Steven R Cummings's research while affiliated with California Pacific Medical Center Research Institute and other places

Publications (916)

Article
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Background We developed a simple tool to estimate the probability of dying from acute COVID-19 illness only with readily available assessments at initial admission. Methods This retrospective study included 13,190 racially and ethnically diverse adults admitted to one of the New York City Health + Hospitals (NYC H+H) system for COVID-19 illness be...
Article
Background despite fall history being a well-known risk factor for falls and fractures, the association between very recent falls and imminent fracture risk is not clearly elucidated. Objective to study the very recent (<4 months) fall-related absolute risk of fractures in the following year. Methods two large prospective cohort studies of women...
Article
We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. Introduct...
Article
Background: Red cell distribution width (RDW), an index for variation of red blood cell (RBC) size, has been proposed as a potential marker for poorer outcomes in several aging-related diseases and conditions. We tested whether greater variability of RBC size, presented as a higher RDW value, predicts poor prognoses among hospitalized patients ove...
Article
The relation between a novel measure of total skeletal muscle mass (assessed by D3‐creatine dilution [D3Cr]) and incident fracture is unknown. In 1363 men (mean age 84.2 years), we determined D3Cr muscle mass; Fracture Risk Assessment Tool (FRAX) 10‐year probability of hip and major osteoporotic (hip, humerus, vertebral, forearm) fracture; and femo...
Article
Background Chronic inflammatory conditions have been linked to dementia, but little is known about the role of atopic eczema, a inflammatory condition recently recognized to be common among older adults. Objective To determine whether active atopic eczema is associated with incident dementia. Methods Longitudinal cohort study of 1,767,667 individ...
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Aging is characterized by increased mortality, functional decline, and exponential increases in the incidence of diseases such as cancer, stroke, cardiovascular disease, neurological disease, respiratory disease, etc. Though the role of aging in these diseases is widely accepted and considered to be a common denominator, the underlying mechanisms a...
Article
Background It is not known how measures of body composition, strength and physical performance are interrelated or how empirical groupings of these measures relate to disability and mobility disability. Methods Muscle mass was assessed by D3-creatine dilution (D3Cr muscle mass) in 1345 men (84.1 ± 4.1 years) enrolled in the Osteoporotic Fractures...
Article
Cellular metabolism and environmental interactions generate molecular damage affecting all levels of biological organization. Accumulation of this damage over time is thought to have a central role in the aging process. Insufficient attention has been paid to the role of molecular damage in aging-related phenotypes, particularly in humans, in part...
Article
Background Muscle mass declines with age, while body adiposity increases. Sarcopenic obesity has been proposed to be particularly deleterious. However, previous methods for estimating muscle mass have been inadequate, and the relative contributions of total body fat vs. muscle fat to adverse outcomes have been unclear. Methods In a large cohort of...
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ABSTRACT Increases in bone mineral density (BMD) with osteoporosis treatment are associated with reduced fracture risk. Increasing BMD is therefore a goal of osteoporosis therapy. Here, we compare the probability of achieving a T‐score of > −2.5 over 3 years at the total hip (TH) or lumbar spine (LS) in women with osteoporosis, ≥55 years of age, af...
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Importance The aging of the population is associated with an increasing burden of fractures worldwide. However, the epidemiological features of fractures in mainland China are not well known. Objective To assess the prevalence of and factors associated with osteoporosis, clinical fractures, and vertebral fractures in an adult population 40 years o...
Article
Background Cut-points to define slow walking speed have largely been derived from expert opinion. Methods Study participants (13,589 men and 5,043 women aged ≥65years) had walking speed (m/s) measured over 4-6 meters (mean ± SD: 1.20 ± 0.27 m/s in men and 0.94 ± 0.24 m/s in women.) Mobility limitation was defined as self-reported any difficulty wi...
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PurposeWe evaluated the association of percent mammographic density (PMD), absolute dense area (DA), and non-dense area (NDA) with risk of “intrinsic” molecular breast cancer (BC) subtypes.Methods We pooled 3492 invasive BC and 10,148 controls across six studies with density measures from prediagnostic, digitized film-screen mammograms. We classifi...
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A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-22613-2
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In patients with surgical repair of a low-trauma hip fracture, zoledronic acid (ZA) reduced the risk of subsequent fractures regardless of pretreatment femoral neck and total hip bone mineral density (BMD). Introduction: Zoledronic acid reduces the risk of subsequent fractures after repair of a hip fracture. It is still unclear whether the benefi...
Article
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Importance Breast cancer screening, surveillance, and diagnostic imaging services were profoundly limited during the initial phase of the coronavirus disease 2019 (COVID-19) pandemic. Objective To develop a risk-based strategy for triaging mammograms during periods of decreased capacity. Design, Setting, and Participants This population-based coh...
Article
Clinical trials conducted at clinical sites are limited to enrolling people who live nearby and are able to attend visits at clinics. Some types of clinical trials can be performed without clinical sites, which enables people to participate regardless of proximity to a clinical site or limitations that make visits difficult. Trials at clinical site...
Article
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The Trial of Parkinson’s And Zoledronic acid (TOPAZ, https://clinicaltrials.gov/ct2/show/NCT03924414) is a unique collaboration between experts in movement disorders and osteoporosis to test the efficacy of zoledronic acid, an FDA-approved parenteral treatment for osteoporosis, for fracture prevention in people with neurodegenerative parkinsonism....
Preprint
Prediction of mortality from COVID-19 infection might help triage patients to hospitalization and intensive care. To estimate the risk of inpatient mortality, we analyzed the data of 13,190 adult patients in the New York City Health + Hospitals system admitted for COVID-19 infection from March 1 to June 30, 2020. They had a mean age 58 years, 40% w...
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Five NIH-funded studies, the Long Life Family Study (LLFS, U19), the Longevity Consortium (LC, U19), Longevity Genomics (U24), and Protective Omics Profiles in Centenarians (UH2) work together to triangulate on mechanisms of extreme longevity and healthy aging with the ultimate goal of discovering predictors and targetable pathways. Linkage analyse...
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We hypothesized that trait associations with genetically mediated gene expression could be used to screen for genes that are good candidates for translational studies of longevity. We compiled a collection of genetically-mediated transcriptome-wide association studies using 33 traits and outcomes from large-scale, publicly-available GWAS meta-analy...
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While many clinical guidelines recommend screening for osteoporosis for early detection and treatment, there is great diversity in the case-finding strategies globally. We sought to compare case-finding strategies, focusing on the approaches used in European and Asian countries. This article provides an overview of the current case-finding strategi...
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signatureSearch is an R/Bioconductor package that integrates a suite of existing and novel algorithms into an analysis environment for gene expression signature (GES) searching combined with functional enrichment analysis (FEA) and visualization methods to facilitate the interpretation of the search results. In a typical GES search (GESS), a query...
Article
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Background: Fractures as a result of osteoporosis and low bone mass are common and give rise to significant clinical, personal, and economic burden. Even after a fracture occurs, high fracture risk remains widely underdiagnosed and undertreated. Common fracture risk assessment tools utilize a subset of clinical risk factors for prediction, and ofte...
Article
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The biological bases of longevity are not well understood, and there are limited biomarkers for the prediction of long life. We used a high‐throughput, discovery‐based proteomics approach to identify serum peptides and proteins that were associated with the attainment of longevity in a longitudinal study of community‐dwelling men age ≥65 years. Bas...
Preprint
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Background: Polygenic risk scores (PRS) have been developed to predict individual cancer risk and their potential clinical utility is receiving a great deal of attention. However, the degree to which the predictive utility of individual cancer-specific PRS may be augmented or refined by the incorporation of other cancer PRS, non-cancer disease PRS,...
Article
Background: Fractures due to osteoporosis and low bone mass are common and give rise to significant clinical, personal, and economic burden. Even after a fracture occurs, high fracture risk remains widely underdiagnosed and undertreated. Common fracture risk assessment tools utilize a subset of clinical risk factors for prediction, and often requi...
Article
Background: We tested whether greater variation in red blood cell size, measured by red cell distribution width (RDW), may predict aging-related degenerative conditions and therefore, serve as a marker of biological aging. Methods: 3,635 community-dwelling elderly men were enrolled in the prospective Osteoporotic Fractures in Men study (MrOS). R...
Preprint
BACKGROUND Fractures due to osteoporosis and low bone mass are common and give rise to significant clinical, personal, and economic burden. Even after a fracture occurs, high fracture risk remains widely underdiagnosed and undertreated. Common fracture risk assessment tools utilize a subset of clinical risk factors for prediction, and often require...
Article
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Context Abaloparatide is an FDA-approved PTHrp analog for treatment of osteoporosis in postmenopausal women at high risk of fracture. Objectives We assessed the cardiovascular safety profile of abaloparatide. Design Review of heart rate (HR), blood pressure (BP), and cardiovascular-related adverse events (AEs), including major adverse cardiovascu...
Article
Rationale & Objective Disordered mineral metabolism complicates chronic kidney disease (CKD), but the effect of reduced kidney function on fracture risk has not been fully established. We conducted a systematic review and meta-analysis of the risks for hip and nonvertebral fractures in people with CKD. We also investigated the effects of age, sex,...
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Produced by senescent cells, the senescence-associated secretory phenotype (SASP) is a potential driver of age-related dysfunction. We tested whether circulating concentrations of SASP proteins reflect age and medical risk in humans. We first screened senescent endothelial cells, fibroblasts, preadipocytes, epithelial cells, and myoblasts to identi...
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Hypertension (HTN) is a significant risk factor for cardiovascular morbidity and mortality. Metabolic abnormalities, including adverse cholesterol and triglycerides (TG) profiles, are frequent comorbid findings with HTN and contribute to cardiovascular disease. Diuretics, which are used to treat HTN and heart failure, have been associated with wors...
Article
Background Whether low muscle mass is a risk factor for disability and mortality is unclear. Associations between approximations of muscle mass (including lean mass from dual energy x-ray absorptiometry (DXA)) and these outcomes are inconsistent. Methods Muscle mass measured by deuterated creatine (D3Cr) dilution and appendicular lean mass (ALM, b...
Article
Background The combination of sarcopenia and obesity has been associated with physical impairment in older people. However, previous research has relied on assessments of lean mass as a surrogate for muscle mass. We postulate that inaccurate measures of muscle mass may have obscured the role of obesity in sarcopenia and related outcomes. Our aim wa...
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Background Previous meta-analyses have reported an increase in the risk of hip fractures in diabetes, but the risk of non-vertebral fractures has not been investigated. In addition, it is not known how the risk of fractures is affected by age, body mass index, diabetes duration and insulin use. To investigate these features, we conducted a meta-ana...
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Fragility fractures due to osteoporosis are common and are associated with significant clinical, personal, and economic burden. Even after a fragility fracture, osteoporosis remains widely underdiagnosed and undertreated. Common fracture risk assessment tools, such as FRAX1 and Garvan,2 confer risk over the long term but do not provide short-term r...
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Background: Declines in bone, muscle and physical performance are associated with adverse health outcomes in older adults. However, few studies have described concurrent age-related patterns of change in these factors. The purpose of this study was to characterize change in four properties of muscle, physical performance, and bone in a prospective...
Article
Alendronate was synthesized in 1970s in a search for inhibitors of calcification. Istituto Gentili investigators identified it as a potent inhibitor of bone resorption and obtained a patent covering its use in the treatment of osteoporosis and other disorders of excessive bone resorption in the 1980s. Merck licensed alendronate in 1988 and its phar...
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Background Diabetes is associated with increased fracture risk but we do not know what affects this risk. We investigated the risk of hip and non-vertebral fractures in diabetes and whether this risk was affected by age, gender, body mass index, diabetes type and duration, insulin use and diabetic complications. Methods We selected a previously pu...
Article
Objectives It is unknown whether muscle mass measured by the D3-creatine dilution method is a superior predictor of incident mobility disability than traditional components of sarcopenia definitions (including grip strength, walking speed, appendicular lean mass). The objective of this study was to determine the relative importance of strength; phy...
Article
Zoledronate is the most potent and most long-acting bisphosphonate in clinical use, and is administered as an intravenous infusion. Its major uses are in osteoporosis, Paget's disease, and in myeloma and cancers to reduce adverse skeletal related events (SREs). In benign disease, it is a first- or second-line treatment for osteoporosis, achieving a...
Conference Paper
Background: Polygenic risk scores (PRS) integrate risk information from breast cancer associated SNPs (single nucleotide polymorphism). The risk scores have mostly been developed in populations of European ancestry, and have been shown to improve risk prediction over standard breast cancer risk models in these populations. The ability of the PRS to...
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Purpose: Diabetes and osteoporosis occur frequently in older adults and are both associated with increased fracture risk. Denosumab treatment reduced new vertebral, nonvertebral, and hip fractures over 3 years, with continued low fracture incidence for up to 10 years in postmenopausal women with osteoporosis. However, its effects in diabetic subje...
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Recent studies suggest that the RANK/RANKL system impacts muscle function and/or mass. In the pivotal placebo‐controlled fracture trial of the RANKL inhibitor denosumab in women with postmenopausal osteoporosis, treatment was associated with a lower incidence of non‐fracture‐related falls (p = 0.02). This ad hoc exploratory analysis pooled data fro...
Article
Red cell distribution width (RDW), routinely assessed as a component of a complete blood count (CBC), quantifies the variation in the size of red blood cells. It increases with age, and increased RDW predicts many aging‐related diseases and mortality. However, whether it also predicts hip fracture is unknown. We prospectively evaluated the associat...
Article
Background Extensive work in basic and clinical science suggests that biological mechanisms of aging are causally related to the development of disease and disability in late life. Modulation of the biological mechanisms of aging can extend both life span and health span in animal models, but translation to humans has been slow. Methods Summary of...
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We have shown that men with low muscle mass assessed by D3Cr (deuterated creatine) dilution are more likely to have worse physical performance and incident fractures, injurious falls and disability. However, the relation between D3Cr muscle mass and mortality is unknown. With data from Year 14 Visit of the MrOS study (N=1400, mean age 84.2 yrs), pr...
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Molecular factors and pathways promoting human longevity and healthy aging can potentially delay or prevent multiple chronic diseases and conditions, but identifying such factors that can be pharmacologically targeted requires an integrated multidisciplinary approach. We describe the design of the five research projects and three cores of the Longe...
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The goals of the Longevity Genomics research group (www.longevitygenomics.org) are to develop translational strategies to promote healthy human aging based on findings from genomic studies of aging. Our investigation began with the previously reported and publicly available GWAS of the top 10% of parental lifespan in the UK Biobank, reported by Pil...
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The biological underpinnings of longevity are poorly elucidated in humans. We used a novel, high-throughput discovery-proteomics approach to identify serum proteins associated with longevity (living beyond 90th percentile of survival) in community-dwelling men age ≥65 years in the MrOs Study. Baseline serum from 2473 men was analyzed using liquid c...
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Background: Given that breast cancer and normal dense fibroglandular tissue have similar radiographic attenuation, we examine whether automated volumetric density measures identify a differential change between breasts in women with cancer and compare to healthy controls. Methods: Eligible cases (n = 1160) had unilateral invasive breast cancer a...
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Background: Muscle mass declines with age. However, common assessments used to quantify muscle mass are indirect. The D3 -creatine (D3 Cr) dilution method is a direct assessment of muscle mass; however, longitudinal changes have not been examined in relation to changes in other measures of muscle mass, strength, and performance. Methods: A conve...
Article
Importance Previous studies have reported that drug treatments, particularly treatment with bisphosphonates, is associated with reduced overall mortality rates in addition to decreased fracture risk. If so, drug treatments should be recommended for this reason alone, regardless of a patient’s risk of fracture. Objective To assess whether randomize...
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Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at...
Article
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Study Objectives Both periodic limb movements during sleep (PLMS) and arousals are associated with sympathetic nervous system activation and may be arrhythmogenic. We hypothesize a temporal relationship exists between individual PLMS, particularly with arousal, and nonsustained ventricular tachycardia (NSVT) events. Methods A bidirectional time-st...
Article
Purpose: Among younger men, lower body mass is associated with fewer urinary symptoms, including incontinence and nocturia. However, lower body mass may have different implications for older men due to age-associated muscle atrophy and decreased strength. Materials and methods: We conducted a prospective analysis of community-dwelling men, aged...
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While the WHO fracture risk algorithm (FRAXTM) is used to predict fracture, the utility of some simple machine learning method, such as classification and regression trees (CART) should be evaluated to determine their performance for fracture prediction. Follow‐up time for the hip fracture analyses of 5977 community‐dwelling US men aged ≥ 65 years...