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- Medina-Gomez, C., et al.
(författare)
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Bone mineral density loci specific to the skull portray potential pleiotropic effects on craniosynostosis
- 2023
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Ingår i: Communications Biology. - 2399-3642. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Skull bone mineral density (SK-BMD) provides a suitable trait for the discovery of key genes in bone biology, particularly to intramembranous ossification, not captured at other skeletal sites. We perform a genome-wide association meta-analysis (n similar to 43,800) of SK-BMD, identifying 59 loci, collectively explaining 12.5% of the trait variance. Association signals cluster within gene-sets involved in skeletal development and osteoporosis. Among the four novel loci (ZIC1, PRKAR1A, AZIN1/ATP6V1C1, GLRX3), there are factors implicated in intramembranous ossification and as we show, inherent to craniosynostosis processes. Functional follow-up in zebrafish confirms the importance of ZIC1 on cranial suture patterning. Likewise, we observe abnormal cranial bone initiation that culminates in ectopic sutures and reduced BMD in mosaic atp6v1c1 knockouts. Mosaic prkar1a knockouts present asymmetric bone growth and, conversely, elevated BMD. In light of this evidence linking SK-BMD loci to craniofacial abnormalities, our study provides new insight into the pathophysiology, diagnosis and treatment of skeletal diseases.
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| 5. |
- Filippini, T, et al.
(författare)
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Dietary Acrylamide Exposure and Risk of Site-Specific Cancer: A Systematic Review and Dose-Response Meta-Analysis of Epidemiological Studies
- 2022
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Ingår i: Frontiers in nutrition. - : Frontiers Media SA. - 2296-861X. ; 9, s. 875607-
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Forskningsöversikt (övrigt vetenskapligt/konstnärligt)abstract
- Diet is a main source of acrylamide exposure to humans. Existing observational data on the relationship between dietary exposure to acrylamide and risk of cancer are inconsistent. We performed a systematic review and dose-response meta-analysis of epidemiological studies evaluating the association between dietary acrylamide exposure and several site-specific cancer. A systematic literature search was conducted in PubMed, Scopus, and Web of Science databases until March 7, 2022. Studies were eligible if they were carried out in non-occupationally exposed adults, assessed dietary acrylamide exposure (μg/day) and reported risk estimates of cancer incidence (all but gynecological cancers). Using a random-effects model, we performed a meta-analysis of site-specific cancer risk comparing the highest vs. lowest category of dietary acrylamide exposure. We also carried out a one-stage dose-response meta-analysis assessing the shape of the association. Out of 1,994 papers screened, 31 were eligible (total of 16 studies), which included 1,151,189 participants in total, out of whom 48,175 developed cancer during the median follow-up period of 14.9 years (range 7.3–33.9). The mean estimated dose of dietary acrylamide across studies was 23 μg/day. Pooled analysis showed no association between the highest vs. lowest dietary acrylamide exposure and each site-specific cancer investigated, with no evidence of thresholds in the dose-response meta-analysis. There were also no associations between dietary acrylamide exposure and the risk of cancers when stratifying by smoking status, except for increased risk of lung cancer in smokers. In conclusion, high dietary acrylamide exposure was not associated with an increased risk of site-specific non-gynecological cancer.
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| 6. |
- Lems, W., et al.
(författare)
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Vertebral fracture : epidemiology, impact and use of DXA vertebral fracture assessment in fracture liaison services
- 2021
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 32:3, s. 399-411
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Tidskriftsartikel (refereegranskat)abstract
- Summary: Vertebral fractures are independent risk factors for vertebral and nonvertebral fractures. Since vertebral fractures are often missed, the relatively new introduction of vertebral fracture assessment (VFA) for imaging of the lateral spine during DXA-measurement of the spine and hips may contribute to detect vertebral fractures. We advocate performing a VFA in all patients with a recent fracture visiting a fracture liaison service (FLS). Fracture liaison services (FLS) are important service models for delivering secondary fracture prevention for older adults presenting with a fragility fracture. While commonly age, clinical risk factors (including fracture site and number of prior fracture) and BMD play a crucial role in determining fracture risk and indications for treatment with antiosteoporosis medications, prevalent vertebral fractures usually remain undetected. However, vertebral fractures are important independent risk factors for future vertebral and nonvertebral fractures. A development of the DXA technology, vertebral fracture assessment (VFA), allows for assessment of the lateral spine during the regular DXA bone mineral density measurement of the lumbar spine and hips. Recent approaches to the stratification of antiosteoporosis medication type according to baseline fracture risk, and differences by age in the indication for treatment by prior fracture mean that additional information from VFA may influence initiation and type of treatment. Furthermore, knowledge of baseline vertebral fractures allows reliable definition of incident vertebral fracture events during treatment, which may modify the approach to therapy. In this manuscript, we will discuss the epidemiology and clinical significance of vertebral fractures, the different methods of detecting vertebral fractures, and the rationale for, and implications of, use of VFA routinely in FLS. Summary points: • Vertebral fracture assessment is a tool available on modern DXA instruments and has proven ability to detect vertebral fractures, the majority of which occur without a fall and without the signs and symptoms of an acute fracture. • Most osteoporosis guidelines internationally suggest that treatment with antiosteoporosis medications should be considered for older individuals (e.g., 65 years +) with a recent low trauma fracture without the need for DXA. • Younger individuals postfracture may be risk-assessed on the basis of FRAX® probability including DXA and associated treatment thresholds. • Future fracture risk is markedly influenced by both site, number, severity, and recency of prior fracture; awareness of baseline vertebral fractures facilitates definition of true incident vertebral fracture events occurring during antiosteoporosis treatment. • Detection of previously clinically silent vertebral fractures, defining site of prior fracture, might alter treatment decisions in younger or older FLS patients, consistent with recent IOF-ESCEO guidance on baseline-risk-stratified therapy, and provides a reliable baseline from which to define new, potentially therapy-altering, vertebral fracture events.
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- Arnesen, E. K., et al.
(författare)
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Nuts and seeds consumption and risk of cardiovascular disease, type 2 diabetes and their risk factors: a systematic review and meta-analysis
- 2023
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Ingår i: Food & Nutrition Research. - : SNF Swedish Nutrition Foundation. - 1654-6628 .- 1654-661X. ; 67
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: We aimed to systematically review studies and evaluate the strength of the evidence on nuts/seeds consumption and cardiometabolic diseases and their risk factors among adults. Methods: A protocol was pre-registered in PROSPERO (CRD42021270554). We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials and Scopus up to September 20, 2021 for prospec-tive cohort studies and >= 12-week randomized controlled trials (RCTs). Main outcomes were cardiovascular disease (CVD), coronary heart disease (CHD), stroke and type 2 diabetes (T2D), secondary total-/low density lipoprotein (LDL)-cholesterol, blood pressure and glycaemic markers. Data extraction and risk of bias (RoB) assessments (using RoB 2.0 and RoB-NObS) were performed in duplicate. Effect sizes were pooled using random-effects meta-analyses and expressed as relative risk (RR) or weighted mean differences with 95% confidence intervals (CI); heterogeneity quantified as I2. One-stage dose-response analyses assessed the linear and non-linear associations with CVD, CHD, stroke and T2D. The strength of evidence was classified per the World Cancer Research Fund criteria. Results: After screening 23,244 references, we included 42 papers from cohort studies (28 unique cohorts, 1,890,573 participants) and 18 RCTs (2,266 participants). In the cohorts, mainly populations with low con-sumption, high versus low total nuts/seeds consumption was inversely associated with total CVD (RR 0.81; 95% CI 0.75, 0.86; I-2 = 67%), CVD mortality (0.77; 0.72, 0.82; I-2 = 59.3%), CHD (0.82; 0.76, 0.89; I-2 = 64%), CHD mortality (0.75; 0.65, 0.87; I-2 = 66.9%) and non-fatal CHD (0.85; 0.75, 0.96; I-2 = 62.2%). According to the non-linear dose-response analyses, consumption of 30 g/day of total nuts/seeds was associated with RRs of similar magnitude. For stroke and T2D the summary RR for high versus low intake was 0.91 (95% CI 0.85, 0.97; I-2 = 24.8%) and 0.95 (0.75, 1.21; I-2 = 82.2%). Intake of nuts (median similar to 50 g/day) lowered total (-0.15 mmol/L; -0.22, -0.08; I-2 = 31.2%) and LDL-cholesterol (-0.13 mmol/L; -0.21, -0.05; I-2 = 68.6%), but not blood pressure. Findings on fasting glucose, HbA1c and insulin resistance were conflicting. The results were robust to sensitivity and subgroup analyses. We rated the associations between nuts/seeds and both CVD and CHD as probable. There was limited but suggestive evidence for no association with stroke. No conclusion could be made for T2D. Conclusion: There is a probable relationship between consumption of nuts/seeds and lower risk of CVD, mostly driven by CHD, possibly in part through effects on blood lipids. More research on stroke and T2D may affect the conclusions. The evidence of specific nuts should be further investigated.
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| 8. |
- Arnesen, E. K., et al.
(författare)
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Protein intake in children and growth and risk of overweight or obesity: A systematic review and meta-analysis
- 2022
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Ingår i: Food & Nutrition Research. - : SNF Swedish Nutrition Foundation. - 1654-6628 .- 1654-661X. ; 66, s. 1-23
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of this study was to examine the evidence for an association between the dietary protein intake in children and the growth and risk of overweight or obesity up to 18 years of age in settings relevant for the Nordic countries. Methods: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus up to February 26, 2021 for randomized controlled trials (RCTs) or prospective cohort studies assessing for protein intake from foods (total and from different sources) in children. The outcomes include weight, height/length, adiposity indices, and/or risk of overweight and/or obesity. The risk of bias was evaluated with instruments for each respective design (Cochrane's Risk of Bias 2.0 and RoB-NObS). A meta-analysis of five cohort studies was performed. The evidence was classified according to the criteria of the World Cancer Research Fund. Results: The literature search resulted in 9,132 abstracts, of which 55 papers were identified as potentially relevant. In total, 21 studies from 27 publications were included, of which five were RCTs and 16 were cohort studies. The RCTs found generally null effects of high-protein intake in infants on weight gain, nor that lower protein diets negatively affected growth. All included RCTs had some concern regarding the risk of bias and were limited by small sample sizes. Total protein intake and BMI were assessed in 12 co-horts, of which 11 found positive associations. The meta-analysis revealed a pooled effect estimate of 0.06 (95% CI 0.03, 0.1) kg/m2 BMI per one E% increment in total protein (I2 = 15.5). Therefore, the evidence for a positive relationship between total protein intake and BMI was considered probable. Furthermore, there was probable evidence for an association between higher intake of animal protein and increased BMI. There was limited, suggestive evidence for an effect of total protein intake and higher risk of overweight and/or obesity, while no conclusions could be made on the associations between animal vs. plant protein intake and risk of overweight and/or obesity. Discussion: In healthy, well-nourished children of Western populations, there is probably a causal relationship between a high-protein intake in early childhood (<= 18 months) - particularly protein of animal origin - and higher BMI later in childhood, with consistent findings across cohort studies. A lack of RCTs precluded a stronger grading of the evidence.
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| 9. |
- Bartosch, P., et al.
(författare)
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In community-dwelling women frailty is associated with imminent risk of osteoporotic fractures
- 2021
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 32:9, s. 1735-1744
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Tidskriftsartikel (refereegranskat)abstract
- Summary: Frailty reflects an accelerated health decline. Frailty is a consequence of fracture and contributes to fracture. Greater frailty was associated with higher fracture risk. Frail women were at immediate risk (within 24 months) of a hip or major fracture. Fracture prevention could be improved by considering frailty status. Introduction: Frailty encompasses the functional decline in multiple systems, particularly the musculoskeletal system. Frailty can be a consequence of and contribute to fracture, leading to a cycle of further fractures and greater frailty. This study investigates this association, specifically time frames for risk, associated fracture types, and how grade of frailty affects risk. Methods: The study is performed in the OPRA cohort of 1044, 75-year-old women. A frailty index was created at baseline and 5 and 10 years. Women were categorized as frail or nonfrail and in quartiles (Q1 least frail; Q4 most frail). Fracture risk was assessed over short (1 and 2 years) and long terms (5 and 10 years). Fracture risk was defined for any fracture, major osteoporotic fractures (MOFs), and hip and vertebral fracture, using models including bone mineral density (BMD) and death as a competing risk. Results: For women aged 75, frailty was associated with higher risk of fracture within 2 years (Hip SHRadj. 3.16 (1.34–7.47)) and MOF (2 years SHRadj. 1.88 (1.12–3.16)). The increased risk continued for up to 5 years (Hip SHRadj. 2.02 (1.07–3.82)); (MOF SHRadj. 1.43 (0.99–2.05)). Grade of frailty was associated with increased 10-year probability of fracture (p = 0.03). Frailty predicted fracture independently of BMD. For women aged 80, frailty was similarly associated with fracture. Conclusion: Frail elderly women are at immediate risk of fracture, regardless of bone density and continue to be at risk over subsequent years compared to identically aged nonfrail women. Incorporating regular frailty assessment into fracture management could improve identification of women at high fracture risk.
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| 10. |
- Bärebring, Linnea, et al.
(författare)
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Intake of vitamin B12 in relation to vitamin B12 status in groups susceptible to deficiency: a systematic review
- 2023
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Ingår i: Food & Nutrition Research. - 1654-6628 .- 1654-661X. ; 67
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Forskningsöversikt (refereegranskat)abstract
- Objective: To systematically review the evidence for whether habitual or different levels of experimental intake of vitamin B12 from diet and supplements is sufficient to ensure adequate B12 status in groups most susceptible to vitamin B12 deficiency.Methods: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials and Scopus up to 21 May 2021, for intervention studies, prospective cohort studies and case-control studies assessing B12 intake from diet and/or supplements in relation to B12 status (s/p-B12, holotranscobalamin, methylmalonic acid, homocysteine or breastmilk B12). Cross-sectional studies were eligible for studies conducted during pregnancy and lactation. Included populations were children (0-18 years), young adults (18-35 years), pregnant or lactating women, older adults (& GE;65 years) and vegans or vegetarians. Study selection, data extraction and risk of bias assessment were conducted by two assessors independently. The evidence was synthesized qualitatively and classified according to the World Cancer Research Fund.Results: The searches yielded 4855 articles of which 89 were assessed in full text and 18 included. Three studies were conducted during pregnancy and three during lactation or infancy - all observational. Eight studies were conducted among older adults; most were interventions among B12-deficient participants. Four studies were eligible for vegetarian and vegans, all interventions. The strength of evidence that habitual B12 intake or an intake in line with the current Nordic recommended intake (RI) is sufficient to ensure adequate status was considered Limited - no conclusion for all included populations.Conclusion: Evidence is insufficient to assess if or which level of B12 intake is sufficient to maintain adequate status for all included populations. Population-based cohort studies and low-to-moderate dose interventions that address this question are highly warranted.
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