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Minimal data exist on whether the acid-base balance of the diet is linked to muscle strength. The aim of this study was to determine if dietary acid load is associated with grip strength in a nationally representative sample of middle- to older-age adults. We examined the cross-sectional association of grip strength with dietary acid load quantified through potential renal acid load (PRAL) and net endogenous acid production (NEAP) in 4,059 adults aged 50 years and older in the 2011-2014 NHANES survey cycles. PRAL and NEAP were estimated from two 24-h recalls and categorized into sex-specific quartiles. Grip strength was measured on a dynamometer. Multiple linear regression models were used to determine the associations of PRAL and NEAP (as quartiles) with grip strength for men and women separately, adjusting for total energy, age, race/ethnicity, weight, physical activity, smoking, serum 25-hydroxyvitamin D, and estimated glomerular filtration rate. Mean grip strength was 26.8 ± 0.2 kg in women and 43.0 ± 0.4 kg in men. Adjusted grip strength was inversely associated with quartiles of PRAL (p trend  = 0.049) and NEAP (p trend  = 0.034) in women with quartile 4 vs 1 differences of - 1.21 and - 1.08 kg (both p < 0.05), respectively. Adjusted grip strength was not associated with PRAL or NEAP in men. Overall, we found inverse associations between dietary acid load and grip strength in middle- and older-age women, suggesting that an alkaline diet may be important in maintaining muscle strength in this population. There was no association between dietary acid load and grip strength in men., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This position paper of the International Osteoporosis Foundation reports the findings of an IOF Commission to consider to recommend rules of partnership with scientists belonging to a country which is currently responsible for an armed conflict, anywhere in the world. The findings and recommendations have been adopted unanimously by the Board of IOF., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Evidence on the effects of Vitamin D, omega-3s, and exercise on areal bone mineral density (aBMD) in healthy older adults is limited. We examined whether vitamin D3, omega-3s, or a simple home-based exercise program (SHEP), alone or in combination, over 3 years, improve lumbar spine (LS), femoral neck (FN), or total hip (TH) aBMD assessed by DXA. Areal BMD was a secondary outcome in DO-HEALTH, a 3-year, multicenter, double-blind, randomized 2 × 2 × 2 factorial design trial in generally healthy older adults age ≥ 70 years. The study interventions were vitamin D3 (2000IU/d), omega-3s (1 g/d), and SHEP (3 × 30 min/wk), applied alone or in combination in eight treatment arms. Mixed effects models were used, adjusting for age, sex, BMI, prior fall, study site, and baseline level of the outcome. Main effects were assessed in the absence of an interaction between the interventions. Subgroup analyses by age, sex, physical activity level, dietary calcium intake, serum 25(OH)D levels, and fracture history were conducted. DXA scans were available for 1493 participants (mean age 75 years; 80.4% were physically active, 44% had 25(OH)D levels <20 ng/mL). At the LS and FN sites, none of the treatments showed a benefit. At the TH, vitamin D versus no vitamin D treatment showed a significant benefit across 3 years (difference in adjusted means [AM]: 0.0035 [95% CI, 0.0011, 0.0059] g/cm). Furthermore, there was a benefit for vitamin D versus no vitamin D treatment on LS aBMD in the male subgroup (interaction P = .003; ∆AM: 0.0070 [95% CI, 0.0007, 0.0132] g/cm). Omega-3s and SHEP had no benefit on aBMD in healthy, active, and largely vitamin D replete older adults. Our study suggests a small benefit of 2000 IU vitamin D daily on TH aBMD overall and LS aBMD among men; however, effect sizes were very modest and the clinical impact of these findings is unclear., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Three recently-completed, large clinical trials in the U.S, New Zealand, and Australia, referred to herein as the 'mega-trials', were conducted to determine the impact of supplemental vitamin D on a variety of outcomes including falls and fractures. The trials were similar in design and collectively included over 50,000 generally vitamin D replete, older men and women. The mega-trials established that vitamin D supplementation with the equivalent of 2000 to 3300 IU/d of vitamin D 3 had no favorable effect on risk of falls or fractures. This review focuses on specific design elements of the trials and how they likely influenced these trial findings. While these trials were in progress, evidence emerged that circulating 25-hydroxyvitamin D levels have a U-shaped association with risk of falling, raising concern about a potential untoward effect of high dose supplementation. There is compelling evidence that in older, vitamin D- and calcium-insufficient nursing home residents, the combination of vitamin D and calcium in modest replacement doses dramatically reduces the risk of hip and other fractures. Community-dwelling older adults in many populous countries around the globe have widespread vitamin D and calcium insufficiency. It is time to follow the evidence trail and determine the effect of vitamin D and calcium replacement on their risk of falls and fractures., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author.)

Objective: To test whether transdermal testosterone at a dose of 75 mg per day and/or monthly 24'000 IU Vitamin D reduces the fall risk in pre-frail hypogonadal men aged 65 and older., Design: 2 × 2 factorial design randomized controlled trial, follow up of 12 months., Methods: Hypogonadism was defined as total testosterone <11.3 nmol/L and pre-frailty as ≥1 Fried- frailty criteria and/or being at risk for falling at the time of screening. The primary outcomes were number of fallers and the rate of falls, assessed prospectively. Secondary outcomes were appendicular lean mass (ALM), sit-to-stand, gait speed, and the short physical performance test battery. Analyses were adjusted for age, BMI, fall history and the respective baseline measurement., Results: We aimed to recruit 168 men and stopped at 91 due to unexpected low recruitment rate (1266 men were pre-screened). Mean age was 72.2 years, serum total testosterone was 10.8 ± 3.0 nmol/l, and 20.9% had 25(OH)D levels below 20 ng/mL. Over 12 months, 37 participants had 72 falls. Neither the odds of falling nor the rate of falls were reduced by testosterone or by vitamin D. Testosterone improved ALM compared to no testosterone (0.21 kg/m 2 [0.06, 0.37]), and improved gait speed (0.11 m/s, [0.03, 0.20]) compared to placebo., Conclusion: Transdermal testosterone did not reduce fall risk but improved ALM and gait speed in pre-frail older men. Monthly vitamin D supplementation had no benefit., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: Although aging has a strong impact on visual acuity (VA) and falls, their interaction is understudied in generally healthy older adults. This study aimed to examine if and to what extent baseline VA is associated with an increased risk of all and injurious falls over 3 years in generally healthy community-dwelling older adults., Design: Observational analysis of DO-HEALTH, a double-blind, randomized controlled trial., Setting and Participants: Multicenter trial with 7 European centers: Zurich, Basel, Geneva (Switzerland), Berlin (Germany), Innsbruck (Austria), Toulouse (France), and Coimbra (Portugal), including 2157 community-dwelling adults aged 70 years and older without any major health events in the 5 years prior to enrollment, sufficient mobility, and good cognitive status., Methods: The numbers of all and injurious falls were recorded prospectively by diary and in-person assessment every 3 months. Decreased VA at baseline was defined as better-eye VA lower than 1.0. We applied negative binomial regression models for all and injurious falls, adjusted for age, sex, prior falls, treatment allocation, study site, baseline body mass index, and use of walking aids., Results: Among the 2131 participants included in this analysis (mean age: 74.9 years, 61.7% were women, 82.6% at least moderately physically active), 1464 (68.7%) had decreased VA. Overall, 3290 falls including 2116 injurious falls were recorded over 3 years. Decreased VA at baseline was associated with a 22% increased incidence rate of all falls [adjusted incidence rate ratio (aIRR) = 1.22, 95% CI 1.07, 1.38, P = .003] and 20% increased incidence rate of injurious falls (aIRR = 1.20, 95% CI 1.05, 1.37, P = .007)., Conclusions and Implications: Our findings suggest that decreased VA is an independent predictor of an about 20% increased risk of all and injurious falls, highlighting the importance of regular eye examinations and VA measurements for fall prevention, even in generally healthy and active older adults., Competing Interests: Disclosure As part of the DO-HEALTH independent and investigator-initiated clinical trial, H.A.B.-F. reports, as the principal investigator of the DO-HEALTH trial, grants from the European Commission, the University of Zurich, Nestec, Pfizer Consumer Healthcare, and Streuli Pharma, and nonfinancial support from DSM Nutritional Products and Roche Diagnostics. Further, H.A.B.-F. reports speaker fees from Wild, Pfizer, Vifor, Mylan, Roche Diagnostics, and independent and investigator-initiated grants from Pfizer and from Vifor, outside of the submitted work. E.J.O. was also funded by DO-HEALTH. J.A.K. is a director of Osteoporosis Research Ltd. that maintains FRAX. M.D.B. reports speaking engagements for Roche Pharma (Schweiz) AG and consulting roles for Hoffmann-La Roche Ltd., Roche Pharma (Schweiz) AG, and ZEISS meditec (Deutschland). He is a lead user for Oertli (Schweiz) and holds patents and equity in Ophthorobotics AG. His contracted research includes work with Roche Pharma (Schweiz) AG, Novertis Pharma Schweiz AG, Chengdu Kanghong, and Bayer (Schweiz) AG. He has also received grant support from the W.H. Spross Stiftung zur Förderung der Augenheilkunde and the Stiftung für wissenschaftliche Forschung am Stadtspital Zürich. All other authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet may slow cognitive decline in older adults. A potential mechanism could be possible anti-inflammatory properties of the MIND-diet., Objective: To examine whether adherence to the MIND diet at baseline is associated with the odds of mild cognitive impairment (MCI) and changes in biomarkers of inflammation (High-sensitivity C-reactive Protein(hsCRP), interleukin-6(IL-6)) over three years in adults ≥70 years., Methods: Adherence to the MIND diet was assessed by food frequency questionnaire (FFQ) at baseline and after three years. Presence of MCI based on the Montreal Cognitive Assessment (MoCA) was defined as <26 (MCI 26 ), or <24 (MCI 24 ). We performed a minimally adjusted model controlling for sex, prior fall, linear spline at age 85, time, treatment and study site. The fully adjusted model also adjusted for education, BMI, physical activity, depression score, daily energy intake, and comorbidity score. To assess the change in inflammatory markers from baseline, we used linear-mixed-effect models adjusted for the same variables plus the respective baseline concentrations. Sensitivity analyses accounting for practice effects of repeated cognitive tests using the reliable change index for both MoCA cut-offs were done., Results: We included 2028 of 2157 DO-HEALTH participants (60.5% women; mean age 74.88 years) with complete data. Adherence to the MIND diet at baseline was not associated with cognitive decline over three years, neither at MoCA < 26 (OR (95%CI) = 0.99 (0.94-1.04)) nor at MoCA < 24 (OR (95%CI) = 1.03 (0.96-1.1)). Applying the reliable change index to the two cut-offs confirmed the findings. Further, the MIND diet adherence was not associated with the change in MoCA score from baseline in DO-HEALTH. For inflammatory biomarkers MIND-diet baseline adherence was not associated with changes in hsCRP or IL-6., Conclusion: Adherence to the MIND-diet was neither associated with the odds of MCI, nor with hsCRP or IL-6 at baseline. Moreover, change in MIND-diet over three years was not associated with changes in hsCRP or IL-6., (Copyright © 2023 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

The relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm., Introduction: Previous falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD)., Methods: The resource comprised 906,359 women and men (66.9% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients., Results: Falls in the past year were reported in 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33-1.51) and men (HR 1.53, 95% CI 1.41-1.67). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.53 (95% CI 1.27-1.84) in men vs. HR 1.32 (95% CI 1.20-1.45) in women, P for interaction = 0.013). The HRs associated with previous falls decreased with age in women and with duration of follow-up in men and women for most fracture outcomes. There was no evidence of an interaction between falls and BMD for fracture risk. Subsequent risk for a major osteoporotic fracture increased with each additional previous fall in women and men., Conclusions: A previous self-reported fall confers an increased risk of fracture that is largely independent of BMD. Previous falls should be considered as an additional risk factor in future iterations of FRAX to improve fracture risk prediction., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Context: Anamorelin, a ghrelin receptor agonist known to stimulate the pulsatile release of GH from the pituitary, has the potential to improve musculoskeletal health in adults with osteosarcopenia., Objective: To determine the effect of anamorelin treatment for 1 year on muscle mass and strength and on biochemical markers of bone turnover in adults with osteosarcopenia (OS)., Design: Randomized, placebo-controlled, 1-year anamorelin intervention trial., Setting: The Bone Metabolism Laboratory at the USDA Nutrition Center at Tufts University., Participants: 26 men and women, age 50 years and older, with OS., Main Outcome Measures: Muscle mass by D3-creatine dilution and lean body mass (LBM) and bone mineral density (BMD) by dual-energy X-ray absorptiometry, muscle strength, serum IGF-1, and bone turnover markers, serum procollagen 1 intact N-terminal (P1NP), and C-terminal telopeptide (CTX)., Results: Anamorelin did not have a significant effect on muscle mass or LBM; it significantly increased knee flexion torque at 240°/s by 20% (P = .013) and had a similar nonstatistically significant effect on change in knee extension; it increased bone formation (P1NP) by 75% (P = .006) and had no significant effect on bone resorption (CTX) or BMD. Serum IGF-1 increased by 50% in the anamorelin group and did not change in the placebo group (P = .0001 for group difference)., Conclusion: In this pilot study, anamorelin did not significantly alter muscle mass; however, it may potentially improve lower extremity strength and bone formation in addition to increasing circulating IGF-1 levels in adults with OS. Further study of anamorelin in this population is warranted., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Data suggest an association between GH secretion and circulating levels of the myokine irisin and inflammatory cytokinesIL-6 and high-sensitivity C-reactive protein (hsCRP). The impact of GH secretagogues on these markers is unknown., Objectives: To determine the effect of treatment with the GH secretagogue anamorelin on 12-month changes in serum irisin, IL-6, and hsCRP levels and to assess whether baseline irisin levels modulate the glycemic response to treatment with anamorelin., Methods: This is an ancillary study in 26 older adults with osteosarcopenia who participated in a 12-month trial examining the effect of anamorelin 100 mg/day vs placebo on musculoskeletal outcomes. Serum irisin, IL-6, and hsCRP were measured at baseline and 12 months., Results: Treatment with anamorelin, compared with placebo, did not significantly alter irisin levels [12-month change = 0.50 ± 1.2 (SD) ng/mL in anamorelin group and -0.08 ± 2.3 ng/mL in placebo; P = .191]. Baseline irisin levels were not significantly correlated with 2-month change in fasting glucose levels in the anamorelin group (r = -0.222, P = .46) or the placebo group (r = 0.30, P = .34); however, the slopes of the 2 regression lines describing the relationship by group tended to differ ( P = .0547). Anamorelin treatment for 12 months had no significant effect on serum IL-6 or hsCRP levels., Conclusion: In this small sample of older adults with osteosarcopenia, treatment with the GH secretagogue anamorelin did not significantly alter levels of irisin, IL-6, or hsCRP. Higher baseline irisin levels may attenuate the glycemic response to anamorelin treatment; however, a larger study is needed to confirm this possibility., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)