[Metabolic bone diseases : what's new in 2023]. / Maladies osseuses : ce qui a changé en 2023.

The sequential effects of romosozumab and denosumab in osteoporosis are shown in real-life, while the mechanisms of post-denosumab rebound are reviewed extensively. A network meta-analysis confirms the superiority of anabolics vs anti-resorptives on fracture reduction, while the latter shown a reduction of mortality in a large population-based study. Fracture risk prediction by FRAXPlus is improved. New meta-analyses confirm the benefits of Vitamin D on fractures and falls. Finally, multiples trials with new molecules for the treatment of rare bone diseases, including osteogenesis imperfecta, fibrous dysplasia and hypoparathyroidism, shown promising results.

Dans l'ostéoporose, les effets séquentiels du romosozumab et du dénosumab se précisent et les mécanismes du rebond à l'arrêt de ce dernier font l'objet d'une revue détaillée. Une méta-analyse en réseau confirme la supériorité des traitements anaboliques sur les antirésorbtifs, alors que l'effet de ces derniers sur la réduction de la mortalité est démontré dans une large étude populationnelle. La prédiction du risque fracturaire est améliorée par l'outil FRAXPlus. De nouvelles méta-analyses des bénéfices de la vitamine D sur le risque de fractures et de chutes sont également disponibles. Enfin, de nombreuses études encourageantes sur l'efficacité de nouveaux traitements dans de multiples maladies osseuse rares, telles l'ostéogenèse imparfaite, la dysplasie fibreuse et l'hypoparathyroïdie, ont été publiées.

Odyssey of a Misclassified Genomic Variant: Insight from an Incidental Finding Assessment.

Genetic evaluation of a teenager with seizure found no pathogenic variant in a large gene panel, but an incidental likely pathogenic HNF4A variant, deemed to cause MODY1 diabetes. Diabetes history was absent and glycated hemoglobin normal, but serum calcium was severely low, with abnormally high parathyroid hormone. Thus, pseudohypoparathyroidism was suspected and confirmed by molecular genetic testing. Calcium and calcitriol supplementation led to calcium normalization and neurological symptom improvement. Given the absence of personal or family diabetes history, the HNF4A variant was reassessed and found to encode an alternative transcript with poor expression and activity levels, hence downgraded on expert advice from 'likely pathogenic' to 'likely benign'. Besides illustrating the importance of structured medical workup before launching extensive targeted exome sequencing, this case highlights the need for caution in incidental finding interpretation in patients lacking compatible phenotype or family history, and the value of expert advice in such variant interpretation.

Hypnosis to reduce fear of falling in hospitalized older adults: a feasibility randomized controlled trial.

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

[Rare causes of Hypophosphatemia: diagnostic approach]. / Hypophosphatémies de causes rares : approche diagnostique.

Hypophosphatemia is common and may be overlooked due to its asymptomatic nature or non-specific symptoms. Two main mechanisms are at its origin: a shift towards the intracellular sector and an increase in urinary phosphate excretion. A measurement of the urinary phosphate reabsorption threshold allows a diagnostic orientation. Alongside common forms of parathyroid hormone-dependent hypophosphatemia, one should not ignore rare FGF23-mediated forms, in particular X-linked hypophosphatemic rickets. The treatment, above all etiological, also includes the administration of phosphate and, in the event of an excess of FGF23, supplementation with calcitriol. In cases of oncogenic osteomalacia and X-linked hypophosphatemic rickets, the use of burosumab, an anti-FGF23 antibody, must be considered.

L'hypophosphatémie est fréquente. Pourtant, elle peut parfois être méconnue de par son caractère asymptomatique ou ses symptômes non spécifiques. Deux grands mécanismes sont à son origine : un shift vers le secteur intracellulaire et une augmentation de l'excrétion urinaire de phosphate. Une mesure du seuil de réabsorption urinaire de phosphate permet une orientation diagnostique. À côté de formes communes d'hypophosphatémies parathormone-dépendantes, il ne faut pas méconnaître des formes rares FGF23 médiées, en particulier le rachitisme hypophosphatémique lié à l'X. Le traitement, avant tout étiologique comporte aussi l'administration de phosphate et lors d'un excès de FGF23, une supplémentation en calcitriol. En cas d'ostéomalacie oncogénique et de rachitisme hypophosphatémique lié à l'X, l'emploi de burosumab, anticorps anti-FGF23, doit être considéré.

Functional brain changes in sarcopenia: evidence for differential central neural mechanisms in dynapenic older women.

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.

Time for Revival of Bone Biopsy with Histomorphometric Analysis in Chronic Kidney Disease (CKD): Moving from Skepticism to Pragmatism.

Bone Biopsy (BB) with histomorphometric analysis still represents the gold standard for the diagnosis and classification of different forms of renal osteodystrophy. Bone biopsy is the only technique able to provide comprehensive information on all bone parameters, measuring static and dynamic parameters of turnover, cortical and trabecular microarchitecture, and mineralization defects. In nephrological practice, bone biopsy yields relevant indications to support therapeutic choices in CKD, heavily impacting the management and prognosis of uremic patients. Unfortunately, the use of bone biopsy has decreased; a lack of expertise in performing and interpreting, perceived procedure invasiveness and pain, and reimbursement issues have all contributed to this decline. Nevertheless, both bone biomarkers and instrumental images cannot be considered reliable surrogates for histological findings, being insufficiently accurate to properly evaluate underlying mineral and bone disorders. This is a multidisciplinary position paper from the Nephrology and Osteoporosis Italian Scientific Societies with the purpose of restating the role of bone biopsy in CKD patient management and of providing strong solutions to allow diffusion of this technique in Italy, but potentially also in other countries. The Italian approach through the optimization and standardization of bone biopsy procedure, the construction of the Italian Hub and Spoke network, and a request for adjustment and national homogenization of reimbursement to the Italian Health Ministry has led the way to implement bone biopsy and to improve CKD patient management and prognosis.

Interdisciplinary management of FGF23-related phosphate wasting syndromes: a Consensus Statement on the evaluation, diagnosis and care of patients with X-linked hypophosphataemia.

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.

Sarcopenia in Chronic Kidney Disease: A Scoping Review of Prevalence, Risk Factors, Association with Outcomes, and Treatment.

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.

[PTH-replacement therapy in hypoparathyroidism : what benefits ?] / Traitement hormonal substitutif de l'hypoparathyroïdie : quels bénéfices ?

Hypoparathyroidism is a rare disease. In the last decade, important publications have described clinical disease progression and long-term complications. Furthermore, this condition has benefited from major therapeutic advances with the emergence of a hormonal substitution therapy with injectable parathyroid hormone, rhPTH (1-84) (Recombinant human parathyroid hormone, 1-84). Conventional therapy, with calcium supplements and active vitamin D analogue, is effective but does not always fulfill all therapeutic targets and is associated with hypercalciuria. In most patients, therapy with rhPTH (1-84) is associated with a substantial reduction of at least 50% in the need for calcium and active vitamin D along with maintenance of serum calcium. Additionally, rhPTH (1-84) is associated with decreased in 24h urinary calcium excretion with preservation of renal function, which can be a major asset.

L'hypoparathyroïdie est une maladie rare. Au cours de la dernière décennie, d'importantes publications ont décrit son évolution et ses complications à long terme. Cette maladie a également bénéficié d'avancées majeures sur le plan thérapeutique avec l'avènement d'un traitement substitutif à base de parathormone injectable, la rhPTH (1-84) (hormone parathyroïdienne 1,84 recombinante). La thérapie conventionnelle à base de suppléments calciques et de vitamine D active est efficace, mais ne permet pas toujours d'atteindre les objectifs thérapeutiques et est associée à l'hypercalciurie. La rhPTH (1-84) aide à maintenir une calcémie dans la cible en diminuant d'au moins 50 % les doses de calcium et de vitamine D active. De plus, elle est associée à une diminution de la calciurie de 24 heures avec une préservation de la fonction rénale, ce qui peut constituer un atout majeur.

Validation of the Perform-FES: a new fear of falling scale for hospitalized geriatric patients.

BACKGROUND: Fear 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. METHODS: In 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. RESULTS: The 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. CONCLUSION: Findings 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.

Update on the ESCEO recommendation for the conduct of clinical trials for drugs aiming at the treatment of sarcopenia in older adults.

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.

Feasibility and safety of high-intensity interval training for the rehabilitation of geriatric inpatients (HIITERGY) a pilot randomized study.

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.

The Role of Hip Abductor Strength in Identifying Older Persons at Risk of Falls: A Diagnostic Accuracy Study.

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.

Age-related changes in attention control and their relationship with gait performance in older adults with high risk of falls.

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 ±â€¯2.5) and thirty-four old participants (72 years ±â€¯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.

[Osteoporosis in patients with chronic renal failure : evaluation and management ? Role of bone biopsy]. / Ostéoporose chez l'insuffisant rénal : quelle évaluation et quel traitement ? Place de la biopsie osseuse.

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.

Effect of 24-month physical activity on cognitive frailty and the role of inflammation: the LIFE randomized clinical trial.

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.

Effect of Physical Activity on Frailty: Secondary Analysis of a Randomized Controlled Trial.

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.

Functional Performances on Admission Predict In-Hospital Falls, Injurious Falls, and Fractures in Older Patients: A Prospective Study.

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 < 0.001 for all). In multivariate analysis controlling for age, sex, previous falls, and fall as cause of admission, poorer functional performances on all functional tests predicted in-hospital falls and injurious falls (p < 0.001 for all). The SPPB only significantly predicted serious injurious falls (adjusted odds ratio [OR] = 0.76; 95% confidence interval [CI] 0.60-0.96) and fractures (adjusted OR = 0.76; 95% CI 0.59-0.98). In conclusion, poor functional performances, as assessed by SPPB, are independent predictors of in-hospital falls, injurious falls, and fractures in patients admitted to a geriatric hospital. These findings should help to design preventive strategies for in-hospital falls and support the adoption of objective performance-based functional measures into routine hospital practice. © 2018 American Society for Bone and Mineral Research.

[Hypophosphatasia]. / Hypophosphatasie de l'adulte.

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.