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- Gerdhem, Paul, et al.
(författare)
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Associations between homocysteine, bone turnover, BMD, mortality, and fracture risk in elderly women
- 2007
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 22:1, s. 127-134
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Tidskriftsartikel (refereegranskat)abstract
- Homocysteine has been suggested to be a risk factor for fracture, but the causal relationship is not clear. In 996 women from the OPRA study, high homocysteine level was associated with high bone marker levels and low BMD at baseline. During a mean 7-year follow-up, high homocysteine level was associated with mortality, but no clear association to fracture risk existed.
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| 2. |
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| 3. |
- Ivaska, Kaisa, et al.
(författare)
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Bone Turnover Markers and Prediction of Fracture: A Prospective Follow-Up Study of 1040 Elderly Women for a Mean of 9 Years
- 2010
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 25:2, s. 393-403
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Tidskriftsartikel (refereegranskat)abstract
- Osteoporosis is characterized by compromised bone mass and strength, predisposing to an increased risk of fracture. Increased bone metabolism has been suggested to be a risk factor for fracture. The aim of this study was to evaluate whether baseline bone turnover markers are associated with long-term incidence of fracture in a population-based sample of 1040 women who were 75 years old (Malmo OPRA study). Seven bone markers (S-TRACP5b, S-CTX-1, S-OC[1-49], S-TotaIOC, S-cOC, S-boneALP, and urinary osteocalcin) were measured at baseline and 1-year follow-up visit. During the mean follow-up of 9.0 years (range 7.4-10.9), 363 women sustained at least one fracture of any type, including 116 hip fractures and 103 clinical vertebral fractures. High S-TRACP5b and S-CTX-1 levels were associated with increased risk of any fracture with hazard ratios [HRs (95% confidence interval)] of 1.16 (1.04-1.29) and 1.13 (1.01-1.27) per SD increase, respectively. They also were associated with increased risk of clinical vertebral fracture with HRs of 1.22 (1.01-1.48) and 1.32 (1.05-1.67), respectively. Markers were not associated with risk for hip fracture. Results were similar when we used resorption markers, including urinary osteocalcin, measured at the 1-year visit or an average of the two measurements. The HRs were highest for any fracture in the beginning of the follow-up period, 2.5 years from baseline. For vertebral fractures, the association was more pronounced and lasted for a longer period of time, at least for 5 years. In conclusion, elevated levels of S-TRACP5b, S-CTX-1, and urinary osteocalcin are associated with increased fracture risk for up to a decade in elderly women. (C) 2010 American Society for Bone and Mineral Research.
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| 4. |
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| 5. |
- Ivaska, Kaisa, et al.
(författare)
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Serial assessment of serum bone metabolism markers identifies women with the highest rate of bone loss and osteoporosis risk.
- 2008
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; May 6, s. 2622-2632
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Tidskriftsartikel (refereegranskat)abstract
- Context: One of the important challenges in the management of osteoporosis is to identify women who are at high risk of developing osteoporosis and fragility fractures. Objective: To evaluate if assessment of bone metabolism at multiple occasions can identify women with the highest risk for bone loss. Design: The Malmö OPRA study is an ongoing longitudinal study. Participants have been evaluated at baseline and after 1, 3 and 5 years. Setting: Population-based study. Participants: 1044 women, all 75 years old at baseline. Main outcome measures: Seven bone turnover markers were assessed at baseline, 1, 3 and 5 years (n=573). Five year change in areal bone mineral density (aBMD) was also determined. Results: Baseline markers correlated weakly to change in total body aBMD. The associations were more pronounced when the average of the baseline and 1-year measurements was used (standardized regression coefficients -0.12 to -0.23, p<0.01). Adding the 3-year and 5-year measurement further strengthened the correlation (regression coefficients up to -0.30 (p<0.001)). Women with constantly high turnover lost significantly more bone at total body (-2.6%) than women with intermediate (-1.6%) or low turnover (-0.2%, p for trend <0.001). They also had a greater decrease in hip BMD (-8.3%, -6.0% and -5.1%, respectively, p=0.010). Results were similar also in the subgroup of women with osteopenia. Conclusions: Our results suggest that serial assessment of bone turnover improves the identification of women with the highest rate of bone loss and osteoporosis risk.
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| 6. |
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| 7. |
- McGuigan, Fiona, et al.
(författare)
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Osteocalcin gene polymorphisms influence concentration of serum osteocalcin and enhance fracture identification.
- 2010
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; Apr 7, s. 1392-1399
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Tidskriftsartikel (refereegranskat)abstract
- Osteoporosis is a major health problem affecting more than 75 million people throughout Europe, USA and Japan. Epidemiological studies have determined that both genetic and environmental factors contribute to the pathogenesis of osteoporosis. We have investigated the association between polymorphisms at the osteocalcin locus and variables linked to bone health. Osteocalcin provides a link between bone and energy metabolism, hence its potential importance as an osteoporosis candidate gene. In this study, we included a total of 996 women (all aged 75 years) from the OPRA cohort. We sequenced the osteocalcin gene along with flanking region to search for novel coding polymorphisms. We also analyzed four polymorphisms selected from within and flanking regions of the osteocalcin gene to study their association with serum total osteocalcin levels (S-TotalOC), total body (TB) bone mineral density (BMD), fracture, TB fat mass and BMI. The promoter polymorphism rs1800247 was significantly associated with S-TotalOC (p = 0.012) after controlling for BMI and TB BMD. The polymorphism rs1543297 was significantly associated with prospectively occurring fractures (p = 0.008). In a model taking into account rs1543297 and rs1800247 along with TB BMD, BMI, smoking and S-TotalOC, the polymorphisms together were able to identify an additional 6% of women who sustained a fracture (p = 0.02). We found no association between the polymorphisms and TB BMD, BMI or TB fat mass. In conclusion, polymorphisms in and around the osteocalcin locus are significantly associated with S-TotalOC and fracture. Genotyping at the osteocalcin locus could add valuable information in the identification of women at risk of osteoporosis. (c) 2010 American Society for Bone and Mineral Research.
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| 8. |
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| 9. |
- Swanberg, Maria, et al.
(författare)
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Polymorphisms in the Inflammatory Genes CIITA, CLEC16A and IFNG Influence BMD, Bone Loss and Fracture in Elderly Women.
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:10
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Tidskriftsartikel (refereegranskat)abstract
- Osteoclast activity and the fine balance between bone formation and resorption is affected by inflammatory factors such as cytokines and T lymphocyte activity, mediated by major histocompatibility complex (MHC) molecules, in turn regulated by the MHC class II transactivator (MHC2TA). We investigated the effect of functional polymorphisms in the MHC2TA gene (CIITA), and two additional genes; C-type lectin domain 16A (CLEC16A), in linkage disequilibrium with CIITA and Interferon-γ (IFNG), an inducer of CIITA; on bone density, bone resorption markers, bone loss and fracture risk in 75 year-old women followed for up to 10 years (OPRA n = 1003) and in young adult women (PEAK-25 n = 999). CIITA was associated with BMD at age 75 (lumbar spine p = 0.011; femoral neck (FN) p = 0.049) and age 80 (total body p = 0.015; total hip p = 0.042; FN p = 0.028). Carriers of the CIITA rs3087456(G) allele had 1.8-3.4% higher BMD and displayed increased rate of bone loss between age 75 and 80 (FN p = 0.013; total hip p = 0.030; total body p = 3.8E(-5)). Despite increasing bone loss, the rs3087456(G) allele was protective against incident fracture overall (p = 0.002), osteoporotic fracture and hip fracture. Carriers of CLEC16A and IFNG variant alleles had lower BMD (p<0.05) and ultrasound parameters and a lower risk of incident fracture (CLEC16A, p = 0.011). In 25-year old women, none of the genes were associated with BMD. In conclusion, variation in inflammatory genes CIITA, CLEC-16A and INFG appear to contribute to bone phenotypes in elderly women and suggest a role for low-grade inflammation and MHC class II expression for osteoporosis pathogenesis.
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| 10. |
- Swanberg, Maria, et al.
(författare)
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Polymorphisms in the macrophage migration inhibitory factor gene and bone loss in postmenopausal women.
- 2010
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Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 47:2, s. 424-9
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Tidskriftsartikel (refereegranskat)abstract
- Osteoporosis is a severe condition in postmenopausal women and a common cause of fracture. Osteoporosis is a complex disease with a strong genetic impact, but susceptibility is determined by many genes with modest effects and environmental factors. Only a handful of genes consistently associated with osteoporosis have been identified so far. Inflammation affects bone metabolism by interfering with the interplay between bone resorption and formation, and many inflammatory mediators are involved in natural bone remodeling. The cytokine macrophage migration inhibitory factor (MIF) has been shown to affect bone density in rodents, and polymorphisms in the human MIF promoter are associated with inflammatory disorders such as rheumatoid arthritis. We investigated the association of polymorphisms in the MIF gene with bone mineral density (BMD) and bone loss in 1002 elderly women using MIF promoter polymorphisms MIF-CATT(5-8) and rs755622(G/C) located -794 and -173 bp upstream of the transcriptional start site. Bone loss was estimated both by the change in BMD over 5 years and by the levels of bone resorption markers in serum measured at four occasions during a 5-year period. The MIF-CATT(7)/rs755622(C) haplotype was associated with increased rate of bone loss during 5 years at the femoral neck (p<0.05) and total hip (p<0.05). In addition, the MIF-CATT(7)/rs755622(C) haplotype carriers had higher levels of the bone turnover marker serum C-terminal cross-linking telopeptide of type I collagen (S-CTX-I, p<0.01) during the 5 year follow-up period. There was no association between MIF-CATT(7)/rs755622(C) and baseline BMD at femoral neck, total hip or lumbar spine. We conclude that MIF promoter polymorphisms have modest effects on bone remodeling and are associated with the rate of bone loss in elderly women.
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