Genetic Effects on Bone Loss in Peri- and Postmenopausal Women: A Longitudinal Twin Study

This longitudinal twin study was designed to assess the heritability of bone loss in peri- and postmenopausal women. A sample of 724 female twins was studied. Baseline and repeat BMD measurements were performed. Results of genetic model-fitting analysis indicated genetic effects on bone loss account for similar to 40% of the between-individual variation in bone loss at the lumbar spine, forearm, and whole body. Introduction: BMD and bone loss are important predictors of fracture risk. Although the heritability of peak BMD is well documented, it is not clear whether bone loss is also under genetic regulation. This study was designed to assess the heritability of bone loss in peri- and postmenopausal women. Materials and Methods: A sample of 724 female twins (177 monozygotic [MZ] and 185 dizygotic [DZ] pairs), 45-82 yr of age, was studied. Each individual had baseline BMD measurements at the lumbar spine, hip, forearm, and total body by DXA and at least one repeat measure, on average 4.9 yr later. Change in BMD (Delta BMD) was expressed as percent of gain or loss per year. Intraclass correlation coefficients for ABMD were calculated for MZ and DZ pairs. Genetic model-fitting analysis was conducted to partition the total variance of ABMD into three components: genetic (G), common environment (C), and specific environment, including measurement error (E). The index of heritability was estimated as the ratio of genetic variance over total variance. Results: The mean annual Delta BMD was -0.37 +/- 1.43% (SD) per year at the lumbar spine, -0.27 +/- 1.32% at the total hip, -0.77 +/- 1.66% at the total forearm, -0.36 +/- 56% at the femoral neck, and -0.16 +/- 0.81% at the whole body. Intraclass correlation coefficients were significantly higher in MZ than in DZ twins for all studied parameters, except at the hip sites. Results of genetic model-fitting analysis indicated that the indices of heritability for ABMD were 0.38, 0.49, and 0.44 for the lumbar spine, total forearm, and whole body, respectively. However, the genetic effect on ABMD at all hip sites was not significant. Conclusions: These data suggest that, although genetic effects on bone loss with aging are less pronounced than on peak bone mass, they still account for similar to 40% of the between-individual variation in bone loss for the lumbar spine, total forearm, and whole body in peri- and postmenopausal women. These findings are relevant for studies aimed at identification of genes that are involved in the regulation of bone loss

Does combined osteopenia/osteoporosis and sarcopenia confer greater risk of falls and fracture than either condition alone in older men? The Concord Health and Ageing in Men Project

Background It is unclear whether older men with osteopenia/osteoporosis and sarcopenia (so-called osteosarcopenia) are at greater risk of falls and fractures than those with either condition alone. Methods One thousand five hundred seventy-five community-dwelling men aged ≥70 years had appendicular lean mass, total hip and lumbar spine bone mineral density determined by dual-energy x-ray absorptiometry, and completed hand grip strength and gait speed tests. Osteopenia/osteoporosis was defined as a T-score at any site ≤−1.0 SD. Sarcopenia was defined using the European Working Group on Sarcopenia algorithm. Participants were contacted every 4 months for 6 ± 2 years to ascertain incident fractures (confirmed by radiographic reports) and for 2 years for incident falls. Results Prevalence of osteosarcopenia was 8%, while 34% of participants had osteopenia/osteoporosis alone and 7% had sarcopenia alone. Men with osteosarcopenia had significantly increased fall (incidence rate ratio: 1.41; 95% confidence interval [CI]: 1.02 to 1.95) and fracture risk (hazard ratio: 1.87; 95% CI: 1.07 to 3.26) compared with men with neither osteopenia/osteoporosis nor sarcopenia. There was no statistical interaction between osteopenia/osteoporosis and sarcopenia, and falls and fracture risk were not different for osteosarcopenia compared with either condition alone (all p > .05). Conclusions Community-dwelling older men with combined osteopenia/osteoporosis and sarcopenia do not have increased falls and fracture risk compared with those with either condition. Further research is required to clarify whether the term “osteosarcopenia” has any meaning above and beyond either term alone and therefore potential clinical utility for falls and fracture prediction.NHMRC (project grant number 301916) and the Ageing and Alzheimer’s Institute. D.Scott is supported by a NHRMC Career Development Fellowship (GNT1123014

Health and Functional Status of Adults with Intellectual Disability Referred to the Specialist Health Care Setting: A Five-Year Experience

Aims and Method. The Developmental Disability Database in the Department of Rehabilitation Medicine at a metropolitan hospital was audited for observations on adults with Intellectual Disability living in the local region (total population 180,000) who were seen in an identified multidisciplinary specialist clinic, during 2006–2010. Results. There were 162 people (representing half the known number of adults with Intellectual Disability living in the region): 77 females, 85 males, age range 16–86 years. The most common complex disabilities referred to the specialists in this clinic were epilepsy (52%), challenging or changing behavior (42%) and movement disorders (34%). Early onset dementia was a feature of the group (7%). The prevalence of prescription of medications for gastro-oesophageal reflux was high (36%) and similar to the numbers of people taking psychotropic medications. The rates of chronic cardiovascular disease (2%), chronic respiratory disease (10%) and generalised arthritis (11%) were low overall, but did rise with increasing age. Conclusions. Complex neurological disabilities are common, and chronic medical illnesses are uncommon in adults with Intellectual Disability referred to specialist clinicians in this region. A combined, coordinated, multidisciplinary clinic model addresses some of the barriers experienced by adults with Intellectual Disability in the secondary health system

Evaluating Calculated Free Testosterone as a Predictor of Morbidity and Mortality Independent of Testosterone for Cross-sectional and 5-Year Longitudinal Health Outcomes in Older Men: The Concord Health and Ageing in Men Project

To determine whether calculated free testosterone (cFT) provides prognostic information independent of serum T for predicting morbidity and mortality in older men in cross-sectional and 5-year longitudinal analyses. We studied men aged ≥70 years at baseline (n = 1,705), 2-year and 5-year measuring serum T (liquid chromatography-mass spectrometry), SHBG (immunoassay), cFT (an assumption-free empirical formula) together with 24 morbidity and 4 mortality outcomes. For cross-sectional and longitudinal analyses we employed a joint prediction model using generalized estimating equation models adjusted for age, smoking, comorbidities, and body mass index (BMI) with men having both normal T and normal cFT as referent group. Most morbidity and mortality outcomes were predicted by a combination of low T and cFT (LL). By contrast, only a single morbidity outcome in cross-sectional and none in longitudinal analysis was predicted by low T/normal cFT (LN) or normal T/low cFT (NL) without significant LL associations (isolated discordance). While for the few outcomes that predicted morbidity in men with discordances (LN or NL), these predictions only occurred when LL was also significant. Hence, for morbidity or mortality prediction in older men, discordance between cFT and T is unusual and isolated discordance is rare, so that cFT provides minimal independent prognostic information over serum T.NHMRC, Sydney Medical School Foundation, and Ageing and Alzheimer’s Institute

A Multidomain Intervention Program for Older People with Dementia: A Pilot Study

Background: Multidomain interventions have been shown to be effective in improving cognition, quality of life, reducing neuropsychiatric symptoms and delaying progression of functional impairment or disability in dementia patients. To investigate the multidomain intervention in other populations and diverse cultural and geographical settings, this pilot study will assess the feasibility of a multidomain intervention for older people with dementia in nursing homes in Vietnam. Methods: Participants will be randomized into two equal groups, to receive either a multidomain intervention (intervention group) or regular health advice (control group). The intervention will include physical, cognitive, and social interventions as well as management of metabolic and vascular risk factors. We will hypothesize that the multidomain intervention will be feasible in Vietnam, and participants who receive the intervention will show improvement in quality of life, behaviors, functional ability, cognitive function, sleep, and in reduction of falls, use of healthcare services, and death rate compared to those in the control group during the 6 months intervention period and after the 6 months extended follow-up. Discussion: This is the first study to evaluate the feasibility of a multidomain intervention program for older people with dementia in nursing homes in Vietnam. The results from the trial will inform clinicians and the public of the possibility of comprehensive treatment beyond simply drug treatments for dementia. This paves the way for further studies to evaluate the long-term effects of multidomain interventions in dementia patients. Furthermore, the research results will provide information on the effectiveness of multidomain interventions which will inform policy development on dementia. Trial Registration: The trial is registered with ClinicalTrials.gov identifier: NCT04948450 on 02/07/2021

Association between pain and the frailty phenotype in older men: longitudinal results from the Concord Health and Ageing in Men Project (CHAMP)

Objectives to determine whether pain increases the risk of developing the frailty phenotype and whether frailty increases the risk of developing chronic or intrusive pain, using longitudinal data. Design/Setting longitudinal data from the Concord Health and Ageing in Men Project (CHAMP), a prospective population based cohort study. Participants a total of 1,705 men aged 70 years or older, living in an urban area of New South Wales, Australia. Measurements data on the presence of chronic pain (daily pain for at least 3 months), intrusive pain (pain causing moderate to severe interference with activities) and the criteria for the Cardiovascular Health Study (CHS) frailty phenotype were collected in three waves, from January 2005 to October 2013. Data on age, living arrangements, education, smoking status, alcohol consumption, body mass index, comorbidities, cognitive function, depressive symptoms and history of vertebral or hip fracture were also collected and included as covariates in the analyses. Results a total of 1,705 participants were included at baseline, of whom 1,332 provided data at the 2-year follow-up and 940 at the 5-year follow-up. Non-frail (robust and pre-frail) men who reported chronic pain were 1.60 (95% confidence interval (CI): 1.02–2.51, P = 0.039) times more likely to develop frailty at follow-up, compared to those with no pain. Intrusive pain did not significantly increase the risk of future frailty. Likewise, the frailty status was not associated with future chronic or intrusive pain in the adjusted analysis. Conclusions the presence of chronic pain increases the risk of developing the frailty phenotype in community-dwelling older men.NHMRC, The Ageing and Alzheimer's Institut

Community-dwelling men with dementia are at high risk of hip but not any other fracture: The Concord Health and Ageing in Men Project

Aim The aim of the present longitudinal study of community‐dwelling older men was to examine the association between cognitive status at baseline, and falls, fractures and bone loss over time. Methods In the Concord Health and Aging in Men Project, 1705 community‐dwelling men aged 70–97 years had detailed baseline clinical assessment of cognitive status (dementia, mild cognitive impairment [MCI] and normal cognition), as well as depression, physical activity, neuromuscular function, health status, sociodemographics, comorbidities, medication use and serum 25 hydroxyvitamin D, 1,25 dihydroxyvitamin D and parathyroid hormone levels. During a mean follow‐up period of 6 years, participants were contacted 4‐monthly to ascertain incident falls and fractures, the latter being confirmed by radiographic reports. Bone mineral density was measured by dual X‐ray absorptiometry at multiple time‐points. Results At baseline, 120 men were assessed to have MCI and 93 men to have dementia. Over time, there were 162 first incident fractures, including 43 hip and 32 vertebral fractures. In univariate models, baseline dementia, but not MCI, predicted an increased incidence of hip fracture (HR 6.95, 95% CI 3.47–13.96), but not vertebral (HR 2.26, 95% CI 0.79–6.46) or non‐hip non‐vertebral fracture (HR 0.73, 95% CI 0.27–1.99). The strong risk of hip fractures associated with dementia remained after accounting for potential confounders (HR 4.44, 95% CI 1.97–9.98). In multivariate analyses, dementia (incidence rate ratio 2.26, 95% CI 1.70–2.99), but not MCI, was associated with an increased risk of falls compared with normal cognition. There was no association between baseline dementia and change in bone mineral density. Conclusions Older men with dementia, but not MCI, have a greater tendency to fall and sustain hip fractures, but not any other types of fractures.NHMRC, Ageing and Alzheimer's Institute, Sydney Medical School Foundatio

Development of a rating scale for objective assessment of performance in laparoscopic appendicectomy surgery

First published: 26 March 2022Backgrounds: Laparoscopic appendicectomy (LA) is the most common index procedure for junior surgical trainees. Despite the shift towards competency-based training, there is no method of quantitatively assessing performance during LA. This study aimed to obtain expert consensus regarding the items required to create a LA Rating Scale (LARS). Methods: A list of steps required for LA surgery, as well as descriptors of “poor”, “average” and “excellent” performance for each of these steps were created for potential inclusion into an objective assessment tool for LA surgery. Using a Delphi method, 20 experts from multiple institutions rated on a Likert scale from 1 to 5 the suitability of these steps and descriptors of performance. Responses were obtained until consensus (Cronbach’s α > 0.8) was achieved. Results: Fifteen experts participated in the study. Consensus was achieved for all items during the first iteration of the Delphi with a Cronbach’s α of 0.96. The Cronbach’s α for the steps was 0.87 and 0.92 for the descriptors of performance. Steps and descriptors of performance that >80% of experts rated as ≥4 were used to create the final LARS tool. Conclusion: Multi-institutional expert consensus was obtained regarding the steps and, for the first time, descriptors of performance for LA, demonstrating their face and content validity, as well as generalisability. Subsequently, the LARS tool was created that can be used to quantitatively assess intra-operative performance. This instrument can be used to identify weaknesses in performance and facilitate deliberate practice, thus shifting training in LA to a competency-based approach.Pramudith Sirimanna, Stephen Boyce, Prashanth Gunanayagam, Marc A. Gladman, and Vasi Naganatha

Genetic Effects on Bone Loss in Peri- and Postmenopausal Women: A Longitudinal Twin Study

This longitudinal twin study was designed to assess the heritability of bone loss in peri- and postmenopausal women. A sample of 724 female twins was studied. Baseline and repeat BMD measurements were performed. Results of genetic model-fitting analysis indicated genetic effects on bone loss account for similar to 40% of the between-individual variation in bone loss at the lumbar spine, forearm, and whole body. Introduction: BMD and bone loss are important predictors of fracture risk. Although the heritability of peak BMD is well documented, it is not clear whether bone loss is also under genetic regulation. This study was designed to assess the heritability of bone loss in peri- and postmenopausal women. Materials and Methods: A sample of 724 female twins (177 monozygotic [MZ] and 185 dizygotic [DZ] pairs), 45-82 yr of age, was studied. Each individual had baseline BMD measurements at the lumbar spine, hip, forearm, and total body by DXA and at least one repeat measure, on average 4.9 yr later. Change in BMD (Delta BMD) was expressed as percent of gain or loss per year. Intraclass correlation coefficients for ABMD were calculated for MZ and DZ pairs. Genetic model-fitting analysis was conducted to partition the total variance of ABMD into three components: genetic (G), common environment (C), and specific environment, including measurement error (E). The index of heritability was estimated as the ratio of genetic variance over total variance. Results: The mean annual Delta BMD was -0.37 +/- 1.43% (SD) per year at the lumbar spine, -0.27 +/- 1.32% at the total hip, -0.77 +/- 1.66% at the total forearm, -0.36 +/- 56% at the femoral neck, and -0.16 +/- 0.81% at the whole body. Intraclass correlation coefficients were significantly higher in MZ than in DZ twins for all studied parameters, except at the hip sites. Results of genetic model-fitting analysis indicated that the indices of heritability for ABMD were 0.38, 0.49, and 0.44 for the lumbar spine, total forearm, and whole body, respectively. However, the genetic effect on ABMD at all hip sites was not significant. Conclusions: These data suggest that, although genetic effects on bone loss with aging are less pronounced than on peak bone mass, they still account for similar to 40% of the between-individual variation in bone loss for the lumbar spine, total forearm, and whole body in peri- and postmenopausal women. These findings are relevant for studies aimed at identification of genes that are involved in the regulation of bone loss

Recruiting older people at nutritional risk for clinical trials: what have we learned?

BACKGROUND: The difficulty of recruiting older people to clinical trials is well described, but there is limited information about effective ways to screen and recruit older people into trials, and the reasons for their reluctance to enrol. This paper examines recruitment efforts for a community-based health intervention study that targeted older adults. METHODS: One year randomized control trial. Undernourished men and women, aged ≥ 65 years and living independently in the community were recruited in three Australian states. Participants were allocated to either oral testosterone undecanoate and high calorie oral nutritional supplement or placebo medication and low calorie oral nutritional supplementation. Hospital admissions, functional status, nutritional health, muscle strength, and other variables were assessed. RESULTS: 4023 potential participants were identified and 767 were screened by a variety of methods: hospital note screening, referrals from geriatric health services, advertising and media segments/appearances. 53 participants (7% of total screened) were recruited. The majority of potentially eligible participants declined participation in the trial after reading the information sheet. Media was the more successful method of recruiting, whereas contacting people identified by screening a large number of hospital records was not successful in recruiting any participants. CONCLUSION: Recruitment of frail and older participants is difficult and multiple strategies are required to facilitate participation. TRIAL REGISTRATION: Australian Clinical Trial Registry: ACTRN 12610000356066 date registered 4/5/2010.Cynthia Piantadosi, Ian M Chapman, Vasi Naganathan, Peter Hunter, Ian D Cameron, and Renuka Visvanatha