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- Alfvén, Tobias, et al.
(författare)
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Low-level cadmium exposure and osteoporosis.
- 2000
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Ingår i: Journal of Bone and Mineral Research. - 0884-0431 .- 1523-4681. ; 15, s. 1579-1586
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Tidskriftsartikel (refereegranskat)abstract
- Osteoporosis is a major cause of morbidity worldwide. A number of risk factors, such as age and gender, are well established. High cadmium exposure causes renal damage and in severe cases also causes osteoporosis and osteomalacia, We have examined whether long-term Pow-level cadmium exposure increases the risk of osteoporosis. Bone mineral density (BMD) in the forearm was measured in 520 men and 544 women, aged 16-81 years, environmentally or occupationally exposed to cadmium, using dual-energy X-ray absorptiometry (DXA) technique. Cadmium in urine was used as the dose estimate and protein HC was used: as a marker of renal tubular damage. There was a clear dose-response relation between cadmium dose and the prevalence of tubular proteinuria. Inverse relations were found between cadmium dose, tubular proteinuria, and BMD, particularly apparent in persons over 60 years of age, There was a dose-response relation between cadmium dose and osteoporosis. The odds ratios (ORs) for men were 2.2 (95% CI, 1.0-4.8) in the dose group 0.5-3 nmol Cd/mmol creatinine and 5.3 (2.0-14) in the highest dose category (greater than or equal to 3 nmol/mmol creatinine) compared with the lowest dose group (<0.5 nmol Cd/mmol creatinine). For women, the OR was 1.8 (0.65-5.3) in the dose group 0.53 nmol Cd/mmol creatinine. We conclude that exposure to low levels of cadmium is associated with an increased risk of osteoporosis.
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| 2. |
- Aspenberg, Per, et al.
(författare)
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The bone morphogenetic proteins antagonist noggin inhibits membranous ossification
- 2001
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 16:3, s. 497-500
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Tidskriftsartikel (refereegranskat)abstract
- Bone morphogenetic proteins (BMPs) are expressed and secreted during fracture repair. Although they are likely to be required for this process, little is known about their physiological role in bone regeneration. Noggin is a protein that specifically binds and inactivates several BMPs, It plays fundamental roles during early embryonal development and limb morphogenesis by this BMP-inactivating activity. This study shows that Noggin can modify bone formation in vivo in the adult animal and, thus, indirectly, that BMP signaling is indispensable in this process. A noggin mutein (hNg Delta B2-Fc) engineered so as to display increased bioavailability was used. Bilateral titanium bone chambers mere inserted in 70 rats, and side comparisons for bone formation in the chambers were done. The hNg Delta B2-Fc had no effect on total amount of tissue formed in the chamber but decreased the amount of bone compared with both buffer controls and a control made up of an Fc-tagged IL-6R alpha protein, which had no effects of its own, Also, wild-type noggin inhibited bone formation. Thus, endogenous BMP signaling is necessary for normal bone regeneration.
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| 5. |
- Johansson, Helena, 1981, et al.
(författare)
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Optimization of BMD measurements to identify high risk groups for treatment--a test analysis.
- 2004
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Ingår i: Journal of bone and mineral research. - : Wiley. - 0884-0431 .- 1523-4681. ; 19:6, s. 906-13
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The aim of this study was to develop a methodology to optimize the role of BMD measurements in a case finding strategy. We studied 2113 women > or = 75 years of age randomly selected from Sheffield, UK, and adjacent regions. Baseline assessment included hip BMD and clinical risk factors. Outcomes included death and fracture in women followed for 6723 person-years. MATERIALS AND METHODS: Poisson models were used to identify significant risk factors for all fractures and for death with and without BMD and the hazard functions were used to compute fracture probabilities. Women were categorized by fracture probability with and without a BMD assessment. A 10-year fracture probability threshold of 35% was taken as an intervention threshold. Discordance in categorization of risk (i.e., above or below the threshold probability) between assessment with and without BMD was examined by logistic regression as probabilities of re-classification. Age, prior fracture, use of corticosteroids, and low body mass index were identified as significant clinical risk factors. RESULTS: A total of 16.8% of women were classified as high risk based on these clinical risk factors. The average BMD in these patients was approximately 1 SD lower than in low-risk women; 21.5% of women were designated to be at high risk with the addition of BMD. Fifteen percent of all women were reclassified after adding BMD to clinical risk factors, most of whom lay near the intervention threshold. When a high probability of reclassification was accepted (without a BMD test) for high risk to low risk (p1< or = 0.8) and a low probability accepted for low to high risk (P2 < or = 0.2), BMD tests would be required in only 21% of the population. CONCLUSION: We conclude that the use of clinical risk factors can identify elderly women at high fracture risk and that such patients have a low average BMD. BMD testing is required, however, in a minority of women--a fraction that depends on the probabilities accepted for classification and the thresholds of risk chosen. These findings need to be validated in other cohorts at different ages and from different regions of the world.
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| 6. |
- Kanis, John A, et al.
(författare)
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A meta-analysis of prior corticosteroid use and fracture risk.
- 2004
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Ingår i: Journal of bone and mineral research. - 0884-0431 .- 1523-4681. ; 19:6, s. 893-9
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Tidskriftsartikel (refereegranskat)abstract
- The relationship between use of corticosteroids and fracture risk was estimated in a meta-analysis of data from seven cohort studies of approximately 42,000 men and women. Current and past use of corticosteroids was an important predictor of fracture risk that was independent of prior fracture and BMD. INTRODUCTION: The aims of this study were to validate that corticosteroid use is a significant risk factor for fracture in an international setting and to explore the effects of age and sex on this risk. MATERIALS AND METHODS: We studied 42,500 men and women from seven prospectively studied cohorts followed for 176,000 patient-years. The cohorts comprised the EPOS/EVOS study, CaMos, the Rotterdam Study, Dubbo Osteoporosis Epidemiology Study (DOES), and prospective cohorts at Sheffield, Rochester, and Gothenburg. The effect of ever use of corticosteroids, BMD, age, and sex on all fracture, osteoporotic fracture, and hip fracture risk alone was examined using Poisson regression in each cohort and for each sex. The results of the different studies were merged from the weighted beta coefficients. RESULTS: Previous corticosteroid use was associated with a significantly increased risk of any fracture, osteoporotic fracture, and hip fracture when adjusted for BMD. Relative risk of any fracture ranged from 1.98 at the age of 50 years to 1.66 at the age of 85 years. For osteoporotic fracture, the range of relative risk was 2.63-1.71, and for hip fracture 4.42-2.48. The estimate of relative risk was higher at younger ages, but not significantly so. No significant difference in risk was seen between men and women. The risk was marginally and not significantly upwardly adjusted when BMD was excluded from the model. The risk was independent of prior fracture. In the three cohorts that documented current corticosteroid use, BMD was significantly reduced at the femoral neck, but fracture risk was still only partly explained by BMD. CONCLUSION: We conclude that prior and current exposure to corticosteroids confers an increased risk of fracture that is of substantial importance beyond that explained by the measurement of BMD. Its identification on an international basis validates the use of this risk factor in case-finding strategies.
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| 7. |
- Kanis, JA, et al.
(författare)
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International variations in hip fracture probabilities: Implications for risk assessment
- 2002
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 17:7, s. 1237-1244
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Tidskriftsartikel (refereegranskat)abstract
- It is recommended that intervention thresholds should be based on absolute fracture risk, but there is a large variation in hip fracture incidence from different regions of the world. The aim of this study was to examine heterogeneity of hip fracture probability in different regions from recent estimates of hip fracture incidence and mortality to adjust intervention thresholds. Ten-year probabilities of hip fracture were computed in men and women at 10-year intervals from the age of 50 years and lifetime risks at the age of 50 years from the hazard functions of hip fracture and death. Lifetime risk at the age of 50 years varied from 1% in women from Turkey to 28.5% in women from Sweden. High lifetime risks in women were associated with high lifetime risks in men (r = 0.83). There also were significant correlations of 10-year risk at any age between men and women. Ten-year probability was standardized to that of men and women from Sweden (set at 1.0). There was a 15-fold range in 10-year probability from 1.24 in Norway to 0.08 in Chile. Countries were categorized by 10-year probabilities comprising very high risk (Norway, Iceland, Sweden, Denmark, and the United States), high risk (China [Taiwan {TW}], Germany, Switzerland, Finland, Greece, Canada, The Netherlands, Hungary, Singapore, Italy, United Kingdom, Kuwait, Australia, and Portugal), medium risk (China [Hong Kong {HK}], France, Japan, Spain, Argentina, and China), and low risk (Turkey, Korea, Venezuela, and Chile). The categorization of hip fracture probabilities can be used to adjust intervention thresholds based on age, sex, and relative risk from a reference population such as Sweden.
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| 9. |
- Lehenkari, Petri, et al.
(författare)
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The effects of tamoxifen and toremifene on bone cells involve changes in plasma membrane ion conductance
- 2003
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 18:3, s. 473-481
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Tidskriftsartikel (refereegranskat)abstract
- Selective estrogen receptor modulators (SERMs), tamoxifen (Tam) and toremifene (Tor), are widely used in the treatment of breast cancer. In addition, they have been demonstrated to prevent estrogen deficiency-induced bone loss in postmenopausal women. These effects are thought to be caused by the interaction of the SERMs with the estrogen receptor, although SERMs have also been shown to conduct non-receptor-mediated effects such as rapid changes in membrane functions. We compared the effects of Tam, Tor, and 17β-estradiol (E2) on the viability of rat osteoclasts and osteoblasts. Both Tam and Tor were found to cause osteoclast apoptosis in in vitro cultures, which was reversed by E2. In addition, at higher concentration (10 μM), both SERMs had an estrogen receptor-independent effect, which involved interaction with the plasma membrane as demonstrated with UMR-108 osteosarcoma cells by Tam and Tor, but not E2. A leak of protons leading to changes in intracellular pH was shown both in medullary bone derived membrane vesicles and in intact cells. These effects were followed by a rapid loss of cell viability and subsequent cell lysis. Our results show that both Tam and Tor have an ionophoric effect on the plasma membranes of bone cells and that these SERMs differed in this ability: Tor induced rapid membrane depolarization only in the presence of high concentration of potassium. These non-receptor-mediated effects may be involved in therapeutic responses and explain some clinical side effects associated with the treatment of patients with these SERMs
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