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Kharazmi, M., Michaëlsson, K., Schilcher, J., Eriksson, N., Melhus, H., Wadelius, M. & Hallberg, P. (2019). A Genome-Wide Association Study of Bisphosphonate-Associated Atypical Femoral Fracture. Calcified Tissue International, 105(1), 51-67
Open this publication in new window or tab >>A Genome-Wide Association Study of Bisphosphonate-Associated Atypical Femoral Fracture
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2019 (English)In: Calcified Tissue International, ISSN 0171-967X, E-ISSN 1432-0827, Vol. 105, no 1, p. 51-67Article in journal (Refereed) Published
Abstract [en]

Atypical femoral fracture is a well-documented adverse reaction to bisphosphonates. It is strongly related to duration of bisphosphonate use, and the risk declines rapidly after drug withdrawal. The mechanism behind bisphosphonate-associated atypical femoral fracture is unclear, but a genetic predisposition has been suggested. With the aim to identify common genetic variants that could be used for preemptive genetic testing, we performed a genome-wide association study. Cases were recruited mainly through reports of adverse drug reactions sent to the Swedish Medical Products Agency on a nation-wide basis. We compared atypical femoral fracture cases (n=51) with population-based controls (n=4891), and to reduce the possibility of confounding by indication, we also compared with bisphosphonate-treated controls without a current diagnosis of cancer (n=324). The total number of single-nucleotide polymorphisms after imputation was 7,585,874. A genome-wide significance threshold of p<5x10(-8) was used to correct for multiple testing. In addition, we performed candidate gene analyses for a panel of 29 genes previously implicated in atypical femoral fractures (significance threshold of p<5.7x10(-6)). Compared with population controls, bisphosphonate-associated atypical femoral fracture was associated with four isolated, uncommon single-nucleotide polymorphisms. When cases were compared with bisphosphonate-treated controls, no statistically significant genome-wide association remained. We conclude that the detected associations were either false positives or related to the underlying disease, i.e., treatment indication. Furthermore, there was no significant association with single-nucleotide polymorphisms in the 29 candidate genes. In conclusion, this study found no evidence of a common genetic predisposition for bisphosphonate-associated atypical femoral fracture. Further studies of larger sample size to identify possible weakly associated genetic traits, as well as whole exome or whole-genome sequencing studies to identify possible rare genetic variation conferring a risk are warranted.

Place, publisher, year, edition, pages
SPRINGER, 2019
Keywords
Genome-wide association study, Atypical fractures, Bisphosphonate, Drug-related side effects and adverse reactions, Pharmacogenetics
National Category
Orthopaedics Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-386428 (URN)10.1007/s00223-019-00546-9 (DOI)000469477400005 ()31006051 (PubMedID)
Funder
Swedish Research Council, 521-2011-2440; 521-2014-337; 2015-035270Swedish Heart Lung FoundationScience for Life Laboratory - a national resource center for high-throughput molecular bioscienceErik, Karin och Gösta Selanders FoundationÖstergötland County Council
Available from: 2019-06-25 Created: 2019-06-25 Last updated: 2019-06-25Bibliographically approved
MacDowall, A., Canto Moreira, N., Marques, C., Skeppholm, M., Lindhagen, L., Robinson, Y., . . . Olerud, C. (2019). Artificial disc replacement versus fusion in patients with cervical degenerative disc disease and radiculopathy: a randomized controlled trial with 5-year outcomes. Journal of Neurosurgery: Spine, 30(3), 323-331
Open this publication in new window or tab >>Artificial disc replacement versus fusion in patients with cervical degenerative disc disease and radiculopathy: a randomized controlled trial with 5-year outcomes
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2019 (English)In: Journal of Neurosurgery: Spine, ISSN 1547-5654, E-ISSN 1547-5646, Vol. 30, no 3, p. 323-331Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE

The method of artificial disc replacement (ADR) has been developed as an alternative treatment to fusion surgery after decompression for cervical degenerative disc disease (DDD) with radiculopathy. Preserving the motion of ADR devices aims to prevent immobilization side effects such as adjacent-segment pathology (ASP). However, long-term follow-up evaluations using MRI are needed to investigate if this intent is achieved.

METHODS

The authors performed a randomized controlled trial with 153 patients (mean age 47 years) undergoing surgery for cervical radiculopathy. Eighty-three patients received an ADR and 70 patients underwent fusion surgery. Outcomes after 5 years were assessed using patient-reported outcome measures using the Neck Disability Index (NDI) score as the primary outcome; motion preservation and heterotopic ossification by radiography; ASP by MRI; and secondary surgical procedures.

RESULTS

Scores on the NDI were approximately halved in both groups: the mean score after 5 years was 36 (95% confidence interval [CI] 31–41) in the ADR group and 32 (95% CI 27–38) in the fusion group (p = 0.48). There were no other significant differences between the groups in six other patient-related outcome measures. Fifty-four percent of the patients in the ADR group preserved motion at the operated cervical level and 25% of the ADRs were spontaneously fused. Seventeen ADR patients (21%) and 7 fusion patients (10%) underwent secondary surgery (p = 0.11), with 5 patients in each group due to clinical ASP.

CONCLUSIONS

In patients with cervical DDD and radiculopathy decompression as well as ADR, surgery did not result in better clinical or radiological outcomes after 5 years compared with decompression and fusion surgery.

Keywords
artificial disc replacement, treatment outcome, Neck Disability Index, cervical radiculopathy, adjacent-segment pathology
National Category
Orthopaedics Neurology
Research subject
Orthopaedics
Identifiers
urn:nbn:se:uu:diva-345965 (URN)10.3171/2018.9.SPINE18659 (DOI)000462447900004 ()30641852 (PubMedID)
Projects
Cervical radiculopathy, studies on pain analysis and treatment
Note

Title in thesis list of papers: Artificial Disc Replacement versus Fusion in Patients with Cervical Degenerative Disc Disease with radiculopathy ‒ 5-year Outcomes

Available from: 2018-03-13 Created: 2018-03-13 Last updated: 2019-04-16Bibliographically approved
MacDowall, A., Skeppholm, M., Lindhagen, L., Robinson, Y., Löfgren, H., Michaëlsson, K. & Olerud, C. (2019). Artificial Disc Replacement versus Fusion in Patients with Cervical Degenerative Disc Disease with radiculopathy: 5-year Outcomes from the National Swedish Spine Register. Journal of Neurosurgery: Spine, 30(2), 159-167
Open this publication in new window or tab >>Artificial Disc Replacement versus Fusion in Patients with Cervical Degenerative Disc Disease with radiculopathy: 5-year Outcomes from the National Swedish Spine Register
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2019 (English)In: Journal of Neurosurgery: Spine, ISSN 1547-5654, E-ISSN 1547-5646, Vol. 30, no 2, p. 159-167Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: The long-term efficacy of artificial disc replacement (ADR) surgery compared with fusion after decompression for the treatment of cervical degenerative disc disease and radiculopathy has not previously been investigated in a population-based setting.

METHODS: All patients with cervical degenerative disc disease and radiculopathy who were in the national Swedish Spine Registry (Swespine) beginning in January 1, 2006, were eligible for the study. Follow-up information was obtained up to November 15, 2017. The authors compared, using propensity score matching, patients treated with anterior decompression and insertion of an ADR with patients who underwent anterior decompression combined with fusion surgery. The primary outcome was the Neck Disability Index (NDI), a patient-reported function score ranging from 0% to 100%, with higher scores indicating greater disability and a minimum clinically important difference of > 15%.

RESULTS: A total of 3998 patients (2018: 1980 women/men) met the inclusion criteria, of whom 204 had undergone arthroplasty and 3794 had undergone fusion. After propensity score matching, 185 patients with a mean age of 49.7 years remained in each group. Scores on the NDI were approximately halved in both groups after 5 years, but without a significant mean difference in NDI (3.0%; 95% CI -8.4 to 2.4; p = 0.28) between the groups. There were no differences between the groups in EuroQol-5 Dimensions or in pain scores for the neck and arm.

CONCLUSIONS: In patients with cervical degenerative disc disease and radiculopathy, decompression plus ADR surgery did not result in a clinically important difference in outcomes after 5 years, compared with decompression and fusion surgery.

Keywords
Cervical radiculopathy, Artificial disc replacement, Surgical treatment outcome, Anterior decompression and fusion
National Category
Orthopaedics
Research subject
Orthopaedics
Identifiers
urn:nbn:se:uu:diva-345976 (URN)10.3171/2018.7.SPINE18657 (DOI)000461013000002 ()30485205 (PubMedID)
Projects
Cervical radiculopathy, studies on pain analysis and treatment
Available from: 2018-03-13 Created: 2018-03-13 Last updated: 2019-04-16Bibliographically approved
Yuan, S., Michaëlsson, K., Wan, Z. & Larsson, S. C. (2019). Associations of Smoking and Alcohol and Coffee Intake with Fracture and Bone Mineral Density: A Mendelian Randomization Study. Calcified Tissue International, 105(6), 582-588
Open this publication in new window or tab >>Associations of Smoking and Alcohol and Coffee Intake with Fracture and Bone Mineral Density: A Mendelian Randomization Study
2019 (English)In: Calcified Tissue International, ISSN 0171-967X, E-ISSN 1432-0827, Vol. 105, no 6, p. 582-588Article in journal (Refereed) Published
Abstract [en]

The causal associations of smoking and alcohol and coffee intake with fracture and bone mineral density are unknown. We investigated the associations using Mendelian randomization (MR). Summary-level data from UK Biobank for bone fractures (main outcome) (53,184 cases; 373,611 non-cases) and estimated bone mineral density (eBMD) (n = 426,824 individuals) were used. Single-nucleotide polymorphisms associated with smoking initiation (n = 378) and alcohol (n = 99) and coffee (n = 15) intake at the genome-wide significance threshold (P = 5 x 10(-8)) were identified from published genome-wide association studies. Univariable and multivariable inverse-variance weighted, weighted median, MR-Egger, and MR-PRESSO methods were used for statistical analyses. Genetic predisposition to smoking initiation was associated with fracture but not eBMD. The odds ratio of fracture per one-unit increase in log odds of smoking was 1.09 (95% confidence interval 1.04, 1.15; P = 8.58 x 10(-4)) after adjustment for alcohol intake in the multivariable MR analysis. The association remained in complementary analyses. Genetically predicted alcohol and coffee intake was not associated with fracture or eBMD. Nevertheless, genetic liability to alcohol dependence, based on variants in the ALD1B gene, was associated with fracture and lower eBMD. The odds ratio was 1.06 (95% confidence interval 1.01, 1.12; P = 0.018) per genetically predicted one-unit higher log odds of liability to alcohol dependence. This MR study strengthens the causal inference on an association between smoking and higher fracture risk but found no linear association of modestly higher alcohol and coffee intake with fracture or BMD. However, alcohol dependence may increase fracture risk.

Keywords
Alcohol, Bone mineral density, Coffee, Fracture, Mendelian randomization, Smoking
National Category
Orthopaedics
Identifiers
urn:nbn:se:uu:diva-397666 (URN)10.1007/s00223-019-00606-0 (DOI)000493763200002 ()31482193 (PubMedID)
Available from: 2019-11-28 Created: 2019-11-28 Last updated: 2019-11-28Bibliographically approved
Warensjö Lemming, E., Byberg, L., Stattin, K., Ahmad, S., Lind, L., Elmsfahl, S., . . . Michaëlsson, K. (2019). Dietary Pattern Specific Protein Biomarkers for Cardiovascular Disease: A Cross-Sectional Study in 2 Independent Cohorts. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 8(11), Article ID e011860.
Open this publication in new window or tab >>Dietary Pattern Specific Protein Biomarkers for Cardiovascular Disease: A Cross-Sectional Study in 2 Independent Cohorts
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2019 (English)In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 8, no 11, article id e011860Article in journal (Refereed) Published
Abstract [en]

Background: Mechanisms related to the influence of diet on the development of cardiovascular disease are not entirely understood, and protein biomarkers may help to understand these pathways. Studies of biomarkers identified with multiplex proteomic methods and dietary patterns are largely lacking.

Methods and Results: Dietary patterns were generated through principal component analysis in 2 population‐based Swedish cohorts, the EpiHealth (EpiHealth study; n=20 817 men and women) and the SMCC (Swedish Mammography Cohort Clinical [n=4650 women]). A set of 184 protein cardiovascular disease biomarkers were measured with 2 high‐throughput, multiplex immunoassays. Discovery and replication multivariable linear regression analyses were used to investigate the associations between the principal component analysis–generated dietary patterns and the cardiovascular disease–associated protein biomarkers, first in the EpiHealth (n=2240) and then in the Swedish Mammography Cohort Clinical. Four main dietary patterns were identified in the EpiHealth, and 3 patterns were identified in the Swedish Mammography Cohort Clinical. The healthy and the Western/traditional patterns were found in both cohorts. In the EpiHealth, 57 protein biomarkers were associated with 3 of the dietary patterns, and 41 of these associations were replicated in the Swedish Mammography Cohort Clinical, with effect estimates ranging from 0.057 to 0.083 (P‐value range, 5.0×10−2–1.4×10−9) for each SD increase in the relative protein concentration. Independent associations were established between dietary patterns and the 21 protein biomarkers. Two proteins, myeloperoxidase and resistin, were associated with both the healthy and the light meal pattern but in opposite directions.

Conclusions: We have discovered and replicated independent associations between dietary patterns and 21 biomarkers linked to cardiovascular disease, which have a role in the pathways related to inflammation, endothelial and immune function, cell adhesion, and metabolism

Keywords
cardiovascular disease, dietary patterns, EpiHealth study, inflammation, proteomics, Swedish Mammography Cohort Clinical
National Category
Nutrition and Dietetics
Identifiers
urn:nbn:se:uu:diva-394981 (URN)10.1161/JAHA.118.011860 (DOI)000484576200019 ()31433701 (PubMedID)
Funder
Swedish Research Council, 2017-06100Swedish Research Council, 2015-05997Swedish Research Council, 2015-03257Forte, Swedish Research Council for Health, Working Life and Welfare, 2017-00721Swedish Research Council, 2017/49 (180)
Available from: 2019-10-11 Created: 2019-10-11 Last updated: 2019-10-11Bibliographically approved
Karasik, D., Zillikens, M. C., Hsu, Y.-H., Aghdassi, A., Akesson, K., Amin, N., . . . Ohlsson, C. (2019). Disentangling the genetics of lean mass. American Journal of Clinical Nutrition, 109(2), 276-287
Open this publication in new window or tab >>Disentangling the genetics of lean mass
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2019 (English)In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 109, no 2, p. 276-287Article in journal (Refereed) Published
Abstract [en]

Background: Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass. Objectives: To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci. Methods: We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age(2), and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms). Results: Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R). In contrast, loci with an impact specifically on LMwere termed "body builder" loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection. Conclusions: In conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.

Place, publisher, year, edition, pages
Oxford University Press, 2019
Keywords
body composition, skeletal muscle, body fat, meta-analysis of genome-wide association studies, metabolic profile
National Category
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-380499 (URN)10.1093/ajcn/nqy272 (DOI)000460615600007 ()30721968 (PubMedID)
Available from: 2019-04-23 Created: 2019-04-23 Last updated: 2019-04-23Bibliographically approved
Ludvigsson, J. F., Mahl, M., Sachs, M. C., Björk, J., Michaëlsson, K., Ekbom, A., . . . Olen, O. (2019). Fracture Risk in Patients With Inflammatory Bowel Disease: A Nationwide Population-Based Cohort Study From 1964 to 2014. American Journal of Gastroenterology, 114(2), 291-304
Open this publication in new window or tab >>Fracture Risk in Patients With Inflammatory Bowel Disease: A Nationwide Population-Based Cohort Study From 1964 to 2014
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2019 (English)In: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 114, no 2, p. 291-304Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION:Most studies on fractures in inflammatory bowel disease (IBD) are based on patients from tertiary centers or patients followed up before the introduction of immunomodulators or biologics. In addition, the role of corticosteroids in fracture risk has rarely been examined.METHODS:We conducted a nationwide population-based cohort study of 83,435 patients with incident IBD (ulcerative colitis [UC]: n = 50,162, Crohn's disease [CD]: n = 26,763, and IBD unclassified: 6,510) and 825,817 reference individuals from 1964 to 2014. Using multivariable Cox regression, we estimated hazard ratios (HRs) for hip fracture and any fracture and the association with cumulative corticosteroid exposure.RESULTS:During 1,225,415 person-years of follow-up in patients with IBD, there were 2,491 first-time hip fractures (203/100,000 person-years) compared with 20,583 hip fractures during 12,405,642 person-years in reference individuals (159/100,000 person-years). This corresponded to an HR of 1.42 (95% confidence interval [CI] = 1.36-1.48). The risk for hip fracture was higher in CD compared with UC (P < 0.001). Inflammatory bowel disease was also associated with any fracture (IBD: HR = 1.18; 95% CI = 1.15-1.20). Hazard ratios for hip fracture had not changed since the introduction of immunomodulators or biologics. Increasing exposure to corticosteroids was associated with hip fracture in both IBD and non-IBD individuals (P < 0.001), but only in elderly (>60 years) patients with IBD. The association between IBD and hip fracture was nonsignificant among individuals without corticosteroids (HR = 1.11; 95% CI = 0.86-1.44).CONCLUSIONS:Inflammatory bowel disease (CD and UC) is associated with an increased risk of hip fracture and any fracture, but not in individuals without a history of corticosteroid treatment. The association between corticosteroids and hip fracture was restricted to elderly patients with IBD.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2019
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-382476 (URN)10.14309/ajg.0000000000000062 (DOI)000463158000020 ()30730858 (PubMedID)
Funder
Swedish Foundation for Strategic Research Swedish Cancer SocietySwedish Society of MedicineStockholm County CouncilThe Karolinska Institutet's Research Foundation
Available from: 2019-04-30 Created: 2019-04-30 Last updated: 2019-04-30Bibliographically approved
Yuan, S., Jiang, X., Michaëlsson, K. & Larsson, S. C. (2019). Genetic Prediction of Serum 25-Hydroxyvitamin D, Calcium, and Parathyroid Hormone Levels in Relation to Development of Type 2 Diabetes: A Mendelian Randomization Study. Diabetes Care, 42(12), 2197-2203
Open this publication in new window or tab >>Genetic Prediction of Serum 25-Hydroxyvitamin D, Calcium, and Parathyroid Hormone Levels in Relation to Development of Type 2 Diabetes: A Mendelian Randomization Study
2019 (English)In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 42, no 12, p. 2197-2203Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE We conducted a Mendelian randomization study to investigate the associations of genetically predicted serum 25-hydroxyvitamin D (S-25OHD), calcium (S-Ca), and parathyroid hormone (S-PTH) levels with type 2 diabetes (T2DM). RESEARCH DESIGN AND METHODS Seven, six, and five single nucleotide polymorphisms (SNPs) associated with S-25OHD, S-Ca, and S-PTH levels, respectively, were used as instrumental variables. Data on T2DM were available for 74,124 case subjects with T2DM and 824,006 control subjects. The inverse variance-weighted method was used for the primary analyses, and the weighted median and Mendelian randomization (MR)-Egger methods were used for supplementary analyses. RESULTS Genetically predicted S-25OHD but not S-Ca and S-PTH levels were associated with T2DM in the primary analyses. For 1 SD increment of S-25OHD levels, the odds ratio (OR) of T2DM was 0.94 (95% CI 0.88-0.99; P = 0.029) in an analysis based on all seven SNPs and 0.90 (95% CI 0.83-0.98; P = 0.011) in an analysis based on three SNPs within or near genes involved in vitamin D synthesis. Only the association based on the SNPs involved in vitamin D synthesis remained in the weighted median analysis, and no pleiotropy was detected (P = 0.153). Pleiotropy was detected in the analysis of S-Ca (P = 0.013). After correcting for this bias using MR-Egger regression, the OR of T2DM per 1 SD increment of S-Ca levels was 1.41 (95% CI 1.12-1.77; P = 0.003). CONCLUSIONS Modest lifelong higher S-25OHD levels were associated with reduced odds of T2DM, but the association was only robust for SNPs in the vitamin D synthesis pathway. The possible role of S-Ca levels for T2DM development requires further research.

Place, publisher, year, edition, pages
AMER DIABETES ASSOC, 2019
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-400010 (URN)10.2337/dc19-1247 (DOI)000498634000014 ()31548248 (PubMedID)
Funder
Swedish Research CouncilForte, Swedish Research Council for Health, Working Life and Welfare
Available from: 2019-12-19 Created: 2019-12-19 Last updated: 2019-12-19Bibliographically approved
Cerani, A., Zhou, S., Forgetta, V., Morris, J. A., Trajanoska, K., Rivadeneira, F., . . . Richards, J. B. (2019). Genetic predisposition to increased serum calcium, bone mineral density, and fracture risk in individuals with normal calcium levels: mendelian randomisation study. BMJ. British Medical Journal, 366, Article ID l4410.
Open this publication in new window or tab >>Genetic predisposition to increased serum calcium, bone mineral density, and fracture risk in individuals with normal calcium levels: mendelian randomisation study
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2019 (English)In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 366, article id l4410Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To determine if genetically increased serum calcium levels are associated with improved bone mineral density and a reduction in osteoporotic fractures. DESIGN Mendelian randomisation study.

SETTING: Cohorts used included: the UK Biobank cohort, providing genotypic and estimated bone mineral density data; 25 cohorts from UK, USA, Europe, and China, providing genotypic and fracture data; and 17 cohorts from Europe, providing genotypic and serum calcium data (summary level statistics).

PARTICIPANTS: A genome-wide association meta-analysis of serum calcium levels in up to 61 079 individuals was used to identify genetic determinants of serum calcium levels. The UK Biobank study was used to assess the association of genetic predisposition to increased serum calcium with estimated bone mineral density derived from heel ultrasound in 426 824 individuals who had, on average, calcium levels in the normal range. A fracture genome-wide association metaanalysis comprising 24 cohorts and the UK Biobank including a total of 76 549 cases and 470 164 controls, who, on average, also had calcium levels in the normal range was then performed.

RESULTS: A standard deviation increase in genetically derived serum calcium (0.13 mmol/L or 0.51 mg/dL) was not associated with increased estimated bone mineral density (0.003 g/cm(2), 95% confidence interval -0.059 to 0.066; P=0.92) or a reduced risk of fractures (odds ratio 1.01, 95% confidence interval 0.89 to 1.15; P=0.85) in inverse-variance weighted mendelian randomisation analyses. Sensitivity analyses did not provide evidence of pleiotropic effects.

CONCLUSIONS: Genetic predisposition to increased serum calcium levels in individuals with normal calcium levels is not associated with an increase in estimated bone mineral density and does not provide clinically relevant protection against fracture. Whether such predisposition mimics the effect of short term calcium supplementation is not known. Given that the same genetically derived increase in serum calcium is associated with an increased risk of coronary artery disease, widespread calcium supplementation in the general population could provide more risk than benefit.

Place, publisher, year, edition, pages
BMJ PUBLISHING GROUP, 2019
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-392134 (URN)10.1136/bmj.l4410 (DOI)000479164000001 ()31371314 (PubMedID)
Available from: 2019-09-02 Created: 2019-09-02 Last updated: 2019-09-02Bibliographically approved
Kaluza, J., Håkansson, N., Harris, H. R., Orsini, N., Michaëlsson, K. & Wolk, A. (2019). Influence of anti-inflammatory diet and smoking on mortality and survival in men and women: two prospective cohort studies.. Journal of Internal Medicine, 285(1), 75-91
Open this publication in new window or tab >>Influence of anti-inflammatory diet and smoking on mortality and survival in men and women: two prospective cohort studies.
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2019 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 285, no 1, p. 75-91Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The associations between an anti-inflammatory diet and both all-cause and cause-specific mortality have been studied previously; however, the influence of an anti-inflammatory diet on survival time has not been investigated. Moreover, the potential modification of these associations by smoking status remains unclear.

OBJECTIVE: The aims of this study were to examine the associations between an anti-inflammatory diet index (AIDI) and all-cause and cause-specific mortality, to determine the association between the AIDI and differences in survival time and to assess effect modification by smoking status.

METHODS: The study population included 68 273 Swedish men and women (aged 45-83 years) at baseline. The anti-inflammatory potential of the diet was estimated using the validated AIDI, which includes 11 potential anti-inflammatory and five potential pro-inflammatory foods. Cox proportional hazards and Laplace regression were used to estimate hazard ratios and differences in survival time.

RESULTS: During 16 years of follow-up (1 057 959 person-years), 16 088 deaths [5980 due to cardiovascular disease (CVD) and 5252 due to cancer] were recorded. Participants in the highest versus lowest quartile of the AIDI had lower risks of all-cause (18% reduction, 95% CI: 14-22%), CVD (20%, 95% CI: 14-26%) and cancer (13%, 95% CI: 5-20%) mortality. The strongest inverse associations between the highest and lowest quartiles of AIDI and risk of mortality were observed in current smokers: 31%, 36% and 22% lower risks of all-cause, CVD and cancer mortality, respectively. The difference in survival time between current smokers in the lowest AIDI quartile and never smokers in the highest quartile was 4.6 years.

CONCLUSION: Adherence to a diet with high anti-inflammatory potential may reduce all-cause, CVD and cancer mortality and prolong survival time especially amongst smokers.

Keywords
anti-inflammatory index, diet, inflammation, mortality, prospective study, survival time
National Category
Orthopaedics
Identifiers
urn:nbn:se:uu:diva-367524 (URN)10.1111/joim.12823 (DOI)000453771200006 ()30209831 (PubMedID)
Available from: 2018-11-30 Created: 2018-11-30 Last updated: 2019-01-16Bibliographically approved
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