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| 2. |
- Teumer, A., et al.
(författare)
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Genomewide meta-analysis identifies loci associated with IGF-I and IGFBP-3 levels with impact on age-related traits
- 2016
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Ingår i: Aging Cell. - : Wiley. - 1474-9718 .- 1474-9726. ; 15:5, s. 811-824
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Tidskriftsartikel (refereegranskat)abstract
- The growth hormone/insulin-like growth factor (IGF) axis can be manipulated in animal models to promote longevity, and IGF-related proteins including IGF-I and IGF-binding protein-3 (IGFBP-3) have also been implicated in risk of human diseases including cardiovascular diseases, diabetes, and cancer. Through genomewide association study of up to 30884 adults of European ancestry from 21 studies, we confirmed and extended the list of previously identified loci associated with circulating IGF-I and IGFBP-3 concentrations (IGF1, IGFBP3, GCKR, TNS3, GHSR, FOXO3, ASXL2, NUBP2/IGFALS, SORCS2, and CELSR2). Significant sex interactions, which were characterized by different genotype–phenotype associations between men and women, were found only for associations of IGFBP-3 concentrations with SNPs at the loci IGFBP3 and SORCS2. Analyses of SNPs, gene expression, and protein levels suggested that interplay between IGFBP3 and genes within the NUBP2 locus (IGFALS and HAGH) may affect circulating IGF-I and IGFBP-3 concentrations. The IGF-I-decreasing allele of SNP rs934073, which is an eQTL of ASXL2, was associated with lower adiposity and higher likelihood of survival beyond 90years. The known longevity-associated variant rs2153960 (FOXO3) was observed to be a genomewide significant SNP for IGF-I concentrations. Bioinformatics analysis suggested enrichment of putative regulatory elements among these IGF-I- and IGFBP-3-associated loci, particularly of rs646776 at CELSR2. In conclusion, this study identified several loci associated with circulating IGF-I and IGFBP-3 concentrations and provides clues to the potential role of the IGF axis in mediating effects of known (FOXO3) and novel (ASXL2) longevity-associated loci. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
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| 3. |
- Axelsson, Kristian F, 1973, et al.
(författare)
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Association Between Alendronate Use and Hip Fracture Risk in Older Patients Using Oral Prednisolone
- 2017
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Ingår i: Jama-Journal of the American Medical Association. - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 318:2, s. 146-155
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Oral glucocorticoid treatment increases fracture risk, and evidence is lacking regarding the efficacy of alendronate to protect against hip fracture in older patients using glucocorticoids. OBJECTIVE To investigate whether alendronate treatment in older patients using oral prednisolone is associated with decreased hip fracture risk and adverse effects. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study using a national database (N = 433 195) of patients aged 65 years or older undergoing a health evaluation (baseline) at Swedish health care facilities; 1802 patients who were prescribed alendronate after at least 3 months of oral prednisolone treatment (>= 5mg/d) were identified. Propensity score matching was used to select 1802 patients without alendronate use from 6076 patients taking prednisolone with the same dose and treatment time criteria. Follow-up occurred between January 2008 and December 2014. EXPOSURES Alendronate vs no alendronate use; no patients had previously taken alendronate at the time of prednisolone initiation. MAIN OUTCOMES AND MEASURES The primary outcome was incident hip fracture. RESULTS Of the 3604 included patients, the mean age was 79.9 (SD, 7.5) years, and 2524 (70%) were women. After a median follow-up of 1.32 years (interquartile range, 0.57-2.34 years), there were 27 hip fractures in the alendronate group and 73 in the no-alendronate group, corresponding to incidence rates of 9.5 (95% CI, 6.5-13.9) and 27.2 (95% CI, 21.6-34.2) fractures per 1000 person-years, with an absolute rate difference of -17.6 (95% CI, -24.8 to -10.4). The use of alendronate was associated with a lower risk of hip fracture in a multivariable-adjusted Cox model (hazard ratio, 0.35; 95% CI, 0.22-0.54). Alendronate treatment was not associated with increased risk of mild upper gastrointestinal tract symptoms (alendronate vs no alendronate, 15.6 [95% CI, 11.6-21.0] vs 12.9 [95% CI, 9.3-18.0] per 1000 person-years; P=.40) or peptic ulcers (10.9 [95% CI, 7.7-15.5] vs 11.4 [95% CI, 8.0-16.2] per 1000 person-years; P=.86). There were no cases of incident drug-induced osteonecrosis and only 1 case of femoral shaft fracture in each group. CONCLUSIONS AND RELEVANCE Among older patients using medium to high doses of prednisolone, alendronate treatment was associated with a significantly lower risk of hip fracture over a median of 1.32 years. Although the findings are limited by the observational study design and the small number of events, these results support the use of alendronate in this patient group.
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| 4. |
- Axelsson, K. F., et al.
(författare)
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Effectiveness of a minimal resource fracture liaison service
- 2016
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Ingår i: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 27:11, s. 3165-3175
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The purpose of this study was to investigate if a 2-year intervention with a minimal resource fracture liaison service (FLS) was associated with increased investigation and medical treatment and if treatment was related to reduced re-fracture risk.METHODS: The FLS started in 2013 using existing secretaries (without an FLS coordinator) at the emergency department and orthopaedic wards to identify risk patients. All patients older than 50 years of age with a fractured hip, vertebra, shoulder, wrist or pelvis were followed during 2013-2014 (n = 2713) and compared with their historic counterparts in 2011-2012 (n = 2616) at the same hospital. Re-fractures were X-ray verified. A time-dependent adjusted (for age, sex, previous fracture, index fracture type, prevalent treatment, comorbidity and secondary osteoporosis) Cox model was used.RESULTS: The minimal resource FLS increased the proportion of DXA-investigated patients after fracture from 7.6 to 39.6 % (p < 0.001) and the treatment rate after fracture from 12.6 to 31.8 %, which is well in line with FLS types using the conventional coordinator model. Treated patients had a 51 % lower risk of any re-fracture than untreated patients (HR 0.49, 95 % CI 0.37-0.65 p < 0.001).CONCLUSIONS: We found that our minimal resource FLS was effective in increasing investigation and treatment, in line with conventional coordinator-based services, and that treated patients had a 51 % reduced risk of new fractures, indicating that also non-coordinator based fracture liaison services can improve secondary prevention of fractures.
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| 5. |
- Axelsson, Kristian F, 1973, et al.
(författare)
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Fracture risk after gastric bypass surgery – a retrospective cohort study
- 2018
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Ingår i: Journal of Bone and Mineral Research. - : Wiley-Blackwell Publishing Inc.. - 0884-0431 .- 1523-4681. ; 33:12, s. 2122-2131
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Tidskriftsartikel (refereegranskat)abstract
- Gastric bypass surgery constitutes the most common and effective bariatric surgery to treat obesity. Gastric bypass leads to bone loss, but fracture risk following surgery has been insufficiently studied. Furthermore, the association between gastric bypass and fracture risk has not been studied in patients with diabetes, which is a risk factor for fracture and affected by surgery. In this retrospective cohort study using Swedish national databases, 38 971 obese patients undergoing gastric bypass were identified, 7758 with diabetes and 31 213 without. An equal amount of well-balanced controls were identified through multivariable 1:1 propensity score matching. The risk of fracture and fall injury was investigated using Cox proportional hazards and flexible parameter models. Fracture risk according to weight loss and degree of calcium and vitamin D supplementation one-year post- surgery was investigated. During a median follow-up time of 3.1 (IQR 1.7-4.6) years, gastric bypass was associated with increased risk of any fracture, in patients with and without diabetes using a multivariable Cox model (HR 1.26, 95% CI 1.05- 1.53 and HR 1.32, 95% CI 1.18-1.47, respectively). Using flexible parameter models, the fracture risk appeared to increase with time. The risk of fall injury without fracture was also increased after gastric bypass. Larger weight loss or poor calcium and vitamin D supplementation after surgery were not associated with increased fracture risk. In conclusion, gastric bypass surgery is associated with an increased fracture risk, which appears to be increasing with time and not associated with degree of weight loss or calcium and vitamin D supplementation following surgery. An increased risk of fall injury was seen after surgery, which could contribute to the increased fracture risk. This article is protected by copyright. All rights reserved.
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| 6. |
- Axelsson, K. F., et al.
(författare)
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Hip fracture risk and safety with alendronate treatment in the oldest-old
- 2017
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 282:6, s. 546-559
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Tidskriftsartikel (refereegranskat)abstract
- Background. There is high evidence for secondary prevention of fractures, including hip fracture, with alendronate treatment, but alendronate's efficacy to prevent hip fractures in the oldest-old (80 years old), the population with the highest fracture risk, has not been studied. Objective. To investigate whether alendronate treatment amongst the oldest-old with prior fracture was related to decreased hip fracture rate and sustained safety. Methods. Using a national database of men and women undergoing a fall risk assessment at a Swedish healthcare facility, we identified 90 795 patients who were 80 years or older and had a prior fracture. Propensity score matching (four to one) was then used to identify 7844 controls to 1961 alendronate-treated patients. The risk of incident hip fracture was investigated with Cox models and the interaction between age and treatment was investigated using an interaction term. Results. The case and control groups were well balanced in regard to age, sex, anthropometrics and comorbidity. Alendronate treatment was associated with a decreased risk of hip fracture in crude (hazard ratio (HR) 0.62 (0.49-0.79), P < 0.001) and multivariable models (HR 0.66 (0.51-0.86), P < 0.01). Alendronate was related to reduced mortality risk (HR 0.88 (0.82-0.95) but increased risk of mild upper gastrointestinal symptoms (UGI) (HR 1.58 (1.12-2.24). The alendronate association did not change with age for hip fractures or mild UGI. Conclusion. In old patients with prior fracture, alendronate treatment reduces the risk of hip fracture with sustained safety, indicating that this treatment should be considered in these high-risk patients.
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| 8. |
- Brembeck, Petra, 1977, et al.
(författare)
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Changes in cortical volumetric bone mineral density and thickness, and trabecular thickness in lactating women postpartum.
- 2015
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 100:2, s. 535-543
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Tidskriftsartikel (refereegranskat)abstract
- Context: Lactation is associated with decreased areal bone mineral density (aBMD). Replenishment occurs especially after ceased lactation. Changes in volumetric BMD (vBMD), microstructure and dimensional parameters are unknown and may clarify the role of lactation for skeletal health. Objective: and main outcomes: To test the hypothesis that lactation is associated with changes in aBMD, vBMD, microstructure and dimensional parameters. Design: At baseline (0.5 months after delivery) and 4, 12 and 18 months thereafter bone was assessed using dual energy x-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT). Participants: and setting: Eighty-one fair-skinned postpartum women and 21 controls aged 25-40 years were recruited. Completion ratio was 73%. Postpartum women were categorized depending on duration of lactation; 0-3.9, 4-8.9 and ≥9 months. Results: During the first 4 months, aBMD decreased at several sites (geometric mean±SE; -0.73±0.21% to -3.98±0.76%) in women lactating at least 4 months. During the same time, cortical vBMD at ultra-distal tibia decreased in women lactating 4-8.9 months (-0.26±0.08%) and ≥9 months (-0.49±0.10%). At 12 months postpartum, also cortical thickness (≥9 months, -2.48±0.41%) and trabecular thickness (4-8.9 months, -2.14±0.92%; ≥9 months, -2.56±1.21%) were lower than baseline. No decreases were found in women lactating less than 4 months or in controls in these parameters. At 18 months postpartum, both cortical vBMD (≥9 months, -0.77±0.17%) and trabecular thickness (4-8.9 months, -2.25±1.25%; ≥9 months, -3.21±1.41%) were lower in women with long lactation. Conclusions: Decreases in cortical vBMD, thickness, and trabecular thickness at ultra-distal tibia were found in women lactating 4 months or longer. Longer follow-up is needed to confirm whether women with extended lactation recover fully, or whether the changes could potentially lead to increased risk of fracture in later life.
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| 9. |
- Brembeck, Petra, 1977, et al.
(författare)
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Determinants of microstructural, dimensional and bone mineral changes postpartum in Swedish women.
- 2016
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Ingår i: The British journal of nutrition. - 1475-2662. ; 116:10, s. 1736-44
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Tidskriftsartikel (refereegranskat)abstract
- During lactation, areal (a) and volumetric (v) bone mineral density (BMD) are known to temporarily decrease. Factors that affect skeletal changes postpartum are not fully elucidated. The aim was to study determinants of the previously observed changes in aBMD at lumbar spine, and cortical vBMD, microstructure and dimensions at ultra-distal tibia postpartum. Women (25-40 years) were studied longitudinally at 2 weeks (baseline) and 4 months (n 81), 12 months (n 79) and 18 months (n 58) postpartum. At each visit, blood samples were collected, body weight and height were measured and information about lactation habits, oestrogen contraceptives and physical activity was obtained. Ca intake was measured using 4-d food diaries at 4 months postpartum. Serum 25-hydroxyvitamin D (25OHD) was analysed by liquid chromatography-tandem MS. Skeletal changes were assessed with dual-energy X-ray absorptiometry and high-resolution peripheral quantitative computed tomography. Mean baseline BMI was 24·8 (sd 3·1) kg/m2. Median (quartiles 1-3) duration of total lactation was 8·1 (6·8-10·4) months. Longer duration of full lactation was associated with larger decreases of lumbar spine aBMD and tibia vBMD and microstructure. Higher baseline body weight was associated with smaller decreases in tibia vBMD and microstructure. Higher Ca intake was associated with smaller decreases in tibia cortical vBMD and thickness. Higher baseline 25OHD was only associated with larger decreases in lumbar spine aBMD. In conclusion, lactation and body weight were the main determinants of skeletal changes during the first 18 months postpartum. Ca intake and serum concentrations of 25OHD appear to have different associations with cortical and trabecular bone.
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| 10. |
- Chotiyarnwong, P., et al.
(författare)
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Temporal changes in access to FRAX (R) in Thailand between 2010 and 2018
- 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
- The usage of FRAX (R) tool in Thailand and other countries was explored using Google Analytics data. Over the period 2010-2018, Thailand ranked 35th in the world for FRAX usage (the US is ranked first). Incorporation of FRAX into a national osteoporosis guideline in Thailand appears to have increased its usage.PurposeTo document access to the web-based FRAX (R) tool and specifically its access in Thailand between 2010 and 2018.MethodsA descriptive retrospective study using data from Google Analytics that provides numerical and geographical information on internet access to the FRAX tool website worldwide.ResultIn Thailand, Bangkok is the highest ranked site for FRAX access with more than 20,000 usage sessions since 2010 (3.6 usage session per 1000 population) followed by Khon Kaen and Chiang Mai. It has been accessed from within 76 out of 77 provinces (98.7%). There was a steady increase in access to FRAX from within Thailand of approximately 1000 usage sessions per year between 2010 and 2016. After the FRAX fracture risk calculation was included in the national guideline for osteoporosis management published in late 2016, the rate of increase in access was four-fold higher compared with the previous period. In world ranking, the USA is the country with the most frequent access to the FRAX tool, whereas Thailand was ranked 35th in the world. There were weak but significant correlations between the absolute number of FRAX sessions and population size (r=0.165, p=0.011) and land area (r=0.375, p<0.001).ConclusionAccess to the FRAX tool website is increasing in Thailand. The incorporation of FRAX into national guidelines, in parallel to the adoption of osteoporosis fracture prevention into national policy, has had a rapid and significant impact on its use.
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