Reference ranges for bone densitometers adopted Australia-wide : Geelong Osteoporosis Study

Bone densitometry reports a measure of fracture risk in comparison with young adults (T-scores) and age-matched peers (Z-scores). To date, each manufacturer has provided its own reference range resulting in lack of uniformity. The Australia and New Zealand Bone and Mineral Society and Osteoporosis Australia have recognized the need to standardize the reference range and have recommended that data generated by the Geelong Osteoporosis Study (GOS) be used Australia-wide. The GOS recruited a random, population-based sample of adult women and measured bone mineral density (BMD) at the proximal femur and spine using a Lunar DPX-L. These data were used to establish reference ranges for Lunar machines and, using conversion equations, for Norland and Hologic machines. The new standardized Australian reference ranges for BMD will enable consistent diagnosis of osteoporosis and categorization of fracture risk across different types of densitometers.

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.

Identification of incident fractures : the Geelong Osteoporosis Study

Background: Complete fracture ascertainment is critical for fracture cost estimates and planning for future health care facilities. Virtually complete ascertainment is possible for hip fractures because they nearly always require hospitalisation.

Aims: To validate the use of radiological reports as a resource for ascertaining fracture cases, using hip fracture as a model.

Methods: Hip fracture rates obtained from radiological reports were compared with rates obtained from hospital discharge summaries of medical records using International Classification of Diseases-9 (ICD-9) codes 820.0–820.9 and 733.1 over a three-year period.

Results: Hip fracture cases numbered 589 using radiological reports and 585 using medical records. Discharge summaries failed to identify 15 cases ascertained through radiology reports whereas 11 cases ascertained through medical records were not identified from X-ray reports. The age-specific incidence rates for radiological ascertainment were within the 95% confidence limits of the rates derived from medical records.

Conclusions: Among a population of patients generally admitted to hospital for treatment of their fracture, we were able to identify more cases from radiological reports than from medical records. Incidence rates for hip fracture were comparable using the two methods. Radiological reports provide a valuable resource for identifying incident fractures. This method of case ascertainment would be suitable for identifying both major and minor fractures in regions with self-contained health services where access to all radiological reports is possible.

Seasonal periodicity of serum vitamin D and parathyroid hormone, bone resorption, and fractures : the Geelong Osteoporosis Study

In this population-based study, seasonal periodicity was seen with reduced serum vitamin D, increased serum PTH, and increased bone resorption in winter. This was associated with an increased proportion of falls resulting in fracture and an increased risk of wrist and hip fractures.

Introduction: In a population of women who reside in a temperate climate and do not generally receive dietary vitamin D supplementation, we investigated whether seasonal vitamin D insufficiency is associated with increased risk of fracture.

Materials and Methods: An observational, cross-sectional, population-based study set in southeastern Australia (latitude 38–39° S). Participants were drawn from a well-defined community of 27,203 women ≥55 years old: 287 randomly selected from electoral rolls, 1635 with incident fractures, and 1358 presenting to a university hospital with falls. The main outcome measures were annual periodicities of ultraviolet radiation, serum 25-hydroxyvitamin D [25(OH)D], serum parathyroid hormone (PTH), serum C-telopeptide (CTx), BMD, falls, and fractures.

Results: Cyclic variations in serum 25(OH)D lagged 1 month behind ultraviolet radiation, peaking in summer and dipping in winter (p < 0.001). Periodicity of serum PTH was the inverse of serum 25(OH)D, with a phase shift delay of 1 month (p = 0.004). Peak serum CTx lagged peak serum PTH by 1–2 months. In late winter, a greater proportion of falls resulted in fracture (p < 0.001). Seasonal periodicity in 439 hip and 307 wrist fractures also followed a simple harmonic model (p = 0.078 and 0.002, respectively), peaking 1.5–3 months after the trough in 25(OH)D.

Conclusions: A fall in 25(OH)D in winter is accompanied by increases in (1) PTH levels, (2) bone resorption, (3) the proportion of falls resulting in fracture, and (4) the frequency of hip and wrist fracture. Whether vitamin D supplementation in winter can reduce the population burden of fractures requires further investigation.

Vitamin D status of women in the Geelong Osteoporosis Study : association with diet and casual exposure to sunlight

Objective: To assess vitamin D intake and casual exposure to sunshine in relation to serum 25-hydroxyvitamin D (25OHD) levels.

Design: Cross-sectional study of a population-based, random sample of women aged 20-92 years, assessed between 1994 and 1997.

Setting and participants: 861 women from the Barwon Statistical Division (population, 218 000), which includes the city of Geelong (latitude 38° south) in Victoria.

Main outcome measures: Vitamin D intake; serum 25OHD level; season of assessment; exposure to sunshine.

Results: Median intake of vitamin D was 1.2 μg/day (range, 0.0-11.4 μg/day). Vitamin D supplements, taken by 7.9% of participants, increased intake by 8.1% to 1.3 μg/day (range, 0.0-101.2 μg/day) (P < 0.001). A dose-response relationship in serum 25OHD levels was observed for sunbathing frequency before and after adjusting for age (P < 0.05). During winter (May-October), serum 25OHD levels were dependent on vitamin D intake (partial r2 = 0.01; P < 0.05) and were lower than during summer (November-April) (age-adjusted mean, 59 nmol/L [95% CI, 57-62] v 81 nmol/L [95% CI, 78-84]; P < 0.05). No association was detected between serum 25OHD and vitamin D intake during summer. The prevalences of low concentrations of serum 25OHD were, for <28 nmol/L, 7.2% and 11.3% overall and in winter, respectively; and, for <50 nmol/L, 30.0% and 43.2% overall and in winter, respectively.

Conclusions: At latitude 38° south, the contribution of vitamin D from dietary sources appears to be insignificant during summer. However, during winter vitamin D status is influenced by dietary intake. Australia has no recommended dietary intake (RDI) for vitamin D, in the belief that adequate vitamin D can be obtained from solar irradiation alone. Our results suggest that an RDI may be needed.

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.

Calcium intakes among Australian women : Geelong Osteoporosis Study

Background: Dietary calcium deficiency may be a risk factor for osteoporosis.

Aims: To estimate habitual calcium intakes and prevalence of calcium supplementation among free-living Australian women and validate a calcium-specific food-frequency questionnaire.

Methods: Calcium intakes for 1045 randomly selected women (20–92 years) were estimated by questionnaire which was tested against estimates from four day weighed records kept by 32 randomly selected women.

Results: The mean difference between calcium estimates was not statistically significantly different from zero (mean difference=121 mg; standard deviation of differences=357 mg; p>0.05). There was moderate agreement (weighted κ=0.4) between methods in ranking subjects into tertiles of calcium intake. Mean dietary calcium intakes were 615 mg/day for 20–54 years, 646 mg/day for 55–92 years and 782 mg/day for lactating women. Seventy-six per cent of women aged 20–54 years, 87% of older and 82% of lactating women had intakes below the recommended dietary intake (RDI). There was no association detected between calcium intake and age. Dairy foods provided 79.0% of dietary calcium intake. Calcium supplements were used by 6.6% and multivitamins by a further 4.3% of women. Supplementation was independent of dietary calcium intake and more likely used by postmenopausal women.

Conclusions: Our results suggest that 76% of women consume less than the RDI even when supplemental calcium is included. Furthermore, 14% have less than the minimal requirement of 300 mg/day and would, therefore, be in negative calcium balance and at risk of bone loss. Despite advertising campaigns promoting better nutrition and increased awareness of osteoporosis, many women are failing to achieve an adequate calcium intake.

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.

The exclusion of high trauma fractures may underestimate the prevalence of bone fragility fractures in the community : the Geelong Osteoporosis Study

Fractures associated with severe trauma are generally excluded from estimates of the prevalence of osteoporotic fractures in the community. Because the degree of trauma is difficult to quantitate, low bone mass may contribute to fractures following severe trauma. We ascertained all fractures in a defined population and compared the bone mineral density (BMD) of women who sustained fractures in either 'low' or 'high' trauma events with the BMD of a random sample of women from the same population. BMD was measured by dual-energy X-ray absorptiometry and expressed as a standardized deviation (Z score) adjusted for age. The BMD Z scores (mean ± SEM) were reduced in both the low and high trauma groups, respectively: spine-posterior-anterior (- 0.50 ± 0.05 and -0.21 ± 0.08), spine-lateral (-0.28 ± 0.06 and -0.19 ± 0.10), femoral neck (-0.42 ± 0.04 and -0.26 ± 0.09), Ward's triangle (- 0.44 ± 0.04 and -0.28 ± 0.08), trochanter (-0.44 ± 0.05 and -0.32 ± 0.08), total body (-0.46 ± 0.06 and -0.32 ± 0.08), ultradistal radius (- 0.47 ± 0.05 and -0.42 ± 0.07), and midradius (-0.52 ± 0.06 and -0.33 ± 0.09). Except at the PA spine, the deficits were no smaller in the high trauma group. Compared with the population, the age-adjusted odds ratio for osteoporosis (t-score < -2.5) at one or more scanning sites was 3.1 (95% confidence interval 1.9, 5.0) in the high trauma group and 2.7 (1.9, 3.8) in the low trauma group. The data suggest that the exclusion of high trauma fractures in women over 50 years of age may result in underestimation of the contribution of osteoporosis to fractures in the community. Bone density measurement of women over 50 years of age who sustain fractures may be warranted irrespective of the classification of trauma.

Geelong Osteoporosis Study Health Database

The database contains the following clinical, questionnaire and socio-demographic data suitable for cross-sectional and longitudinal analyses:
-Body composition: dual-energy x-ray absorptiometry (DXA) measures of the lumbar spine (posterior-anterior projection), proximal femur, whole body and forearm (ultradistal forearm and distal 33%)
-Other clinical assessments: body weight, height, arm span, waist and hip circumferences, blood pressure, visual acuity, muscle strength, functional reach test and timed ‘up-&-go’ test.
-Mental health: Major axis psychiatric disorders diagnosed using a Structured Clinical Interview.
-Blood and urine collections: blood and urine collected after an overnight fast.
-Questionnaires: exposure to disease, use of medications and supplements, diet, mobility, physical activity, sleep, sun exposure, falls and fractures, alcohol and tobacco use, reproductive history, family history of fractures and disease, quality of life, pain, anxiety and depression.
-Socio-demographics: Country of birth, ethnicity, marital status, education, housing and employment status, occupation, socioeconomic Index for Areas (SEIFA) scores.