| 1. |
- Gyllenberg, A, et al.
(författare)
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Age-dependent variation of genotypes in MHC II transactivator gene (CIITA) in controls and association to type 1 diabetes
- 2012
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Ingår i: Genes and Immunity. - Stockholm : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 76:2, s. 202-203
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Tidskriftsartikel (refereegranskat)abstract
- The major histocompatibility complex class II transactivator (CIITA) gene (16p13) has been reported to associate with susceptibility to multiple sclerosis, rheumatoid arthritis and myocardial infarction, recently also to celiac disease at genome-wide level. However, attempts to replicate association have been inconclusive. Previously, we have observed linkage to the CIITA region in Scandinavian type 1 diabetes (T1D) families. Here we analyze five Swedish T1D cohorts and a combined control material from previous studies of CIITA. We investigate how the genotype distribution within the CIITA gene varies depending on age, and the association to T1D. Unexpectedly, we find a significant difference in the genotype distribution for markers in CIITA (rs11074932, P=4 × 10(-5) and rs3087456, P=0.05) with respect to age, in the collected control material. This observation is replicated in an independent cohort material of about 2000 individuals (P=0.006, P=0.007). We also detect association to T1D for both markers, rs11074932 (P=0.004) and rs3087456 (P=0.001), after adjusting for age at sampling. The association remains independent of the adjacent T1D risk gene CLEC16A. Our results indicate an age-dependent variation in CIITA allele frequencies, a finding of relevance for the contrasting outcomes of previously published association studies.
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| 2. |
- Banefelt, Jonas, et al.
(författare)
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Total Hip Bone Mineral Density as an Indicator of Fracture Risk in Bisphosphonate-Treated Patients in a Real-World Setting
- 2022
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 37:1, s. 52-58
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Tidskriftsartikel (refereegranskat)abstract
- Bone mineral density (BMD) is an established measure used to diagnose patients with osteoporosis. In clinical trials, change in BMD has been shown to provide a reliable estimate of fracture risk reduction, and achieved BMD T-score has been shown to reflect the near-term risk of fracture. We aimed to test the association between BMD T-score and fracture risk in patients treated for osteoporosis in a real-world setting. This retrospective, observational cohort study included Swedish females aged ≥55 years who had a total hip BMD measurement at one of three participating clinics. Patients were separated into two cohorts: bisphosphonate-treated and bisphosphonate-naïve prior to BMD measurement, stratified by age and prior nonvertebral fracture status. The primary outcome was cumulative incidence of clinical fractures within 24 months of BMD measurement, with other fracture types included as secondary outcomes. Associations between T-score and fracture risk were estimated using proportional hazards regression and restricted cubic splines. A total of 15,395 patients were analyzed: 11,973 bisphosphonate-naïve and 3422 bisphosphonate-treated. In the 24 months following BMD measurement, 6.3% (95% confidence interval [CI], 5.9–6.7) of bisphosphonate-naïve and 8.4% (95% CI, 7.5–9.4) of bisphosphonate-treated patients experienced a clinical fracture. Strong inverse relationships between BMD T-score and fracture incidence were observed in both cohorts. Among bisphosphonate-naïve patients, this relationship appeared to plateau around T-score −1.5, indicating smaller marginal reductions in fracture risk above this value; bisphosphonate-treated patients showed a more consistent marginal change in fracture risk across the evaluated T-scores (−3.0 to –0.5). Trends remained robust regardless of age and prior fracture status. This real-world demonstration of a BMD–fracture risk association in both bisphosphonate-naïve and bisphosphonate-treated patients extends evidence from clinical trials and recent meta-regressions supporting the suitability of total hip BMD as a meaningful outcome for the clinical management of patients with osteoporosis.
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| 3. |
- Lauppe, Rosa, et al.
(författare)
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Differing impact of clinical factors on the risk of fracture in younger and older women in the general population and an osteoporosis clinic population
- 2019
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Ingår i: Archives of Osteoporosis. - : Springer Science and Business Media LLC. - 1862-3522 .- 1862-3514. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Summary: This study assesses the impact of risk factors for fracture in women aged 80+ and 60–79. The results suggest that risk assessment which fits younger women may not be suited for the 80+ strata as many common risk factors are less predictive in the older compared to the younger cohort. Purpose: This study assesses whether the impact of classical risk factors for fracture due to osteoporosis is different in women aged 80+ and women aged 60–79. Since most prior research on the contribution of risk factors is based on patients below 80 years of age, this study aims to fill this knowledge gap to increase the accuracy of risk assessment in the oldest old. Methods: Retrospective, observational cohort study using Swedish national health register data and BMD data from osteoporosis clinics. Women aged at least 60 were identified from a random sample of the general population and from the BMD databases and allocated to two populations representing patients at different stages of risk assessment. The relative impact of risk factors on fracture risk was assessed using multivariate competing risk regression with fracture as outcome and death as competing event. Results: A total of 163,329 women were included from the general population (52,499 aged 80+) and 22,378 from the BMD databases (4563 aged 80+). The clinical risk factors with relatively highest effect on fracture risk in the older patients were prior fracture and hip T-score below − 2.5 SD. Other included risk factors showed lower impact in the older compared to the younger strata. Conclusions: This study confirms our understanding of the key risk factors for fracture: age, prior fracture, and a low T-score. Regarding remaining risk factors, risk assessment which fits younger women may not be suited for the 80+ strata as many common risk factors are less predictive in the older compared to the younger cohort.
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| 4. |
- Söreskog, Emma, et al.
(författare)
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Risk of major osteoporotic fracture after first, second and third fracture in Swedish women aged 50 years and older
- 2020
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 134
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Tidskriftsartikel (refereegranskat)abstract
- Background: Osteoporosis affects approximately one in five European women and leads to fragility fractures, which result in poor health, social and economic consequences. Fragility fractures are a strong risk factor for subsequent major osteoporotic fracture (MOF), with risk of MOF being elevated in the 1–2 years following an earlier fracture, a concept described as “imminent risk”. This study examines risk of subsequent MOF in patients with one, two or three prior fractures by age and type of fracture. Methods: In this retrospective, observational cohort study, Swedish women aged ≥50 years with ≥1 any clinical fragility fracture between July 1, 2006 and December 31, 2012 were identified from Sweden's National Patient Register. Each patient was age- and sex-matched to three controls without history of fracture. Group 1 women included those with one fragility fracture during the study period; Group 2 included those with two fragility fractures; and Group 3 included those with three fragility fractures. “Index fracture” was defined as the first fracture during the study period for Group 1; the second for Group 2; and the third for Group 3. Patients in each cohort and matched controls were followed for up to 60 months or until subsequent MOF (hip, vertebra, forearm, humerus), death or end of data availability. Results: 231,769 women with at least one fracture were included in the study and therefore constituted Group 1; of these, 39,524 constituted Group 2 and of those, 7656 constituted Group 3. At five years, cumulative incidence of subsequent MOF was higher in patients with a history of fracture as compared to controls (Group 1: 20.7% vs 12.3%; Group 2: 32.0% vs 15.3%). Three-year cumulative incidence for Group 3 was 12.1% (vs 10.7% for controls). After adjusting for baseline covariates, risk of subsequent MOF was highest within 0–24 months following an index fracture, then decreased but remained elevated as compared to controls. Having two prior fractures, vertebral fractures and younger age at time of index fracture were associated with greater relative risk. Conclusions: Women with a history of osteoporotic fracture are at increased risk of subsequent fracture, which is highest during the first 24 months following a fracture. Younger women and those with vertebral fractures are at greatest relative risk, suggesting that treatment should target these patients and be timely enough to impact the period of imminent risk.
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| 5. |
- Toth, Emese, et al.
(författare)
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History of Previous Fracture and Imminent Fracture Risk in Swedish Women Aged 55 to 90 Years Presenting With a Fragility Fracture
- 2020
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 35:5, s. 861-868
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Tidskriftsartikel (refereegranskat)abstract
- The term “fracture cascade” refers to the sequence of fragility fractures resulting from the increased fracture risk that occurs with aging and following fractures. Here, we evaluate the sequence of previous fractures in women aged 55 to 90 years presenting with a fragility fracture and subsequent (12 to 24 months) fracture incidence. In this retrospective, observational study, women aged 55 to 90 years with an “index” fragility fracture in 2013 were identified from Swedish national registries. A history of previous fractures (2001 to 2012) and osteoporosis treatment was used to characterize fracture cascade patterns. Cumulative incidence of new fractures within 12 to 24 months following the index fracture, based on index fracture type and age, were used to describe the risk of subsequent fractures. A total of 35,146 women with a mean age of 73.8 years were included (7180 hip, 2786 clinical vertebral, and 25,180 nonhip/nonvertebral [NHNV] index fractures); 38% of women with hip, 38% with clinical vertebral, and 25% with NHNV index fractures had one or more previous fractures. Across all index fracture types, the proportion of women with any previous fracture increased with age; 34% to 46% of index hip or clinical vertebral fractures in women ≥70 years were not their first fracture. Following any index fracture, cumulative incidence of a new fracture over 24 months was over 11% (index clinical vertebral 18%; index hip 14%). Osteoporosis treatment rates were low both in patients with (27%) and without (18%) a previous fracture. These descriptive data demonstrate that almost one-third of women aged 55 to 90 years suffering a new fracture have had a previous fragility fracture. Fracture location influences incidence and type of subsequent fracture during the 24 months following a fragility fracture, with clinical vertebral fractures carrying the greatest imminent fracture risk. These data highlight the clinical impact and need for early, effective treatment soon after any fragility fracture.
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