Association of polymorphism at the type I collagen (COL1A1) locus with reduced bone mineral density, increased fracture risk, and increased collagen turnover.
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OBJECTIVE: To examine the relationship between a common polymorphism within intron 1 of the COL1A1 gene and osteoporosis in a nested case-control study. METHODS: We studied 185 healthy women (mean +/- SD age 54.3+/-4.6 years). Bone mineral density (BMD) was measured using dual x-ray absorptiometry, and fractures were determined radiographically. The COL1A1 genotype was assessed using the polymerase chain reaction and Bal I endonuclease digestion. RESULTS: Genotype frequencies were similar to those previously observed and in Hardy-Weinberg equilibrium: SS 61.1%, Ss 36.2%, and ss 2.7%. Carriage of at least one copy of the "s" allele was associated with a significant reduction in lumbar spine BMD (P = 0.02) and an increased risk of total fracture (P = 0.04). Urinary pyridinoline levels were significantly elevated in those with the risk allele (P < 0.05). CONCLUSION: These data support the findings that the COL1A1 gene polymorphism is associated with low BMD and fracture risk, and suggest a possible physiologic effect on total body turnover of type I collagen. (+info)
Immunoradiometric assay for intact human osteocalcin(1-49) without cross-reactivity to breakdown products.
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BACKGROUND: Osteocalcin (Oc), a serum marker of bone turnover, circulates in several forms. We developed an assay for intact human Oc and investigated its clinical features. METHODS: We generated goat antibodies and N- and C-terminal Oc. The former was used on solid phase (polystyrene beads), and the latter was used as the tracer in an IRMA. RESULTS: The assay was linear with no cross-reactivity to Oc(1-43), total imprecision (CV) of <10%, and recovery of 100% +/- 10%. Assay values for intact Oc in EDTA plasma samples were unchanged at 18-25 degrees C for 6 h. Values for intact Oc in serum, EDTA plasma, and heparin plasma samples did not change after storage on ice for 8 h. Serum samples from patients with various conditions were stored at -70 or -135 degrees C for up to 5 years and yielded z-scores comparable to an Oc(1-43) IRMA for all conditions except for renal failure. In renal failure, the Oc(1-43) assay values were increased, whereas the intact assay values were in the reference interval. CONCLUSION: Decreases in Oc assay values are inhibited by calcium chelation, and slowed by reduced temperatures. The described assay for intact Oc allows improved specificity for bone compared with an assay for Oc(1-43). (+info)
Health screening in older women.
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Health screening is an important aspect of health promotion and disease prevention in women over 65 years of age. Screening efforts should address conditions that cause significant morbidity and mortality in this age group. In addition to screening for cardiovascular disease, cerebrovascular disease and cancer, primary care physicians should identify risk factors unique to an aging population. These factors include hearing and vision loss, dysmobility or functional impairment, osteoporosis, cognitive and affective disorders, urinary incontinence and domestic violence. Although screening for many conditions cannot be proved to merit an "A" recommendation (indicating conclusive proof of benefit), special attention to these factors can decrease morbidity and improve quality of life in aging women. (+info)
Effects of single and concurrent intermittent administration of human PTH (1-34) and incadronate on cancellous and cortical bone of femoral neck in ovariectomized rats.
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The purpose of this study is to determine the efficacy of concurrent treatment with human parathyroid hormone, hPTH (1-34), and bisphosphonate (incadronate) in augmenting cortical and cancellous bone mass of femoral neck in ovariectomized (OVX) rats. Forty-eight 11-week-old female Sprague-Dawley rats were divided into eight groups (six animals in each group). The baseline control group was killed at the beginning of the experiment, at 11 weeks of age. An ovariectomy was performed in thirty rats and twelve rats were subjected to a sham surgery. OVX rats were untreated for the first four weeks of postsurgery to allow for the development of moderate osteopenia. These animals were then subjected to various treatments with either PTH, incadronate, or PTH+ incadronate for a period of 4 weeks. Right proximal femora (femoral necks) were used for bone histomorphometry. After OVX 8 weeks, there was a significant decrease in cancellous bone mass and cortical bone area of femoral neck in the OVX rats when compared to the sham control rats. In OVX rats treated with PTH alone or PTH+ incadronate were completely restored lost cancellous and cortical bone mass of femoral neck by increase bone formation. The bone formation parameters (OS/ BS, MS/BS) and bone turnover (BFR/BV) seen with PTH plus incadronate were similar to those seen with PTH treatment alone. This indicates that incadronate did not blunt the anabolic action of PTH when used concurrently. Our results suggest the followings: 1) the femoral neck of OVX rats is a suitable sample site for preclinical studies of the prevention of bone loss induced by estrogen depletion; 2) concurrent use of incadronate did not blunt the anabolic effect of PTH; 3) concurrent treatment showed the best results in restoring cancellous and cortical bone mass; and 4) it had additional benefits for bone strength independent of that achieved by the increase in bone mass. (+info)
Estrogen's bone-protective effects may involve differential IL-1 receptor regulation in human osteoclast-like cells.
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Declining estrogen levels during the first postmenopausal decade lead to rapid bone loss and increased fracture risk that can be reversed by estrogen replacement therapy. The bone-protective effects of estrogen may involve suppression of inflammatory cytokines that promote osteoclastogenesis and bone resorption, such as IL-1, TNF-alpha, and IL-6. We investigated whether estrogen modulates IL-1 actions on human osteoclasts (OCs) and other bone cell types. Isolated human OCs and primary bone marrow-derived OC-like cells expressed both the signaling (IL-1RI) and decoy (IL-1RII) IL-1 receptors, whereas only IL-1RI was detected in osteoblasts. IL-1RII/IL-1RI mRNA ratios and release of soluble IL-1RII (sIL-1RII) were lower in OC-like cells derived from women in the late postmenopausal period compared with younger women, but were unrelated to male donor age, suggesting that estrogen might play a role in regulating IL-1 receptor levels in vivo. Estrogen directly reduced in vitro OC-like cell IL-1RI mRNA levels while increasing IL-1RII mRNA levels and sIL-1RII release. These estrogenic events were associated with inhibited IL-1-mediated cytokine (IL-8) mRNA induction and cell survival, i.e., increased apoptosis. In contrast, estrogen did not alter IL-1R levels or IL-1 responsiveness in primary human osteoblasts or bone marrow stromal cells. We conclude that one novel mechanism by which estrogen exerts bone-protective effects may include a selective modulation of IL-1R isoform levels in OC or OC-like cells, thereby reducing their IL-1 responsiveness and cell survival. Conversely, this restraint on IL-1 actions may be lost as estrogen levels decline in aging women, contributing to an enhanced OC-mediated postmenopausal bone loss. (+info)
Habitual physical activity and bone mineral density in postmenopausal women in England.
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BACKGROUND: Reduced levels of physical activity have been found to be associated with an increased risk of osteoporotic fracture in a number of epidemiological studies, and intervention studies have shown beneficial effects of exercise regimes on bone mineral density. It is not yet established, however, which specific forms of customary physical activity are most strongly associated with bone mineral density in postmenopausal women. METHODS: A cross-sectional study was conducted in 580 postmenopausal women, aged 45-61 years, resident in Nottingham, England. The participants completed a detailed interviewer-administered activity questionnaire. Physical activity was assessed as total hours of participation per week in activities including housework, walking, gardening and sports. Stair-climbing and self-reported walking pace were also reported. Bone mineral density measurements were made using dual energy x-ray absorptiometry, measurements at five sites were used in analysis. RESULTS: The strongest associations between the activity measures and bone mineral density were for stair-climbing and walking pace, which both gave statistically significant positive associations at the trochanter hip site and the whole body. In women reporting a fairly brisk or fast walking pace, bone mineral density at the proximal femur was also significantly and positively associated with the frequency of walking at least a mile. There were no significant associations with aggregate measures of total customary physical activity. CONCLUSIONS: This study has identified two forms of physical activity, namely stair-climbing and brisk walking which are associated with increased bone mineral density at the hip and whole body in postmenopausal women. Both are feasible forms of activity for promoting to middle-aged women. (+info)
Association of race and other potential risk factors with nonvertebral fractures in community-dwelling elderly women.
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This study determined potential associations of sociodemographic, lifestyle, health, and drug use factors known to affect bone metabolism with incident nonvertebral fractures. The baseline sample consisted of 2,590 female, nonproxy subjects from the Duke Established Populations for Epidemiologic Studies of the Elderly, which focuses on five adjacent counties in the Piedmont area of North Carolina. Information about potential risk factors was collected during a baseline in-home interview during 1986-1987. Subsequent nonvertebral fractures were reported at follow-up interviews during the annual follow-up periods (1988-1993). The authors used multivariate analyses in which weighted data were adjusted for sampling design. After controlling for other potential confounding sociodemographic, lifestyle, health, and drug use factors, they found that African American race (adjusted odds ratio (OR) = 0.43, 95% confidence interval (CI) 0.31-0.58), age (adjusted OR = 1.04, 95% CI 1.01-1.06), alcohol consumption (adjusted OR = 1.61, 95% CI 1.01-2.57), being underweight (adjusted OR = 1.63, 95% CI 1.13-2.34), cognitive impairment (adjusted OR = 1.67, 95% CI 1.12-2.48), impaired mobility (adjusted OR = 1.15, 95% CI 1.03-1.29), and phenytoin use (adjusted OR = 2.93, 95% CI 1.04-8.30) were associated with first fracture occurrence. Similar findings were observed for nonhip, nonvertebral fractures. African Americans were less likely than Whites to have nonvertebral fractures, and these differences were not related to lifestyle or health factors examined in this study. (+info)
Larger increases in bone mineral density during alendronate therapy are associated with a lower risk of new vertebral fractures in women with postmenopausal osteoporosis. Fracture Intervention Trial Research Group.
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OBJECTIVE: To investigate whether the incidence of vertebral fractures is related to the magnitude of change in bone mineral density (BMD) during alendronate treatment. METHODS: Women in this study were age 55-81 years (n = 2,984). While participating in the Fracture Intervention Trial, they received 5 mg/day of alendronate for 2 years followed by 10 mg/day for the remaining 12-30 months of the study. Their BMD was measured at baseline and at 12 and 24 months, and spine radiographs were obtained at baseline and again at 36 or 48 months to identify new vertebral fractures. RESULTS: After 12 months of alendronate treatment, 35% of participants had increases of > or =3% in total hip BMD, and 21% had either decreased total hip BMD or no change. Women who had larger increases in total hip BMD during the first 12 months had a lower incidence of new vertebral fractures during the entire followup period. Only 3.2% of women with increases of > or =3% in total hip BMD experienced new vertebral fractures, whereas twice as many women (6.3%) whose BMD declined or stayed the same experienced new fractures (adjusted odds ratio 0.45, 95% confidence interval 0.27-0.72). Similar patterns were observed for spine BMD at 12 months, and for both sites using change in BMD at 24 months. CONCLUSION: Women with increases of > or =3% in BMD during the first 1 or 2 years of alendronate treatment had the lowest incidence of new vertebral fractures. These findings suggest that, among women taking antiresorptive agents, greater increases in BMD are associated with lower risk of new vertebral fractures. (+info)