Association between Circulating Osteoprogenitor Cells and Sarcopenia.

BACKGROUND: Circulating osteoprogenitor (COP) cells are a surrogate of the bone marrow mesenchymal stem cells with high levels observed in osteoporosis and the initial stages of fracture healing. Conversely, a low percentage of COP cells (%COP) is strongly associated with frailty and disability. However, it is unknown whether %COP is associated with sarcopenia, a musculoskeletal disease closely related to frailty. OBJECTIVES: This study sought to determine the associations between %COP and sarcopenia defined using the Sarcopenia Definitions and Outcomes Consortium (SDOC) criteria. METHODS: Data from a random sample of 73 community-dwelling older persons enrolled in the Nepean Osteoporosis and Frailty study (median age 74 years; 60% female) were analyzed. %COP was quantified by flow cytometry using selective gating of CD45/osteocalcin (OCN) + cells. Sarcopenia was defined using handgrip strength and gait speed with cut points as per the SDOC criteria. Linear regression was used for analysis. RESULTS: Sarcopenia was identified in 19% of participants, all of whom were frail. After adjusting for age, sex, and interleukin 6, sarcopenic participants had 36% lower %COP (95% confidence interval [CI] -56%, -6%, p = 0.024). Both grip strength and gait speed showed associations with %COP (p = 0.065 and 0.002, respectively); however, after adjusting for age and frailty, only gait speed remained associated with %COP (0.1 m/s increase in gait velocity was associated with a 5% increase in %COP cells (95% CI 0%, 10%, p = 0.052). CONCLUSIONS: High levels of %COP are associated with better muscle function. Future longitudinal studies are required to elucidate the clinical utility of %COP as a potential biomarker or disease stratifier for sarcopenia.

Evaluating Effectiveness of an Acute Rehabilitation Program in Hospital-Associated Deconditioning.

BACKGROUND AND PURPOSE: Acute hospitalization can result in significant decline in functional ability, known as hospital-associated deconditioning. Older adults are most vulnerable, with resultant functional difficulties and increased risk of institutionalization. This study evaluates the effectiveness of a multidisciplinary acute rehabilitation program in hospital-associated deconditioning on routinely collected outcome data to examine its impact to determine whether a controlled trial is warranted. METHODS: We conducted a retrospective review of the hospital database for the national rehabilitation clinical registry for 2013 and 2014. We analyzed responses from patient feedback questionnaires over a 2-year period to assess patient experience of the rehabilitation program. RESULTS AND DISCUSSION: The analysis included 289 patients referred to our acute rehabilitation program. Most patients were aged 81-90 years, representing 47% (n = 137) of all admissions. The main impairment group was deconditioning (54%). The median entry time to the acute rehabilitation program for this impairment group was 5 days from admission and length of stay in the rehabilitation program was 9 days. Many of these patients (57%) were directly discharged home, with only 21% needing transfer for inpatient rehabilitation. The average Functional Independence Measure score gain was 22 for the patients directly discharged home, with an average discharge Functional Independence Measure score of 94/126. Of the patient feedback responses received (response rate: 24%), 96% rated the program as very good or good. We observed improved functional outcomes among program participants, with the majority directly discharged home, reduced transfer to rehabilitation hospitals, and patient acceptance of this acute rehabilitation program. CONCLUSION: These promising results suggest that a more rigorous evaluation of this acute rehabilitation program in the management of hospital-associated deconditioning is warranted.

Lamin A expression in circulating osteoprogenitors as a potential biomarker for frailty: The Nepean Osteoporosis and Frailty (NOF) Study.

Lamin A is a protein of the nuclear lamina. Low levels of lamin A expression are associated with osteosarcopenia in mice. In this study, we hypothesized that low lamin A expression is also associated with frailty in humans. We aimed to develop a non-invasive method to quantify lamin A expression in epithelial and circulating osteoprogenitor (COP) cells, and to determine the relationship between lamin A expression and frailty in older individuals. COP cells and buccal swabs were obtained from 66 subjects (median age 74; 60% female; 26 non-frail, 23 pre-frail, and 17 frail) participating at the Nepean Osteoporosis and Frailty (NOF) Study. We quantified physical performance and disability, and stratified frailty in this population. Lamin A expression in epithelial and COP cells was quantified by flow cytometry. Linear regression models estimated the relationship between lamin A expression in buccal and COP cells, and prevalent disability and frailty. Lamin A expression in buccal cells showed no association with either disability or frailty. Low lamin A expression values in COP cells were associated with frailty. Frail individuals showed 60% lower levels of lamin A compared to non-frail (95% CI -36 to -74%, p<0.001) and 62% lower levels compared to pre-frail (95%CI -40 to -76%, p<0.001). In summary, we have identified lamin A expression in COP cells as a strong indicator of frailty. Further work is needed to understand lamin A expression as a risk stratifier, biomarker, or therapeutic target in frail older persons.

Age, gender, and percentage of circulating osteoprogenitor (COP) cells: The COP Study.

Circulating osteoprogenitor (COP) cells are blood-borne cells which express a variety of osteoblastic markers and are able to form bone nodules in vivo. Whereas a high percentage of COP cells (%COP) is associated with vascular calcification, low %COP has been associated with disability and frailty. However, the reference range of %COP in age- and gender-matching populations, and the age-related changes in %COP remain unknown. A cross-sectional study was undertaken in 144 healthy volunteers in Western Sydney (20-90year-old, 10 male and 10 female subjects per decade). %COP was quantified by flow cytometry. A high inter-and intra-rater reliability was found. In average, in this healthy population average of %COP was 0.42. There was no significant difference in %COP among the age groups. Similarly, no significant difference was found in %COP with gender, weight, height or BMI. In addition, we identified a normal reference range of %COP of 0.1-3.8%. In conclusion, in addition to the identification of steady levels of COP cells with age, we also identified a normal reference range of %COP, which could be used in future studies looking at musculoskeletal diseases in older populations.

Association Between Circulating Osteogenic Progenitor Cells and Disability and Frailty in Older Persons: The Nepean Osteoporosis and Frailty Study.

Circulating osteogenic progenitor (COP) cells are considered as surrogates of the mesenchymal repository in the body. In this study, we hypothesized that COP cells decrease with age and that lower levels of COP cells are associated with greater frailty and disability in older persons. Using well-established clinical criteria, we quantified physical performance and disability and stratified frailty in a random sample of community-dwelling individuals enrolled in the Nepean Osteoporosis and Frailty (NOF) Study (mean age 82.8; N = 77; 70% female; 27 nonfrail, 23 prefrail, and 27 frail). Percentage of COP cells was quantified by flow cytometry. Logistic regression models estimated the relationship between the percentage of COP cells and prevalent disability, poor physical performance, and frailty. We found that aging is associated with a significant decrease in COP cells (p < .001). Lower percentages of COP cells were associated with disability and poor physical performance (p < .001). Older adults with COP cells in the lower quartile were more likely to be frail (odds ratio 2.65, 95% confidence interval 2.72-3.15, p < .001). In conclusion, COP cells in the circulation decrease with age. Lower percentages of COP cells in late life are associated with prevalent frailty and disability. Further longitudinal studies are needed to understand COP cells as a risk stratifier, biomarker, or therapeutic target and to predict disability in frail older persons.

Phenotype of sarcopenic obesity in older individuals with a history of falling.

BACKGROUND: Although sarcopenic obesity is associated with disability in middle-aged community-dwelling individuals, the phenotype of sarcopenic obesity in people 65 and older, especially those with a history of falls, remain unknown. To fill this knowledge gap, the goal of this study was to obtain a comprehensive phenotype of sarcopenic obesity in this high-risk population. METHODS: Cross-sectional study of 680 subjects (mean age=79±9, 65% female) assessed between 2009 and 2013 at the Falls and Fractures Clinic, Nepean Hospital (Penrith, Australia). The assessment included a comprehensive examination, posturography, gait velocity, grip strength, bone densitometry and body composition by DXA, and blood tests for biochemical status. Patients were divided into four groups based on DXA and clinical criteria: 1) sarcopenic obese; 2) non-sarcopenic obese; 3) sarcopenic and; 4) non-sarcopenic/non-obese. The difference between groups was assessed by one-way ANOVA, chi-square analysis, and multivariable linear regression. RESULTS: Sarcopenic obese subjects were older (81.1±7.3), mostly female and more likely to have lower bone mineral density, lower grip strength, slower gait velocity, and poor balance. Sarcopenic obese individuals also showed significantly higher parathyroid hormone and lower vitamin D. CONCLUSIONS: We identified a particular set of clinical and biochemical characteristics in our subgroup of sarcopenic obese older fallers. Identification of these particular characteristics in the clinical setting is essential in order to prevent poor outcomes in this high-risk population.

Yield and cost-effectiveness of laboratory testing to identify metabolic contributors to falls and fractures in older persons.

UNLABELLED: Falls and fractures constitute a major cause of morbidity and mortality among older adults. Although falls and fractures share similar risk factors, there is no integrated approach to identifying secondary causes of both entities. We report a cost-effective approach to identify metabolic causes of falls and fractures in the clinical setting. PURPOSE: Falls and fractures are a major cause of morbidity and mortality among older adults. Metabolic disorders contributing to the combined risk of falls and fractures are frequent but often go undetected. The most efficient and cost-effective laboratory screening strategy to unmask these disorders remains unknown. The purpose of this study was to identify the most cost-effective laboratory tests to detect undiagnosed metabolic contributors and to decide treatment of these disorders in older persons. METHODS: This is a cross-sectional study design, which included all participants attending the Falls & Fractures Clinic, Nepean Hospital (Penrith, Australia) between 2008 and 2013. Chemistry profile included 25(OH) vitamin D, parathyroid hormone (PTH), albumin, creatinine, calcium, phosphate, vitamin B-12, folate, and thyroid-stimulating hormone (TSH) for all patients, and serum testosterone in men. The number of new diagnoses identified and their cost-effectiveness (cost in US$ per patient screened and cost per new diagnosis) were calculated. RESULTS: A total of 739 participants (mean age 79, 71 % female) were assessed. Among 233 participants with complete laboratory tests, previously undiagnosed disorders were identified in 148 (63.5 %). Vitamin D deficiency (27 %) and hyperparathyroidism (21.5 %) were the most frequent diagnoses. A testing strategy including serum vitamin D, calcium, PTH, creatinine/estimated glomerular filtration rate (eGFR), and TSH for all patients and serum testosterone in men would have been sufficient to identify secondary causes of falls and fractures in 94 % of patients at an estimated cost of $190.19 per patient screened and $257.64 per diagnosis. CONCLUSIONS: The minimum cost-effective battery for occult metabolic disorders in older adults at risk of falls and fractures should include serum vitamin D, PTH, TSH, creatinine/eGFR, testosterone (in men), and calcium.

Phenotype of osteosarcopenia in older individuals with a history of falling.

OBJECTIVES: 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. However, the particular clinical, biochemical, and functional characteristics of the osteosarcopenic (OS) patients remain unknown. In this study, we used a clinical definition of osteosarcopenia aiming to determine the clinical, functional, and biochemical features that are unique to these patients within a population of older people who fall. DESIGN: Cross-sectional study. SETTING: Falls and Fractures Clinic, Nepean Hospital (Penrith, NSW, Australia). PARTICIPANTS: A total of 680 people (mean age = 79, 65% women) assessed between 2009 and 2013. MEASUREMENTS: Assessment included medical history, physical examination, bone densitometry and body composition by dual-energy X-ray absorptiometry, posturography, grip strength, gait parameters (GaitRITE), and blood tests for nutrition and secondary causes of sarcopenia and osteoporosis. Patients were divided into 4 groups: (1) osteopenic (BMD <-1.0 SD), (2) sarcopenic, (3) OS, and (4) nonsarcopenic/nonosteopenic. Difference between groups was assessed with 1-way ANOVA and χ(2) analysis. Multivariable linear regression evaluated the association between the groups and measures of physical function. Multivariable logistic regression evaluated risk factors for being in the OS group. RESULTS: Mean age of the OS patients was 80.4 ± 7.0 years. Our analyses showed that OS patients are older, mostly women, are at high risk for depression and malnutrition, have body mass index lower than 25, and showed a higher prevalence of peptic disease, inflammatory arthritis, maternal hip fracture, history of atraumatic fracture, and impaired mobility. CONCLUSION: We have reported a set of characteristics that are highly prevalent in OS patients. This study could be used to inform the design of future trials and to develop interventions to prevent institutionalization and poor outcomes in this particular set of high-risk patients.

Postoperative prevention of falls in older adults with fragility fractures.

The postoperative period after correction of a fragility fracture is usually associated with functional deconditioning. This deconditioning is caused by multiple factors associated with a higher risk of falls during the immediate postoperative period and after discharge. Identification of risk and appropriate fall prevention interventions in these patients are pivotal. In this article, an overview is presented of the strategies to identify falls risk in postoperative patients after suffering a fragility fracture. Evidence is presented favoring targeted multicomponent intervention for falls prevention rather than a single intervention in fractured older patients at high risk of new falls and fractures.

Evaluation of a blended learning model in geriatric medicine: a successful learning experience for medical students.

BACKGROUND: Despite the increasingly ageing population, teaching geriatric medicine at medical schools is a challenge due to the particularities of this subspecialty and the lack of student interest in this subject. METHODS: We assessed a blended system that combines e-learning and person-to-person interaction. Our program offered the students a hands-on learning experience based on self-reflection, access to technology, interactive learning, frequent interaction with the multidisciplinary team, more exposure to patients, and regular feedback. RESULTS: Our results indicate that the students appreciate this system as a rich and effective learning experience demonstrated by their positive feedback and by their significant improvement in knowledge assessed at the end of their rotation. CONCLUSION: Implementing an interactive blended system is a beneficial approach to teaching geriatric medicine in medical schools and to motivating medical students' interest in this important medical subspecialty.