Publications by authors named "Kristine Ensrud"

462 Publications

Actigraphy-Derived Sleep Health Profiles and Mortality in Older Men and Women.

Sleep 2022 Jan 17. Epub 2022 Jan 17.

Department of Psychiatry, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA.

Study Objectives: To identify actigraphy sleep health profiles in older men (Osteoporotic Fractures in Men Study; N=2,640) and women (Study of Osteoporotic Fractures; N=2.430), and to determine whether profile predicts mortality.

Methods: We applied a novel and flexible clustering approach (Multiple Coalesced Generalized Hyperbolic mixture modeling) to identify sleep health profiles based on actigraphy midpoint timing, midpoint variability, sleep interval length, maintenance, and napping/inactivity. Adjusted Cox models were used to determine whether profile predicts time to all-cause mortality.

Results: We identified similar profiles in men and women: High Sleep Propensity [HSP] (20% of women; 39% of men; high napping and high maintenance); Adequate Sleep [AS] (74% of women; 31% of men; typical actigraphy levels); and Inadequate Sleep [IS] (6% of women; 30% of men; low maintenance and late/variable midpoint). In women, IS was associated with increased mortality risk (Hazard Ratio [HR]=1.59 for IS vs. AS; 1.75 for IS vs. HSP). In men, AS and IS were associated with increased mortality risk (1.19 for IS vs. HSP; 1.22 for AS vs. HSP).

Conclusions: These findings suggest several considerations for sleep-related interventions in older adults. Low maintenance with late/variable midpoint is associated with increased mortality risk and may constitute a specific target for sleep health interventions. High napping/inactivity co-occurs with high sleep maintenance in some older adults. Although high napping/inactivity is typically considered a risk factor for deleterious health outcomes, our findings suggest that it may not increase risk when it occurs in combination with high sleep maintenance.
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http://dx.doi.org/10.1093/sleep/zsac015DOI Listing
January 2022

Lower urinary tract symptoms and incident functional limitations among older community-dwelling men.

J Am Geriatr Soc 2021 Dec 24. Epub 2021 Dec 24.

Oregon Health and Science University-Portland State University School of Public Health, Portland, Oregon, USA.

Background: Lower urinary tract symptoms (LUTS) are associated with frailty phenotype, a risk factor for functional decline. Our objective was to determine the association between baseline LUTS and 2-year risk of new functional limitation among older men.

Methods: We analyzed data from the Osteoporotic Fractures in Men (MrOS) study with baseline at Year 7 and follow-up through Year 9. Participants included 2716 community-dwelling men age ≥ 71 years without any baseline self-reported functional limitation. LUTS severity (American Urologic Association Symptom Index) was classified as none/mild (score 0-7), moderate (8-19), and severe (20-35). At baseline and follow-up, men reported their ability to complete several mobility, activities of daily living (ADLs), and cognition-dependent tasks. Risk was estimated for 3 incident functional limitation outcomes: (1) mobility (any difficulty walking 2-3 blocks or climbing 10 steps), (2) ADL (any difficulty bathing, showering, or transferring), and (3) cognition-dependent (any difficulty managing money or medications). We used Poisson regression with a robust variance estimator to model adjusted risk ratios (ARR) and 95% CIs controlling for age, site, and comorbidities; other demographic/lifestyle factors did not meet criteria for inclusion.

Results: Overall, the 2-year risk was 15% for mobility, 10% for ADLs, and 4% for cognition-dependent task limitations. Compared to none/mild LUTS, risk of incident mobility limitations was increased for moderate (ARR = 1.35, 95% CI: 1.12, 1.63) and severe LUTS (ARR = 1.98, 95% CI: 1.48, 2.64). Men were also at higher risk for incident ADL limitations if they reported moderate (ARR = 1.32, 95% CI: 1.05, 1.67) and severe LUTS (ARR = 1.62, 95% CI: 1.07,2.43). Results were somewhat attenuated after adjusting for the frailty phenotype but remained statistically significant. LUTS were not associated with incident cognition-dependent task limitations.

Conclusions: LUTS severity is associated with incident mobility and ADL limitations among older men. Increased clinical attention to risk of functional limitations among older men with LUTS is likely warranted.
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http://dx.doi.org/10.1111/jgs.17633DOI Listing
December 2021

Assessment of Frailty and Association With Progression of Benign Prostatic Hyperplasia Symptoms and Serious Adverse Events Among Men Using Drug Therapy.

JAMA Netw Open 2021 11 1;4(11):e2134427. Epub 2021 Nov 1.

San Francisco Veterans Affairs Medical Center, San Francisco, California.

Importance: Benign prostatic hyperplasia (BPH) in older men can cause lower urinary tract symptoms (LUTS), which are increasingly managed with medications. Frailty may contribute to both symptom progression and serious adverse events (SAEs), shifting the balance of benefits and harms of drug therapy.

Objective: To assess the association between a deficit accumulation frailty index and clinical BPH progression or SAE.

Design, Setting, And Participants: This cohort study used data from the Medical Therapy of Prostatic Symptoms trial, which compared placebo, doxazosin, finasteride, and combination therapy in men with moderate-to-severe LUTS, reduced urinary flow rate, and no prior BPH interventions, hypotension, or elevated prostate-specific antigen. Enrollment was from 1995 to 1998, and follow-up was through 2001. Data were assessed in February 2021.

Exposures: A frailty index (score range, 0-1) using 68 potential deficits collected at baseline was used to categorized men as robust (score ≤0.1), prefrail (score 0.1 to <0.25), or frail (score ≥0.25).

Main Outcomes And Measures: Primary outcomes were time to clinical BPH progression and time to SAE, as defined in the parent trial. Adjusted hazard ratios (AHRs) were estimated using Cox proportional hazards regressions adjusted for demographic variables, treatment group, measures of obstruction, and comorbidities.

Results: Among 3047 men (mean [SD] age, 62.6 [7.3] years; range, 50-89 years) in this analysis, 745 (24%) were robust, 1824 (60%) were prefrail, and 478 (16%) were frail at baseline. Compared with robust men, frail men were older (age ≥75 years, 12 men [2%] vs 62 men [13%]), less likely to be White (646 men [87%] vs 344 men [72%]), less likely to be married (599 men [80%] vs 342 men [72%]), and less likely to have 16 years or more of education (471 men [63%] vs 150 men [31%]). During mean (SD) follow-up of 4.0 (1.5) years, the incidence rate of clinical BPH progression was 2.2 events per 100 person-years among robust men, 2.9 events per 100 person-years among prefrail men (AHR, 1.36; 95% CI, 1.02-1.83), and 4.0 events per 100 person-years among frail men (AHR, 1.82; 95% CI, 1.24-2.67; linear P = .005). Larger point estimates were seen among men who received doxazosin or combination therapy, although the test for interaction between frailty index and treatment group did not reach statistical significance (P for interaction = .06). Risk of SAE was higher among prefrail and frail men (prefrail vs robust AHR, 1.81; 95% CI, 1.48-2.23; frail vs robust AHR, 2.86; 95% CI, 2.21-3.69; linear P < .001); this association was similar across treatment groups (P for interaction = .76).

Conclusions And Relevance: These findings suggest that frailty is independently associated with greater risk of both clinical BPH progression and SAEs. Older frail men with BPH considering initiation of drug therapy should be counseled regarding their higher risk of progression despite combination therapy and their likelihood of experiencing SAEs regardless of treatment choice.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.34427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8613596PMC
November 2021

Physical functioning and mental health treatment initiation and retention for veterans with posttraumatic stress disorder: a prospective cohort study.

BMC Health Serv Res 2021 Sep 23;21(1):1005. Epub 2021 Sep 23.

Center for Care Delivery & Outcomes Research, Minneapolis VA Health Care System, One Veterans Dr, MN, 55417, Minneapolis, United States.

Background: Most US adults with posttraumatic stress disorder (PTSD) do not initiate mental health treatment within a year of diagnosis. Increasing treatment uptake can improve health and quality of life for those with PTSD. Individuals with PTSD are more likely to report poor physical functioning, which may contribute to difficulty with treatment initiation and retention. We sought to determine the effects of poor physical functioning on mental health treatment initiation and retention for individuals with PTSD.

Methods: We used data for a national cohort of veterans in VA care; diagnosed with PTSD in June 2008-July 2009; with no mental health treatment in the prior year; and who responded to baseline surveys on physical functioning and PTSD symptoms (n = 6,765). Physical functioning was assessed using Veterans RAND 12-item Short Form Health Survey, and encoded as limitations in physical functioning and role limitations due to physical health. Treatment initiation (within 6 months of diagnosis) was determined using VA data and categorized as none (reference), only medications, only psychotherapy, or both. Treatment retention was defined as having ≥ 4 months of appropriate antidepressant or ≥ 8 psychotherapy encounters.

Results: In multinomial models, greater limitations in physical functioning were associated with lower odds of initiating only psychotherapy (OR 0.82 [95 % CI 0.68, 0.97] for limited a little and OR 0.74 [0.61, 0.90] for limited a lot, compared to reference "Not limited at all"). However, it was not associated with initiation of medications alone (OR 1.04 [0.85, 1.28] for limited a little and OR 1.07 [0.86, 1.34] for limited a lot) or combined with psychotherapy (OR 1.03 [0.85, 1.25] for limited a little and OR 0.95 [0.78, 1.17] for limited a lot). Greater limitations in physical functioning were also associated with lower odds of psychotherapy retention (OR 0.69 [0.53, 0.89] for limited a lot) but not for medications (e.g., OR 0.96 [0.79, 1.17] for limited a lot). Role limitations was only associated with initiation of both medications and psychotherapy, but there was no effect gradient (OR 1.38 [1.03, 1.86] for limitations a little or some of the time, and OR 1.18 [0.63, 1.06] for most or all of the time, compared to reference "None of the time"). Accounting for chronic physical health conditions did not attenuate associations between limitations in physical functioning (or role limitations) and PTSD treatment; having more chronic conditions was associated with lower odds of both initiation and retention for all treatments (e.g., for 2 + conditions OR 0.53 [0.41, 0.67] for initiation of psychotherapy).

Conclusions: Greater limitations in physical functioning may be a barrier to psychotherapy initiation and retention. Future interventions addressing physical functioning may enhance uptake of psychotherapy.
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http://dx.doi.org/10.1186/s12913-021-07035-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457897PMC
September 2021

Anabolic Therapy for Osteoporosis.

JAMA 2021 Jul;326(4):350-351

HealthPartners Institute, Bloomington, Minnesota.

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http://dx.doi.org/10.1001/jama.2021.0233DOI Listing
July 2021

The Associations of Handgrip Strength and Leg Extension Power Asymmetry on Incident Recurrent Falls and Fractures in Older Men.

J Gerontol A Biol Sci Med Sci 2021 08;76(9):e221-e227

California Pacific Medical Center Research Institute, San Francisco Coordinating Center, USA.

Background: Evaluating asymmetries in muscle function could provide important insights for fall risk assessments. We sought to determine the associations of (i) handgrip strength (HGS) asymmetry and (ii) leg extension power (LEP) asymmetry on risk of incident recurrent falls and fractures in older men.

Method: There were 5 730 men with HGS asymmetry data and 5 347 men with LEP asymmetry data from the Osteoporotic Fractures in Men (MrOS) study. A handgrip dynamometer measured HGS and a Nottingham Power Rig ascertained LEP. Percent difference in maximal HGS between hands was calculated, and asymmetric HGS was defined as men in the highest quartile of dissimilarity for HGS between hands. The same approach was used to determine asymmetric LEP. Participants self-reported falls every 4 months after the baseline exam, and persons with ≥2 falls in the first year were considered recurrent fallers. Fractures and their dates of occurrence were self-reported and confirmed with radiographic reports.

Results: Older men in the highest HGS asymmetry quartile had a 1.20 (95% confidence interval [CI]: 1.01-1.43) relative risk for incident recurrent falls. Likewise, men in the highest HGS asymmetry quartile had a higher risk for incident fractures: 1.41 (CI: 1.02-1.96) for hip, 1.28 (CI: 1.04-1.58) for major osteoporotic, and 1.24 (CI: 1.06-1.45) for nonspine. There were no significant associations between LEP asymmetry and recurrent falls or fractures.

Conclusions: Asymmetric HGS could be a novel risk factor for falls and fractures that is more feasible to measure than LEP. Fall risk assessments should consider evaluating muscle function, including HGS asymmetry.
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http://dx.doi.org/10.1093/gerona/glab133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8499308PMC
August 2021

Life-space mobility and healthcare costs and utilization in older men.

J Am Geriatr Soc 2021 08 7;69(8):2262-2272. Epub 2021 May 7.

Center for Care Delivery & Outcomes Research, VA Health Care System, Minneapolis, Minnesota, USA.

Objectives: To determine the association of life-space score with subsequent healthcare costs and utilization.

Design: Prospective cohort study (Osteoporotic Fracture in Men [MrOS]).

Setting: Six U.S. sites.

Participants: A total of 1555 community-dwelling men (mean age 79.3 years; 91.5% white, non-Hispanic) participating in the MrOS Year 7 (Y7) examination linked with their Medicare claims data.

Measurements: Life-space during the past month was assessed as 0 (daily restriction to one's bedroom) to 120 (daily trips outside one's town without assistance) and categorized (0-40, 41-60, 61-80, 81-100, 101-120). Total annualized direct healthcare costs and utilization were ascertained during 36 months after the Y7 examination.

Results: Mean total annualized costs (2020 U.S. dollars) steadily increased across category of life-space score, from $7954 (standard deviation [SD] 16,576) among men with life-space scores of 101-120 to $26,430 (SD 28,433) among men with life-space scores of 0-40 (p < 0.001). After adjustment for demographics, men with a life-space score of 0-40 versus men with a life-space score of 101-120 had greater mean total costs (cost ratio [CR] = 2.52; 95% confidence interval [CI] = 1.84-3.45) and greater risk of subsequent hospitalization (odds ratio [OR] 4.72, 95% CI 2.61-8.53) and skilled nursing facility (SNF) stay (OR 7.32, 95% CI 3.65-14.66). Life-space score was no longer significantly associated with total healthcare costs (CR for 0-40 vs 101-120 1.29; 95% CI 0.91-1.84) and hospitalization (OR 1.76, 95% CI 0.89-3.51) after simultaneous consideration of demographics, medical factors, self-reported health and function, and the frailty phenotype; the association of life-space with SNF stay remained significant (OR 2.86, 95% CI 1.26-6.49).

Conclusion: Our results highlight the importance of function and mobility in predicting future healthcare costs and suggest the simple and convenient life-space score may in part capture risks from major geriatric domains and improve identification of older, community-dwelling men likely to require costly care.
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http://dx.doi.org/10.1111/jgs.17187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8542432PMC
August 2021

Sarcopenia Definitions as Predictors of Fracture Risk Independent of FRAX , Falls, and BMD in the Osteoporotic Fractures in Men (MrOS) Study: A Meta-Analysis.

J Bone Miner Res 2021 07 8;36(7):1235-1244. Epub 2021 Apr 8.

Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK.

Dual-energy X-ray absorptiometry (DXA)-derived appendicular lean mass/height (ALM/ht ) is the most commonly used estimate of muscle mass in the assessment of sarcopenia, but its predictive value for fracture is substantially attenuated by femoral neck (fn) bone mineral density (BMD). We investigated predictive value of 11 sarcopenia definitions for incident fracture, independent of fnBMD, fracture risk assessment tool (FRAX ) probability, and prior falls, using an extension of Poisson regression in US, Sweden, and Hong Kong Osteoporois Fractures in Men Study (MrOS) cohorts. Definitions tested were those of Baumgartner and Delmonico (ALM/ht only), Morley, the International Working Group on Sarcopenia, European Working Group on Sarcopenia in Older People (EWGSOP1 and 2), Asian Working Group on Sarcopenia, Foundation for the National Institutes of Health (FNIH) 1 and 2 (using ALM/body mass index [BMI], incorporating muscle strength and/or physical performance measures plus ALM/ht ), and Sarcopenia Definitions and Outcomes Consortium (gait speed and grip strength). Associations were adjusted for age and time since baseline and reported as hazard ratio (HR) for first incident fracture, here major osteoporotic fracture (MOF; clinical vertebral, hip, distal forearm, proximal humerus). Further analyses adjusted additionally for FRAX-MOF probability (n = 7531; calculated ± fnBMD), prior falls (y/n), or fnBMD T-score. Results were synthesized by meta-analysis. In 5660 men in USA, 2764 Sweden and 1987 Hong Kong (mean ages 73.5, 75.4, and 72.4 years, respectively), sarcopenia prevalence ranged from 0.5% to 35%. Sarcopenia status, by all definitions except those of FNIH, was associated with incident MOF (HR = 1.39 to 2.07). Associations were robust to adjustment for prior falls or FRAX probability (without fnBMD); adjustment for fnBMD T-score attenuated associations. EWGSOP2 severe sarcopenia (incorporating chair stand time, gait speed, and grip strength plus ALM) was most predictive, albeit at low prevalence, and appeared only modestly influenced by inclusion of fnBMD. In conclusion, the predictive value for fracture of sarcopenia definitions based on ALM is reduced by adjustment for fnBMD but strengthened by additional inclusion of physical performance measures. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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http://dx.doi.org/10.1002/jbmr.4293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611727PMC
July 2021

Sex-specific 25-hydroxyvitamin D threshold concentrations for functional outcomes in older adults: PRoject on Optimal VItamin D in Older adults (PROVIDO).

Am J Clin Nutr 2021 07;114(1):16-28

California Pacific Medical Center Research Institute, San Francisco, CA, USA.

Background: Threshold serum 25-hydroxyvitamin D [25(OH)D] concentrations for extraskeletal outcomes are uncertain and could differ from recommendations (20-30 ng/mL) for skeletal health.

Objectives: We aimed to identify and validate sex-specific threshold 25(OH)D concentrations for older adults' physical function.

Methods: Using 5 large prospective, population-based studies-Age, Gene/Environment Susceptibility-Reykjavik (n = 4858, Iceland); Health, Aging, and Body Composition (n = 2494, United States); Invecchiare in Chianti (n = 873, Italy); Osteoporotic Fractures in Men (n = 2301, United States); and Study of Osteoporotic Fractures (n = 5862, United States)-we assessed 16,388 community-dwelling adults (10,376 women, 6012 men) aged ≥65 y. We analyzed 25(OH)D concentrations with the primary outcome (incident slow gait: women <0.8 m/s; men <0.825 m/s) and secondary outcomes (gait speed, incident self-reported mobility, and stair climb impairment) at median 3.0-y follow-up. We identified sex-specific 25(OH)D thresholds that best discriminated incident slow gait using machine learning in training data (2/3 cohort-stratified random sample) and validated using the remaining (validation) data and secondary outcomes.

Results: Mean age in the cohorts ranged from 74.4 to 76.5 y in women and from 73.3 to 76.6 y in men. Overall, 1112/6123 women (18.2%) and 494/3937 men (12.5%) experienced incident slow gait, 1098/7011 women (15.7%) and 474/3962 men (12.0%) experienced incident mobility impairment, and 1044/6941 women (15.0%) and 432/3993 men (10.8%) experienced incident stair climb impairment. Slow gait was best discriminated by 25(OH)D <24.0 ng/mL compared with 25(OH)D ≥24.0 ng/mL in women (RR: 1.29; 95% CI: 1.10, 1.50) and 25(OH)D <21.0 ng/mL compared with 25(OH)D ≥21.0 ng/mL in men (RR: 1.43; 95% CI: 1.01, 2.02). Most associations between 25(OH)D and secondary outcomes were modest; estimates were similar between validation and training datasets.

Conclusions: Empirically identified and validated sex-specific threshold 25(OH)D concentrations for physical function for older adults, 24.0 ng/mL for women and 21.0 ng/mL for men, may inform candidate reference concentrations or the design of vitamin D intervention trials.
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http://dx.doi.org/10.1093/ajcn/nqab025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246604PMC
July 2021

Joint Associations of Prevalent Radiographic Vertebral Fracture and Abdominal Aortic Calcification With Incident Hip, Major Osteoporotic, and Clinical Vertebral Fractures.

J Bone Miner Res 2021 05 17;36(5):892-900. Epub 2021 Mar 17.

University of Minnesota, Minneapolis, MN, USA.

Prevalent vertebral fractures (PVFx) and abdominal aortic calcification (AAC) are both associated with incident fractures and can be ascertained on the same lateral spine images, but their joint association with incident fractures is unclear. Our objective was to estimate the individual and joint associations of PVFx and AAC with incident major osteoporotic, hip, and clinical vertebral fractures in 5365 older men enrolled in the Osteoporotic Fractures in Men (MrOS) Study, using Cox proportional hazards and Fine and Gray subdistribution hazards models to account for competing mortality. PVFx (Genant SQ grade 2 or 3) and 24-point AAC score were ascertained on baseline lateral spine radiographs. Self-reports of incident fractures were solicited every 4 months and confirmed by review of clinical radiographic reports. Compared with men without PVFx and AAC-24 score 0 or 1, the subdistribution hazard ratio (SHR) for incident major osteoporotic fracture was 1.38 (95% confidence interval [CI] 1.13-1.69) among men with AAC-24 score ≥2 alone, 1.71 (95% CI 1.37-2.14) for men with PVFx alone, and 2.35 (95% CI 1.75-3.16) for men with both risk factors, after accounting for conventional risk factors and competing mortality. Wald statistics showed improved prediction model performance by including both risk factors compared with including only AAC (chi-square = 17.3, p < .001) or including only PVFx (chi-square = 8.5, p = .036). Older men with both PVFx and a high level of AAC are at higher risk of incident major osteoporotic fracture than men with either risk factor alone. Assessing prevalent radiographic vertebral fracture and AAC on the same lateral spine images may improve prediction of older men who will have an incident major osteoporotic fracture, even after accounting for traditional fracture risk factors and competing mortality. © 2021 American Society for Bone and Mineral Research (ASBMR).
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http://dx.doi.org/10.1002/jbmr.4257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131243PMC
May 2021

Height Loss in Old Age and Fracture Risk Among Men in Late Life: A Prospective Cohort Study.

J Bone Miner Res 2021 06 19;36(6):1069-1076. Epub 2021 Mar 19.

Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.

To assess the association of height loss in old age with subsequent risk of hip and any clinical fracture in men late in life while accounting for the competing risk of mortality, we used data from 3491 community-dwelling men (mean age 79.2 years). Height loss between baseline and follow-up (mean 7.0 years between examinations) was categorized as <1 cm (referent group), ≥1 to <2 cm, ≥2 to <3 cm, and ≥3 cm. Men were contacted every 4 months after the follow-up examination to ask about fractures (confirmed by radiographic reports) and ascertain vital status (deaths verified by death certificates). Competing risk methods were used to estimate absolute probabilities of fracture outcomes by height loss category and calculate adjusted risks of fracture outcomes by height loss. During an average of 7.8 years, 158 (4.5%) men experienced a hip fracture and 1414 (40.5%) died before experiencing this event. The absolute 10-year probability of fracture events accounting for the competing risk of death increased with greater height loss. For example, the hip fracture probability was 2.7% (95% confidence interval [CI] 1.9-3.8%) among men with height loss <1 cm increasing to 11.6% (95% CI 8.0-16.0%) among men with height loss ≥3 cm. After adjustment for demographics, fall history, multimorbidity, baseline height, weight change, and femoral neck bone mineral density and considering competing mortality risk, men with height loss ≥3 cm versus <1 cm had a nearly twofold (subdistribution hazard ratio [HR] = 1.94, 95% CI 1.06-3.55) higher risk of hip fracture and a 1.4-fold (subdistribution HR = 1.42, 95% CI 1.05-1.91) increased risk of any clinical fracture. Height loss ≥3 cm in men during old age was associated with higher subsequent risk of clinical fractures, especially hip fractures, even after accounting for the competing risk of death and traditional skeletal and non-skeletal risk factors. © 2021 American Society for Bone and Mineral Research (ASBMR).
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http://dx.doi.org/10.1002/jbmr.4278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255268PMC
June 2021

Opportunistic Osteoporosis Screening Using Low-Dose Computed Tomography (LDCT): Promising Strategy, but Challenges Remain.

J Bone Miner Res 2021 03 18;36(3):425-426. Epub 2021 Feb 18.

Department of Medicine and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.

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http://dx.doi.org/10.1002/jbmr.4266DOI Listing
March 2021

Response to "Red Cell Distribution Width Is a Risk Factor for Hip Fracture in Elderly Men Without Anemia".

J Bone Miner Res 2021 06 28;36(6):1203. Epub 2021 Jan 28.

San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA, USA.

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http://dx.doi.org/10.1002/jbmr.4242DOI Listing
June 2021

Reframing Hospital to Home Discharge from "Should We?" to "How Can We?": COVID-19 and Beyond.

J Am Geriatr Soc 2021 03 6;69(3):608-609. Epub 2021 Feb 6.

Veterans Affairs Health Services Research and Development Center for Care Delivery and Outcomes Research, Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota, USA.

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http://dx.doi.org/10.1111/jgs.17036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014114PMC
March 2021

Bisphosphonates for Postmenopausal Osteoporosis.

JAMA 2021 01;325(1):96

University of Minnesota, Minneapolis VA Health Care System, Minneapolis.

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http://dx.doi.org/10.1001/jama.2020.2923DOI Listing
January 2021

A Menopause Strategies-Finding Lasting Answers for Symptoms and Health (MsFLASH) Investigation of Self-Reported Menopausal Palpitation Distress.

J Womens Health (Larchmt) 2021 04 20;30(4):533-538. Epub 2020 Nov 20.

Department of Family Medicine and Public Health, University of California, San Diego, California, USA.

Study to describe the degree of menopausal palpitation distress and its demographic, clinical, symptom, and quality-of-life (QOL) correlates. Analysis of existing, baseline, data from peri- and postmenopausal women, 42 to 62 years of age, who participated in the Menopause Strategies-Finding Lasting Answers for Symptoms and Health (MsFLASH) clinical trials testing interventions for vasomotor symptoms ( = 759). Up to 46.8% of menopausal women report having palpitations, yet the symptom is relatively understudied. Little is known about palpitation distress or its correlates. Degree of distress from "heart racing or pounding" was self-reported over the past two weeks as "not at all," "a little bit," "moderately," "quite a bit," or "extremely." Other measures included self-report forms, clinic-verified body mass index (BMI), vasomotor symptom diaries, and validated symptom and QOL tools. The percentage who reported palpitation distress was 19.6%, 25.2%, and 33.5% in the three trials or 25.0% overall. In multivariate analysis, the odds of reporting palpitation distress was lower in past smokers (odds ratio [OR] = 0.59 [95% confidence interval (CI) 0.38-0.90]) and current smokers (OR = 0.48 [0.27-0.87]) relative to never-smokers and lower with every 5 kg/m higher BMI (OR = 0.82 [0.69-0.98]).The odds of reporting palpitation distress was higher with every five point more severe insomnia (OR = 1.28 [1.05-1.54]), five point worse depressive symptoms (OR = 1.47 [1.11-1.95]), five point worse perceived stress (OR = 1.19 [1.01-1.39]), and one point worse menopausal QOL (OR = 1.29 [1.06-1.57]). Menopausal palpitation distress is common and associated with demographic, clinical, symptom, and QOL factors. Findings can be used for screening in clinical practice and to justify additional research on this understudied symptom.
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http://dx.doi.org/10.1089/jwh.2020.8586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064942PMC
April 2021

Clinically Important Differences for Mobility Measures Derived from the Testosterone Trials.

J Am Geriatr Soc 2021 02 18;69(2):517-523. Epub 2020 Nov 18.

Section of Geriatric Medicine, Yale School of Medicine, New Haven, Connecticut, USA.

Background/objectives: Accurate estimates of clinically important difference (CID) are required for interpreting the clinical importance of treatments to improve physical function, but CID estimates vary in different disease populations. We determined the CID for two common measures of walking ability in mobility-limited older men.

Design: Longitudinal, multisite placebo-controlled trial.

Setting/participants: Men enrolled in the Testosterone Trials who had self-reported mobility limitation and gait speed less than 1.2 m/second (n = 429). Testosterone- and placebo-allocated participants were combined for this study.

Results: Mean changes from baseline, adjusting for time-in-intervention and site, were 29.6, 13.2, 12.5, -2.4, and -32.6 m for 6MWD, and 15.4, 7.2, 2.1, -3.4, and -7.2 for PF10 in men who reported their mobility was "very/much better," "little better," "no change," "little worse," or "much worse," respectively. CID estimates using regression, ROC, and eCDF varied from 5.0-29.6 m for 6MWD, and 5.0-15.2 points for PF10.

Conclusion: CID estimates vary by the population studied and by the method and precision of measurement. Increases of 16 to 30 m for 6MWD and 5 to 15 points for PF10 over 12 months appear to be clinically meaningful in mobility-limited, older hypogonadal men. These CID estimates may be useful in the design of efficacy trials of therapies to improve physical function.
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http://dx.doi.org/10.1111/jgs.16942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500528PMC
February 2021

Association Between Variation in Red Cell Size and Multiple Aging-Related Outcomes.

J Gerontol A Biol Sci Med Sci 2021 06;76(7):1288-1294

San Francisco Coordinating Center, California.

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: Three thousand six hundred and thirty-five community-dwelling older men were enrolled in the prospective Osteoporotic Fractures in Men Study. RDW was categorized into 4 groups (≤13.0%, 13.1%-14.0%, 14.1%-15.0%, and ≥15.1%). Functional limitations, frailty, strength, physical performance, and cognitive function were measured at baseline and 7.4 years later. Falls were recorded in the year after baseline; hospitalizations were obtained for 2 years after baseline. Mortality was assessed during a mean of 8.3 years of follow-up.

Results: Participants with greater variability in red cell size were weaker, walked more slowly, and had a worse cognitive function. They were more likely to have functional limitations (35.2% in the highest RDW category vs 16.0% in the lowest, p < .001) and frailty (30.3% vs 11.3%, p < .001). Those with greater variability in red cell size were more likely to develop new functional limitations and to become frail. The risk of having 2 or more falls was also greater (highest 19.2% vs lowest 10.3%, p < .001). The risk of hospitalization was higher in those with the highest variability (odds ratio [95% confidence interval], 1.8 [1.3-2.5]) compared with the lowest. Variability in red cell size was related to total and cause-specific mortality.

Conclusion: Greater variability in red cell size is associated with diverse aging-related outcomes, suggesting that it may have potential value as a marker for biological aging.
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http://dx.doi.org/10.1093/gerona/glaa217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202142PMC
June 2021

Implications of Frailty among Men with Implantable Cardioverter Defibrillators.

South Med J 2020 09;113(9):427-431

From the Division of Cardiology, Minneapolis VA Health Care System, Minneapolis, and the Division of Epidemiology & Community Health, University of Minnesota, Minneapolis, Minnesota.

Objectives: Frailty is associated with adverse outcomes, but little is known of the impact of frailty on patients with implantable cardioverter defibrillators (ICDs). This study sought to determine the prevalence of frailty, based on quantitative assessment, and assessed its potential impact on outcomes among community-dwelling men with ICDs.

Methods: A total of 124 ICD-treated men presenting for a routine device clinic appointment between May and October 2016 underwent frailty assessment consisting of three components: shrinking (weight loss ≥5% during the past year), weakness (inability to rise from a chair without using their arms), and self-reported poor energy level. Patients who had no components were considered robust, those with 1 component were intermediate stage, and those with ≥2 components were deemed frail.

Results: Mean age was 70.4 (±9.7) years. Of the 124 men, 31 (25%) were considered to be frail, 65 (52%) were intermediate, and 28 (23%) were robust. Frail men were older and were more likely to have symptomatic heart failure, chronic kidney disease, and hypertension ( < 0.05 for all) compared with nonfrail men. During a follow-up of 16 months, frail men were significantly more likely to die compared with nonfrail men (29% vs 5.4%, < 0.0003). The incidence of appropriate ICD shocks (16.1% vs 6.5%) or hospitalizations (38.7% vs 23.7%) tended to be higher among frail versus nonfrail patients, but neither reached statistical significance ( = 0.10).

Conclusions: Almost one-fourth of men with ICD are frail. Almost one-third of frail ICD patients died within 16 months. It may be useful to assess frailty in patients with ICD.
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http://dx.doi.org/10.14423/SMJ.0000000000001137DOI Listing
September 2020

Co-Occurrence of Lower Urinary Tract Symptoms and Frailty among Community-Dwelling Older Men.

J Am Geriatr Soc 2020 12 21;68(12):2805-2813. Epub 2020 Aug 21.

Department of Orthopaedics and Rehabilitation, Oregon Health and Science University, Portland, Oregon, USA.

Background/objectives: To estimate associations between lower urinary tract symptoms (LUTS) and phenotypic frailty in older men.

Design: Cross-sectional study.

Setting: Community-dwelling men recruited from 2000 to 2002 from six U.S. academic centers for the Osteoporotic Fractures in Men Study.

Participants: A total of 5,979 men aged 65 and older.

Measurements: The independent variable was LUTS severity (none/mild, moderate, or severe) assessed with the American Urologic Association Symptom Index. Participants were categorized as frail, intermediate stage, or robust using an adapted Cardiovascular Health Study index (components: low lean mass, weakness, exhaustion, slowness, and low physical activity). Associations were estimated with odds ratios and 95% confidence intervals (CIs) from multivariable multinomial logistic regression models adjusted for potential confounders of age, other demographics, health-related behaviors, and comorbidities.

Results: The prevalence of frailty was 7%, 11%, and 18% among men with none/mild, moderate, and severe LUTS, respectively. Moderate and severe LUTS, overall and by storage and voiding subscores, were associated with higher odds of both intermediate stage and frailty in all models. After adjustment for confounders, the odds of frailty was 1.41 times higher among men with moderate LUTS (95% CI = 1.14-1.74) and 2.51 times higher among men with severe LUTS (95% CI = 1.76-3.55), compared with none/mild LUTS. Severe LUTS was associated with a greater odds of individual frailty components exhaustion and low physical activity.

Conclusion: The prevalence of phenotypic frailty is higher among older community-dwelling men with moderate or severe LUTS compared with those with mild or no LUTS. The positive association between LUTS severity and frailty among older men appears independent of age and known frailty risk factors. Although the temporal direction of this association and the utility of LUTS or frailty interventions in this population remain unclear, the high co-occurrence of these conditions could lead to earlier identification of frailty when clinically appropriate.
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http://dx.doi.org/10.1111/jgs.16766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744321PMC
December 2020

Serial Bone Density Measurement and Incident Fracture Risk Discrimination in Postmenopausal Women.

JAMA Intern Med 2020 09;180(9):1232-1240

Division of Epidemiology & Community Health, Department of Medicine, University of Minnesota and Veterans Affairs Health Care System, Minneapolis.

Importance: Repeated bone mineral density (BMD) testing to screen for osteoporosis requires resources. For patient counseling and optimal resource use, it is important for clinicians to know whether repeated BMD measurement (compared with baseline BMD measurement alone) improves the ability to discriminate between postmenopausal women who will and will not experience a fracture.

Objective: To assess whether a second BMD measurement approximately 3 years after the initial assessment is associated with improved ability to estimate fracture risk beyond the baseline BMD measurement alone.

Design, Setting, And Participants: The Women's Health Initiative is a prospective observational study. Participants in the present cohort study included 7419 women with a mean (SD) follow-up of 12.1 (3.4) years between 1993 and 2010 at 3 US clinical centers. Data analysis was conducted between May 2019 and December 2019.

Main Outcomes And Measures: Incident major osteoporotic fracture (ie, hip, clinical spine, forearm, or shoulder fracture), hip fracture, baseline BMD, and absolute change in BMD were assessed. The area under the receiver operating characteristic curve (AU-ROC) for baseline BMD, absolute change in BMD, and the combination of baseline BMD and change in BMD were calculated to assess incident fracture risk discrimination during follow-up.

Results: Of 7419 participants, the mean (SD) age at baseline was 66.1 (7.2) years, the mean (SD) body mass index was 28.7 (6.0), and 1720 (23%) were nonwhite individuals. During the study follow-up (mean [SD] 9.0 [3.5] years after the second BMD measurement), 139 women (1.9%) experienced hip fractures, and 732 women (9.9%) experienced major osteoporotic fracture. In discriminating between women who experience hip fractures and those who do not, AU-ROC values were 0.71 (95% CI, 0.67-0.75) for baseline total hip BMD, 0.61 (95% CI, 0.56-0.65) for change in total hip BMD, and 0.73 (95% CI, 0.69-0.77) for the combination of baseline total hip BMD and change in total hip BMD. Femoral neck and lumbar spine BMD values had similar discrimination for hip fracture. For discrimination of major osteoporotic fracture, AU-ROC values were 0.61 (95% CI, 0.59-0.63) for baseline total hip BMD, 0.53 (95% CI, 0.51-0.55) for change in total hip BMD, and 0.61 (95% CI, 0.59-0.63) for the combination of baseline total hip BMD and change in total hip BMD. Femoral neck and lumbar spine BMD values had similar ability to discriminate between women who experienced major osteoporotic fracture and those who did not. Associations between change in bone density and fracture risk did not differ by subgroup, including diabetes, age, race/ethnicity, body mass index, or baseline BMD T score.

Conclusions And Relevance: The findings of this study suggest that a second BMD assessment approximately 3 years after the initial measurement was not associated with improved discrimination between women who did and did not experience subsequent hip fracture or major osteoporotic fracture beyond the baseline BMD value alone and should not routinely be performed.
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http://dx.doi.org/10.1001/jamainternmed.2020.2986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385675PMC
September 2020

Delayed Denosumab Injections and Fracture Risk.

Ann Intern Med 2020 10 28;173(7):582-583. Epub 2020 Jul 28.

HealthPartners Institute and University of Minnesota, Minneapolis, Minnesota (J.T.S.).

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http://dx.doi.org/10.7326/M20-4802DOI Listing
October 2020

Effects of pharmacologic and nonpharmacologic interventions on menopause-related quality of life: a pooled analysis of individual participant data from four MsFLASH trials.

Menopause 2020 10;27(10):1126-1136

Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.

Objective: The Menopause Strategies: Finding Lasting Answers for Symptoms and Health network conducted three randomized clinical trials (RCTs) testing six interventions treating vasomotor symptoms (VMS), and also collected menopause-related quality of life (QOL) measures. A fourth RCT assessed an intervention for insomnia symptoms among women with VMS. We describe these seven interventions' effects on menopause-related QOL relative to control in women with VMS.

Methods: We pooled individual-level data from 1,005 peri- and postmenopausal women with 14 or more VMS/week across the four RCTs. Interventions included escitalopram 10 to 20 mg/d; yoga/aerobic exercise; 1.8 g/d omega-3-fatty acids; oral 17-beta-estradiol 0.5 mg/d; venlafaxine XR 75 mg/d; and cognitive behavioral therapy for insomnia (CBT-I). Outcomes measures were the Menopause-specific Quality of Life scale and its subscales.

Results: Significant improvements in total Menopause-specific Quality of Life from baseline were observed with estradiol, escitalopram, CBT-I, and yoga, with mean decreases of 0.3 to 0.5 points relative to control. The largest improvement in the vasomotor subscale was observed with estradiol (-1.2 points), with more modest but significant effects seen with escitalopram, yoga, and CBT-I. Significant improvements in the psychosocial subscale were observed for escitalopram, venlafaxine, and CBT-I. For the physical subscale, the greatest improvement was observed for CBT-I and exercise, whereas for the sexual subscale, the greatest improvement was observed for CBT-I, with yoga and estradiol demonstrating smaller effects.

Conclusions: These results suggest that for menopause-related QOL, women have a variety of treatment strategies to choose from and can select an approach based on most bothersome symptoms and individual preferences.
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http://dx.doi.org/10.1097/GME.0000000000001597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034544PMC
October 2020

Association between post-stroke disability and 5-year hip-fracture risk: The Women's Health Initiative.

J Stroke Cerebrovasc Dis 2020 Aug 10;29(8):104976. Epub 2020 Jun 10.

Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN. Electronic address:

Background: Hip fractures are a significant post-stroke complication. We examined predictors of hip fracture risk after stroke using data from the Women's Health Initiative (WHI). In particular, we examined the association between post-stroke disability levels and hip fracture risk.

Methods: The WHI is a prospective study of 161,808 postmenopausal women aged 50-79 years. Trained physicians adjudicated stroke events and hip fractures. Our study included stroke survivors from the observational and clinical trial arms who had a Glasgow Outcome Scale of good recovery, moderately disabled, or severely disabled and survived more than 7 days post-stroke. Hip fracture-free status was compared across disability levels. Secondary analysis examined hip fracture risk while accounting for competing risk of death.

Results: Average age at time of stroke was 74.6±7.2 years; 84.3% were white. There were 124 hip fractures among 4,640 stroke survivors over a mean follow-up time of 3.1±1.8 years. Mortality rate was 23.3%. Severe disability at discharge (Hazard Ratio (HR): 2.1 (95% Confidence Interval (CI): 1.4-3.2), but not moderate disability (HR: 1.1 (95%CI: 0.7-1.7), was significantly associated with an increased risk of hip fracture compared to good recovery status. This association was attenuated after accounting for mortality. White race, increasing age and higher Fracture Risk Assessment Tool (FRAX)-predicted hip fracture risk (without bone density information) were associated with an increased hip fracture risk. After accounting for mortality, higher FRAX risk and white race remained significant.

Conclusion: Severe disability after stroke and a higher FRAX risk score were associated with risk of subsequent hip fracture. After accounting for mortality, only the FRAX risk score remained significant. The FRAX risk score appears to identify stroke survivors at high risk of fractures. Our results suggest that stroke units can consider the incorporation of osteoporosis screening into care pathways.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.104976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7394038PMC
August 2020

Putative Cut-Points in Sarcopenia Components and Incident Adverse Health Outcomes: An SDOC Analysis.

J Am Geriatr Soc 2020 07 7;68(7):1429-1437. Epub 2020 Jul 7.

Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Objectives: Analyses performed by the Sarcopenia Definitions and Outcomes Consortium (SDOC) identified cut-points in several metrics of grip strength for consideration in a definition of sarcopenia. We describe the associations between the SDOC-identified metrics of low grip strength (absolute or standardized to body size/composition); low dual-energy x-ray absorptiometry (DXA) lean mass as previously defined in the literature (appendicular lean mass [ALM]/ht ); and slowness (walking speed <.8 m/s) with subsequent adverse outcomes (falls, hip fractures, mobility limitation, and mortality).

Design: Individual-level, sex-stratified pooled analysis. We calculated odds ratios (ORs) or hazard ratios (HRs) for incident falls, mobility limitation, hip fractures, and mortality. Follow-up time ranged from 1 year for falls to 8.8 ± 2.3 years for mortality.

Setting: Eight prospective observational cohort studies.

Participants: A total of 13,421 community-dwelling men and 4,828 community-dwelling women. MEASUREMENTS Grip strength by hand dynamometry, gait speed, and lean mass by DXA.

Results: Low grip strength (absolute or standardized to body size/composition) was associated with incident outcomes, usually independently of slowness, in both men and women. ORs and HRs generally ranged from 1.2 to 3.0 for those below vs above the cut-point. DXA lean mass was not consistently associated with these outcomes. When considered together, those who had both muscle weakness by absolute grip strength (<35.5 kg in men and <20 kg in women) and slowness were consistently more likely to have a fall, hip fracture, mobility limitation, or die than those without either slowness or muscle weakness.

Conclusion: Older men and women with both muscle weakness and slowness have a higher likelihood of adverse health outcomes. These results support the inclusion of grip strength and walking speed as components in a summary definition of sarcopenia. J Am Geriatr Soc 68:1429-1437, 2020.
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http://dx.doi.org/10.1111/jgs.16517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508260PMC
July 2020

To the Editor.

Menopause 2020 07;27(7):836-837

Public Health Sciences Fred Hutchinson Cancer Research Center Seattle, WA.

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http://dx.doi.org/10.1097/GME.0000000000001606DOI Listing
July 2020

Muscle Mass Assessed by the D3-Creatine Dilution Method and Incident Self-reported Disability and Mortality in a Prospective Observational Study of Community-Dwelling Older Men.

J Gerontol A Biol Sci Med Sci 2021 01;76(1):123-130

Department of Nutrition Sciences, University of California, Berkeley.

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, by DXA) were assessed at the Year 14 Visit (2014-2016) of the prospective Osteoporotic Fractures in Men study (N = 1,425, age 77-101 years). Disability in activities of daily living (ADLs), instrumental ADLs, and mobility tasks was self-reported at the Year 14 visit and 2.2 years later; deaths were centrally adjudicated over 3.3 years. Relative risks and 95% confidence intervals (CI) were estimated per standard deviation decrement with negative binomial, logistic regression, or proportional hazards models.

Results: In age- and clinical center-adjusted models, the relative risks per decrement in D3Cr muscle mass/wgt was 1.9 (95% CI: 1.2, 3.1) for incident self-reported ADL disability; 1.5 (95% CI: 1.3, 1.9) for instrumental ADL disability; and 1.8 (95% CI: 1.5, 2.2) for mobility disability. In age-, clinical center-, and weight-adjusted models, the relative risks per decrement in D3Cr muscle mass was 1.8 (95% CI: 1.5, 2.2) for all-cause mortality. In contrast, lower DXA ALM was not associated with any outcome. Associations of D3Cr muscle mass with these outcomes were slightly attenuated after adjustment for confounding factors and the potentially mediating effects of strength and physical performance.

Conclusions: Low muscle mass as measured by D3Cr dilution is a novel risk factor for clinically meaningful outcomes in older men.
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http://dx.doi.org/10.1093/gerona/glaa111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756711PMC
January 2021

Frailty Phenotype and Healthcare Costs and Utilization in Older Men.

J Am Geriatr Soc 2020 09 13;68(9):2034-2042. Epub 2020 May 13.

Division of Epidemiology & Community Health, University of Minnesota, Minneapolis, Minnesota, USA.

Objectives: To determine the association of the frailty phenotype with subsequent healthcare costs and utilization.

Design: Prospective cohort study (Osteoporotic Fracture in Men [MrOS]).

Setting: Six US sites.

Participants: A total of 1,514 community-dwelling men (mean age = 79.3 years) participating in the MrOS Year 7 (Y7) examination linked with their Medicare claims data.

Measurements: At Y7, the frailty phenotype was operationalized using five components and categorized as robust, pre-frail, or frail. Multimorbidity and a frailty indicator (approximating the deficit accumulation index) were derived from claims data. Functional limitations were assessed by asking about difficulty performing instrumental activities of daily living. Total direct healthcare costs and utilization were ascertained during 36 months following Y7.

Results: Mean of total annualized costs (2018 dollars) was $5,707 (standard deviation [SD] = 8,800) among robust, $8,964 (SD = 18,156) among pre-frail, and $20,027 (SD = 27,419) among frail men. Compared with robust men, frail men (cost ratio [CR] = 2.35; 95% confidence interval [CI] = 1.88-2.93) and pre-frail men (CR = 1.28; 95% CI = 1.11-1.48) incurred greater total costs after adjustment for demographics, multimorbidity, and cognitive function. Associations of phenotypic pre-frailty and frailty with higher total costs were somewhat attenuated but persisted after further consideration of functional limitations and a claims-based frailty indicator. Each individual frailty component was also associated with higher total costs. Frail vs robust men had higher odds of hospitalization (odds ratio [OR] = 2.62; 95% CI = 1.75-3.91) and skilled nursing facility (SNF) stay (OR = 3.36; 95% CI = 1.83-6.20). A smaller but significant effect of the pre-frail category on SNF stay was present.

Conclusion: Phenotypic pre-frailty and frailty were associated with higher subsequent total healthcare costs in older community-dwelling men after accounting for a claims-based frailty indicator, functional limitations, multimorbidity, cognitive impairment, and demographics. Assessment of the frailty phenotype or individual components such as slowness may improve identification of older community-dwelling adults at risk for costly extensive care.
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http://dx.doi.org/10.1111/jgs.16522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666024PMC
September 2020

Individual and joint trajectories of change in bone, lean mass and physical performance in older men.

BMC Geriatr 2020 05 5;20(1):161. Epub 2020 May 5.

Oregon Health and Science University, Portland, OR, USA.

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 cohort study of older men.

Methods: Using repeated longitudinal data from up to four visits across 6.9 years from up to 4681 men (mean age at baseline 72.7 yrs. ±5.3) participating in the Osteoporotic Fractures in Men (MrOS) Study, we used group-based trajectory models (PROC TRAJ in SAS) to identify age-related patterns of change in four properties of muscle, physical performance, and bone: total hip bone mineral (BMD) density (g/m) and appendicular lean mass/ht (kg/m), by DXA; grip strength (kg), by hand dynamometry; and walking speed (m/s), by usual walking pace over 6 m. We also described joint trajectories in all pair-wise combinations of these measures. Mean posterior probabilities of placement in each trajectory (or joint membership in latent groups) were used to assess internal reliability of the model. The number of trajectories for each individual factor was limited to three, to ensure that the pair-wise determination of joint trajectories would yield a tractable number of groups as well as model fit considerations.

Results: The patterns of change identified were generally similar for all measures, with three district groups declining over time at roughly similar rates; joint trajectories revealed similar patterns with no cross-over or convergence between groups. Mean posterior probabilities for all trajectories were similar and consistently above 0.8 indicating reasonable model fit to the data.

Conclusions: Our description of trajectories of change with age in bone mineral density, grip strength, walking speed and appendicular lean mass found that groups identified by these methods appeared to have little crossover or convergence of change with age, even when considering joint trajectories of change in these factors.
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http://dx.doi.org/10.1186/s12877-020-01560-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201689PMC
May 2020

Endogenous Testosterone Levels and the Risk of Incident Cardiovascular Events in Elderly Men: The MrOS Prospective Study.

J Endocr Soc 2020 May 24;4(5):bvaa038. Epub 2020 Mar 24.

Division of General Internal Medicine, University of California at San Francisco, San Francisco, California.

Context: Observational studies show discordant links between endogenous testosterone levels and cardiovascular diseases (CVD).

Objective: We assessed whether sex hormones and sex hormone-binding globulin (SHBG) are associated with CVD in community-dwelling elderly men.

Design Setting And Participants: Prospective study of incident CVD among 552 men ≥ 65 years in the MrOS Sleep Study without prevalent CVD and no testosterone therapy at baseline.

Outcomes: Fasting serum levels of total testosterone and estradiol were measured using liquid chromatography-mass spectrometry, and SHBG by chemiluminescent substrate. The association of sex hormones and SHBG with incident coronary heart disease (CHD), cerebrovascular (stroke and transient ischemic attack) and peripheral arterial disease (PAD) events were assessed by quartile and per SD increase in proportional hazards models.

Results: After 7.4 years, 137 men (24.8%) had at least 1 CVD event: 90 CHD, 45 cerebrovascular and 26 PAD. The risk of incident CVD events was not associated with quartiles of baseline sex hormones or SHBG (all  ≥ 0.16). For +1 SD in total testosterone, the multivariate-adjusted hazard ratio was 1.04 (95% CI, 0.80-1.34) for CHD, 0.86 (0.60-1.25) for cerebrovascular, and 0.81 (0.52-1.26) for PAD events. When analyzed as continuous variables or comparing highest to low quartile, levels of bioavailable testosterone, total estradiol, testosterone/estradiol ratio and SHBG were not associated with CVD events.

Conclusions: In community-dwelling elderly men, endogenous levels of testosterone, estradiol, and SHBG were not associated with increased risk of CHD, cerebrovascular, or PAD events. These results are limited by the small number of events and should be explored in future studies.
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http://dx.doi.org/10.1210/jendso/bvaa038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173399PMC
May 2020
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