Application of epidemiology to change health policy : defining age-related thresholds of bone mineral density for primary prevention of fracture

In Australia, benefits for antifracture therapies have been available for patients with osteoporosis and a prior fracture. No benefits were available to those with no prior fracture. We aimed to define, in women with no prior fracture, age-related thresholds of bone mineral density (BMD) associated with fracture risk equivalent to that of women with prior fracture and osteoporosis. A case-control study of women (≥50 yr) was conducted, including 291 fracture cases and 823 controls. BMD was measured at the proximal femur and posterior anterior (PA) spine. A fracture risk score (FRS) for the group with no prior fracture was calculated with discriminant analysis. The thresholds for equivalent fracture risk between those with no prior fracture and those with prior fracture were assessed using logistic regression. Increasing the FRS to +0.98 in women with no prior fracture resulted in equivalent odds of sustaining a fracture to those with prior fracture and osteoporosis. The corresponding T-score thresholds at the spine were −4.6 at 50 yr, −3.9 at 60 yr, −3.1 at 70 yr, and −2.4 at 80 yr. The femoral neck T-score thresholds were lower by 0.5 standard deviation. The high-risk individuals defined by this study should be considered for primary fracture prevention therapy.

Fracture risk (FRISK) score : Geelong Osteoporosis Study

Purpose: To develop and evaluate a fracture risk (FRISK) score based on multiple-site bone mineral density (BMD) measurements and other risk factors, to enable prediction of future fracture occurrence.

Materials and Methods: All participants gave written informed consent, and the study was approved by the Barwon Health Research and Ethics Advisory Committee. BMD was measured at the femoral neck and spine in two concurrently recruited groups: women 60 years of age or older who had sustained a low-trauma fracture of the hip, spine, humerus or distal forearm during a 2-year ascertainment period (n = 231; mean age, 74 years ± 7 [standard deviation]) and a population-based random sample of women who had not sustained a fracture during the recruitment period (n = 448; mean age, 72 years ± 8). Falls in the previous year and the number of self-reported fractures in adult life were recorded. Coefficients of a multiple logistic regression model were used as weightings for a combined model. A longitudinal population-based sample was used to assess the fracture risk equation (n = 600; median age, 74 years; interquartile range, 67–82 years).

Results: The FRISK score was obtained from the following equation: 9.304 − 4.735BMDSP − 4.530BMDFN + 1.127FS + 0.344NPF + 0.037W, where BMDSP is spinal BMD (in grams per square centimeter), BMDFN is femoral neck BMD, FS is falls score, NPF is number of previous fractures, and W is weight (in kilograms). The FRISK score successfully predicted 75% of fractures 2 years after baseline measurements in subjects in the longitudinal study with 68% specificity.

Conclusion: This study resulted in the derivation of a fracture risk score that successfully predicted 75% of fractures 2 years after baseline.

Assessment of fracture risk : value of random population-based samples - the Geelong Osteoporosis Study

Fracture risk is determined by bone mineral density (BMD). The T-score, a measure of fracture risk, is the position of an individual's BMD in relation to a reference range. The aim of this study was to determine the magnitude of change in the T-score when different sampling techniques were used to produce the reference range. Reference ranges were derived from three samples, drawn from the same region: (1) an age-stratified population-based random sample, (2) unselected volunteers, and (3) a selected healthy subset of the population-based sample with no diseases or drugs known to affect bone. T-scores were calculated using the three reference ranges for a cohort of women who had sustained a fracture and as a group had a low mean BMD (ages 35-72 yr; n = 484). For most comparisons, the T-scores for the fracture cohort were more negative using the population reference range. The difference in T-scores reached 1.0 SD. The proportion of the fracture cohort classified as having osteoporosis at the spine was 26, 14, and 23% when the population, volunteer, and healthy reference ranges were applied, respectively. The use of inappropriate reference ranges results in substantial changes to T-scores and may lead to inappropriate management.

Fracture thresholds revisited : Geelong Osteoporosis Study

Osteoporosis, in the absence of fracture, is defined as a deficit in bone mineral density (BMD) of 2.5 SD or more below the young adult reference mean in postmenopausal Caucasian populations. BMD is a measure of fracture risk but not the sole predictor. We have assessed a combination of easily accessible measures of age, height, weight, and BMD to improve fracture risk assessment. Women with low trauma fractures and a control group were recruited from south-eastern Australia. Discriminant analysis derived multivariate equations that assessed fracture risk. Age was not in the best models at the spine and forearm sites. Weight and height contributed to the relationship for the forearm sites only. At the proximal femur, the BMD level that separates fracture cases from nonfracture cases, increases with age. These separation levels of BMD were higher than the WHO's level of osteoporosis (T-score < −2.5 SD) at ages older than 62 years. This increasing BMD threshold with age suggests that other age-related risk factors assume increasing importance among the elderly.

β-Adrenergic blockers reduce the risk of fracture partly by increasing bone mineral density : Geelong Osteoporosis Study

This population-based study documented β-blocker use in 59/569 cases with incident fracture and 112/775 controls. OR for fracture associated with β-blocker use was 0.68 (95%CI, 0.49–0.96). β-Blockers were associated with higher BMD at the total hip (2.5%) and UD forearm (3.6%) after adjusting for age, anthropometry, and thiazide use. β-Blocker use is associated with reduced fracture risk and higher BMD.

Introduction: Animal data suggests that bone formation is under β-adrenergic control and that β-blockers stimulate bone formation and/or inhibit bone resorption.

Materials and Methods: We evaluated the association between β-blocker use, bone mineral density (BMD), and fracture risk in a population-based study in Geelong, a southeastern Australian city with a single teaching hospital and two radiological centers providing complete fracture ascertainment for the region. β-Blocker use was documented for 569 women with radiologically confirmed incident fractures and 775 controls without incident fracture. Medication use and lifestyle factors were documented by questionnaire.

Results: Odds ratio for fracture associated with β-blocker use was 0.68 (95% CI, 0.49–0.96) for any fracture. Adjusting for age, weight, medications, and lifestyle factors had little effect on the odds ratio. β-Blocker use was associated with a higher BMD at the total hip (2.5%, p = 0.03) and ultradistal forearm (3.6%, p = 0.04) after adjustment for age, anthropometry, and thiazide use.

Conclusion: β-Blockers are associated with a reduction in fracture risk and higher BMD.

Statin use, bone mineral density, and fracture risk: Geelong Osteoporosis Study

Background Recent data suggest that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) decrease fracture risk and increase bone mineral density (BMD).

Methods This cross-sectional study is set in southeastern Australia. We evaluated the association between statin use, fracture risk, and BMD in 1375 women (573 with incident fractures and 802 without incident fracture, all drawn from the same community). Fractures were identified radiologically. Medication use and lifestyle factors were documented by questionnaire.

Results Unadjusted odds ratio for fracture associated with statin use was 0.40 (95% confidence interval [CI], 0.23-0.71). Adjusting for BMD at the femoral neck, spine, and whole body increased the odds ratio to 0.45 (95% CI, 0.25-0.80), 0.42 (95% CI, 0.24-0.75), and 0.43 (95% CI, 0.24-0.78), respectively. Adjusting for age, weight, concurrent medications, and lifestyle factors had no substantial effect on the odds ratio for fracture. Statin use was associated with a 3% greater adjusted BMD at the femoral neck (P = .08), and BMD tended to be greater at the spine and whole body but did not achieve statistical significance.

Conclusion The substantial 60% reduction in fracture risk associated with statin use is greater than would be expected from increases in BMD alone.

Hormone therapy and risk of non-vertebral fracture : Geelong Osteoporosis Study

In this population-based study, we evaluated the association between exposure to hormone therapy (HT), bone mineral density (BMD) and the prevalence of non-vertebral fractures. The study was set in a region located in southeastern Australia where complete fracture ascertainment was determined from radiological reports. Current HT use for at least 6 months was ascertained in women with non-vertebral fractures [median age 70.9 years; inter-quartile range (IQR) 66.5–75.9 years] and randomly selected controls (median age 70.8 years; IQR 65.2–75.0 years). Current HT use was documented in 20 of 262 cases and 49 of 364 controls. The odds ratio (OR) for non-vertebral fracture associated with HT use was 0.53 (95% CI 0.31–0.92). HT use was associated with 2.6–7.5% higher BMD at axial and appendicular sites. HT use is associated with a halving of risk for non-vertebral fractures and higher BMD.

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.

Fracture rates lower in rural than urban communities : the Geelong Osteoporosis Study

Background: Urban and rural communities differ in the incidence of several diseases including coronary heart disease and some cancers. Lower hip fracture rates among rural than urban populations have been reported but few studies have compared rural and urban fractures at sites other than the hip.

Objective: To compare total and site specific fracture rates among adult residents of rural and urban communities within the same population.

Design and setting: This is a population based study on osteoporosis in Australia. All fractures occurring in adult residents over a two year period were ascertained using radiological reports. The rural and urban areas are in close proximity, with the same medical, hospital, and radiological facilities permitting uniform fracture ascertainment.

Main outcome measures: All fracture rates were age adjusted and sex adjusted to the Australian population according to the 1996 census of the Australian Bureau of Statistics and described as the rate per 10 000 person years. The p values refer to the adjusted rate difference.

Results: The hip fracture rate (incidence per 10 000 person years) was 32% lower (39 v 57, p<0.001), and the total fracture rate 15% lower (160 v 188, p=0.004) among rural than urban residents, respectively. The lower fracture rates in the rural population were also apparent for pelvic fractures.

Conclusion: In the older rural population, lower fracture rates at sites typically associated with osteoporosis suggest environmental factors may have a different impact on bone health in this community. If the national rate of hip fracture could be reduced to that of the rural population, the projected increase in hip fracture number attributable to aging of the population could be prevented.