Short-term risk of fracture is increased by deficits in cortical and trabecular bone microarchitecture independent of DXA BMD and FRAX: bone microarchitecture international consortium (BoMIC) prospective cohorts.

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

Identifying individuals at risk for short-term fracture (within 2-years) is essential to offer prompt treatment. We examined bone microarchitecture at arm and lower leg for prediction of short-term fractures in 7327 older adults, independent of the common clinical practice measures ­ DXA-BMD and FRAX. After adjusting for other factors, we found that measures of failure load, cortical and trabecular bone microarchitecture and density predicted short-term risk of fracture beyond the usual clinical measures of DXA and FRAX. These measures of bone that indicate deficits in microarchitecture may be a useful adjunct to traditional assessment of fracture risk in older adults.

Fracture risk based on high-resolution peripheral quantitative computed tomography measures does not vary with age in older adults-the bone microarchitecture international consortium prospective cohort study.

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

Immune response to the recombinant herpes zoster vaccine in people living with HIV over 50 years of age compared to non-HIV age-/gender-matched controls (SHINGR'HIV): a multicenter, international, non-randomized clinical trial study protocol.

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

Validation of a fall rate prediction model for community-dwelling older adults: a combined analysis of three cohorts with 1850 participants.

BACKGROUND: Fragility fractures in older adults are often caused by fall events. The estimation of an expected fall rate might improve the identification of individuals at risk of fragility fractures and improve fracture prediction. METHODS: A combined analysis of three previously developed fall rate models using individual participant data (n = 1850) was conducted using the methodology of a two-stage meta-analysis to derive an overall model. These previously developed models included the fall history as a predictor recorded as the number of experienced falls within 12 months, treated as a factor variable with the levels 0, 1, 2, 3, 4 and ≥ 5 falls. In the first stage, negative binomial regression models for every cohort were fit. In the second stage, the coefficients were compared and used to derive overall coefficients with a random effect meta-analysis. Additionally, external validation was performed by applying the three data sets to the models derived in the first stage. RESULTS: The coefficient estimates for the prior number of falls were consistent among the three studies. Higgin's I2 as heterogeneity measure ranged from 0 to 55.39%. The overall coefficient estimates indicated that the expected fall rate increases with an increasing number of previous falls. External model validation revealed that the prediction errors for the data sets were independent of the model to which they were applied. CONCLUSION: This analysis suggests that the fall history treated as a factor variable is a robust predictor of estimating future falls among different cohorts.

Role of fermented dairy products in the health benefits of a mediterranean diet.

Mediterranean diet includes fermented dairy products like yogurt and cheese. These foods provide calcium, phosphorus, fat, carbohydrates and protein, all nutrients influencing various systems including bone, cardiovascular system, intermediary metabolism, cancer, central nervous system, and inflammation. In addition, they contain prebiotics and provide probiotics which are capable of modifiying microbiota composition and metabolism, potentially acting also indirectly on the various systems. A large body of evidence indicates that fermented dairy products consumption significantly contributes to the beneficial effects of a Mediterranean diet on various systems' health.

[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.

Multidisciplinary and Coordinated Management of Osteoporotic Vertebral Compression Fractures: Current State of the Art.

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

A meta-analysis of previous falls and subsequent fracture risk in cohort studies.

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

Narrative Review of Effects of Glucagon-Like Peptide-1 Receptor Agonists on Bone Health in People Living with Obesity.

Glucagon-like peptide-1 Receptor agonists (GLP-1Ras) such as liraglutide and semaglutide have been recently approved as medications for chronic weight management in people living with obesity (PwO); GLP-1 may enhance bone metabolism and improve bone quality. However, the effects of GLP-1Ras on skeletal health remain to be determined and that's the purpose of this narrative review. Nevertheless, bone consequences of intentional weight loss interventions in PwO are well known: (i) significant weight loss induced by caloric restriction and bariatric surgery results in accelerated bone turnover and bone loss, and (ii) unlike caloric restriction interventions, PwO experience a substantial deterioration in bone microarchitecture and strength associated with an increased risk of fracture after bariatric surgery especially malabsorptive procedures. Liraglutide seems to have a positive effect on bone material properties despite significant weight loss in several rodent models. However, most of positive effects on bone mineral density and microarchitecture were observed at concentration much higher than approved for obesity care in humans. No data have been reported in preclinical models with semaglutide. The current evidence of the effects of GLP-1Ra on bone health in PwO is limited. Indeed, studies on the use of GLP-1Ra mostly included patients with diabetes who were administered a dose used in this condition, did not have adequate bone parameters as primary endpoints, and had short follow-up periods. Further studies are needed to investigate the bone impact of GLP-1Ra, dual- and triple-receptor agonists for GLP-1, glucose-dependent insulin releasing polypeptide (GIP), and glucagon in PwO.

Unusual phosphaturic mesenchymal tumor mimicking osteoid osteoma.

Phosphaturic mesenchymal tumor is a rare tumor characterized by paraneoplastic osteomalacia. The diagnosis is often delayed because of nonspecific symptoms and difficulty to localize the tumor. In this study we report a case of PMT of the left femur detected by Ga-68-DOTATATE PET-CT with radiological features mimicking osteoid osteoma. We report a 31-year-old female patient who presented to our hospital for evaluation due to progressive bone pain and muscle weakness. Her laboratory data showed hypophosphatemia and increased fibroblast growth factor 23 (FGF-23) together with reduced bone mineral density on bone densitometry. The diagnosis of PMT was suspected and the tumor was identified on Ga-68-DOTATATE PET-CT as a focal uptake in a lucent lesion of the left femoral head with a central sclerotic dot mimicking a nidus as seen in osteoid osteoma. The lesion was treated with percutaneous radiofrequency ablation. Laboratory tests and bone densitometry rapidly improved post-treatment. The present case emphasizes the difficulty to diagnose PMT due to its nonspecific biochemical and clinical presentation and the relevance of functional imaging for locating these tumors despite different radiological presentation.

A Fracture Risk Assessment Tool for High Resolution Peripheral Quantitative Computed Tomography.

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

[Bone consequences of intentional weight loss in overweight or obese patients]. / Conséquences osseuses de la perte de poids intentionnelle des patients en surpoids ou obèses.

Although weight loss results in significant improvements in most comorbidities in people with overweight/obesity, one possible side effect is its negative impact on bone health. This review summarizes the effects of intentional weight loss achieved by non-surgical (lifestyle changes, drugs) and surgical (bariatric surgery) interventions on bone outcomes in individuals with overweight/obesity and discusses strategies to monitor and preserve bone health during weight loss.

Bien que la perte de poids entraîne des améliorations significatives de la plupart des comorbidités des patients en surpoids/obésité, elle s'associe à un impact négatif sur la santé osseuse. Cet article résume les effets de la perte de poids intentionnelle, induite par des interventions non chirurgicales (régimes alimentaires, médicaments) ou par la chirurgie bariatrique, sur la santé osseuse chez les personnes en surpoids/obèses. Il propose également les modalités de surveillance et de prévention de la perte osseuse dans ces contextes.

[New reimbursement criteria for vitamin D measurements: what about our migrant patients?] / Nouveaux critères de remboursement du dosage de la vitamine D : et nos patients migrants ?

Vitamin D deficiency is a global health burden, which has been subject to debate in recent years. Although its consequences on patients' general health are debatable, the association between severe vitamin D deficiency and osteomalacia are clearly established. Since the 1st of July 2022, blood testing in individuals who do not meet the recognized risk factors for deficiency is no longer reimbursed in Switzerland. Being a migrant (or refugee) does not constitute a risk factor even though it has repeated been shown that this population is at high risk of deficiency, in particular sever deficiency. This article aims to establish new recommendations for vitamin D deficiency diagnosis and substitution for this population. It is sometimes necessary to adapt our national recommendations to take into account our cultural diversity.

Le déficit en vitamine D est un problème de santé publique au cœur de l'actualité. Si les répercussions sur la santé générale des patients sont débattues, l'association entre déficit sévère et ostéomalacie est clairement établie. En Suisse, depuis le 1er juillet 2022, l'assurance obligatoire de soins ne rembourse plus son dosage sanguin, sauf si le patient présente des facteurs de risque avérés. Le fait d'être migrant (ou réfugié) n'est pas considéré comme l'un d'eux. Pourtant, plusieurs études attestent que cette population est à haut risque de déficit, notamment sévère. Cet article a pour but d'établir de nouvelles recommandations de dépistage et de substitution qui s'adaptent à cette population. Il est parfois nécessaire d'adapter les recommandations nationales pour prendre en compte la diversité culturelle populationnelle.

Development of a personalized fall rate prediction model in community-dwelling older adults: a negative binomial regression modelling approach.

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

Orbital myositis induced by alendronate: A case report.

BACKGROUND AND PURPOSE: Bisphosphonates are widely used, notably for osteoporosis treatment. Their common side effects are well known. However, they can trigger less common effects such as orbital inflammation. Here, the case is reported of an orbital myositis triggered by alendronate. METHODS: This is a case report at an academic medical center. An orbital magnetic resonance imaging scan, a thoraco-abdominal computed tomography scan and blood sample analyses were performed. RESULTS: A 66-year-old woman treated by alendronate for her osteoporosis was investigated. She developed an orbital myositis after the first intake. Neurological examination revealed a painful diplopia with decreased downward and adduction movements of the right eye and edema of the upper eyelid. Orbital magnetic resonance imaging showed an orbital myositis of the right eye. No other cause of orbital myositis was found than the alendronate intake. After alendronate arrest and a short course of prednisone, the symptoms resolved. CONCLUSION: This case highlights that alendronate can cause an orbital myositis whose early diagnosis is of major importance because it is a treatable side effect.

High frequency of heterozygous rare variants of the SLC34A1 and SLC9A3R1 genes in patients with atypical femur fracture.

OBJECTIVE: Atypical femur fractures (AFFs) are rare fragility fractures originating at the lateral cortex of the femur, affecting the subtrochanteric or diaphyseal area of thebone with a transverse morphology. Occurrence of AFF is specifically associated with a small number of rare monogenic congenital metabolic bone disorders, such as hypophosphatasia, and with long-term treatment with antiresorptiondrugs. The exact pathogenesis of these fractures remains poorly understood and, except for cases of diagnosed HPP or other AFF-causing bone diseases, it is not possible to assess which patients are at higher riskof developing AFFs as a consequence of anti-resorption therapy. DESIGN: We genetically screened 25 unrelated patients who had developed at least one AFF. INTERVENTION: Genetic screening was performed through a nextgeneration sequencing analysis with a customized panel containing 76 human genes involved in the regulation of the mineralization processWe genetically screened 25 unrelated patients who had developed at least one AFF. RESULTS: We found a relatively high frequency (32.0%) of heterozygous rare variants inthe SLC34A1 and SLC9A3R1 genes, two genes whose heterozygous inactivating mutations have been respectively associated with autosomal dominant hypophosphatemic nephrolithiasis/osteoporosis types 1 and 2 (NPHLOP1and NPHLOP2). Other heterozygous rare variants were found in the BMPR1B, CYP27B1, FBN1, MEPE, PIGO, and PHOSPHO1 genes, each in a single AFF case (4.0%). CONCLUSIONS AND RELEVANCE: Our findings suggest that rarevariants of SLC34A1 and SLC9A3R1 could represent a possible genetic risk factor for the occurrence of AFFs. On the other hand, AFFs could represent an unsuspected clinical manifestation and/or an anti-resorption therapycorrelatedadverse event in patients with NPHLOP disorders.

The effects of time-restricted eating and weight loss on bone metabolism and health: a 6-month randomized controlled trial.

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

Dietary recommendations in the prevention and treatment of osteoporosis.

INTRODUCTION: This article presents the initial recommendations of the French Rheumatology Society (Société Française de Rhumatologie - SFR) and the Osteoporosis Research and Information Group (Groupe de Recherche et d'Informations sur les Ostéoporoses - GRIO) on the role of diet in the prevention and treatment of osteoporosis. METHODS: The recommendations were produced by a working group composed of rheumatologists, physician nutrition specialists and a geriatrician. Fifteen (15) questions pertaining to "daily practices" were preselected by the working group. For the literature review, the working group focussed mainly on the effects of diet on bone mineral density (BMD) and fractures, and primarily on meta-analyses of longitudinal studies and dietary intervention studies. RESULTS: A Mediterranean-type diet and the daily consumption of 2 to 3 dairy products are recommended. Together, these provide the calcium and "high quality" protein required to maintain a normal calcium-phosphorus balance and bone metabolism, and are associated with lower fracture risk. Conversely, unbalanced Western diets, vegan diets, weight-loss diets in non-overweight individuals, alcohol consumption and daily consumption of sodas are advised against. In terms of the beneficial effects on bone mineral density and fracture risk, current scientific data are either insufficient or too divergent to recommend increasing or restricting the consumption of tea or coffee, vitamins other than vitamin D, vitamin D-enriched or phytoestrogen-rich foods, calcium-enriched plant-based beverages, oral nutritional supplements, or dietary sources of prebiotics and probiotics. CONCLUSIONS: These are the first set of recommendations addressing the role of diet in the prevention and treatment of osteoporosis. More research is necessary to direct and support guidelines.

Management of patients at very high risk of osteoporotic fractures through sequential treatments.

Osteoporosis care has evolved markedly over the last 50 years, such that there are now an established clinical definition, validated methods of fracture risk assessment and a range of effective pharmacological agents. Currently, bone-forming (anabolic) agents, in many countries, are used in those patients who have continued to lose bone mineral density (BMD), patients with multiple subsequent fractures or those who have fractured despite treatment with antiresorptive agents. However, head-to-head data suggest that anabolic agents have greater rapidity and efficacy for fracture risk reduction than do antiresorptive therapies. The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) convened an expert working group to discuss the tools available to identify patients at high risk of fracture, review the evidence for the use of anabolic agents as the initial intervention in patients at highest risk of fracture and consider the sequence of therapy following their use. This position paper sets out the findings of the group and the consequent recommendations. The key conclusion is that the current evidence base supports an "anabolic first" approach in patients found to be at very high risk of fracture, followed by maintenance therapy using an antiresorptive agent, and with the subsequent need for antiosteoporosis therapy addressed over a lifetime horizon.