DS-MS-TCN: Otago Exercises Recognition with a Dual-Scale Multi-Stage Temporal Convolutional Network.

The Otago Exercise Program (OEP) represents a crucial rehabilitation initiative tailored for older adults, aimed at enhancing balance and strength. Despite previous efforts utilizing wearable sensors for OEP recognition, existing studies have exhibited limitations in terms of accuracy and robustness. This study addresses these limitations by employing a single waist-mounted Inertial Measurement Unit (IMU) to recognize OEP exercises among community-dwelling older adults in their daily lives. A cohort of 36 older adults participated in laboratory settings, supplemented by an additional 7 older adults recruited for at-home assessments. The study proposes a Dual-Scale Multi-Stage Temporal Convolutional Network (DS-MS-TCN) designed for two-level sequence-to-sequence classification, incorporating them in one loss function. In the first stage, the model focuses on recognizing each repetition of the exercises (micro labels). Subsequent stages extend the recognition to encompass the complete range of exercises (macro labels). The DS-MS-TCN model surpasses existing state-of-the-art deep learning models, achieving f1-scores exceeding 80% and Intersection over Union (IoU) f1-scores surpassing 60% for all four exercises evaluated. Notably, the model outperforms the prior study utilizing the sliding window technique, eliminating the need for post-processing stages and window size tuning. To our knowledge, we are the first to present a novel perspective on enhancing Human Activity Recognition (HAR) systems through the recognition of each repetition of activities.

When and How to Evaluate Vitamin D Status? A Viewpoint from the Belgian Bone Club.

Low serum vitamin D levels have been associated with a variety of health conditions which has led the medical community but also the general population to evaluate vitamin D status quite liberally. Nevertheless, there remain questions about the efficacy and cost-effectiveness of such a broad and untargeted approach. This review therefore aims to summarize the current evidence and recommendations on when and how to evaluate vitamin D status in human health and disease. For the general population, most guidelines do not recommend universal screening but suggest a targeted approach in populations at risk. Also, some guidelines do not even recommend evaluating vitamin D status when vitamin D substitution is indicated anyway, such as in children or patients receiving anti-osteoporosis drugs. In those guidelines that recommend the screening of vitamin D status, serum 25(OH)D levels are universally proposed as the preferred screening tool. However, little attention is given to analytical considerations and almost no guidelines discuss the timing and frequency of screening. Finally, there is the known variability in diagnostic thresholds for defining vitamin D insufficiency and deficiency. Overall, the existing guidelines on the evaluation of vitamin D status differ broadly in screening strategy and screening implementation, and none of these guidelines discusses alternative screening modes, for instance, the vitamin metabolic ratio. Efforts to harmonize these different guidelines are needed to enhance their efficacy and cost-effectiveness.

Associations between gut microbiota and sarcopenia or its defining parameters in older adults: A systematic review.

Altered gut microbiota (GM) potentially contribute to development or worsening of sarcopenia through a gut-muscle axis. This systematic review aims to compare GM between persons with sarcopenia or low sarcopenia-defining parameters (muscle mass, strength, and physical performance) to those with preserved muscle status, as well as to clarify possible associations between sarcopenia (-defining parameters) and relative abundance (RA) of GM-taxa or GM-(α- or ß) diversity indices, in order to clarify whether there is robust evidence of the existence of a GM signature for sarcopenia. This systematic review was conducted according to the PRISMA-reporting guideline and pre-registered on PROSPERO (CRD42021259597). PubMed, Web of Science, Embase, ClinicalTrials.gov, and Cochrane library were searched until 20 July 2023. Included studies reported on GM and sarcopenia or its defining parameters. Observational studies were included with populations of mean age ≥50 years. Thirty-two studies totalling 10 781 persons (58.56% ♀) were included. Thirteen studies defined sarcopenia as a construct. Nineteen studies reported at least one sarcopenia-defining parameter (muscle mass, strength or physical performance). Studies found different GM-taxa at multiple levels to be significantly associated with sarcopenia (n = 4/6), muscle mass (n = 13/14), strength (n = 7/9), and physical performance (n = 3/3); however, directions of associations were heterogeneous and also conflicting for specific GM-taxa. Regarding ß-diversity, studies found GM of persons with sarcopenia, low muscle mass, or low strength to cluster differently compared with persons with preserved muscle status. α-diversity was low in persons with sarcopenia or low muscle mass as compared with those with preserved muscle status, indicating low richness and diversity. In line with this, α-diversity was significantly and positively associated with muscle mass (n = 3/4) and muscle strength (n = 2/3). All reported results were significant (P < 0.05). Persons with sarcopenia and low muscle parameters have less rich and diverse GM and can be separated from persons with preserved muscle mass and function based on GM-composition. Sarcopenia and low muscle parameters are also associated with different GM-taxa at multiple levels, but results were heterogeneous and no causal conclusions could be made due to the cross-sectional design of the studies. This emphasizes the need for uniformly designed cross-sectional and longitudinal trials with appropriate GM confounder control in large samples of persons with sarcopenia and clearly defined core outcome sets in order to further explore changes in GM-taxa and to determine a sarcopenia-specific GM-signature.

Hospitalizations for hip and non-hip osteoporotic fractures in Belgium: nationwide trends between 2010 and 2021.

This study aimed to describe the incidence of hospitalizations for osteoporotic fractures in patients aged 50 years and over in Belgium between 2010 and 2021. A declining trend in crude and age-adjusted hospitalization incidence was observed, however, the absolute number of hospitalisations for osteoporotic fractures increased due to demographic changes. PURPOSE: The secular trends of hospitalizations for hip and other osteoporotic fractures between 2010 and 2021 in patients aged 50 years and over in Belgium are unknown. This study aimed to describe the incidence of hospitalizations for osteoporotic fractures in patients aged 50 years and over in Belgium between 2010 and 2021. METHODS: Population-based, retrospective study based on hospitalization data extracted by the national database NIHDI and demographical data retrieved from the Belgian Federal Bureau for Statistics. Data were combined to determine the crude and age-standardized hospitalization incidence of fractures of the hip, distal femur, pelvis, humerus, wrist, and spine (2010 as the reference year). RESULTS: A total of 445,234 hospitalizations for osteoporotic fractures were reported between 2010 and 2021 (excluding 2015). Hospitalizations increased by 5.8% between 2010 and 2021 (p = 0.013) with a higher increase in men (12.1%; p = 0.001) compared to women (4.1%; p = 0.041). The crude incidence of hospitalizations for all fractures per 100,000 persons per year decreased from 990 to 910 between 2010 and 2021 (p = 0.572). The age-standardized incidence for hospitalizations of any osteoporotic fracture in men declined from 5.30/1,000 to 4.42/1,000 (p = 0.010). In women, a similar decrease was observed (13.84/1,000 to 11.62/1,000; p = 0.003). Both age-standardized hospitalizations for hip and non-hip fractures showed a decrease in both sexes. CONCLUSION: Although a declining trend in the crude incidence per 100,000 and in the age-adjusted incidence of hospitalizations for osteoporotic fractures was observed, the absolute number of hospitalizations for osteoporotic fractures increased due to the demographic change of an ageing population.

Meta-analysis on the interrelationship between sarcopenia and mild cognitive impairment, Alzheimer's disease and other forms of dementia.

Sarcopenia has been associated with adverse health outcomes, including cognitive dysfunction. However, its specific interrelationship with neurocognitive disorders such as mild cognitive impairment (MCI), Alzheimer's disease (AD) or other types of dementia has not been thoroughly explored. This meta-analysis aims to summarize the existing evidence on this interrelationship. This systematic review was pre-registered on PROSPERO (CRD42022366309) and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Databases, including PubMed, Embase, CINAHL, Scopus, Web of Science, PEDro, SPORTDiscus and the Cochrane Central Register of Controlled Trials, and the data registry ClinicalTrials.gov were searched from inception to 8 June 2023. Observational studies (cross-sectional and cohort) and interventional studies reporting on the association and prevalence of sarcopenia in MCI, AD or other types of dementia in adults ≥50 years were included. For the meta-analysis, pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated for the association of sarcopenia with the neurocognitive disorders using random-effects/fixed-effects models. Subgroup analyses were performed to identify potential sources of heterogeneity. A total of 77 studies consisting of 92 058 subjects were finally included in the qualitative analysis (71 cross-sectional, 4 cohort and 2 interventional studies). Studies were heterogeneous, using different diagnostic criteria to define both sarcopenia and cognitive status. The majority of studies (n = 38) included Asian community-dwelling older adults. Most studies investigated the association of sarcopenia with AD (33/77) and MCI (32/77). For studies focusing on other forms of dementia, two studies included Lewy body dementia and one study included Parkinson's dementia, whereas the remaining studies did not specify dementia aetiology (n = 21). Three cohort studies explored the association between sarcopenia and incident MCI, whereas only one cohort study explored the association between dementia and incident sarcopenia. Two interventional studies investigated whether an exercise programme could prevent the progression of sarcopenia in older adults with dementia or AD. The information for the meta-analysis was extracted from 26 studies. Sarcopenia was significantly associated with MCI (pooled OR = 1.58, 95% CI 1.42-1.76) (n = 14), AD (pooled OR = 2.97, 95% CI 2.15-4.08) (n = 3) and non-AD dementia (pooled OR = 1.68, 95% CI 1.09-2.58) (n = 9). The significance and magnitude of the associations differed in subgroup analyses by study design, population, definition of sarcopenia or used tool to measure cognitive status. This meta-analysis showed that sarcopenia is significantly associated with MCI, AD and other types of dementia. These findings suggest the importance of early screening and prevention of sarcopenia in older people with cognitive dysfunction, although further longitudinal research is needed to clarify the causal relationship.

Cost-effectiveness of romosozumab for the treatment of postmenopausal women with osteoporosis at high risk of fracture in Belgium.

This study evaluated the cost-effectiveness of sequential treatment with romosozumab-to-alendronate compared to alendronate monotherapy and teriparatide-to-alendronate, in postmenopausal osteoporotic women from a Belgian healthcare perspective. Romosozumab-to-alendronate was found to be cost-effective compared to alendronate monotherapy and dominant compared to teriparatide-to-alendronate for osteoporotic women at high risk of fracture in Belgium. PURPOSE: This study aimed to evaluate the cost-effectiveness of sequential treatment with romosozumab followed by alendronate compared to alendronate monotherapy and teriparatide followed by alendronate, in postmenopausal osteoporotic women at high risk of fracture, from a Belgian healthcare perspective. Romosozumab is reimbursed in Belgium since December 2021. METHODS: A Markov microsimulation model was used to evaluate the cost-effectiveness of romosozumab-to-alendronate compared to alendronate monotherapy and to teriparatide-to-alendronate over a lifetime horizon. Patients transition between five different health states every 6 months based on fracture risks or death. The model was populated with Belgium-specific epidemiological and cost data, where available. The fracture risk reduction of romosozumab treatment was collated from the ARCH study, and from a published network meta-analysis. Costs were included from a healthcare perspective (NIHDI). Cost-effectiveness was reported in terms of costs per quality-adjusted life year (QALY), reported in Euro (€) 2022. Deterministic (DSA) and probabilistic sensitivity analyses (PSA) were performed. RESULTS: Romosozumab-to-alendronate was associated with 0.12 additional QALYs at an additional cost of €2314 compared to alendronate monotherapy, resulting in an ICER of €19,978. Compared to teriparatide-to-alendronate, romosozumab-to-alendronate was found to be dominant, with higher QALYs and lower costs. The base-case results were robust to uncertainty in the input parameters when conducting the sensitivity analysis. CONCLUSION: Sequential treatment with romosozumab followed by alendronate was found to be cost-effective compared to alendronate monotherapy and dominant compared to teriparatide followed by alendronate for postmenopausal women with osteoporosis at high risk of fracture in Belgium.

Predictors of mortality one year after pelvic fractures in an older population: a retrospective cohort study.

The goal was to investigate if patient characteristics can be used to predict 1-year post-fracture mortality after pelvic fracture. Multivariate logistic regression identified male gender, comorbidities and presence of in-hospital complications as predictors of 1-year mortality. PURPOSE: Osteoporotic pelvic fractures have significant mortality and morbidity in the older population. The aim of this study was to investigate the factors predicting one-year mortality of patients sustaining a low-impact pelvic fracture (pelvic ring and acetabulum). METHODS: A total of 282 patients aged ≥ 65 years presenting with a low-energy pelvic ring (n =254) or acetabular (n =28) fracture to the emergency department at the University Hospitals Leuven were included. Demographic and clinical data were retrospectively collected and predictors for mortality one year after pelvic ring fractures were evaluated. RESULTS: The one-year mortality after osteoporotic pelvic ring fractures and acetabular fractures was respectively 20.4% (95% CI 15.7-26.0) and 14% (95% CI 4.0-32.7). Multivariate logistic regression adjusted for confounders identified male gender (OR 3.18; 95% CI (1.06-9.49), p =0.038), a higher number of comorbidities (OR 1.5; 95% CI (1.16-1.95), p =0.002) and in-hospital complications (OR 5.00; 95% CI (1.39-17.97), p =0.014) as independent predictors of one-year mortality after pelvic ring fractures. CONCLUSION: The one-year mortality after low-energy pelvic is high and can be predicted by different patient characteristics. These findings can guide pelvis fracture treatment decisions in the older population.

Otago Exercises Monitoring for Older Adults by a Single IMU and Hierarchical Machine Learning Models.

Otago Exercise Program (OEP) is a rehabilitation program for older adults to improve frailty, sarcopenia, and balance. Accurate monitoring of patient involvement in OEP is challenging, as self-reports (diaries) are often unreliable. The development of wearable sensors and their use in Human Activity Recognition (HAR) systems has lead to a revolution in healthcare. However, the use of such HAR systems for OEP still shows limited performance. The objective of this study is to build an unobtrusive and accurate system to monitor OEP for older adults. Data was collected from 18 older adults wearing a single waist-mounted Inertial Measurement Unit (IMU). Two datasets were recorded, one in a laboratory setting, and one at the homes of the patients. A hierarchical system is proposed with two stages: 1) using a deep learning model to recognize whether the patients are performing OEP or activities of daily life (ADLs) using a 10-minute sliding window; 2) based on stage 1, using a 6-second sliding window to recognize the OEP sub-classes. Results showed that in stage 1, OEP could be recognized with window-wise f1-scores over 0.95 and Intersection-over-Union (IoU) f1-scores over 0.85 for both datasets. In stage 2, for the home scenario, four activities could be recognized with f1-scores over 0.8: ankle plantarflexors, abdominal muscles, knee bends, and sit-to-stand. These results showed the potential of monitoring the compliance of OEP using a single IMU in daily life. Also, some OEP sub-classes are possible to be recognized for further analysis.

Does testosterone influence the association between sleep and frailty in men: results from the European Male Aging Study.

BACKGROUND: Previous studies have suggested an association between sleep disturbance and frailty. The mechanism is unknown, although it has been suggested that hormonal factors may play a role. METHODS: The aim was to determine the association between sleep duration, sleep quality and frailty, and to determine whether testosterone influenced this association. Males aged 40-79 years were recruited from eight European centres to the European Male Aging Study (EMAS). Subjects completed an interviewer-assisted questionnaire including questions regarding sleep quality and duration. Sleep quality was scored 0-20 and categorised as 0-4, 5-9, 10-14, and 15-20, with higher scores indicating poorer quality. A 39-component frailty index (FI) was constructed. Total testosterone levels were measured. The association between sleep duration, sleep quality and the FI was assessed using negative binomial regression, with adjustment for putative confounders including testosterone level. RESULTS: Two thousand three hundred ninety-three participants contributed data to the analysis. The mean age was 63.3 years and mean sleep duration was 7.01 h. The mean frailty index was 0.15. Mean testosterone levels declined with decreasing sleep quality. After adjustment, compared to those with a sleep score of 0-4, the FI was 57% (95% CI 38%, 78%) higher among those with a sleep score of 15-20. After adjustment compared to those with normal sleep duration (6-9 h), those with a short (< 6 h) and long (≥ 9 h) sleep duration had a 16% (95% CI 6%, 28%) and 11% (95% CI 0%, 23%) higher FI, respectively. Adjustment for testosterone did not influence the strength of either association. CONCLUSION: Frailty is associated with impaired sleep quality and sleep duration. The association cannot, however, be explained by variation in testosterone levels.

Trial in Elderly with Musculoskeletal Problems due to Underlying Sarcopenia-Faeces to Unravel the Gut and Inflammation Translationally (TEMPUS-FUGIT): protocol of a cross-sequential study to explore the gut-muscle axis in the development and treatment of sarcopenia in community-dwelling older adults.

BACKGROUND: Gut microbiota (GM) might play a role in muscle metabolism and physiological processes through a hypothesized gut-muscle axis, influencing muscle mass and function and thus, sarcopenia. The Trial in Elderly with Musculoskeletal Problems due to Underlying Sarcopenia-Faeces to Unravel the Gut and Inflammation Translationally (TEMPUS-FUGIT) aims to explore the gut-muscle axis in sarcopenia. METHODS: First, in a cross-sectional case-control phase, 100 community-dwelling adults without sarcopenia will be compared to 100 community-dwelling adults (≥ 65 years) with sarcopenia of similar age-, gender and BMI-ratio, participating in the ongoing 'Exercise and Nutrition for Healthy AgeiNg' (ENHANce; NCT03649698) study. Sarcopenia is diagnosed according to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria. GM composition and intestinal inflammatory markers (fecal calprotectin, lactoferrin and S100A12) will be determined in fecal samples. Systemic inflammatory markers (hs-CRP, IL-4, IL-6, TNF-α, IL-13, IL-1ß and creatine kinase) will be determined in fasted blood samples. Both groups will be compared using appropriate statistical testing, whereas linear regression will be used for cross-sectional associations between gut, inflammatory and sarcopenia parameters. Second, in the longitudinal phase, sarcopenic older adults will be requested to deliver five fecal samples during the 12-week intervention to assess the effects of protein, omega-3 and a physical exercise program on the GM. DISCUSSION: TEMPUS-FUGIT aims to explore the gut-muscle axis by comparing GM composition between sarcopenic and non-sarcopenic older adults and to determine the association of GM with intestinal and systemic inflammatory markers and sarcopenia-defining parameters (muscle mass, muscle strength and physical performance). Furthermore, effects of single or combined, optimized and individualized anabolic interventions (exercise, protein and omega-3 supplementation), on GM will be explored in persons with sarcopenia. TEMPUS-FUGIT aims to impact clinical practice by clarifying the relationship between the gut-muscle axis and sarcopenia. TEMPUS-FUGIT is expected to contribute to the discovery of clinical and microbial biomarkers for sarcopenia and insights in its pathophysiology, opening possible future perspectives for novel sarcopenia treatment strategies targeting GM. TRIAL REGISTRATION: ClinicalTrails.gov NCT05008770, registered on August 17, 2021; first participant enrolled on September 21 2021.

Skeletal response to teriparatide in real-life setting: effects of age, baseline bone density and prior denosumab use.

OBJECTIVES: Teriparatide (TPD) is an osteoanabolic agent used in patients with high osteoporotic fracture risk. Predictors of therapeutic response to TPD in real-life setting are not well characterised. This study investigated the influence of previous antiresorptive therapy, age and other patient characteristics on the skeletal response to TPD. METHODS: Retrospective study at the metabolic bone clinic, University Hospitals Leuven, Belgium. Patients with osteoporosis and a high fracture burden received TPD for 9-18 months. Bone mineral density (BMD) was measured at baseline, 9 and 18 months at lumbar spine (LS), femoral neck (FN) and total hip (TH). RESULTS: BMD at LS increased at 9 months (change mean (standard error) 6.8 % (0.7) p < 0.001) and at 18 months (8.0 % (0.9) p < 0.001), while BMD at FN and TH did not change significantly. Non-response in BMD change at the LS was seen with prior denosumab use (odds ratio 0.21, 95% confidence interval (CI) 0.049-0.912, p = 0.037). Changes in BMD at TH were significantly greater in younger patients and in patients with a lower baseline BMD. CONCLUSION: TPD-induced changes in BMD at TH might depend on age and baseline BMD and at LS on prior denosumab use. The results suggest that these factors may be relevant for clinical decision making when initiating TPD treatment, although larger studies are needed to confirm these findings.

Sarcopenia, osteoporosis and frailty.

Muscles and bones are intricately connected tissues displaying marked co-variation during development, growth, aging, and in many diseases. While the diagnosis and treatment of osteoporosis are well established in clinical practice, sarcopenia has only been classified internationally as a disease in 2016. Both conditions are associated with an increased risk of adverse health outcomes such as fractures, dysmobility and mortality. Rather than focusing on one dimension of bone or muscle mass or weakness, the concept of musculoskeletal frailty captures the overall loss of physiological reserves in the locomotor system with age. The term osteosarcopenia in particular refers to the double jeopardy of osteoporosis and sarcopenia. Muscle-bone interactions at the biomechanical, cellular, paracrine, endocrine, neuronal or nutritional level may contribute to the pathophysiology of osteosarcopenia. The paradigm wherein muscle force controls bone strength is increasingly facing competition from a model centering on the exchange of myokines, osteokines and adipokines. The most promising results have been obtained in preclinical models where common drug targets have been identified to treat these conditions simultaneously. In this narrative review, we critically summarize the current understanding of the definitions, epidemiology, pathophysiology, and treatment of osteosarcopenia as part of an integrative approach to musculoskeletal frailty.

Are inflammatory markers associated with sarcopenia-related traits in older adults with sarcopenia? - A cross-sectional analysis of the ENHANce study.

AIMS: To explore the relationship between inflammatory markers and sarcopenia-related traits in sarcopenic older adults. METHODS: Baseline data of the ongoing Exercise and Nutrition for Healthy AgeiNg (ENHANce) study were used for a secondary, exploratory, cross-sectional analysis. ENHANce is a 5-armed triple blinded randomized controlled trial, in older adults (>65y) with sarcopenia defined according to the revised criteria of the European Working Group of Sarcopenia in Older People (EWGSOP2) aiming to assess the effect of combined anabolic interventions (protein supplement, omega-3 supplement and physical exercise) on physical performance, compared to single/placebo interventions. Inflammatory markers C-reactive protein (hs-CRP), albumin, interleukin-1ß (IL-1ß), IL-6, IL-8, and tumour necrosis factor-α (TNF-α) were assessed at baseline. Spearman's rho (ρ) correlation coefficients were calculated to associate these inflammatory markers with baseline sarcopenia-defining parameters (handgrip strength, chair stand test, appendicular lean mass [aLM], gait speed, Short Physical Performance Battery), physical activity (step count) and quality of life (SF-36, SarQoL). RESULTS: We included 40 sarcopenic subjects (15 men/25 women, age 77.1 ± 6.8 years). Contrary to expectations, the pro-inflammatory IL-1ß correlated positively with handgrip strength (ρ: 0.376; p = 0.024) and IL-6 with aLM (ρ: 0.334; p = 0.0433). IL-6 inversely correlated with step count (ρ:-0.358; p = 0.048). Subgroup analysis revealed important gender differences. IL-8 inversely correlated with handgrip strength in women (ρ: -0.425; p = 0.034) but not in men. In contrast, pro-inflammatory cytokines CRP (ρ: -0.615; p = 0.019), IL-6 (ρ: -0.604; p = 0.029) and TNF-α (ρ: -0.615; p = 0.025) inversely correlated with the SF-36 physical component score in men but not in women. CONCLUSION: Although Inflammageing might play a role in sarcopenia-related traits, this exploratory study highlights an important role of gender. Future research should take this into account when elucidating the Inflammageing-sarcopenia interplay.

Are dietary intake and nutritional status of specific polyunsaturated fatty acids correlated with sarcopenia outcomes in community-dwelling older adults with sarcopenia? - Exploratory results from ENHANce.

AIMS: To explore the relationship between dietary polyunsaturated fatty acids (PUFAs) intake, nutritional PUFAs status and sarcopenia outcomes in sarcopenic older adults. METHODS: The Exercise and Nutrition for Healthy AgeiNg (ENHANce) is an ongoing 5-armed triple blinded randomized controlled trial, in sarcopenic older adults (> 65y) aiming to assess the effect of combined anabolic interventions (protein, omega-3 supplement and exercise) on physical performance in these adults, compared to single/placebo interventions. Baseline data were used for a secondary, exploratory, cross-sectional analysis. Dietary PUFAs intake was assessed with 4-day food records, status with RBC membrane fatty acids profiles. Spearman's rho(ρ) correlation coefficients were calculated to explore associations of PUFAs intake and status with sarcopenia-defining parameters (muscle strength, mass and physical performance), physical activity (step count) and quality of life (SF-36, SarQoL). RESULTS: In total, 29 subjects (9♂/20♀, mean age 76.3 ± 5.4y) were included. Total omega-3 intake of participants (1.99 ± 0.99 g/d) was below the recommended intake (♂:2.8-5.6 g/d; ♀:2.2-4.4 g/d). Intake and status of PUFAs were not correlated. Regarding correlations with outcomes, α-linolenic acid status was inversely associated with appendicular lean mass (aLM) (ρ:-0.439; p = 0.017), whereas docosahexaenoic acid status was positively associated with aLM (ρ:0.388; p = 0.038). Some omega-3 PUFAs intake and status markers were positively associated with step count, SF-36 and SarQoL scores, whereas gamma-linolenic acid status was inversely associated with SF-36 physical component summary score (ρ = -0.426; p = 0.024). CONCLUSIONS: Although intake of omega-3 and omega-6 was low, the present exploratory study generated new hypotheses for potential correlations of PUFAs intake and status with sarcopenia outcomes in older adults with sarcopenia.

Sarcopenia-defining parameters, but not sarcopenia, are associated with cognitive domains in middle-aged and older European men.

BACKGROUND: Previous research suggests that sarcopenia is associated with lower cognitive functioning. Evidence on the longitudinal relationship between cognition and sarcopenia, according to the revised criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2), is scarce. This study aimed to investigate both cross-sectional and longitudinal associations between sarcopenia and its defining parameters (muscle strength, muscle mass and physical performance) and cognitive performance in middle-aged and older men. METHODS: This was a secondary analysis of data from the European Male Ageing Study (EMAS), a multicentre cohort study of men aged 40-79 years, recruited from population registers in eight European centres. Cognitive functioning was assessed by using a battery of three neuropsychological tests, measuring fluid intelligence: Rey-Osterrieth Complex Figure (ROCF-Copy and ROCF-Recall), Camden Topographical Recognition Memory (CTRM) and Digit Symbol Substitution Test (DSST). Sarcopenia-defining parameters appendicular lean mass (aLM), gait speed (GS), chair stand test (CST) and handgrip strength (HGS) were measured. Sarcopenia was diagnosed according to the criteria of the EWGSOP2. All measurements were performed at baseline and after a follow-up of 4.3 years. Cross-sectional associations between cognition, sarcopenia-defining parameters and prevalent sarcopenia (EWGSOP2) were analysed. Longitudinally, the predictive value of baseline cognition on decline in sarcopenia-defining parameters, onset of new sarcopenia and vice versa was examined. Linear and logistic regression were used and adjusted for putative confounders. RESULTS: In the whole cohort (n = 3233), ROCF-Copy (ß = 0.016; P < 0.05), ROCF-Recall (ß = 0.010; P < 0.05), CTRM (ß = 0.015; P < 0.05), DSST score (ß = 0.032; P < 0.05) and fluid cognition (ß = 0.036; P < 0.05) were significantly and independently associated with GS at baseline. In the Leuven + Manchester subcohorts (n = 456), ROCF-Copy (ß = 1.008; P < 0.05), ROCF-Recall (ß = 0.908; P < 0.05) and fluid cognition (ß = 1.482; P < 0.05) were associated with HGS. ROCF-Copy (ß = 0.394; P < 0.05), ROCF-Recall (ß = 0.316; P < 0.05), DSST (ß = 0.393; P < 0.05) and fluid cognition (ß = 0.765; P < 0.05) were associated with aLM. The prevalence of sarcopenia in this population was 17.8%. No associations were detected between cognition and prevalent or incident sarcopenia. Longitudinal analysis showed that low ROCF-Copy score at baseline was associated with an increase in CST in men ≥70 years (ß = -0.599; P < 0.05). In addition, a decrease in ROCF-Recall was associated with a decrease in GS, and a decrease in DSST was associated with an increase in CST (ß = 0.155; P < 0.0001, ß = -0.595; P < 0.001, respectively) in persons with the highest change in both cognition and muscle function. CONCLUSIONS: Sarcopenia was not associated with cognitive performance in this population, whereas several components of sarcopenia were associated with domain-specific cognitive performance. Longitudinally, baseline and change in subdomains of cognition predicted change in muscle function in specific subgroups.

Risk of medication-related osteonecrosis of the jaw after dental extractions in patients receiving antiresorptive agents - A retrospective study of 240 patients.

This study investigated the incidence, risk factors, and outcome of medication-related osteonecrosis of the jaw after dental extractions in patients receiving antiresorptive agents for osteoporosis or bone metastases. 240 patients with a median drug exposure of 43 months were retrospectively studied. The incidence of MRONJ after dental extraction in the osteoporosis cohort was 2.7 % per person-year (95 % CI 1.6-4.6 %) (n = 13/126), and for the bone metastases cohort 26.4 % per person-year (95 % CI 20.4-34.2 %) (n = 58/114). 92 % of MRONJ cases were stage 1. Dental infection as the reason for extraction increased the osteonecrosis risk in the osteoporosis (OR 22.77; 95 % CI 2.85-181.62; p = 0.003) and bone metastases cohorts (OR 2.72; 95 % CI 1.28-5.81; p = 0.010). Using leukocyte and platelet-rich fibrin reduced this risk by 84 % (p = 0.003), as did antibiotics use by 86-93 % (p = 0.013). Within the bone metastases cohort, an interval since last administration of at least 3 months reduced risk of MRONJ (OR 0.83; 95 % CI 0.72-0.97; p = 0.018). Mucosal healing occurred in 11/13 patients (84.6 %; 95 % CI 54.5-98.1 %) with osteoporosis and 31/58 patients (53.4 %; 95 % CI 40.0-66.7 %) with bone metastases. In conclusion, though the MRONJ risk in this selected population taking antiresorptive agents and presenting to the Oral Maxillofacial Surgery clinic for a dental extraction is considerable and higher in those with dental infections, preventive measures such as antibiotics and use of LRPF membranes may significantly reduce that risk.

Local radiographic risk factors for MRONJ in osteoporotic patients undergoing tooth extraction.

OBJECTIVE: To identify local radiographic risk factors for Medication-Related Osteonecrosis of the Jaws (MRONJ) in osteoporotic patients treated with antiresorptive drugs (ARD) and undergoing tooth extraction. MATERIAL AND METHODS: Patients were included in this retrospective, longitudinal, case-control study, if having at least one administration of ARD, underwent tooth extraction(s), and had pre- and post-operative panoramic radiographs. Additionally, a matched control group was selected. Three calibrated, blinded, and independent observers assessed each tooth extraction site. Statistical analysis compared control against study group, and within the latter, sites MRONJ+ and MRONJ-. RESULTS: In total, 120 patients (99 females/21 males) with 354 tooth extractions were included, from which nine patients (7.5%) and eleven tooth extraction sites (3.1%) developed MRONJ. When comparing control with study group, the latter showed significantly more thickened lamina dura, persistence of the alveolar socket, heterogeneous bone patterns, and sequestrum formation. In the study group, MRONJ developed significantly more in males (19%, p = 0.049), smokers (25%, p = 0.008), in the mandible (82%, p = 0.027), when identifying a radiolucent or sclerotic trabecular pattern (p = 0.004) or when extracting teeth with furcation involvement (p < 0.001), root remnants (p = 0.017), or unrestored caries lesions (p = 0.005). CONCLUSIONS: Tooth extraction sites showing radiographic signs of chronic dental infection are prone to MRONJ.

Romosozumab efficacy and safety in European patients enrolled in the FRAME trial.

In this post hoc analysis, we assessed romosozumab efficacy and safety in European patients enrolled in FRAME. Romosozumab treatment through 12 months, followed by denosumab for a further 24 months, resulted in early and sustained risk reduction for major fracture categories, associated with large gains in bone mineral density. INTRODUCTION: In the multinational FRAME phase 3 trial of romosozumab in postmenopausal women with osteoporosis, marked differences between clinical and non-vertebral fracture outcomes were observed among patients from Central and Southern America versus rest of world. This post hoc analysis assessed romosozumab efficacy and safety in European patients enrolled in the FRAME trial and extension study. METHODS: In FRAME (NCT01575834), patients were randomised 1:1 to romosozumab 210 mg or placebo monthly (QM) for 12 months, followed by open-label denosumab 60 mg Q6M to month 36, including a 12-month extension study. We report incidence of major fracture outcomes, bone mineral density (BMD) change from baseline and safety for European patients enrolled in FRAME. RESULTS: In FRAME, 3013/7180 (41.96%) patients were European; 1494 received romosozumab and 1519 received placebo. Through 12 months, romosozumab reduced fracture risk versus placebo for non-vertebral fracture (1.4% versus 3.0%; p = 0.004), clinical fracture (1.4% versus 3.6%; p < 0.001), new vertebral fracture (0.4% versus 2.1%; p < 0.001) and major osteoporotic fracture (0.9% versus 2.8%; p < 0.001), with results sustained through 36 months following transition to denosumab. Hip fractures were numerically reduced with romosozumab at month 12 (0.2% versus 0.6%; p = 0.092). Romosozumab increased BMD versus placebo at month 12; all patients in the romosozumab and placebo groups experienced further increases by month 36 after transition to denosumab. Adverse events were balanced between groups. CONCLUSIONS: Among European patients in FRAME, romosozumab resulted in early and sustained risk reduction for all major fracture categories, associated with large BMD gains that continued after transition to denosumab.

Prevention and Treatment of Glucocorticoid-Induced Osteoporosis in Adults: Consensus Recommendations From the Belgian Bone Club.

Glucocorticoids are effective immunomodulatory drugs used for many inflammatory disorders as well as in transplant recipients. However, both iatrogenic and endogenous glucocorticoid excess are also associated with several side effects including an increased risk of osteoporosis and fractures. Glucocorticoid-induced osteoporosis (GIOP) is a common secondary cause of osteoporosis in adults. Despite availability of clear evidence and international guidelines for the prevention of GIOP, a large treatment gap remains. In this narrative review, the Belgian Bone Club (BBC) updates its 2006 consensus recommendations for the prevention and treatment of GIOP in adults. The pathophysiology of GIOP is multifactorial. The BBC strongly advises non-pharmacological measures including physical exercise, smoking cessation and avoidance of alcohol abuse in all adults at risk for osteoporosis. Glucocorticoids are associated with impaired intestinal calcium absorption; the BBC therefore strongly recommend sufficient calcium intake and avoidance of vitamin D deficiency. We recommend assessment of fracture risk, taking age, sex, menopausal status, prior fractures, glucocorticoid dose, other clinical risk factors and bone mineral density into account. Placebo-controlled randomized controlled trials have demonstrated the efficacy of alendronate, risedronate, zoledronate, denosumab and teriparatide in GIOP. We suggest monitoring by dual-energy X-ray absorptiometry (DXA) and vertebral fracture identification one year after glucocorticoid initiation. The trabecular bone score might be considered during DXA monitoring. Extended femur scans might be considered at the time of DXA imaging in glucocorticoid users on long-term (≥ 3 years) antiresorptive therapy. Bone turnover markers may be considered for monitoring treatment with anti-resorptive or osteoanabolic drugs in GIOP. Although the pathophysiology of solid organ and hematopoietic stem cell transplantation-induced osteoporosis extends beyond GIOP alone, the BBC recommends similar evaluation, prevention, treatment and follow-up principles in these patients. Efforts to close the treatment gap in GIOP and implement available effective fracture prevention strategies into clinical practice in primary, secondary and tertiary care are urgently needed.

Rebound-associated vertebral fractures after denosumab discontinuation in a lung cancer patient with bone metastases.

Denosumab is a commonly used antiresorptive treatment in patients with osteoporosis or solid tumours with bone metastases. Upon denosumab discontinuation, a rebound phenomenon can occur that results in an increased (vertebral) fracture risk. This phenomenon is well-known in the setting of osteoporosis but rarely reported in cancer patients with bone metastases discontinuing denosumab. We present the case of a 43-year old women with lung cancer and bone metastases who suffered multiple vertebral fractures after discontinuation of denosumab.