Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50502 (Hip)
 7,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Taiwanese people have spinal bone mineral density (BMD) values similar to those of Caucasians, whereas their hip BMD values are 10% to 15% lower. In 1992, the prevalence of vertebral fractures, diagnosed according to the -3 SD morphometric criteria, was 18% for women and 12% for men older than 65 years in the major cities of Taiwan. Despite this high prevalence of vertebral fractures, the incidence of hip fractures in the elderly of both sexes was only 203 per 100,000 in 1996, which was lower than in Caucasians and similar to that in mainland Chinese. Hip and vertebral fractures are both associated with lower BMD values. The risk factors for low BMD in Taiwan include a lighter body weight and aging in both sexes, and menopause for women. An increased bone turnover rate is associated with a lower BMD in both men and postmenopausal women, although the rate seems to increase in women but decrease in men with aging. In Taipei City, daily calcium intake is relatively low (mean intake +/- SD; 640 +/- 240 mg), but the vitamin D stores seem to be generally adequate for middle-aged and elderly women. There was a significant association between a higher daily calcium intake and a higher BMD/lower bone turnover rate for women in this age group. Vitamin D receptor allelic polymorphism was not an important factor in low BMD and rapid bone turnover.
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PMID:Osteoporotic fracture rate, bone mineral density, and bone metabolism in Taiwan. 934 79

We have identified the rat and Caenorhabditis elegans homologues of a 'core ATPase'-encoding Hsp70-like gene, designated Stch. We observed that the human, rat, and C. elegans Stch genes have conserved a stop codon immediately distal to the sequence encoding the Hsp70 ATPase domain. This results in the functional equivalent of an N-terminal, proteolytically cleaved fragment of Hsc70/BiP. Each homologue contains a hydrophobic signal sequence, demonstrates striking identity within the Hsp70 ATPase domain, and retains a similar C-terminal sequence (STCH specific cluster III) that is unique among Hsp70 proteins and which truncates the peptide binding domain. In addition, we have identified an internal 35-aa region that is homologous to the minimal sequence of the Hip chaperone co-factor that is required for direct binding to the ATPase domain of Hsp70. Adjacent to this region, the rat and human STCH protein sequences diverge within a short internal 'insertion' sequence that interrupts the ATPase subdomain between the phosphate-2 and adenosine ATP-binding sites. We have also demonstrated that both human and rat Stch are constitutively produced and are induced by the calcium ionophore A23187, but not by heat shock. The recognition that the truncated 'core ATPase' structure of the STCH molecule is conserved in human, rat, and C. elegans tissues suggests an important role for this unique member of the membrane-bound Hsp70 family.
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PMID:A 'core ATPase', Hsp70-like structure is conserved in human, rat, and C. elegans STCH proteins. 935 68

Hip fractures in men account for one third of all hip fractures and have a higher mortality than in women. The public health burden will increase as the increase in the numbers of elderly men in the community increases. In addition, the age-specific incidence of hip fractures may be increasing in some, but not all, countries. Vertebral fractures may be a public health problem as recent studies suggest that the prevalence in the community is 20-30%, similar to that reported in women. Forearm fractures should probably not be regarded as a public health problem. Peak bone mass is higher in men than women because men have bigger bones. Peak bone mineral density is the same. The amount of trabecular bone lost at the spine and iliac crest during ageing is similar in men and women. Cortical bone loss is less in men because endocortical resorption is less and periosteal formation is greater. Bone loss accelerates in elderly men because endocortical resorption and increasing cortical porosity increase the surface available for resorption. Bone fragility is less in men than women because: (a) the cross-sectional surface of the bone is larger; (b) trabecular bone loss is less as a percentage of the higher peak bone mass; (c) trabecular bone loss occurs by thinning rather than perforation; and (d) periosteal appositional growth compensates for endocortical resorption by maintaining the bending strength of bone. Reduced BMD in men with fractures may be due to reduced peak bone size and mass, and bone loss. Bone loss occurs by reduced bone formation. Whether men with fractures have increased bone fragility due to reduced periosteal appositional growth during ageing is unknown. The age-related decline in testosterone, adrenal androgens, growth hormone, and insulin-like growth factor 1 may contribute to reduced bone formation and bone loss. Men with vertebral fractures often have hypogonadism or illnesses with few clinical features that should be considered with a high index of suspicion (alcoholism, myeloma, malabsorption, primary hyperparathyroidism, haemochromatosis, Cushing's disease). Secondary hyperparathyroidism may contribute to bone loss by activating bone turnover and so increasing the number of bone remodelling units with impaired bone formation in each. There is no proven treatment for osteoporosis in men because there have been no trials using anti-fracture efficacy as an end point. Testosterone replacement should be considered in men with proven hypogonadism and vitamin D deficiency should be corrected if present. Calcium supplements and bisphosphonates are reasonable options given the lack of information.
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PMID:Osteoporosis in men. 936 40

The earliest assessments of bone "mass" involved metacarpal morphometry that provided insight into age-related changes, the effects of low habitual dietary calcium intake, and the effects of estrogen deficiency and replacement. Single photon absorptiometry (SPA) made quantitative mass measurement possible but this was intellectually unsatisfactory since osteoporotic fractures are more of a concern at the spine and hip than at the wrist. Necessity forced the development of axial bone mass measurement (dual photon absorptiometry--DPA, dual energy xray absorptiometry--DXA, quantitative computed tomography--QCT). Hip measurements provide a better prediction of hip fracture risk than measurements at any other skeletal site. For every standard deviation decrement of bone mass at the hip, relative risk of fracture is 3.0. At non-hip sites the relative risk is only 2.0 for each standard deviation decrement in bone mass. However measurement at non-hip sites provide a fracture risk prediction that is at least the equal of blood pressure measurement for predicting risk of CVA, and substantially better than the risk assessment of acute MI afforded by cholesterol measurement. An important caveat of the superiority of hip measurement is that the data are derived from short-term studies in older women (> 70 years). The relative risk data from phalangeal, forearm, and heel measurements have all been obtained from longer-term studies in younger women. From a community health perspective, bone density measurements, no matter how accurate, precise, and meaningful, have limited value if access to the technology is limited. Peripheral measurements can be obtained on existing radiographic equipment (phalanges), or small, portable, inexpensive dedicated equipment (forearm, heel). This technology is more likely to make it to the office of the primary care physician than the larger, more expensive, dedicated equipment needed for hip measurements. The peripheral measurement technology is also suitable for high traffic areas, just as blood pressure and cholesterol measurements are widely available. This presentation reviewed the scientific validity of peripheral bone mass measurement and explored the potential for making this technology available at non-traditional facilities such as pharmacies, shopping malls, health clubs, etc.
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PMID:Peripheral bone densitometry: an old friend revisited. 960 Nov 28

To test the hypotheses that baseline concentrations of sex steroids, sex hormone binding globulin (SHBG), and calciotropic hormones predict rates of bone loss in elderly women, sera were stored at -190 degrees, and calcaneal bone mineral density (BMD) was measured in 9704 community-dwelling white women aged 65 and over (1986-1988). Hip BMD was measured 2 years later (1900). Repeat measurements of a calcaneal and hip BMD were obtained in 1993-1994, after 5.7 and 3.5 years of follow-up, respectively. In 1994, sera were assayed for circulating hormone levels in random subcohorts of 231 and 218 women who did not report current use of hormone replacement therapy at baseline. Lower levels of endogenous estrogens and higher SHBG concentrations were associated with more rapid subsequent bone loss from both the calcaneus and hip. After adjusting for age and weight, women with high SHBG levels (highest quartile < or = 2.3 micrograms/dI) experienced an average of 2.2% (95% confidence interval = 1.6%, 2.9%) calcaneal bone loss per year compared with 1.2% (0.7%, 1.2%) among women with low SHBG concentrations (lowest quartile < 1.1 micrograms/dI; p < 0.01). This association was independent of concentrations of other sex hormones. Women with estradiol levels > or = 10 pg/ml averaged only 0.1% (-0.7%, 0.5%) annual hip bone loss while women with levels below 5 pg/ml averaged 0.8% (0.3, 1.2) hip bone loss per year. Lower 25-hydroxyvitamin D levels were associated with increased hip but not calcaneal bone loss. Levels of parathyroid hormone, 1,25-dihydroxyvitamin D, and Calcium were not significantly associated with bone loss from the calcaneus or hip.
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PMID:Hormonal predictors of bone loss in elderly women: a prospective study. The Study of Osteoporotic Fractures Research Group. 966 Oct 81

Osteoporosis is a disease of low bone mass that may not manifest until a patient has a fracture. Hip fracture is the most devastating, but vertebral fracture is the most common, occurring in 25% of women over 50 years of age and 40% of those age 80-85 years. Although 60% of vertebral fractures are clinically silent, they are easily diagnosed radiographically. They are associated with height loss, deformity, impaired mobility, and pain. Patients should be evaluated for the cause of both the fracture and osteoporosis. Therapy includes education about the disease, an exercise program, and advice about tailoring routine activities. Pharmacotherapy includes annual influenza vaccines, and daily calcium (1200-1500 mg elemental calcium/day) and vitamin D (400-800 IU/day) supplements. New antiresorptive agents alendronate, hormone replacement therapy, and salmon calcitonin should be offered to all patients as they reduce fracture rates.
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PMID:Management of patients with vertebral compression fractures. 991 58

Peak bone mass has been shown to be a significant predictor of risk for osteoporosis. Previous studies have demonstrated that skeletal mass accumulation is under strong genetic control, and efforts have been made to identify candidate loci. Determinants of peak bone mass also include diet, physical activity, hormonal status, and other clinical factors. The overall contribution of these factors, genetic and nongenetic, and their interaction in determining peak bone density status have not been delineated. Six hundred and seventy-seven healthy unrelated Caucasian women ages 18-35 years were assessed. A detailed, standardized interview was conducted to evaluate lifestyle factors, menstrual and reproductive history, medical conditions, medication use, and family history of osteoporosis. Bone mineral density (BMD) was measured at the lumbar spine (L2-L4) and the femoral neck (hip) using dual-energy X-ray absorptiometry. Genotyping of the vitamin D receptor (VDR) locus at three polymorphic sites (BsmI, ApaI, and TaqI) was performed. In bivariate analyses, BMD at the lumbar spine and hip was positively correlated with weight, height, body mass index (BMI), and level of physical activity, both now and during adolescence, but negatively correlated with a family history of osteoporosis. Hip, but not spine BMD, correlated positively with dietary intake of calcium, and negatively with amenorrhea of more than 3 months, with caffeine intake, and with age. Spine, but not hip BMD, correlated positively with age and with number of pregnancies. VDR haplotype demonstrated significant associations with BMD at the hip, level of physical activity currently, and BMI. In multivariate analysis, independent predictors of greater BMD (at the hip or spine) were: age (younger for the hip, older for the spine), greater body weight, greater height (hip only), higher level of physical activity now and during adolescence, no family history of osteoporosis, and VDR genotype (hip only). Weight, age, level of physical activity, and family history are independent predictors of peak BMD. Of these factors, weight accounts for over half the explained variability in BMD. VDR alleles are significant independent predictors of peak femoral neck, but not lumbar spine BMD, even after adjusting for family history of osteoporosis, weight, age, and exercise. However, the overall contribution of this genetic determinant is modest. Taken together, these factors explained approximately 17% and 21% of the variability in peak spine and hip BMD, respectively, in our cohort. Future research should be aimed at further evaluation of genetic determinants of BMD. Most importantly, understanding the critical interactive nature between genes and the environment will facilitate development of targeted strategies directed at modifying lifestyle factors as well as earlier intervention in the most susceptible individuals.
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PMID:Determinants of peak bone mass: clinical and genetic analyses in a young female Canadian cohort. 1023 86

A polymorphism at the first of two potential translation initiation codons in the vitamin D receptor (VDR) gene defined by the FokI restriction endonuclease has been associated with reduced bone mineral density (BMD) among Caucasian, Asian, and Mexican-American women. We tested the hypothesis that the FokI polymorphism is related to markers of osteoporotic risk in 104 community-dwelling African-American women aged 65 years and older. Six percent of the African-American women had the ff genotype, 32% were heterozygous, and 63% had the FF genotype. FokI genotype frequencies did not differ from Hardy-Weinberg expectations. Hip and calcaneal BMD, calcaneal ultrasound attenuation and hip geometry from pelvic radiographs did not differ significantly by FokI genotypes or between women with and without the rare FokI allele. There was also no association between the FokI polymorphism and biochemical markers of bone turnover or fractional calcium absorption. We conclude that the VDR start codon polymorphism does not have a major influence on osteoporotic risk in older African-American women.
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PMID:Vitamin D receptor translation initiation codon polymorphism and markers of osteoporotic risk in older African-American women. 1045 Apr 9

Hip fractures are recognized as a major public health problem worldwide. Demographic changes will lead to enormous increases in the number of hip fractures and projections indicate that the number of hip fractures occurring worldwide each year will rise from 1.26 million in 1990 to 4.5 million by 2050. However, preventive strategies are available. Supplementation with Ca2+ and vitamin D restores bone quality through suppression of secondary hyperparathyroidism and decreases the risk of falling through improvement of neuromuscular coordination and body sway. This leads to a reduction of hip fracture risk of 43% in the vitamin D-insufficient elderly. Treatment with the bisphosphonate alendronate increases bone strength and results in a 51% reduction of hip fracture risk. Hip protectors absorb energy during a fall and reduce hip fracture risk by 56%. Combining these three procedures could prevent a large proportion of hip fractures in the future.
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PMID:Vitamin D and Hip Fracture. 1054

Hip fractures on the paretic side are a serious post-stroke complication and may result from disuse hemiosteopenia, hypovitaminosis D, and an increasing risk of falls. To evaluate short-term immobilization effects, we assessed calcium metabolism in 89 patients 1 week after the hemiplegic stroke and in 36 controls. Patient activity was rated using the Barthel index (BI). Sera from stroke patients and control subjects were assayed for ionized calcium, parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OHD), 1, 25-dihydroxyvitamin D (1,25-(OH)(2)D), bone Gla protein (BGP; a bone formation marker) and pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP; a bone resorption marker). Patients' serum concentrations of ionized calcium and ICTP were higher than in controls and correlated negatively with BI; their BGP concentrations were low, correlating positively with BI. Concentrations of serum 25-OHD, 1,25-(OH)(2)D, and PTH also were low; serum 25-OHD was at a deficient level (<10 ng/ml) in nine patients (10%), an insufficient level (10-20 ng/ml) in 56 (63%), and a sufficient level (>20 ng/ml) in only 24 (27%). PTH correlated negatively with calcium and 1,25-(OH)(2)D. Hypovitaminosis D is common in acute stroke patients. Immobilization from acute hemiplegia can increase bone resorption and serum calcium, and inhibit PTH secretion and 1,25-(OH)(2)D production to add to the effects of hypovitaminosis D.
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PMID:Influence of immobilization upon calcium metabolism in the week following hemiplegic stroke. 1083 74


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