Serum hsCRP is an independent risk marker for de novo major depressive disorder in women. This supports an aetiological role for inflammatory activity in the pathophysiology of depression.
Reducing the population burden of fractures requires attention to women with osteopenia, as well as osteoporosis, because over half of the fragility fractures in the population arise in these individuals, and women with osteopenia plus a prevalent fracture have the same fracture risk as women with osteoporosis.
Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low bone mineral density (BMD) is a major predisposing factor to fracture and is known to be highly heritable. Site-, gender-, and age-specific genetic effects on BMD are thought to be significant, but have largely not been considered in the design of genome-wide association studies (GWAS) of BMD to date. We report here a GWAS using a novel study design focusing on women of a specific age (postmenopausal women, age 55–85 years), with either extreme high or low hip BMD (age- and gender-adjusted BMD z-scores of +1.5 to +4.0, n = 1055, or −4.0 to −1.5, n = 900), with replication in cohorts of women drawn from the general population (n = 20,898). The study replicates 21 of 26 known BMD–associated genes. Additionally, we report suggestive association of a further six new genetic associations in or around the genes CLCN7, GALNT3, IBSP, LTBP3, RSPO3, and SOX4, with replication in two independent datasets. A novel mouse model with a loss-of-function mutation in GALNT3 is also reported, which has high bone mass, supporting the involvement of this gene in BMD determination. In addition to identifying further genes associated with BMD, this study confirms the efficiency of extreme-truncate selection designs for quantitative trait association studies.
Evidence from cross-sectional and longitudinal data suggests that smoking increases the risk of major depressive disorder in women.
In this population-based study, seasonal periodicity was seen with reduced serum vitamin D, increased serum PTH, and increased bone resorption in winter. This was associated with an increased proportion of falls resulting in fracture and an increased risk of wrist and hip fractures.
This population-based study documented -blocker use in 59/569 cases with incident fracture and 112/775 controls. OR for fracture associated with -blocker use was 0.68 (95%CI, 0.49 -0.96). -Blockers were associated with higher BMD at the total hip (2.5%) and UD forearm (3.6%) after adjusting for age, anthropometry, and thiazide use. -Blocker use is associated with reduced fracture risk and higher BMD.Introduction: Animal data suggests that bone formation is under -adrenergic control and that -blockers stimulate bone formation and/or inhibit bone resorption. Materials and Methods:We evaluated the association between -blocker use, bone mineral density (BMD), and fracture risk in a population-based study in Geelong, a southeastern Australian city with a single teaching hospital and two radiological centers providing complete fracture ascertainment for the region. -Blocker use was documented for 569 women with radiologically confirmed incident fractures and 775 controls without incident fracture. Medication use and lifestyle factors were documented by questionnaire. Results: Odds ratio for fracture associated with -blocker use was 0.68 (95% CI, 0.49 -0.96) for any fracture. Adjusting for age, weight, medications, and lifestyle factors had little effect on the odds ratio. -Blocker use was associated with a higher BMD at the total hip (2.5%, p ϭ 0.03) and ultradistal forearm (3.6%, p ϭ 0.04) after adjustment for age, anthropometry, and thiazide use. Conclusion: -Blockers are associated with a reduction in fracture risk and higher BMD.
BackgroundChanging perspectives on the natural history of celiac disease (CD), new serology and genetic tests, and amended histological criteria for diagnosis cast doubt on past prevalence estimates for CD. We set out to establish a more accurate prevalence estimate for CD using a novel serogenetic approach.MethodsThe human leukocyte antigen (HLA)-DQ genotype was determined in 356 patients with ‘biopsy-confirmed’ CD, and in two age-stratified, randomly selected community cohorts of 1,390 women and 1,158 men. Sera were screened for CD-specific serology.ResultsOnly five ‘biopsy-confirmed’ patients with CD did not possess the susceptibility alleles HLA-DQ2.5, DQ8, or DQ2.2, and four of these were misdiagnoses. HLA-DQ2.5, DQ8, or DQ2.2 was present in 56% of all women and men in the community cohorts. Transglutaminase (TG)-2 IgA and composite TG2/deamidated gliadin peptide (DGP) IgA/IgG were abnormal in 4.6% and 5.6%, respectively, of the community women and 6.9% and 6.9%, respectively, of the community men, but in the screen-positive group, only 71% and 75%, respectively, of women and 65% and 63%, respectively, of men possessed HLA-DQ2.5, DQ8, or DQ2.2. Medical review was possible for 41% of seropositive women and 50% of seropositive men, and led to biopsy-confirmed CD in 10 women (0.7%) and 6 men (0.5%), but based on relative risk for HLA-DQ2.5, DQ8, or DQ2.2 in all TG2 IgA or TG2/DGP IgA/IgG screen-positive subjects, CD affected 1.3% or 1.9%, respectively, of females and 1.3% or 1.2%, respectively, of men. Serogenetic data from these community cohorts indicated that testing screen positives for HLA-DQ, or carrying out HLA-DQ and further serology, could have reduced unnecessary gastroscopies due to false-positive serology by at least 40% and by over 70%, respectively.ConclusionsScreening with TG2 IgA serology and requiring biopsy confirmation caused the community prevalence of CD to be substantially underestimated. Testing for HLA-DQ genes and confirmatory serology could reduce the numbers of unnecessary gastroscopies.
In this population-based, observational study, we document the personal burden of fracture and utilization of community and health services for women during the 12-month period following a fracture. Participants were 598 women (aged 35-92 years) with incident fracture in the years 1994-1996 who were enrolled in the Geelong Osteoporosis Study. Almost all hip fracture cases and 27% of nonhip fracture cases were hospitalized. Homes were modified in 14% of cases, and 32% of the women purchased or hired equipment to assist with activities of daily living. Three-quarters of women with hip, pelvis, or lower limb fractures were confined to the home, had to walk with a walking aid, or could walk only short distances for several weeks. After a year, nearly one-half had not regained prefracture mobility. One-seventh of women with upper-limb fractures did not venture outside the home for at least 6 weeks. Nearly half of all fracture cases needed help with personal care and housework during the first 6 weeks. After 6 months, 3.4% of all patients and 19.6% of hip, 12.8% of humeral, and 4.7% of spine fracture patients required assistance with bathing and showering. After a year, more than half of the hip fracture cases remained restricted regarding housework, gardening, and transport. These findings have important implications for rehabilitation therapy. A fracture, regardless of site, had a major impact on a woman's lifestyle and well-being. Most women were restricted in their activities of daily living and suffered loss of confidence and independence. Short-term morbidity was common for all fractures, with varying degrees of prolonged morbidity often extending to at least a year postfracture.
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