Skeletal morbidity among survivors of critical illness

Objectives: To describe the incident fracture rate in survivors of critical illness and to compare fracture risk with populationmatched control subjects.

Design: Retrospective longitudinal case– cohort study.

Setting: A tertiary adult intensive care unit in Australia. Patients: All patients ventilated admitted to intensive care and requiring mechanical ventilation for >48 hrs between January 1998 and December 2005.

Interventions: None.

Measurements and Main Results: New fractures were identified in the study population for the postintensive care unit period (intensive care unit discharge to January 2008). The incident fracture rate and age-adjusted fracture risk of the female intensive care unit population were compared with the general population adult females derived from the Geelong Osteoporosis Study. Over the 8-yr period, a total of 739 patients (258 women, 481 men) were identified. After a median follow-up of 3.7 yrs (interquartile range, 2.0–5.9 yrs) for women and 4.0 yrs (interquartile range, 2.1–6.1 yrs) for men, incident fracture rates (95% confidence interval) per 100 patient years were 3.84 (2.58 –5.09) for females 2.41 (1.73–3.09) for males. Compared with an age-matched random population-based sample of women, elderly women were at increased risk for sustaining an osteoporosisrelated fracture after critical illness (hazard ratio, 1.65; 95% confidence interval, 1.08 –2.52; p .02).

Conclusions: The increase in fracture risk observed in postintensive care unit older females suggests an association between critical illness and subsequent skeletal morbidity. The explanation for this association is not explored in this study and includes the effects of pre-existing patient factors and/or direct effects of critical illness. Prospective research evaluating risk factors, the relationship between critical illness and bone turnover, the extent and duration of bone loss, and the associated morbidity in this population is warranted.

Morphometric vertebral fractures of the lower thoracic and lumbar spine, physical function and quality of life in men

The epidemiology and sequelae of morphometric vertebral fracture (MVF) are poorly documented. We found that MVFs of the lower thoracic and lumbar spine were associated with poor quality of life and impaired physical function in men. We recommend that morphometric X-ray absorptiometry be included in routine requests for bone densitometry.

Behavioural and physical characteristics associated with vitamin D status in women

For most people in Australia, the primary source of vitamin D is casual exposure to sunlight. Hypovitaminosis D has been reported for high-risk populations, but little has been documented for women of all ages living in the community. Using cross-sectional data, we aimed to describe physical and behavioural characteristics associated with serum 25-hydroxyvitamin D (25OHD) for such women and to determine the association of serum 25OHD with hypertension and bone health. Serum 25OHD, parathyroid hormone (PTH), blood pressure, bone mineral density (BMD) and anthropometry were measured in a random sample of 861 women aged 20–92 years enrolled in the Geelong Osteoporosis Study, set in a temperate region at latitude 38–39°S. Lifestyle factors (including diet, smoking, medication use, socio-economic status, residence, education, occupation, and physical activity) were documented by questionnaire. In season-adjusted models for women aged 20–54 years, physical activity and living with a partner were independently and positively associated with serum 25OHD; associations with weight and waist–hip ratio were negative. Among older women, physical activity, vitamin D intake and urban dwelling were positively associated with serum 25OHD; age, weight and smoking were negative. Compared with the lowest tertile, those in the highest serum 25OHD tertile were less likely to have elevated serum PTH (adjusted OR = 0.25, 95% CI 0.16–0.41) and high blood pressure (adjusted OR = 0.40, 95% CI 0.22–0.72), and more likely to have normal hip and spine BMD (adjusted OR = 1.65, 95% CI 1.08–2.52). In multivariable models adjusting for season, age, weight (and height), BMD was associated with serum 25OHD at the spine, hip and whole body; no associations were detected at the forearm and no other characteristics were identified as confounders. Factors associated with high vitamin D status generally reflected healthy body habitus and active lifestyles. In contrast, excessive weight and smoking were associated with poorer vitamin D status. Women with high vitamin D were less likely to have elevated PTH, hypertension or bone deficits than women with poor levels.

Antioxidant vitamin supplements and markers of bone turnover in a community sample of nonsmoking women

Background: Whereas several epidemiological studies suggest that low dietary intake of vitamins C and E is linked to increased hip fracture in smokers and antioxidants (dietary and endogenous) are reduced in elderly osteoporotic women, none has demonstrated an effect of supplemental antioxidants on bone turnover.

Methods: In an observational study of 533 randomly selected women, we investigated the associations among the use of antioxidant supplements, vitamins C and E, serum levels of biochemical markers of bone turnover (C-telopeptide [CTx] and bone-specific alkaline phosphatase [BSAP]), and whole body bone mineral density (BMD).

Results: Twenty-two women were identified as current users of supplemental vitamin C or E. Duration of antioxidant supplement use was negatively associated with age-adjusted and weight-adjusted serum CTx, such that mean CTx levels (natural log transformed) were 0.022 units lower for each year of exposure. No significant differences were detected for adjusted serum BSAP or whole body BMD.

Conclusions: Our results suggest that antioxidant vitamin E or C supplements may suppress bone resorption in nonsmoking postmenopausal women. Coupling of bone formation and resorption may explain the absence of an effect on bone formation markers, given evidence of enhanced effects of antioxidants on osteoblast differentiation; this warrants further investigation. This work adds to the growing body of evidence that antioxidants may play a role in preventing osteoporosis.

Health outcomes associated with hormone therapy in Australian women

The risks and benefits of hormone therapy (HT) in the treatment of postmenopausal women remain controversial. In this population-based, observational study, we documented health outcomes among postmenopausal Australian women using HT. Women aged 60-80 years were recruited into the Geelong Osteoporosis Study 1994-7 and followed over a median period of 6.6 years. Mortality, and the development of vascular events, breast and colorectal cancers were documented for 67 HT-users and 521 non-users. Median duration of HT-use was 5.0 years (IQR 3.0-10.0). There was no excess in all-cause mortality associated with HT-use. Based on 92 deaths (six HT-users, 86 non-users), the adjusted odds ratio (OR) for all-cause mortality was 0.79 (95%CI 0.32-1.97). With 99 reports of vascular events (13 HTusers, 86 non-users), the adjusted OR for vascular events was 1.30 (95%CI 0.66-2.57). There were insufficient numbers of breast or colorectal cancer cases (21 breast cancer cases, all non-HT users; and 7 colorectal cancer cases, one HT-user and six non-users) to adequately calculate the risk associated with exposure to HT. Although the sample size was small, these results do not support an association between HT and mortality, despite a possible link between HT and increased risk of developing vascular disease.

Prevalence of obesity and the relationship between the body mass index and body fat : cross-sectional, population-based data

Background: Anthropometric measures such as the body mass index (BMI) and waist circumference are widely used as convenient indices of adiposity, yet there are limitations in their estimates of body fat. We aimed to determine the prevalence of obesity using criteria based on the BMI and waist circumference, and to examine the relationship between the BMI and body fat.

Methodology/Principal Findings: This population-based, cross-sectional study was conducted as part of the Geelong Osteoporosis Study. A random sample of 1,467 men and 1,076 women aged 20–96 years was assessed 2001–2008. Overweight and obesity were identified according to BMI (overweight 25.0–29.9 kg/m2; obesity $30.0 kg/m2) and waist circumference (overweight men 94.0–101.9 cm; women 80.0–87.9 cm; obesity men $102.0 cm, women $88.0 cm); body fat mass was assessed using dual energy X-ray absorptiometry; height and weight were measured and lifestyle factors documented by self-report. According to the BMI, 45.1% (95%CI 42.4–47.9) of men and 30.2% (95%CI 27.4–33.0) of women were overweight and a further 20.2% (95%CI 18.0–22.4) of men and 28.6% (95%CI 25.8–31.3) of women were obese. Using waist circumference, 27.5% (95%CI 25.1–30.0) of men and 23.3% (95%CI 20.8–25.9) of women were overweight, and 29.3% (95%CI 26.9–31.7) of men and 44.1% (95%CI 41.2–47.1) of women, obese. Both criteria indicate that approximately 60% of the population exceeded recommended thresholds for healthy body habitus. There was no consistent pattern apparent between BMI and energy intake. Compared with women, BMI overestimated adiposity in men, whose excess weight was largely attributable to muscular body builds and greater bone mass. BMI also underestimated adiposity in the elderly. Regression models including gender, age and BMI explained 0.825 of the variance in percent body fat.

Conclusions/Significance: As the BMI does not account for differences in body composition, we suggest that gender- and age-specific thresholds should be considered when the BMI is used to indicate adiposity.

Femoral neck dimensions are unlikely to be associated with age at menarche

Hip axis length (HAL) has been reported as an independent risk factor for hip fracture. Later puberty may increase bone size because of delayed epiphyseal fusion. We sought to identify associations between bone size at the proximal femur with age at menarche and other indices of growth such as stature. Femoral neck dimensions were measured from dual-energy X-ray absorptiometry scans of the proximal femur in a random sample of 203 premenopausal Caucasian women (age 20–30 years). There were no associations between age at menarche and HAL, femoral axis length (FAL) or femoral neck width (FNW). Age at menarche was associated with height (r= 0.2, p= 0.02). Variations in HAL, FAL and FNW do not appear to be related to age at menarche.

The human cost of fracture

In this population-based, observational study, we document the personal burden of fracture and utilization of community and health services for women during the 12-month period following a fracture. Participants were 598 women (aged 35-92 years) with incident fracture in the years 1994-1996 who were enrolled in the Geelong Osteoporosis Study. Almost all hip fracture cases and 27% of nonhip fracture cases were hospitalized. Homes were modified in 14% of cases, and 32% of the women purchased or hired equipment to assist with activities of daily living. Three-quarters of women with hip, pelvis, or lower limb fractures were confined to the home, had to walk with a walking aid, or could walk only short distances for several weeks. After a year, nearly one-half had not regained prefracture mobility. One-seventh of women with upper-limb fractures did not venture outside the home for at least 6 weeks. Nearly half of all fracture cases needed help with personal care and housework during the first 6 weeks. After 6 months, 3.4% of all patients and 19.6% of hip, 12.8% of humeral, and 4.7% of spine fracture patients required assistance with bathing and showering. After a year, more than half of the hip fracture cases remained restricted regarding housework, gardening, and transport. These findings have important implications for rehabilitation therapy. A fracture, regardless of site, had a major impact on a woman's lifestyle and well-being. Most women were restricted in their activities of daily living and suffered loss of confidence and independence. Short-term morbidity was common for all fractures, with varying degrees of prolonged morbidity often extending to at least a year postfracture.

Health burden of hip and other fractures in Australia beyond 2000

Objective: To calculate the expected increase in the number of fractures in adults attributable to the predicted increase in the number of elderly Australians.

Data sources: All fractures in adult residents (> 35 years) of the Barwon Statistical Division (total population, 218 000) were identified from radiological reports from February 1994 to February 1996. The Australian Bureau of Statistics supplied predictions of Australia's population (1996 to 2051).

Main outcome measure: The projected annual number of fractures in Australian adults up to 2051 (based on stable rates of fracture in each age group).

Results: The number of fractures per year is projected to increase 25% from 1996 to 2006 (from 83 000 fractures to 104 000). Hip fractures are projected to increase 36% (from 15 000 to 21 000) because of a substantial rise in the number of elderly aged 85 years and over. Hip fractures are expected to double by 2026 and increase fourfold by 2051.

Conclusions: In contrast to Europe and North America, where numbers of hip fractures are expected to double by 2026 and then stabilise, in Australia hip fractures will continue to place a growing demand on healthcare resources for many decades. These projections can be used for setting goals and evaluating the costs and benefits of interventions in Australia.

Age- and gender-specific rate of fractures in Australia : a population-based study

There is little population-based data concerning fracture rates in Australia. We ascertained all fractures occurring during 2 years in adults aged 35 years and over residing within a defined region (population 218 000), representative of the Australian population. The major strength of this study is the comprehensive ascertainment of fractures, which was ensured by regular searches of the only two radiologic providers in the Geelong Osteoporosis Study region. Nevertheless, vertebral fractures are likely to be underestimated since our ascertainment relied on a clinical indication for a medical imaging procedure. Among those aged 35 – 55 years, the fracture rate (persons per 10 000/year) in men was about double the rate in women (65 vs 35). The fracture rate was almost 7 times higher in women over 60 years versus women less than 55 years of age. In contrast, the fracture rate in men over 60 years was only 50% higher than in men less than 55 years of age (72 vs 104). Fracture rates in women and men were highest at the hip (28 and 10 respectively), spine (21 and 7), distal forearm (Colles’) (18 and 4) and humerus (11 and 3), and were 3–4 times higher in women than men. These fractures accounted for 63% of all fractures in women and 32% in men. By contrast, the rate of lower leg and ankle fractures was less than 10 per 10 000 in both women and men and did not increase to the same extent with age. Hip fracture rates appear high, particularly among the older age strata, compared with retrospective ascertainment in other populations. In Australia, as in many other countries, there is an increasing longevity of the population. The number of women aged 90 years and over increased by 32% and the number of men of this age increased by 48% in the 5 years between the Australian national census of 1991 and 1996. Given stable fracture rates, the substantial health burden imposed by age-related fractures, particularly hip fractures, will continue to escalate in both women and men.

Alleles of RUNX2/CBFA1 gene are associated with differences in bone mineral density and risk of fracture

The aim of this study was to determine if DNA polymorphism within runt-related gene 2 (RUNX2)/core binding factor A1 (CBFA1) is related to bone mineral density (BMD). RUNX2 contains a glutamine-alanine repeat where mutations causing cleidocranial dysplasia (CCD) have been observed. Two common variants were detected within the alanine repeat: an 18-bp deletion and a synonymous alanine codon polymorphism with alleles GCA and GCG (noted as A and G alleles, respectively). In addition, rare mutations that may be related to low BMD were observed within the glutamine repeat. In 495 randomly selected women of the Geelong Osteoporosis Study (GOS), the A allele was associated with higher BMD at all sites tested. The effect was maximal at the ultradistal (UD) radius (p = 0.001). In a separate fracture study, the A allele was significantly protective against Colles' fracture in elderly women but not spine and hip fracture. The A allele was associated with increased BMD and was protective against a common form of osteoporotic fracture, suggesting that RUNX2 variants may be related to genetic effects on BMD and osteoporosis.

Forearm bone mineral density and incidence of hip fractures in Swedish urban and rural men 1987-2002

Background: It is not known whether the recently described break in the trend in hip fracture incidence in many settings applies in both women and men, depends on changes in bone mineral density (BMD) or changes in other risk factors, or whether it is apparent in both urban and rural settings. Methods: We evaluated changes in annual hip fracture incidence from 1987 to 2002 in Swedish men aged ≥60 years in one urban (n=25,491) and one rural population (n=16,432) and also secular differences in BMD, measured by single-photon absorptiometry at the distal radius and multiple other risk factors for hip fracture in a population-based sub-sample of the urban and the rural men aged 60–80 years in 1988/89 (n=202 vs. 121) and in 1998/99 (n=79 vs. 69). Results: No statistically significant changes in the annual age-adjusted hip fracture incidence per 10,000 were apparent from 1987 to 2002 in urban (0.38 per year, 95% CI-0.12 to 0.88) or rural men (-0.05 per year, 95% CI -0.63 to 0.53). BMD was similar in 1988/89 and 1998/99 when examining both urban (-19.6 mg/cm², 95% CI -42.6 to 3.5) and rural (-23.0 mg/cm², 95% CI -52.1 to 6.1) men. Conclusions: Since no secular change in age-adjusted hip fracture incidence was found during the study period, a levelling off in hip fracture incidence is present also in Swedish men. Because BMD on a group level was similar in 1988/89 and 1998/99, changes in other risk factors ought to be either of minor importance or counteracted by changes in different risk factors.

Don't worry, be active : positive affect and habitual physical activity

Objective: The aim of ths study was to examine the association between habitual physical activity and positive and negative affect.

Method: This cross-sectional study included 276 women aged 20 +, from the Geelong Osteoporosis Study. Habitual physical activity and other lifestyle exposures were assessed by questionnaire, concurrent with anthropometric assessments. Physical activity was categorized as very active, moderately active or sedentary. Positive and negative affect scores were derived from the validated 20 item Positive and Negative Affect Schedule (PANAS) self-report and were categorized into tertiles.

Results: There was a pattern of lower positive affect scores for lower levels of physical activity. With very active as the reference category, the odds for having a positive affect score in the highest tertile were sequentially lower for those who were moderately active (OR = 0.53, 95%CI 0.28–1.01) and sedentary (OR = 0.28, 95%CI 0.10–0.75). Associations were sustained after adjusting for body mass index and polypharmacy (OR = 0.50, 95%CI 0.26–0.96 and OR = 0.25, 95%CI 0.09–0.72, respectively). These associations were not explained by age, negative affect score or other exposures. No association was detected between physical activity and negative affect scores.

Conclusions: This study reports that higher positive affect scores, encompassing emotions such as interest, excitement, enthusiasm and alertness, are associated with higher levels of habitual physical activity. These observations warrant further investigations into possible mechanistic interplay between neurobiological and psychosocial factors that underpin this association.

Vitamin D and the musculoskeletal health of older adults

The scientific literature related to vitamin D and bone health in older adults is extensive.

This article aims to summarise key practice points regarding vitamin D and bone health in older adults, relevant to general practitioners, and to provide an overview of the background literature to enable GPs to appreciate the extent of the supporting evidence.

Vitamin D supplementation can prevent falls, particularly in the vitamin D deficient elderly. However, adequate vitamin D levels and dietary calcium intake are needed for effective primary fracture prevention with greatest benefits occurring in the elderly with vitamin D deficiency and/or low dietary calcium intakes. For secondary fracture prevention, ie. preventing further fractures in the elderly who have already sustained a fragility fracture, specific anti-osteoporosis treatment is necessary. However, to maximise the benefits of these medications, vitamin D deficiency should be corrected and adequate dietary calcium consumed.