Piumali Gunawardene

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.

Comprehensive nutritional status in sarco-osteoporotic older fallers

ObjectivesIn older persons, the combination of osteoporosis and sarcopenia has been proposed as a subset of frailer individuals at higher risk of falls and fractures. However, the particular nutritional status of the sarco-osteoporotic (SOP) patients remains unknown. The goal of this study was to obtain a comprehensive picture of nutritional status in SOP patients.DesignCross-sectional study.SettingFalls & Fractures Clinic, Nepean Hospital (Penrith, Australia).Participants680 subjects (mean age=79, 65% female) assessed between 2008–2013.MeasurementsAssessment included medical history, mini-nutritional assessment, physical examination, bone densitometry and body composition by DXA, and blood tests for nutritional status (albumin, creatinine, hemoglobin, vitamin D, vitamin B-12, calcium, phosphate and folate). Patients were divided in 4 groups: 1) osteopenia/osteoporosis (BMD<−1.0 SD); 2) sarcopenia; 3) SOP; and 4) normal (no sarcopenia/no osteoporosis). Difference between groups was assessed with one-way ANOVA and chi square analysis. Multivariable linear regression evaluated the association between the groups and measures of nutritional parameters.ResultsSarcopenia was present in 47.4% of those with osteopenia (167/352) and 62.7% in those with osteoporosis (91/145). Mean age of the SOP was 80.4±7 years. SOP patients showed significantly higher prevalence of falls and fractures. Univariate analyses showed that SOP were more likely than normal to have a BMI< 25 (OR 2.42 95%CI 1.45–4.041, p<0.001), a MNA score <12 (OR 2.0, 95%CI 1.15–3.49, p<0.05), serum folate <20 nmol/L (OR 4.0 95%CI 1.35–11.87, p<0.01) and hemoglobin <120g/L (OR 2.0 95%CI 1.28–3.30, p<0.01). Multivariate analysis showed that a MNA score <12 was independently associated with SOP compared to normal when adjusted for age and gender. Hemoglobin <120g/L, BMI <25, and GDS >6 remained independently associated with SOP after adjustment for all variables including inflammatory conditions. Hypoalbuminemia (<35 g/L) was associated with just osteopenia/osteoporosis (OR: 2.03, 95%CI 1.08–3.81, p<0.01) and just sarcopenia (OR: 1.77, 95%CI 1.0–3.0, p<0.01) compared to normal. No differences in vitamin D, glomerular filtration rate, albumin, corrected calcium, phosphate, red blood cells folate or vitamin B12 levels were found between the subgroups.ConclusionsIn approaching SOP patients, early prevention protocols directed to optimize their nutritional status would be a key strategy to prevent poor outcomes such as falls and fractures in this high risk population. Therefore, nutritional assessment and early nutritional supplementation should be essential domains in this strategy.

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

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.

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.

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

Abstract 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 (20–90 year‐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. HighlightsPercentage of circulating osteoprogenitor (COP) cells is not affected by age.The normal reference range of %COP in the blood of a normal population is 0.1–3.8%.Age‐related changes in osteogenic differentiation of COP cells remain to be elucidated.

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

&NA; 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. HighlightsQuantification of lamin A expression in COP cells is feasibleLow levels of lamin A expression in COP cells are associated with disability and frailtyThis novel method has the potential to become a risk stratifier, biomarker, or therapeutic target in frail older persons. Abbreviations: COP: circulating osteoprogenitor; NOF: Nepean Osteoporosis and Frailty; HGPS: Hutchinson Gilford Progeria Syndrome; MMSE: mini mental state examination; GDS: geriatric depression scale; CCI: Charlson comorbidity index; BMI: body mass index; OARS: Older Americans Resource Scale; ADL: activities of daily living; IADL: instrumental activities of daily living; PASE: Physical Activity Scale for the Elderly; CES‐D: f; CSHA: Canadian Study of Health and Aging; QUS: quantitative ultrasound; SOS: speed of sound; BUA: broadband ultrasound attenuation; SI: stiffness index; TSH: thyroid stimulating hormone; EDTA: ethylenediaminetetraacetic acid; PBMC: peripheral blood mononuclear cells; FMO: fluorescence minus one; PMT: photomultiplier tube; G‐MFI: general median fluorescence intensity; IL‐6: interleukin 6.