MicroRNAs and their Modulatory Effect on the Hallmarks of Osteosarcopenia.

PURPOSE OF THE REVIEW: Osteosarcopenia is a geriatric syndrome associated with disability and mortality. This review summarizes the key microRNAs that regulate the hallmarks of sarcopenia and osteoporosis. Our objective was to identify components similarly regulated in the pathology and have therapeutic potential by influencing crucial cellular processes in both bone and skeletal muscle. RECENT FINDINGS: The simultaneous decline in bone and muscle in osteosarcopenia involves a complex crosstalk between these tissues. Recent studies have uncovered several key mechanisms underlying this condition, including the disruption of cellular signaling pathways that regulate bone remodeling and muscle function and regeneration. Accordingly, emerging evidence reveals that dysregulation of microRNAs plays a significant role in the development of each of these hallmarks of osteosarcopenia. Although the recent recognition of osteosarcopenia as a single diagnosis of bone and muscle deterioration has provided new insights into the mechanisms of these underlying age-related diseases, several knowledge gaps have emerged, and a deeper understanding of the role of common microRNAs is still required. In this study, we summarize current evidence on the roles of microRNAs in the pathogenesis of osteosarcopenia and identify potential microRNA targets for treating this condition. Among these, microRNAs-29b and -128 are upregulated in the disease and exert adverse effects by inhibiting IGF-1 and SIRT1, making them potential targets for developing inhibitors of their activity. MicroRNA-21 is closely associated with the occurrence of muscle and bone loss. Conversely, microRNA-199b is downregulated in the disease, and its reduced activity may be related to increased myostatin and GSK3ß activity, presenting it as a target for developing analogues that restore its function. Finally, microRNA-672 stands out for its ability to protect skeletal muscle and bone when expressed in the disease, highlighting its potential as a possible therapy for osteosarcopenia.

Challenges in Delivering Effective Care for Older Persons with Fragility Fractures.

Fragility fractures occur because of low-impact trauma or even spontaneously in individuals with osteoporosis. Caring for older persons with fragility fractures can present several challenges due to the unique needs and vulnerabilities of this population. Older individuals commonly have multiple medical conditions, such as osteoporosis, arthritis, cardiovascular diseases, and diabetes. These comorbidities can complicate fracture management and increase the risk of complications. Fracture repair through surgery may be more complex in older patients due to poor bone quality, decreased tissue elasticity, and higher chances of anesthesia complications. In addition, mobility and functional limitations post-fracture are highly prevalent in this population, affecting their independence and increasing their risk of institutionalization. Addressing these challenges requires a multidisciplinary approach involving orthopedic surgeons, geriatricians, physical and rehabilitation physicians, physiotherapists, occupational therapists, dieticians, social workers, and caregivers. Preventive measures, such as fall prevention strategies and osteoporosis management, can also play a vital role in reducing the incidence of fragility fractures in older persons.

Using minimal clinically important differences to measure long-term transitions of osteosarcopenia: The New Mexico Aging Process Study.

BACKGROUND/OBJECTIVE: By having a better understanding of transitions in osteosarcopenia, interventions to reduce morbidity and mortality can be better targeted. The aim of this study was to show the rationale and method of using minimal clinically important differences (MCID's) to classify transitions, and the effects of demographic variables on transitions in a 9-year follow-up data from the New Mexico Aging Process Study (NMAPS). METHODS: Transitions were identified in four aspects of osteosarcopenia: bone mineral density (BMD), appendicular skeletal muscle mass/body mass index ratio (ASM/BMI), grip strength and gait speed. Transitions were identified using a MCID score. As there is currently no available MCID for BMD and ASM/BMI, those were determined using a distribution-based and an anchor-based method. Total transitions were calculated for all four measures of osteosarcopenia in all transition categories (maintaining a health status, beneficial transition, harmful transitions). Poisson regression was used to test for effects of demographic variables, including age, sex, physical activity, medication, and health status, on transitions. RESULTS: Over the 9-year follow-up, a total of 2163 MCID-derived BMD transitions were reported, 1689 ASM/BMI transitions, 2339 grip strength transitions, and 2151 gait speed transitions. Additionally, some MCID-derived transition categories were associated with sex, age, and health status. CONCLUSION: Use of MCID-derived transitions reflected the fluctuation and the dynamic nature of health in older adults. Future research should focus on transitions of modifiable markers in osteosarcopenia to design intervention trials.

The Association of Osteosarcopenia With Functional Disability in Community-Dwelling Mexican Adults 50 and Older.

Background: Osteosarcopenia (OS) has recently been described as a predictor of negative outcomes in older adults. However, this alteration in body composition has not been widely studied. In Mexico and Latin America, no information is available on its frequency or associated factors. Objective: To analyze the association between OS with FD in community-dwelling Mexican adults 50 and older. Design: Cross-sectional secondary data analysis was performed using primary data from a prospective study Frailty, Dynapenia and Sarcopenia Study in Mexican Adults (FraDySMex). Setting and Participants: Eight hundred and twenty-five people were included, 77.1% women, aged 70.3 ± 10.8 years old. Methods: OS was defined as when the person was diagnosed with sarcopenia (SP) plus osteopenia/osteoporosis. The SP diagnosis was evaluated in accordance with the criteria of the European Working Group for the Definition and Diagnosis of Sarcopenia (EWGSOP), and the osteoporosis diagnosis using World Health Organization (WHO) criteria. Muscle mass and bone mass were evaluated using dual-energy X-ray absorptiometry (DXA). FD was evaluated using the basic activities of daily living (BADL) and the instrumental activities of daily living (IADL). Additional sociodemographic and health co-variables were also included, such as sex, age, education, cognitive status, depression, comorbidity, hospitalization, polypharmacy, urinary incontinence, and nutrition variables such as risk of malnutrition and obesity. Associations between OS with FD were evaluated using multiple logistic regression. Results: The prevalence of OS was 8.9% and that of FD was 8.9%. OS was associated with FD [odds ratio (OR): 1.92; CI 95%: 1.11-3.33]. Conclusions and Implications: Comprehensive OS assessment could help clinicians identify risk factors early, and thus mitigate the impact on FD in older people.

Dysmobility syndrome: a case-series study describing a musculoskeletal syndrome in postmenopausal Mexican women.

"Dysmobility Syndrome" (DS) is a term that correlates sarcopenia and osteoporosis together with mobility disturbances, obesity, fractures, and falls. The prevalence of DS is of 74% in this study. Further research with bigger sample sizes is needed to describe if prevalence and DS characteristics are similar in other studies. PURPOSE: "Dysmobility Syndrome" (DS) correlates sarcopenia and osteoporosis together with mobility disturbances, obesity, fractures, and falls, all of which are related to adverse outcomes in the health of the elderly; however, there are no studies of DS in Mexican patients. In this study, we aimed to describe the characteristics of DS in Mexican postmenopausal women from a private practice. METHODS: A case-series study was conducted; women of 60 years and older were invited to participate from August to December of 2019, a total of 50 patients were included. Medical history, physical tests, bone densitometry, and body composition analysis were performed; patients who met 3 or more of the following criteria were diagnosed with DS: osteoporosis: T-score ≤ -2.5, falls in a previous year, lean appendicular mass: ≤ 5.45 kg/m2, walking speed: < 1.0 m/s, grip strength: < 20 kg, and body fat percentage: > 40%. RESULTS: Out of the total 50 patients, 37 were diagnosed with DS, with a prevalence of 74% in our study. Sixteen patients had a history of a non-vertebral fragility fracture, of which 14 had a diagnosis of DS (87%). CONCLUSIONS: DS has a high frequency in our study group, and was found to be closely related to the presence of non-vertebral fragility fractures. More research is needed to describe the prevalence and characteristics of DS with a stronger statistical significance within our population, and among others across the country, to get an extensive understanding of its presentation in Mexican women. KEY POINTS: • The frequency of DS in this study is higher than the one that is described in global literature. • DS diagnosis is closely related to the antecedent of non-vertebral fragility fracture.

Osteosarcopenia Predicts Falls, Fractures, and Mortality in Chilean Community-Dwelling Older Adults.

OBJECTIVES: The objective of this study was to describe the prevalence of osteosarcopenia and its association with falls, fractures, and mortality in community-dwelling older adults. DESIGN: Follow-up of ALEXANDROS cohorts designed to study disability associated with obesity in older adults. SETTING AND PARTICIPANTS: Community-dwelling people aged 60 years and older living in Chile. MEASURES: At baseline, 1119 of 2372 participants had a dual-energy X-ray absorptiometry scan and the measurements for the diagnosis of sarcopenia. World Health Organization standards for bone mineral density were used to classify them as normal, osteopenia, and osteoporosis. Sarcopenia was identified using the algorithm from the European Working Group on Sarcopenia in Older People 1, validated for the Chilean population. Osteosarcopenia was defined as having sarcopenia plus osteoporosis or osteopenia. RESULTS: The sample of 1119 participants (68.5% female) had a mean age of 72 years. At baseline, osteoporosis was identified in 23.2%, osteopenia in 49.8%, sarcopenia in 19.5%, and osteosarcopenia in 16.4% of the sample. The prevalence of osteosarcopenia increases with age, reaching 33.7% for those older than 80 years. Sarcopenia was found in 34.4% of osteoporotic people and osteoporosis in 40.8% of those with sarcopenia. After 5640 person-years of follow-up, 86 people died. The mortality was significantly higher for the group with osteosarcopenia (15.9%) compared with those without the condition (6.1%). After an adjusted Cox Regression analysis, the hazard ratio for death in people with osteosarcopenia was 2.48. Falls, fractures, and functional impairment were significantly more frequent in osteosarcopenic patients. CONCLUSIONS AND IMPLICATIONS: Osteosarcopenia is a common condition among older adults and is associated with an increased risk of falls, fractures, functional impairment, and mortality. Considering the high proportion of sarcopenia among osteoporotic patients and vice versa, screening for the second condition when the first is suspected should be advised.

Birth weight associated with dual energy X-ray absorptiometry-determined muscle-bone unit in young healthy women from the Nutritionists' Health Study.

Muscle and bone have been considered a functional unit that grows together early in life, deteriorates with aging, and can cause osteosarcopenia. Due to its importance in public health, detecting risk factors in early life is desirable. This study examined whether birth weight (BW) was associated with muscle-bone unit using dual energy X-ray absorptiometry (DXA) parameters in young women from the Nutritionists' Health Study (NutriHS), a cohort study of undergraduates and Nutrition graduates. This cross-sectional analysis included 170 young healthy women who answered early life events-questionnaire, and had anthropometric, muscle tests and DXA-determined body composition and bone densitometry (iDXA-Lunar®). A blood sample was obtained for a subsample of 148 participants. Appendicular skeletal muscle mass index (ASMI) was calculated. BW was categorized in quartiles (BWq) and variables of interest compared by ANOVA. Associations of BWq with calf circumference (CC), handgrip, muscle performance tests, ASMI, bone mineral density and content (BMD and BMC), and plasma glucose, lipids, insulin, and 25-hydroxyvitamin D were performed using multiple linear regression and directed acyclic graph-recommended adjustments. Mean values of age, body mass index, and BW were 23.0 years (20.0-28.0), 22.9 ± 2.9 kg/m2, and 3199 ± 424 g, respectively. Comparing variables across BWq, significant differences in CC, handgrip, ASMI, and total body BMC were detected. Regression models adjusted for confounders showed associations of BWq with CC (ß = 0.72, p = 0.005), handgrip (ß = 1.53, p = 0.001), ASMI (ß = 0.16, p = 0.022), total body BMC (ß = 64.8, p = 0.005), total femur BMC (ß = 0.70, p = 0.041), total body BMD (ß = 0.02, p = 0.043), and lumbar spine BMD (ß = 0.03, p = 0.028). We conclude that BW is associated with muscle-bone unit using DXA-parameters in Brazilian young healthy women from the NutriHS, suggesting a role for intrauterine environment for musculoskeletal health.

Osteosarcopenia: beyond age-related muscle and bone loss.

PURPOSE: Osteosarcopenia is a geriatric syndrome characterized by declines in bone density and microarchitecture and muscle mass and strength, which has gained clinical interest due to its association with falls and fragility fractures. METHODS: This review discusses the epidemiology of osteosarcopenia including clinical assessment, the pathophysiological aspects leading to the loss of muscle and bone mass, and efficacious therapeutic strategies to combat this syndrome. RESULTS: The etiology of osteosarcopenia is thought to include genetic and environmental factors which interact with muscle and bone at the cellular level, reinforcing that these tissues are interconnected not only by mechanical aspects, but also by humoral factors. Osteosarcopenia is identified by low muscle and bone mass and impaired strength of these tissues via imaging and physical performance measures. CONCLUSION: The diagnosis of osteosarcopenia is of clinical importance since early interventions, particularly resistance exercise, and adequate intake of protein, vitamin D and calcium, may delay the onset of individual components (osteopenia/sarcopenia) of osteosarcopenia.

Osteosarcopenia: del envejecimiento de la unidad óseo-muscular a la enfermedad / Osteosarcopenia: from muscle-bone unit aging to disease

Aunque la masa muscular y la ósea tienen igual origen embriológico, desarrollo y función, por lo que constituyen la unidad hueso-músculo, las enfermedades asociadas al envejecimiento de esta unidad se consideran de manera independiente. Sin embargo, en los últimos años se evidencia el efecto aditivo nocivo que genera la sarcopenia y la osteopenia/osteoporosis en la calidad de vida y la salud del adulto mayor y aparece el concepto de osteosarcopenia. Entre los adultos mayores se reporta la disminución progresiva de la masa y la fuerza musculares, y las caídas accidentales en el hogar (probables por fragilidad) que están entre las principales causas de muerte, lo que sugiere que un grupo de estos adultos mayores pudieran tener osteosarcopenia. Por ello se requiere desarrollar capacidades para su prevención. Se realiza una revisión narrativa para actualizar aspectos del envejecimiento de la unidad óseo-muscular, la importancia de la osteosarcopenia, sus criterios diagnósticos y opciones terapéuticas. Se estudiaron artículos completos, en idioma inglés y español, obtenidos de las bases de datos Pubmed, Scielo Regional y Google Scholar. La infiltración grasa de la unidad músculo-hueso es el evento más importante del envejecimiento, pero no existe uniformidad en el diagnóstico de la sarcopenia. Hasta el presente un aporte proteico de calcio y vitamina D, unido a ejercicios de fuerza, son las principales opciones terapéuticas. No se dispone de fármacos que actúen al unísono sobre las dos entidades que conforman la osteosarcopenia(AU)

Muscle and bone mass have the same embryological origin, development and function constituting the bone-muscle unit. However, the diseases associated with aging of this unit are considered independently. In recent years, the additive effect of sarcopenia and osteopenia / osteoporosis on the quality of life and health of the elderly has been revealed, and thus the concept of Osteosarcopenia emerged. In older adults, reporting a progressive decrease in muscle mass and strength. Along with the above, accidental falls at home (by fragility?) are among its main causes of death, suggesting that a group of these aging people may have undiagnosed Osteosarcopenia. To develop capacities for its prevention the objective of this narrative revision are update aspects related to the aging of muscle. Bone unit and diagnostic criteria and therapeutic options for Osteosarcopenia. Exhaustive review of complete articles, in English and Spanish, downloaded manually and published between 2010 and 2019, obtained from the Pubmed, Scielo Regional and Google Scholar databases. the fatty infiltration of the muscle-bone unit It is the most important event of aging, there is no uniformity in the diagnosis of sarcopenia and adequate protein intake, calcium and D vitamin and strength exercises are principal therapeutic options. There are no drugs with on both entities(AU)

Effects of the falls and fractures clinic as an integrated multidisciplinary model of care in Australia: a pre-post study.

OBJECTIVES: Traditionally, the approach to fracture prevention has focused on increasing bone mineral density while typically lacking a combined clinical approach to falls prevention and vice versa. To resolve this gap, we implemented and evaluated a novel combined model of care to the assessment and prevention of osteoporosis and falls in the outpatients setting. SETTING: Falls and Fractures Clinic (FFC) at Nepean Hospital (Penrith, NSW, Australia). PARTICIPANTS: Pre-effects and posteffects assessment of 106 community-dwelling older patients referred from the community. PRIMARY AND SECONDARY OUTCOME MEASURES: Previous falls and fractures were recorded. Clinical, functional and paraclinical evaluations were performed. A comprehensive multidisciplinary care plan was then tailored based on the presence of risk factors. Six-month follow-ups were performed assessing the incidence of falls and fractures, change in risk factors for falls and level of risk, with the recommended plan. RESULTS: We report that 97% of patients had a fall in the preceding 6 months, 47.6% of whom experienced a fracture from the fall. Furthermore, 64% of patients had a marked risk for falling by Physiological Profile Assessment (PPA), 90% had intermediate-high 10-year probability of fracture according to FRAX and 78% had sarcopenia. At 6-month follow-up, we observed more than an 80% reduction in falls and recurrent falls, and 50% reduction in fractures. In addition, 65% of patients had reduced PPA and a 57% reduction in 10-year fracture probability. CONCLUSIONS: In conclusion, we suggest that a multidisciplinary FFC can provide substantial reductions in falls and fractures for high-risk older people, even over a relatively short 6-month time period. The current model of service provision via traditional falls clinics could be significantly improved by encompassing fracture prevention within the multifactorial approach to interventions.

Stages of sarcopenia, bone mineral density, and the prevalence of osteoporosis in older women.

A better understanding of the relationship between osteoporosis and sarcopenia may help to develop effective preventive and therapeutic strategies. In the present study, the association between different stages of sarcopenia, BMD, and osteoporosis was examined. The salient findings indicate that a dose-response relationship exists between sarcopenia stages and bone-related phenotypes. PURPOSE: To assess the association between sarcopenia stages, bone mineral density (BMD), and the prevalence of osteoporosis in older women. METHODS: Two hundred thirty-four women (68.3 ± 6.3 years) underwent body composition and BMD measurements using dual-energy X-ray absorptiometry. Quadriceps isokinetic torque was evaluated, and the timed up-and-go test was conducted as a measure of function. Sarcopenia stages were classified according to European Working Group on Sarcopenia in Older People (EWGSOP): nonsarcopenia, presarcopenia, sarcopenia, and severe sarcopenia. Osteoporosis was defined as BMD value (hip or spine) 2.5 standard deviations below a young-adult reference population. Between-group differences were examined using ANOVA for continuous variables and chi-squared for categorical variables. Logistic regression was performed to evaluate the association between sarcopenia stages and osteoporosis. RESULTS: Rates of osteoporosis were 15.8%, 19.2%, 35.3%, and 46.2% for nonsarcopenia, presarcopenia, sarcopenia, and severe sarcopenia, respectively (P = 0.002). Whole-body and femoral neck BMD values were significantly lower among all sarcopenia stages when compared to nonsarcopenia (all P values < 0.05, η2p 0.113 to 0.109). The severe sarcopenia group also showed significantly lower lumbar spine BMD values and T-scores (both P values < 0.05; η2p 0.035 and 0.037, respectively). When clustered, sarcopenia and severe sarcopenia exhibited lower BMD values for all sites (all P values < 0.01), and presented a significantly higher risk for osteoporosis (odds ratio 3.445; 95% CI 1.521-7.844). CONCLUSION: The observed results provide support for the concept that a dose-response relationship exists between sarcopenia stages, BMD, and the presence of osteoporosis. These findings strengthen the clinical significance of the EWGSOP sarcopenia definition and indicate that severe sarcopenia should be viewed with attention by healthcare professionals.

Osteosarcopenia: where bone, muscle, and fat collide.

As the world's population ages, the prevalence of chronic diseases increases. Sarcopenia and osteoporosis are two conditions that are associated with aging, with similar risk factors that include genetics, endocrine function, and mechanical factors. Additionally, bone and muscle closely interact with each other not only anatomically, but also chemically and metabolically. Fat infiltration, a phenomenon observed in age-related bone and muscle loss, is highly prevalent and more severe in sarcopenic and osteoporotic subjects. Clinically, when individuals suffer a combination of both disorders, negative outcomes such as falls, fractures, loss of function, frailty, and mortality increase, thus generating significant personal and socio-economic costs. Therefore, it is suggested that when bone mineral density loss is synchronic with decreased muscle mass, strength, and function, it should be interpreted as a single diagnosis of osteosarcopenia, which may be preventable and treatable. Simple interventions such as resistance training, adequate protein and calcium dietary intake, associated with maintenance of appropriate levels of vitamin D, have a dual positive effect on bone and muscle, reducing falls, fractures, and, consequently, disability. It is essential that fracture prevention approaches-including postfracture management-involve assessment and treatment of both osteoporosis and sarcopenia. This is of particular importance as in older persons the combination of osteopenia/osteoporosis and sarcopenia has been proposed as a subset of frailer individuals at higher risk of institutionalization, falls, and fractures. This review summarizes osteosarcopenia epidemiology, pathophysiology, diagnosis, outcomes, and management strategies.

Osteosarcopenia: un factor de riesgo para fracturas osteoporoticas / Osteosarcopenia: a risk factor for osteoporotic fractures / Osteo-sarcopenia: um fator de risco para fraturas osteoporóticas

La sarcopenia asociada a la edad es una condicion caracterizada por una disminucion de la masa y fuerza muscular de causa multifactorial. El hueso y el musculo son dos tejidos que se encuentran interrelacionados entre si. Las fuerzas mecanicas aplicadas sobre el hueso son aquellas originadas por la contraccion muscular, lo cual condiciona las propiedades del hueso como masa, tamano, forma y arquitectura. Por la tanto, la disminucion de la masa y fuerza muscular conduciran a una disminucion de la cantidad y calidad osea. De esta manera, la sarcopenia es una condicion que en adultos mayores incrementa el riesgo de caidas y fracturas por fragilidad osea, por lo que se propone el termino de osteosarcopenia para identificar aquellos adultos mayores con mayor riesgo de fracturas por fragilidad osea. En la actualidad, el desarrollo de un consenso sobre los criterios diagnosticos de osteosarcopenia son demandados por la comunidad medica ya que estos permitirian identificar a los pacientes con mayor riesgo de desarrollar fracturas osteoporoticas, realizar intervenciones terapeuticas adecuadas y mejorar la calidad de vida de los adultos mayores.

Age-related sarcopenia is a condition which typically shows a decline in muscle mass and strength due to multifactorial causes. Bones and muscles are two interrelated tissues. The mechanical forces applied on bones are those derived from muscle contraction, conditioning bone properties, such as mass, size, shape and architecture. Therefore, the decline of muscle mass and strength would lead to a decrease in bone quality and quantity resulting in bone frailty. For this reason, sarcopenia is a condition that increases the risk of suffering falls and fractures in older adults. Currently, osteosarcopenia is the term used to identify those older adults with a greater risk of fractures due to bone frailty; however, a consensus of the medical community is needed for developing diagnostic criteria which makes it possible to identify patients with a high risk of developing osteoporotic fractures, to perform adequate therapeutic interventions and to improve the quality of life of older adults.

A sarcopenia associada à idade é uma condição caracterizada por uma diminuição da massa e da força muscular derivada de uma série de causas. O osso e o músculo são dois tecidos que se encontram inter-relacionados entre si. As forças mecânicas aplicadas sobre o osso são aquelas originadas pela contração muscular, que condiciona as propriedades do osso, tais como a massa, o tamanho, a forma e a arquitetura. Portanto, a diminuição da massa e da força muscular conduzirão à uma diminuição da quantidade e da qualidade ósseas. Desta maneira, a sarcopenia é uma condição que em adultos idosos incrementa o risco de quedas e fraturas em razão da fragilidade óssea, razão pela qual se propõe o termo osteo-sarcopenia para identificar a aqueles idosos com maior risco de fraturas por fragilidade óssea. Na atualidade, o desenvolvimento de um consenso sobre os critérios diagnósticos da osteo-sarcopenia é demanda da comunidade médica, na medida em que permitiria identificar os pacientes com maior risco de desenvolver fraturas osteoporóticas, realizar intervenções terapêuticas adequadas e melhorar a qualidade de vida dos idosos.