Glutamine repeat variants in human RUNX2 associated with decreased femoral neck BMD, broadband ultrasound attenuation and target gene transactivation.

RUNX2 is an essential transcription factor required for skeletal development and cartilage formation. Haploinsufficiency of RUNX2 leads to cleidocranial displaysia (CCD) a skeletal disorder characterised by gross dysgenesis of bones particularly those derived from intramembranous bone formation. A notable feature of the RUNX2 protein is the polyglutamine and polyalanine (23Q/17A) domain coded by a repeat sequence. Since none of the known mutations causing CCD characterised to date map in the glutamine repeat region, we hypothesised that Q-repeat mutations may be related to a more subtle bone phenotype. We screened subjects derived from four normal populations for Q-repeat variants. A total of 22 subjects were identified who were heterozygous for a wild type allele and a Q-repeat variant allele: (15Q, 16Q, 18Q and 30Q). Although not every subject had data for all measures, Q-repeat variants had a significant deficit in BMD with an average decrease of 0.7SD measured over 12 BMD-related parameters (p = 0.005). Femoral neck BMD was measured in all subjects (-0.6SD, p = 0.0007). The transactivation function of RUNX2 was determined for 16Q and 30Q alleles using a reporter gene assay. 16Q and 30Q alleles displayed significantly lower transactivation function compared to wild type (23Q). Our analysis has identified novel Q-repeat mutations that occur at a collective frequency of about 0.4%. These mutations significantly alter BMD and display impaired transactivation function, introducing a new class of functionally relevant RUNX2 mutants.

Ethnicity and falls in older men: low rate of falls in Italian-born men in Australia.

BACKGROUND: past research suggests that fall rates in older persons may differ by ethnicity. The aim of this study was to compare the incidence of falls between older male Italian-born immigrants and their Australian-born counterparts. METHODS: this study analysed data from 335 Italian-born and 848 Australian-born men aged 70 years and over participating in the Concord Health and Ageing in Men Project (CHAMP). Prospective falls data were collected by 4 monthly phone calls (mean follow-up time: 26.7 months). Negative binomial regression compared falls incidence rate ratios (IRR) between the two groups of men. RESULTS: there were 37 (11%) Italian-born men and 185 (22%) Australian-born men who had two or more falls during follow-up (P < 0.001). Negative binomial analysis demonstrated that Italian-born men had half the incidence rate of falls compared with Australian-born men (IRR = 0.51, 95% CI = 0.38-0.67). After adjustment for falls risk factors, Italian-born men remained significantly less likely to fall with a 43% lower fall rate (IRR = 0.57, 95% CI = 0.39-0.85). CONCLUSION: older male Italian-born immigrants are less likely to fall than their Australian-born counterparts. Differences in fall rates between the two groups are not explained by established falls risk factors.

Associations between drug burden index and falls in older people in residential aged care.

OBJECTIVES: To evaluate the association between the Drug Burden Index (DBI), a measure of a person's total exposure to anticholinergic and sedative medications that includes principles of dose-response and maximal effect and is associated with impaired physical function in community-dwelling older people, and falls in residents of residential aged care facilities (RACFs). DESIGN: Data were drawn from participants in a randomized controlled trial that investigated falls and fractures. SETTING: RACFs in Sydney, Australia. PARTICIPANTS: Study participants (N=602; 70.9% female) were recruited from 51 RACFs. Mean age was 85.7 ± 6.4, and mean DBI was 0.60 ± 0.66. MEASUREMENTS: Medication history was obtained on each participant. Drugs were classified as anticholinergic or sedative and a DBI was calculated. Falls were measured over a 12-month period. Comorbidity, cognitive impairment (Mini-Mental State Examination) and depression (Geriatric Depression Scale) were determined. RESULTS: There were 998 falls in 330 individuals during a follow-up period of 574.2 person-years, equating to an average rate of 1.74 falls per person-year. The univariate negative binomial regression model for falls showed incidence rate ratios of 1.69 (95% confidence interval (CI)=1.22-2.34) for low DBI (<1) and 2.11 (95% CI=1.47-3.04) for high DBI (≥1) when compared with those who had a DBI of 0. After adjusting for age, sex, history of falling, cognitive impairment, depression, use of a walking aid, comorbidities, polypharmacy, and incontinence, incident rate ratios of 1.61 (95% CI=1.17-2.23) for low DBI and 1.90 (95% CI=1.30-2.78) for high DBI were obtained. CONCLUSION: DBI is significantly and independently associated with falls in older people living in RACFs. Interventional studies designed for this population are needed to determine whether reducing DBI, through dose reduction or cessation of anticholinergic and sedative drugs, can prevent falls.

Back pain in older male Italian-born immigrants in Australia: the importance of socioeconomic factors.

Back pain is common in older people and is associated with functional disability and poor self-rated health. Older persons are under-represented in back pain research, and research on back pain in older persons from ethnic minorities is particularly sparse. We investigated differences in back pain characteristics, effects and medication use in a population-based sample of 335 Italian-born immigrants and 849 Australian-born men aged 70 years and over. There were 189 (62%) Italian-born men and 507 (63%) Australian-born men who reported experiencing back pain in the past 12 months. Despite no difference in the reported prevalence of back pain between the two groups of men, Italian-born men were more likely to report that their pain was frequent, severe and chronic. Italian-born men were also more likely to report having other sites of pain and that they had limited their activities in the past 12 months due to back pain. Despite these differences, the use of analgesic medication was the same in both groups. Multivariate analyses showed that differences in pain characteristics and effects between the two groups of men were explained by socioeconomic factors such as years of education and occupation history.

Fracture risk assessment in frail older people using clinical risk factors.

BACKGROUND: this study aims to develop and evaluate a simple fracture risk index for use in frail older people. METHODS: clinical risk factors were assessed at baseline for 2,005 older people (473 males, 1,532 females; mean age 85.7 years, SD 7.1 years) living in aged-care facilities. Fractures were ascertained for 2 years from baseline. Cox regression model was used to identify significant risk factors for fracture. Hazard ratios (HRs) from the model were assigned as weights. The risk index was calculated by multiplying the weights of all risk factors. RESULTS: during a mean follow-up of 1.64 years, 401 fractures occurred in 338 participants. Significant independent clinical risk factors for fracture were institution type, balance, history of previous fracture, cognitive function, number of medications, weight and lower leg length (n = 1,813). The index was capable of identifying higher-risk individuals, with almost an 8-fold increase in the risk of fracture for residents from the lowest 15% to the highest 18% of the score. Among 1-year survivors, a high score (>or=15) indicated approximately a one-in-six chance of fracture, while a low score (<8) indicated only a one-in-forty chance of fracture within a year. The area under the receiver operating characteristic (ROC) curve was 0.69 (95% CI: 0.65-0.72) and 0.68 (95% CI: 0.65-0.71) for identifying someone who would have a fracture in 1 and 2 years respectively. CONCLUSIONS: this risk index could identify individuals at higher fracture risk among institutionalised older people, and thus, could help to rationalise the provision of fracture prevention programs in this population.