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1.
Eur Respir Rev ; 28(154)2019 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-31722892

RESUMO

COPD is associated with a progressive loss of muscle mass and function. However, there is an unmet need to define and standardise methods to estimate the prevalence of sarcopenia in COPD patients.We performed a systematic review and meta-analysis of the prevalence of this extrapulmonary manifestation in COPD patients. We searched Embase, Medline (Ovid), CINAHL (EBSCO), Web of Science, Scopus and Google Scholar for studies published up to January 17, 2019, assessing sarcopenia in COPD patients based on low muscle mass and decreased muscle function. Interventional studies, in vitro experiments, protocols or reviews and meta-analyses were excluded. We estimated heterogeneity (I2) and assessed significance (Q) using a Chi-squared test for estimates obtained from random-effects models.4465 articles were initially identified. After removing the duplicates and applying the selection criteria, we reviewed 62 full-text articles. Finally, 10 articles (n=2565 COPD patients) were included in this systematic review and meta-analyses. Overall, the prevalence of sarcopenia in patients with COPD was 21.6% (95% CI 14.6-30.9%, I2=94%), ranging from 8% in population-based to 21% in clinic-based studies, and 63% in COPD patients residing in nursing homes.Sarcopenia is frequently observed in COPD patients, with varying prevalence across population settings. Sarcopenia in COPD should be assessed using standardised tests and cut-off points from sarcopenia consensus criteria for clinical practice and international comparisons.

2.
Calcif Tissue Int ; 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31608419

RESUMO

Loop diuretics (LD) may affect bone health by inhibiting renal calcium reuptake. However, whether vitamin D status and dietary calcium intake modify the association between LD and bone outcome is unclear. Therefore, this study aimed to evaluate whether vitamin D level or calcium intake modify the association between LD and various indices of bone health including bone mineral density (BMD) and Trabecular Bone Score (TBS). From The Rotterdam Study, a prospective population-based cohort study, we used data from 6990 participants aged > 45 year with a DXA scan (2002-2008), 6908 participants with femoral neck (FN)-BMD, 6677 participants with lumbar spine (LS)-BMD and 6476 participants with LS-TBS measurements. Use of LD was available from pharmacy dispensing records. Vitamin D (25(OH)D) level was measured in serum, and dietary calcium intake was measured with a validated food frequency questionnaire. Almost eight percent of the participants used LD. The association between LD (past-users compared to never-users) and LS-TBS was significantly different by 25(OH)D concentrations (P for interaction = 0.04). A significantly lower LS-TBS among LD past-users was observed for 25(OH)D ≥ 50 nmol/l compared to ≤ 20 and 20-50 nmol/l (ß = - 0.036, 95% CI - 0.060; - 0.013 vs. ß = - 0.012, 95% CI - 0.036; 0.013 and ß = - 0.031, 95% CI - 0.096; 0.034, respectively). However, no other significant effect modification by 25(OH)D and dietary calcium intake was found in the associations between LD use and bone health outcomes (P-interaction > 0.13). This study suggests that the association between LD use and indices of bone health is not consistently modified by vitamin D or dietary calcium intake.

3.
Diabetes Care ; 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31658976

RESUMO

OBJECTIVE: We aimed to assess whether individuals with type 2 diabetes (T2D) have increased risk of vertebral fractures (VFs) and to estimate nonvertebral fracture and mortality risk among individuals with both prevalent T2D and VFs. RESEARCH DESIGN AND METHODS: A systematic PubMed search was performed to identify studies that investigated the relationship between T2D and VFs. Cohorts providing individual-participant data (IPD) were also included. Estimates from published summary data and IPD cohorts were pooled in a random-effects meta-analysis. Multivariate Cox-regression models were used to estimate nonvertebral fracture and mortality risk among individuals with T2D and VFs. RESULTS: Across 15 studies comprising 852,705 men and women, individuals with T2D had lower risk of prevalent (odds ratio [OR] 0.84 [95% CI 0.74-0.95]; I 2 = 0.0%; P het = 0.54) but increased risk of incident VFs (OR 1.35 [95% CI 1.27-1.44]; I 2 = 0.6%; P het = 0.43). In the IPD cohorts (N = 19,820), risk of nonvertebral fractures was higher in those with both T2D and VFs compared with those without T2D or VFs (hazard ratio [HR] 2.42 [95% CI 1.86-3.15]), with VFs (HR 1.73 [95% CI 1.32-2.27]), or T2D (HR 1.94 [95% CI 1.46-2.59]) alone. Individuals with both T2D and VFs had increased mortality compared with individuals without T2D and VFs (HR 2.11 [95% CI 1.72-2.59]) or with VFs alone (HR 1.84 [95% CI 1.49-2.28]) and borderline increased compared with individuals with T2D alone (HR 1.23 [95% CI 0.99-1.52]). CONCLUSIONS: Based on our findings, individuals with T2D should be systematically assessed for presence of VFs, and, as in individuals without T2D, their presence constitutes an indication to start osteoporosis treatment for the prevention of future fractures.

4.
BMJ ; 366: l4410, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31371314

RESUMO

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 meta-analysis 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/cm2, 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.


Assuntos
Densidade Óssea/genética , Cálcio/sangue , Predisposição Genética para Doença , Fraturas por Osteoporose/sangue , Fraturas por Osteoporose/genética , Adenosina Trifosfatases/genética , Diacilglicerol Quinase/genética , Feminino , Fator de Transcrição GATA3/genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Receptores de Detecção de Cálcio/genética , Medição de Risco , Vitamina D3 24-Hidroxilase/genética , Vitamina K Epóxido Redutases/genética
5.
J Bone Miner Res ; 34(7): 1254-1263, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31074909

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide. Obesity is a major risk factor for NAFLD and recently, low skeletal muscle mass emerged as additional risk factor for NAFLD. However, the different contributions of body mass index (BMI) to the risk of NAFLD are not yet well-known. We therefore studied body composition and muscle function with NAFLD in an elderly population-based study. Participants of European descent underwent dual-energy X-ray absorptiometry (DXA) and hepatic ultrasonography. NAFLD was defined as liver steatosis in absence of secondary causes for steatosis. Skeletal muscle index (SMI) was defined as appendicular lean mass/height2 and (pre)sarcopenia was defined using the European Working Group on Sarcopenia in Older People (EWGSOP) consensus guidelines. All analyses were stratified by sex and BMI (cut point: 25 kg/m2 ) and adjusted for age, weight, height, homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides, and android-fat-to-gynoid-fat ratio (AGR). We included 4609 participants, of whom 1623 had NAFLD (n = 161 normal-weight and n = 1462 overweight). Presarcopenia and sarcopenia prevalence was low (5.9% and 4.5%, respectively) and both were not associated with NAFLD. SMI was associated with less NAFLD in normal-weight women (OR, 0.48; 95% CI, 0.29 to 0.80). A similar association for SMI and NAFLD was seen in normal-weight men, but significance dissipated after adjustment for AGR (OR, 0.63; 95% CI, 0.39 to 1.02). Generally, fat mass was a better predictor for NAFLD than lean mass. In particular, android fat mass was associated with all NAFLD subgroups (OR from 1.77 in overweight men to 8.34 in normal-weight women, pmax = 0.001), whereas substitution of gynoid fat mass for other body components had a significant protective association with NAFLD in every subgroup, but normal-weight men. Likewise, AGR was the best performing predictor for NAFLD prevalence (OR from 1.97 in normal-weight men to 4.81 in normal-weight women, pmax < 0.001). In conclusion, both high fat mass and low SMI were associated with normal-weight NAFLD. However, fat distribution (as assessed by AGR) could best predict NAFLD prevalence. © 2019 American Society for Bone and Mineral Research.

6.
Nat Commun ; 10(1): 2358, 2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31127096

RESUMO

The original HTML version of this Article was updated shortly after publication to add links to the Peer Review file.In addition, affiliations 16 and 17 incorrectly read 'School of Medicine Sydney, University of Notre Dame Australia, Sydney, WA, 6160, Australia' and 'St Vincent's Clinical School, University of New South Wales Medicine, University of New South Wales, Sydney, NSW, 2052, Australia.' This has now been corrected in both the PDF and HTML versions of the Article.

7.
Nat Commun ; 10(1): 2054, 2019 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-31053729

RESUMO

Bone area is one measure of bone size that is easily derived from dual-energy X-ray absorptiometry (DXA) scans. In a GWA study of DXA bone area of the hip and lumbar spine (N ≥ 28,954), we find thirteen independent association signals at twelve loci that replicate in samples of European and East Asian descent (N = 13,608 - 21,277). Eight DXA area loci associate with osteoarthritis, including rs143384 in GDF5 and a missense variant in COL11A1 (rs3753841). The strongest DXA area association is with rs11614913[T] in the microRNA MIR196A2 gene that associates with lumbar spine area (P = 2.3 × 10-42, ß = -0.090) and confers risk of hip fracture (P = 1.0 × 10-8, OR = 1.11). We demonstrate that the risk allele is less efficient in repressing miR-196a-5p target genes. We also show that the DXA area measure contributes to the risk of hip fracture independent of bone density.


Assuntos
Densidade Óssea/genética , Fraturas do Quadril/genética , MicroRNAs/genética , Osteoartrite/genética , Absorciometria de Fóton , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Estatura/genética , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/fisiologia , Estudos de Casos e Controles , Colágeno Tipo XI/genética , Feminino , Seguimentos , Loci Gênicos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Fator 5 de Diferenciação de Crescimento/genética , Fraturas do Quadril/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/epidemiologia , Fatores de Risco
9.
Bone ; 126: 2-10, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30980960

RESUMO

Osteoporosis and fracture risk are common complex diseases, caused by an interaction of numerous disease susceptibility genes and environmental factors. With the advances in genomic technologies, large-scale genome-wide association studies (GWAS) have been performed which have broadened our understanding of the genetic architecture and biological mechanisms of complex disease. Currently, more than ~90 loci have been found associated with DXA derived bone mineral density (BMD), over ~500 loci with heel estimated BMD and several others with other less widely available bone parameters such as bone geometry, shape, and microarchitecture. Notably, several of the pathways identified by the GWAS efforts correspond to pathways that are currently targeted for the treatment of osteoporosis. Overall, tremendous progress in the field of the genetics of osteoporosis has been achieved with the discovery of WNT16, EN1, DAAM2, and GPC6 among others. Assessment of the function and biological mechanisms of the remaining genes may further untangle the complex genetic landscape of osteoporosis and fracture risk. With this review we aimed to provide a general overview of the existing GWAS studies on osteoporosis traits and fracture risk.

10.
J Bone Miner Res ; 34(7): 1284-1296, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30888730

RESUMO

Hip geometry is an important predictor of fracture. We performed a meta-analysis of GWAS studies in adults to identify genetic variants that are associated with proximal femur geometry phenotypes. We analyzed four phenotypes: (i) femoral neck length; (ii) neck-shaft angle; (iii) femoral neck width, and (iv) femoral neck section modulus, estimated from DXA scans using algorithms of hip structure analysis. In the Discovery stage, 10 cohort studies were included in the fixed-effect meta-analysis, with up to 18,719 men and women ages 16 to 93 years. Association analyses were performed with ∼2.5 million polymorphisms under an additive model adjusted for age, body mass index, and height. Replication analyses of meta-GWAS significant loci (at adjusted genomewide significance [GWS], threshold p ≤ 2.6 × 10-8 ) were performed in seven additional cohorts in silico. We looked up SNPs associated in our analysis, for association with height, bone mineral density (BMD), and fracture. In meta-analysis (combined Discovery and Replication stages), GWS associations were found at 5p15 (IRX1 and ADAMTS16); 5q35 near FGFR4; at 12p11 (in CCDC91); 11q13 (near LRP5 and PPP6R3 (rs7102273)). Several hip geometry signals overlapped with BMD, including LRP5 (chr. 11). Chr. 11 SNP rs7102273 was associated with any-type fracture (p = 7.5 × 10-5 ). We used bone transcriptome data and discovered several significant eQTLs, including rs7102273 and PPP6R3 expression (p = 0.0007), and rs6556301 (intergenic, chr.5 near FGFR4) and PDLIM7 expression (p = 0.005). In conclusion, we found associations between several genes and hip geometry measures that explained 12% to 22% of heritability at different sites. The results provide a defined set of genes related to biological pathways relevant to BMD and etiology of bone fragility. © 2019 American Society for Bone and Mineral Research.

11.
Curr Osteoporos Rep ; 17(2): 86-95, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30820831

RESUMO

PURPOSE OF REVIEW: To summarize the evidence from recent studies on the shared genetics between bone and muscle in humans. RECENT FINDINGS: Genome-wide association studies (GWAS) have successfully identified a multitude of loci influencing the variability of different bone or muscle parameters, with multiple loci overlapping between the traits. In addition, joint analyses of multiple correlated musculoskeletal traits (i.e., multivariate GWAS) have underscored several genes with possible pleiotropic effects on both bone and muscle including MEF2C and SREBF1. Notably, several of the proposed pleiotropic genes have been validated using human cells or animal models. It is clear that the study of pleiotropy may provide novel insights into disease pathophysiology potentially leading to the identification of new treatment strategies that simultaneously prevent or treat both osteoporosis and sarcopenia. However, the role of muscle factors (myokines) that stimulate bone metabolism, as well as osteokines that affect muscles, is in its earliest stage of understanding.

12.
Bone ; 122: 150-155, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30798002

RESUMO

Bone modeling is an important process in the growing skeleton. An inadequate bone modeling in response to mechanical loads would lead some children to develop weaker bones than others. The resulting higher stresses in the bones would render them more susceptible to fracture. We aimed to examine the association between femoral stress (FS) derived from structural parameters and BMD in relation to incident fractures in children. Bone stress was evaluated at the medial femoral neck, a skeletal site subject to large forces during normal locomotion. This study comprises 1840 children from the Generation R Study, with whole body and hip DXA scans at a mean age of 6.01 years. Hip structural analysis (HSA) was used to measure femur geometry for the FS calculation. Data on fractures occurring over the following 4 years after the DXA assessment were obtained by questionnaire. Incident fracture was observed in 7.6% of the participating children. Cox-multivariate regression analysis, described as hazard ratios (HR), showed that after adjustment for sex, ethnicity, age, weight and lean mass fraction, there was a significant increase in the risk of incident fracture for every standard deviation (SD) decrease in total body BMD (HR: 1.35, 95% CI 1.05-1.74, p-value = 0.021), femoral neck BMD (HR: 1.31, 95% CI 1.09-1.58, p-value = 0.005) and narrow neck BMD (HR: 1.39, 95% CI 1.14-1.68, p-value = 0.001). Whereas, every increment of one SD in femoral stress resulted in 1.33 increased risk of incident fractures (HR: 1.33, 95% CI 1.13-1.57, p-value = 0.001). This association remained (borderline) significant after the adjustment for DXA derived BMD measurements. Our results show that increased bone stress may underlie greater susceptibility to traumatic fractures in children (partially independent of BMD) and underscore the utility of hip DXA scans for the assessment of paediatric bone health and specifically fracture risk.

13.
Bone ; 121: 227-231, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30677542

RESUMO

Fracture rate in childhood is increasing and its consequences may affect health and developmental processes and cause school absence and restricted activity days. There are scarce epidemiologic studies regarding fractures in children. The aim of this study was to evaluate if pediatric fractures show disparities across sexes and ethnic groups. This study was conducted based on data from 3632 participants of the Generation R Study. Prevalent fractures were assessed using a questionnaire at a mean age of 9.7 years. Child's ethnicity was determined based on country of birth of the parents using questionnaires (geographic ancestry) or admixture analysis (genetic ancestry). Associations between fracture occurrence and sex or ethnicity were evaluated using logistic regression models adjusted for age, weight, lean mass fraction, bone mineral density (BMD) and sex/ethnicity. Fracture was reported for 525 (14.5%) children. The great majority of these children were classified as European (N = 3164), followed by African (N = 283) and Asian (N = 185) based on geographic ancestry. Similarly, the highest proportion of Europeans was observed based on genetic ancestry. Prevalence of fractures was not different between boys and girls, even after adjustment for possible confounders (OR: 1.03, 95% CI 0.84-1.27, p-value = 0.8). However, odds of prevalent fractures were two times higher in European when compared to Asian children (OR: 2.01, 95% CI 1.17-3.45, p-value = 0.01), and 1.5 times higher when compared to African children (OR: 1.50, 95% CI 1.00-2.26, p-value = 0.05). Overall, in this study, European children showed a highest risk of prevalent fractures independently of factors such as body composition and BMD, while no difference in the prevalence of fractures between boys and girls was observed.

14.
15.
Nat Genet ; 51(2): 258-266, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30598549

RESUMO

Osteoporosis is a common aging-related disease diagnosed primarily using bone mineral density (BMD). We assessed genetic determinants of BMD as estimated by heel quantitative ultrasound in 426,824 individuals, identifying 518 genome-wide significant loci (301 novel), explaining 20% of its variance. We identified 13 bone fracture loci, all associated with estimated BMD (eBMD), in ~1.2 million individuals. We then identified target genes enriched for genes known to influence bone density and strength (maximum odds ratio (OR) = 58, P = 1 × 10-75) from cell-specific features, including chromatin conformation and accessible chromatin sites. We next performed rapid-throughput skeletal phenotyping of 126 knockout mice with disruptions in predicted target genes and found an increased abnormal skeletal phenotype frequency compared to 526 unselected lines (P < 0.0001). In-depth analysis of one gene, DAAM2, showed a disproportionate decrease in bone strength relative to mineralization. This genetic atlas provides evidence linking associated SNPs to causal genes, offers new insight into osteoporosis pathophysiology, and highlights opportunities for drug development.


Assuntos
Densidade Óssea/genética , Predisposição Genética para Doença/genética , Osteoporose/genética , Adulto , Idoso , Animais , Feminino , Fraturas Ósseas/genética , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único/genética
17.
Curr Osteoporos Rep ; 16(5): 531-540, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30203249

RESUMO

PURPOSE OF REVIEW: This review summarizes the basic principles of Mendelian randomization (MR) and provides evidence for the causal effect of multiple modifiable factors on bone outcomes. RECENT FINDINGS: Several studies using MR approach have provided support for the causal effect of obesity on bone mineral density (BMD). Strikingly, studies have failed to prove a causal association between elevated 25(OH) D concentrations and higher BMD in community-dwelling individuals. The MR approach has been successfully used to evaluate multiple factors related to bone mineral density variation and/or fracture risk. The MR approach avoids some of the classical observational study limitations and provides more robust causal evidence, ensuring bigger success of the clinical trials. The selection of interventions based on genetic evidence could have a substantial impact on clinical practice.

18.
BMJ ; 362: k3225, 2018 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-30158200

RESUMO

OBJECTIVES: To identify the genetic determinants of fracture risk and assess the role of 15 clinical risk factors on osteoporotic fracture risk. DESIGN: Meta-analysis of genome wide association studies (GWAS) and a two-sample mendelian randomisation approach. SETTING: 25 cohorts from Europe, United States, east Asia, and Australia with genome wide genotyping and fracture data. PARTICIPANTS: A discovery set of 37 857 fracture cases and 227 116 controls; with replication in up to 147 200 fracture cases and 150 085 controls. Fracture cases were defined as individuals (>18 years old) who had fractures at any skeletal site confirmed by medical, radiological, or questionnaire reports. Instrumental variable analyses were performed to estimate effects of 15 selected clinical risk factors for fracture in a two-sample mendelian randomisation framework, using the largest previously published GWAS meta-analysis of each risk factor. RESULTS: Of 15 fracture associated loci identified, all were also associated with bone mineral density and mapped to genes clustering in pathways known to be critical to bone biology (eg, SOST, WNT16, and ESR1) or novel pathways (FAM210A, GRB10, and ETS2). Mendelian randomisation analyses showed a clear effect of bone mineral density on fracture risk. One standard deviation decrease in genetically determined bone mineral density of the femoral neck was associated with a 55% increase in fracture risk (odds ratio 1.55 (95% confidence interval 1.48 to 1.63; P=1.5×10-68). Hand grip strength was inversely associated with fracture risk, but this result was not significant after multiple testing correction. The remaining clinical risk factors (including vitamin D levels) showed no evidence for an effect on fracture. CONCLUSIONS: This large scale GWAS meta-analysis for fracture identified 15 genetic determinants of fracture, all of which also influenced bone mineral density. Among the clinical risk factors for fracture assessed, only bone mineral density showed a major causal effect on fracture. Genetic predisposition to lower levels of vitamin D and estimated calcium intake from dairy sources were not associated with fracture risk.

19.
J Clin Endocrinol Metab ; 103(11): 4125-4134, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30020476

RESUMO

Context: Although the skeleton is a well-known thyroid hormone target organ, very little data are available on the association of thyroid function with bone outcomes during childhood. Objective: To study the association of thyroid function with bone mass during childhood. Design, Setting, and Participants: Population-based prospective cohort including 4204 children with TSH and free T4 (FT4) measured at the age of 6 years. Main Outcome Measures: Bone density was assessed by a total body dual-energy X-ray absorptiometry scan at the median age of 6 years (95% range, 5.6 to 7.9) and at the age of 10 years (95% range, 9.0 to 10.9) in 4204 and 3404 participants, respectively. Results: There was an inverse association of TSH with bone mineral density (BMD) at the age of 6 (ß -0.028 ± 0.011, P = 0.009) and with follow-up measurements at the age of 10 (ß -0.027 ± 0.011, P = 0.014), but not with bone mineral content (BMC) at the age of 6 (ß -0.028 ± 0.015, P = 0.06) or for follow-up measurements of BMC at the age of 10 (ß -0.011 ± 0.015, P = 0.47). There was an inverse association of FT4 with BMD (ß -0.016 ± 0.006, P = 0.014) and BMC (ß -0.023 ± 0.009, P = 0.009) cross-sectionally, and also at the age of 10 years (BMD: ß -0.018 ± 0.007, P = 0.007; BMC: ß -0.021 ± 0.009, P = 0.020). Conclusion: A higher FT4 concentration is associated with lower bone mass at the age of 6 and at the age of 10 years. These data provide insights into the effects of thyroid function on bone physiology during childhood.

20.
Bone ; 114: 116-124, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29885926

RESUMO

Fracture incidence needs to be evaluated over time to assess the impact of the enlarging population burden of fractures (due to increase in lifespan) and the efficacy of fracture prevention strategies. Therefore, we aimed to evaluate the association of femoral neck bone mineral density (FN-BMD) measured using dual-energy X-ray absorptiometry (DXA) at baseline with fracture risk over a long follow-up time period. Incident non-vertebral fractures were assessed in 14,613 individuals participating in the Rotterdam Study with up to 20 years of follow-up. During a mean follow-up of 10.7 ±â€¯6.2 years, 2971 (20.3%) participants had at least one incident non-vertebral fracture. The risk for any non-vertebral fracture was 1.37 (95% Confidence Interval (CI): 1.25-1.49) and 1.42 (95%CI: 1.35-1.50) for men and women, respectively. The majority (79% in men and 75% in women) of all fractures occurred among participants a normal or osteopenic T-score. The incidence rates per 1000 person-years for the most common fractures were 5.3 [95%CI: 5.0-5.7] for hip, 4.9 [95%CI: 4.6-5.3] for wrist and 2.3 [95%CI: 2.0-2.5] for humerus. To examine the predictive ability of BMD through follow-up time we determined fracture hazard ratios (HR) per standard deviation decrease in femoral neck BMD across five year bins. No differences were observed, with a HR of 2.5 (95%CI: 2.0-3.1) after the first 5 years, and of 1.9 (95%CI: 1.1-3.3) after 20 years. To assess secular trends in fracture incidence at all skeletal sites we compared participants at an age of 70-80 years across two time periods: 1989-2001 (n = 2481, 60% women) and 2001-2013 (n = 2936, 58% women) and found no statistically significant difference (p < 0.05) between fracture incidence rates (i.e., incidence of non-vertebral fractures of 26.4 per 1000 PY [95%CI: 24.4-28.5]) between 1989 and 2001, and of 25.4 per 1000 PY [95%CI: 23.0-28.0] between 2001 and 2013. In conclusion, BMD is still predictive of future fracture over a long period of time. While no secular changes in fractures rates seem to be observed after a decade, the majority of fractures still occur above the osteoporosis threshold, emphasizing the need to improve the screening of osteopenic patients.

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