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Menopause is a high-risk period for osteoporosis, which may be exacerbated by HIV and/or antiretroviral therapy (ART).To study the impact of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) on bone mineral density (BMD) in peri and early post-menopausal women living with HIV.A randomized, international, multicenter study of an early vs delayed (48-week) switch. BMD measured by DXA scan.Thirty-four women enrolled; 19 in the immediate and 15 in the delayed switch arm Sept 2017 to April 2019; 30 completed the 96-week protocol. The study closed for futility during the COVID pandemic. The median (IQR) age was 51 years (47, 53), with a median (IQR) of 16.5 years (14, 23) since HIV diagnosis, median (IQR) 14 years (11, 20) of ART, and mean 8.6 years TDF. At enrollment, TDF was used in combination with a boosted protease inhibitor (n=7), a non-nucleoside reverse transcriptase inhibitor (n=13), an integrase inhibitor (n= 11) or more than one ART class (n=3). The median (95% CI) % change in BMD at the lumbar spine from 0-48 weeks in the immediate switch group was 1.97% (-1.15, 5.49) compared to a median (95% CI) decrease of 2.32% (- 5.11, 0.19) in the delayed arm. The median (95% CI) % change in BMD from 0-96 weeks was 2.33% (0, 4.51) in the immediate arm compared to 0.70% (-3.19, 2.47) in the delayed arm.We demonstrated a trend to increased BMD at the lumbar spine following a switch from TDF to TAF in peri-and early post menopausal women living with HIV.

Exercise and nutrition interventions are often recommended for frailty; however, effective strategies are required for real-world implementation. Our primary aim was to assess the feasibility and acceptability of telephone and virtual delivery of MoveStrong, an 8-week exercise and nutrition program with a 4-week follow-up for older pre-frail and frail adults. A priori criteria for success included: recruitment (≥25/12 weeks), retention at follow-up (≥80%), and adherence to exercise and nutrition sessions (≥70%). We recruited community-dwelling Ontario residents; ≥60 years, ≥1 chronic condition, ≥1 FRAIL scale score. Participants received mailed materials, a personalized exercise program, 11 remote one-on-one training sessions with an exercise physiologist and 3 online dietitian-led nutrition education sessions. We completed exploratory analyses of secondary outcomes including physical function and dietary protein intake. Semi-structured interviews supported program evaluation. In total, 30 participants were enrolled. 28 (93%) participants completed program and follow-up assessments. Adherence to exercise and nutrition sessions (CI) was 84% (77%–91%) and 82% (70%–93%) respectively. At program end and follow-up [mean change (CI)], significant improvements were measured in 30-second chair stand test [3.50 (1.12–5.86), 4.54 (1.94–7.13) chair stands] and dietary protein intake [12.9 (5.7–20.0), 9.2 (0.4–18.1) g]. Overall, participants were satisfied with program delivery. Trial registration number: NCT04663685.

Introduction Cet essai pilote randomisé par étapes de huit semaines a permis d’évaluer le programme MoveStrong, qui vise à enseigner aux adultes présentant une fragilité ou une préfragilité un entraînement à l’équilibre et à la force musculaire ainsi qu’un apport suffisant en protéines pour prévenir les chutes et améliorer la mobilité. Méthodologie Nous avons recruté des personnes âgées de 60 ans ou plus, ayant un score de 1 ou plus sur l’échelle FRAIL et au moins une affection chronique et ne faisant pas d’entraînement musculaire. Le programme consistait en 16 séances de groupe d’une heure animées par un physiologiste de l’exercice et 2 séances de nutrition d’une heure animées par une diététiste. Nous avons analysé les résultats secondaires – poids, vitesse de marche, force de préhension, capacité physique (niveau de fatigue), transition assisdebout, équilibre dynamique, qualité de vie liée à la santé (QVLS), niveau d’activité physique et apport en protéines – à l’aide d’un test t d’échantillons appariés et d’une équation d’estimation généralisée (EEG). Résultats Sur les 44 participants (âge moyen [É.-T.] : 79 ans [9,82]), 35 étaient préfragiles et 9 étaient fragiles. Au moment du suivi, les participants avaient considérablement amélioré leur force de préhension (1,63 kg; IC à 95 % : 0,62 à 2,63), leur capacité à effectuer des transitions assis-debout (2 transitions assis-debout; IC à 95 % : 1 à 3) et leur équilibre dynamique (1,68 s; IC à 95 % : 0,47 à 2,89). Il n’y a pas eu d’amélioration statistiquement significative de la vitesse de marche, des scores QVLS, de l’autoévaluation de la santé, des niveaux d’activité physique (activité aérobique et entraînement musculaire) ou de l’apport en protéines. L’analyse par EEG a révélé une interaction entre l’exposition à MoveStrong et la vitesse de marche, la capacité à effectuer des transitions assisdebout, l’équilibre dynamique et les scores QVLS. Le coût total de mise en oeuvre du programme et de l’achat d’équipement s’est élevé à 14 700 $ CA, soit 377 $ CA par participant. Conclusion Les analyses exploratoires indiquent que les exercices MoveStrong améliorent la vitesse de marche, la capacité à effectuer des transitions assisdebout, l’équilibre dynamique et les scores QVLS chez les personnes âgées fragiles et préfragiles.

What is this summary about? This is a plain language summary of an article originally published in the Journal of Bone and Mineral Research. People with fibrodysplasia ossificans progressiva (FOP) become physically disabled over time as new bone forms in places where it is not usually found, such as in muscles and ligaments. Until recently, there were no treatments for FOP that had been proven through clinical trials; however, a drug called palovarotene has been tested in clinical trials and may be effective. Here, we describe the MOVE trial, which investigated how effectively palovarotene works, as well as its safety in treating patients with FOP. What were the results? Results from MOVE suggest that palovarotene may reduce extra bone formation outside the normal skeleton. Patients with FOP who took palovarotene formed less new bone than those who did not take palovarotene. The most common side effects involved the skin, and included dryness and irritation. Some children who were still growing when they took palovarotene had a side effect that resulted in the (normal) growth of their skeleton stopping too soon. What do the results of the trial mean? Palovarotene may be a useful treatment option for FOP. Patients, caregivers, and doctors would need to consider the benefits and risks of treatment with palovarotene, particularly with growing children. Clinical Trial Registration: NCT03312634 ( ClinicalTrials.gov )

BackgroundFibrodysplasia ossificans progressiva (FOP), an ultra-rare disorder caused by mutations in the gene encoding activin A receptor type 1 (ACVR1), is characterized by painful flare-ups and cumulative heterotopic ossification (HO). Garetosmab, a fully-human monoclonal antibody blocking activin A, prevents HO in FOP mice.MethodsLUMINA-1 (NCT03188666) was a phase 2, multi-center, randomized, double-blind, placebo-controlled study evaluating the safety, tolerability, and effects on HO of intravenous (IV) garetosmab 10 mg/kg every 4 weeks (Q4W). Adult patients with FOP were randomized to garetosmab or placebo for 28 weeks (Period_1), followed by an open-label period (Period_2). After Period_2, patients were allowed to stay on garetosmab in an open-label extension. For Period_1, primary endpoints were HO total lesion activity (HO-TLA) by18F-sodium fluoride positron emission tomography (18F-NaF PET) and HO total lesion volume by computed tomography (CT). The Period_2 primary endpoint compared the number of new lesions in Period_2 versus Period_1. The safety primary endpoint was incidence and severity of TEAEs through the end of the Period 1 at week 28.FindingsPatients (n=44) were randomized to garetosmab (n=20) or placebo (n=24). In Period_1, there was a trend for garetosmab to decrease HO-TLA versus placebo (24.6%;P=0.07), primarily driven by near complete prevention of new lesions (97% decrease by18F-NaF PET, post-hocP=0.009; 90% relative reduction by CT, post-hocP=0.017); flare-ups were significantly reduced (P=0.0005). For placebo patients transitioning to garetosmab in Period_2, no patients developed new HO lesions (0% in Period_2 versus 40.9% in Period_1;P=0.0027) by CT. All 44 patients met primary safety endpoint of at least one TEAE during Period 1. Garetosmab was associated with more adverse events than placebo: mild recurrent epistaxis, madarosis, and skin/soft tissue infections. Overall, the AEs were predominantly mild in severity, with no effect on patients’ ability to receive garetosmab. Five deaths (5/44; 11.4%) occurred either in Period_2 or the open-label extension. The deaths were associated with baseline disease severity in some, preexisting comorbidities in others and occurred following 8-16 doses (median: 15) of garetosmab in the open label/follow-up periods.InterpretationGaretosmab reduced flare-ups and prevented new HO lesions in FOP patients. Although side effects were mild to moderate, there were a relatively high number of deaths for a small study; the deaths were not related to epistaxis and considered unlikely to be related to garetosmab.FundingRegeneron Pharmaceuticals, Inc.

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare, severely disabling genetic disorder of progressive heterotopic ossification (HO). The single-arm, open-label, phase 3 MOVE trial (NCT03312634) assessed efficacy and safety of palovarotene, a selective retinoic acid receptor gamma agonist, in patients with FOP. Findings were compared with FOP natural history study (NHS; NCT02322255) participants untreated beyond standard of care. Patients aged ≥4 years received palovarotene once daily (chronic: 5 mg; flare-up: 20 mg for 4 weeks, then 10 mg for ≥8 weeks; weight-adjusted if skeletally immature). The primary endpoint was annualized change in new HO volume versus NHS participants (by low-dose whole-body computed tomography [WBCT]), analyzed using a Bayesian compound Poisson model (BcPM) with square-root transformation. Twelve-month interim analyses met futility criteria; dosing was paused. An independent Data Monitoring Committee recommended trial continuation. Post hoc 18-month interim analyses utilized BcPM with square-root transformation and HO data collapsed to equalize MOVE and NHS visit schedules, BcPM without transformation, and weighted linear mixed-effects (wLME) models, alongside prespecified analysis. Safety was assessed throughout. Eighteen-month interim analyses included 97 MOVE and 101 NHS individuals with post-baseline WBCT. BcPM analyses without transformation showed 99.4% probability of any reduction in new HO with palovarotene versus NHS participants (with transformation: 65.4%). Mean annualized new HO volume was 60% lower in MOVE versus the NHS. wLME results were similar (54% reduction fitted; nominal p = 0.039). All palovarotene-treated patients reported ≥1 adverse event (AE); 97.0% reported ≥1 retinoid-associated AE; 29.3% reported ≥1 serious AE, including premature physeal closure (PPC)/epiphyseal disorder in 21/57 (36.8%) patients aged

BackgroundThere remains significant uncertainty in the definition of the long COVID disease, its expected clinical course, and its impact on daily functioning. Social media platforms can generate valuable insights into patient-reported health outcomes as the content is produced at high resolution by patients and caregivers, representing experiences that may be unavailable to most clinicians.ObjectiveWe aim to determine the validity and effectiveness of advanced NLP approaches built to derive insight into Long COVID-related patient-reported health outcomes from social media platforms.MethodologyWe use Transformer-based BERT models to extract and normalize long COVID Symptoms and Conditions (SyCo) from English posts on Twitter and Reddit. Furthermore, we estimate the occurrence and co-occurrence of SyCo terms at any point or across time and locations. Finally, we compare the extracted health outcomes with human annotations and highly utilized clinical outcomes grounded in the medical literature.ResultBased on our findings, the top three most commonly occurring groups of long COVID symptoms are systemic (such as “fatigue”), neuropsychiatric (such as “anxiety” and “brain fog”), and respiratory (such as “shortness of breath”). Regarding the co-occurring symptoms, the pair of ‘fatigue & headaches’ is most common. In addition, we show that other conditions, such as infection, hair loss, and weight loss, as well as mentions of other diseases, such as flu, cancer, or Lyme disease, are among the top reported terms by social media users.ConclusionThe outcome of our social media-derived pipeline is comparable with the outcomes of peer-reviewed articles relevant to long COVID symptoms. Overall, this study provides unique insights into patient-reported health outcomes from long COVID and valuable information about the patient’s journey that can help healthcare providers anticipate future needs.

International variations in osteoporosis and fracture rates have been reported, with temporal trends differing between populations. We observed higher BMD and lower fracture prevalence in a recently recruited cohort compared to that of a cohort recruited 20 years ago, even after adjusting for multiple covariates.We explored sex-specific differences in femoral neck bone mineral density (FN-BMD) and in prevalent major osteoporotic fractures (MOF) using two Canadian cohorts recruited 20 years apart.We included men and women aged 50-85 years from the Canadian Multicentre Osteoporosis Study (CaMos, N = 6,479; 1995-1997) and the Canadian Longitudinal Study on Aging (CLSA, N = 19,534; 2012-2015). We created regression models to compare FN-BMD and fracture risk between cohorts, adjusting for important covariates. Among participants with prevalent MOF, we compared anti-osteoporosis medication use.Mean (SD) age in CaMos (65.4 years [8.6]) was higher than in CLSA (63.8 years [9.1]). CaMos participants had lower mean body mass index and higher prevalence of smoking (p 0.001). Adjusted linear regression models (estimates [95%CI]) demonstrated lower FN-BMD in CaMos women (- 0.017 g/cmHigher BMD and lower fracture prevalence were noted in the more recently recruited CLSA cohort compared to CaMos, even after adjusting for multiple covariates. We noted an increase in bisphosphonate use in the recent cohort, but it remained very low in men.

There have been over 500 million confirmed cases of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), also known as coronavirus disease 2019 (COVID-19), across the globe. To date, a broad spectrum of neurological manifestations following acute infections as well as COVID-19 vaccines have been reported. The aim of this study was to describe the spectrum of neurological manifestations seen in the 'COVID-19 clinic' established in a tertiary Movement Disorders clinic.In this consecutive case-series study over the period March 2020-January 2022, clinical information regarding demographic data, clinical history and examination findings, investigation results and video recordings of outpatients with motor manifestations associated with COVID-19 infection or vaccination were reviewed.Twenty-one adult patients were reviewed in this ad hoc clinic at Toronto Western Hospital. The majority of the patients were female (76%) and the mean (range) age was 50.7 ± 17.2 (21-80) years. Nine patients (43%) presented with motor manifestations following COVID-19 infection. Twelve patients (57%) developed neurological symptoms following at least one dose of the mRNA or viral vector-based COVID-19 vaccine. The most common manifestation observed was a functional movement disorder (43%). The vaccine group demonstrated a higher number of functional disorders compared to the infection group (58% vs. 22%; p = 0.08).Functional motor manifestations can be associated with COVID-19 and are likely to be under-reported. In view of the co-existence of functional symptoms, movement disorders and mental health conditions observed in this study, we would advocate the use of dedicated COVID-19 Neurology clinics with full access to an experienced multidisciplinary team.

RESUME CONTEXTE: Les caracteristiques des patients, les soins cliniques, l’utilisation des ressources et les issues cliniques des personnes atteintes de la maladie a coronavirus 2019 (COVID-19) hospitalisees au Canada ne sont pas bien connus. METHODES: Nous avons recueilli des donnees sur tous les adultes hospitalises atteints de la COVID-19 ou de l’influenza ayant obtenu leur conge d’unites medicales ou d’unites de soins intensifs medicaux et chirurgicaux entre le 1er novembre 2019 et le 30 juin 2020 dans 7 centres hospitaliers de Toronto et de Mississauga (Ontario). Nous avons compare les issues cliniques des patients a l’aide de modeles de regression multivariee, en tenant compte des facteurs sociodemographiques et de l’intensite des comorbidites. Nous avons valide le degre d’exactitude de 7 scores de risque mis au point a l’externe pour determiner leur capacite a predire le risque de deces chez les patients atteints de la COVID-19. RESULTATS: Parmi les hospitalisations retenues, 1027 patients etaient atteints de la COVID-19 (âge median de 65 ans, 59,1 % d’hommes) et 783 etaient atteints de l’influenza (âge median de 68 ans, 50,8 % d’hommes). Les patients âges de moins de 50 ans comptaient pour 21,2 % de toutes les hospitalisations dues a la COVID-19 et 24,0 % des sejours aux soins intensifs. Comparativement aux patients atteints de l’influenza, les patients atteints de la COVID-19 presentaient un taux de mortalite perhospitaliere (mortalite non ajustee 19,9 % c. 6,1 %; risque relatif [RR] ajuste 3,46 %, intervalle de confiance [IC] a 95 % 2,56–4,68) et un taux d’utilisation des ressources des unites de soins intensifs (taux non ajuste 26,4 % c. 18,0 %; RR ajuste 1,50, IC a 95 % 1,25–1,80) significativement plus eleves, ainsi qu’une duree d’hospitalisation (duree mediane non ajustee 8,7 jours c. 4,8 jours; rapport des taux d’incidence ajuste 1,45; IC a 95 % 1,25–1,69) significativement plus longue. Le taux de rehospitalisation dans les 30 jours n’etait pas significativement different (taux non ajuste 9,3 % c. 9,6 %; RR ajuste 0,98 %, IC a 95 % 0,70–1,39). Trois scores de risque utilisant un pointage pour predire la mortalite perhospitaliere ont montre une bonne discrimination (aire sous la courbe [ASC] de la fonction d’efficacite du recepteur [ROC] 0,72–0,81) et une bonne calibration. INTERPRETATION: Durant la premiere vague de la pandemie, l’hospitalisation des patients atteints de la COVID-19 etait associee a des taux de mortalite et d’utilisation des ressources des unites de soins intensifs et a une duree d’hospitalisation significativement plus importants que les hospitalisations des patients atteints de l’influenza. De simples scores de risque peuvent predire avec une bonne exactitude le risque de mortalite perhospitaliere des patients atteints de la COVID-19.

Patients with osteoporosis and chronic kidney disease (CKD) are at increased risk of fracture and associated negative outcomes, including increased mortality. The present post hoc analysis of two randomized, multicenter, phase 3 clinical trials-Fracture Study in Postmenopausal Women with Osteoporosis (FRAME) and Active-Controlled Fracture Study in Postmenopausal Women with Osteoporosis at High Risk (ARCH)-investigated the efficacy and safety of romosozumab in postmenopausal women with osteoporosis and mild-to-moderate CKD. The analysis included data from 7147 patients from FRAME and 4077 from ARCH. Eighty-one percent of patients from FRAME and 85% from ARCH had mild or moderate reduction in estimated glomerular filtration rate (eGFR) at baseline, and part of this reduction is likely age related. During the 1-year double-blind phases of the trials, patients received romosozumab 210 mg sc or placebo monthly in FRAME and romosozumab 210 mg sc monthly or alendronate 70 mg po weekly in ARCH. Bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck and vertebral and nonvertebral fractures were assessed at baseline and month 12. In both trials, the least-square mean percent change from baseline BMD was significantly greater in the romosozumab groups versus controls across all kidney function categories at month 12. Romosozumab reduced the relative risk of new vertebral fractures at month 12 among patients with eGFR of 30-59, 60-89, and ≥90 mL/min by 72% (95% confidence interval [CI] 14-91; p = 0.017), 70% (40-85; p

This 8-week pilot stepped-wedge randomized controlled trial evaluated the MoveStrong program for teaching adults who have frailty/pre-frailty about balance and functional strength training and sufficient protein intake to prevent falls and improve mobility.We recruited individuals aged 60 years and over, with a FRAIL scale score of 1 or higher and at least one chronic condition, who were not currently strength training. The program included 16 exercise physiologist-led hour-long group sessions and two dietitian-led hour-long nutrition sessions. We analyzed secondary outcomes-weight, gait speed, grip strength, physical capacity (fatigue levels), sit-to-stand functioning, dynamic balance, health-related quality of life (HRQoL), physical activity levels and protein intake-using a paired t test and a generalized estimating equation (GEE).Of 44 participants (mean [SD] age 79 [9.82] years), 35 were pre-frail and 9 were frail. At follow-up, participants had significantly improved grip strength (1.63 kg, 95% CI: 0.62 to 2.63); sit-to-stand functioning (2 sit-to-stands, 95% CI: 1 to 3); and dynamic balance (1.68 s, 95% CI: 0.47 to 2.89). There were no significant improvements in gait speed, HRQoL index scores, self-rated health, physical activity levels (aerobic activity and strength training) or protein intake. GEE analysis revealed an interaction between exposure to MoveStrong and gait speed, sit-to-stand functioning, dynamic balance and HRQoL index scores. The total cost to administer the program and purchase equipment was CAD 14 700, equivalent to CAD 377 per participant.Exploratory analyses suggest MoveStrong exercises may improve gait speed, sit-to-stand functioning, dynamic balance and HRQoL index scores in older individuals who are frail and pre-frail.Cet essai pilote randomisé par étapes de huit semaines a permis d’évaluer le programme MoveStrong, qui vise à enseigner aux adultes présentant une fragilité ou une préfragilité un entraînement à l’équilibre et à la force musculaire ainsi qu’un apport suffisant en protéines pour prévenir les chutes et améliorer la mobilité.Nous avons recruté des personnes âgées de 60 ans ou plus, ayant un score de 1 ou plus sur l’échelle FRAIL et au moins une affection chronique et ne faisant pas d’entraînement musculaire. Le programme consistait en 16 séances de groupe d’une heure animées par un physiologiste de l’exercice et 2 séances de nutrition d’une heure animées par une diététiste. Nous avons analysé les résultats secondaires – poids, vitesse de marche, force de préhension, capacité physique (niveau de fatigue), transition assisdebout, équilibre dynamique, qualité de vie liée à la santé (QVLS), niveau d’activité physique et apport en protéines – à l’aide d’un test t d’échantillons appariés et d’une équation d’estimation généralisée (EEG).Sur les 44 participants (âge moyen [É.-T.] : 79 ans [9,82]), 35 étaient préfragiles et 9 étaient fragiles. Au moment du suivi, les participants avaient considérablement amélioré leur force de préhension (1,63 kg; IC à 95 % : 0,62 à 2,63), leur capacité à effectuer des transitions assis-debout (2 transitions assis-debout; IC à 95 % : 1 à 3) et leur équilibre dynamique (1,68 s; IC à 95 % : 0,47 à 2,89). Il n’y a pas eu d’amélioration statistiquement significative de la vitesse de marche, des scores QVLS, de l’autoévaluation de la santé, des niveaux d’activité physique (activité aérobique et entraînement musculaire) ou de l’apport en protéines. L’analyse par EEG a révélé une interaction entre l’exposition à MoveStrong et la vitesse de marche, la capacité à effectuer des transitions assisdebout, l’équilibre dynamique et les scores QVLS. Le coût total de mise en oeuvre du programme et de l’achat d’équipement s’est élevé à 14 700 $ CA, soit 377 $ CA par participant.Les analyses exploratoires indiquent que les exercices MoveStrong améliorent la vitesse de marche, la capacité à effectuer des transitions assisdebout, l’équilibre dynamique et les scores QVLS chez les personnes âgées fragiles et préfragiles.The MoveStrong program teaches older adults who are pre-frail and frail about balance and functional strength training and sufficient protein intake. The program may improve grip strength, sit-to-stand functioning and dynamic balance. The program may be associated with improvements in other outcomes, such as health-related quality of life and gait speed.Le programme MoveStrong apprend aux personnes âgées préfragiles et fragiles à s’entraîner à l’équilibre et à la force musculaire et à consommer suffisamment de protéines. Le programme permet d’améliorer la force de préhension, la capacité à effectuer des transitions assis-debout et l’équilibre dynamique. Le programme contribue aussi à l’améliorations d’autres résultats, comme la qualité de vie liée à la santé et la vitesse de marche.

1) To assess the precision of high resolution peripheral quantitative computed tomography (HR-pQCT)-derived Achilles tendon (AT) cross-sectional area (HR AT-CSA) and density, and 2) to validate HR AT-CSA against ultrasound-derived AT-CSA (US AT-CSA).Women and men (≥50 years) had HR-pQCT (0.082mm isotropic) and US scans (B-mode) performed on the non-dominant ankle. Linear regression and Bland-Altman analyses assessed systematic differences between HR-pQCT and US-derived AT-CSA. Precision measured by % root mean square coefficients of variation (%RMSCV) and agreement by type 2,1 intraclass correlation coefficients (ICCAmong 44 participants, HR and US AT-CSA were strongly correlated (RHR-pQCT can examine AT-morphometry with acceptable analytical precision. Future studies should explore these metrics' association with functional outcomes and ankle-bone structural and mechanical properties.

High-resolution peripheral computed tomography (HR-pQCT) was developed to image bone microarchitecture in vivo at peripheral skeletal sites. Since the introduction of HR-pQCT in 2005, clinical research to gain insight into pathophysiology of skeletal fragility and to improve prediction of fractures has grown. Meanwhile, the second-generation HR-pQCT device has been introduced, allowing novel applications such as hand joint imaging, assessment of subchondral bone and cartilage thickness in the knee, and distal radius fracture healing. This article provides an overview of the current clinical applications and guidance on interpretation of results, as well as future directions. Specifically, we provide an overview of (1) the differences and reference data for HR-pQCT variables by age, sex, and race/ethnicity; (2) fracture risk prediction using HR-pQCT; (3) the ability to monitor response of anti-osteoporosis therapy with HR-pQCT; (4) the use of HR-pQCT in patients with metabolic bone disorders and diseases leading to secondary osteoporosis; and (5) novel applications of HR-pQCT imaging. Finally, we summarize the status of the application of HR-pQCT in clinical practice and discuss future directions. From the clinical perspective, there are both challenges and opportunities for more widespread use of HR-pQCT. Assessment of bone microarchitecture by HR-pQCT improves fracture prediction in mostly normal or osteopenic elderly subjects beyond DXA of the hip, but the added value is marginal. The prospects of HR-pQCT in clinical practice need further study with respect to medication effects, metabolic bone disorders, rare bone diseases, and other applications such as hand joint imaging and fracture healing. The mostly unexplored potential may be the differentiation of patients with only moderately low BMD but severe microstructural deterioration, which would have important implications for the decision on therapeutical interventions. These guidelines have been reviewed and endorsed by the Committee of Scientific Advisors of the International Osteoporosis Foundation, the American Society for Bone and Mineral Research, and the European Calcified Tissue Society

Coronavirus disease 2019 (COVID-19) can lead to a diverse range of clinical manifestations, ranging from an asymptomatic infection to an acute respiratory distress syndrome, and multiorgan failure with high mortality rates [1]. It is established that SARS-CoV-2 not only infects the respiratory tract but that the ensuing viral replication and immune response also affects multiple organ systems, in addition to an acute systemic inflammatory response and in some cases accompanying tissue hypoxia and shock.\ud \ud While many who have been infected have uncomplicated recoveries, some have prolonged illness. Prolonged course of illness has been reported in adults and children and is affecting both those who were hospitalised with COVID-19 and those who were not [2,3,4,5,6,7].\ud \ud In December 2020 ISARIC (the International Severe Acute Respiratory and emerging Infection Consortium), the research funders group GloPID-R (The Global Research Collaboration for Infectious Disease Preparedness) and global group, Long Covid Support, jointly organised a ‘Long Covid Forum’ [8]. This public forum aimed to gain a better understanding of ‘Long Covid’ and to define research priorities for funders and researchers to take forward.

ImportanceEvidence suggests that individuals with schizophrenia are at an increased risk of hip fractures; however, the sex-specific burden of hip fractures among adults with schizophrenia has not been quantified and compared with the general population.ObjectiveTo describe sociodemographic and clinical characteristics of patients with hip fracture and schizophrenia and to quantify their sex-specific annual hip fracture rates relative to those without schizophrenia.Design, Setting, and ParticipantsThis repeated population-based, cross-sectional study leveraged multiple individually linked health administrative databases for patients in Ontario, Canada. We included patients aged 40 to 105 years with hip fracture–related hospitalization between April 1, 2009, and March 31, 2019. Statistical analysis was performed between November 2021 and February 2023.ExposureSchizophrenia diagnosis, ascertained using a validated algorithm.Main Outcomes and MeasuresThe main outcome was sex-specific age-standardized annual hip fracture rate per 10 000 individuals and annual percent change in age-standardized rates. Rates were direct adjusted to the 2011 Ontario population, and joinpoint regression analysis was performed to evaluate annual percent change.ResultsWe identified 117 431 hip fracture records; of these, there were 109 908 index events. Among the 109 908 patients with hip fracture, 4251 had schizophrenia and 105 657 did not. Their median age was 83 years (IQR, 75-89 years), and 34 500 (31.4%) were men. Patients with hip fracture and schizophrenia were younger at the index event compared with those without schizophrenia. Men had a median age of 73 vs 81 years (IQR, 62-83 vs 71-87 years; standardized difference, 0.46), and women had a median age of 80 vs 84 years (IQR, 71-87 vs 77-89 years; standardized difference, 0.32). A higher proportion of patients with vs without schizophrenia had frailty (53.7% vs 34.2%; standardized difference, 0.40) and previous fragility fractures (23.5% vs 19.1%; standardized difference, 0.11). The overall age-standardized rate per 10 000 individuals with vs without schizophrenia was 37.5 (95% CI, 36.4 to 38.6) vs 16.0 (95% CI, 15.9 to 16.1). Age-standardized rates were 3-fold higher in men with vs without schizophrenia (31.0 [95% CI, 29.5 to 32.6] vs 10.1 [95% CI, 10.0 to 10.2]) and more than 2-fold higher in women with vs without schizophrenia (43.4 [95% CI, 41.9 to 44.9] vs 21.4 [95% CI, 21.3 to 21.6]). Overall, joinpoint regression analysis identified a steady annual decrease of 0.7% (95% CI, −1.1% to −0.3%) in age-standardized rates for both study groups.Conclusions and RelevanceThe findings of this cross-sectional study suggest that individuals with schizophrenia experience an earlier age of onset and considerably higher rate of hip fractures compared with the general population, with implications for targeted fracture prevention and optimization of clinical bone health management over the course of their psychiatric illness.

ObjectivesTo describe episodic nature of disability among adults living with Long COVID.MethodsWe conducted a community-engaged qualitative descriptive study involving online semi-structured interviews and participant visual illustrations. We recruited participants via collaborator community organizations in Canada, Ireland, United Kingdom, and United States.ParticipantsAdults who self-identified as living with Long COVID. We purposively recruited for diversity in age, gender, race/ethnicity, sexual orientation, and duration since initial COVID-19 infection.Main Outcome Measure(s)We used a semi-structured interview guide to explore experiences of disability living with Long COVID, specifically health-related challenges and how they were experienced over time. We asked participants to draw their health trajectory and conducted a group-based content analysis.ResultsAmong the 40 participants, the median age was 39 years (interquartile range: 32, 49); majority were women (63%), white (73%), heterosexual (75%), and living with Long COVID for ≥1 year (83%). Participants described their disability experiences as episodic in nature, characterized by fluctuations in presence and severity of health-related challenges (disability) that may occur both within a day and over the long-term living with Long COVID. They described living with ‘ups and downs’, ‘flare-ups’, and ‘peaks’ followed by ‘crashes’, ‘troughs’, and ‘valleys’, likened to a ‘yo-yo’ ‘rolling hills’, and ‘rollercoaster ride’ with ‘relapsing/remitting’, ‘waxing/waning’, ‘fluctuations’ in health. Drawn illustrations demonstrated variety of trajectories across health dimensions, some more episodic than others. Uncertainty intersected with the episodic nature of disability, characterized as unpredictability of episodes, their length, severity and triggers, and process of long-term trajectory, which had implications on broader health.ConclusionsAmong this sample of adults living with Long COVID, experiences of disability were described as episodic, characterized by fluctuating health challenges, which may be unpredictable in nature. Results help to better understand experiences of disability among adults living with Long COVID to inform healthcare and rehabilitation.KEY MESSAGESWhat is already known on this topic:Globally, a growing number of individuals are living with persistent and prolonged signs and symptoms following infection consistent with COVID-19, referred to as Long COVID, Post COVID-19 Condition (PCC) or Post-acute sequelae of SARS-CoV2 (PASC). Individuals living with Long COVID are experiencing a range of symptoms and impairments that impact their ability to carry out day to day activities or engage in social and community life roles.What this study adds:Disability living with Long COVID was described as episodic, characterized by fluctuations in presence and severity of health related challenges, which may be unpredictable in nature, occurring both within the day, and over the long-term of months and years living with Long COVID.How this study might affect research, practice or policy:Results will help researchers, healthcare providers, policymakers, employers, and community members to better understand experiences of disability among adults living with Long COVID, to inform future disability measurement, health and rehabilitation care and service delivery, programs and policies for insurance, return to work, and workplace accommodations.

Most adherence studies only consider treatment following a first prescription. Using an extended follow-up, we found that 60% of seniors starting oral bisphosphonate therapy were exposed for ≥ 3 years (48% for ≥ 5 years). Studies are needed to examine the benefits and harms of continuing bisphosphonate therapy beyond 3 years. The purpose of this study was to identify and describe patterns of long-term oral bisphosphonate use among seniors using a novel methodological approach that considers extended follow-up. Among Ontarians aged 66 years or older, we identified subjects with a first dispensing of alendronate or risedronate between November 2000 and December 2016. We followed them until death or December 2019 to identify patients with ≥ 3 years of bisphosphonate use, defined as a proportion of days covered ≥ 80%, using 3-year rolling windows. We calculated the proportion of patients with long-term therapy (≥ 3 years of use) using Kaplan-Meier estimates. We described patterns of long-term use and compared patient characteristics between patients with and without long-term therapy. We identified 260,784 eligible seniors initiating bisphosphonate therapy. Of these, 60% continued therapy ≥ 3 years (77% women), and 48% continued ≥ 5 years. Characteristics did not meaningfully differ between patients with or without long-term therapy. The median length of long-term therapy was 7.0 (IQR 5.1) years for women and 6.1 (IQR 4.3) years for men. Only 20% experienced a treatment gap before long-term therapy, yet 50% experienced a treatment gap of ≥ 120 days after a median 5.3 years of therapy. Eighty-one percent who returned to therapy following a treatment gap re-initiated an oral bisphosphonate, with 18% switching to denosumab. Among seniors initiating oral bisphosphonates, we found that 60% receive at least 3 years of therapy when using an extended follow-up. Studies are needed to examine the benefits and harms of continuing bisphosphonate therapy beyond 3 years.

Background: The initiation of Androgen Deprivation Therapy (ADT) results in rapid and profound hypogonadism, resulting in significant bone and muscle loss, increasing the risk for osteoporosis (OP), falls, and fractures. Despite this, there exist very low rates of guideline adherent care regarding bone health in this population. We developed and implemented a healthy bone prescription tool entitled BoneRx to facilitate the uptake of guideline-concordant bone health care into practice and increase patient awareness and promote the uptake of health bone behaviours (HBBs). Methods: We conducted a cross-sectional pre-BoneRx implementation (n = 143) vs. post-implementation (n = 149) cohort study to evaluate the impact on (i) bone health care, patient engagement in HBB, and patient knowledge and health beliefs regarding OP. Results: There was a significant difference pre- vs. post BoneRx implementation on receipt of baseline BMD (34.7% vs. 59.5%, p < 0.0001) and bone health counselling (32.4% vs. 59.9%, p < 0.0001). More participants in the post-BoneRx implementation cohort reported taking vitamin D supplements 57% vs. 81% (p < 0.001) and calcium supplements 39% vs. 61% (p < 0.001). Physical activity levels also significantly increased (p = 0.021). No differences were detected in OP knowledge or feelings of OP susceptibility, seriousness, or health motivation. Conclusion: BoneRx is a simple, cost-effective, and acceptable strategy that could improve the care of PCa survivors receiving ADT.

Purpose: The purpose of this study was to estimate the association between pain and the number, severity, and location of fractures in women with osteoporotic vertebral fractures. Method: We used an 11-point numeric pain rating scale to assess pain during movement in the preceding week and lateral spinal radiographs to confirm number, location, and severity of vertebral fractures. In model 1, we assessed the association between pain during movement and the number, severity, and location of fractures. We adjusted model 2 for pain medication use and age. Results: The mean age of participants was 76.4 (SD 6.9) years. We found no statistically significant associations between pain and fracture number (estimated β = 0.23, 95% CI: –0.27, 0.68), fracture severity (estimated β = –0.46, 95% CI: –1.38, 0.49), or fracture location at T4–T8 (estimated β = 0.06, 95% CI: –1.26, 1.34), T9–L1 (estimated β = 0.35, 95% CI: –1.17, 1.74), or L2–L4 (estimated β = 0.40, 95% CI: –1.01, 1.75). Age and pain medication use were not significantly associated with pain. Model 1 accounted for 4.7% and model 2 for 7.2% of the variance in self-reported pain. Conclusion: The number, location, and severity of fractures do not appear to be the primary explanation for pain in women with vertebral fractures. Clinicians must consider other factors contributing to pain.

The accumulation of INTERmuscular fat and INTRAmuscular fat (IMF) has been a hallmark of individuals with diabetes, those with mobility impairments such as spinal cord injuries and is known to increase with aging. An elevated amount of IMF has been associated with fractures and frailty, but the imprecision of IMF measurement has so far limited the ability to observe more consistent clinical associations. Magnetic resonance imaging has been recognized as the gold standard for portraying these features, yet reliable methods for quantifying IMF on magnetic resonance imaging is far from standardized. Previous investigators used manual segmentation guided by histogram-based region-growing, but these techniques are subjective and have not demonstrated reliability. Others applied fuzzy classification, machine learning, and atlas-based segmentation methods, but each is limited by the complexity of implementation or by the need for a learning set, which must be established each time a new disease cohort is examined. In this paper, a simple convergent iterative threshold-optimizing algorithm was explored. The goal of the algorithm is to enable IMF quantification from plain fast spin echo (FSE) T1-weighted MR images or from water-saturated images. The algorithm can be programmed into Matlab easily, and is semiautomated, thus minimizing the subjectivity of threshold-selection. In 110 participants from 3 cohort studies, IMF area measurement demonstrated a high degree of reproducibility with errors well within the 5% benchmark for intraobserver, interobserver, and test–retest analyses; in contrast to manual segmentation which already yielded over 20% error for intraobserver analysis. This algorithm showed validity against manual segmentations (r > 0.85). The simplicity of this technique lends itself to be applied to fast spin echo images commonly ordered as part of standard of care and does not require more advanced fat-water separated images.

Study Purpose: Morphometric methods categorize potential osteoporotic vertebral fractures (OVF) on the basis of loss of vertebral height. A particular example is the widely used semiquantitative morphometric tool proposed by Genant (GSQ). A newer morphologic algorithm-based qualitative (mABQ) tool focuses on vertebral end-plate damage in recognizing OVF. We used data from both sexes in the Canadian Multicentre Osteoporosis Study (CaMos) to compare the 2 methods in identifying OVF at baseline and during 10 years of follow-up. Materials and Methods: We obtained lateral thoracic and lumbar spinal radiographs (T4-L4) 3 times, at 5-year intervals, in 828 participants of the population-based CaMos. Logistic regressions were used to study the association of 10-year changes in bone mineral density (BMD) with incident fractures. Results: At baseline, 161 participants had grade 1 and 32 had grade 2 GSQ OVF; over the next 10 years, only 9 of these participants had sustained incident GSQ OVF. Contrastingly, 21 participants at baseline had grade 1 and 48 grade 2 mABQ events; over the next 10 years, 79 subjects experienced incident grade 1 or grade 2 mABQ events. Thus, incident grades 1 and 2 morphologic fractures were 8 times more common than morphometric deformities alone. Each 10-year decrease of 0.01 g/cm2 in total hip BMD was associated with a 4.1% (95% CI: 0.7-7.3) higher odds of having an incident vertebral fracture. Conclusions: This analysis further suggests that morphometric deformities and morphologic fractures constitute distinct entities; morphologic fractures conform more closely to the expected epidemiology of OVF.

Objective The objective is to provide an update of the 2019 Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society Clinical Practice Guideline for the pharmacological management of osteoporosis in postmenopausal women using romosozumab. Conclusions We reviewed findings from the meta-analysis and primary clinical trials assessing the efficacy of romosozumab, a monoclonal antibody targeting sclerostin, for the prevention of fractures and concluded that this agent can be considered a treatment option for postmenopausal women at very high risk for osteoporotic fracture. The romosozumab label has a boxed warning, recommending careful consideration by the treating clinician as to cardiovascular risk profile in the individual woman who might receive this agent, since clinical trial data from an active comparator study show an imbalance in serious cardiovascular adverse events between romosozumab and alendronate.