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Fermented dairy products have recently gained popularity due to their purported health benefits, nevertheless, their role in ageing remains uncertain. This narrative review aims to evaluate evidence from observational (prospective) and interventional studies on the potential benefits of fermented dairy product consumption for musculoskeletal and mental health in older adults. Additionally, it seeks to determine whether any observed benefits surpass those of non-fermented dairy products and to identify directions for future research. Prospective studies support either favourable or neutral associations of fermented dairy products with outcomes of musculoskeletal health or neutral associations with mental health outcomes, whilst it remains unclear if the benefits observed with fermented dairy products go beyond those of the non-fermented dairy foods. Few interventional studies suggest overall favourable effects of yogurt and cheese on musculoskeletal health in older adults but given their small number (N = 6) and heterogeneity, they do not allow a clear assessment or definitive recommendations for fermented dairy intake. Interventional studies reporting mental health outcomes are largely lacking for this age group (N = 1). Given the very limited evidence for the effectiveness of fermented dairy products, future well-designed prospective and randomized controlled trials are needed to better understand their benefits (especially compared to those of non-fermented dairy foods), their characteristics and the quantities required to offer protection against musculoskeletal and/or mental health ageing., (© 2024. The Author(s).)

Identifying individuals at risk for short-term fracture is essential to offer prompt beneficial treatment, especially since many fractures occur in those without osteoporosis by DXA-aBMD. We evaluated whether deficits in bone microarchitecture and density predict short-term fracture risk independent of the clinical predictors, DXA-BMD and FRAX. We combined data from eight cohorts to conduct a prospective study of bone microarchitecture at the distal radius and tibia (by HR-pQCT) and 2-year incidence of fracture (non-traumatic and traumatic) in 7327 individuals (4824 women, 2503 men, mean 69 ± 9 years). We estimated sex-specific hazard ratios (HR) for associations between bone measures and 2-year fracture incidence, adjusted for age, cohort, height and weight, and then additionally adjusted for femoral neck (FN) aBMD or FRAX for major osteoporotic fracture. Only 7% of study participants had FN T-score ≤ -2.5, whereas 53% had T-scores between -1.0 to -2.5 and 37% had T-scores ≥-1.0. Two-year cumulative fracture incidence was 4% (296/7327). Each SD decrease in radius cortical bone measures increased fracture risk by 38%-76% for women and men. After additional adjustment for FN-aBMD, risks remained increased by 28%-61%. Radius trabecular measures were also associated with 2-year fracture risk independently of FN-aBMD in women (HRs range: 1.21 per SD for trabecular separation to 1.55 for total vBMD). Decreased failure load was associated with increased fracture risk in both women and men (FN-aBMD ranges of adjusted HR = 1.47-2.42). Tibia measurement results were similar to radius results. Findings were also similar when models were adjusted for FRAX. In older adults, failure load and HR-pQCT measures of cortical and trabecular bone microarchitecture and density with strong associations to short-term fractures improved fracture prediction beyond aBMD and FRAX. Thus, HR-pQCT may be a useful adjunct to traditional assessment of short-term fracture risk in older adults, including those with T-scores above the osteoporosis range., (© The Author(s) [2024]. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Osteoanabolic-first treatment sequences are superior to oral bisphosphonates for fracture reduction and bone mineral density (BMD) gain. However, data comparing osteoanabolic medications, with the more potent antiresorptive, denosumab (DMAb), are limited. We analyzed FRAME and FRAME Extension data to assess BMD and fracture incidence in patients treated with romosozumab (Romo) followed by DMAb (Romo/DMAb) versus DMAb (DMAb/DMAb) for 24 months. In FRAME, women aged ≥55 years (total hip [TH] or femoral neck [FN] T-score: -2.5 to -3.5) were randomized to Romo or placebo for 12 months followed by DMAb for 12 months. In FRAME Extension, both cohorts received DMAb for another 12 months. This post hoc analysis compared BMD change and fracture incidence in patients on Romo/DMAb (months 0-24) versus DMAb/DMAb (months 12-36). Patient characteristics were balanced by propensity score weighting (PSW) and sensitivity analyses were conducted using PSW with multiple imputation (PSW-MI) and propensity score matching (PSM). Unmeasured confounding was addressed using E-values. After PSW, over 24 months, compared with DMAb/DMAb, treatment with Romo/DMAb produced significantly greater BMD increases at the lumbar spine [LS], TH, and FN (mean differences: 9.3%, 4.4%, and 4.1%, respectively; all p<0.001). At month 24, in women with a baseline T-score of -3.0, the probability of achieving a T-score > -2.5 was higher with Romo/DMAb versus DMAb/DMAb (LS: 92% versus 47%; TH: 50% versus 5%). In the Romo/DMAb versus DMAb/DMAb cohorts, new vertebral fractures were significantly reduced (0.62% versus 1.26% [odds ratio = 0.45; p=0.003]) and rates of clinical, nonvertebral, and hip fractures were lower (differences not significant). Similar BMD and fracture outcomes were observed with PSW-MI and PSM sensitivity analyses. The sequence of Romo/DMAb resulted in greater BMD gains and higher probability of achieving T-scores > -2.5, significantly reduced new vertebral fracture incidence, and numerically lowered the incidence (not significant) of clinical, nonvertebral, and hip fractures versus DMAb only through 24 months., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Task Force on 'Clinical Algorithms for Fracture Risk' commissioned by the American Society for Bone and Mineral Research (ASBMR) Professional Practice Committee has recommended that FRAX® models in the US do not include adjustment for race and ethnicity. This position paper finds that an agnostic model would unfairly discriminate against the Black, Asian and Hispanic communities and recommends the retention of ethnic and race-specific FRAX models for the US, preferably with updated data on fracture and death hazards. In contrast, the use of intervention thresholds based on a fixed bone mineral density unfairly discriminates against the Black, Asian and Hispanic communities in the US. This position of the Working Group on Epidemiology and Quality of Life of the International Osteoporosis Foundation (IOF) is endorsed both by the IOF and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO)., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Bone forming agents, also known as anabolic therapies, are essential in managing osteoporosis, particularly for patients at very high-risk of fractures. Identifying candidates who will benefit the most from these treatments is crucial. For example, this group might include individuals with severe osteoporosis, multiple vertebral fractures, a recent fragility fracture or those unresponsive to antiresorptive treatments. Definitions of patients with a very high fracture risk vary across nations, are often based on fracture history, bone mineral density (BMD), and/or fracture risk calculated by FRAX® or other algorithms. However, for very high-risk patients, anabolic agents such as teriparatide, abaloparatide, or romosozumab are commonly recommended as first-line therapies due to their ability to stimulate new bone formation and improve bone microarchitecture, offering significant benefits in rapid fracture reduction over antiresorptive therapies. The cost-effectiveness of these agents is a critical consideration for decision-makers. Despite their higher costs, their effectiveness in significantly reducing fracture risk and improving quality of life can justify the investment, especially when long-term savings from reduced fracture rates and associated healthcare costs are considered. Additionally, after completing a course of anabolic therapy, transitioning to antiresorptive agents like bisphosphonates or denosumab is crucial to maintain the gains in bone density and minimize subsequent fracture risks. This sequential treatment approach ensures sustained protection and optimal resource utilization. In summary, the effective use of bone forming agents in osteoporosis requires a comprehensive strategy that includes accurate patient identification, consideration of cost-effectiveness, and implementation of appropriate sequential treatments, ultimately maximizing patient outcomes and healthcare efficiency., (© 2024. The Author(s).)

Vitamin D is important for musculoskeletal health. Concentrations of 25-hydroxyvitamin D, the most commonly measured metabolite, vary markedly around the world and are influenced by many factors including sun exposure, skin pigmentation, covering, season and supplement use. Whilst overt vitamin D deficiency with biochemical consequences presents an increased risk of severe sequelae such as rickets, osteomalacia or cardiomyopathy and usually warrants prompt replacement treatment, the role of vitamin D supplementation in the population presents a different set of considerations. Here the issue is to keep, on average, the population at a level whereby the risk of adverse health outcomes in the population is minimised. This position paper, which complements recently published work from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, addresses key considerations regarding vitamin D assessment and intervention from the population perspective. This position paper, on behalf of the International Osteoporosis Foundation Vitamin D Working Group, summarises the burden and possible amelioration of vitamin D deficiency in global populations. It addresses key issues including screening, supplementation and food fortification., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Antiresorptive medications do not negatively affect fracture healing in humans. Teriparatide may decrease time to fracture healing. Romosozumab has not shown a beneficial effect on human fracture healing., Background: Fracture healing is a complex process. Uncertainty exists over the influence of osteoporosis and the medications used to treat it on fracture healing., Methods: Narrative review authored by the members of the Fracture Working Group of the Committee of Scientific Advisors of the International Osteoporosis Foundation (IOF), on behalf of the IOF and the Société Internationale de Chirurgie Orthopédique et de Traumatologie (SICOT)., Results: Fracture healing is a multistep process. Most fractures heal through a combination of intramembranous and endochondral ossification. Radiographic imaging is important for evaluating fracture healing and for detecting delayed or non-union. The presence of callus formation, bridging trabeculae, and a decrease in the size of the fracture line over time are indicative of healing. Imaging must be combined with clinical parameters and patient-reported outcomes. Animal data support a negative effect of osteoporosis on fracture healing; however, clinical data do not appear to corroborate with this. Evidence does not support a delay in the initiation of antiresorptive therapy following acute fragility fractures. There is no reason for suspension of osteoporosis medication at the time of fracture if the person is already on treatment. Teriparatide treatment may shorten fracture healing time at certain sites such as distal radius; however, it does not prevent non-union or influence union rate. The positive effect on fracture healing that romosozumab has demonstrated in animals has not been observed in humans., Conclusion: Overall, there appears to be no deleterious effect of osteoporosis medications on fracture healing. The benefit of treating osteoporosis and the urgent necessity to mitigate imminent refracture risk after a fracture should be given prime consideration. It is imperative that new radiological and biological markers of fracture healing be identified. It is also important to synthesize clinical and basic science methodologies to assess fracture healing, so that a convergence of the two frameworks can be achieved., (© 2024. The Author(s).)

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.)

Context: There are limited comparative studies between one anastomosis gastric bypass (OAGB) versus Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on body composition and musculoskeletal health., Objective: To compare changes in body composition, areal bone mineral density (aBMD), muscle strength, and physical function in the first year following OAGB, RYGB and SG within a UK-based healthcare setting., Methods: This is a secondary analysis of the BARI-LIFESTYLE trial in 119 adults (77% women; mean±SD, age: 45.9±10.3 years; BMI: 43.6±5.5 kg/m2) who underwent OAGB (n=19), RYGB (n=39) and SG (n=61). Body composition and aBMD by dual energy x-ray absorptiometry, handgrip strength, sit-to-stand (STS) test and 6-minute walking test (6MWT) were assessed pre-surgery and at 12 months post-surgery., Results: OAGB, RYGB, and SG exhibited similar reductions in body weight, body fat and lean mass (within-group comparisons, p<0.001). All surgery types were associated with reductions in aBMD at the total hip, femoral neck, and lumbar spine, which were more pronounced after OAGB and RYGB compared to SG (all p<0.03), though no difference between OAGB and RYGB. Despite reductions in absolute handgrip strength, relative handgrip strength, STS test and 6MWT improved post-surgery (all p<0.02), with no differences by surgical procedure., Conclusion: OAGB, RYGB, and SG resulted in comparable weight loss, changes in body composition and improvements in relative muscle strength and physical function. OAGB and RYGB, compared with SG, led to greater BMD reductions at clinically relevant sites. Future long-term studies should explore whether these BMD reductions translate into a greater fracture risk., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Radiofrequency Echographic Multi Spectrometry (REMS) is a radiation-free, portable technology, which can be used for the assessment and monitoring of osteoporosis at the lumbar spine and femoral neck and may facilitate wider access to axial BMD measurement compared with standard dual-energy x-ray absorptiometry (DXA).There is a growing literature demonstrating a strong correlation between DXA and REMS measures of BMD and further work supporting 5-year prediction of fracture using the REMS Fragility Score, which provides a measure of bone quality (in addition to the quantitative measure of BMD).The non-ionising radiation emitted by REMS allows it to be used in previously underserved populations including pregnant women and children and may facilitate more frequent measurement of BMD.The portability of the device means that it can be deployed to measure BMD for frail patients at the bedside (avoiding the complications in transfer and positioning which can occur with DXA), in primary care, the emergency department, low-resource settings and even at home.The current evidence base supports the technology as a useful tool in the management of osteoporosis as an alternative to DXA., (© 2024. The Author(s).)

Fracture risk increases with lower areal bone mineral density (aBMD); however, aBMD-related estimate of risk may decrease with age. This may depend on technical limitations of 2-dimensional (2D) dual energy X-ray absorptiometry (DXA) which are reduced with 3D high-resolution peripheral quantitative computed tomography (HR-pQCT). Our aim was to examine whether the predictive utility of HR-pQCT measures with fracture varies with age. We analyzed associations of HR-pQCT measures at the distal radius and distal tibia with two outcomes: incident fractures and major osteoporotic fractures. We censored follow-up time at first fracture, death, last contact or 8 years after baseline. We estimated hazard ratios (HR) and 95%CI for the association between bone traits and fracture incidence across age quintiles. Among 6835 men and women (ages 40-96) with at least one valid baseline HR-pQCT scan who were followed prospectively for a median of 48.3 months, 681 sustained fractures. After adjustment for confounders, bone parameters at both the radius and tibia were associated with higher fracture risk. The estimated HRs for fracture did not vary significantly across age quintiles for any HR-pQCT parameter measured at either the radius or tibia. In this large cohort, the homogeneity of the associations between the HR-pQCT measures and fracture risk across age groups persisted for all fractures and for major osteoporotic fractures. The patterns were similar regardless of the HR-pQCT measure, the type of fracture, or the statistical models. The stability of the associations between HR-pQCT measures and fracture over a broad age range shows that bone deficits or low volumetric density remain major determinants of fracture risk regardless of age group. The lower risk for fractures across measures of aBMD in older adults in other studies may be related to factors which interfere with DXA but not with HR-pQCT measures., (© 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 email: journals.permissions@oup.com.)

Currently, robust evidence is lacking to support one exercise type over another in the prevention of physical and cognitive decline and falls among older adults, primarily because of the lack of comparative trials of proven interventions. Therefore, a 12-month randomized, single-blind, comparative effectiveness trial is conducted, in which 142 older adults at high risk for falls are randomized (1:1) to receive an evidence-based Dalcroze Eurhythmics (DE) exercise program (once weekly, group-based) or an evidence-based multicomponent (MULTI) exercise program incorporating balance, functional, and strength training activities (twice weekly, group- and home-based), for 12 months. The primary outcome is gait variability under dual-task at 12 months. At 12 months, the DE group has significant improvements compared with MULTI group on gait under both dual-task (adjusted β for stride variability: -2.3, 95%CI, -3.1 to -1.4; p < 0.001) and single-task, and on a variety of secondary physical and cognitive/executive function outcomes. The adjusted hazard ratio for falls is 0.58 (95%CI, 0.37 to 0.93) for the DE group compared with MULTI group. In conclusion, DE exercise is more effective than MULTI exercise in improving physical and cognitive function and reducing falls in older adults. The mechanisms underlying DE exercise-induced benefits remain to be fully elucidated., (© 2024 The Authors. Advanced Biology published by Wiley‐VCH GmbH.)

Romosozumab treatment in women with postmenopausal osteoporosis increases bone formation while decreasing bone resorption, resulting in large BMD gains to reduce fracture risk within 1 yr. DXA-based 3D modeling of the hip was used to assess estimated changes in cortical and trabecular bone parameters and map the distribution of 3D changes in bone parameters over time in patients from 2 randomized controlled clinical trials: FRAME (romosozumab vs placebo followed by denosumab) and ARCH (romosozumab vs alendronate followed by alendronate). For each study, data from a subset of ~200 women per treatment group who had TH DXA scans at baseline and months 12 and 24 and had provided consent for future research were analyzed post hoc. 3D-SHAPER software v2.11 (3D-SHAPER Medical) was used to generate patient-specific 3D models from TH DXA scans. Percentage changes from baseline to months 12 and 24 in areal BMD (aBMD), integral volumetric BMD (vBMD), cortical thickness, cortical vBMD, cortical surface BMD (sBMD), and trabecular vBMD were evaluated. Data from 377 women from FRAME (placebo, 190; romosozumab, 187) and 368 women from ARCH (alendronate, 185; romosozumab, 183) with evaluable 3D assessments at baseline and months 12 and 24 were analyzed. At month 12, treatment with romosozumab vs placebo in FRAME and romosozumab vs alendronate in ARCH resulted in greater increases in aBMD, integral vBMD, cortical thickness, cortical vBMD, cortical sBMD, and trabecular vBMD (P < .05 for all). At month 24, cumulative gains in all parameters were greater in the romosozumab-to-denosumab vs placebo-to-denosumab sequence and romosozumab-to-alendronate vs alendronate-to-alendronate sequence (P < .05 for all). 3D-SHAPER analysis provides a novel technique for estimating changes in cortical and trabecular parameters from standard hip DXA images. These data add to the accumulating evidence that romosozumab improves hip bone density and structure, thereby contributing to the antifracture efficacy of the drug., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Number and age-standardized incidences of femoral fractures by sex and localization were determined annually between 1998 and 2021 in subjects aged 45 years or older living in Switzerland. The number and incidences of femoral neck, pertrochanteric, subtrochanteric, and femoral shaft fractures followed distinct unexpected trend patterns., Introduction: Long-term incidence trends for femoral fractures by individual localizations are unknown., Methods: Annual absolute number of hospitalizations and median age at hospital admission between 1998 and 2021 were extracted from the medical database of the Swiss Federal Office of Statistics by sex and 10-year age groups for the following 10th International Classification of Diseases (ICD-10) codes: femoral neck (ICD-10 S72.0), pertrochanteric (S72.1), subtrochanteric (S72.2), and femoral shaft fractures (S72.3). Age-standardized incidence rates (ASI) and corresponding trends were calculated., Results: Over 24 years, the number of femoral neck fractures increased in men (+ 45%) but decreased in women (- 7%) with ASI significantly decreasing by 20% and 37% (p < 0.001 for trend for both), respectively. By contrast, the number of pertrochanteric fractures increased by 67% and 45% in men and women, respectively, corresponding to a horizontal ASI-trend in men (n.s.) and a modest significant decreasing ASI-trend in women (p < 0.001). The number of subtrochanteric fractures increased in both sexes with corresponding modest significant reductions in ASI-trends (p = 0.015 and 0.002, respectively). Femoral shaft fractures almost doubled in men (+ 71%) and doubled in women (+ 100%) with corresponding significant increases in ASI-trends (p = 0.001 and p < 0.001, respectively). Age at admission increased for all fracture localizations, more so in men than in women and more so for subtrochanteric and shaft fractures than for "typical" hip fractures., Conclusion: Incidence changes of pertrochanteric fractures and femoral shaft fractures deserve increased attention, especially in men. Pooling diagnostic codes for defining hip fractures may hide differing patterns by localization and sex., (© 2024. The Author(s).)

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.)

Historically, osteoporosis has been viewed as a disease of women, with research, trials of interventions and guidelines predominantly focused as such. It is apparent, however, that this condition causes a substantial health burden in men also, and that its assessment and management must ultimately be addressed across both sexes. In this article, an international multidisciplinary working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases presents GRADE-assessed recommendations for the diagnosis, monitoring and treatment of osteoporosis in men. The recommendations are based on a comprehensive review of the latest research related to diagnostic and screening approaches for osteoporosis and its associated high fracture risk in men, covering disease burden, appropriate interpretation of bone densitometry (including the use of a female reference database for densitometric diagnosis in men) and absolute fracture risk, thresholds for treatment, and interventions that can be used therapeutically and their health economic evaluation. Future work should specifically address the efficacy of anti-osteoporosis medications, including denosumab and bone-forming therapies., (© 2024. Springer Nature Limited.)

Background: Fragility fractures in older adults are often caused by fall events. The estimation of an expected fall rate might improve the identification of individuals at risk of fragility fractures and improve fracture prediction., Methods: A combined analysis of three previously developed fall rate models using individual participant data (n = 1850) was conducted using the methodology of a two-stage meta-analysis to derive an overall model. These previously developed models included the fall history as a predictor recorded as the number of experienced falls within 12 months, treated as a factor variable with the levels 0, 1, 2, 3, 4 and ≥ 5 falls. In the first stage, negative binomial regression models for every cohort were fit. In the second stage, the coefficients were compared and used to derive overall coefficients with a random effect meta-analysis. Additionally, external validation was performed by applying the three data sets to the models derived in the first stage., Results: The coefficient estimates for the prior number of falls were consistent among the three studies. Higgin's I 2 as heterogeneity measure ranged from 0 to 55.39%. The overall coefficient estimates indicated that the expected fall rate increases with an increasing number of previous falls. External model validation revealed that the prediction errors for the data sets were independent of the model to which they were applied., Conclusion: This analysis suggests that the fall history treated as a factor variable is a robust predictor of estimating future falls among different cohorts., (© 2024. The Author(s).)

Background: The burden of herpes zoster (shingles) virus and associated complications, such as post-herpetic neuralgia, is higher in older adults and has a significant impact on quality of life. The incidence of herpes zoster and post-herpetic neuralgia is increased in people living with HIV (PLWH) compared to an age-matched general population, including PLWH on long-term antiretroviral therapy (ART) with no detectable viremia and normal CD4 counts. PLWH - even on effective ART may- exhibit sustained immune dysfunction, as well as defects in cells involved in the response to vaccines. In the context of herpes zoster, it is therefore important to assess the immune response to varicella zoster virus vaccination in older PLWH and to determine whether it significantly differs to that of HIV-uninfected healthy adults or younger PLWH. We aim at bridging these knowledge gaps by conducting a multicentric, international, non-randomised clinical study (SHINGR'HIV) with prospective data collection after vaccination with an adjuvant recombinant zoster vaccine (RZV) in two distinct populations: in PLWH on long-term ART (> 10 years) over 50 years of and age/gender matched controls., Methods: We will recruit participants from two large established HIV cohorts in Switzerland and in France in addition to age-/gender-matched HIV-uninfected controls. Participants will receive two doses of RZV two months apart. In depth-evaluation of the humoral, cellular, and innate immune responses and safety profile of the RZV will be performed to address the combined effect of aging and potential immune deficiencies due to chronic HIV infection. The primary study outcome will compare the geometric mean titer (GMT) of gE-specific total IgG measured 1 month after the second dose of RZV between different age groups of PLWH and between PLWH and age-/gender-matched HIV-uninfected controls., Discussion: The SHINGR'HIV trial will provide robust data on the immunogenicity and safety profile of RZV in older PLWH to support vaccination guidelines in this population., Trial Registration: ClinicalTrials.gov NCT05575830. Registered on 12 October 2022. Eu Clinical Trial Register (EUCT number 2023-504482-23-00)., (© 2024. The Author(s).)

Hypophosphatasia (HPP) is an inborn error of metabolism caused by reduced or absent activity of the tissue non-specific alkaline phosphatase (TNSALP) enzyme, resulting from pathogenic variants in the ALPL gene. Clinical presentation of HPP is highly variable, including lethal and severe forms in neonates and infants, a benign perinatal form, mild forms manifesting in adulthood, and odonto-HPP. Diagnosis of HPP remains a challenge in adults, as signs and symptoms may be mild and non-specific. Disease presentation varies widely; there are no universal signs or symptoms, and the disease often remains underdiagnosed or misdiagnosed, particularly by clinicians who are not familiar with this rare disorder. The absence of diagnosis or a delayed diagnosis may prevent optimal management for patients with this condition. Formal guidelines for the diagnosis of adults with HPP do not exist, complicating efforts for consistent diagnosis. To address this issue, the HPP International Working Group selected 119 papers that explicitly address the diagnosis of HPP in adults through a Medline, Medline In-Process, and Embase search for the terms "hypophosphatasia" and "HPP," and evaluated the pooled prevalence of 17 diagnostic characteristics, initially selected by a group of HPP clinical experts, in eligible studies and in patients included in these studies. Six diagnostic findings showed a pooled prevalence value over 50% and were considered for inclusion as major diagnostic criteria. Based on these results and according to discussion and consideration among members of the Working Group, we finally defined four major diagnostic criteria and five minor diagnostic criteria for HPP in adults. Authors suggested the integrated use of the identified major and minor diagnostic criteria, which either includes two major criteria, or one major criterion and two minor criteria, for the diagnosis of HPP in adults., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

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.)

Background: This manuscript provides a summary of the current evidence to support the criteria for diagnosing a child or adult with hypophosphatasia (HPP). The diagnosis of HPP is made on the basis of integrating clinical features, laboratory profile, radiographic features of the condition, and DNA analysis identifying the presence of a pathogenic variant of the tissue nonspecific alkaline phosphatase gene (ALPL). Often, the diagnosis of HPP is significantly delayed in both adults and children, and updated diagnostic criteria are required to keep pace with our evolving understanding regarding the relationship between ALPL genotype and associated HPP clinical features., Methods: An International Working Group (IWG) on HPP was formed, comprised of a multidisciplinary team of experts from Europe and North America with expertise in the diagnosis and management of patients with HPP. Methodologists (Romina Brignardello-Petersen and Gordon Guyatt) and their team supported the IWG and conducted systematic reviews following the GRADE methodology, and this provided the basis for the recommendations., Results: The IWG completed systematic reviews of the literature, including case reports and expert opinion papers describing the phenotype of patients with HPP. The published data are largely retrospective and include a relatively small number of patients with this rare condition. It is anticipated that further knowledge will lead to improvement in the quality of genotype-phenotype reporting in this condition., Conclusion: Following consensus meetings, agreement was reached regarding the major and minor criteria that can assist in establishing a clinical diagnosis of HPP in adults and children., (© 2023. Crown.)

Osteoporotic vertebral compression fractures (OVCFs) present a significant health concern, affecting a substantial portion of the older adult population worldwide. This narrative review explores the prevalence, diagnostic challenges and management strategies for OVCFs. Despite the increasing incidence and impact on morbidity and mortality, existing clinical guidelines lack consistency and clear diagnostic and therapeutic recommendations. The review addresses key questions faced by physicians dealing with older adult patients experiencing acute back pain, offering insights into triage, radiological assessments and classification systems. We propose a comprehensive algorithm for clearing OVCF, considering clinical presentation, radiological findings and morphological aspects. Emphasis is placed on the importance of medically treating osteoporosis alongside OVCF management. The review encompasses relevant literature from 1993 to 2023, provides a detailed discussion on triage issues and incorporates a clinically oriented classification system developed by the German Society for Orthopaedics and Trauma. The Material and Methods section outlines the extensive literature search carried out in PUBMED, encompassing clinical and experimental studies, systematic reviews and meta-analyses. The articles retained focused mainly on answering critical questions regarding radiological assessments, imaging modalities and the presence of a specific classification system for OVCFs. The review emphasises that the evaluation and management of OVCFs necessitates a multidisciplinary approach involving spine specialists and bone disease experts. It also addresses the role of conservative versus surgical treatments, with a focus on percutaneous vertebral augmentation. The conclusion summarises the algorithm derived for use in emergency departments and general practice, aiming to streamline OVCF management, reduce unnecessary examinations and ensure optimal patient care. The algorithm recommends primary diagnosis using computed tomography, with magnetic resonance imaging reserved for specific cases. The review advocates a holistic approach, integrating medical and surgical interventions to address the complex challenges posed by OVCFs in ageing populations.

Background: The effects of non-pharmaceutical interventions in the prevention of cardiovascular diseases (CVD) in older adults remains unclear. Therefore, the aim was to investigate the effect of 2000 IU/day of vitamin D 3 , omega-3 fatty acids (1 g/day), and a simple home strength exercise program (SHEP) (3×/week) on lipid and CVD biomarkers plasma changes over 3 years, incident hypertension and major cardiovascular events (MACE)., Methods: The risk of MACE (coronary heart event or intervention, heart failure, stroke) was an exploratory endpoint of DO-HEALTH, incident hypertension and change in biomarkers were secondary endpoints. DO-HEALTH is a completed multicentre, randomised, placebo-controlled, 2 × 2 × 2 factorial design trial enrolling 2157 Europeans aged ≥70 years., Results: Participants' median age was 74 [72, 77] years, 61.7% were women, 82.5% were at least moderately physically active, and 40.7% had 25(OH)D < 20 ng/mL at baseline. Compared to their controls, omega-3 increased HDL-cholesterol (difference in change over 3 years: 0.08 mmol/L, 95% CI 0.05-0.10), decreased triglycerides (-0.08 mmol/L, (95%CI -0.12 to -0.03), but increased total- (0.15 mmol/L, 95%CI 0.09; 0.2), LDL- (0.11 mmol/L, 0.06; 0.16), and non-HDL-cholesterol (0.07 mmol/L, 95%CI 0.02; 0.12). However, neither omega-3 (adjustedHR 1.00, 95%CI 0.64-1.56), nor vitamin D 3 (aHR 1.37, 95%CI 0.88-2.14), nor SHEP (aHR 1.18, 95%CI 0.76-1.84) reduced risk of MACE or incident hypertension compared to control., Conclusion: Among generally healthy, active, and largely vitamin D replete, older adults, treatment with omega-3, vitamin D 3 , and/or SHEP had no benefit on MACE prevention. Only omega-3 supplementation changed lipid biomarkers, but with mixed effects. TRIAL REGISTRATION CLINICALTRIALS., Gov Identifier: NCT01745263., (Copyright © 2024. Published by Elsevier Masson SAS.)

Hypophosphatasia (HPP) is a rare inborn error of metabolism that presents variably in both age of onset and severity. HPP is caused by pathogenic variants in the ALPL gene, resulting in low activity of tissue nonspecific alkaline phosphatase (TNSALP). Patients with HPP tend have a similar pattern of elevation of natural substrates that can be used to aid in diagnosis. No formal diagnostic guidelines currently exist for the diagnosis of this condition in children, adolescents, or adults. The International HPP Working Group is a comprised of a multidisciplinary team of experts from Europe and North America who have expertise in the diagnosis and management of patients with HPP. This group reviewed 93 papers through a Medline, Medline In-Process, and Embase search for the terms "HPP" and "hypophosphatasia" between 2005 and 2020 and that explicitly address either the diagnosis of HPP in children, clinical manifestations of HPP in children, or both. Two reviewers independently evaluated each full-text publication for eligibility and studies were included if they were narrative reviews or case series/reports that concerned diagnosis of pediatric HPP or included clinical aspects of patients diagnosed with HPP. This review focused on 15 initial clinical manifestations that were selected by a group of clinical experts.The highest agreement in included literature was for pathogenic or likely pathogenic ALPL variant, elevation of natural substrates, and early loss of primary teeth. The highest prevalence was similar, including these same three parameters and including decreased bone mineral density. Additional parameters had less agreement and were less prevalent. These were organized into three major and six minor criteria, with diagnosis of HPP being made when two major or one major and two minor criteria are present., (© 2023. The Author(s).)

A large international meta-analysis using primary data from 64 cohorts has quantified the increased risk of fracture associated with a previous history of fracture for future use in FRAX., Introduction: The aim of this study was to quantify the fracture risk associated with a prior fracture on an international basis and to explore the relationship of this risk with age, sex, time since baseline and bone mineral density (BMD)., Methods: We studied 665,971 men and 1,438,535 women from 64 cohorts in 32 countries followed for a total of 19.5 million person-years. The effect of a prior history of fracture on the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture, and hip fracture alone was examined using an extended Poisson model in each cohort. Covariates examined were age, sex, BMD, and duration of follow-up. The results of the different studies were merged by using the weighted β-coefficients., Results: A previous fracture history, compared with individuals without a prior fracture, was associated with a significantly increased risk of any clinical fracture (hazard ratio, HR = 1.88; 95% CI = 1.72-2.07). The risk ratio was similar for the outcome of osteoporotic fracture (HR = 1.87; 95% CI = 1.69-2.07), major osteoporotic fracture (HR = 1.83; 95% CI = 1.63-2.06), or for hip fracture (HR = 1.82; 95% CI = 1.62-2.06). There was no significant difference in risk ratio between men and women. Subsequent fracture risk was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any clinical fracture (14%), osteoporotic fracture (17%), and for hip fracture (33%). The risk ratio for all fracture outcomes related to prior fracture decreased significantly with adjustment for age and time since baseline examination., Conclusion: A previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by BMD. The effect is similar in men and women. Its quantitation on an international basis permits the more accurate use of this risk factor in case finding strategies., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Intermittent fasting (IF) is a promising strategy for weight loss and improving metabolic health, but its effects on bone health are less clear. This review aims to summarise and critically evaluate the preclinical and clinical evidence on IF regimens ( the 5:2 diet , alternate-day fasting (ADF) and time-restricted eating (TRE)/time-restricted feeding and bone health outcomes. Animal studies have utilised IF alongside other dietary practices known to elicit detrimental effects on bone health and/or in models mimicking specific conditions; thus, findings from these studies are difficult to apply to humans. While limited in scope, observational studies suggest a link between some IF practices (e.g. breakfast omission) and compromised bone health, although lack of control for confounding factors makes these data difficult to interpret. Interventional studies suggest that TRE regimens practised up to 6 months do not adversely affect bone outcomes and may even slightly protect against bone loss during modest weight loss (< 5 % of baseline body weight). Most studies on ADF have shown no adverse effects on bone outcomes, while no studies on the ‘5–2’ diet have reported bone outcomes. Available interventional studies are limited by their short duration, small and diverse population samples, assessment of total body bone mass exclusively (by dual-energy X-ray absorptiometry) and inadequate control of factors that may affect bone outcomes, making the interpretation of existing data challenging. Further research is required to better characterise bone responses to various IF approaches using well-controlled protocols of sufficient duration, adequately powered to assess changes in bone outcomes and designed to include clinically relevant bone assessments.

Purpose: There has been a persistent claim that dairy products contain calcium-leaching proteins, although the soundness of such a claim has been challenged. A meta-analysis of randomized controlled trials (RCTs) on the effects of milk-derived protein supplementation on bone health indices in adults was performed to reconcile the controversy surrounding the potential skeletal safety concerns of proteins of dairy origin., Methods: The PubMed and Web of Science databases were searched for relevant RCTs. A random-effects model was used to generate pooled effect sizes and 95% confidence intervals., Results: Milk-derived protein supplementation did not significantly affect whole-body BMD (n = 7 RCTs) and BMD at the lumbar spine (n = 10), hip (n = 8), femoral neck (n = 9), trochanter (n = 5), intertrochanter (n = 2), and ultradistal radius (n = 2). The concentrations of bone formation markers (bone-specific alkaline phosphatase [n = 11], osteocalcin [n = 6], procollagen type 1 amino-terminal propeptide [n = 5]), bone resorption markers (N-terminal telopeptide of type 1 collagen [n = 7], C-terminal telopeptide of type 1 collagen [n = 7], deoxypyridinoline [n = 4]), and parathyroid hormone (n = 7) were not significantly affected. However, increased insulin-like growth factor-1 (IGF-1) concentrations (n = 13) were observed. Reduced IGF-1 concentrations were observed when soy protein was used as a comparator, and increased IGF-1 concentrations were observed when carbohydrate was used., Conclusion: Our findings do not support the claim that proteins of dairy origin are detrimental to bone health., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Background: Locomotor capacity (LC) is an important domain of intrinsic capacity and key determinant of functional ability and well-being in older age. The United Nations Decade of Healthy Ageing (2021-2030) calls for strengthening data and research on healthy ageing, including the measurement of older persons' LC. To advance the measurement and monitoring of LC, there is pressing need to identify valid and reliable measures., Objective: To identify all the available tools that were validated for measurement of LC or of its specific attributes in older people and to assess the methodological quality of the studies and measurement properties of the tools., Design: Systematic review., Setting: Anywhere (Community-dwelling; long-term care facility; etc.)., Subjects: Older people., Methods: We used highly sensitive search strategies to search the following databases: Medline, Embase, Scopus, CINAHL and PsycINFO. The study was conducted following the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) methodology for systematic review of outcome measurement instruments., Results: A total of 125 studies were included, which assessed tools for balance (n = 84), muscle power (n = 12), muscle strength (n = 32, including four studies about tools for balance and muscle power) and endurance (n = 1). No studies on tools for muscle function, joint function, or locomotor capacity overall, were retrieved. We identified 69 clinician-report or objective assessment tools for balance, 30 for muscle strength, 12 for muscle power and 1 endurance assessment tool. The GRADE assessment of quality of evidence showed that only a few tools have high quality evidence for both sufficient validity and reliability: The Balance Evaluation Systems Test (BESTest), the Mini-Balance Evaluation Systems Test (Mini-BESTest), the Berg Balance Scale (BBS) and the Timed Up and Go (TUG) test., Conclusions: A few tools with high quality evidence for sufficient validity and reliability are currently available for balance assessment in older people that may be recommended for use in clinical and research settings. Further validation studies are required for muscle strength, muscle power and endurance assessment tools., (© World Health Organization, 2023. All rights reserved. The World Health Organization has granted the Publisher permission for the reproduction of this article.)

Most fracture risk assessment tools use clinical risk factors combined with bone mineral density (BMD) to improve assessment of osteoporosis; however, stratifying fracture risk remains challenging. This study developed a fracture risk assessment tool that uses information about volumetric bone density and three-dimensional structure, obtained using high-resolution peripheral quantitative compute tomography (HR-pQCT), to provide an alternative approach for patient-specific assessment of fracture risk. Using an international prospective cohort of older adults (n = 6802) we developed a tool to predict osteoporotic fracture risk, called μFRAC. The model was constructed using random survival forests, and input predictors included HR-pQCT parameters summarizing BMD and microarchitecture alongside clinical risk factors (sex, age, height, weight, and prior adulthood fracture) and femoral neck areal BMD (FN aBMD). The performance of μFRAC was compared to the Fracture Risk Assessment Tool (FRAX) and a reference model built using FN aBMD and clinical covariates. μFRAC was predictive of osteoporotic fracture (c-index = 0.673, p < 0.001), modestly outperforming FRAX and FN aBMD models (c-index = 0.617 and 0.636, respectively). Removal of FN aBMD and all clinical risk factors, except age, from μFRAC did not significantly impact its performance when estimating 5-year and 10-year fracture risk. The performance of μFRAC improved when only major osteoporotic fractures were considered (c-index = 0.733, p < 0.001). We developed a personalized fracture risk assessment tool based on HR-pQCT that may provide an alternative approach to current clinical methods by leveraging direct measures of bone density and structure. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Childhood and adolescence are critical periods for optimizing skeletal growth. Dairy products are valuable sources of bone-beneficial nutrients, particularly calcium and protein. A random-effects meta-analysis of published randomized controlled trials was performed to quantitatively assess the effects of dairy supplementation on bone health indices in children and adolescents. The PubMed and Web of Science databases were searched. Dairy supplementation increased whole-body bone mineral content (BMC) (+25.37 g) and areal bone mineral density (aBMD) (+0.016 g/cm 2 ), total hip BMC (+0.49 g) and aBMD (+0.013 g/cm 2 ), femoral neck BMC (+0.06 g) and aBMD (+0.030 g/cm 2 ), lumbar spine BMC (+0.85 g) and aBMD (+0.019 g/cm 2 ), and height (0.21 cm). When expressed as a percentage difference, whole-body BMC was increased by 3.0%, total hip BMC by 3.3%, femoral neck BMC by 4.0%, lumbar spine BMC by 4.1%, whole-body aBMD by 1.8%, total hip aBMD by 1.2%, femoral neck aBMD by 1.5%, and lumbar spine aBMD by 2.6%. Dairy supplementation increased serum insulin-like growth factor I concentrations (19.89 nmol/L) and reduced concentrations of urinary deoxypyridinoline (-1.78 nmol/mmol creatinine) and serum parathyroid hormone (-10.46 pg/mL) but did not significantly affect the serum concentrations of osteocalcin, bone alkaline phosphatase, and C-terminal telopeptide of type 1 collagen. Serum 25-hydroxyvitamin D concentrations (+4.98 ng/mL) increased with vitamin D-fortified dairy supplementation. The positive effects on bone mineral mass parameters and height were generally consistent across subgroups defined by sex, geographical region, baseline calcium intake, calcium from the supplementation, trial duration, and Tanner stages. In summary, dairy supplementation during growth leads to a small but significant increase in bone mineral mass parameters, and these findings are generally supported by the changes in several biochemical parameters related to bone health., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Fear of falling is associated with numerous negative health outcomes in older adults and can limit the rehabilitation process. Hypnosis is now recognized as an effective treatment for a variety of conditions, especially anxiety and pain, which can be integrated safely with conventional medicine. The objective of this study was to assess the feasibility and acceptability of a hypnosis intervention in hospitalized older adults to reduce fear of falling., Methods: In this feasibility randomized controlled trial, 32 older patients, hospitalized in geriatric rehabilitation wards, were randomly allocated (1:1 ratio) to either an intervention group (hypnosis, 2 sessions, one per week, plus usual rehabilitation program) or a control group (usual rehabilitation program only). Clinical assessors and statistician were blinded to group allocation. Primary outcomes were recruitment rate, retention rate, and adherence to the intervention. Exploratory outcomes, analyzed according to the intention-to-treat principle, included impact of hypnosis on fear of falling (assessed by a new scale perform-FES), functional status, in-hospital falls, and length of hospital stay., Results: Recruitment rate was 1.3 patients per week. The recruitment of the population sample was achieved in 5.5 months. The retention rate did not differ significantly between groups and a good adherence to the hypnosis intervention was achieved (77% of patients received the full intervention). No adverse event related to the hypnosis intervention was observed. Regarding exploratory clinical outcomes, no differences were found between groups on any outcome., Conclusion: Hypnosis is feasible and well accepted in a geriatric hospitalized population undergoing rehabilitation. Further pilot work should be conducted, with an increased number of hypnosis sessions, before conducting a full-scale trial to conclude whether, or not, hypnosis is effective to reduce fear of falling., Trial Registration: NCT04726774., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: To examine the association between the baseline number of chronic diseases and multimorbidity with regard to the incidence of all and injurious falls over 3 years among European 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 main outcomes were the number of all falls and injurious falls experienced over 3 years. The number of chronic diseases and multimorbidity, defined as the presence of 3 or more chronic diseases at baseline, were assessed with the Self-Administered Comorbidity Questionnaire by Sangha et al., Results: Among the 2155 participants included in the analyses (mean age: 74.9 years, 62% were women, 52% were physically active more than 3 times a week), 569 (26.4%) had multimorbidity at baseline. Overall, each 1-unit increase in the baseline number of chronic diseases was linearly associated with a 7% increased incidence rate of all falls [adjusted incidence rate ratio (aIRR) 1.07, 95% CI 1.03-1.12, P < .001] and a 6% increased incidence rate of injurious falls (aIRR 1.06, 95% CI 1.02-1.11, P = .003). Baseline multimorbidity was associated with a 21% increased incidence rate of all falls (aIRR 1.21, 95% CI 1.07-1.37, P = .002) and a 17% increased incidence rate of injurious falls (aIRR 1.17, 95% CI 1.03-1.32, P = .02)., Conclusions and Implications: Baseline number of prevalent chronic diseases and multimorbidity in generally healthy and active community-dwelling older adults were associated with increased incidence rates of all and injurious falls over 3 years. These findings support that multimorbidity may need consideration as a risk factor for falls, even in generally healthy and active older adults., (Copyright © 2022 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To review the comparative effectiveness of osteoporosis treatments, including the bone anabolic agents, abaloparatide and romosozumab, on reducing the risk of fractures in postmenopausal women, and to characterise the effect of antiosteoporosis drug treatments on the risk of fractures according to baseline risk factors., Design: Systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials., Data Sources: Medline, Embase, and Cochrane Library to identify randomised controlled trials published between 1 January 1996 and 24 November 2021 that examined the effect of bisphosphonates, denosumab, selective oestrogen receptor modulators, parathyroid hormone receptor agonists, and romosozumab compared with placebo or active comparator., Eligibility Criteria for Selecting Studies: Randomised controlled trials that included non-Asian postmenopausal women with no restriction on age, when interventions looked at bone quality in a broad perspective. The primary outcome was clinical fractures. Secondary outcomes were vertebral, non-vertebral, hip, and major osteoporotic fractures, all cause mortality, adverse events, and serious cardiovascular adverse events., Results: The results were based on 69 trials (>80 000 patients). For clinical fractures, synthesis of the results showed a protective effect of bisphosphonates, parathyroid hormone receptor agonists, and romosozumab compared with placebo. Compared with parathyroid hormone receptor agonists, bisphosphonates were less effective in reducing clinical fractures (odds ratio 1.49, 95% confidence interval 1.12 to 2.00). Compared with parathyroid hormone receptor agonists and romosozumab, denosumab was less effective in reducing clinical fractures (odds ratio 1.85, 1.18 to 2.92 for denosumab v parathyroid hormone receptor agonists and 1.56, 1.02 to 2.39 for denosumab v romosozumab). An effect of all treatments on vertebral fractures compared with placebo was found. In the active treatment comparisons, denosumab, parathyroid hormone receptor agonists, and romosozumab were more effective than oral bisphosphonates in preventing vertebral fractures. The effect of all treatments was unaffected by baseline risk indicators, except for antiresorptive treatments that showed a greater reduction of clinical fractures compared with placebo with increasing mean age (number of studies=17; β=0.98, 95% confidence interval 0.96 to 0.99). No harm outcomes were seen. The certainty in the effect estimates was moderate to low for all individual outcomes, mainly because of limitations in reporting, nominally indicating a serious risk of bias and imprecision., Conclusions: The evidence indicated a benefit of a range of treatments for osteoporosis in postmenopausal women for clinical and vertebral fractures. Bone anabolic treatments were more effective than bisphosphonates in the prevention of clinical and vertebral fractures, irrespective of baseline risk indicators. Hence this analysis provided no clinical evidence for restricting the use of anabolic treatment to patients with a very high risk of fractures., Systematic Review Registration: PROSPERO CRD42019128391., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare support from UCB and Amgen for the submitted work: MNH, IC, CvB, JFR, AU, SMN, and RC report grants from UCB and Amgen paid to the Parker Institute to conduct the study; J-JB reports personal fees from UCB during the conduct of the study and personal fees from UCB and Sandoz outside the submitted work; MLB reports fees as honorarium, speaker, grants, and consultant from Amgen, Bruno Farmaceutici, Calcilytix, Kyowa Kirin, UCB, Abiogen, Alexion, Echolight, Eli Lilly, Kyowa Kirin, SPA, Theramex, and Amolyt outside the submitted work; AD-P has received speaker fees from Amgen, Lilly, and Theramex and is a shareholder of Active Life; PH reports personal fees from UCB during the conduct of the study and personal fees from UCB, Amgen, Gedeon Richter, Stada, and Theramex outside the submitted work; MKJ reports personal fees and non-financial support from UCB during the conduct of the study, and grants, personal fees, and non-financial support from Amgen and UCB outside the submitted work; MKJ was also supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and the views expressed are those of the author and not necessarily those of the NHS, the NIHR, or the Department of Health; WFL reports speakers fee/advisory board from UCB, Amgen, Pfizer, and Lilly; XN has received fees for consulting from UCB and Amgen and for lectures from UCB, Amgen, and Lilly; CR reports personal fees from UCB during the conduct of the study, and grants and personal fees from Alexion, Regeneron, Sanofi, and Amgen outside the submitted work; SM reports fees as speaker and advisory board from Abiogen, Amgen, Bruno Farmaceutici, Diasorin, Eli Lilly, Shire, Sandoz, Takeda, Abiogen, Kyowa Kirin, Pfizer and UCB outside the submitted work; TT reports personal fees from UCB during the conduct of the study, personal fees from Amgen, Arrow, and Biogen, personal fees from Grunenthal, Jansen, LCA, Lilly, MSD, Nordic, Novartis, Pfizer, Sanofi, Thuasne, and Theramex, grants and personal fees from Chugai and UCB, and grants from Bone Therapeutics outside the submitted work; SLF reports grants from Amgen, consulting and lecture honorarium from UCB, consulting honorarium from Radius, and grants and consulting honorarium from Agnovos outside the submitted work; DP-A's department received consultancy fees related to this work, DP-A reports grants and fees for speaker services and advisory board membership from Amgen, grants, non-financial support, and fees for consultancy services from UCB Biopharma, grants from Les Laboratoires Servier and UCB outside the submitted work, DP-A is an HTA Funding Committee membership, and Janssen, on behalf of Innovative Medicines Initiative (IMI) funded European Health Data and Evidence Network (EHDEN) and European Medical Information Framework (EMIF) consortiums, and Synapse Management Partners, have supported training programmes organised by DP-A's department that are open to external participants; BL reports personal fees from UCB during the conduct of the study and BL has received funding to her institution from Amgen and Novo Nordisk and personal fees from Amgen, UCB, Eli Lilly, Gedeon-Richter, and Gilead outside the submitted work; BA reports personal fees from UCB during the conduct of the study, grants and personal fees from UCB and Kyowa-Kirin UK, personal fees from Amgen, grants from Novartis, and grants and personal fees from Pharmacosmos outside the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The European Working Group on Sarcopenia in Older People (EWGSOP2) recently revised its definition and diagnostic criteria for sarcopenia, placing muscle strength at the forefront. The pathogenesis of dynapenia (or low muscle strength) is still not fully understood, but there is emerging evidence that central neural factors constitute critical determinants., Methods: Our cross-sectional study included 59 community-dwelling older women (mean age 73.1 ± 4.9 years). Participants underwent detailed skeletal muscle assessments for muscle strength defined by handgrip strength and chair rise time measurements using the recently published EWGSOP2 cut-off points. Functional magnetic resonance imaging (fMRI) was assessed during the performance of a cognitive dual-task paradigm, consisting of a baseline, two single-tasks (motor and arithmetic) and one dual-task (motor and arithmetic combined)., Results: Forty-seven percent (28/59) of participants were classified as dynapenic. fMRI results revealed a differential recruitment of motor circuits in the brain during the dual-task condition in dynapenic as compared with non-dynapenic participants. In particular, while the brain activity during the single-tasks did not differ between the two groups, only during the dual-task non-dynapenic participants showed significant increased activation in dorsolateral prefrontal and premotor cortex, and in supplementary motor area as compared to dynapenic participants., Conclusion: Our results point to a dysfunctional involvement of brain networks associated with motor control in dynapenia in a multi-tasking paradigm. A better knowledge of the link between dynapenia and brain functions could provide new impulses in the diagnosis and interventions for sarcopenia., (© 2023. The Author(s).)

Background: Around a third of adults aged 65 and older fall every year, resulting in unintentional injuries in 30% of the cases. Fractures are a frequent consequence of falls, primarily caused in individuals with decreased bone strength who are unable to cushion their falls. Accordingly, an individual's number of experienced falls has a direct influence on fracture risk. The aim of this study was the development of a statistical model to predict future fall rates using personalized risk predictors., Methods: In the prospective cohort GERICO, several fall risk factor variables were collected in community-dwelling older adults at two time-points four years apart (T1 and T2). Participants were asked how many falls they experienced during 12 months prior to the examinations. Rate ratios for the number of reported falls at T2 were computed for age, sex, reported fall number at T1, physical performance tests, physical activity level, comorbidity and medication number with negative binomial regression models., Results: The analysis included 604 participants (male: 122, female: 482) with a median age of 67.90 years at T1. The mean number of falls per person was 1.04 and 0.70 at T1 and T2. The number of reported falls at T1 as a factor variable was the strongest risk factor with an unadjusted rate ratio [RR] of 2.60 for 3 falls (95% confidence interval [CI] 1.54 to 4.37), RR of 2.63 (95% CI 1.06 to 6.54) for 4 falls, and RR of 10.19 (95% CI 6.25 to 16.60) for 5 and more falls, when compared to 0 falls. The cross-validated prediction error was comparable for the global model including all candidate variables and the univariable model including prior fall numbers at T1 as the only predictor., Conclusion: In the GERICO cohort, the prior fall number as single predictor information for a personalized fall rate is as good as when including further available fall risk factors. Specifically, individuals who have experienced three and more falls are expected to fall multiple times again., Trial Registration: ISRCTN11865958, 13/07/2016, retrospectively registered., (© 2023. The Author(s).)

Introduction: Osteoporosis is currently diagnosed based on areal bone mineral density (aBMD) computed from 2D DXA scans. However, aBMD is a limited surrogate for femoral strength since it does not account for 3D bone geometry and density distribution. QCT scans combined with finite element (FE) analysis can deliver improved femoral strength predictions. However, non-negligible radiation dose and high costs prevent a systematic usage of this technique for screening purposes. As an alternative, the 3D-Shaper software (3D-Shaper Medical, Spain) reconstructs the 3D shape and density distribution of the femur from 2D DXA scans. This approach could deliver a more accurate estimation of femoral strength than aBMD by using FE analysis on the reconstructed 3D DXA. Methods: Here we present the first independent evaluation of the software, using a dataset of 77 ex vivo femora. We extend a prior evaluation by including the density distribution differences, the spatial correlation of density values and an FE analysis. Yet, cortical thickness is left out of this evaluation, since the cortex is not resolved in our FE models. Results: We found an average surface distance of 1.16 mm between 3D DXA and QCT images, which shows a good reconstruction of the bone geometry. Although BMD values obtained from 3D DXA and QCT correlated well ( r 2 , more than one-third of the 3D DXA BMD. Furthermore, the low correlation ( 3 = 0.48) between density values of both images indicates a limited reconstruction of the 3D density distribution. FE results were in good agreement between QCT and 3D DXA images, with a high coefficient of determination ( r 2 = 0.48) between density values of both images indicates a limited reconstruction of the 3D density distribution. FE results were in good agreement between QCT and 3D DXA images, with a high coefficient of determination ( r 2 = 0.88). However, this correlation was not statistically different from a direct prediction by aBMD. Moreover, we found differences in the fracture patterns between the two image types. QCT-based FE analysis resulted mostly in femoral neck fractures and 3D DXA-based FE in subcapital or pertrochanteric fractures. Discussion: In conclusion, 3D-Shaper generates an altered BMD distribution compared to QCT but, after careful density calibration, shows an interesting potential for deriving a standardized femoral strength from a DXA scan., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dudle, Gugler, Pretterklieber, Ferrari, Lippuner and Zysset.)

Objective: This study explored the impact of time-restricted eating (TRE) versus standard dietary advice (SDA) on bone health., Methods: Adults with ≥1 component of metabolic syndrome were randomized to TRE (ad libitum eating within 12 hours) or SDA (food pyramid brochure). Bone turnover markers and bone mineral content/density by dual energy x-ray absorptiometry were assessed at baseline and 6-month follow-up. Statistical analyses were performed in the total population and by weight loss response., Results: In the total population (n = 42, 76% women, median age 47 years [IQR: 31-52]), there were no between-group differences (TRE vs. SDA) in any bone parameter. Among weight loss responders (≥0.6 kg weight loss), the bone resorption marker β-carboxyterminal telopeptide of type I collagen tended to decrease after TRE but increase after SDA (between-group differences p = 0.041), whereas changes in the bone formation marker procollagen type I N-propeptide did not differ between groups. Total body bone mineral content decreased after SDA (p = 0.028) but remained unchanged after TRE (p = 0.31) in weight loss responders (between-group differences p = 0.028). Among nonresponders (<0.6 kg weight loss), there were no between-group differences in bone outcomes., Conclusions: TRE had no detrimental impact on bone health, whereas, when weight loss occurred, it was associated with some bone-sparing effects compared with SDA., (© 2022 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Background: Knee osteoarthritis (OA) is a common condition, associated with a high rate of disability and poor quality of life. Despite the importance of such evidence in public health, no umbrella review (i.e., a review of other systematic reviews and meta-analyses) has systematically assessed evidence on association between knee OA and adverse health outcomes., Aims: To map and grade all health outcomes associated with knee OA using an umbrella review approach., Methods: The search was made across several databases up to 22 April 2022. We used an umbrella review of systematic reviews with meta-analyses of observational studies assessing the effect sizes, based on random effect summary, 95% prediction intervals, heterogeneity, small study effects, and excess significance bias. The evidence was then graded from convincing (class I) to weak (class IV)., Results: Among 3,847 studies initially considered, five meta-analyses were included for a total of five different outcomes. Three adverse outcomes were significantly associated with knee OA (i.e., cardiovascular mortality, falls, and subclinical atherosclerosis). The presence of knee OA was associated with a significantly higher risk of cardiovascular mortality (odds ratio, OR = 1.17; 95%CI, confidence intervals: 1.02-1.34), falls (RR = 1.34; 95%CI: 1.10-1.64), and conditions associated with subclinical atherosclerosis (OR = 1.43; 95%CI: 1.003-2.05). The certainty of each of this evidence was weak., Conclusions: Our umbrella review suggests that knee OA can be considered as putative risk factor for some medical conditions, including cardiovascular diseases and falls, however, it is important to note that the evidence is affected by potential biases., (© 2022. The Author(s).)