 1206 30

Decreased bone mineral density is a frequent finding in gastrointestinal disease. Factors contributing to this are (1) malabsorption of vitamin D, calcium and possibly vitamin K and other nutrients; (2) treatment with glucocorticoids; (3) inflammatory cytokines in inflammatory bowel disease; and (4) hypogonadism induced by gastrointestinal disease. A low bone mineral density has been reported in (1) patients who have undergone gastrectomy (27-44% with Z-scores of < -1); (2) pernicious anaemia; (3) coeliac disease (8-22% with Z-scores of < -2); (4) Crohn's disease (mean 32-38% with Z-scores of < -1); and (5) ulcerative colitis (mean 23-25% with Z-scores of < -1). Reduced bone mineral density is thus prevalent in these individuals and is compounded by age related bone loss, leading to the development of severe bone disease in some patients.
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PMID:Bone loss associated with gastrointestinal disease: prevalence and pathogenesis. 1286 93

Patients with fragility fractures may have abnormalities in bone structural and material properties such as larger or smaller bone size, fewer and thinner trabeculae, thinned and porous cortices, and tissue mineral content that is either too high or too low. Bone models and remodels throughout life; however, with advancing age, less bone is replaced than was resorbed within each remodeling site. Estrogen deficiency at menopause increases remodeling intensity: a greater proportion of bone is remodeled on its endosteal (inner) surface, and within each of the many sites even more bone is lost as more bone is resorbed while less is replaced, accelerating architectural decay. In men, there is no midlife increase in remodeling. Bone loss within each remodeling site proceeds by reduced bone formation, producing trabecular and cortical thinning. Hypogonadism in 20-30% of elderly men contributes to bone loss. In both sexes, calcium malabsorption and secondary hyperparathyroidism increase remodeling: more bone is removed from an ever-diminishing bone mass. As bone is removed from the endosteal envelope, concurrent bone formation on the periosteal (outer) bone surface during aging partly offsets bone loss and increases bone's cross-sectional area. Periosteal apposition is less in women than in men; therefore, women have more net bone loss because they gain less on the periosteal surface, not because they resorb more on the endosteal surface. More women than men experience fractures because their smaller skeleton incurs greater architectural damage and adapts less by periosteal apposition.
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PMID:Invited Review: Pathogenesis of osteoporosis. 1455 75

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is caused by mutations in the autoimmune regulator (AIRE) gene, which has a central function in maintaining immunological tolerance. A number of conditions with proven or likely autoimmune pathogenesis occur in APECED: hypoparathyroidism, adrenocortical insufficency, candidiasis, hypogonadism, type 1 diabetes, hypothyroidism, hypophysitis, hepatitis, malabsorption, nail dystrophy, enamel hypoplasia and keratopathy. It is not clear which factors are responsible for variation in clinical picture of APECED, but human leukocyte antigen (HLA) genotype may be important. The authors report the first description of a case of primary pulmonary hypertension (PPH) in patient with APECED, caused by R257X mutation in AIRE. The HLA genotype of the patient (DRB1*01/DRB1*11, DQB1*0301/DQB1*0501) has been previously reported as a predisposing factor to PPH. The findings from this study, provided that other similar cases are reported, suggest that immune deregulation plays a role in the pathogenesis of primary pulmonary hypertension.
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PMID:Fatal primary pulmonary hypertension in a 30-yr-old female with APECED syndrome. 1458 26

Decreased bone mineral density is a frequent finding in patients with inflammatory bowel disease. Factors contributing to this are: 1) malabsorption of vitamin D, calcium and possibly vitamin K and other nutrients, 2) treatment with corticosteroids, 3) inflammatory cytokines in inflammatory bowel disease, and 4) hypogonadism induced by the inflammatory bowel disease. Among patients with Crohn's disease from 32% to 38% have osteopenia (Z-scores <-1), and among patients with ulcerative colitis 23% to 25% have osteopenia. The mean deficit was 0.44+/-0.08 Z-scores in the spine in Crohn's disease and 0.34+/-0.08 in ulcerative colitis. A similar deficit was seen in the hip in both conditions. From these deficits, an increase in overall fracture risk of 1.1-1.3 should be expected. The observed excess fracture risk was limited compared to the general population in both Crohn's disease (RR=1.2, 95% CI: 0.9-1.6 for any fracture and 2.2, 95% CI: 1.2-4.0 for spine fractures) and ulcerative colitis (RR=1.1, 95% CI: 1-1.2 for any fracture, and 1.5, 95% CI: 0.9-2.5 for spine fractures). The observed excess fracture risk was close to that expected from the changes in BMD. Despite the limited excess fracture risk, a relatively large percentage of all fractures may be attributable to corticosteroid use among users of corticosteroids.
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PMID:Prevalence and pathogenesis of osteoporosis in patients with inflammatory bowel disease. 1578 32

Osteoporosis is a frequent finding in patients with Crohn's disease and ulcerative colitis. The prevalence of vertebral fractures in those patients with significantly reduced bone mineral density is up to 22%. Factors contributing to osteoporosis in inflammatory bowel disease (IBD) patients are treatment with glucocorticoids, increased cytokine production by the inflammation itself, malabsorption and possibly hypogonadism. Therefore, consequent treatment of the underlying IBD and minimising therapy with systemic glucocorticoids, as well as the adequate intake of calcium and vitamin D, may be very important measures to prevent bone loss in IBD. In patients with osteoporosis associated with Crohn's disease or ulcerative colitis, various treatment strategies, such as sodium fluoride and aminobisphosphonates, are discussed. Unfortunately, interventional studies in secondary osteoporosis are often limited by the small study population. The efficacy in prevention of vertebral fractures is not proven in any of the described treatment modalities in these patients. Therefore, guidelines are based on data using bone density as the most accepted surrogate marker and treatment guidelines are based on data from patients with postmenopausal and steroid-induced osteoporosis.
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PMID:Diagnosis and management of osteoporosis in inflammatory bowel disease. 1578 33

During growth, estrogen deficiency in females may produce increased bone size as a result of removal of inhibition of periosteal apposition, while failed endosteal apposition produces thin cortices and trabeculae in the smaller bone. In males, androgen deficiency produces reduced periosteal and endosteal apposition, reduced bone size, and cortical and trabecular thickness. At completion of longitudinal growth, advancing age is associated with emergence of a negative bone balance in each basic multicellular unit (BMU) because of reduced bone formation. Bone loss occurs, but slowly because the remodeling rate is slow. In midlife, in females, estrogen deficiency increases remodeling rate, increases the volume of bone resorbed, and decreases the volume of bone formed in each of the numerous BMUs remodeling bone on its endosteal (endocortical, trabecular, intracortical) surfaces so bone loss accelerates. In males, remodeling rate remains slow and is driven largely by reduced bone formation in the BMU. Hypogonadism in 20% to 30% of elderly men contributes to bone loss. In both sexes, calcium malabsorption and secondary hyperparathyroidism may partly be sex-hormone dependent and contributes to cortical bone loss. Concurrent periosteal apposition partly offsets endosteal bone loss, but less so in women than in men. More women than men fracture because their smaller skeleton incurs greater architectural damage and adapts less by periosteal apposition. Sex hormone deficiency during growth and aging is pivotal in the pathogenesis of bone fragility.
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PMID:Estrogen, androgen, and the pathogenesis of bone fragility in women and men. 1603 88

A 17-year-old boy had a 3-year history of diabetes mellitus, malabsorption syndrome, and skin changes consisting of induration, hyperpigmentation, and hypertrichosis on the anterior aspect of both thighs, lower abdomen, and scrotum. Physical examination found hypogonadism, hepatomegaly, gynecomastia, growth retardation, and ankle edema. There was no neuropathy or plasma cell dyscrasia. However, the characteristic skin changes and the combination of symptoms suggest polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes syndrome. This is a rare multisystemic disorder of obscure pathogenesis and no conspicuous heredity. Overproduction of vascular endothelial growth factor is thought to cause microangiopathy, neovascularization, and accelerated vasopermeability causing the multiorgan deterioration. Cyclophosphamid cytostatic therapy seems beneficial.
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PMID:POEMS in childhood. 1665 Feb 24


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