John T. Schousboe

Vasomotor symptoms, including hot flashes and night sweats, are common and burdensome for perimenopausal and postmenopausal females. This systematic review and meta-analysis evaluates the efficacy,... Background: Vasomotor symptoms (VMS) are common in perimenopausal and postmenopausal females. Purpose: To evaluate benefits, harms, patient values and preferences, and cost-effectiveness of pharmac...

Background: In a pooled analysis of 4 prospective cohort studies linked with Medicare claims (2002–2011), claims-derived predictors and cohort-derived functional impairments and phenotypic frailty were associated with higher subsequent healthcare expenditures in community-dwelling beneficiaries. Objective: Determine calibration and discrimination of published cost prediction models among a nationally representative sample of US community-dwelling older adults in an independent sample (external validation) and at a different time-point (temporal validation). Design: Prospective cohort study Setting: National Healthy Aging and Trends Study (NHATS) 2015 cohort Participants: 3,322 community-dwelling NHATS participants enrolled in Medicare fee-for-service. Measurements: Self-reported functional impairments (difficulty performing four activities of daily living) and frailty phenotype (operationalized using five components) derived from cohort data. Weighted (CMS Hierarchical Conditions Categories index) and unweighted (count of conditions) multimorbidity measures and frailty index derived from claims. Annualized healthcare costs ascertained for 36 months following 2015 examination. Cost ratios estimated from generalized linear models stratified by sex and adjusted for geographic region. Model calibration (predicted vs. observed costs by quintile) and discrimination (area under curve [AUC]) assessed. Results: In external and temporal validation cohorts, calibration was acceptable for all models with substantial agreement between predicted and observed costs. In the external cohort, the full model including claims- and cohort-derived variables had AUC = 0.78, 95% CI (0.74–0.82) in women and AUC = 0.77, 95% CI (0.73–0.81) in men, slightly higher than models limited to only claims-derived variables. Similar findings were noted in the temporal validation cohort. Conclusions: Performance of a model predicting total healthcare costs including self-reported functional impairments and phenotypic frailty together with claims-derived cost indicators is similar in a new independent cohort and in a subset of the original cohort at a later time-point. These results support clinical assessment of these geriatric syndromes for predicting risk of subsequent healthcare burden.

Background: Poor glycemic control is associated with cardiovascular disease (CVD) risk. However, it is unknown whether glycemic control is related to abdominal aortic calcification (AAC), a marker of subclinical CVD. We investigated the association between glycated hemoglobin (HbA1c) and moderate-to-high automated AAC among middle-aged to older adults from the general population. Methods: We included UK Biobank Imaging Study participants free of atherosclerotic CVD at baseline. HbA1c was measured at baseline (2006-2010) and categorized as normoglycemia (<39.0 mmol/mol), prediabetes (39.0–47.9 mmol/mol), undiagnosed diabetes (HbA1c ≥48 mmol/mol) and diagnosed diabetes. Machine learning derived AAC24 (ML-AAC24) scores were estimated using a validated automated algorithm applied to dual-energy X-ray absorptiometry lateral spine images (2014-2022). The associations of HbA1c with Moderate-to-high ML-AAC24 (defined as a score ≥2) were assessed using logistic regression adjusting for cardiovascular risk factors. Results: Of the included 48,912 participants (mean ± SD age 55 ± 7.6 years, 52% women), 9.7% had prediabetes (HbA1c 39.0–47.9 mmol/mol [5.7-6.4%]), 0.4% had undiagnosed diabetes and 2.7% diagnosed diabetes. Each 1-SD increase in log-transformed HbA1c was associated with higher odds of moderate-to-high ML-AAC24 (adjusted odds ratio [aOR] 1.12, 95%CI: 1.09-1.16). Amongst individuals with normal HbA1c this association was consistent but somewhat weaker for each 1-SD increase in log-transformed HbA1c (aOR 1.07, 95%CI 1.03-1.10). Compared to participants with normal HbA1c, those with prediabetes (aOR 1.19, 95%CI: 1.08-1.30) or diagnosed diabetes (1.64, 95%CI: 1.39-1.94) had higher odds of moderate-to-high ML-AAC24. These associations were consistent in stratified analyses by sex, age groups, body mass index, smoking status and total cholesterol Conclusions: Linear associations between HbA1c levels and ML-AAC24 were observed in UK adults, even in those with normal HbA1c level. These findings indicate that AAC may develop early in the dysglycemic continuum, supporting earlier cardiometabolic risk assessment even amongst people with “normal” levels.

Clinical cardiovascular disease (CVD) is often present in frail individuals. However, it remains unclear whether subclinical CVD, e.g., abdominal aortic calcification (AAC), is associated with frailty. This study investigated the cross-sectional relationship between AAC scored using a validated machine learning model (ML-AAC24) and physical frailty. 49,081 participants from the UK Biobank Imaging Study without atherosclerotic CVD (ASCVD) diagnosis were included. ML-AAC24 extent was categorised as low, moderate and high, based on established severity categories. Physical frailty was based on a modified Fried’s frailty phenotype comprising weak hand grip strength, slow walking speed, weight loss, exhaustion, and physical inactivity. Individuals with three or more deficits were considered frail, while one or two deficits was considered pre-frail. Multivariable-adjusted multinominal logistic regression models were used to test the associations between ML-AAC24 extent and frailty status. One in five individuals had moderate or high ML-AAC24. Compared to individuals with low ML-AAC24, those with moderate and high ML-AAC24 had greater odds of being pre-frail (ORs 1.06 95%CI 1.00–1.12 moderate; 1.14 95%CI 1.04–1.26 high) or frail (ORs 1.27 95%CI 1.12–1.44 moderate; 1.58 95%CI 1.31–1.91 high), adjusted for multiple covariates. When stratified by sex, similar results for frailty were recorded. In a population, those with moderate and high ML-AAC24 were more likely to present as pre-frail and frail. AAC identified from lateral spine images obtained during routine bone density testing, could serve as a useful marker for the early detection of frailty, highlighting the importance of multimodality care. Graphical Abstract

Emerging evidence suggests that vascular disease is linked with poorer muscle strength and higher falls risk. We evaluated the association between abdominal aortic calcification (AAC), scored using a well-established and validated 24-point machine learning algorithm (ML-AAC24), with MRI-derived fat-free muscle volume (FFMV, n = 33 640) and muscle fat infiltration (MFI, n = 33 640), appendicular lean mass (ALM, n = 36 526), handgrip strength (HGS, n = 49 049), sarcopenia (n = 35 834), and incident falls (n = 48 482) in community-dwelling adults (mean age 64.6 ± 7.8 yr, 50.9% women). ML-AAC24 was assessed on DXA-derived lateral spine images and classified into established categories based on severity: low (<2), moderate (2-5), and high (≥6). Age- and sex-specific cut-points for low FFMV and sex-specific high MFI were based on previous work. Low ALM, weak HGS, and sarcopenia were based on the revised European sarcopenia guidelines. The associations between ML-AAC24 extent, odds of having poorer muscle health measures and incident falls were tested in multivariable-adjusted logistic and Cox proportional hazards regressions, respectively. Individuals with moderate and high, compared to low ML-AAC24, had greater odds for low FFMV (1.58, 95% CI: 1.28-1.95 and 2.52, 95% CI: 1.88-3.38, respectively), high MFI (1.09, 95% CI: 1.01-1.18 and 1.45, 95% CI: 1.29-1.64, respectively), and low ALM (1.14, 95% CI: 1.04-1.24 and 1.28, 95% CI: 1.11-1.47, respectively). They also had higher odds for weak HGS (1.18, 95% CI: 1.07-1.29 and 1.24, 95% CI: 1.09-1.42, respectively) and sarcopenia (1.40, 95% CI: 1.12-1.76 and 1.69, 95% CI: 1.24-2.29, respectively). Compared to low ML-AAC24, high ML-AAC24 was associated with greater hazards for an incident fall-related hospitalization (1.31, 95% CI: 1.02-1.68). Greater ML-AAC24 extent, which can be opportunistically identified during routine bone density testing, was associated with poorer muscle composition and, function, sarcopenia, and incident falls in community-dwelling adults. Such findings may explain previous reports between AAC and higher fall and fracture risk, supporting a nexus between vascular and musculoskeletal health.

Atypical femoral fractures (AFFs) are an uncommon complication of bisphosphonate (BP) treatment for osteoporosis. The purpose of this report was to determine differences in mortality among men treated with BPs who experienced AFFs, hip fractures, or typical subtrochanteric/femoral shaft (ST/FS) fractures. We included men from the Veterans Affairs Corporate Data Warehouse who filled at least one BP prescription over a nearly 20-yr span (October 1, 1999, to December 31, 2022). Typical ST/FS and hip fractures after a first filled prescription for a BP were identified using ICD codes. Radiographic review was conducted for ST/FS fractures to determine which were AFFs using the American Society of Bone and Mineral Research 2014 criterion. Demographic and clinical characteristics and cumulative duration of BP exposure prior to the incident fracture were determined. There were 23 men with an AFF, 4591 with a hip fracture, and 225 with a (non-AFF) ST/FS fracture. At 12-mo post-fracture, 4% of men with an AFF had died, compared with 25% of men with a hip fracture and 15% of men with an ST/FS fracture. Over 5 yrs. of follow-up, mortality following fracture differed among the 3 different fracture groups (χ2 = 6.21, d.f. = 2, p = .045) with death occurring in 7 of 23 (30%) men with an AFF, 2380 of 4591 (52%) men with a hip fracture and 109 of 225 (48%) men with a ST/FS fracture. In Cox proportional hazard models, over 5 yrs, with and without adjustment for covariates, there were no significant differences in mortality following an AFF compared with a hip fracture or an AFF compared with a ST/FS fracture (p > .10 for all). It is possible that mortality is lower following AFF compared with a hip or ST/FS fracture; however, limited sample size among those with AFF may have precluded ascertainment of such a difference.

The Osteoporotic Fractures in Men study (MrOS) is among the largest and longest running, prospective cohort studies of older men. MrOS determined how fracture risk was related to bone mass, bone geometry, lifestyle, anthropometric and neuromuscular measures, comorbidity, biomarkers, and fall propensity. The cohort consisted of 5994 community-dwelling, ambulatory US men aged 65 yr or older recruited at 6 US academic clinical centers in 2000-2002 and followed through November 2024. After enrollment, men were contacted by mail/phone every 4 mo to ascertain information on incident falls, fractures, and deaths/loss to follow-up. All fractures were confirmed by imaging reports. Over the 25-yr study, 95% of active surviving participants had complete follow-up. The MrOS study had 5 major clinic visits; while an ancillary sleep study had 2 additional clinic visits. MrOS has provided a comprehensive analysis of factors associated with areal (a) and volumetric (v) BMD and clinical risk factors for aBMD loss among men. Further analyses identified risk factors for hip, all non-spine, rib, wrist, and vertebral fractures. MrOS was the largest single cohort to estimate associations of aBMD with incident fractures in men and results indicated stronger associations in men than in women. MrOS also analyzed other structural features from DXA and both central and peripheral quantitative computed tomography in relationship to fractures in men. Serum, urine, and DNA were collected at clinic visits, and extensive analyses have been performed with respect to sex steroid and calciotropic hormones, bone turnover, and other novel measures of bone health. Several analyses evaluated the performance of formal tools in estimating the absolute risk of fractures in older men; however, findings indicated that better fracture prediction tools are needed. MrOS encourages outside investigators to make use of the publicly available data and to access the biospecimen bank at https://mrosonline.ucsf.edu.