Age-related decline in muscle strength is an important public health issue for older adults. Dietary protein has been associated with maintenance of muscle mass, yet its relation to muscle strength ...remains unclear.
We determined the association of dietary protein (total, animal, and plant) intake, measured by food frequency questionnaire, with change in grip strength over 6 years in 1,746 men and women from the Framingham Offspring cohort.
Mean age at baseline was 58.7 years (range: 29-85), and mean total, animal, and plant protein intakes were 79, 57, and 22 g/d, respectively. Adjusted baseline mean grip strength did not differ across quartiles of energy-adjusted total, animal or protein intake. Greater protein intake, regardless of source, was associated with less decrease in grip strength (all p for trend ≤.05): participants in the lowest quartiles lost 0.17% to 0.27% per year while those in the highest quartiles gained 0.52% to 0.60% per year. In analyses stratified by age, participants aged 60 years or older (n = 646) had similar linear trends on loss of grip strength for total and animal (all p for trend <.03) but not plant protein, while the trends in participants younger than 60 years (n = 896) were not statistically significant.
Higher dietary intakes of total and animal protein were protective against loss of grip strength in community-dwelling adults aged 60 years and older. Increasing intake of protein from these sources may help maintain muscle strength and support prevention of mobility impairment in older adults.
ABSTRACT
The musculoskeletal system evolved in mammals to perform diverse functions that include locomotion, facilitating breathing, protecting internal organs, and coordinating global energy ...expenditure. Bone and skeletal muscles involved with locomotion are both derived from somitic mesoderm and accumulate peak tissue mass synchronously, according to genetic information and environmental stimuli. Aging results in the progressive and parallel loss of bone (osteopenia) and skeletal muscle (sarcopenia) with profound consequences for quality of life. Age‐associated sarcopenia results in reduced endurance, poor balance, and reduced mobility that predispose elderly individuals to falls, which more frequently result in fracture because of concomitant osteoporosis. Thus, a better understanding of the mechanisms underlying the parallel development and involution of these tissues is critical to developing new and more effective means to combat osteoporosis and sarcopenia in our increasingly aged population. This perspective highlights recent advances in our understanding of mechanisms coupling bone and skeletal muscle mass, and identify critical areas where further work is needed.
Clinical studies often face the difficult problem of how to account for participants who die without experiencing the study outcome of interest. In a geriatric population with considerable ...comorbidities, the competing risk of death is especially high. Traditional approaches to describe risk of disease include Kaplan‐Meier survival analysis and Cox proportional hazards regression, but these methods can overestimate risk of disease by failing to account for the competing risk of death. This report discusses traditional survival analysis and competing risk analysis as used to estimate risk of disease in geriatric studies. Furthermore, it illustrates a competing risk approach to estimate risk of second hip fracture in the Framingham Osteoporosis Study and compares the results with traditional survival analysis. In this example, survival analysis overestimated the 5‐year risk of second hip fracture by 37% and the 10‐year risk by 75% compared with competing risk estimates. In studies of older individuals in which a substantial number of participants die during a long follow‐up, the cumulative incidence competing risk estimate and competing risk regression should be used to determine incidence and effect estimates. Use of a competing risk approach is critical to accurately determining disease risk for elderly individuals and therefore best inform clinical decision‐making.
Low muscle mass and weakness are common and potentially disabling in older adults, but in order to become recognized as a clinical condition, criteria for diagnosis should be based on clinically ...relevant thresholds and independently validated. The Foundation for the National Institutes of Health Biomarkers Consortium Sarcopenia Project used an evidence-based approach to develop these criteria. Initial findings were presented at a conference in May 2012, which generated recommendations that guided additional analyses to determine final recommended criteria. Details of the Project and its findings are presented in four accompanying manuscripts.
The Foundation for the National Institutes of Health Sarcopenia Project used data from nine sources of community-dwelling older persons: Age, Gene/Environment Susceptibility-Reykjavik Study, Boston Puerto Rican Health Study, a series of six clinical trials, Framingham Heart Study, Health, Aging, and Body Composition, Invecchiare in Chianti, Osteoporotic Fractures in Men Study, Rancho Bernardo Study, and Study of Osteoporotic Fractures. Feedback from conference attendees was obtained via surveys and breakout groups.
The pooled sample included 26,625 participants (57% women, mean age in men 75.2 ±6.1 SD and in women 78.6 ±5.9 years). Conference attendees emphasized the importance of evaluating the influence of body mass on cutpoints. Based on the analyses presented in this series, the final recommended cutpoints for weakness are grip strength <26kg for men and <16kg for women, and for low lean mass, appendicular lean mass adjusted for body mass index <0.789 for men and <0.512 for women.
These evidence-based cutpoints, based on a large and diverse population, may help identify participants for clinical trials and should be evaluated among populations with high rates of functional limitations.
IMPORTANCE: Age-adjusted hip fracture incidence is decreasing in the US. The decrease has been attributed to osteoporosis treatment, but the cause is unknown. OBJECTIVE: To examine the decrease in ...hip fracture incidence over the past 40 years in the US. DESIGN, SETTING, AND PARTICIPANTS: A population-based cohort study using participants in the Framingham Heart Study was conducted. A total of 4918 men and 5634 women were followed up prospectively for the first hip fracture between January 1, 1970, and December 31, 2010. Data were analyzed from May 1, 2019, to May 30, 2020. MAIN OUTCOMES AND MEASURES: Incidence of hip fracture and contemporaneous prevalence of risk factors for hip fractures analyzed with age-period-cohort models. RESULTS: The study contained more than 105 000 person-years in 10 552 individuals with a gradual shift toward the offspring participants in the 1980s and 1990s. Women represented more than 55% of the study sample over the years. Adjusted for age, the incidence of hip fracture decreased by 4.4% (95% CI, 6.8%-1.9%) per year from 1970 to 2010. Both period associations (P < .001) and birth cohort associations (P < .001) were statistically significant. For example, in persons aged 85 to 89 years, the incidence of hip fracture was 759 per 100 000 person-years in the offspring group compared with 2018 per 100 000 person-years in the original cohort. The decrease in hip fracture incidence was coincident with a decrease in smoking and heavy drinking. Smoking decreased from 38% in the 1970s to 15% in the late 2000s, while heavy drinking decreased from 7.0% to 4.5%. The prevalence of other risk factors for hip fracture, such as underweight (body mass index <18.5), obesity (body mass index >30), and early menopause (age <45 years) were stable over the study period. When persons who never smoked were evaluated, a change in the incidence of −3.2% (95% CI, −6.0% to −0.4%) per year was observed. The difference between the decrease of the entire population and nonsmokers of 1.5% per year was similar to the hazard ratio conferred by smoking (hazard ratio, 1.5; 95% CI, 1.14-1.96). CONCLUSIONS AND RELEVANCE: In this study, individuals born more recently appeared to have a low risk for hip fracture. Reductions in smoking and heavy drinking were the risk factor changes coincident with the observed decrease in hip fracture. Attributing the decrease in hip fracture incidence up to 2010 solely to better treatment is not supported by these data, emphasizing the need to treat patients with osteoporosis while continuing to encourage public health interventions for smoking cessation and heavy drinking.
Context:
The primary goals of genome-wide association studies (GWAS) are to discover new molecular and biological pathways involved in the regulation of bone metabolism that can be leveraged for drug ...development. In addition, the identified genetic determinants may be used to enhance current risk factor profiles.
Evidence Acquisition:
There have been more than 40 published GWAS on skeletal phenotypes, predominantly focused on dual-energy x-ray absorptiometry-derived bone mineral density (BMD) of the hip and spine.
Evidence Synthesis:
Sixty-six BMD loci have been replicated across all the published GWAS, confirming the highly polygenic nature of BMD variation. Only seven of the 66 previously reported genes (LRP5, SOST, ESR1, TNFRSF11B, TNFRSF11A, TNFSF11, PTH) from candidate gene association studies have been confirmed by GWAS. Among 59 novel BMD GWAS loci that have not been reported by previous candidate gene association studies, some have been shown to be involved in key biological pathways involving the skeleton, particularly Wnt signaling (AXIN1, LRP5, CTNNB1, DKK1, FOXC2, HOXC6, LRP4, MEF2C, PTHLH, RSPO3, SFRP4, TGFBR3, WLS, WNT3, WNT4, WNT5B, WNT16), bone development: ossification (CLCN7, CSF1, MEF2C, MEPE, PKDCC, PTHLH, RUNX2, SOX6, SOX9, SPP1, SP7), mesenchymal-stem-cell differentiation (FAM3C, MEF2C, RUNX2, SOX4, SOX9, SP7), osteoclast differentiation (JAG1, RUNX2), and TGF-signaling (FOXL1, SPTBN1, TGFBR3). There are still 30 BMD GWAS loci without prior molecular or biological evidence of their involvement in skeletal phenotypes. Other skeletal phenotypes that either have been or are being studied include hip geometry, bone ultrasound, quantitative computed tomography, high-resolution peripheral quantitative computed tomography, biochemical markers, and fractures such as vertebral, nonvertebral, hip, and forearm.
Conclusions:
Although several challenges lie ahead as GWAS moves into the next generation, there are prospects of new discoveries in skeletal biology. This review integrates findings from previous GWAS and provides a roadmap for future directions building on current GWAS successes.
The genetics of vitamin D Jiang, Xia; Kiel, Douglas P.; Kraft, Peter
Bone (New York, N.Y.),
09/2019, Letnik:
126
Journal Article
Recenzirano
Vitamin D plays an essential role in human health as it influences immune function, cell proliferation, differentiation and apoptosis. Vitamin D deficiency has been associated with numerous health ...outcomes, including bone disease, cancer, autoimmune disease, cardiovascular conditions and more. However, the causal role of vitamin D beyond its importance for bone health remains unclear and is under much debate. Twin and familial studies from past decades have demonstrated a nontrivial heritability of circulating vitamin D concentrations. Several large-scale genome-wide association studies (GWAS) have discovered associations of GC, NADSYN1/DHCR7, CYP2R1, CYP24A1, SEC23A, AMDHD1 with serum levels of vitamin D. A recent whole genome sequencing (WGS) study, combined with deep imputation of genome-wide genotyping, has identified a low-frequency synonymous coding variant at CYP2R1. Information on these genetic variants can be used as tools for downstream analysis such as Mendelian randomization. Here, we review the genetic determinants of circulating vitamin D levels by focusing on new findings from GWAS and WGS, as well as results from Mendelian randomization analyses conducted so far for vitamin D with various traits and diseases. The amount of variation in vitamin D explained by genetics is still small, and the putative causal relationship between vitamin D and other diseases remains to be demonstrated.
•Twin and familial studies have demonstrated a heritability of serum vitamin D levels.•Common SNPs (GC/NADSYN1/CYP2R1/CYP24A1/SEC23A/AMDHD1) are associated with vitamin D.•A low-frequency coding SNP at CYP2R1 is associated with vitamin D.•The causal role of vitamin D with diseases remains unclear and is under much debate.
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