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During aging, changes in endosteal and periosteal boundaries of cortical bone occur that differ between men and women. We here develop a new procedure that uses high‐resolution peripheral quantitative CT (HR‐pQCT) imaging and 3D registration to identify such changes within the timescale of longitudinal studies. A first goal was to test the sensitivity of the approach. A second goal was to assess differences in periosteal/endosteal expansion over time between men and women. Rigid 3D registration was used to transform baseline and all follow‐up (FU) images to a common reference configuration for which the region consisting of complete slices (largest common height) was determined. Periosteal and endosteal contours were transformed to the reference position to determine the net periosteal and endosteal expansion distances. To test the sensitivity, images from a short‐term reproducibility study were used (15 female, aged 21 to 47 years, scanned three times). To test differences between men and women, images from a subset of the Geneva Retirees Cohort were used (248 female, 61 male, average age 65 years, 3.5 and 7 years FU). The sensitivity study indicated a least significant change for detecting periosteal/endosteal expansion of 41/31 microns for the radius and 17/26 microns for the tibia. Results of the cohort study showed significant net endosteal retraction only in females at the radius and tibia after 3.5 years (38.0 and 38.4 microns, respectively) that further increased at 7 years FU (70.4 and 70.8 microns, respectively). No significant net periosteal changes were found for males or females at 7 years. The results demonstrate that it is possible to measure changes in endosteal contours in longitudinal studies within several years. For the investigated cohort, significant endosteal retraction was found in females but not in males. Whether these changes in cortical geometry are related to fracture risk remains to be investigated in larger cohorts © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Resume L’osteosarcopenie se definit par l’association de la sarcopenie et de l’osteoporose. Il est possible, mais pas acquis, que les deux pathologies interagissent biologiquement du fait du lien anatomique entre le muscle et l’os, par l’intermediaire des contraintes mecaniques, de cytokines et d’hormones. La prevalence augmente avec l’âge et pourrait representer 5–10 % des personnes de plus de 80 ans. L’osteosarcopenie est un facteur de risque de chute et de fracture et s’associe a l’alteration des capacites fonctionnelles et a la mortalite de toutes causes. L’evaluation clinique geriatrique doit etre exhaustive et comprendre la mesure de la densite minerale osseuse, la recherche des criteres diagnostiques de la sarcopenie, et la recherche des causes secondaires, a savoir d’autres maladies chroniques, les causes nutritionnelles, liees a l’activite physique, et iatrogeniques. Le traitement comprend l’activite physique en resistance, la correction des carences nutritionnelles (notamment en vitamine D), l’augmentation de l’apport proteique et le traitement medicamenteux de l’osteoporose.

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

Objective: Arterial calcification is associated with high cardiovascular risk. Our aim was to assess the utility of peripheral arterial calcification (PAC) in distal forearm and distal leg for the prediction of acute coronary syndrome (ACS) and major adverse cardiovascular event in older men. Approach and Results: In 815 home-dwelling older men, PAC was assessed on the scans of distal forearm and leg obtained by high-resolution peripheral quantitative computed tomography. PAC score (0–12) was calculated on the basis of the number and severity in small peripheral arteries. The information on ACS and major adverse cardiovascular event was collected prospectively for 8 years. PAC severity increased with age and body mass index ( P P P P P Conclusions: Severe PAC is associated with higher risk of ACS and major adverse cardiovascular event in older home-dwelling men, also in men without known ischemic heart disease. Incidentally found severe PAC can be a serious warning indicating high cardiovascular risk.

International audience; Objectifs:Nous proposons des recommandations destinées à tous les médecins amenés à prendre en charge des hommes ayant une ostéoporose ou à risque d’une telle maladie.Méthodes:Le contenu de ces recommandations a été rédigé en conformité avec la méthode HAS et validé par un groupe de travail. Lorsque les données de la littérature étaient insuffisantes, les recommandations ont été basées sur un accord professionnel prenant en compte l’état des pratiques et les opinions d’experts. Les recommandations ont été soumises à un groupe de lecture.Résultats:Nous proposons 15 recommandations détaillant la population cible, les moyens d’évaluation, le traitement et le suivi. Nous insistons sur les points suivants : 1) une fracture spontanée ou provoquée par un traumatisme mineur doit faire rechercher une maladie osseuse fragilisante ; 2) le risque de fracture et de mortalité après fracture sévère augmente avec l’âge, rapidement à partir de 70–75 ans ; 3) les indications thérapeutiques dépendent de la présence ou non d’une fracture, du type de fracture (sévère/non sévère) et de la valeur la plus basse du T-score de la DMO ; 4) l’évaluation du risque de chute et sa prise en charge doivent faire partie de la prise en charge de l’ostéoporose ; 5) le suivi clinique est indispensable pour adapter la prise en charge à l’évolution du risque de fracture.Conclusions :Ces premières recommandations françaises, que nous avons souhaitées proches de celles concernant les femmes ménopausées, visent à améliorer le dépistage et la prise en charge de l’ostéoporose masculine.

BackgroundRheumatoid arthritis (RA) is characterized by synovium inflammation leading to joint destruction. No sensitive serum biochemical marker of synovial tissue activity is currently available. The aims of this study were to develop a new sensitive serum biochemical marker of synovium turnover and evaluate its performance in patients with RA.Methods We developed an enzyme-linked immunosorbent assay to measure synovial collagen fragments in serum (SynCol) using an antibody recognizing a specific 11 amino acid sequence from the triple helical portion of human type III collagen. The specificity of the antibody was evaluated by competitive inhibition with several collagen-related peptides. Immunohistochemistry was performed to localize the SynCol fragments in RA synovium. Serum SynCol was measured in patients with RA (n=66, 73% women, mean age 62 years, median disease activity score 28 (DAS 28) 2.6) participating in randomized clinical trials and in sex and age matched healthy controls (n=70, 76% women, mean age 59 years). ResultsThe SynCol ELISA demonstrated adequate analytical performances. Competitive inhibition experiments showed that the antibody used in the ELISA recognizes a neoepitope resulting from the cleavage of type III collagen molecules and also the homologous sequences of type IV collagen, but does not cross-react with intact type III and IV collagens. Immunohistochemistry of synovial tissue from a RA subject showed staining of SynCol fragments in the lining layer where destructive fibroblasts are localized and around blood vessels which are rich in type IV collagen. SynCol staining co-localized with matrix metalloproteinase 9 (MMP-9) immunostaining. Serum SynCol levels were significantly increased in patients with RA compared to healthy controls (+ 247 %, p 3.2, n=20) had levels which were 888 % (pConclusions The SynCol ELISA is a sensitive and precise assay measuring circulating type III and IV collagen degradation fragments originating from synovial tissue turnover. Serum SynCol levels are markedly increased in patients with RA, particularly in those with active disease. Trial Registration- Role of the ANS Dysregulation in the Persistence of Fatigue in Rheumatoid Arthritis Patients Treated with Anti-TNF (ANSRA) NCT02475486- Bone MicroArchitecture Abatacept (BMA2) NCT02675218- Impact of the Persistence of Inflammation at Doppler Ultrasound Level on the Structural Evolution of Erosion in Rheumatoid Arthritis Treated with Biotherapy. NCT02531061IRB for synovial tissue 2019-A02742-55 (Comité de Protection des Personnes Sud-Méditerranée I

Poor vitamin D status and high parathyroid hormone (PTH) level are associated with impaired bone microarchitecture, but these data are mainly cross-sectional. We studied the association of the baseline PTH and 25-hydroxycholecalciferol (25OHD) levels with the prospectively assessed deterioration of bone microarchitecture and in estimated bone strength in older men. Distal radius and tibia bone microarchitecture was assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline, then after 4 and 8 years in 826 men aged 60-87 years. At distal radius, total bone mineral density (Tt.BMD), cortical thickness (Ct.Th

Objective To analyse the risk of incident vertebral and non-vertebral fracture in men with DISH. Methods In 782 men ages 50–85 years, DISH was diagnosed using Resnick’s criteria. In men followed prospectively for 7.5 years, a radiographic incident vertebral fracture was defined by a decrease of ≥20% or ≥4mm in any vertebral height vs baseline. Self-reported incident non-vertebral fractures were confirmed by medical records. Results Men with DISH had higher BMD at the lumbar spine (P 0.9 g/cm2; ΔAUC = +0.189, P Conclusion DISH is associated with higher vertebral fracture risk, independently of other risk factors. Assessment of the intervertebral space dysfunction components may improve the vertebral fracture prediction in older men.

Objective.The aim of this multireader exercise was to assess the reliability and change over time of erosion measurements in patients with rheumatoid arthritis (RA) using high-resolution peripheral quantitative computed tomography (HR-pQCT).Methods.HR-pQCT scans of 23 patients with RA were assessed at baseline and 12 months. Four experienced readers examined the dorsal, palmar, radial, and ulnar surfaces of the metacarpal head (MH) and phalangeal base (PB) of the second and third digits, blinded to time order. In total, 368 surfaces (23 patients´ 16 surfaces) were evaluated per timepoint to characterize cortical breaks as pathological (erosion) or physiological, and to quantify erosion width and depth. Reliability was evaluated by intraclass correlation coefficients (ICC), percentage agreement, and Light k; change over time was defined by means ± SD of erosion numbers and dimensions.Results.ICC for the mean measurements of width and depth of the pathological breaks ranged between 0.819–0.883, and 0.771–0.907, respectively. Most physiological cortical breaks were found at the palmar PB, whereas most pathological cortical breaks were located at the radial MH. There was a significant increase in both the numbers and the dimensions of erosions between baseline and follow-up (P= 0.0001 for erosion numbers, width, and depth in axial plane;P= 0.001 for depth in perpendicular plane).Conclusion.This exercise confirmed good reliability of HR-pQCT erosion measurements and their ability to detect change over time.

Objectives: PsA prevalence among skin psoriasis is ∼30%. Nail psoriasis, especially onycholysis, is present in >70% of PsA and the risk of developing PsA is more than doubled in patients with nail involvement. We hypothesized that onycholysis may be associated with early bone erosions of the DIP joint without harbouring PsA symptoms. Methods: We compared tendon thickness, assessed by US, and bone erosions, assessed by high-resolution peripheral quantitative CT, of the DIP joint in patients with psoriatic onycholysis without PsA (ONY) with those in patients with cutaneous psoriasis only (PSO). We used patients with PsA as reference (PsA group), and healthy age-matched controls (CTRL). Differences between groups were assessed by analysis of variance tests followed by post hoc analysis using the Scheffe method. Results: Mean (s.e.m.) age of the 87 participants (61% males) was 45.2 (1.3) years. The mean extensor tendon thickness was significantly larger in ONY than in PSO patients. In the PsA group, 68% of patients exhibited erosions of three different shapes: V-, Omega- A nd U-shape. Association with erosions was greater in the ONY group than in the PSO group (frequency: 57 vs 14%; P < 0.001; mean number of erosions: 1.10 (0.35) vs 0.03 (0.03); P < 0.001). Conclusion: Onycholysis was associated with significant enthesopathy and bone erosions in our cohort. These data support the pathogenic role of enthesopathy in PsA. Onycholysis may be considered as a surrogate marker of severity in psoriasis., SCOPUS: ar.j, info:eu-repo/semantics/published

Long-term glucocorticoid (GC) therapy induces glucocorticoid-induced osteoporosis (GIOP) and its associated fractures. Most specialty organizations recommend bisphosphonates as first-line therapies based only on bone mineral density efficacy data. Effective treatment of GIOP based on head-to-head trials with fracture endpoint has not yet been established. The pathophysiologic mechanisms of GIOP that lead to the detrimental effects on bone are not yet fully elucidated. Although GCs in an early and transitory period promote osteoclastic activity, in the current paper, we outline why GIOP is in fact a disease of the bone formation and then provide the rationale for the use of bone-forming agents as first-line therapy for patients with high fracture risk in GIOP.

Resume Les indications de biopsie osseuse guidee comportent le diagnostic des images osteolytiques, condensantes ou sclerotiques non faisables avec l’imagerie. La fluoroscopie, l’echo-Doppler, l’IRM et le scanner permettent de guider la procedure. Les regles de prelevement carcinologiques doivent etre bien respectees. La biopsie osseuse transiliaque s’utilise pour l’analyse histomophometrique de l’os, surtout pour le diagnostic de l’osteodystrophie renale. La biopsie osteomedullaire, deux fois plus petite et peu traumatisante, est indiquee dans le diagnostic des pathologies hematologiques.

Summary Objective Identifying objective risk-indicators for total joint replacement (TJR) is useful to enrich population at high risk in OA clinical trials. We investigate the association of urinary CTX-II, a biochemical marker of cartilage breakdown, with the risk of TJR. Method 478 postmenopausal women (mean age 65.5 ± 7.5 yr) from the OFELY cohort were studied. CTX-II, serum CTX-I (bone resorption) and PINP (bone formation), were measured at baseline. Association between CTX-II and incidence of TJR was assessed by Cox Hazard Regression. Results During a median (95%CI) 17.8 (15.0–18.1) years follow-up, 38 women sustained a TJR, including hip (n = 29) or knee (n = 9) replacement. CTX-II -but not CTX-I or PINP- was higher in patients with TJR (+34%, P = 0.001 vs women with no TJR). Increased baseline CTX-II levels were associated with a higher risk of TJR with a Hazard Ratio (HR) (95 CI) of 1.45 (1.13–1.85) per 1 SD increase after adjustment for age, BMI and total hip BMD. CTX-II remained significantly associated with the risk of TJR after further adjustment for total WOMAC, prevalent knee OA (KL ≥ 2) and self-reported hip OA [HR (95 CI): 1.31 (1.01–1.71), P = 0,04]. When women were categorized as low and high CTX-II (lower and above the 95 percentile of healthy premenopausal women, respectively), subjects with high levels had an age-BMI-hip BMD adjusted HR (95 CI) of 3.00 (1.54–5.85) compared to women with low levels which remained significant after further adjustment for WOMAC, knee and/or hip OA [HR (95 CI): 2.45 (1.25–4.89), P = 0.01]. Conclusion CTX-II is an independent risk indicator of TJR in postmenopausal women suggesting that it may be useful to identify subjects at high risk of TJR.

In a randomized clinical trial in patients initiating glucocorticoid therapy (GC-I) or on long-term therapy (GC-C), denosumab every 6 months increased spine and hip bone mineral density at 12 and 24 months significantly more than daily risedronate. The aim of this study was to evaluate the effects of denosumab compared with risedronate on bone strength and microarchitecture measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) in GC-I and GC-C. A subset of 110 patients had high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the distal radius and tibia at baseline and at 12 and 24 months. Cortical and trabecular microarchitecture were assessed with standard analyses and failure load (FL) with micro-finite element analysis. At the radius at 24 months, FL remained unchanged with denosumab and significantly decreased with risedronate in GC-I (-4.1%, 95% confidence interval [CI] -6.4, -1.8) and, in GC-C, it significantly increased with denosumab (4.3%, 95% CI 2.1, 6.4) and remained unchanged with risedronate. Consequently, FL was significantly higher with denosumab than with risedronate in GC-I (5.6%, 95% CI 2.4, 8.7, p < 0.001) and in GC-C (4.1%, 95% CI 1.1, 7.2, p = 0.011). We also found significant differences between denosumab and risedronate in percentage changes in cortical and trabecular microarchitectural parameters in GC-I and GC-C. Similar results were found at the tibia. To conclude, this HR-pQCT study shows that denosumab is superior to risedronate in terms of preventing FL loss at the distal radius and tibia in GC-I and in increasing FL at the radius in GC-C, based on significant differences in changes in the cortical and trabecular bone compartments between treatment groups in GC-I and GC-C. These results suggest that denosumab could be a useful therapeutic option in patients initiating GC therapy or on long-term GC therapy and may contribute to treatment decisions in this patient population. (c) 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). PG reports grants from Amgen, grants and other from AbbVie, grants from Celgene, grants from Lilly, grants from Merck, grants from Pfizer, grants from Roche, grants from UCB, grants from Fresenius, grants from Mylan, and grants from Sandoz outside the submitted work. BR reports personal fees from Scanco Medical AG outside the submitted work. EL reports personal fees from Amgen; personal fees from Lilly; grants, personal fees, and nonfinancial support from Celgene; personal fees from Expanscience; personal fees from AbbVie; personal fees from Sublimed; grants, personal fees, and non-financial support from UCB; and grants, personal fees, and non-financial support from MSD outside the submitted work. BO reports personal fees from Raffo, personal fees from Baliarda, personal fees from Shire, personal fees from Takeda, personal fees from Gador, personal fees from Amgen, and personal fees from Ultragenyx outside the submitted work. RC reports grants from Amgen during the conduct of the study; grants and personal fees from UCB; personal fees from Lilly; personal fees from BMS; personal fees from AbbVie; personal fees from Pfizer; grants and personal fees from Chugai; personal fees from Sanofi; personal fees from Novartis; and grants and other from Fresenius Kiabi outside the submitted work. AC is employed by Amgen and has equity in Amgen. SH is an employee of and has equity in Amgen. KGS reports grants from Amgen, Horizon Pharma, Swedish Orphan Biovitrum AB, Shanton Pharma Co. LTD, Dyve Bioscience, and LG Chem outside the submitted work. JPB reports grants from Amgen, grants from UCB, and grants from Lilly the outside the submitted work. All authors had full access to the data, and there were no restrictions regarding content to include in the manuscript. This study was funded by Amgen Inc. Authors’ roles: Investigation: PG, OM, EL, BO, RC, and KGS. Formal analysis: KE, AC, and SH. Writing—original draft: PG and MB. Writing—review & editing: PG, MB, BR, OM, EL, BO, RC, KE, AC, SH, KGS, and JPB.

Poor medication adherence is a serious barrier to successful chronic disease management. Previous reviews reported that low health literacy could be associated with medication non-adherence but conclusions were uncertain.The aim of this systematic review was to clarify the relationship between health literacy and medication adherence in adults with chronic diseases. A secondary objective was to identify the factors that influence medication adherence.Publications analyzing the relationship between health literacy and adherence in adults with chronic diseases were identified through 6 databases between 2015 and 2020. A quality assessment was conducted in order to improve the interpretation of the relationship between health literacy and medication adherence. A narrative synthesis was then performed to describe the relationship between health literacy and medication adherence. The factors influencing medication adherence were then analyzed as a secondary outcome.Among the 27 studies, 17 and 10 were considered to be of good and medium methodological quality, respectively. Concerning the relationship between health literacy and adherence, 14 reported a positive relationship, 1 study suggested a negative relationship, 3 found mixed results, and 9 reported not finding a relationship. Patient-related factors such as medication beliefs, self-efficacy, or medication knowledge, as well as demographic factors such as ethnic minority and incomes influence medication adherence.The present review confirms an unclear relationship between health literacy and medication adherence. Although health literacy plays a substantial role in medication adherence, other factors must be taken into account when addressing non-adherence.

Prevalence of osteoporosis is more than 50% in older adults, yet current clinical methods for diagnosis that rely on areal bone mineral density (aBMD) fail to detect most individuals who have a fragility fracture. Bone fragility can manifest in different forms, and a "one-size-fits-all" approach to diagnosis and management of osteoporosis may not be suitable. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides additive information by capturing information about volumetric density and microarchitecture, but interpretation is challenging because of the complex interactions between the numerous properties measured. In this study, we propose that there are common combinations of bone properties, referred to as phenotypes, that are predisposed to different levels of fracture risk. Using HR-pQCT data from a multinational cohort (n = 5873, 71% female) between 40 and 96 years of age, we employed fuzzy c-means clustering, an unsupervised machine-learning method, to identify phenotypes of bone microarchitecture. Three clusters were identified, and using partial correlation analysis of HR-pQCT parameters, we characterized the clusters as low density, low volume, and healthy bone phenotypes. Most males were associated with the healthy bone phenotype, whereas females were more often associated with the low volume or low density bone phenotypes. Each phenotype had a significantly different cumulative hazard of major osteoporotic fracture (MOF) and of any incident osteoporotic fracture (p 0.05). After adjustment for covariates (cohort, sex, and age), the low density followed by the low volume phenotype had the highest association with MOF (hazard ratio = 2.96 and 2.35, respectively), and significant associations were maintained when additionally adjusted for femoral neck aBMD (hazard ratio = 1.69 and 1.90, respectively). Further, within each phenotype, different imaging biomarkers of fracture were identified. These findings suggest that osteoporotic fracture risk is associated with bone phenotypes that capture key features of bone deterioration that are not distinguishable by aBMD. © 2021 American Society for Bone and Mineral Research (ASBMR).

Assessment of the progression of abdominal aortic calcification (AAC) may be a surrogate marker of the impact of physical function on cardiovascular risk. Our aim was to assess the risk of rapid AAC progression in older men with low relative appendicular lean mass (RALM) and poor physical function.Prospective cohort study.Community-dwelling older men.621 men aged 50-85 followed prospectively (baseline, 3 and 7.5 years).Body composition was assessed by DXA. Poor physical function was defined as incapacity to perform ≥1 of 5 clinical tests (balance, muscle strength). AAC was assessed using Kauppila's semiquantitative score. Reclassification improvement was assessed by comparing the areas under the curve (AUC) using DeLong's method.Rapid AAC progression (0.6 point/year) was found in 168 men (27.1%). After adjustment for confounders including baseline AAC, the risk of rapid AAC progression increased with lower RALM (OR=1.42/SD, 95%CI: 1.09-1.86, p0.01) and was higher in the lowest (7.5kg/m2) vs. highest (8.6kg/m2) quartile (OR=2.15, 95%CI: 1.17-3.95, p0.01). Poor physical performance was associated with rapid AAC progression (OR=2.76, 95%CI: 1.48-5.91, p0.005). Low RALM (7.84kg/m2 defined using Youden's index) and poor physical function contributed to the risk of rapid AAC progression jointly. Men who had low RALM and poor physical function had higher risk of rapid AAC progression vs. men without these traits (OR=4.66, 95%CI: 1.72-12.62, p0.05). RALM and physical function improved the identification of men with rapid AAC progression (DAUC=0.026, 95%CI: 0.005-0.046, p0.05) after adjustment for confounders including baseline AAC score.Low RALM and poor physical function are associated with higher risk of rapid AAC progression and possibly represent another measure of cardiovascular risk.

Mazabraud's syndrome (MZB) is a rare condition in which fibrous dysplasia of bone/the McCune-Albright syndrome (FD/MAS) co-exists with intramuscular myxomas. Both FD and the myxomas harbor the GNAS-mutation. Recent studies have shown that extraskeletal, GNAS-related features are associated with a more severe phenotype of FD/MAS. However, patients with MZB are often only seen by orthopedic surgeons. We therefore evaluated MZB patients seen in tertiary referral centers from the Netherlands (LUMC), USA (National Institutes of Health) and France (INSERM UMR 1033 (Lyos), Hopital Edouard Herriot). All FD/MAS patients known in these centers with an additional diagnosis of a myxoma were included. Demographic information and data on disease extent and extraskeletal manifestations of FD/MAS such as precocious puberty (PP) or cafe-au-lait patches (CAL) were retrieved from patient's medical records. Thirty MZB patients were included: 20 women (67%) and 10 men (33%). Patients received a diagnosis of MZB (median 42 years, range 16-19) significantly later than the diagnosis of FD/MAS (median 30 years, range 0-60), p < 0.01. Twenty-six patients were diagnosed with polyostotic disease (87%). In 97% the myxoma was located near the skeletal FD lesion. The combination of MZB and MAS was made in 13 patients in whom PP (n = 7), CAL (n = 7), GH-excess (n = 3) and hyperthyroidism (n = 3) were present. Other extraskeletal features were (multinodular) goiter (n = 2) and thyroid cysts (n = 1). Furthermore, in this cohort of patients with MZB several (pre-)malignant tumors were observed; ductal carcinoma in situ of the breast in 3 patients (10%), breast cancer in 1 patient (3.3%), intra pancreatic mucinous neoplasms in 3 patients (10%) and liver adenomas in 2 patients (6.6%). A total of 47% of patients with MZB had an additional extraskeletal feature such as an endocrinopathy. In MZB, 87% of patients suffer from polyostotic FD, 43% of patients have extraskeletal GNAS-features such as an hyperfunctioning endocrinopathy and 30% (pre-)malignant tumors. We therefore advocate that MZB patients should undergo a complete screening and long-term follow-up for extent of bone disease, but also extraskeletal GNAS features of FD/MAS.

Background To assess current practice regarding the management of rheumatoid arthritis patients among general practitioners of a French region, and their perception about the deployment of a multidisciplinary collaboration. Methods A cross-sectional online survey was sent to the general practitioners of a French region. The questionnaire comprised of 3 sections to collect data regarding 1/demographics, 2/practice and knowledge in rheumatoid arthritis, and 3/perception about the deployment of a multidisciplinary collaboration. Results 1/A total of 247 general practitioners (M/F ratio: 1.4; mean age: 46.7 years) completed the survey. 2/More than half of general practitioners believed that their role was very or extremely important in disease diagnosis (72.5%), and management of comorbidities (67.2%). Among respondents, 6.1% considered that they did not face any difficulty concerning the patient management and 61.5% had already identified causes of non-adherence. 3/A total of 151 (61.1%) general practitioners were willing to participate in a multidisciplinary programme to improve medication adherence in rheumatoid arthritis. Conclusions General practitioners are motivated to contribute to an overall management of rheumatoid arthritis patients. Nevertheless, they need professional education about rheumatoid arthritis treatment and training in motivational interviews before getting involved in a multidisciplinary collaboration.

Recently, the bone strain index (BSI), a new index of bone strength based on a finite element model (FEA) from dual X-ray absorptiometry (DXA), has been developed. BSI represents the average equivalent strain inside the bone, assuming that a higher strain level (high BSI) indicates a condition of higher risk. Our study aimed to analyze the relationship between BSI and age, BMI and areal BMD in pre- and postmenopausal women and to prospectively investigate fracture prediction (Fx) by BSI in postmenopausal women. Methods. At the 14th annual follow-up of the OFELY study, BSI was measured at spine (Spine BSI) and femoral scans (Neck and Total Hip BSI), in addition to areal BMD with DXA (Hologic QDR 4500) in 846 women, mean (SD) age 60 yr (15). The FRAX® (fracture risk assessment tool) for major osteoporotic fractures (MOF) was calculated with FN areal BMD (aBMD) at baseline; incident fragility fractures were annually registered until January 2016. Results. In premenopausal women (n = 261), Neck and Total Hip BSI were slightly negatively correlated with age (Spearman r = -0.13 and -0.15 respectively, p = 0.03), whereas all BSIs were positively correlated with BMI (r = +0.20 to 0.37, p 0.01) and negatively with BMD (r = -0.69 to -0.37, p 0.0001). In postmenopausal women (n = 585), Neck and Total Hip BSI were positively correlated with age (Spearman r = +0.26 and +0.31 respectively, p 0.0001), whereas Spine BSI was positively correlated with BMI (r = +0.22, p 0.0001) and all BSIs were negatively correlated with BMD (r = -0.81 to -0.60, p 0.0001). During a median [IQ] 9.3 [1.0] years of follow-up, 133 postmenopausal women reported an incident fragility Fx, including 80 women with a major osteoporotic Fx (MOF) and 26 women with clinical vertebral Fx (VFx). Each SD increase of BSI value was associated with a significant increase of the risk of all fragility Fx with an age-adjusted HR of 1.23 for Neck BSI (p = 0.02); 1.27 for Total Hip BSI (p = 0.004) and 1.35 for Spine BSI (p 0.0001). After adjustment for FRAX®, the association remained statistically significant for Total Hip BSI (HR 1.24, p = 0.02 for all fragility Fx; 1.31, p = 0.01 for MOF) and Spine BSI (HR 1.33, p 0.0001 for all fragility Fx; 1.33, p = 0.005 for MOF; 1.67, p = 0.002 for clinical VFx). In conclusion, spine and femur BSI, an FEA DXA derived index, predict incident fragility fracture in postmenopausal women, regardless of FRAX®.

International audience; The worldwide global increase in serum 25-hydroxyvitamin D (25(OH)D) measurements has led some countries to restrict reimbursement for certain clinical situations only. Another approach could consist in providing physicians with screening tools in order to better target blood test prescription. The objective of the SCOPYD study was to identify the best combination of predictors of serum VitD concentration among adults aged 18–70 years. Potential risk factors for VitD deficiency were collected using a comprehensive self-administered questionnaire. A multivariable linear regression was used to build a predictive model of serum 25(OH)D concentration. Among 2488 participants, 1080 (43.4%) had VitD deficiency (

Osteoporosis (OP) is a major public health concern, but still OP care does not meet guidelines. Interventions have been developed to improve appropriate OP management. The objective of the present study was to systematically review the current literature to ascertain the efficacy of interventions to improve OP care and characterize interventions taking into account elements related to their potential cost and feasibility. Studies published from 2003 to 2018 were retrieved from PubMed/MEDLINE, Science Direct, Web of Science, Cochrane, and Wiley Online Library databases. Screening of references and quality assessment were independently performed by two reviewers. We classified interventions into three types according to the target of the intervention: health system (structural interventions), healthcare professional (HCP), and patient. Meta-analysis was performed by type of intervention and their effect on two outcomes: prescription of BMD measurement and prescription of OP therapy. A total of 4268 records were screened; 32 studies were included in the qualitative analysis and 29 studies in the quantitative analysis. Structural interventions strongly and significantly improved prescription of BMD measurement (OR = 9.99, 95% CI 2.05; 48.59) and treatment prescription (OR = 3.82, 95% CI 2.16; 6.75). The impact of HCP-centered interventions on BMD measurement prescription did not reach statistical significance (OR = 2.19, 95% CI 0.84; 5.73) but significantly improved treatment prescription (OR = 3.82, 95% CI 2.16; 6.75). Interventions involving patients significantly improved the prescription of BMD measurement (OR = 2.16, 95% CI 1.62; 2.89) and treatment prescription (OR = 1.70, 95% CI 1.35; 2.14). Interventions to improve OP management had a significant positive impact on prescription of BMD measurement but a more limited impact on treatment prescription.

In older men, low estrogen levels are associated with poor bone microarchitecture. Data on androgens are discordant. We studied the link between baseline sex steroid levels (total 17β -estradiol [17βE2], total testosterone [tT], calculated bioavailable 17βE2 [bio-17βE2], and apparent free testosterone concentration [AFTC]) and bone microarchitecture deterioration assessed prospectively in a 820 older men followed for 8 years. Bone microarchitecture was assessed by HR-pQCT at baseline, then after 4 and 8 years. At both the skeletal sites, the bone microarchitecture deterioration rate did not correlate with serum levels of tT and 17βE2. At the distal radius, cortical area (Ct.Ar) decreased more rapidly in the lowest versus the highest AFTC quartile. At the distal tibia, cortical thickness (Ct.Th) decreased and trabecular area (Tb.Ar) increased more rapidly in the highest versus the lowest AFTC quartile. At the tibia, bone mineral content (BMC), total volumetric bone mineral density (Tt.vBMD), Ct.Th, and Ct.Ar decreased, whereas Tb.Ar increased faster in the lowest versus the highest bio-17βE2 quartile. In men who had both AFTC and bio-17βE2 in the lowest quartile (high-risk group), distal radius cortical vBMD (Ct.vBMD) decreased more rapidly compared with men who had both hormones in the three upper quartiles (reference group). At the distal tibia, Tt.vBMD, Ct.Th, Ct.Ar, and Ct.vBMD decreased, whereas Tb.Ar increased more rapidly in the high-risk group versus the reference group. In men receiving androgen deprivation therapy (ADT) for prostate cancer, BMC, Tt.vBMD, Ct.Th, Ct.Ar, and Ct.vBMD decreased, whereas Tb.Ar increased more rapidly than in men not receiving ADT at both the skeletal sites. Thus, in older men followed up prospectively, low levels of bio-17βE2, and to a smaller extent AFTC, are associated with accelerated cortical bone deterioration. Cortical bone deterioration was strongly accelerated in men receiving ADT who had very low levels of all sex steroids. © 2019 American Society for Bone and Mineral Research.

Sclerostin, a protein produced by osteocytes, inhibits bone formation. Administration of sclerostin antibody results in increased bone formation in multiple animal models. Romosozumab, a humanized sclerostin antibody, has a dual effect on bone, transiently increasing serum biochemical markers of bone formation and decreasing serum markers of bone resorption, leading to increased BMD and reduction in fracture risk in humans. We aimed to evaluate the effects of romosozumab on bone tissue. In a subset of 107 postmenopausal women with osteoporosis in the multicenter, international, randomized, double‐blind, placebo‐controlled Fracture Study in Postmenopausal Women with Osteoporosis (FRAME), transiliac bone biopsies were performed either after 2 (n = 34) or 12 (n = 73) months of treatment with 210 mg once monthly of romosozumab or placebo to evaluate histomorphometry and microcomputed tomography‐based microarchitectural endpoints. After 2 months, compared with either baseline values assessed after a quadruple fluorochrome labeling or placebo, significant increases (P

High-resolution peripheral quantitative computed tomography (HR-pQCT) evaluates different components of bone fragility. The positioning and length of the region of interest (ROI) in growing populations remain to be defined.Using HR-pQCT at the ultradistal tibia, we compared a single-center cohort of 28 teenagers with chronic kidney disease (CKD) at a median age of 13.6 (range, 10.2-19.9) years to local age-, gender-, and puberty-matched healthy peers. Because of the potential impact of short stature, bone parameters were assessed on two different leg-length-adjusted ROIs in comparison to the standard analysis, namely the one applied in adults. The results are presented as median (range).After matching, SDS height was -0.9 (-3.3;1.6) and 0.3 (-1.4;2.0) in patients and controls, respectively (P0.001). In younger children (e.g., prepubertal, n=11), bone texture parameters and bone strength were not different using standard analysis. However, using a height-adjusted ROI enabled better characterization of cortical bone structure. In older patients (e.g., pubertal, n=17), there were no differences for height between patients and controls: with the standard evaluation, cortical bone area and cortical thickness were significantly lower in CKD patients: 85 (50-124) vs. 108 (67-154) mmAdapting the ROI to leg length enables better assessment of bone structure, especially when height discrepancies exist between controls and patients. Larger cohorts are required to prospectively validate this analytic HR-pQCT technique.

Resume Introduction La polyarthrite rhumatoide presente un faible niveau d’adhesion medicamenteuse. A l’etranger, le pharmacien de ville a un impact positif sur l’adhesion des patients dans plusieurs pathologies chroniques. En France, les missions des pharmaciens d’officine se developpent avec la mise en place d’entretiens pharmaceutiques. Objectif Evaluer les perceptions des pharmaciens de ville sur l’interet et la faisabilite d’entretiens pharmaceutiques dans la polyarthrite rhumatoide. Methode Des entretiens semi-diriges ont ete realises entre aout et octobre 2017, aupres de pharmaciens de ville de la region Auvergne-Rhone-Alpes. L’analyse inductive du verbatim des entretiens a ete effectuee par deux personnes independantes. Resultats Les 15 entretiens ont souligne des difficultes de recrutement des patients pour les entretiens actuellement possibles a l’officine, la complexite de l’organisation et des modalites de financement, une faiblesse du lien ville-hopital. Neanmoins les pharmaciens etaient motives pour elargir le dispositif a d’autres pathologies. Concernant des entretiens dans la polyarthrite rhumatoide, les pharmaciens les verraient sous forme d’entretiens structures, preferentiellement a l’officine, en lien, voire « prescrits » par les medecins pour une pluriprofessionnalite et un partage d’information optimaux. Une formation prealable ainsi qu’un financement de ces entretiens devront etre envisages pour motiver les pharmaciens a cette activite. Conclusion Cette etude a permis d’aborder avec les pharmaciens de ville leurs attentes et besoins pour elargir le dispositif d’entretiens pharmaceutiques dans la polyarthrite rhumatoide. Ces resultats devront etre pris en compte pour construire un modele d’entretiens d’accompagnement des patients dans la polyarthrite rhumatoide qui puisse s’integrer dans l’exercice officinal.

Context High fracture risk in individuals with low muscle strength is attributed to high risk of falls. Objective This work aims to study the association of muscle mass and physical performance with bone microarchitecture decline and risk of fall and nonvertebral fracture in men. Methods A prospective, 8-year follow-up of a cohort was conducted among the general population. A total of 821 volunteer men aged 60 and older participated. Hip areal bone mineral density (aBMD) and appendicular lean mass (ALM) were assessed at baseline by dual x-ray absorptiometry. Lower-limb relative ALM (RALM-LL) is ALM-LL/(leg length)2. The physical performance score reflects the ability to perform chair stands and static and dynamic balance. Bone microarchitecture was assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline and after 4 and 8 years. Statistical analyses were adjusted for shared risk factors. Outcome measurements included the rate of change in the HR-pQCT indices, incident falls, and fractures. Results Cortical bone loss and estimated bone strength decline were faster in men with low vs normal RALM-LL (failure load: –0.74 ± 0.09 vs –0.43 ± 0.10%/year; P Conclusion Rapid decline of bone microarchitecture and estimated strength in men with poor physical performance and low RALM-LL may contribute to higher fracture risk.

Introduction Une augmentation de la production d’interleukine-6 (IL-6) par les cellules souches mutees a ete observee dans le tissu dysplasique des patients atteints de dysplasie fibreuse des os (DF). Elle participe a l’augmentation de la resorption osseuse et pourrait jouer un role dans la douleur osseuse caracteristique de la maladie. Nous avons donc teste la valeur de l’inhibition de l’action de l’IL-6 dans une etude pilote pour determiner si cela reduirait la resorption et la douleur osseuses. Patients et methodes L’essai TOCIDYS etait un essai randomise, controle contre placebo, sur une duree d’un an, en plan croise, conduit chez des patients qui ne repondaient pas aux bisphosphonates. Les patients recevaient une perfusion intra-veineuse mensuelle de tocilizumab a la dose de 8 mg/kg ou un placebo identique pendant 6 mois. Pendant les 6 mois suivants, ils recevaient le tocilizumab s’ils avaient eu le placebo initialement, et vice-versa. Le critere de jugement principal etait la variation de CTX serique apres 6 mois de traitement, par rapport a l’inclusion. Les autres criteres de jugement etaient la variation de douleur osseuse au site le plus douloureux, la variation de P1NP, de phosphatase alcaline osseuse, d’osteocalcine et d’ICTP, ainsi que la modification de qualite de vie. L’analyse statistique a repose sur une analyse de variance incluant la sequence, la periode et le traitement, et en tenant compte de l’effet carry-over potentiel. Resultats Nous avons randomise 8 patients avec une DF dans chaque sequence (14 femmes, 2 hommes, d’âge moyen 50,5 ± 1,2 ans), dont 5 avec le syndrome de McCune-Albright, qui ont tous termine la periode des 6 premiers mois de traitement. Pendant la deuxieme periode, un patient dans le groupe placebo a retire son consentement, alors que dans le groupe tocilizumab un patient a arrete l’etude a cause d’evenements indesirables et un a retire son consentement. L’analyse d’efficacite porte donc sur 13 patients. L’effet carry-over n’etant pas statistiquement significatif, les deux periodes ont pu etre analysees. Le niveau de douleur median a l’inclusion etait de 6/10 (5 ;6). Nous n’avons pas observe de variation significative du CTX et des autres marqueurs biochimiques osseux entre les deux groupes. De meme, il n’y a pas eu de reduction significative de la douleur sous tocilizumab, meme si 3 patients ont eu une baisse franche de douleur sous traitement actif, avec une rechute progressive sous placebo pour deux d’entre eux. Les divers domaines de l’echelle SF-36 de qualite de vie n’ont pas varie significativement dans le temps et selon les groupes. Discussion Cet essai clinique a ete lance avant qu’un modele animal de la DF n’existe. Cette etude a ete conduite dans un groupe particulier de malades atteints de DF qui avaient recu des doses substantielles de bisphosphonates auparavant. Conclusion Le tocilizumab n’a pas reduit le remodelage osseux dans la DF. Le tocilizumab n’a pas reduit la douleur osseuse chez la plupart des patients, meme si un effet ne peut etre exclu chez certains individus, dans cet essai ayant suffisamment de puissance pour les marqueurs osseux mais pas pour la douleur.

This observational study prospectively assessed direct and indirect costs related to patient management over 18 months following hip, clinical vertebral, humeral, or distal forearm fracture events in France. It appears that their levels were much higher than the previous estimates, raising the burden of osteoporosis-related fractures on public health expenditures.This prospective observational study assessed the costs related to patient management over the 18-month period following the event of a hip, clinical vertebral, humeral, or distal forearm fracture in France.Individuals aged ≥ 50 years old with the diagnosis of a fragility fracture in six French University Hospitals were enrolled in the International Costs and Utilities Related to Osteoporotic Fractures Study (ICUROS). All resources used over the defined period and related to fracture and the underlying osteoporosis management were collected by questionnaires at baseline, 4 months, 12 months, and 18 months. Information was collected by direct or phone contact completed by patients' records and interviews of partner, family, and general practitioners. Costs were estimated from a societal perspective, including direct and indirect costs. We implemented recursive partitioning analysis (RPA), a statistical learning algorithm to identify predictors of costs.Four hundred thirty-one patients (mean age 72.5 years; 84.6% women) were evaluated. Among them, 17.6% had a prior fracture in the last 5 years. Approximately half of the whole group lived alone in the community, and 56.8% were from a low- or middle-income category. Over the 18-month period of evaluation, total costs (including initial fracture-related and follow-up ones) were 23 926 €, 14 561 €, and 6 905 € for the hip, clinical vertebral, and distal forearm fracture, respectively. Over a year, costs related to a humeral fracture were 10 319 €. The RPA identified mobility impairment prior to fracture as a predictor of increase in costs related to fracture.Our study for the first time prospectively assessed total costs related to the four main osteoporotic fractures in France. It appears that their levels were much higher than previous estimates, raising the burden of osteoporosis-related fractures on public health expenditures.

Objectives Medication reconciliation is time-consuming and its complete deployment can be difficult. The implementation of a simplified process, such as patient interviews at admission without full reconciliation, may contribute to improve patient care. The objective of the present study was to describe the feasibility and assess the potential effectiveness of implementing pharmacist-led interviews at patient admission to a rheumatology department. Methods This is a prospective observational study of pharmacist-led interviews at patient admission conducted between April 2015 and May 2017 in the 34-bed rheumatology department of Edouard Herriot Hospital, a French university hospital. These interviews were structured to explore patient medication management at home. The main outcome was the number of medication errors at admission. Other outcomes were the total number of interviews, the number of interviews with at least one new item of information provided by the patient, the number of interviews with at least one medication error detected, and the number of interviews leading to a modification of the hospital medication order. Results A total of 247 interviews were carried out; there was an increase in the number of interviews over the study period (n=54 in 2015, n=98 in 2016, and n=95 for the first 5 months of 2017). Among the interviews conducted, 135 (55%) provided new information concerning patient medication management and 117 medication errors were identified in hospital orders (0.47/patient). There were 76 interviews (31%) with at least one medication error; all led to a medication order modification. Conclusions The study found that pharmacist-led interviews at patient admission were effective in detecting medication errors. They could be an alternative to a full medication reconciliation process in targeted situations. When the patient interview does not provide sufficiently robust information, full medication reconciliation may be performed.

In recent years, markers research has focused on the structural components of cartilage matrix. Specifically, a second generation of degradation markers has been developed against type II collagen neoepitopes generated by specific enzymes. A particular effort has been made to measure the degradation of minor collagens III and X of the cartilage matrix. However, because clinical data, including longitudinal controlled studies, are very scarce, it remains unclear whether they will be useful as an alternative to or in combination with current more established collagen biological markers to assess patients with osteoarthritis (OA). In addition, new approaches using high-throughput technologies allowed to detect new types of markers and improve the knowledge about the metabolic changes linked to OA. The relative advances coming from phenotype research are a first attempt to classify the heterogeneity of OA, and several markers could improve the phenotype characterization. These phenotypes could improve the selection of patients in clinical trials limiting the size of the studies by selecting patients with OA characteristics corresponding to the metabolic pathway targeted by the molecules evaluated. In addition, the inclusion of rapid progressors only in clinical trials would facilitate the demonstration of efficacy of the investigative drug to reduce joint degradation. The combination of selective biochemical markers appears as a promising and cost-effective approach to fulfill this unmet clinical need. Among the various potential roles of biomarkers in OA, their ability to monitor drug efficacy is probably one of the most important, in association with clinical and imaging parameters. Biochemical markers have the unique property to detect changes in joint tissue metabolism within a few weeks.

Bone microarchitecture assessed by high-resolution peripheral quantitative computed tomography varies across populations of different origin. The study presents a reference dataset of microarchitectural parameters in a homogeneous group of participants aged within 22-27 range determined by a discriminant analysis of a larger cross-sectional cohort of 339 women. INTRODUCTION High-resolution peripheral quantitative computed tomography (HR-pQCT) non-invasively measures three-dimensional bone microarchitectural parameters and volumetric bone mineral density. Previous studies established normative reference HR-pQCT datasets for several populations, but there were few data assessed in a reference group of young women with Caucasian ethnicity living in Western Europe. It is important to obtain different specific reference dataset for a valid interpretation of cortical and trabecular microarchitecture data. The aim of our study was to find the population with the most optimal bone status in order to establish a descriptive reference HR-pQCT dataset in a young and healthy normal-weight female cohort living in a European area including Geneva, Switzerland, Lyon and Saint-Etienne, France. METHODS We constituted a cross-sectional cohort of 339 women aged 19-41 years with a BMI > 18 and

Rheumatoid arthritis (RA) is considered a major risk factor for fragility fractures. We examined the quality of management of bone fragility in RA patients in a real-life setting.We performed a longitudinal case-control retrospective study in a 1/97th random sample of French health care claims database from 2014 to 2016 to determine the extent of bone fragility management in patients with RA compared with non-RA matched controls.Compared to their non-RA controls (n=4652), RA patients (n=1008; mean age: 61.1years; methotrexate: 69.7%; other conventional disease-modifying antirheumatic drugs (cDMARDs): 26.8%; biologic: 26.0%; corticosteroids: 36.9%) had more reimbursements for bone mineral density (BMD) measurements (21.6 vs. 9.2%; OR=2.7 [2.3; 3.3]; P0.01) and for bisphosphonates (7.1 vs. 3.6%, OR=2.0 [1.5; 2.7]; P0.05). In patients exposed to corticosteroids, RA patients underwent more BMD assessments than non-RA controls (28.0 vs. 18.8%; OR=1.7 [1.3; 2.2]; P0.05). RA patients exposed to corticosteroids were more likely to sustain fracture than non-exposed RA patients (5.7 vs. 2.4%, P0.01). In addition, only when comparing patients exposed to corticosteroids, was there statistical evidence of an association between RA and an increased fracture rate (6.2 vs. 3.5%, P0.05).Patients with RA exposed to corticosteroids are at high risk of fracture. Patients with RA had more bone fragility management than controls.

Data on the association between bone microarchitecture and cardiovascular disease (CVD) in men are scarce. We studied the link of bone microarchitecture and areal bone mineral density (aBMD) with the risk of major adverse coronary event (MACE) in a cohort of men aged 60 to 87 years followed prospectively for 8 years. At baseline, aBMD was measured using a Hologic Discovery-A device. Bone microarchitecture was assessed at distal radius and tibia by high-resolution peripheral quantitative computed tomography (XtremeCT Scanco device). During the study, 53 men had incident MACE. The analyses were adjusted for confounders related to bone and CVD. In 813 men (53 MACEs), higher aBMD at the lumbar spine, hip, whole body, and radius was associated with lower risk of MACE (hazard ratio [HR] = 0.44-0.71/SD, p

INTRODUCTION Recent technological advances with dual-energy quantitative computed tomography (DEQCT) allow to combine two images of different level of energy to obtain simulated mono-energetic images at 60 keV (SIM60KeV-QCT) with improved image contrast in clinical practice. This study includes three topics: (1) compare bone mineral content (BMC), areal and volumetric bone mineral density (aBMD, vBMD) obtained with SIM60KeV-QCT, single-energy QCT (SEQCT), and dual X-ray absorptiometry (DXA); (2) compare ash density and weight with respective vBMD and BMC assessed on SIM60KeV-QCT, SEQCT, and DXA; and (3) compare the influence of reconstruction kernels on the accuracy of vBMD and BMC using ash density and ash weight as the reference values. METHODS DXA, SEQCT, and DEQCT acquisitions were performed ex vivo on 42 human femurs. Standard kernel (SK) and bone kernel (BK) were applied to each stack of images. Ten diaphyses and 10 femoral necks were cut, scanned, and reconstructed using the techniques described above. Finally, the bone specimens were calcined to obtain the ash weight. RESULTS QCT analysis (SEQCT, SIM60KeV-QCT) underestimated BMC value compared to DXA. For femoral necks, all QCT analyses provided an unbiased estimate of ash weight but underestimated ash density regardless of the kernel used. For femoral diaphysis, SEQCT BK, SIM60KeV-QCT BK, and SK underestimated ash weight but not ash density. CONCLUSION BMC and vBMD quantifications with the SIM60KeV-QCT gave similar results as the SEQCT. Further studies are needed to optimize the use of SIM60KeV-QCT in clinical situations. SK should be used given the effect of kernels on QCT assessment.

Background Dual X-ray absorptiometry body composition measurements are widely used for clinical and research settings. It is well known that measurements vary across instruments, needing caution for longitudinal monitoring or multicentric studies. This study was to quantify intra- and inter-center variability of bone mineral content, bone mineral density, fat and lean body composition measurements between Hologic Discovery models in order to calculate the corrective factors to be applied for multicenter research projects. Materials and methods A whole body phantom composed of materials representing the thickness and percentage of bone, lean and fat mass in the human physiological range was analyzed ten times in three different centers using dual energy X-ray absorptiometry scanners (Two Hologic Discovery QDR A and one QDR W). In addition, we used a morphometric vertebral phantom to monitor stability and a three steps block phantom to check accuracy. Results We found a good long-term stability and accuracy for the three devices. Intra-center coefficients of variation were within the range of the manufacturer acceptable values (bone mineral density: 1.40%, bone mineral content: 1%, area: 1.50%, fat mass: 0.89%, lean mass: 0.76%, total mass: 0.12%). Whereas the inter-center coefficient of variation exceeded 8% (bone mineral density: 8.18%, bone mineral content: 3.03%, area: 8.63%: fat mass: 3,92%, lean mass: 7.89%, total mass: 2.85%). Conclusion Our study showed that the discrepancies across centers remain a major concern, particularly with regard to body composition results. Our study highlight the need of cross calibration between densitometers and proposes corrective factors evaluated from a whole body phantom to lead multicentric studies adjustment.

Odanacatib (ODN) was investigated as an osteoporosis treatment in 292 men. Compared with placebo, odanacatib improved bone mineral density and led to sustained bone resorption decreases while producing relatively little bone formation reduction that leveled off with time. However, increased risk of stroke in another study stopped further odanacatib development.INTRODUCTION: ODN, a selective oral cathepsin K inhibitor, was in development for osteoporosis treatment. This phase 3, double-blind, randomized, placebo-controlled, 24-month study investigated ODN safety and efficacy in men with osteoporosis.METHODS: Men with idiopathic osteoporosis or osteoporosis due to hypogonadism and a lumbar spine or hip (total hip [TH], femoral neck [FN], or trochanter) bone mineral density (BMD) T-score of ≤ - 2.5 to ≥ - 4.0 without prior vertebral fracture or ≤ - 1.5 to ≥ - 4.0 with one prior vertebral fracture were randomized (1:1) to once-weekly ODN 50 mg or placebo. All received 5600 IU vitamin D3 weekly and calcium supplementation as needed (≥ 1200 mg daily). The primary efficacy outcome was changed from baseline in lumbar spine BMD versus placebo.RESULTS: Overall, 292 men, mean age 68.8 years, were randomly assigned to ODN or placebo. Versus placebo, ODN increased BMD from baseline at the lumbar spine, TH, FN, and trochanter by 5.6%, 2.0%, 1.7%, and 2.1%, respectively (all p CONCLUSION: Though a promising osteoporosis therapy for men, ODN development was discontinued due to increased risk of stroke in the LOFT phase 3 trial.TRIAL REGISTRATION: Clinicaltrials.gov NCT01120600 (registered May 11, 2010).

Bisphosphonates (BPs) are the most widely used drugs for the treatment of osteoporosis but prolonged use of BPs might increase the risk of atypical femur fracture (AFF). There are only a few studies that address the bone material quality in patients on long-term BP treatment with or without AFFs. We analyzed 52 trans-iliac bone biopsies from patients on long-term BP therapy with (n = 26) and without (n = 26) AFF. At the microscopic level, the degree of mineralization of bone (DMB) was assessed on whole bone by X-ray digitized microradiography while microhardness by Vickers microindentation, and bone matrix characteristics by Fourier transform infrared microspectroscopy (FTIRM) (mineral/organic ratio, mineral maturity and crystallinity, and collagen maturity) were measured at random focal areas. The AFF patients were treated longer than non-AFF patients (9.7 ± 3.3 years versus 7.9 ± 2.7 years). As expected, bone remodeling was low in both groups, without difference between them. The AFF group had significantly higher DMB in cortical bone (+2.9%, p = .001), which remained so after adjusting for treatment duration (p = .007), and showed a trend in cancellous bone (+1.6%, p = .05). Consistent with higher DMB, heterogeneity index (HI) was lower in the AFF than in the non-AFF group, illustrating lower heterogeneity of mineralization in the AFF group. A significant positive correlation between the duration of treatment and DMB in cortical bone was found in AFF, and not in the non-AFF group. Microhardness and bone matrix characteristics were similar between groups. We conclude that the AFF group had a duration-dependent increase in DMB leading to a significantly higher DMB than the non-AFF. Because BPs have high affinity to bone mineral and lining the walls of the osteocyte lacunae, the accumulation of matrix-bound BPs in AFF could lead to inhibition of the osteocyte cytoskeleton blunting their response to mechanical strains, a hypothesis to be further investigated. © 2021 American Society for Bone and Mineral Research (ASBMR).