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Bone mineral density and osteoporosis risk in young adults with atopic dermatitis.

ABSTRACT: Atopic dermatitis (AD) has been increasing worldwide over the past few decades. AD has been reported to be associated with an increased risk of osteoporosis and fractures in adult AD patients. The aim of this study was to investigate the bone mineral density (BMD) to evaluate osteoporosis risk in young adults with AD by sex. This was a case-control cohort study using a national dataset from the Korea National Health and Nutrition Examination Survey 2007-2009. We included young adult AD patients (men aged 19 ≤ and < 50 years, premenopausal women aged 19 ≤ and < 50 years) and 1:5 propensity score weighting controls by age, sex, body mass index (BMI), vitamin D level, and alcohol/smoking status. BMD was measured by double energy X-ray absorptiometry at the lumbar spine, femur neck, and total femur. The prevalence of low BMD, defined by a Z-score ≤ - 2.0, was compared between AD and without AD. We analyzed 311 (weighted n = 817,014) AD patients and 8,972 (weighted n = 20,880,643) controls. BMD at the lumbar spine was significantly lower in the male AD group than in the male control group (mean ± SE, 0.954 ± 0.016 vs. 0.989 ± 0.002, P = 0.03). The prevalence of low BMD (Z-score) did not significantly differ between AD and non-AD subjects in both men (3.8% vs. 2.7%, P = 0.56) and women (6.4% vs. 3.3%, P = 0.40). Among AD patients, early age at diagnosis of AD, longer duration of AD, lower BMI, rural residence (for men), less education, low vitamin D level, late menarche, and more pregnancies (for women) were associated with low BMD. In conclusion, low BMD did not occur more frequently in young adults with AD than in non-AD controls. However, early-onset/longer AD duration and lower BMI were associated with low BMD among young adult patients with AD.

SUBMITTER: Kim S

PROVIDER: S-EPMC8688494 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Osteoporosis, a disease characterized by low bone mineral density (BMD), increases the risk for fractures. Conventional risk factors alone do not completely explain measured BMD or osteoporotic fracture risk. Metabolomics may provide additional information. We aim to identify BMD-associated metabolomic markers that are predictive of fracture risk. We assessed 209 plasma metabolites by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in 1552 Framingham Offspring Study participants, and measured femoral neck (FN) and lumbar spine (LS) BMD 2 to 10 years later using dual-energy X-ray absorptiometry. We assessed osteoporotic fractures up to 27-year follow-up after metabolomic profiling. We identified 27 metabolites associated with FN-BMD or LS-BMD by LASSO regression with internal validation. Incorporating selected metabolites significantly improved the prediction and the classification of osteoporotic fracture risk beyond conventional risk factors (area under the curve [AUC] = 0.74 for the model with identified metabolites and risk factors versus AUC = 0.70 with risk factors alone, p = .001; net reclassification index = 0.07, p = .03). We replicated significant improvement in fracture prediction by incorporating selected metabolites in 634 participants from the Hong Kong Osteoporosis Study (HKOS). The glycine, serine, and threonine metabolism pathway (including four identified metabolites: creatine, dimethylglycine, glycine, and serine) was significantly enriched (false discovery rate [FDR] p value = .028). Furthermore, three causally related metabolites (glycine, phosphatidylcholine [PC], and triacylglycerol [TAG]) were negatively associated with FN-BMD, whereas PC and TAG were negatively associated with LS-BMD through Mendelian randomization analysis. In summary, metabolites associated with BMD are helpful in osteoporotic fracture risk prediction. Potential causal mechanisms explaining the three metabolites on BMD are worthy of further experimental validation. Our findings may provide novel insights into the pathogenesis of osteoporosis. © 2021 American Society for Bone and Mineral Research (ASBMR).

Project description:BackgroundOsteoporosis is diagnosed by the measurement of bone mineral density, which is a highly heritable and multifactorial trait. We aimed to identify genetic loci that are associated with bone mineral density.MethodsIn this genome-wide association study, we identified the most promising of 314 075 single nucleotide polymorphisms (SNPs) in 2094 women in a UK study. We then tested these SNPs for replication in 6463 people from three other cohorts in western Europe. We also investigated allelic expression in lymphoblast cell lines. We tested the association between the replicated SNPs and osteoporotic fractures with data from two studies.FindingsWe identified genome-wide evidence for an association between bone mineral density and two SNPs (p<5x10(-8)). The SNPs were rs4355801, on chromosome 8, near to the TNFRSF11B (osteoprotegerin) gene, and rs3736228, on chromosome 11 in the LRP5 (lipoprotein-receptor-related protein) gene. A non-synonymous SNP in the LRP5 gene was associated with decreased bone mineral density (rs3736228, p=6.3x10(-12) for lumbar spine and p=1.9x10(-4) for femoral neck) and an increased risk of both osteoporotic fractures (odds ratio [OR] 1.3, 95% CI 1.09-1.52, p=0.002) and osteoporosis (OR 1.3, 1.08-1.63, p=0.008). Three SNPs near the TNFRSF11B gene were associated with decreased bone mineral density (top SNP, rs4355801: p=7.6x10(-10) for lumbar spine and p=3.3x10(-8) for femoral neck) and increased risk of osteoporosis (OR 1.2, 95% CI 1.01-1.42, p=0.038). For carriers of the risk allele at rs4355801, expression of TNFRSF11B in lymphoblast cell lines was halved (p=3.0x10(-6)). 1883 (22%) of 8557 people were at least heterozygous for these risk alleles, and these alleles had a cumulative association with bone mineral density (trend p=2.3x10(-17)). The presence of both risk alleles increased the risk of osteoporotic fractures (OR 1.3, 1.08-1.63, p=0.006) and this effect was independent of bone mineral density.InterpretationTwo gene variants of key biological proteins increase the risk of osteoporosis and osteoporotic fracture. The combined effect of these risk alleles on fractures is similar to that of most well-replicated environmental risk factors, and they are present in more than one in five white people, suggesting a potential role in screening.

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Bone mineral density and osteoporosis risk in young adults with atopic dermatitis.

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