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Type 2 diabetes mellitus and lower weight are both associated with osteoporotic fractures, but the roles of variability and trajectory are less clear. The associations of these factors among older adults with dysglycemia, who are at highest risk of fracture, with fracture risk and BMD remain uncertain. We followed 775 men and 1080 women from the Cardiovascular Health Study (mean age 77.4 years) with abnormal oral glucose tolerance testing in 1989-1990. We measured their weights yearly through 1994-1995 and derived intra-individual mean weight, weight slope, and weight variability. We also used growth mixture modeling to derive 4 latent BMI trajectories over time. We used Cox proportional hazards models to calculate hazard ratios (HRs) and 95% CI for subsequent hip fracture through 2015 and linear regression models to estimate cross-sectional associations with BMD of the hip. Each 10 kg higher mean weight was associated with a lower risk of subsequent hip fracture overall (HR 0.81; CI, 0.70-0.94) and among women (HR 0.76; CI, 0.64-0.91) and with higher BMD (p <.001). Higher weight variability was directly associated with incident hip fracture among women (HR 1.18; CI, 1.03-1.35). Compared with a stable trajectory, a "progressive overweight" trajectory was associated with lower risk of hip fracture (HR 0.66; CI, 0.44-0.99). An uncommon trajectory of "accelerating obesity" was associated with higher BMD. Among older adults with dysglycemia at high risk for fracture, lower mean weight is associated with higher fracture risk, but variability and trajectory may also contribute. These results highlight the complex effects of weight in older age., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Frailty defined by the Cardiovascular Health Study (CHS) phenotype is associated with higher healthcare expenditures in community-dwelling Medicare beneficiaries after accounting for claims-based cost indicators. However, frailty assessment using the CHS phenotype is often not feasible in routine clinical practice. We evaluated whether frailty identified by the simple Study of Osteoporotic Fractures (SOF) phenotype is associated with subsequent incremental costs after accounting for claims-derived cost indicators., Methods: Prospective study utilizing data from four cohort studies of older adults linked with Medicare claims composed of 8264 community-dwelling fee-for-service beneficiaries (4389 women, 3875 men). SOF Frailty Phenotype (three components: weight loss, poor energy, and inability to rise from chair five times without using arms) and CHS Frailty Phenotype (operationalized using five components) derived from cohort data. Participants were classified as robust, prefrail, or frail using each phenotype. Multimorbidity index (CMS Hierarchical Conditions Categories score) and Kim frailty indicator (approximating the deficit accumulation index) derived from claims. Annualized total and sector-specific healthcare costs ascertained for 36 months after frailty assessment., Results: Average annualized total healthcare costs (2023 US dollars) were $15,021 in women and $15,711 in men. After accounting for claims-based multimorbidity and frailty indicators, average incremental costs of SOF phenotypic frailty (two or three components) versus robust (none) were $7142 in women and $5961 in men, only modestly lower than incremental costs of CHS phenotypic frailty ($9422 in women, $6479 in men). SOF phenotypic frailty in both sexes was associated with higher subsequent expenditures in the inpatient, skilled nursing facility, and home healthcare sectors., Conclusions: As observed with CHS phenotypic frailty, SOF phenotypic frailty is associated with higher subsequent total and sector-specific expenditures after accounting for claims-derived indicators. The parsimonious SOF phenotype can be readily assessed in space-constrained and time-limited practice settings to improve identification of older adults at high risk of costly care., (© 2024 The Author(s). Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: Life-space mobility captures the daily, enacted mobility of older adults. We determined cross-sectional associations between life-space mobility and cognitive impairment (CI) among community-dwelling women in the 9th and 10th decades of life., Methods: A total of 1375 (mean age 88 years; 88% White) community-dwelling women enrolled in a prospective cohort of older women. Life-space score was calculated with range 0 (daily restriction to one's bedroom) to 120 (daily trips leaving town without assistance) and categorized (0-20, 21-40, 41-60, 61-80, 81-120). The primary outcome was adjudicated CI defined as mild cognitive impairment or dementia; scores on a 6-test cognitive battery were secondary outcomes., Results: Compared to women with life-space scores of 81-120 and after adjustment for demographics and depressive symptoms, the odds of CI was 1.4-fold (OR 1.36, 95% CI 0.91-2.03) higher for women with life-space scores of 61-80, twofold (OR 1.98, 95% CI 1.33-2.94) higher for women with life-space scores of 41-60, 2.6-fold (OR 2.62, 95% CI 1.71-4.01) higher for women with life-space scores of 21-40, and 2.7-fold (OR 2.71, 95% CI 1.27-5.79) higher for women with life-space scores of 0-20. The association of life-space scores with adjudicated CI was primarily due to higher odds of dementia; the odds of dementia versus normal cognition was eightfold (OR 8.63, 95% CI 3.20-23.26) higher among women with life-space scores of 0-20 compared to women with life-space scores of 81-120. Lower life-space scores were associated in a graded manner with lower mean scores on tests of delayed recall (California Verbal Learning Test-II delayed recall) and language and executive function (phonemic fluency, category fluency, and Trails B). Life-space score was not associated with scores on tests of attention and working memory (forward and backward digit span)., Conclusions: Lower life-space mobility is associated in a graded manner with CI among community-dwelling White women in the 9th and 10th decades of life., (© 2024 The Author(s). Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Although low back pain (LBP) may persist or recur over time, few studies have evaluated the individual course of LBP over a long-term period, particularly among older adults. Based on data from the longitudinal Osteoporotic Fractures in Men (MrOS) Study, we aimed to identify and describe different LBP trajectories in older men and characterize members in each trajectory group. A total of 5 976 community-dwelling men (mean age = 74.2) enrolled at 6 U.S. sites were analyzed. Participants self-reported LBP (yes/no) every 4 months for a maximum of 10 years. Latent class growth modeling was performed to identify unique LBP trajectory groups that explained variation in the LBP data. The association of baseline characteristics with trajectory group membership was assessed using univariable and multivariable multinominal logistic regression. A 5-class solution was chosen; no/rare LBP (n = 2 442/40.9%), low frequency-stable LBP (n = 1 040/17.4%), low frequency-increasing LBP (n = 719/12%), moderate frequency-decreasing LBP (n = 745/12.5%), and high frequency-stable LBP (n = 1 030/17.2%). History of falls (OR = 1.52), history of LBP (OR = 6.37), higher physical impairment (OR = 1.51-2.85), and worse psychological function (OR = 1.41-1.62) at baseline were all associated with worse LBP trajectory groups in this sample of older men. These findings present an opportunity for targeted interventions and/or management to older men with worse or increasing LBP trajectories and associated modifiable risk factors to reduce the impact of LBP and improve quality of life., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

As there are effective treatments to reduce hip fractures, identification of patients at high risk of hip fracture is important to inform efficient intervention strategies. To obtain a new tool for hip fracture prediction, we developed a protein-based risk score in the Cardiovascular Health Study using an aptamer-based proteomic platform. The proteomic risk score predicted incident hip fractures and improved hip fracture discrimination in two Trøndelag Health Study validation cohorts using the same aptamer-based platform. When transferred to an antibody-based proteomic platform in a UK Biobank validation cohort, the proteomic risk score was strongly associated with hip fractures (hazard ratio per s.d. increase, 1.64; 95% confidence interval 1.53-1.77). The proteomic risk score, but not available polygenic risk scores for fractures or bone mineral density, improved the C-index beyond the fracture risk assessment tool (FRAX), which integrates information from clinical risk factors (C-index, FRAX 0.735 versus FRAX + proteomic risk score 0.776). The developed proteomic risk score constitutes a new tool for stratifying patients according to hip fracture risk; however, its improvement in hip fracture discrimination is modest and its clinical utility beyond FRAX with information on femoral neck bone mineral density remains to be determined., (© 2024. The Author(s).)

Objective: We evaluated whether more severe back pain phenotypes-persistent, frequent, or disabling back pain-are associated with higher mortality rate among older men., Methods: In this secondary analysis of a prospective cohort, the Osteoporotic Fractures in Men (MrOS) study, we evaluated mortality rates by back pain phenotype among 5215 older community-dwelling men (mean age, 73 years, SD = 5.6) from 6 sites in the United States. The primary back pain measure used baseline and Year 5 back pain questionnaire data to characterize participants as having no back pain, nonpersistent back pain, infrequent persistent back pain, or frequent persistent back pain. Secondary measures of back pain from the Year 5 questionnaire included disabling back pain phenotypes. The main outcomes measured were all-cause and cause-specific death., Results: After the Year 5 exam, during up to 18 years of follow-up (mean follow-up = 10.3 years), there were 3513 deaths (1218 cardiovascular, 764 cancer, 1531 other). A higher proportion of men with frequent persistent back pain versus no back pain died (78% versus 69%; sociodemographic-adjusted HR = 1.27, 95% CI = 1.11-1.45). No association was evident after further adjustment for health-related factors, such as self-reported general health and comorbid chronic health conditions (fully adjusted HR = 1.00; 95% CI = 0.86-1.15). Results were similar for cardiovascular deaths and other deaths, but we observed no association of back pain with cancer deaths. Secondary back pain measures, including back-related disability, were associated with increased mortality risk that remained statistically significant in fully adjusted models., Conclusion: Although frequent persistent back pain was not independently associated with risk of death in older men, additional secondary disabling back pain phenotypes were independently associated with increased mortality rate. Future investigations should evaluate whether improvements in disabling back pain affect general health and well-being or risk of death., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The aim of this study was to examine associations between empirically derived dietary pattern scores and cognition, as well as risk of cognitive decline, over an average of 4.6 (± 0.3) years in older men., Materials and Methods: This analysis was conducted as part of the Osteoporotic Fractures in Men (MrOS) prospective cohort study. Diet was assessed at Visit 1 (3/2000-4/2002) by food frequency questionnaire, and dietary patterns (Western and Prudent) were derived by factor analysis. The analytic cohort comprised 4231 community-dwelling American men who were aged 65 years or more. Cognitive function was assessed with the Modified Mini-Mental State exam (3MS) and the Trails B test at Visit 1 and at Visit 2 (3/2005-5/2006). Associations between dietary pattern score and cognition and risk of cognitive decline were estimated using mixed effects regression models. Model 1 was adjusted for age, clinic site and total energy intake (TEI). Model 2 was further adjusted for calcium and vitamin D supplement use, body mass index (BMI), physical activity, smoking, diabetes and hypertension (Western diet group) and education, calcium and vitamin D supplement use, depression, BMI, physical activity, smoking and stroke (Prudent diet group)., Results: Adherence to the Western dietary pattern was associated with higher 3MS scores and shorter Trails B test time at Visit 1 in Model 2. Adherence to the Prudent dietary pattern was associated with higher 3MS scores in Model 1 but not Model 2. There were no independent associations between dietary pattern scores and risk of cognitive decline 4.6 (± 0.3) years later at Visit 2., Conclusion: The results do not support a robust protective effect of the Prudent dietary pattern on cognition in the MrOS cohort. Associations between the Western dietary pattern and better cognitive scores should be interpreted with caution. Further research is needed to understand the complex interactions between dietary patterns and cognition in older men., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Published by Elsevier B.V.)

This study examined if the amino acids phenylalanine or tyrosine contribute to risk of hip fracture or frailty in older adults. We determined that neither phenylalanine nor tyrosine are important predictors of hip fracture or frailty. We suggest advice on protein intake for skeletal health consider specific amino acid composition., Purpose: Protein is essential for skeletal health, but the specific amino acid compositions of protein may have differential associations with fracture risk. The aim of this study was to determine the association of serum levels of the aromatic amino acids phenylalanine and tyrosine with risk for incident hip fractures over twelve years of follow-up and cross sectional associations with frailty., Methods: We included 131 older men and women from the Cardiovascular Health Study (CHS) who sustained a hip fracture over twelve years of follow-up and 131 men and women without an incident hip fracture over this same period of time. 42% of this cohort were men and 95% were Caucasian. Weighted multivariable Cox hazards molecules were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) of incident hip fracture associated with a one standard deviation (SD) higher serum level of phenylalanine or tyrosine. Relative risk regression was used to determine the cross-sectional association of these amino acids with Freid's frailty index., Results: Neither serum levels of phenylalanine (HR 0.85 (95% CI 0.62-1.16) or tyrosine (HR 0.82 (95% CI 0.62-1.1) were significantly associated with incident hip fractures or cross sectionally with frailty (frail compared with prefrail/not frail) (HR 0.92 (95% CI 0.48-1.76) and HR (0.86 (95% CI 0.46-1.61) respectively., Conclusion: Phenylalanine and tyrosine are not significant contributors to hip fractures or frailty in older men and women., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Importance: While adults aged 80 years and older account for 70% of hip fractures in the US, performance of fracture risk assessment tools in this population is uncertain., Objective: To compare performance of the Fracture Risk Assessment Tool (FRAX), Garvan Fracture Risk Calculator, and femoral neck bone mineral density (FNBMD) alone in 5-year hip fracture prediction., Design, Setting and Participants: Prognostic analysis of 3 prospective cohort studies including participants attending an index examination (1997 to 2016) at age 80 years or older. Data were analyzed from March 2023 to April 2024., Main Outcomes and Measures: Participants contacted every 4 or 6 months after index examination to ascertain incident hip fractures and vital status. Predicted 5-year hip fracture probabilities calculated using FRAX and Garvan models incorporating FNBMD and FNBMD alone. Model discrimination assessed by area under receiver operating characteristic curve (AUC). Model calibration assessed by comparing observed vs predicted hip fracture probabilities within predicted risk quintiles., Results: A total of 8890 participants were included, with a mean (SD) age at index examination of 82.6 (2.7) years; 4906 participants (55.2%) were women, 866 (9.7%) were Black, 7836 (88.1%) were White, and 188 (2.1%) were other races and ethnicities. During 5-year follow-up, 321 women (6.5%) and 123 men (3.1%) experienced a hip fracture; 818 women (16.7%) and 921 men (23.1%) died before hip fracture. Among women, AUC was 0.69 (95% CI, 0.67-0.72) for FRAX, 0.69 (95% CI, 0.66-0.72) for Garvan, and 0.72 (95% CI, 0.69-0.75) for FNBMD alone (FNBMD superior to FRAX, P = .01; and Garvan, P = .01). Among men, AUC was 0.71 (95% CI, 0.66-0.75) for FRAX, 0.76 (95% CI, 0.72-0.81) for Garvan, and 0.77 (95% CI, 0.72-0.81) for FNBMD alone (P < .001 Garvan and FNBMD alone superior to FRAX). Among both sexes, Garvan greatly overestimated hip fracture risk among individuals in upper quintiles of predicted risk, while FRAX modestly underestimated risk among those in intermediate quintiles of predicted risk., Conclusions and Relevance: In this prognostic study of adults aged 80 years and older, FRAX and Garvan tools incorporating FNBMD compared with FNBMD alone did not improve 5-year hip fracture discrimination. FRAX modestly underpredicted observed hip fracture probability in intermediate-risk individuals. Garvan markedly overpredicted observed hip fracture probability in high-risk individuals. Until better prediction tools are available, clinicians should prioritize consideration of hip BMD, life expectancy, and patient preferences in decision-making regarding drug treatment initiation for hip fracture prevention in late-life adults.

Background: Most fractures occur in women aged ≥80 years but competing mortality unrelated to fracture may limit the benefit of osteoporosis drug therapy for some women in late life. Our primary aim was to develop separate prediction models for non-spine fracture (NSF) and mortality before fracture to identify subsets of women with varying fracture versus mortality risks., Methods: Separate prediction models were developed for NSF and mortality before NSF for 4895 women aged ≥80 years enrolled in the Study of Osteoporotic Fractures (SOF) or the Health Aging and Body Composition (HABC) study. Proportional hazards models modified to account for competing mortality were used to identify candidate risk factors for each outcome. Predictors associated with NSF or mortality (p < 0.2) were included in separate competing risk models to estimate the cumulative incidence of NSF and mortality before NSF during 5 years of follow-up. This process was repeated to develop separate prediction models for hip fracture and mortality before hip fracture., Results: Significant predictors of NSF (race, total hip BMD, grip strength, prior fracture, falls, and use of selective serotonin reuptake inhibitors, benzodiazepines, or oral/transdermal estrogen) differed from predictors of mortality before NSF (age, walking speed, multimorbidity, weight change, shrinking, smoking, self-rated health, dementia, and use of warfarin). Within nine subsets of women defined by tertiles of risk, 5-year outcomes varied from 28% NSF and 8% mortality in the high-risk NSF/low-risk mortality subset, to 9% NSF and 22% mortality in the low-risk NSF/high-risk mortality subset. Similar results were seen for predictors of hip fracture and mortality before hip fracture., Conclusion: Considerable variation in 5-year competing mortality risk is present among women in late life with similar 5-year NSF risk. Both fracture risk and life expectancy should inform shared clinical decision-making regarding initiation or continuation of osteoporosis drug therapy for women aged ≥80 years., (© 2024 The American Geriatrics Society.)

Hip fractures are associated with significant disability, high cost, and mortality. However, the exact biological mechanisms underlying susceptibility to hip fractures remain incompletely understood. In an exploratory search of the underlying biology as reflected through the circulating proteome, we performed a comprehensive Circulating Proteome Association Study (CPAS) meta-analysis for incident hip fractures. Analyses included 6430 subjects from two prospective cohort studies (Cardiovascular Health Study and Trøndelag Health Study) with circulating proteomics data (aptamer-based 5 K SomaScan version 4.0 assay; 4979 aptamers). Associations between circulating protein levels and incident hip fractures were estimated for each cohort using age and sex-adjusted Cox regression models. Participants experienced 643 incident hip fractures. Compared with the individual studies, inverse-variance weighted meta-analyses yielded more statistically significant associations, identifying 23 aptamers associated with incident hip fractures (conservative Bonferroni correction 0.05/4979, P < 1.0 × 10-5). The aptamers most strongly associated with hip fracture risk corresponded to two proteins of the growth hormone/insulin growth factor system (GHR and IGFBP2), as well as GDF15 and EGFR. High levels of several inflammation-related proteins (CD14, CXCL12, MMP12, ITIH3) were also associated with increased hip fracture risk. Ingenuity pathway analysis identified reduced LXR/RXR activation and increased acute phase response signaling to be overrepresented among those proteins associated with increased hip fracture risk. These analyses identified several circulating proteins and pathways consistently associated with incident hip fractures. These findings underscore the usefulness of the meta-analytic approach for comprehensive CPAS in a similar manner as has previously been observed for large-scale human genetic studies. Future studies should investigate the underlying biology of these potential novel drug targets., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Background: Stressful life events, such as loss of a partner, loss of a pet or financial problems, are more common with increasing age and may impact the experience of pain. The aim of the current study is to determine the cross-sectional and prospective association between stressful life events and low back pain reporting in the Osteoporotic Fracture in Men Study, a cohort of older men aged ≥65 years., Methods: At a study visit (March 2005-May 2006), 5149 men reported whether they had experienced a stressful life event or low back pain in the prior 12 months. Following that visit, data on low back pain patients were gathered through triannual questionnaires every 4 months for 1 year. Multivariable logistic regression analyses estimated the association of stressful life events with recent past low back pain or future low back pain., Results: N = 2930, (57%) men reported at least one stressful life event. The presence of a stressful life event was associated with greater odds of any low back pain (OR = 1.42 [1.26-1.59]) and activity-limiting low back pain (OR = 1.74 [1.50-2.01]) in the same period and of any low back pain (OR = 1.56 [1.39-1.74]) and frequent low back pain (OR = 1.80 [1.55-2.08]) in the following year., Conclusion: In this cohort of men, the presence of stressful life events increased the likelihood of reporting past and future low back pain., Significance: Stressful life events such as accident or illness to a partner are common in later life and may impact the experience of pain. We present cross-sectional and prospective data highlighting a consistent association between stressful life events and low back pain in older men. Further, there is evidence to suggest that this relationship is upregulated by an individual's living situation. This information may be used to strengthen a biopsychosocial perspective of an individual's pain experience., (© 2023 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC ®.)