Publications by authors named "Pawel Szulc"

102 Publications

Body composition in patients with psoriatic arthritis and changes during interleukin 12/23 inhibition.

Arthritis Care Res (Hoboken) 2021 May 10. Epub 2021 May 10.

Univ. Lille, CHU Lille, Department of Rheumatology, 59000, Lille, France.

Objective: Little is known about body composition in patients with PsA. We compared body composition parameters in PsA patients and healthy controls, and then investigated the effects of ustekinumab (UST) on body composition in patients with PsA.

Methods: At baseline, 30 PsA patients were compared cross-sectionnally with 60 non-PsA healthy controls matched for age, sex, menopausal status and body mass index. Thirty active PsA patients treated with UST were included in a 6-month open follow-up study. Body composition parameters were measured at baseline and 6 months of treatment.

Results: Body composition parameters were different in PsA patients compared to healthy controls: in PsA patients, total and appendicular lean mass were lower (p=0.013 and p=0.010 respectively), whereas total fat mass was higher (p<0.001). In 30% of the PsA patients, skeletal muscle mass was below the cut-off for low muscle quantity (men 7.26 kg/m2, women 5.5 kg/m2), whereas no such change was observed in the control group. After 6 months of treatment with UST, there was no significant change in BMI in 18 of the PsA patients. Total lean mass decreased slightly (p=0.046), whereas fat mass tended to increase, but not significantly. No significant changes in appendicular lean mass and skeletal muscle mass index were observed.

Conclusion: In this study, we found that PsA patients had higher fat mass and lower lean mass than healthy controls. At 6-months of treatment, total lean mass decreased slightly, whereas fat mass tended to increase, but not significantly.
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http://dx.doi.org/10.1002/acr.24623DOI Listing
May 2021

High Cardiovascular Risk in Older Men With Severe Peripheral Artery Calcification on High-Resolution Peripheral QCT Scans: The STRAMBO Study.

Arterioscler Thromb Vasc Biol 2021 May 1;41(5):1818-1829. Epub 2021 Apr 1.

INSERM UMR 1033, University of Lyon, Hôpital Edouard Herriot, France (P.S., C.P., D.F., R.C.).

[Figure: see text].
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http://dx.doi.org/10.1161/ATVBAHA.120.315289DOI Listing
May 2021

Joint Associations of Prevalent Radiographic Vertebral Fracture and Abdominal Aortic Calcification With Incident Hip, Major Osteoporotic, and Clinical Vertebral Fractures.

J Bone Miner Res 2021 Mar 17. Epub 2021 Mar 17.

University of Minnesota, Minneapolis, MN, USA.

Prevalent vertebral fractures (PVFx) and abdominal aortic calcification (AAC) are both associated with incident fractures and can be ascertained on the same lateral spine images, but their joint association with incident fractures is unclear. Our objective was to estimate the individual and joint associations of PVFx and AAC with incident major osteoporotic, hip, and clinical vertebral fractures in 5365 older men enrolled in the Osteoporotic Fractures in Men (MrOS) Study, using Cox proportional hazards and Fine and Gray subdistribution hazards models to account for competing mortality. PVFx (Genant SQ grade 2 or 3) and 24-point AAC score were ascertained on baseline lateral spine radiographs. Self-reports of incident fractures were solicited every 4 months and confirmed by review of clinical radiographic reports. Compared with men without PVFx and AAC-24 score 0 or 1, the subdistribution hazard ratio (SHR) for incident major osteoporotic fracture was 1.38 (95% confidence interval [CI] 1.13-1.69) among men with AAC-24 score ≥2 alone, 1.71 (95% CI 1.37-2.14) for men with PVFx alone, and 2.35 (95% CI 1.75-3.16) for men with both risk factors, after accounting for conventional risk factors and competing mortality. Wald statistics showed improved prediction model performance by including both risk factors compared with including only AAC (chi-square = 17.3, p < .001) or including only PVFx (chi-square = 8.5, p = .036). Older men with both PVFx and a high level of AAC are at higher risk of incident major osteoporotic fracture than men with either risk factor alone. Assessing prevalent radiographic vertebral fracture and AAC on the same lateral spine images may improve prediction of older men who will have an incident major osteoporotic fracture, even after accounting for traditional fracture risk factors and competing mortality. © 2021 American Society for Bone and Mineral Research (ASBMR).
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http://dx.doi.org/10.1002/jbmr.4257DOI Listing
March 2021

High Cardiovascular Risk in Older Men with Poor Bone Microarchitecture-The Prospective STRAMBO Study.

J Bone Miner Res 2021 Feb 2. Epub 2021 Feb 2.

INSERM UMR 1033, University of Lyon, Hôpital Edouard Herriot, Lyon, France.

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 < .025 to < .001). In 745 men having valid distal radius scan (47 MACEs), higher cortical density (Ct.BMD) and higher cortical thickness (Ct.Th ) were associated with lower risk of MACE. This risk was higher in men in the lowest quintile of cortical measures versus the four upper quintiles combined (Ct.BMD: HR = 2.12, 95% confidence interval [CI] 1.08-4.17, p < .025). Findings were similar in 779 men having valid distal tibia scan (48 MACEs). At both sites, higher estimated stiffness and higher failure load were associated with a lower risk of MACE. The risk of MACE was higher in men in the lowest quintile of the measures of bone strength versus four upper quintiles jointly (distal radius stiffness: HR = 2.46, 95% CI 1.27-4.74, p < .01). Similar results were obtained in 638 men without prior fragility fracture and in 689 men without ischemic heart disease at baseline. Thus, in older men followed prospectively for 8 years, higher aBMD, preserved cortical bone status, and higher estimated bone strength were associated with lower risk of MACE after adjustment for relevant confounders. © 2021 American Society for Bone and Mineral Research (ASBMR).
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http://dx.doi.org/10.1002/jbmr.4261DOI Listing
February 2021

Prognostic Value of Abdominal Aortic Calcification: A Systematic Review and Meta-Analysis of Observational Studies.

J Am Heart Assoc 2021 Jan 13;10(2):e017205. Epub 2021 Jan 13.

Centre for Kidney Research School of Public Health Faculty of Medicine and Health Children's Hospital at WestmeadThe University of Sydney New South Wales Australia.

Background The prognostic importance of abdominal aortic calcification (AAC) viewed on noninvasive imaging modalities remains uncertain. Methods and Results We searched electronic databases (MEDLINE and Embase) until March 2018. Multiple reviewers identified prospective studies reporting AAC and incident cardiovascular events or all-cause mortality. Two independent reviewers assessed eligibility and risk of bias and extracted data. Summary risk ratios (RRs) were estimated using random-effects models comparing the higher AAC groups combined (any or more advanced AAC) to the lowest reported AAC group. We identified 52 studies (46 cohorts, 36 092 participants); only studies of patients with chronic kidney disease (57%) and the general older-elderly (median, 68 years; range, 60-80 years) populations (26%) had sufficient data to meta-analyze. People with any or more advanced AAC had higher risk of cardiovascular events (RR, 1.83; 95% CI, 1.40-2.39), fatal cardiovascular events (RR, 1.85; 95% CI, 1.44-2.39), and all-cause mortality (RR, 1.98; 95% CI, 1.55-2.53). Patients with chronic kidney disease with any or more advanced AAC had a higher risk of cardiovascular events (RR, 3.47; 95% CI, 2.21-5.45), fatal cardiovascular events (RR, 3.68; 95% CI, 2.32-5.84), and all-cause mortality (RR, 2.40; 95% CI, 1.95-2.97). Conclusions Higher-risk populations, such as the elderly and those with chronic kidney disease with AAC have substantially greater risk of future cardiovascular events and poorer prognosis. Providing information on AAC may help clinicians understand and manage patients' cardiovascular risk better.
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http://dx.doi.org/10.1161/JAHA.120.017205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955302PMC
January 2021

Reliability of the assessment of disc degeneration on the lateral DXA scans.

Joint Bone Spine 2021 05 17;88(3):105123. Epub 2020 Dec 17.

INSERM UMR 1033, University of Lyon, 69437 Lyon, France; Department of Rheumatology and Bone Pathology, Hôpital Édouard-Herriot, Pavillon F, place d'Arsonval, 69437 Lyon, France. Electronic address:

Introduction: Given the prevalence and costs induced by osteoarthritis (OA), it is necessary to find a cheap and safe technique to evaluate it reliably.

Objective: To assess the value of the lateral dual energy X-ray absorptiometry (DXA) spine scans for the diagnosis of disc degeneration.

Method: Seventy-seven individuals aged 18 and over, with or without disc degeneration, had both lateral thoracolumbar spine radiographs and DXA spine scans (≤6months between both exams). Disc degeneration was assessed using the Lane score. The images of 20 randomly selected individuals were assessed by two readers.

Results: Almost 13% of the thoracic levels were not assessable on the DXA scans. For the identification of the intervertebral levels on the DXA scans as interpretable or not, the intra-reader agreement was good (κ=0.81) and the inter-reader agreement was fair (κ=0.27-0.36). For the diagnostic criteria (osteophytes, disc space narrowing, osteosclerosis, overall grade), the intra-reader agreement was excellent for the radiographs (κ=0.89-0.92), good for the DXA scans (κ=0.64-0.83) and fair to moderate for the between-method comparison (κ=0.25-0.44). The inter-reader agreement was moderate to good for the radiographs (κ=0.49-0.66) and fair to good for the DXA scans (κ=0.32-0.74). In the per patient analysis (the most severe grade), the intra-reader agreement was excellent for the radiographs (κ=0.85-0.94), moderate to excellent for the DXA scans (κ=0.53-0.85) and poor to good for the between-methods comparison (κ=0.17-0.63).

Conclusion: Our results do not support the use of DXA scans for the assessment of thoracolumbar disc degeneration.
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http://dx.doi.org/10.1016/j.jbspin.2020.105123DOI Listing
May 2021

Relationship between diffuse idiopathic skeletal hyperostosis and fragility vertebral fracture: a prospective study in older men.

Rheumatology (Oxford) 2020 Nov 17. Epub 2020 Nov 17.

Service de Rhumatologie, Hôpital Edouard Herriot, Pavillon F, Lyon.

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 < 0.05), but not at other skeletal sites. After adjustment for confounders including disc space narrowing (DSN) and endplate irregularity, the risk of vertebral fracture was higher in men with DISH vs men without DISH [10/164 (6.1%) vs 16/597 (2.7%), P < 0.05; odds ratio (OR) 2.89 (95% CI 1.15, 7.28), P < 0.05]. DISH and low spine BMD were each associated with a higher vertebral fracture risk. The vertebral fracture risk was higher in men who had both DISH and severe DSN. DISH and endplate irregularities (EIs) were each associated with higher vertebral fracture risk. DISH, DSN and EIs define the intervertebral space dysfunction, which was associated with higher vertebral fracture risk [OR 3.99 (95% CI 1.45, 10.98), P < 0.01]. Intervertebral space dysfunction improved the vertebral fracture prediction (ΔAUC = +0.111, P < 0.05), mainly in men with higher spine BMD (>0.9 g/cm2; ΔAUC = +0.189, P < 0.001). DISH was not associated with the risk of non-vertebral fracture.

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.
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http://dx.doi.org/10.1093/rheumatology/keaa517DOI Listing
November 2020

Implementation, mechanisms of impact and key contextual factors involved in outcomes of the Modification of Diet, Exercise and Lifestyle (MODEL) randomised controlled trial in Australian adults: protocol for a mixed-method process evaluation.

BMJ Open 2020 11 11;10(11):e036395. Epub 2020 Nov 11.

School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.

Introduction: The Modification of Diet, Exercise and Lifestyle (MODEL) study aims to examine the impact of providing visualisation and pictorial representation of advanced structural vascular disease (abdominal aortic calcification), on 'healthful' improvements to diet and lifestyle. This paper reports the protocol for the process evaluation for the MODEL study.

Methods And Analysis: The overall aim of the process evaluation is to understand the processes that took place during participation in the MODEL study trial and which elements were effective or ineffective for influencing 'healthful' behavioural change, and possible ways of improvement to inform wider implementation strategies. A mixed-method approach will be employed with the use of structured questionnaires and semistructured in-depth interviews. All 200 participants enrolled in the trial will undertake the quantitative component of the study and maximum variation sampling will be used to select a subsample for the qualitative component. The sample size for the qualitative component will be determined based on analytical saturation. Interviews will be digitally recorded and transcribed verbatim. Qualitative data will be analysed thematically and reported according to the Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines.

Ethics And Dissemination: The MODEL study process evaluation has received approval from Edith Cowan University Human Research Ethics Committee (Project Number: 20513 HODGSON). Written informed consent will be obtained from all participants before they are included in the study. The study results will be shared with the individuals and institutions associated with this study as well as academic audiences through peer-reviewed publication and probable presentation at conferences.

Trial Registration Number: ACTRN12618001087246.
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http://dx.doi.org/10.1136/bmjopen-2019-036395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661373PMC
November 2020

Modification of diet, exercise and lifestyle (MODEL) study: a randomised controlled trial protocol.

BMJ Open 2020 11 11;10(11):e036366. Epub 2020 Nov 11.

School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.

Introduction: Most cardiovascular disease (CVD)-related events could be prevented or substantially delayed with improved diet and lifestyle. Providing information on structural vascular disease may improve CVD risk factor management, but its impact on lifestyle change remains unclear. This study aims to determine whether providing visualisation and pictorial representation of structural vascular disease (abdominal aortic calcification (AAC)) can result in healthful diet and lifestyle change.

Methods And Analysis: This study, including men and women aged 60-80 years, is a 12-week, two-arm, multisite randomised controlled trial. At baseline, all participants will have AAC assessed from a lateral spine image captured using a bone densitometer. Participants will then be randomised to receive their AAC results at baseline (intervention group) or a usual care control group that will receive their results at 12 weeks. All participants will receive information about routinely assessed CVD risk factors and standardised (video) diet and lifestyle advice with three simple goals: (1) increase fruit and vegetable (FV) intake by at least one serve per day, (2) improve other aspects of the diet and (3) reduce sitting time and increase physical activity. Clinical assessments will be performed at baseline and 12 weeks.

Outcomes: The primary outcome is a change in serum carotenoid concentrations as an objective measure of FV intake. The study design, procedures and treatment of data will adhere to Standard Protocol Items for Randomized Trials guidelines.

Ethics And Dissemination: Ethics approval for this study has been granted by the Edith Cowan University and the Deakin University Human Research Ethics Committees (Project Numbers: 20513 HODGSON and 2019-220, respectively). Results of this study will be published in peer-reviewed academic journals and presented in scientific meetings and conferences. Information regarding consent, confidentiality, access to data, ancillary and post-trial care and dissemination policy has been disclosed in the participant information form.

Trial Registration Number: Australian New Zealand Clinical Trial Registry (ACTRN12618001087246).
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http://dx.doi.org/10.1136/bmjopen-2019-036366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661361PMC
November 2020

Impact of Bone Fracture on Muscle Strength and Physical Performance-Narrative Review.

Authors:
Pawel Szulc

Curr Osteoporos Rep 2020 Dec 8;18(6):633-645. Epub 2020 Oct 8.

INSERM UMR 1033, University of Lyon, Hôpital Edouard Herriot, Lyon, France.

Purpose Of Review: Low muscle strength and poor physical performance are associated with high risk of fracture. Many studies assessed clinical and functional outcomes of fractures. Fewer studies analyzed the impact of fractures on muscle strength and physical performance.

Recent Findings: Vertebral fractures (especially multiple and severe ones) are associated with back pain, back-related disability, lower grip strength, lower strength of lower limbs, lower gait speed, and poor balance. Patients with hip fracture have slower gait and lower quadriceps strength. Non-vertebral fractures were associated with lower strength of the muscles adjacent to the fracture site (e.g., grip strength in the case of distal radius fracture, knee extensors in the case of patellar fracture) and poor physical function dependent on the muscles adjacent to the fracture site (e.g., limited range of motion of the shoulder in the case of humerus fracture, gait disturbances in the case of the ankle fracture). Individuals with a fracture experience a substantial deterioration of muscle strength and physical performance which exceeds that related to aging and is focused on the period close to the fracture occurrence. After fracture, muscle strength increased and physical performance improved. The rate of normalization depended partly on the therapeutic approach and on the rehabilitation program. A subgroup of patients, mainly the elderly, never returns to the pre-fracture level of physical performance. The permanent decline of physical function after fracture may be related to the limitation of movements due to pain, low physical activity, poor health before the fracture, and reduced efficacy of retraining after immobilization.
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http://dx.doi.org/10.1007/s11914-020-00623-1DOI Listing
December 2020

A Signature of Circulating miRNAs Associated With Fibrous Dysplasia of Bone: the mirDys Study.

J Bone Miner Res 2020 10 21;35(10):1881-1892. Epub 2020 Jul 21.

Department of Rheumatology, Edouard Herriot University Hospital, Lyon, France.

Fibrous dysplasia (FD) is a rare bone disease caused by activating mutations of GNAS encoding the Gsα protein, enhancing cyclic adenosine monophosphate (cAMP) production by overstimulation of adenylyl cyclase and impairing osteoblastic differentiation. The clinical presentation ranges from asymptomatic to polyostotic forms with severe disability, explained by the mosaic distribution of the GNAS mutation. Physicians have to deal with the gap of knowledge in FD pathogenesis, the absence of prognostic markers and the lack of specific treatment. The identification of specific biomarkers for FD is an important step to improve the clinical and therapeutic approaches. An epigenetic regulation driven by microRNAs (miRNAs), known as promising biomarkers in bone disease, could be involved in FD. We have sought circulating miRNAs that are differentially expressed in FD patients compared to controls and would reflect dysregulations of osteogenesis-related genes and bone disorder. The global miRNA profiling was performed using Next Generation Sequencing in patient serum collected from a discovery cohort of 20 patients (10 polyostotic and 10 monostotic) and 10 controls. From these, we selected 19 miRNAs for a miRNA validation phase from serum of 82 patients and 82 controls, using real-time qPCR. Discovery screening identified 111 miRNAs differentially expressed in patient serum, after adjusting for the false discovery rate (FDR). Among the 82 patients, 55% were polyostotic, and 73% were women with a mean age of 42 years. Six miRNAs (miR-25-3p, miR-93-5p, miR-182-5p, miR-324-5p, miR-363-3p, and miR-451a) were significantly overexpressed in serum, with FDR <0.05. The expression level of these six miRNAs was not associated with the FD severity. In conclusion, we identified a signature of circulating miRNAs associated with FD. These miRNAs are potential negative regulators of gene expression in bone cell progenitors, suggesting their activity in FD by interfering with osteoblastic and osteoclastic differentiation to impair bone mineralization and remodeling processes. © 2020 American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbmr.4111DOI Listing
October 2020

Reply to: "Increase in health care costs due to aorta calcification and low ABI in older men".

Atherosclerosis 2020 05 23;300:56-57. Epub 2020 Mar 23.

University of Minnesota, Minneapolis, MN, USA; Center for Care Delivery & Outcomes Research, VA Health Care System, Minneapolis, MN, USA.

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http://dx.doi.org/10.1016/j.atherosclerosis.2020.03.017DOI Listing
May 2020

Abdominal aortic calcification (AAC) and ankle-brachial index (ABI) predict health care costs and utilization in older men, independent of prevalent clinical cardiovascular disease and each other.

Atherosclerosis 2020 02 19;295:31-37. Epub 2020 Jan 19.

University of Minnesota, Minneapolis, MN, USA; Center for Care Delivery & Outcomes Research, VA Health Care System, Minneapolis, MN, USA.

Background And Aims: Abdominal aortic calcification (AAC) and low ankle-brachial index (ABI) are markers of multisite atherosclerosis. We sought to estimate their associations in older men with health care costs and utilization adjusted for each other, and after accounting for CVD risk factors and prevalent CVD diagnoses.

Methods: This was an observational cohort study of 2393 community-dwelling men (mean age 73.6 years) enrolled in the Osteoporotic Fractures in Men (MrOS) study and U.S. Medicare Fee for Service (FFS). AAC was scored on baseline lateral lumbar spine X-rays using a 24-point scale. ABI was measured as the lowest ratio of arm to right or left ankle blood pressure. Health care costs, hospital stays, and SNF stays were identified from Medicare FFS claims over 36 months following the baseline visit.

Results: Men with AAC score ≥9 (n = 519 [21.7% of analytic cohort]) had higher annualized total health care costs of $1473 (95% C.I. 293, 2654, 2017 U S. dollars) compared to those with AAC score 0-1, after multivariable adjustment. Men with ABI <0.90 (n = 154 [6.4% of analytic cohort]) had higher annualized total health care costs of $2705 (95% CI 634, 4776) compared to men with normal ABI (≥0.9 and < 1.4), after multivariable adjustment.

Conclusions: High levels of AAC and low ABI in older men are associated with higher subsequent health care costs, after accounting for clinical CVD risk factors, prevalent CVD diagnoses, and each other. Further investigations of whether preventing progression of peripheral vascular disease and calcification reduces subsequent health care costs are warranted.
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http://dx.doi.org/10.1016/j.atherosclerosis.2020.01.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026763PMC
February 2020

Serum periostin is associated with cancer mortality but not cancer risk in older home-dwelling men: A 8-year prospective analysis of the STRAMBO study.

Bone 2020 03 5;132:115184. Epub 2019 Dec 5.

INSERM UMR 1033, Lyon, France and Université de Lyon, Lyon, France.

Background: Periostin (POSTN) regulates multiple biological behaviors of tumor cells. We studied the association of serum POSTN with mortality in home-dwelling men.

Methods: POSTN was measured at baseline using immunoassay (USCN life science, China) in 815 home-dwelling men aged 60-87 followed-up for 8 years.

Results: In the entire cohort, higher serum POSTN was associated with higher all-cause mortality [Hazard Ratio (HR) = 1.30 per Standard Deviation (SD), 95% Confidence Interval (CI): 1.13-1.50, p < .001] after adjustment for potential confounders. In a similar model, cancer mortality (n = 69) increased with POSTN levels (HR = 1.44 per SD, 95%CI: 1.16-1.78, p < .001). Cardiovascular mortality (n = 55) and non-cardiovascular-non-cancer mortality (n = 44) was not associated with POSTN levels (p = .28 and p = .94 respectively). In 107 men with prevalent cancer, all-cause mortality (HR = 1.93 per SD, 95%CI: 1.30-2.87, p < .005) and cancer mortality (HR = 2.07 per SD, 95%CI: 1.23-3.47, p < .01) increased with the increasing POSTN concentrations. In 613 men with incident cancer, higher POSTN concentrations were associated with higher cancer mortality (HR = 1.40 per SD, 95%CI: 1.12-1.76, p < .005) but not with the risk of cancer (HR = 1.16 per SD, 95%CI: 0.89-1.46, p = .21).

Conclusions: Higher serum POSTN is associated with higher cancer mortality, but not with the cancer risk in older home-dwelling men.
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http://dx.doi.org/10.1016/j.bone.2019.115184DOI Listing
March 2020

Limited evidence of physical therapy on balance after stroke: A systematic review and meta-analysis.

PLoS One 2019 29;14(8):e0221700. Epub 2019 Aug 29.

Service de médecine physique et réadaptation, hôpital Henry Gabrielle, Hospices Civils de Lyon, Saint-Genis-Laval, France.

Background: Stroke results in balance disorders and these directly affect autonomy and quality of life. The purpose of this systematic review and meta-analysis was to determine the efficacy of physical therapy (PT) on balance and postural control after stroke.

Methods: We included all randomized controlled trials assessing the efficacy of PT on balance and postural control in adult patients after stroke without language restriction. Medline, Embase/Scopus, Cochrane Central Register of Controlled Trials, PEDro, Pascal, and Francis databases were searched until January 2019. Primary outcomes were balance (Berg Balance scale and Postural Assessment Scale for Stroke) and postural control with postural deviation or stability measurement in sitting or standing static evaluation. A pair of independent reviewers selected studies, extracted data, and assessed risk of bias. Meta-analyses with subgroups (categories of PT, time post-stroke, and lesion location) and meta-regression (duration of PT) were conducted.

Results: A total of 145 studies (n = 5912) were selected from the 13,123 records identified. For balance, evidence was found in favor of the efficacy of functional task-training alone (standardized mean difference 0.39, 95% confidence interval [0.09; 0.68], heterogeneity I2 = 63%) or associated with musculoskeletal intervention and/or cardiopulmonary intervention (0.37, [0.19; 0.55], I2 = 48%), electrostimulation (0.91, [0.49; 1.34], I2 = 52%) immediately after intervention, compared to sham treatment or usual care (ST/UC). For postural deviation eyes open, assistive devices were more effective than no treatment (-0.21, [-0.37; -0.05], I2 = 0%) immediately after intervention; for postural stability eyes open, functional task-training and sensory interventions were more effective than ST/UC (0.97, [0.35; 1.59], I2 = 65% and 0.80, [0.46; 1.13], I2 = 37% respectively) immediately after intervention.

Conclusions: Functional task-training associated with musculoskeletal intervention and/or cardiopulmonary intervention and sensory interventions seem to be immediately effective in improving balance and postural stability, respectively. The heterogeneity of PT and the weak methodological quality of studies limited the interpretation and the confidence in findings.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0221700PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715189PMC
March 2020

Algorithm for the Use of Biochemical Markers of Bone Turnover in the Diagnosis, Assessment and Follow-Up of Treatment for Osteoporosis.

Adv Ther 2019 10 22;36(10):2811-2824. Epub 2019 Aug 22.

University of Liège, CHU de Liège, Liège, Belgium.

Introduction: Increased biochemical bone turnover markers (BTMs) measured in serum are associated with bone loss, increased fracture risk and poor treatment adherence, but their role in clinical practice is presently unclear. The aim of this consensus group report is to provide guidance to clinicians on how to use BTMs in patient evaluation in postmenopausal osteoporosis, in fracture risk prediction and in the monitoring of treatment efficacy and adherence to osteoporosis medication.

Methods: A working group with clinical scientists and osteoporosis specialists was invited by the Scientific Advisory Board of European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

Results: Serum bone formation marker PINP and resorption marker βCTX-I are the preferred markers for evaluating bone turnover in the clinical setting due to their specificity to bone, performance in clinical studies, wide use and relatively low analytical variability. BTMs cannot be used to diagnose osteoporosis because of low sensitivity and specificity, but can be of value in patient evaluation where high values may indicate the need to investigate some causes of secondary osteoporosis. Assessing serum levels of βCTX-I and PINP can improve fracture prediction slightly, with a gradient of risk of about 1.2 per SD increase in the bone marker in addition to clinical risk factors and bone mineral density. For an individual patient, BTMs are not useful in projecting bone loss or treatment efficacy, but it is recommended that serum PINP and βCTX-I be used to monitor adherence to oral bisphosphonate treatment. Suppression of the BTMs greater than the least significant change or to levels in the lower half of the reference interval in young and healthy premenopausal women is closely related to treatment adherence.

Conclusion: In conclusion, the currently available evidence indicates that the principal clinical utility of BTMs is for monitoring oral bisphosphonate therapy.
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http://dx.doi.org/10.1007/s12325-019-01063-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822833PMC
October 2019

Correction to: Is There Enough Evidence for Osteosarcopenic Obesity as a Distinct Entity? A Critical Literature Review.

Calcif Tissue Int 2019 Aug;105(2):125-126

WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Liège, Belgium.

The original version of this article unfortunately contained a mistake in one of the co-author's name. The co-author Cyrus Cooper's degree "FMedSci" was incorrectly tagged as family name. This has been corrected with this erratum.
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http://dx.doi.org/10.1007/s00223-019-00587-0DOI Listing
August 2019

Is There Enough Evidence for Osteosarcopenic Obesity as a Distinct Entity? A Critical Literature Review.

Calcif Tissue Int 2019 08 16;105(2):109-124. Epub 2019 May 16.

WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Liège, Belgium.

The co-existence of impaired bone health (osteopenia/osteoporosis), reduced muscle mass and strength (sarcopenia), and increased adiposity (obesity) in middle-aged and older people has been identified in recent studies, leading to a proposal for the existence of "osteosarcopenic obesity" as a distinct entity. Evidence for the pathophysiological overlap of these conditions is mounting, although a causal relationship is yet to be established. Each component condition occurs frequently with increasing age, and with shared risk factors in many instances, thus, an overlap of these three conditions is not surprising. However, whether the concurrent existence of sarcopenia, osteoporosis and obesity leads to an increased risk of adverse musculoskeletal outcomes and mortality above and beyond the risks associated with the sum of the component parts remains to be proven and is a question of research interest. In this article, we review evidence for the existence of osteosarcopenic obesity including the current operational definition of osteosarcopenic obesity, prevalence, pathophysiology, outcomes and exploratory approaches to the management of components. We conclude that, there is insufficient evidence to support a discrete clinical entity of osteosarcopenic obesity at this time. To expand knowledge and understanding in this area, there is a need for consensus on a definition of osteosarcopenic obesity which will allow for identification, further epidemiological studies and comparisons between studies. Additionally, studies should assess whether the clinical outcomes associated with osteosarcopenic obesity are worse than the mere addition of those linked with its components. This will help to determine whether defining a person as having this triad will eventually result in a more effective treatment than addressing each of the three conditions separately.
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http://dx.doi.org/10.1007/s00223-019-00561-wDOI Listing
August 2019

Selected serum microRNA, abdominal aortic calcification and risk of osteoporotic fracture.

PLoS One 2019 14;14(5):e0216947. Epub 2019 May 14.

Service de Rhumatologie et Pathologie Osseuse, Hôpital E Herriot, HCL, Lyon, France.

Context: MicroRNA (miRNA) regulate post-transcriptionally the expression of osteogenesis and angiogenesis associated genes and emerge as potential non-invasive biomarkers in vascular and bone diseases. Severe abdominal aortic calcification (AAC) is associated with higher risk of cardiovascular event and of fragility fracture.

Objective: To identify miRNA linked to the aggravation of AAC and to incident osteoporotic fracture.

Design: Postmenopausal women (>50 years) with available serum at inclusion and data for each outcome (Kauppila score and incident fracture) were selected from the OFELY prospective cohort. We conducted a case-control study in 434 age-matched women, 50% with incident osteoporotic fracture over 20 years of follow-up and a second study in 183 women to explore AAC over 17 years.

Methods: Serum expression of three miRNA involved in vascular calcification and bone turnover regulation (miRs-26a-5p,-34a-5p, and -223-5p) was quantified at baseline by TaqMan Advanced miRNA technology and expressed by relative quantification. Outcomes were the association of miRNA levels with (1) incident osteoporotic fractures during 20 years, (2) AAC aggravation during 17 years.

Results: MiRNA level was not associated with incident fractures (miR-26a-5p: 1.06 vs 0.99, p = 0.07; miR-34a-5p: 1.15 vs 1.26, p = 0.35; miR-223a-5p: 1.01 vs 1.05, p = 0.32). 93 women had an increase in Kauppila score over 17 years while 90 did not. None of the miRNAs was associated with an aggravation in AAC (miR-26a-5p: 1.09 vs 1.10, p = 0.95; miR-34a-5p: 0.78 vs 0.73, p = 0.90; miR-223-5p: 0.97 vs 0.78, p = 0.11).

Conclusions: Circulating miR-26a-5p, -34a-5p and -223-5p are not significantly associated with incident fracture and AAC aggravation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0216947PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6516733PMC
January 2020

Relationship Between Sex Steroids and Deterioration of Bone Microarchitecture in Older Men: The Prospective STRAMBO Study.

J Bone Miner Res 2019 09 27;34(9):1562-1573. Epub 2019 Jun 27.

INSERM UMR 1033, University of Lyon, Hôpital Edouard Herriot, Lyon, France.

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.
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http://dx.doi.org/10.1002/jbmr.3746DOI Listing
September 2019

Abdominal aortic calcification, bone mineral density and fractures: a systematic review and meta-analysis protocol.

BMJ Open 2019 04 2;9(4):e026232. Epub 2019 Apr 2.

The University of Sydney, Centre for Kidney Research, School of Public Health, Sydney Medical School, Children's Hospital at Westmead, New South Wales, Australia.

Introduction: Abdominal aortic calcification (AAC) is associated with low bone mass and increased fracture risk. Two previous meta-analyses have investigated the association between AAC and fracture. However, these meta-analyses only identified articles until December 2016, undertook limited searches and did not explore potential sources of between-study heterogeneity. We aim to undertake a sensitive and comprehensive assessment of the relationship between AAC, bone mineral density (BMD) as well as prevalent and incident fractures.

Methods: We will search MEDLINE, EMBASE, Web of Science core collection and Google Scholar (top 200 articles sorted by relevance) from their inception to 1 June 2018. Reference lists of included studies and previous systematic reviews will be hand searched for additional eligible studies. Retrospective and prospective cohort studies (cross-sectional, case-control and longitudinal) reporting the association between AAC, BMD and fracture at any site will be included. At least two investigators will independently: (A) evaluate study eligibility and extract data, with a third investigator to adjudicate when discrepancies occur, (B) assess study quality by the Newcastle-Ottawa Scale for each cohort/study. The meta-analysis will be reported in adherence to the Meta-analysis of Observational Studies in Epidemiology criteria. AAC will be grouped as either: (1) AAC present or absent, (2) AAC categorised as 'low' (referent-lowest reported group) versus 'high' (all other groups) or (3) dose-response when AAC was assessed in ≥3 groups. Where primary event data were reported in individual studies, pooled risk differences and risk ratios with 95% CI will be calculated, from which, a summary estimate will be determined using DerSimonian-Laird random effects models. For the AAC and BMD pooled analyses, estimates will be expressed as standardised mean difference with 95% CI. We will examine the likelihood of publication bias and where possible, investigate potential reasons for between-study heterogeneity using subgroup analyses and meta-regression.

Ethics And Dissemination: The study will be submitted to a peer- reviewed journal and disseminated via research presentations.

Prospero Registration Number: CRD42018088019.
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http://dx.doi.org/10.1136/bmjopen-2018-026232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500258PMC
April 2019

Cortical and trabecular bone microarchitecture as an independent predictor of incident fracture risk in older women and men in the Bone Microarchitecture International Consortium (BoMIC): a prospective study.

Lancet Diabetes Endocrinol 2019 01 28;7(1):34-43. Epub 2018 Nov 28.

Geriatric Medicine and Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Background: Although areal bone mineral density (aBMD) assessed by dual-energy x-ray absorptiometry (DXA) is the clinical standard for determining fracture risk, most older adults who sustain a fracture have T scores greater than -2·5 and thus do not meet the clinical criteria for osteoporosis. Importantly, bone fragility is due to low BMD and deterioration in bone structure. We assessed whether indices of high-resolution peripheral quantitative CT (HR-pQCT) were associated with fracture risk independently of femoral neck aBMD and the Fracture Risk Assessment Tool (FRAX) score.

Methods: We assessed participants in eight cohorts from the USA (Framingham, Mayo Clinic), France (QUALYOR, STRAMBO, OFELY), Switzerland (GERICO), Canada (CaMos), and Sweden (MrOS). We used Cox proportional hazard ratios (HRs) to estimate the association between HR-pQCT bone indices (per 1 SD of deficit) and incident fracture, adjusting for age, sex, height, weight, and cohort, and then additionally for femoral neck DXA aBMD or FRAX.

Findings: 7254 individuals (66% women and 34% men) were assessed. Mean baseline age was 69 years (SD 9, range 40-96). Over a mean follow-up of 4·63 years (SD 2·41) years, 765 (11%) participants had incident fractures, of whom 633 (86%) had femoral neck T scores greater than -2·5. After adjustment for age, sex, cohort, height, and weight, peripheral skeleton failure load had the greatest association with risk of fracture: tibia HR 2·40 (95% CI 1·98-2·91) and radius 2·13 (1·77-2·56) per 1 SD decrease. HRs for other bone indices ranged from 1·12 (95% CI 1·03-1·23) per 1 SD increase in tibia cortical porosity to 1·58 (1·45-1·72) per 1 SD decrease in radius trabecular volumetric bone density. After further adjustment for femoral neck aBMD or FRAX score, the associations were reduced but remained significant for most bone parameters. A model including cortical volumetric bone density, trabecular number, and trabecular thickness at the distal radius and a model including these indices plus cortical area at the tibia were the best predictors of fracture.

Interpretation: HR-pQCT indices and failure load improved prediction of fracture beyond femoral neck aBMD or FRAX scores alone. Our findings from a large international cohort of men and women support previous reports that deficits in trabecular and cortical bone density and structure independently contribute to fracture risk. These measurements and morphological assessment of the peripheral skeleton might improve identification of people at the highest risk of fracture.

Funding: National Institutes of Health National Institute of Arthritis Musculoskeletal and Skin Diseases.
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http://dx.doi.org/10.1016/S2213-8587(18)30308-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354581PMC
January 2019

Bone turnover: Biology and assessment tools.

Authors:
Pawel Szulc

Best Pract Res Clin Endocrinol Metab 2018 10 26;32(5):725-738. Epub 2018 May 26.

INSERM UMR 1033, University of Lyon, Hôpital Edouard Herriot, Place d'Arsonval, 69437, Lyon, France. Electronic address:

Bone turnover includes two processes: resorption (removal of old bone) and formation (laying down of new bone). N-terminal propeptide of type I procollagen (PINP) and C-telopeptide of type I collagen (CTX-I) are markers of bone formation and resorption, respectively, that the International Osteoporosis Foundation and the International Federation of Clinical Chemistry recommend for clinical use. Bone turnover markers (BTM) are subject to sources of variability, including feeding (lower resorption) and recent fracture (increased levels of all markers). Controllable patient-related factors should be adapted as much as possible (eg blood collection after an overnight fast) to minimize pre-analytical variability. Uncontrollable factors should be considered in the interpretation of the BTM measurements. BTM do not improve prediction of bone loss or fracture within an individual. In osteoporotic patients, BTM may help to assess the response to anabolic and antiresorptive therapies, to assess compliance to the treatment, or to indicate possible secondary causes of osteoporosis. BTM reflect changes in bone metabolism induced by anti-osteoporotic treatment. Anti-resorptive drugs induce a rapid dose-dependent decrease in bone resorption, whereas bone formation stimulating medications increase the levels of bone formations markers. BTM may be used for monitoring anti-osteoporosis therapy. The expected effect during the anti-resorptive therapy is to decrease the PINP by at least 10 ng/mL and to attain the target level of less than 35 ng/mL. The expected effect during the bone formation-stimulating therapy is to increase the PINP by at least 10 ng/mL and to attain the target level of more than 69 ng/mL.
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http://dx.doi.org/10.1016/j.beem.2018.05.003DOI Listing
October 2018

Broken hearts and bones: new insights or falling for unmeasured confounding?

Heart 2019 03 25;105(6):427-428. Epub 2018 Oct 25.

INSERM UMR 1033, University of Lyon, Hospices Civils de Lyon, Lyon, France.

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http://dx.doi.org/10.1136/heartjnl-2018-314099DOI Listing
March 2019

Positive Association of High Leptin Level and Abdominal Aortic Calcification in Men - The Prospective MINOS Study.

Circ J 2018 11 3;82(12):2954-2961. Epub 2018 Oct 3.

Department of Rheumatology, Medical Faculty, Pasteur Hospital, Nice University Hospital, Université Nice Sophia Antipolis.

Background: Severe abdominal aortic calcification (AAC) points to high cardiovascular risk and leptin stimulates arterial calcification; however, clinical data on their association are scarce. We studied the link between serum leptin and AAC severity and progression, and the effect of smoking and lipid levels, on this association in men. Methods and Results: At baseline, 548 community-dwelling men aged 50-85 years underwent blood collection and lateral lumbar spine radiography. In 448 men, X-ray was repeated after 3 and 7.5 years. AAC was assessed using Kauppila's semiquantitative score. In multivariable models, high leptin was associated with higher odds of severe AAC (odds ratio [OR]=1.71 per SD, 95% confidence interval [CI]: 1.22-2.40). The odds of severe AAC were the highest in men who had elevated leptin levels and either were ever-smokers (OR=9.22, 95% CI: 3.43-24.78) or had hypertriglyceridemia (vs. men without these characteristics). Higher leptin was associated with greater AAC progression (OR=1.34 per SD, 95% CI: 1.04-1.74). The risk of AAC progression was the highest in men who had elevated leptin levels and either were current smokers or had high low-density lipoprotein-cholesterol levels (OR=5.91, 95% CI: 2.46-14.16 vs. men without these characteristics). These links remained significant after adjustment for baseline AAC and in subgroups defined according to smoking and low-density lipoprotein-cholesterol levels.

Conclusions: In older men, high leptin levels are associated with greater severity and rapid progression of AAC independent of smoking, low-density lipoprotein-cholesterol or triglycerides.
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http://dx.doi.org/10.1253/circj.CJ-18-0517DOI Listing
November 2018

Long term prognosis of Scheuermann's disease: The association with fragility fracture - The MINOS cohort.

Bone 2018 12 20;117:116-122. Epub 2018 Sep 20.

INSERM UMR 1033, University of Lyon, Lyon, France. Electronic address:

The aim was to assess the association of Scheuermann's disease (SCD) with fracture risk (vertebral, peripheral) and bone mineral density (BMD) in older men. SCD was assessed on the baseline lateral spine radiographs using the Berlin criteria in 766 men aged 50-85. We evaluated the association of SCD and its diagnostic criteria with incident fracture (vertebral over 7.5 years, peripheral over 10 years) and BMD (baseline). SCD prevalence was 25.2%. SCD and its criteria showed inconsistent associations with BMD at different skeletal sites. Eighty-four men had incident fractures. After adjustment for age, weight, spine BMD, prevalent vertebral fractures, prior falls and score of disc space narrowing due to osteoarthritis (DSN-OA), SCD was not associated with vertebral fracture risk. Vertebral endplate irregularities (EI), one of its diagnostic criteria, were associated with higher vertebral fracture risk (OR = 3.26, 95% CI: 1.34-7.94, p < 0.01). Vertebral fracture risk was higher in men with EI and low spine BMD vs. men without these characteristics (OR = 12.84, 95% CI: 3.12-52.83, p < 0.005). EI was associated with higher vertebral fracture risk in men without severe DSN-OA and without prevalent vertebral fractures. Peripheral fracture risk was lower in men with SCD (HR = 0.39, 95% CI: 0.18-0.83, p < 0.02) and EI. Peripheral fracture risk was higher in men without SCD who had low femoral neck BMD vs. men with SCD and normal BMD (HR = 4.68, 95% CI: 1.09-20.03, p < 0.05). In conclusion, EI were associated with high vertebral fracture risk. SCD and EI were associated with lower peripheral fracture risk. The associations of SCD and its criteria with BMD were inconsistent.
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http://dx.doi.org/10.1016/j.bone.2018.09.016DOI Listing
December 2018

Use of CTX-I and PINP as bone turnover markers: National Bone Health Alliance recommendations to standardize sample handling and patient preparation to reduce pre-analytical variability.

Ann Biol Clin (Paris) 2018 Aug;76(4):373-391

ETL Consulting, Seattle, WA 98177, USA, Pacific Biomarkers, Seattle, WA 98119, USA.

The International osteoporosis foundation and the International federation of clinical chemistry (IFCC) Bone marker standards working group have identified N-terminal propeptide of type I procollagen (PINP) and C-terminal telopeptide of type I collagen (CTX-I) in blood to be the reference markers of bone turnover for the fracture risk prediction and monitoring of osteoporosis treatment. Although used in clinical research for many years, bone turnover markers (BTM) have not been widely adopted in clinical practice primarily due to their poor within-subject and between-lab reproducibility. The NBHA bone turnover marker project team aim to reduce pre-analytical variability of CTX-I and PINP measurements through standardized sample handling and patient preparation. Recommendations for sample handling and patient preparations were made based on review of available publications and pragmatic considerations to reduce pre-analytical variability. Controllable and un-controllable patient-related factors were reviewed to facilitate interpretation and sample collection. Samples for CTX-I must be collected consistently in the morning hours in the fasted state. EDTA plasma is preferred for CTX-I for its greater sample stability. Sample collection conditions for PINP are less critical as PINP has minimal circadian variability and is not affected by food intake. Sample stability limits should be observed. The uncontrollable aspects (age, sex, pregnancy, immobility, recent fracture, co-morbidities, anti-osteoporotic drugs, other medications) should be considered in BTM interpretation. Adopting standardized sample handling and patient preparation procedures will significantly reduce controllable pre-analytical variability. The successful adoption of such recommendations necessitates the close collaboration of various stakeholders at the global stage, including the laboratories, the medical community, the reagent manufacturers and the regulatory agencies.
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http://dx.doi.org/10.1684/abc.2018.1363DOI Listing
August 2018

Osteoporotic Vertebral Fracture Prevalence Varies Widely: Reply Letter to the Editor.

Authors:
Pawel Szulc

J Bone Miner Res 2018 08 20;33(8):1548-1549. Epub 2018 Jul 20.

INSERM UMR 1033, University of Lyon, Hôpital Edouard Herriot, Lyon, France.

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http://dx.doi.org/10.1002/jbmr.3542DOI Listing
August 2018

Low Muscle Strength and Mass Is Associated With the Accelerated Decline of Bone Microarchitecture at the Distal Radius in Older Men: the Prospective STRAMBO Study.

J Bone Miner Res 2018 09 7;33(9):1630-1640. Epub 2018 Jun 7.

INSERM UMR 1033, University of Lyon, Hôpital Edouard Herriot, Lyon, France.

Low muscle mass and strength are associated with poor bone microarchitecture. We studied the association of muscle mass and strength with changes in bone microarchitecture of distal radius in 821 older men during an 8-year prospective follow-up. Bone microarchitecture was assessed by high resolution peripheral quantitative computed tomography (XtremeCT-1, Scanco) at baseline, then after 4 and 8 years. Relative appendicular lean mass of the upper limbs (RALM-u.l.) was calculated as DXA-measured lean mass of upper limbs divided by (height) . Relative grip strength was calculated as grip strength divided by height. Decrease in bone mineral content (BMC), total volumetric bone mineral density (Tt.vBMD), cortical thickness (Ct.Th), cortical area (Ct.Ar) and cortical vBMD (Ct.vBMD) accelerated with age. Trabecular area (Tb.Ar) expansion and trabecular bone deterioration accelerated with age. Men in the first RALM-u.l. quartile had more rapid loss of BMC, Tt.vBMD, Ct.Th, Ct.vBMD and Ct.Ar vs. the highest quartile. They had more rapid increase in Tb.Ar. Men in the lowest quartile of grip strength had greater decrease in BMC, Tt.vBMD, Ct.Th, Ct.vBMD, Ct.Ar, and greater increase in Tb.Ar vs. the highest quartile. In the models including ALM-u.l. and grip strength (not corrected for height), both muscle-related variables were associated with more rapid bone microarchitectural deterioration (slightly more so for grip strength). Trabecular vBMD (Tb.vBMD) and Central.Tb.vBMD increased in men having higher muscle mass and strength. Trends in trabecular number and thickness did not differ across the groups in all the analyses. Thus, in men, aging-related deterioration of bone microarchitecture was most rapid after the age of 80. Low grip strength (and slightly more weakly low RALM-u.l.) is associated with the more rapid decrease in Tt.vBMD and cortical variables, and with greater Tb.Ar expansion. In conclusion, dynapenia and sarcopenia contribute to the deterioration of bone microarchitecture in older men. © 2018 American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbmr.3456DOI Listing
September 2018

Prediction of Fractures in Men Using Bone Microarchitectural Parameters Assessed by High-Resolution Peripheral Quantitative Computed Tomography-The Prospective STRAMBO Study.

J Bone Miner Res 2018 08 22;33(8):1470-1479. Epub 2018 May 22.

INSERM UMR 1033, University of Lyon, Hospices Civils de Lyon, Lyon, France.

Areal bone mineral density (aBMD) poorly identifies men at high fracture risk. Our aim was to assess prediction of fractures in men by bone microarchitectural measures. At baseline, 825 men aged 60 to 87 years had the assessment of bone microarchitecture at distal radius and distal tibia by high-resolution peripheral QCT (HR-pQCT; XtremeCT-I, Scanco Medical, Brüttisellen, Switzerland). Bone strength was estimated by micro-finite element analysis. During the prospective 8-year follow-up, 105 men sustained fractures (59 vertebral fractures in 49 men and 70 nonvertebral fractures in 68 men). After adjustment for age, body mass index (BMI), prior falls, and fractures, most HR-pQCT measures at both skeletal sites predicted fractures. After further adjustment for aBMD, low distal radius trabecular number (Tb.N) was most strongly associated with higher fracture risk (hazard ratio [HR] = 1.63 per SD, 95% confidence interval [CI] 1.31-2.03, p < 0.001). In similar models, low Tb.N was associated with higher risk of major osteoporotic fracture (HR = 1.80 per SD, p < 0.001), vertebral fracture (HR = 1.78 per SD, p < 0.01) and nonvertebral fracture (HR = 1.46 per SD, p < 0.01). In comparison with the reference model (age, BMI, falls, fractures, aBMD), the adjustment for distal radius Tb.N increased the estimated fracture probability in men who sustained fractures versus those who did not have ones (difference = 4.1%, 95% CI 1.9-6.3%, p < 0.001). However, the adjustment for distal radius Tb.N did not increase the area under the curve (AUC, p = 0.37). Similar results were found for distal radius trabecular separation (Tb.Sp) and connectivity density (Conn. D). They were predictive of all fracture types and increased the estimated fracture risk, but not AUC, in men who had incident fractures. Thus, poor distal radius trabecular microarchitecture is predictive of fracture after adjustment for age, BMI, falls, fractures, and aBMD. Although distal radius Tb.N, Conn. D, and Tb.Sp improve the discrimination between men who will or who will not have fracture, they do not provide clinically relevant improvement of fracture prediction in older men. © 2018 American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbmr.3451DOI Listing
August 2018