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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.

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 pilot feasibility randomized controlled trial, thirty-two 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: Of the 57 patients screened, 32 were randomized: 15 in the intervention group and 17 in the control group. 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: ClinicalTrials.gov, NCT04726774. Registered 27 january 2021, retrospectively registered, https://clinicaltrials.gov/ct2/show/record/NCT04726774 Funding: Geneva University Hospitals, Research and Development Project (9-2018-I)

Sarcopenia, a condition characterized by loss of skeletal muscle mass and function, has important clinical ramifications. We aimed to map the existing literature about prevalence, risk factors, associated adverse outcomes, and treatment of sarcopenia in individuals with chronic kidney disease (CKD). A scoping review of the literature was conducted to identify relevant articles published from databases’ inception to September 2019. Individuals with CKD, regardless of their disease stage and their comorbidities, were included. Only studies with sarcopenia diagnosed using both muscle mass and function, based on published consensus definitions, were included. For studies on treatment, only randomized controlled trials with at least one sarcopenia parameter as an outcome were included. Our search yielded 1318 articles, of which 60 from were eligible for this review. The prevalence of sarcopenia ranged from 4 to 42% according to the definition used, population studied, and the disease stage. Several risk factors for sarcopenia were identified including age, male gender, low BMI, malnutrition, and high inflammatory status. Sarcopenia was found to be associated with several adverse outcomes, including disabilities, hospitalizations, and mortality. In CKD subjects, several therapeutic interventions have been assessed in randomized controlled trial with a muscle mass, strength, or function endpoint, however, studies focusing on sarcopenic CKD individuals are lacking. The key interventions in the prevention and treatment of sarcopenia in CKD seem to be aerobic and resistance exercises along with nutritional interventions. Whether these interventions are effective to treat sarcopenia and prevent clinical consequences in this population remains to be fully determined. Supplementary Information The online version contains supplementary material available at 10.1007/s00223-021-00898-1.

X-linked hypophosphataemia (XLH) is the most frequent cause of hypophosphataemia-associated rickets of genetic origin and is associated with high levels of the phosphaturic hormone fibroblast growth factor 23 (FGF23). In addition to rickets and osteomalacia, patients with XLH have a heavy disease burden with enthesopathies, osteoarthritis, pseudofractures and dental complications, all of which contribute to reduced quality of life. This Consensus Statement presents the outcomes of a working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, and provides robust clinical evidence on management in XLH, with an emphasis on patients’ experiences and needs. During growth, conventional treatment with phosphate supplements and active vitamin D metabolites (such as calcitriol) improves growth, ameliorates leg deformities and dental manifestations, and reduces pain. The continuation of conventional treatment in symptom-free adults is still debated. A novel therapeutic approach is the monoclonal anti-FGF23 antibody burosumab. Although promising, further studies are required to clarify its long-term efficacy, particularly in adults. Given the diversity of symptoms and complications, an interdisciplinary approach to management is of paramount importance. The focus of treatment should be not only on the physical manifestations and challenges associated with XLH and other FGF23-mediated hypophosphataemia syndromes, but also on the major psychological and social impact of the disease.

Background In 2016, an expert working group was convened under the auspices of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and formulated consensus recommendations for the conduct of clinical trials for drugs to prevent or treat sarcopenia. Aims The objective of the current paper is to provide a 2020 update of the previous recommendations in accordance with the evidence that has become available since our original recommendations. Methods This paper is based on literature reviews performed by members of the ESCEO working group and followed up with face to face meetings organized for the whole group to make amendments and discuss further recommendations. Results The randomized placebo-controlled double-blind parallel-arm drug clinical trials should be the design of choice for both phase II and III trials. Treatment and follow-up should run at least 6 months for phase II and 12 months for phase III trials. Overall physical activity, nutrition, co-prescriptions and comorbidity should be recorded. Participants in these trials should be at least 70-years-old and present with a combination of low muscle strength and low physical performance. Severely malnourished individuals, as well as bedridden patients, patients with extremely limited mobility or individuals with physical limitations clearly attributable to the direct effect of a specific disease, should be excluded. Multiple outcomes are proposed for phase II trials, including, as example, physical performance, muscle strength and mass, muscle metabolism and muscle-bone interaction. For phase III trials, we recommend a co-primary endpoint of a measure of functional performance and a Patient Reported Outcome Measure. Conclusion The working group has formulated consensus recommendations on specific aspects of trial design, and in doing so hopes to contribute to an improvement of the methodological robustness and comparability of clinical trials. Standardization of designs and outcomes would advance the field by allowing better comparison across studies, including performing individual patient-data meta-analyses, and different pro-myogenic therapies.

Background/Objectives Early detection of fall risk in persons older than 65 is of clinical relevance, but the diagnostic accuracy of currently used functional tests (eg short physical performance battery [SPPB] and timed up and go test [TUG]) to assess older persons' fall risks remains moderate. Recent literature highlights the importance of strong hip abductors to prevent falls. We thus aimed to assess the diagnostic accuracy of hip abductor strength measures to assess older persons' fall risks. Methods Hip abductor maximum voluntary isometric strength (ABD MVIS), rate of force generation (ABD RFG), and the SPPB and TUG functional fall risk assessments were assessed in 60 persons aged over 65 years (82.0 ± 6.1 years). The diagnostic accuracy (area under the curve [AUC], sensitivity [sens], specificity [spec], positive predictive value [PPV], negative predictive value [NPV], and positive and negative likelihood ratios [LR+, LR-]) was evaluated at a clinically important 90% sensitivity level. Cut-off values for clinical use were calculated. Results In our population, hip ABD MVIS (AUC 0.8, sens 90.6%, spec 57.1%, PPV 70.7%, NPV 84.2%, LR+ 2.1, LR- 0.2, and cut-off value ≤ 1.1 N/kg) and hip ABD RFG (AUC 0.8, sens 90.6%, spec 46.4%, PPV 65.9%, NPV 81.3%, LR+ 1.7, LR- 0.2, and cut-off ≤ 8.47 N/kg/s) show diagnostic accuracy comparable to other fall risk assessments (SPPB and TUG) and a high net sensitivity when used in a test battery. Conclusion Hip ABD MVIS or RFG shows good diagnostic accuracy to differentiate between older fallers and nonfallers compared to the chosen external criterion history of falls. The high net sensitivity when hip ABD MVIS or RFG is combined with currently used fall risk assessments shows promise in contributing value to a test battery and should be investigated further in longitudinal studies.

BackgroundFear of falling is highly prevalent in older adults and associated with numerous negative health events. The main objective of this study was to validate a scale to assess fear of falling, based on performance in real situation (Perform-FES), in a hospitalized geriatric population.MethodsIn this cross-sectional study, 55 patients (mean age: 85.3 years; 58% women) hospitalized in a geriatric hospital in Geneva (Switzerland) were enrolled. The Perform-FES scale was administered to all patients in conjunction with four other fear of falling scales. We determined the floor and ceiling effects, internal consistency, reliability, construct validity, and discriminative power of the Perform-FES scale.ResultsThe Perform-FES scale did not demonstrate any significant floor or ceiling effect. It had a good internal consistency (Cronbach’s alpha = 0.78) and an excellent reliability (intraclass correlation coefficient = 0.94). Regarding convergent validity, good correlations were shown between the score obtained on the Perform-FES scale and those obtained on other fear of falling scales. Also, the Perform-FES scale was able to discriminate patients with severe functional impairments (area under the ROC curve = 0.81) and had significantly better discriminating performance than other fear of falling scales.ConclusionFindings suggest that the Perform-FES scale has good psychometric properties and may be a relevant tool to assess fear of falling in a geriatric hospitalized population. Future research should focus in particular on assessing the sensitivity to change and the predictive value of this scale in longitudinal studies, and its validity in other populations.

Background High-intensity interval training (HIIT) has been shown to be more effective than moderate-intensity continuous training (MICT) for the physical rehabilitation. However, data on its suitability for older hospitalized patients is scarce. Methods Randomized controlled trial in a hospital setting. Inclusion of 100 patients, ≥65 years old, hospitalized for rehabilitation after an acute medical condition, in a two-week rehabilitation program of either four HIIT or three MICT sessions per week. Completion was defined as participation in all but two planned sessions accomplishing ≥50% of each session. We assessed: upper-limb muscle strength (handgrip isometric strength test), lower-limb muscle strength (quadriceps and ankle flexion and extension tests); gait speed and spatio-temporal parameters (instrumented walkway), and exercise capacity (6-min walk test). All adverse events were recorded as safety endpoints. Results An intention-to-treat analysis showed a 44% completion rate for the HIIT group (95% CI, 30–59) and 77% for MICT (95% CI, 55–82). A modified intention-to-treat analysis restricted to patients who participated in ≥1 session showed an 88% completion rate in the HIIT group (95%CI, 69–97) and an 80% completion rate in MICT (95%CI, 65–90). The exercises most frequently undertaken were the pedal exerciser (54%) and the NuStep (32%). There were no significant differences in the various measures. No serious adverse events occurred. Conclusion A HIIT rehabilitation program for this population was feasible, safe and had a high adherence rate. Trial registration number Clinicatrials.gov ID: NCT02318459. Trial registration date: November 7th, 2014. Retrospectively registered. This study adheres to the CONSORT guidelines.

Falls are common among older inpatients and remain a great challenge for hospitals. Despite the relevance of physical impairments to falls, the prognostic value of performance-based functional measures for in-hospital falls and injurious falls remains unknown. This study aimed to determine the predictive ability and accuracy of various functional tests administered at or close to admission in a geriatric hospital to identify in-hospital fallers and injurious fallers. In this prospective study, conducted in a geriatric hospital in Geneva, Switzerland, 807 inpatients (mean age 85.0 years) were subjected to a battery of functional tests administered by physiotherapists within 3 days (interquartile range 1 to 6) of admission, including Short Physical Performance Battery (SPPB), simplified Tinetti, and Timed Up and Go tests. Patients were prospectively followed up for falls and injurious falls until discharge using mandatory standardized incident report forms and electronic patients' records. During a median length of hospital stay of 23 days (interquartile range 14 to 36), 329 falls occurred in 189 (23.4%) patients, including 161 injurious falls of which 24 were serious. In-hospital fallers displayed significantly poorer functional performances at admission on all tests compared with non-fallers (p

Introduction Les chutes sont extremement frequentes chez le sujet âge et associees a la survenue de nombreux evenements defavorables, y inclus la fracture. L’avancee en âge s’accompagne d’une degenerescence progressive du rachis, resultant typiquement en une deterioration de l’equilibre global, avec la mise en jeu de mecanismes de compensation. Le role de l’equilibre global -sagittal et frontal- du rachis dans le risque de chute n’a jamais ete elucide dans la population generale âgee. De meme, sa contribution dans la deterioration des performances physiques (i.e., facteurs majeurs de risque de chute) reste a etre clarifiee. L’objectif principal de cette etude etait de determiner l’association entre l’equilibre global du rachis, les performances physiques et les chutes chez des sujets âges vivant dans la communaute. Patients et methodes L’etude SAFE est une cohorte prospective, observationnelle, longitudinale conduite aupres de sujets âges vivant dans la communaute et sans antecedent de chirurgie rachidienne instrumentee, actuellement en cours a Geneve (Suisse). La batterie d’evaluation administree inclut notamment : radiographies du squelette entier en position debout a partir du systeme EOS®, absorptiometrie biphotonique a rayons X (Hologic®), examen clinique, historique de chute dans les 12 derniers mois et evaluation de la fonction physique (e.g., test « Short Physical Performance Battery » (SPPB)). Les parametres spino-pelviens mesures incluent notamment, parmi d’autres, l’angle spino-sacre (SSA) et la distance C7-CSL pour l’equilibre global sagittal et frontal, respectivement. Resultats 50 sujets (âge moyen, 74 ans ; 76 % femmes) ont ete inclus dans cette analyse transversale preliminaire. Parmi eux, 18 (36 %) avaient chute au moins une fois durant les 12 derniers mois, 19 (38 %) presentaient un antecedent de fracture a basse energie, 15 (30 %) etaient osteoporotiques, 6 (12 %) etaient sarcopeniques et 12 (24 %) avaient un score SPPB ≤ 9. L’equilibre global sagittal du rachis etait associe de maniere independante aux performances physiques, apres ajustement pour l’âge, le sexe, les comorbidites et les fractures vertebrales (coefficient de regression ajuste SPPB/SSA = 0,09, IC 95 % [0,03, 0,16] ; p = 0,007), tout comme plusieurs mesures sagittales pelviennes ou de la courbure lombaire. Par ailleurs, les sujets non equilibres ou equilibres grâce a des compensations presentaient plus de chutes en comparaison aux sujets equilibres sans compensation (incidence rate ratio = 1,46, IC 95 % [0,13, 2,79 ; p = 0,031]). L’equilibre global frontal du rachis etait associe avec le risque de chute, apres ajustement pour l’âge, le sexe, les comorbidites, les fractures vertebrales et le score SPPB (odds ratio C7-CSL/chute = 2,28, IC 95 % [1,06, 4,92] ; AUC = 0,79, IC 95 % [0,65, 0,92]). Conclusion Ces resultats suggerent que l’equilibre global du rachis est un contributeur independant du risque de chute et de la diminution des performances physiques chez le sujet âge. Les futures analyses longitudinales de cette cohorte devraient permettre de reveler le role des mecanismes de compensation et clarifier dans quelle mesure l’equilibre global du rachis est associe aux chutes et fractures incidentes.

Prospective controlled evidence supporting the efficacy of long-term exercise to prevent physical decline and reduce falls in old age is lacking. The present study aimed to assess the effects of long-term music-based multitask exercise (i.e., Jaques-Dalcroze eurhythmics) on physical function and fall risk in older adults. A 3-year follow-up extension of a 1-year randomized controlled trial (NCT01107288) was conducted in Geneva (Switzerland), in which 134 community-dwellers aged ≥65 years at increased risk of falls received a 6-month music-based multitask exercise program. Four years following original trial enrolment, 52 subjects (baseline mean ± SD age, 75 ± 8 years) who (i) have maintained exercise program participation through the 4-year follow-up visit (“long-term intervention group”, n = 23) or (ii) have discontinued participation following original trial completion (“control group”, n = 29) were studied. They were reassessed in a blind fashion, using the same procedures as at baseline. At 4 years, linear mixed-effects models showed significant gait (gait speed, P = 0.006) and balance (one-legged stance time, P = 0.015) improvements in the long-term intervention group, compared with the control group. Also, long-term intervention subjects did better on Timed Up & Go, Five-Times-Sit-to-Stand and handgrip strength tests, than controls (P

Summary Background & aims Patients with anorexia nervosa (AN) have low serum IGF-I levels that may contribute to a lower bone mineral mass. We investigated the effects of a fermented, protein-fortified, dairy product on serum IGF-I levels in patients with AN during an in-hospital refeeding program. Methods In this multicenter, randomized, double-blind, placebo-controlled, clinical trial conducted at 3 university hospitals and 3 private clinics in France and Switzerland, 62 women recently admitted with confirmed AN and with a baseline low serum IGF-I level were randomized to 2 daily isocaloric fresh cheese pots containing either 15 g/150 g or 3 g/150 g (controls) of protein for 4 weeks. The primary outcome was the change in IGF-I levels. Results In the primary intention-to-treat analysis, mean serum IGF-I levels increased during the intervention phase from 22.9 ± 1.5 to 28.6 ± 1.3 nmol/L (means ± SEM) (+20.2%) in the intervention group and from 20.2 ± 1.2 to 25.7 ± 1.5 nmol/L (+16.8%) in controls. In a preplanned analysis of covariance with repeated measures, the between-group difference was close to statistical significance ( P = 0.071). In a post-hoc mixed-regression model analysis, the difference was statistically significant (4.9 nmol/l increase; P = 0.003), as was the change of the ratio IGF-I/IGF-BP3 ( P = 0.004 ). There was no between-group difference in biochemical markers of bone turnover (osteocalcin, P1NP, CTX) or in serum parathyroid hormone level. Serum calcium levels slightly increased during the intervention phase in the higher protein group ( P = 0.02). IGF-BP2 decreased significantly more in the intervention group during the follow up period at week 4 after supplements cessation (P = 0.019). Conclusions Intake of a fermented, protein-fortified, isocaloric dairy product during 4 weeks may slightly increase serum IGF-I levels in women with AN, without significant changes in bone turnover markers. Clinical Trial Registration Number: NCT01823822 (www.clinicaltrials.gov).

Whether low muscle mass predisposes to fracture is still poorly understood. In the diagnosis of sarcopenia, different thresholds for low lean mass have been proposed but comparative data for these criteria against hard outcomes such as fractures are lacking. This study aimed to investigate the prevalence of low lean mass according to different thresholds used in operational definitions of sarcopenia and their association with 3-year fracture incidence in a cohort of healthy 63- to 67-year-old community dwellers. In a longitudinal analysis of 913 participants (mean age 65.0 ± 1.4 years) enrolled in the Geneva Retirees Cohort (GERICO) study, lean mass was assessed by dual-energy X-ray absorptiometry (DXA), and low trauma clinical fracture incidence was recorded over a 3-year period. Prevalence of low lean mass ranged from 3.5% to 20.2% according to the threshold applied. During a follow-up of 3.4 ± 0.9 years, 40 (4.4%) participants sustained at least one low trauma fracture. After multivariate adjustment including Fracture Risk Assessment Tool (FRAX) probability with femoral neck bone mineral density (BMD), low lean mass, as defined by Baumgartner thresholds, was associated with higher fracture risk (odds ratio [OR], 2.32; 95% CI, 1.04 to 5.18; p = 0.040). It also added significant predictive value beyond FRAX (likelihood ratio test for nested models, 4.28; p < 0.039). No significant association was found for other definition thresholds. The coexistence of sarcopenia and a T-score

To describe the clinical and biochemical profile of patients with primary hyperparathyroidism (PHPT) of the Swiss Hyperparathyroidism Cohort, with a focus on neurobehavioral and cognitive symptoms and on their changes in response to parathyroidectomy. From June 2007 to September 2012, 332 patients were enrolled in the Swiss PHPT Cohort Study, a nationwide prospective and non-interventional project collecting clinical, biochemical, and outcome data in newly diagnosed patients. Neuro-behavioral and cognitive status were evaluated annually using the Mini-Mental State Examination, the Hospital Anxiety and Depression Scale, and the Clock Drawing tests. Follow-up data were recorded every 6 months. Patients with parathyroidectomy had one follow-up visit 3–6 months’ postoperatively. Symptomatic PHPT was present in 43 % of patients. Among asymptomatic patients, 69 % (131/189) had at least one of the US National Institutes for Health criteria for surgery, leaving thus a small number of patients with cognitive dysfunction or neuropsychological symptoms, but without any other indication for surgery. At baseline, a large proportion showed elevated depression and anxiety scores and cognitive dysfunction, but with no association between biochemical manifestations of the disease and test scores. In the 153 (46 %) patients who underwent parathyroidectomy, we observed an improvement in the Mini-Mental State Examination (P = 0.01), anxiety (P = 0.05) and depression (P = 0.05) scores. PHPT patients often present elevated depression and anxiety scores and cognitive dysfunction, but rarely as isolated manifestations. These alterations may be relieved upon treatment by parathyroidectomy.

The management of osteoporosis in patients with mild to moderate chronic kidney disease (CKD) can be established as in general population. In severe or terminal CKD, bone densitometry is indicated. Bone-specific alkaline phosphatase is considered a useful marker for distinguishing among the histologic types of renal osteodystrophy. In ambiguous cases, bone biopsy together with quantitative histomorphometry will be necessary. As far as the treatment is concerned, the bisphosphonates, which had been avoided due to their renal excretion as well as the official warnings against using them in case of renal clearance lower than 30 ml/min, seem to be effective even in advanced stages of renal disease. There are limited data, though, regarding the management of osteoporosis in terminal stages of CKD.La prise en charge des patients en insuffisance rénale légère à modérée peut être calquée sur celle de la population générale. En cas d’insuffisance rénale sévère ou terminale, la densitométrie osseuse reste indiquée. Le type d’ostéodystrophie rénale sera présumé à partir du niveau de phosphatase alcaline osseuse. Dans les cas équivoques, une biopsie osseuse avec histomorphométrie quantitative sera nécessaire. Quant au traitement, les bisphosphonates, longtemps mis à l’écart vu leur élimination rénale et la contre-indication de principe existant pour la plupart d’entre eux pour des niveaux de clairance inférieure à 30 ml/min, sont efficaces même à des stades avancés de l’insuffisance rénale. La prise en charge de l’ostéoporose chez l’insuffisant rénal terminal reste encore un domaine avec des données limitées.

Background Whether physical activity can reduce cognitive frailty—a relatively new “compound” phenotype proposed in 2013—and whether the effect of physical activity differs based on levels of inflammation are unknown. Therefore, this study aimed to evaluate the effect of physical activity on cognitive frailty and whether baseline interleukin-6 (IL-6) levels modified this effect. Methods We used data from the Lifestyle Interventions and Independence for Elders (LIFE) Study, a multicenter, single-blinded randomized trial conducted at eight US field centers between February 2010 and December 2013. The main outcome was cognitive frailty at 24 months, expressed as an ordinal variable based on the six combinations of its two components: frailty (non-frail, pre-frail, and frail) and mild cognitive impairment (yes, no). Frailty and cognition were assessed by the Study of Osteoporotic Fractures (SOF) index and the Modified Mini-Mental State Examination (3MSE) scale, respectively. Plasma IL-6 was measured at baseline. Of the 1635 original randomized sedentary participants (70–89 years), this study included 1298 participants with data on both cognitive frailty and IL-6 assessments at baseline. Results After adjusting for field center, sex, and baseline levels of cognitive frailty, the ordinal logistic regression model revealed that participants in the physical activity group had 21% lower odds (odds ratio, 0.79; 95% confidence interval, 0.64–0.98) of worsening cognitive frailty over 24 months than those in the health education group. The effect of physical activity on cognitive frailty did not differ according to baseline IL-6 levels (P for interaction = 0.919). The results did not change after additional adjustment for IL-6 subgroups and the inverse probability of remaining in the study. Comparable results were observed according to age, sex, ethnicity/race, and short physical performance battery score (P for interaction = 0.835, 0.536, 0.934, and 0.458, respectively). Conclusions A 24-month structured, moderate-intensity physical activity program reduced cognitive frailty compared with a health education program in sedentary older persons, and this beneficial effect did not differ according to baseline levels of inflammatory biomarker IL-6. These findings suggest that the new cognitive frailty construct is modifiable and highlight the potential of targeting cognitive frailty for promoting healthy aging. Trial registration Clinicaltrials.gov, NCT01072500 Electronic supplementary material The online version of this article (10.1186/s12916-018-1174-8) contains supplementary material, which is available to authorized users.

Background Falls are the leading cause of injury-related deaths in the elderly worldwide. Both gait impairment and cognitive decline have been shown to constitute major fall risk factors. However, further investigations are required to establish a more precise link between the influence of age on brain systems mediating executive cognitive functions and their relationship with gait disturbances, and thus help define novel markers and better guide remediation strategies to prevent falls. Methods Event-related functional magnetic resonance imaging (fMRI) was used to evaluate age-related effects on the recruitment of executive control brain network in selective attention task, as measured with a flanker paradigm. Brain activation patterns were compared between twenty young (21 years ± 2.5) and thirty-four old participants (72 years ± 5.3) with high fall risks. We then determined to what extend age-related differences in activation patterns were associated with alterations in several gait parameters, measured with electronic devices providing a precise quantitative evaluation of gait, as well as with alterations in several aspects of cognitive and physical abilities. Results We found that both young and old participants recruited a distributed fronto-parietal-occipital network during interference by incongruent distractors in the flanker task. However, additional activations were observed in posterior parieto-occipital areas in the older relative to the younger participants. Furthermore, a differential recruitment of both the left dorsal parieto-occipital sulcus and precuneus was significantly correlated with higher gait variability. Besides, decreased activation in the right cerebellum was found in the older with poorer cognitive processing speed scores. Conclusions Overall results converge to indicate greater sensitivity to attention interference and heightened recruitment of cortical executive control systems in the elderly with fall risks. Critically, this change was associated with selective increases in gait variability indices, linking attentional control with gait performance in elderly with high risks of falls.

BACKGROUND: Patients with end-stage renal disease (ESRD) and secondary hyperparathyroidism (SHPT) are at high risk of mortality. Whether an increased risk of death persists after a parathyroidectomy (PTX) is not clearly established. SUBJECTS AND METHODS: The survival of 40 patients with ESRD and SHPT who underwent PTX was compared with that of 664 ESRD patients. RESULTS: From first dialysis, a lower mortality rate was found in the group of patients who underwent PTX than in the nonoperated ESRD group (hazard ratio: 0.23; 95% CI: 0.14-0.37). The patients who underwent PTX were younger, had a longer time on dialysis, and had a higher prevalence of kidney transplantation. The mean number of comorbidities was lower (Charlson score 4.2 +/- 2.1 versus 6.4 +/- 2.9, p < 0.001). Then, we randomly selected two matched controls for each PTX case (80 controls, 40 PTX) who had at least an equivalent mean duration of dialysis between the first dialysis and PTX of the PTX group. In a univariate model, there was a trend for PTX being associated with prolonged survival. The mortality was higher both among those at an advanced age and those with a high Charlson score. Adjustments for these covariates made the effect of PTX no more significant. CONCLUSIONS: The risk of death of patients with severe SHPT leading to PTX differed from that of nonoperated subjects. The apparent differences in survival may be related to the number and severity of associated comorbidities. ESRD patients who undergo PTX may represent a subset of healthier subjects.

BACKGROUND: Parathyroid carcinoma (PC) mimics benign primary hyperparathyroidism (PHP), but the diagnosis of PC is seldom available at the time of the first operation. Because PC is plagued by recurrences usually beyond cure, one may wonder whether some of these could be prevented by more extensive resections initially, i.e., if the diagnosis of PC were available at that time. METHODS: Over a 25-year period, 311 consecutive patients with PHP underwent operation in our department: 302 had benign disease (adenomas or hyperplasias), and 9 had PC. Several clinical parameters, serum calcium and parathyroid hormone (PTH) levels, and the weight of the parathyroid tumor removed were compared in both groups. Receiver operating characteristic curves and logistical regression analyses were used to distinguish PC from benign PHP. RESULTS: Eight of 9 patients with PC had symptoms, versus 238 (79%) of 302 with benign PHP (not significant). In the PC subgroup, serum calcium and PTH levels and the tumor weights of the parathyroid glands removed were significantly higher than in the benign PHP cohort, even if these three parameters were regularly flawed by low positive predictive values (14%, 20%, and 15%, respectively). CONCLUSIONS: Serum calcium, PTH levels, and tumor weights were significantly greater in the PC subgroup, even if not invariably in a discriminatory way. However, when PTH is

Background Limited evidence suggests that physical activity may prevent frailty and associated negative outcomes in older adults. Definitive data from large long-term randomized trials are lacking. Objective To determine whether a long-term, structured, moderate-intensity physical activity program is associated with a lower risk for frailty and whether frailty status alters the effect of physical activity on the reduction in major mobility disability (MMD) risk. Design Multicenter, single-blind, randomized trial. Setting 8 centers in the United States. Participants 1635 community-dwelling adults, aged 70 to 89 years, with functional limitations. Intervention A structured, moderate-intensity physical activity program incorporating aerobic, resistance, and flexibility activities or a health education program consisting of workshops and stretching exercises. Measurements Frailty, as defined by the SOF (Study of Osteoporotic Fractures) index, at baseline and 6, 12, and 24 months, and MMD, defined as the inability to walk 400 m, for up to 3.5 years. Results Over 24 months of follow-up, the risk for frailty (n = 1623) was not statistically significantly different in the physical activity versus the health education group (adjusted prevalence difference, -0.021 [95% CI, -0.049 to 0.007]). Among the 3 criteria of the SOF index, the physical activity intervention was associated with improvement in the inability to rise from a chair (adjusted prevalence difference, -0.050 [CI, -0.081 to -0.020]). Baseline frailty status did not modify the effect of physical activity on reducing incident MMD (P for interaction = 0.91). Limitation Frailty status was neither an entry criterion nor a randomization stratum. Conclusion A structured, moderate-intensity physical activity program was not associated with a reduced risk for frailty over 2 years among sedentary, community-dwelling older adults. The beneficial effect of physical activity on the incidence of MMD did not differ between frail and nonfrail participants. Primary funding source National Institute on Aging, National Institutes of Health.

OBJECTIVES: the main objective was to evaluate if the admission functional independence measure (FIM((R))) score could be used to predict the risk of falls in geriatric inpatients. DESIGN: a 10-year retrospective study was performed. SETTING: the study was conducted in a 298-bed geriatric teaching hospital in Geneva, Switzerland. SUBJECTS: all patients discharged from the hospital from 1 January 1997 to 31 December 2006 were selected. Main outcome measures: measures used were FIM((R)) scores at admission using the FIM((R)) instrument and number of falls extracted from the institution's fall report forms. RESULTS: during the study period, there were 23,966 hospital stays. A total of 8,254 falls occurred. Of these, 7,995 falls were linked to 4,651 stays. Falls were recorded in 19.4% of hospital stays, with a mean incidence of 7.84 falls per 1,000 patients-days. Although there was a statistically significant relationship between total FIM((R)) score, its subscales, and the risk of falling, the sensitivity, specificity, positive predictive value and negative predictive value obtained with receiver operating characteristic curves were insufficient to permit fall prediction. This might be due in part to a non-linear relationship between FIM((R)) score and fall risk. CONCLUSION: in this study, the FIM((R)) instrument was found to be unable to predict risk of falls in general geriatric wards. Language: en

Background: in a secondary analysis of a randomised controlled trial, we investigated whether 6 months of music-based multitask training had beneficial effects on cognitive functioning and mood in older adults. Methods: 134 community-dwellers aged ≥65 years at increased risk for falling were randomly assigned to either an intervention group (n = 66) who attended once weekly 1-h supervised group classes of multitask exercises, executed to the rhythm of piano music, or a control group with delayed intervention (n = 68) who maintained usual lifestyle habits, for 6 months. A short neuropsychological test battery was administered by an intervention-blinded neuropsychologist at baseline and Month 6, including the mini-mental state examination (MMSE), the clock-drawing test, the frontal assessment battery (FAB) and the hospital anxiety (HADS-A) and depression scale. Results: intention-to-treat analysis showed an improvement in the sensitivity to interference subtest of the FAB (adjusted between-group mean difference (AMD), 0.12; 95% CI, 0.00 to 0.25; P = 0.047) and a reduction in anxiety level (HADS-A; AMD, −0.88; 95% CI, −1.73 to −0.05; P = 0.039) in intervention participants, as compared with the controls. Within-group analysis revealed an increase in MMSE score (P = 0.004) and a reduction in the number of participants with impaired global cognitive performance (i.e., MMSE score ≤23; P = 0.003) with intervention. Conclusion: six months of once weekly music-based multitask training was associated with improved cognitive function and decreased anxiety in community-dwelling older adults, compared with non-exercising controls. Studies designed to further delineate whether training-induced changes in cognitive function could contribute to dual-task gait improvements and falls reduction, remain to be conducted

Hypophosphatasia (HPP) is an inborn metabolic bone disorder caused by loss-of-function mutations in the gene encoding tissue nonspecific alkaline phosphatase (TNSALP). The adult form can be mistaken with common osteoporosis and/or present recurrent metatarsal fractures, skeletal and muscular pain. Subtrochanteric femoral pseudofractures resembling bisphosphonate-associated atypical femoral fractures can also be present, and Bps are therefore contraindicated in HPP. Early tooth loss and renal calcifications can orient towards the diagnosis. The diagnosis is based on low serum ALP levels (40 U/L) and high ALP substrate levels, such as vitamin B6 (pyridoxin), eventually on genetic testing. Recent development of an enzyme replacement therapy offers new therapeutic perspectives in severe cases.L’hypophosphatasie (HPP) est une maladie rare due à une perte de fonction du gène de la phosphatase alcaline (ALP). La forme adulte peut être facilement confondue avec une ostéoporose banale. Elle se manifeste aussi par des fractures de stress, des douleurs osseuses et des myalgies. Des pseudofractures des fémurs proximaux ressemblent aux fractures atypiques par bisphosphonates, qui sont donc contre-indiqués en cas d’HPP. La perte précoce des dents et des calcifications rénales peuvent mettre sur la piste d’une HPP. Le diagnostic est fondé sur l’histoire clinique et des valeurs basses d’ALP (40 U/l), hautes de ses substrats, notamment la vitamine B6, et finalement sur les tests génétiques. Le développement récent d’un substitut enzymatique offre de nouvelles perspectives thérapeutiques dans les cas sévères.

To give an overview of recent research findings and insights on the role of body composition assessment in fracture risk prediction.While there is to date little doubt that bone mineral density (BMD) is a main pathogenic factor of osteoporotic fractures, recent studies have emphasized the independent contribution of body composition components, especially lean mass, to fracture risk. In this article, we address body composition changes with aging, before to focus on recent studies addressing the contribution of lean and fat mass to fracture risk, together with some hypothesized mechanisms and clinical implications.Recent compelling evidence suggest that clinicians should recognize the potential role of muscle wasting in determining fracture risk among older adults and that measures of lean mass, especially appendicular lean mass - which can be assessed simultaneously with the BMD measurement - should be considered in fracture risk assessment beyond BMD and clinical risk factors. More evidence is needed to support certain fat-related indicators in fracture risk prediction, but regional adiposity measures appear promising. Further studies in the field should help to elucidate whether interventions effective at attenuate, prevent, or ultimately reverse skeletal lean mass loss or fat accumulation, may prevent fractures.

Background:Several guidelines recommend systematic screening for malnutrition in elderly inpatients for early dietary intakes assessment and treatment, but data demonstrating the efficacy of such interventions are scarce. The aim of this study was to evaluate a critical medical pathway for the detection and management of malnutrition in elderly inpatients.Methods:In a 3-month prospective controlled study, 694 recently admitted inpatients were assigned to an intervention group (critical medical pathway; n=465) or a standard care control group (n=229). Nutritional status was assessed at the time of admission with a Mini Nutritional Assessment. A renutrition program tailored to the initial dietary assessment results was applied in the intervention group. The efficacy of the program was verified by measuring the evolution of serum insulin-like growth factor 1 (IGF-I) between admission and 3 weeks later.Results:In the intervention group at baseline, 23% were malnourished, 51% were at risk and 26% were eunourished. Serum IGF-I increased in the intervention group (from 84±45 μg/l to 95±50 μg/l, P

PURPOSE: Gait variables may constitute surrogate outcomes for fall risk. Their reliability in a specific population of older fallers has not been fully established, which limits their research and clinical applications. This study aimed to determine test-retest reliability and minimal detectable change (MDC) values for selected fall-related gait variables in older adults with a recent fall history. METHODS: Community-dwelling (n=30) and hospitalized (n=30) fallers aged≥65 years were assessed twice using an instrumented pressure-sensitive walkway, under single- and dual-task gait conditions. Intraclass correlation coefficient (ICC(2,1)), standard error of measurement (SEM; SEM%) and MDC at 95% confidence level (MDC95; MDC95%), were used as reliability estimates. RESULTS: The ICC(2,1) for gait velocity was greater than 0.84 across all gait conditions and groups; SEM% and MDC95% did not exceed 6.5% and 18.1%, respectively. Gait variability measures returned lower ICC(2,1) (range 0.18-0.79), and markedly higher SEM% (16.3-31.9%) and MDC95% (45.3-88.3%). Overall, hospitalized fallers exhibited larger SEM and MDC95 values for variability measures compared to community-dwellers in all gait conditions, while larger values were found for all variables while dual-tasking compared to single-tasking in both groups. CONCLUSIONS: Gait velocity was found to be highly reliable and likely to be sensitive to change over repeated sessions in community-dwelling and hospitalized older fallers, both under single- and dual-task conditions. Gait variability measures showed lower reliability, irrespective of gait condition or group, displaying consistently larger measurement error, particularly under dual-task conditions. Clinicians should consider MDC95 values before using gait variability variables as evaluative outcome measures at patient level. Language: en

Anemia and malnutrition are highly prevalent, frequently concomitant and associated with negative outcomes and mortality in the elderly.To evaluate the association between these two entities, and test the hypothesis that protein-energy deficit could be etiology of anemia.Prospective case-control study.Geriatric and Rehabilitation Hospital, Geneva University Hospitals, Switzerland.392 patients (mean age 84.8 years old, 68.6% female).Hematological (hemoglobin (Hb)), chemical (iron work up, cyanocobalamin, folates, renal function, C-Reactive Protein (CRP)) and nutrition (albumin, prealbumin) parameters, and mini nutritional assessment short form (MNA-SF).The prevalence of anemia (defined as Hb120 g/l) was 39.3%. Anemic patients were more frequently malnourished or at risk of malnutrition according to the MNA-SF (p=0.047), with lower serum albumin (p0.001) and prealbumin (p0.001) levels. Thirty-eight percent of these patients had multiple causes and 14.3% had no cause found for anemia. Among the latter 90.9% of patients with unexplained anemia had albumin levels lower than 35g/l. After exclusion of iron,vitamin B12 and folic acid deficits, anemic patients had lower albumin (p0.001) and prealbumin (p 0.007) levels. Albumin level explained 84.5% of the variance in anemia. In multivariate analysis albumin levels remain associated with Hb only in anemic patients, explaining 6.4% of Hb variance (adj R2) and 14.7% (adj R2) after excluding inflammatory parameters (CRP10).Albumin levels are strongly associated with anemia in the elderly. Screening for undernutrition should be included in anemia assessment in those patients. Further prospective studies are warranted in order to explore the effect of protein and energy supplementation on hemoglobin level.

Summary: End-stage renal disease (ESRD) patients have a high risk of fractures. We evaluated bone microstructure and finite-element analysis-estimated strength and stiffness in patients with ESRD by high-resolution peripheral computed tomography. We observed an alteration of cortical and trabecular bone microstructure and of bone strength and stiffness in ESRD patients. Introduction: Fragility fractures are common in ESRD patients on dialysis. Alterations of bone microstructure contribute to skeletal fragility, independently of areal bone mineral density. Methods: We compared microstructure and finite-element analysis estimates of strength and stiffness by high-resolution peripheral quantitative computed tomography (HR-pQCT) in 33 ESRD patients on dialysis (17 females and 16 males; mean age, 47.0 ± 12.6years) and 33 age-matched healthy controls. Results: Dialyzed women had lower radius and tibia cortical density with higher radius cortical porosity and lower tibia cortical thickness, compared to controls. Radius trabecular number was lower with higher heterogeneity of the trabecular network. Male patients displayed only a lower radius cortical density. Radius and tibia cortical thickness correlated negatively with bone-specific alkaline phosphatase (BALP). Microstructure did not correlate with parathyroid hormone (PTH) levels. Cortical porosity correlated positively with "Kidney Disease: Improving Global Outcomes” working group PTH level categories (r = 0.36, p

This controlled intervention study in hospitalized oldest old adults showed that a multifactorial fall-and-fracture risk assessment and management program, applied in a dedicated geriatric hospital unit, was effective in improving fall-related physical and functional performances and the level of independence in activities of daily living in high-risk patients. INTRODUCTION: Hospitalization affords a major opportunity for interdisciplinary cooperation to manage fall-and-fracture risk factors in older adults. This study aimed at assessing the effects on physical performances and the level of independence in activities of daily living (ADL) of a multifactorial fall-and-fracture risk assessment and management program applied in a geriatric hospital setting. METHODS: A controlled intervention study was conducted among 122 geriatric inpatients (mean +/- SD age, 84 +/- 7 years) admitted with a fall-related diagnosis. Among them, 92 were admitted to a dedicated unit and enrolled into a multifactorial intervention program, including intensive targeted exercise. Thirty patients who received standard usual care in a general geriatric unit formed the control group. Primary outcomes included gait and balance performances and the level of independence in ADL measured 12 +/- 6 days apart. Secondary outcomes included length of stay, incidence of in-hospital falls, hospital readmission, and mortality rates. RESULTS: Compared to the usual care group, the intervention group had significant improvements in Timed Up and Go (adjusted mean difference [AMD] = -3.7s; 95 % CI = -6.8 to -0.7; P = 0.017), Tinetti (AMD = -1.4; 95 % CI = -2.1 to -0.8; P < 0.001), and Functional Independence Measure (AMD = 6.5; 95 %CI = 0.7-12.3; P = 0.027) test performances, as well as in several gait parameters (P < 0.05). Furthermore, this program favorably impacted adverse outcomes including hospital readmission (hazard ratio = 0.3; 95 % CI = 0.1-0.9; P = 0.02). CONCLUSIONS: A multifactorial fall-and-fracture risk-based intervention program, applied in a dedicated geriatric hospital unit, was effective and more beneficial than usual care in improving physical parameters related to the risk of fall and disability among high-risk oldest old patients.

The aim of this retrospective study was to assess the incidence of late complications occurring ?2 years after allogeneic hematopoietic stem cell transplantation (HSCT) for malignant diseases using a T-cell depletion strategy.

STUDY DESIGN: Case report. OBJECTIVE: To describe a case of polyostotic Paget disease of bone (PDB), with axis, lumbar, and calcaneum involvement. SUMMARY OF BACKGROUND DATA: PDB can involve cervical spine. This can lead to cervical cord compression and cervical myelopathy. A cranio-cervical instability has been rarely described in patients with PDB. METHODS AND RESULTS: We report about the case of a 65-year-old women presenting with a polyostotic PDB, with axis, lumbar, and calcaneum involvement. The C2 vertebral lesion was associated with an atlantoaxial instability due to a pathologic odontoid fracture and was responsible for progressive spinal cervical cord compression. The patient was operated on by a posterior approach allowing spinal cord decompression, C0-C4 stabilization, and pathologic tissue sampling. Pathologic examination confirmed the diagnosis of Paget disease. The bisphosphonate therapy was started. Radiologic follow-up showed a good cranio-cervical alignement and an unchanged axis lesion. CONCLUSION: Even if the treatment of pagetic spinal stenosis symptoms should start with medical therapy, surgery can sometimes be performed earlier to treat neural compression due to spinal instability, with favorable outcome.

Die chronische Niereninsuffizienz ist mit einer verminderten Produktion des aktiven Metaboliten des Vit D, 1 alpha, 25 Dihydroxy-Vitamin D assoziiert. Dies hat mehrere Konsequenzen, die nicht nur auf das Skelettsystem beschränkt sind. In der Tat besitzt Vit D verschiedene Wirkungen, die in diesem Review diskutiert werden. Die Substitution des Vit D wird sehr früh bei der Behandlung der chronischen Niereninsuffizienz in Betracht gezogen, dennoch herrscht noch Unsicherheit über die Art der Substitution. Die Rolle der Vit D-Analoga wird in diesem Review betont, wobei Calcitriol und Paricalcitol verglichen werden.

Aging is associated with progressive increase in body fat and a corresponding decline in lean muscle mass. When the decrease in muscle mass reaches a critical threshold, this may affect muscle strength and consequently limit the ability to cope with the activities of daily living, reducing the independence of elders. It is widely accepted to define sarcopenia as the loss of skeletal muscle mass and strength that occurs with advancing age. It is more difficult to establish cut-off points which are clinically relevant. The purpose of this paper is to summarize the definitions of sarcopenia and the assessment tools that can be used in clinical practice.

This 3-year longitudinal study among older adults showed that declining muscle mass, strength, power, and physical performance are independent contributing factors to increased fear of falling, while declines of muscle mass and physical performance contribute to deterioration of quality of life. Our findings reinforce the importance of preserving muscle health with advancing age. INTRODUCTION: The age-associated loss of skeletal muscle quantity and function are critical determinants of independent physical functioning in later life. Longitudinal studies investigating how decrements in muscle components of sarcopenia impact fear of falling (FoF) and quality of life (QoL) in older adults are lacking. METHODS: Twenty-six healthy older subjects (age, 74.1 +/- 3.7; Short Physical Performance Battery (SPPB) score >/=10) and 22 mobility-limited older subjects (age, 77.2 +/- 4.4; SPPB score

UNLABELLED Osteoporosis and fractures are frequent and important consequences of glucocorticoid therapy. Many factors contribute to bone loss during glucocorticoid therapy, such as underlying disease, malnutrition, vitamin D insufficiency, hypogonadism, and low body weight. Bone loss occurs particularly in the first few months of glucocorticoid treatment and affects more cancellous than cortical bone, with reduced bone formation and increased bone resorption. The risk of fracture increases rapidly in patients with glucocorticoid therapy. The existence of a threshold is not well defined but the risk of fracture is increased in patients with higher doses of glucocorticoids. Other effects include altered production of gonadal sex hormones, inhibition of intestinal calcium absorption, and enhancement of renal excretion of calcium. Prevention of glucocorticoid-induced osteoporosis is based on general measures such as calcium and vitamin D supplementation, adequate protein intake, regular physical exercise, and specific therapies. Bisphosphonates, which are potent bone resorption inhibitors, have been shown to increase bone mineral density and to decrease fracture risk, so that they represent the first choice in the prevention of glucocorticoid-induced osteoporosis. Glucocorticoid-induced osteoporosis is a major burden to those whom it affects. It can be prevented provided efficacious preventive measures are introduced early during glucocorticoid treatment. LEVEL OF EVIDENCE Level V (expert opinion). See the Guidelines for Authors for a complete description of the levels of evidence.

Resume Une lesion osseuse dense fait craindre en premier lieu la presence d’une tumeur primitive ou secondaire. La stabilite radiologique dans le temps est un argument particulierement fort pour evoquer la benignite. L’ilot osseux benin solitaire est habituellement considere comme une lesion stable, non evolutive. Nous presentons le cas d’un patient chez lequel un suivi de 31 ans a permis d’objectiver une augmentation considerable de la taille d’un ilot osseux benin, prouve histologiquement et non fixant a la scintigraphie osseuse. L’aspect radiographique qui est caracteristique, ainsi que l’absence de captation scintigraphique meme en presence d’un processus pourtant evolutif, apparaissent comme des criteres majeurs du diagnostic.

A dense bone lesion raises immediate concern about the possibility of a primary or secondary tumor. Stability of the image over time is a strong argument against a malignancy. Benign solitary bone islands are usually believed to remain stable over time, with no tendency toward growth. We report a case in a patient with 31 years of follow-up, during which marked growth of the island was documented. The bone scan was normal, and histology established the diagnosis of benign bone island. In a patient with an enlarging sclerotic lesion, typical radiographic features and absence of radionuclide uptake are strong arguments in favor of a bone island.

Camurati–Engelmann disease (CED) is a rare autosomal dominant disease characterized by progressive bilateral symmetric sclerosis and thickening of long bone diaphyses (1). Diagnosis is based on phy...