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

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

Long-term effect of denosumab on bone microarchitecture as assessed by tissue thickness-adjusted trabecular bone score in postmenopausal women with osteoporosis: results from FREEDOM and its open-label extension.

In postmenopausal women with osteoporosis, up to 10 years of denosumab treatment significantly and continuously improved bone microarchitecture assessed by tissue thickness-adjusted trabecular bone score, independently of bone mineral density. Long-term denosumab treatment decreased the number of high fracture-risk patients and shifted more patients to lower fracture-risk categories. PURPOSE: To investigate the long-term effect of denosumab on bone microarchitecture assessed by tissue thickness-adjusted trabecular bone score (TBSTT) in post-hoc subgroup analysis of FREEDOM and open-label extension (OLE). METHODS: Postmenopausal women with lumbar spine (LS) or total hip BMD T-score <-2.5 and ≥-4.0 who completed the FREEDOM DXA substudy and continued in OLE were included. Patients received either denosumab 60 mg subcutaneously every 6 months for 3 years and same-dose open-label denosumab for 7 years (long-term denosumab; n=150) or placebo for 3 years and open-label denosumab for 7 years (crossover denosumab; n=129). BMD and TBSTT were assessed on LS DXA scans at FREEDOM baseline, month 1, and years 1-6, 8, and 10. RESULTS: In long-term denosumab group, continued increases from baseline to years 4, 5, 6, 8, and 10 in BMD (11.6%, 13.7%, 15.5%, 18.5%, and 22.4%) and TBSTT (3.2%, 2.9%, 4.1%, 3.6%, and 4.7%) were observed (all P < 0.0001). Long-term denosumab treatment decreased the proportion of patients at high fracture-risk (according to TBSTT and BMD T-score) from baseline up to year 10 (93.7 to 40.4%), resulting in increases in the proportions at medium-risk (6.3 to 53.9%) and low-risk (0 to 5.7%) (P < 0.0001). Similar responses were observed in crossover denosumab group. Changes in BMD and TBSTT were poorly correlated during denosumab treatment. CONCLUSION: In postmenopausal women with osteoporosis, up to 10 years of denosumab significantly and continuously improved bone microarchitecture assessed by TBSTT, independently of BMD, and shifted more patients to lower fracture-risk categories.

Bone density and trabecular bone score to predict fractures in adults aged 20-39 years: a registry-based study.

Trabecular bone score (TBS) enhances fracture risk assessment in older adults; whether this is true in younger people is uncertain. In this registry-based study of adults aged 20-39 years, low BMD, but not low TBS, predicted fracture. PURPOSE: Trabecular bone score (TBS), a bone texture measurement, is associated with fracture risk independent of bone mineral density (BMD) in older adults. In adults aged 20-40 years, TBS remains stable and its role in fracture risk assessment is unclear. We utilized the Manitoba Bone Density Registry to explore the relationship of fracture risk with BMD and TBS in younger adults. METHODS: Women and men aged 20-39 years referred for DXA testing were studied. Incident major and any fractures were captured from health records. Categories based on WHO BMD T-score classification and TBS tertile were considered using Cox regression models to estimate covariate-adjusted (including sex) hazard ratios (aHR, 95%CI) for incident fracture by category, and each SD decrement in BMD and TBS. RESULTS: The study included 2799 individuals (77% female, mean age 32 years). Mean (SD) minimum T-score was - 0.9 (1.1) and TBS 1.355 (0.114); 7% had osteoporosis and 13% were in the lowest TBS tertile. Incident major osteoporotic fracture (MOF) and any fracture risk was elevated in those with osteopenia (aHRs 1.20/1.45) and osteoporosis (aHRs 4.60/5.16). Fracture risk was unrelated to TBS tertile. Each SD decrement in BMD was associated with increased MOF risk (aHR 1.64) and any fracture (aHR 1.71); lower TBS was unrelated to fractures. CONCLUSION: In young adults, low BMD, but not low TBS, was predictive of MOF and any fracture. Routine clinical TBS measurement is not recommended for young adults. Further study is indicated to evaluate whether TBS is beneficial in subsets of younger adults.

Heel quantitative ultrasound (QUS) predicts incident fractures independently of trabecular bone score (TBS), bone mineral density (BMD), and FRAX: the OsteoLaus Study.

This study aimed to better define the role of heel-QUS in fracture prediction. Our results showed that heel-QUS predicts fracture independently of FRAX, BMD, and TBS. This corroborates its use as a case finding/pre-screening tool in osteoporosis management. INTRODUCTION: Quantitative ultrasound (QUS) characterizes bone tissue based on the speed of sound (SOS) and broadband ultrasound attenuation (BUA). Heel-QUS predicts osteoporotic fractures independently of clinical risk factors (CRFs) and bone mineral density (BMD). We aimed to investigate whether (1) heel-QUS parameters predict major osteoporotic fractures (MOF) independently of the trabecular bone score (TBS) and (2) the change of heel-QUS parameters over 2.5 years is associated with fracture risk. METHODS: One thousand three hundred forty-five postmenopausal women from the OsteoLaus cohort were followed up for 7 years. Heel-QUS (SOS, BUA, and stiffness index (SI)), DXA (BMD and TBS), and MOF were assessed every 2.5 years. Pearson's correlation and multivariable regression analyses were used to determine associations between QUS and DXA parameters and fracture incidence. RESULTS: During a mean follow-up of 6.7 years, 200 MOF were recorded. Fractured women were older, more treated with anti-osteoporosis medication; had lower QUS, BMD, and TBS; higher FRAX-CRF risk; and more prevalent fractures. TBS was significantly correlated with SOS (0.409) and SI (0.472). A decrease of one SD in SI, BUA or SOS increased the MOF risk by (OR(95%CI)) 1.43 (1.18-1.75), 1.19 (0.99-1.43), and 1.52 (1.26-1.84), respectively, after adjustment for FRAX-CRF, treatment, BMD, and TBS. We found no association between the change of QUS parameters in 2.5 years and incident MOF. CONCLUSION: Heel-QUS predicts fracture independently of FRAX, BMD, and TBS. Thus, QUS represents an important case finding/pre-screening tool in osteoporosis management. The change in QUS over time was not associated with future fractures, making it inappropriate for patient monitoring.

Trabecular Bone Score (TBS) Cross-Calibration for GE Prodigy and IDXA Scanners.

Dual-energy X-ray absorptiometry (DXA) is used for osteoporosis diagnosis, fracture prediction and to monitor changes in bone mineral density (BMD). Change in DXA instrumentation requires formal cross-calibration and procedures have been described by the International Society for Clinical Densitometry. Whether procedures used for BMD cross-calibration are sufficient to ensure lumbar spine trabecular bone score (TBS) cross-calibration is currently uncertain. The Manitoba Bone Density Program underwent a program-wide upgrade in DXA instrumentation from GE Prodigy to iDXA in 2012, and a representative a sample of 108 clinic patients were scanned on both instruments. Lumbar spine TBS (L1-L4) measurements were retrospectively derived in 2013. TBS calibration phantoms were not available at our site when this was performed. We found excellent agreement for lumbar spine BMD, without deviation from the line of perfect agreement, and low random error (standard error of the estimate [SEE] 2.54% of the mean). In contrast, spine TBS (L1-L4) showed significant deviation from the line of identity: TBS(iDXA) = 0.730 x TBS(Prodigy) + 0.372 (p<0.001 for slope and intercept); SEE 5.12% of the mean with negative bias (r=-0.550). Results were worse for scans acquired in thick versus standard mode, but similar when the population was stratified as BMI < or > 35 kg/m2. In summary, it cannot be assumed that just because BMD cross-calibration is good that this applies to TBS. This supports the need for using TBS phantom calibration to accommodate between-scanner differences as part of the manufacturer's TBS software installation.

Ethnicity and Fracture Risk Stratification from Trabecular Bone Score in Canadian Women: The Manitoba BMD Registry.

Lumbar spine Trabecular Bone Score (TBS), a grey-level texture measure derived from spine dual-energy x-ray absorptiometry (DXA) images, is a bone mineral density (BMD)-independent risk factor for fracture. An unresolved and controversial question is whether there are ethnic differences that affect the utility of TBS for fracture risk assessment. The current analysis examined whether self-identified ethnicity (White, Asian, Black) in women age 40 years and older referred for DXA testing affected fracture risk stratification from TBS using a large clinical registry. The study population comprised 63,078 White women, 1,915 Asian women and 329 Black women (n=329) with mean follow up 9.0±5.2 years. There were between group differences in BMI (Black>White>Asian), lumbar spine fat percentage (Asian>White>Black) and lumbar spine tissue thickness (Black>White>Asian). Despite this, lumbar spine TBS was not significantly different between the subgroups, though there was a significant difference in lumbar spine and total hip BMD (Black >White>Asian). TBS provided significant stratification for MOF and any fracture for all ethnicity subgroups, and for hip fracture in White and Asian subgroups (insufficient numbers for analysis in Black women). No significant difference in White vs. Asian or White vs. Black women were identified using a Bonferroni adjusted p-value. In summary, we found that lumbar spine TBS measurements were similar among White, Asian and Black women referred for DXA assessment in Manitoba, Canada. TBS and BMD measurements significantly stratified fracture risk in all three populations without a meaningful difference between groups. This suggests that TBS does not need to be used differently in White vs. non-White populations.

Fracture Prediction from Trabecular Bone Score is Unaffected by Anti-Resorptive Treatment: A Registry-Based Cohort Study.

Trabecular bone score (TBS) predicts osteoporotic fractures independent of bone mineral density (BMD) and clinical risk factors. The aim of this study was to explore whether anti-resorptive treatment affects fracture risk prediction from TBS using a large clinical registry that includes all dual-energy X-ray absorptiometry (DXA) tests for the Province of Manitoba, Canada. Cohort 1 included 53,863 individuals aged ≥ 40 years (11.4% men; mean age 64.1 years) who had not received any anti-resorptive therapy in the year prior the baseline DXA. Cohort 2 comprised 22,917 individuals aged ≥ 40 years (6% men, mean age 66.7 years) undergoing a second DXA visit. Anti-resorptive medication was initiated in the first year after DXA in 13,439 (25%) individuals from Cohort 1 (87.9% bisphosphonates); among Cohort 2 8,864 (38.7%) had received anti-resorptive medication in the year before DXA (77.8% bisphosphonates). Incident major osteoporotic fracture (MOF), hip fracture and any fracture were identified over mean follow up 8.6 and 7.0 years for Cohorts 1 and 2, respectively. Area under the curve showed significant risk stratification for all fracture types and treatment levels, whether treatment was initiated after TBS measurement (Cohort 1) or prior to TBS measurement (Cohort 2). In Cox regression models, without and with covariate adjustment, fracture prediction from TBS was unaffected by anti-resorptive medication use (p-interaction >0.5 for all analyses). In conclusion, TBS was a robust predictor of fracture in models adjusted for clinical risk factors and BMD. The use of anti-resorptive therapy, either in the year before or following TBS measurement, did not attenuate fracture risk prediction by TBS compared to untreated individuals.

Effects of Severe Lumbar Spine Structural Artifact on Trabecular Bone Score (TBS): The Manitoba BMD Registry.

Trabecular bone score (TBS) is a bone mineral density (BMD)-independent risk factor for fracture. During DXA analysis and BMD reporting, it is standard practice to exclude lumbar vertebral levels affected by structural artifact. Although TBS is relatively insensitive to degenerative artifact, it is uncertain whether TBS is still useful in the presence extreme structural artifact that precludes reliable spine BMD measurement even after vertebral exclusions. Among individuals aged 40 years and older undergoing baseline DXA assessment from September 2012 to March 2018 we identified three mutually exclusive groups: spine BMD reporting performed without exclusions (Group 1, N=12,865), spine BMD reporting performed with vertebral exclusions (Group 2, N=4867), and spine BMD reporting not performed due to severe structural artifact (Group 3, N=1541). No significant TBS difference was seen for Group 2 versus Group 1 (referent), whereas TBS was significantly greater in Group 3 (+0.041 partially adjusted, +0.043 fully adjusted). When analyzed by the reason for vertebral exclusion, multilevel degenerative changes significantly increased TBS (+0.041 partially adjusted, +0.042 fully adjusted), while instrumentation significantly reduced TBS (-0.059 partially adjusted, -0.051 fully adjusted). Similar results were seen when analyses were restricted to those in Group 3 with a single reason for vertebral exclusions, and when follow up scans were also included. During mean follow-up of 2.5 years there were 802 (4.2 %) individuals with one or more incident fractures. L1-L4 TBS showed significant fracture risk stratification in all groups including Group 3 (P-interaction >0.4). In conclusion, lumbar spine TBS can be reliably measured in the majority of lumbar spine DXA scans, including those with artifact affecting up to two vertebral levels. However, TBS is significantly affected by the presence of extreme structural artifact in the lumbar spine, especially those with multilevel degenerative disc changes and/or instrumentation that precludes reliable BMD reporting.

Trabecular Bone Score Vertebral Exclusions Affect Risk Classification and Treatment Recommendations: The Manitoba Bmd Registry.

Lumbar spine trabecular bone score (TBS), a texture measure derived from spine dual-energy x-ray absorptiometry (DXA) images, is a bone mineral density (BMD)-independent risk factor for fracture. Lumbar vertebral levels that show structural artifact are excluded from BMD measurement. TBS is relatively unaffected by degenerative artifact, and it is uncertain whether the same exclusions should be applied to TBS reporting. To gain insight into the clinical impact of vertebral exclusion on TBS, we examined the effect of lumbar vertebral exclusions in routine clinical practice on tertile-based TBS categorization and TBS adjusted FRAX-based treatment recommendations. The study population consisted of 71,209 individuals aged 40 years and older with narrow fan-beam spine DXA examinations and retrospectively-derived TBS. During BMD reporting, 34.3% of the scans had one or more vertebral exclusions for structural artifact. When TBS was derived from the same vertebral levels used for BMD reporting, using fixed L1-L4 tertile cutoffs (1.23 and 1.31 from the McCloskey meta-analysis) reclassified 17.9% to a lower and 6.5% to a higher TBS category, with 75.6% unchanged. Reclassification was reduced from 24.4% overall to 17.2% when level-specific tertile cutoffs from the software manufacturer were used. Treatment reclassification based upon FRAX major osteoporotic fracture probability occurred in 2.9% overall, but in 9.6% of those with baseline risk ≥15%. For treatment based upon FRAX hip fracture probability, reclassification occurred in 3.4% overall, but in 10.4% in those with baseline risk ≥2%. In summary, lumbar spine TBS measurements based upon vertebral levels other than L1-L4 can alter the tertile category and treatment recommendations based upon TBS-adjusted FRAX calculation, especially for those close to or exceeding the treatment cut-off. Manufacturer level-specific tertile cut-offs should be used if vertebral exclusions are applied.

Vertebral Level Variations in Trabecular Bone Score and Effect on Fracture Prediction: The Manitoba BMD Registry.

Trabecular bone score (TBS), a texture measure derived from spine dual-energy x-ray absorptiometry (DXA) images, is a bone mineral density (BMD)-independent risk factor for fracture. TBS is reportedly insensitive to degenerative changes, and it is uncertain whether the same rules for excluding lumbar vertebral levels from BMD measurement should be applied to TBS. The current analysis was performed to explore inter-vertebral variation in TBS measurements from L1 to L4, how this relates to clinically identified structural artifact resulting in vertebral level exclusion from BMD reporting, and area under the curve (AUC) for incident fracture. The study population comprised 70,762 individuals aged 40 years and older at the time of baseline spine DXA assessment (mean age 64.1 years, 89.7% female), among whom 24,289 (34.3%) had one or more vertebral exclusions. Both TBS and BMD showed a similar cranial/caudal inter-vertebral gradient. Compared with L1-4, TBS from L1 alone was lower (mean difference -0.096; -7.6%) while TBS from L4 alone was 0.046 (3.6%) greater, similar in those without and with visual structural artifact. During mean follow-up of 8.7 years, 6744 (9.5%) individuals sustained incident major osteoporotic fractures. TBS from L1 alone gave significantly higher AUC for incident fracture than L1-4, which was in turn significantly higher than L2, L3 and L4 alone, seen in those without and with visual structural artifact. In contrast, AUCs for BMD showed minimal variation from L1 to L4, and was higher for L1-4 than for any individual lumbar vertebral level. In summary, we found inter-vertebral TBS variations within the lumbar spine are overall similar to BMD but are relatively unaffected by visual structural artifact. Fracture outcomes showed the strongest association with TBS measured from L1 alone. Further investigation is need to understand the cause and clinical application of these differences.

Adjusting Trabecular Bone Score (TBS) for Level-Specific Differences Reduces FRAX®-Based Treatment Reclassification in Patients with Vertebral Exclusions: The Manitoba BMD Registry.

Trabecular bone score (TBS) is a FRAX®-independent risk factor for fracture prediction. TBS values increase from cranial to caudal, with the following mean differences between TBSL1-L4 and individual lumbar vertebrae: L1 -0.093, L2 -0.008, L3 +0.055 and L4 +0.046. Excluding vertebral levels can affect FRAX-based treatment recommendations close to the intervention threshold. We examined the effect of adjusting for level-specific TBS differences in individuals with vertebral exclusions due to structural artifact on TBS-adjusted FRAX-based treatment recommendations. We identified 71,209 individuals aged ≥40 years with TBS and FRAX calculations through the Manitoba Bone Density Program. In the 24,428 individuals with vertebral exclusions, adjusting TBS using these level-specific factors agreed with TBSL1-L4 (mean difference -0.001). We compared FRAX-based treatment recommendations for TBSL1-L4 and for non-excluded vertebral levels before and after adjusting for level-specific TBS differences. Among those with baseline major osteoporotic fracture risk ≥15 %, TBS with vertebral exclusions reclassified FRAX-based treatment in 10.6 % of individuals compared with TBSL1-L4, and was reduced to 7.2 % after adjusting for level-specific differences. In 11,131 patients where L1-L2 was used for BMD reporting (the most common exclusion pattern with the largest TBS effect), treatment reclassification was reduced from 13.9 % to 2.4 %, respectively. Among individuals with baseline hip fracture risk ≥2 %, TBS vertebral exclusions reclassified 7.1 % compared with TBSL1-L4, but only 4.5 % after adjusting for level-specific differences. When L1-L2 was used for BMD reporting, treatment reclassification from hip fracture risk was reduced from 9.2 % to 5.2 %. In conclusion, TBS and TBS-adjusted FRAX-based treatment recommendations are affected by vertebral level exclusions for structural artifact. Adjusting for level-specific differences in TBS reduces reclassification in FRAX-based treatment recommendations.

FRAX® Adjustment Using Renormalized Trabecular Bone Score (TBS) from L1 Alone may be Optimal for Fracture Prediction: The Manitoba BMD Registry.

Lumbar spine trabecular bone score (TBS) used in conjunction with FRAX® improves 10-year fracture prediction. The derived FRAX risk adjustment is based upon TBS measured from L1-L4, designated TBSL1-L4-FRAX. In prior studies, TBS measurements that include L1 and exclude L4 give better fracture stratification than L1-L4. We compared risk stratification from TBS-adjusted FRAX using TBS derived from different combinations of upper lumbar vertebral levels renormalized for level-specific differences in individuals from the Manitoba Bone Density Program aged >40 years with baseline assessment of TBS and FRAX. TBS measurements for L1-L3, L1-L2 and L1 alone were calculated after renormalization for level-specific differences. Corresponding TBS-adjusted FRAX scores designated TBSL1-L3-FRAX, TBSL1-L2-FRAX and TBSL1-FRAX were compared with TBSL1-L4-FRAX for fracture risk stratification. Incident major osteoporotic fractures (MOF) and hip fractures were assessed. The primary outcome was incremental change in area under the curve (ΔAUC). The study population included 71,209 individuals (mean age 64 years, 89.8% female). Before renormalization, mean TBS for L1-3, L1-L2 and L1 was significantly lower and TBS-adjusted FRAX significantly higher than from using TBSL1-L4. These differences were largely eliminated when TBS was renormalized for level-specific differences. During mean follow-up of 8.7 years 6745 individuals sustained incident MOF and 2039 sustained incident hip fractures. Compared with TBSL1-L4-FRAX, use of FRAX without TBS was associated with lower stratification (ΔAUC = -0.009, p < 0.001). There was progressive improvement in MOF stratification using TBSL1-L3-FRAX (ΔAUC = +0.001, p < 0.001), TBSL1-L2-FRAX (ΔAUC = +0.004, p < 0.001) and TBSL1-FRAX (ΔAUC = +0.005, p < 0.001). TBSL1-FRAX was significantly better than all other combinations for MOF prediction (p < 0.001). Incremental improvement in AUC for hip fracture prediction showed a similar but smaller trend. In conclusion, this single large cohort study found that TBS-adjusted FRAX performance for fracture prediction was improved when limited to the upper lumbar vertebral levels and was best using L1 alone.

FRAX Adjustment by Trabecular Bone Score with or Without Bone Mineral Density: The Manitoba BMD Registry.

Trabecular bone score (TBS), a texture measure derived from spine dual-energy x-ray absorptiometry (DXA) images, is a FRAX®-independent risk factor for fracture. The TBS adjustment to FRAX assumes the presence of femoral neck BMD in the calculation. However, there are many individuals in whom hip DXA cannot be acquired. Whether the TBS-adjustment would apply to FRAX probabilities calculated without BMD has not been studied. The current analysis was performed to evaluate major osteoporotic fracture (MOF) and hip fracture risk adjusted for FRAX with and without femoral neck BMD. The study cohort consisted of 71,209 individuals (89.8% female, mean age 64.0 years). During mean follow-up 8.7 years, 6743 (9.5%) individuals sustained one or more incident MOF, of which 2037 (2.9%) sustained a hip fracture. Lower TBS was significantly associated with increased fracture risk when adjusted for FRAX probabilities, with a slightly larger effect when BMD was not included. Inclusion of TBS in the risk calculation gave a small but significant increase in stratification for fracture probabilities estimated with and without BMD. Calibration plots showed very minor deviations from the line of identity, indicating overall good calibration. In conclusion, the existing equations for incorporating TBS in FRAX estimates of fracture probability work similarly when femoral neck BMD is not used in the calculation. This potentially extends the range of situations where TBS can be used clinically to those individuals in whom lumbar spine TBS is available but femoral neck BMD is not available.

[Does artificial intelligence have a role in osteoporosis management?] / L'intelligence artificielle a-t-elle un rôle dans la prise en charge de l'ostéoporose ?

The individual and societal burden of osteoporosis is high and will continue to increase due to the demographic situation. Applications based on artificial intelligence models can provide concrete solutions at each step of the management of osteoporosis: screening, diagnostic, therapy management and prognostic assessment. The implementation of such models could assist clinicians in their workflow while improving overall patient care.

L'ostéoporose représente un fléau important, à l'échelle individuelle mais aussi sociétale. Avec le vieillissement de la population, le nombre de patients concernés augmente de manière considérable. Des applications basées sur des modèles d'intelligence artificielle nous apportent des solutions de plus en plus concrètes, à chaque étape de la prise en charge de l'ostéoporose : dépistage, diagnostic, prise en charge médicamenteuse et évaluation pronostique. L'implémentation de tels modèles pourrait aider les professionnels de santé, aussi bien dans l'optimisation du flux du travail que dans la prise en charge clinique du patient.

Effect of very large body mass loss on energetics, mechanics and efficiency of walking in adults with obesity: mass-driven versus behavioural adaptations.

Understanding the mechanisms involved in the higher energy cost of walking (NCw : the energy expenditure above resting per unit distance) in adults with obesity is pivotal to optimizing the use of walking in weight management programmes. Therefore, this study aimed to investigate the mechanics, energetics and mechanical efficiency of walking after a large body mass loss induced by bariatric surgery in individuals with obesity. Nine adults (39.5 ± 8.6 year; BMI: 42.7 ± 4.6 kg m-2 ) walked at five fixed speeds before (baseline) and after the bariatric surgery (post 1 and post 2). Gas exchanges were measured to obtain NCw . A motion analysis system and instrumented treadmill were combined to assess total mechanical work (Wtot ). Mechanical efficiency (Wtot NCw-1 ) was also calculated. Participants lost 25.7 ± 3.4% of their body mass at post 1 (6.6 months; P < 0.001) and 6.1 ± 4.9% more at post 2 (12 months; P = 0.014). Mass-normalized NCw was similar between baseline and post 1 and decreased at post 2 compared to that at baseline (-6.2 ± 2.7%) and post 1 (-8.1 ± 1.9%; P ≤ 0.007). No difference was found in mass-normalized Wtot during follow-up (P = 0.36). Mechanical efficiency was similar at post 1 and post 2 when compared to that at baseline (P ≥ 0.19), but it was higher (+14.1 ± 4.6%) at post 2 than at post 1 (P = 0.013). These findings showed that after a very large body mass loss, individuals with obesity may reorganize their walking pattern into a gait more similar to that of lean adults, thus decreasing their NCw by making their muscles work more efficiently. KEY POINTS: A higher net (above resting) energy cost of walking (lower gait economy) is observed in adults with obesity compared to lean individuals. Understanding the mechanisms (i.e. mass driven, gait pattern and behavioural changes) involved in this extra cost of walking in adults with obesity is pivotal to optimizing the use of walking to promote daily physical activity and improve health in these individuals. We found that very large weight loss induced by bariatric surgery significantly decreased the energy cost of walking per kg of body mass after 1 year with similar total mechanical work per kg of body mass, resulting in an increased mechanical efficiency of walking. Individuals with obesity may reorganize their walking pattern into a gait more similar to that of adults of normal body mass, thus decreasing their energy cost of walking by making their muscles work more efficiently.

Updated trabecular bone score accounting for the soft tissue thickness (TBSTT) demonstrated significantly improved bone microstructure with denosumab in the FREEDOM TBS post hoc analysis.

TBS algorithm has been updated to account for regional soft tissue noise. In postmenopausal women with osteoporosis, denosumab improved tissue thickness-adjusted TBS vs placebo independently of bone mineral density over 3 years, with the magnitude of changes from baseline or placebo numerically greater than body mass index-adjusted TBS. INTRODUCTION: To evaluate the effect of denosumab on bone microarchitecture assessed by trabecular bone score (TBS) in the FREEDOM study using the updated algorithm that accounts for regional soft tissue thickness (TBSTT) in dual-energy X-ray absorptiometry (DXA) images and to compare percent changes from baseline and placebo with classical body mass index (BMI)-adjusted TBS (TBSBMI). METHODS: Postmenopausal women with lumbar spine or total hip bone mineral density (BMD) T score < - 2.5 and ≥ - 4.0 received placebo or denosumab 60 mg subcutaneously every 6 months. TBSBMI and TBSTT were assessed on lumbar spine DXA scans at baseline and months 1, 12, 24, and 36 in a subset of 279 women (129 placebo, 150 denosumab) who completed the 3-year FREEDOM DXA substudy and rolled over to open-label extension study. RESULTS: Baseline characteristics were similar between groups. TBSTT in the denosumab group showed numerically greater changes from both baseline and placebo than TBSBMI at months 12, 24, and 36. Denosumab led to progressive increases in BMD (1.2, 5.6, 8.1, and 10.5%) and TBSTT (0.4, 2.3, 2.6, and 3.3%) from baseline to months 1, 12, 24, and 36, respectively. Both TBS changes were significant vs baseline and placebo from months 12 to 36 (p < 0.0001). As expected, BMD and TBSTT were poorly correlated both at baseline and for changes during treatment. CONCLUSION: In postmenopausal women with osteoporosis, denosumab significantly improved bone microstructure assessed by TBSTT over 3 years. TBSTT seemed more responsive to denosumab treatment than TBSBMI and was independent of BMD.

Bone Texture Assessment on Lateral VFAs Using the Texture Research Investigational Platform (TRIP) and its Fracture Discrimination Ability.

Texture Research Imaging Platform applies trabecular bone score (TBS) measurement principles to images acquired with multiple modalities to assess bone texture at various skeletal sites. This study aimed to assess the bone texture score in dual-energy X-ray absorptiometry-acquired lateral vertebral fracture assessment (VFA) images (BTSVFA), evaluate its reproducibility, and vertebral fracture discrimination ability. Subjects included 178 VF cases and 178 non-VF controls, 136 women and 42 men in each group, age 55-92 years, from two research centers. Cases and controls were matched for age (±5 years), body mass index (±5 kg/m2) and TBS. All participants underwent dual-energy X-ray absorptiometry TBS assessment from standard posterior-anterior lumbar spine scans and BTSVFA assessment. VF presence was determined using VFA images applying the Genant's method. BTSVFA was lower among fractured women compared to non-fractured (0.626 ± 0.109 vs 0.675 ± 0.099, p < 0.01), but not among men. In a binary logistic regression adjusted for study center and sex, for each SD lower BTSVFA, there was a 40% increase (OR 1.40, 95% CI (1.13-1.74)) in the risk of having a prevalent VF; area under the curve (95% CI) 0.616 (0.557-0.675). Inter-assessor and inter-centers ICCs for BTSVFA measurements were very good; 0.96 (0.64-0.99) and 0.98 (0.95-0.99), respectively. The BTSVFA precision (coefficient of variation) was 2.42%. This feasibility study demonstrates the potential to assess trabecular bone texture in lateral VFA images with good reproducibility. BTSVFA can discriminate between fractured and non-fractured women independent of their age, body mass index and TBS. In conclusion, BTSVFA, a potential trabecular texture assessment that excludes the posterior elements, may have value in fracture prediction or as a novel approach to be further investigated in spine surgery planning.

Quantitative Ultrasound (QUS) in the Management of Osteoporosis and Assessment of Fracture Risk: An Update.

Quantitative ultrasound (QUS) presents a low cost and readily available alternative to DXA measurements of bone mineral density (BMD) for osteoporotic fracture risk assessment. It is performed in a variety of skeletal sites, among which the most widely investigated and clinically used are first the calcaneus and then the radius. Nevertheless, there is still uncertainty in the incorporation of QUS in the clinical management of osteoporosis as the level of clinical validation differs substantially upon the QUS models available. In fact, results from a given QUS device can unlikely be extrapolated to another one, given the technological differences between QUS devices. The use of QUS in clinical routine to identify individuals at low or high risk of fracture could be considered primarily when central DXA is not easily available. In this later case, it is recommended that QUS bone parameters are used in combination with established clinical risk factors for fracture. Currently, stand-alone QUS is not recommended for treatment initiation decision making or follow-up. As WHO classification of osteoporosis thresholds cannot apply to QUS, thresholds specific for given QUS devices and parameters need to be determined and cross-validated widely to have a well-defined and certain use of QUS in osteoporosis clinical workflow. Despite the acknowledged current clinical limitations for QUS to be used more widely in daily routine, substantial progresses have been made and new results are promising.

Diurnal Salivary Cortisol in Sarcopenic Postmenopausal Women: The OsteoLaus Cohort.

Sarcopenia, similar to hypercortisolism, is characterized by loss of muscle mass and strength. Cortisol circadian rhythm changes with aging (blunted late-day nadir values) were suggested to contribute to this decline. We aimed to explore the relationship between diurnal salivary cortisol values and sarcopenia diagnosis and its components in postmenopausal women. This is a cross-sectional study within the OsteoLaus population-based cohort in Lausanne (Switzerland). Participants had a body composition assessment by dual X-ray absorptiometry (DXA), a grip strength (GS) measure, and salivary cortisol measures (at awakening, 30 min thereafter, 11 AM (sc-11AM) and 8 PM (sc-8PM)). Associations between salivary cortisol and sarcopenia diagnosed by six different criteria (based on appendicular lean mass (ALM) assessed by DXA, and muscle strength by GS), and its components, were analyzed. 471 women aged > 50 years (63.0 ± 7.5) were included. Various definitions identified different participants as sarcopenic, who consistently presented higher salivary cortisol at 11 AM and/or 8 PM. There were no associations between salivary cortisol levels and ALM measures, either absolute or after correction to height squared (ALM index) or body mass index. GS was inversely correlated to sc-11AM (r = - 0.153, p < 0.001) and sc-8PM (r = - 0.118, p = 0.002). Each 10 nmol/l increase of sc-11AM, respectively sc-8PM, was associated with a GS decrease of 1.758 (SE 0.472) kg, respectively 2.929 (SE 1.115) kg. In postmenopausal women, sarcopenia is associated with higher salivary cortisol levels at 11 AM and 8 PM. An increase of daily free cortisol levels in the physiological range could participate to sarcopenia development by decreasing muscle function in postmenopausal women.

[Towards an individualized bone health report focused on the patient - Bone parameters and treatment options]. / Vers un rapport de santé osseuse individualisé centré sur le patient - Les paramètres osseux et les possibilités de traite.

This article presents a novel approach of osteoporosis management, starting from the DXA scans performance, image quality, BMD and TBS assessment and interpretation, vertebral fracture assessment, decision making on treatment initiation and being finalized with patient`s further follow-up recommendations. A report based on this approach is soon to be implemented by the CiMO at CHUV. Among the thorough evaluation of the densitometric status of the patient, this report presents the first effort to incorporate into the osteoporosis clinical workflow the current evidence on TBS. It suggests practical ways to use TBS as in conjunction with BMD T-score or FRAX score to come up with the final scores that allow treatment initiation. Implementations in other non-Caucasian or non-Swiss clinical settings are to be accompanied by local validations.

Cet article présente une approche nouvelle de la prise en charge de l'ostéoporose, à partir de la performance des DXA, de la qualité de l'image, de l'interprétation combinée de la densité minérale osseuse et du TBS, de la recherche des fractures vertébrales, de la décision de traiter et des stratégies de suivi du patient. Un nouveau rapport densitométrique basé sur cette approche sera bientôt mis en fonction par le Centre interdisciplinaire des maladies osseuses du CHUV. Il présente le premier effort pour incorporer dans le flux de travail clinique de l'ostéoporose les toutes dernières avancées sur le TBS. Il suggère des moyens pratiques pour utiliser le TBS en conjonction avec le T-score de la DMO ou le FRAX pour obtenir les scores finaux en vue d'initier un traitement spécifique pour un profil de risque individuel donné. L'utilisation dans d'autres contextes cliniques non caucasiens/suisses devra être validée.