Estimate Fracture Risk Research Articles

An indirect method for the estimation of osteoporotic fractures from injury and fracture profiles.

Study objective was to develop a valid epidemiological method for the estimation of osteoporotic fracture risk, using administrative databases and accounting for variable baseline risks of injury. Design is the secondary analysis of inpatient and outpatient utilization data. A baseline injury risk was estimated by the incidence of primary utilization of medical services for soft tissue injuries (ICD-9 diagnostic codes 910-929), and the risk profile was compared after normalization with the overall primary utilization rate for fractures (ICD-9 diagnostic codes 800-829). The setting is a county with approximately 100,000 inhabitants in the former East Germany. Participants were all inhabitants of the county who had a physician contact (inpatient or outpatient) during 1987-1988, as well as hospital inpatients for all of Germany in 1989. The number of fractures increased with age, especially in women, when compared to the number of fractures expected from the incidence of soft tissue injury. Similar patterns were identified in hospitalization data from East and West Germany. Estimating the prevalence of osteoporosis directly from certain "osteoporotic" fracture types associated with higher age is potentially biased, since it neglects the underlying risk of injury. Our model distinguished the osteoporotic fracture risk as the excess risk over an expected injury-related fracture risk for a given age and sex, and may allow a more valid quantification of osteoporotic fractures in different populations.

Assessment of vertebral bone mineral density using volumetric quantitative CT.

The purpose of this work was to determine the precision and diagnostic efficacy of bone mineral density (BMD) measures based on volumetric quantitative CT (QCT) of the spine. Volumetric CT scans of L1 and L2 (GE-9800Q; 80 kVp, 140 mAs, 3 mm slices) were acquired in a cohort of 62 osteoporotic women (mean age 70.4 years, T(DXA hip or spine) < -2.5), of whom 20 had vertebral fractures and 42 were nonfractured control subjects. An image analysis technique delineated trabecular, cortical, and integral regions in reference to a vertebra-fixed coordinate system. We computed precision values and fracture control differences for these new regions and for single-slice QCT and dual X-ray absorptiometry (DXA) measures synthesized from the volumetric data. Volumetric trabecular BMD showed higher precision (1.3%) than the synthesized single-slice measures (2.1-2.8%). Volumetric and single-slice trabecular BMD showed equivalent decrements between fractured and nonfractured subjects (17-19%), with integral BMD showing smaller and less significant differences (7-8%). Volumetric and single-slice QCT techniques are equivalent for vertebral fracture risk estimation, but volumetric techniques should be superior for monitoring therapy efficacy.

High turnover bone disease following lung transplantation

Recipients of lung transplants are at very high risk for significant bone loss. Nevertheless, data on bone disease after lung transplantation are still limited. We, therefore, retrospectively evaluated the data of 33 patients surviving at least 1 year after lung transplantation (LTx) who were seen in our outpatient clinic for osteologic evaluation. Results of clinical evaluations, radiographs, and dual-energy X-ray absorptiometry (DXA) were related to each other, to clinical variables, and to serum levels of osteocalcin, parathyroid hormone (PTH), and 25-hydroxyvitamin D: 14 of 33 patients (42%) had vertebral fractures, 9 of whom were diagnosed within 2 years after transplantation. Bone mineral density values (DXA) were markedly decreased and predictive of compression fractures. 25-Hydroxyvitamin D levels were low in 13 patients (39%) and PTH was elevated in 7 (21%). Despite corticosteroids and low 25-hydroxyvitamin D, serum osteocalcin was elevated in 12 patients (36%). This was only partially explained by hyperparathyroidism, low sex hormones, and impaired renal function, and may partly be caused by cyclosporin A. We thus conclude that severe symptomatic bone disease is common in lung transplant recipients and due to a complex situation including high turnover bone loss and hypovitaminosis D. DXA can be used to estimate fracture risk for individual patients.

Hip fracture prediction in elderly men and women: validation in the Rotterdam study.

The aim of our study was to validate a hip fracture risk function, composed of age and femoral neck bone mineral density (BMD). This estimate of the 1-year cumulative risk was previously developed on the basis of Dutch hip fracture incidence data and BMD in men and women. A cohort of 7046 persons (2778 men) aged 55 years and over was followed for an average of 3.8 years. The 1-year hip fracture risk estimate was calculated for each participant according to the risk function and categorized as low (<0.1%), moderate (0.1 to < 1%), or high (> or =1%). Observed first hip fracture incidence was then analyzed for each of these risk categories by age and gender. Additionally, we calculated the relative risk per standard deviation (SD) decrease in femoral neck BMD in this population. At baseline, 2360 individuals were categorized as low risk, 2567 as moderate risk, and 378 as high risk During follow-up, 110 first hip fractures were observed corresponding to an incidence rate of 4.1/1000 person-years (pyrs) (95% confidence interval 3.4-5.0). The observed incidence rate in the low risk group was 0.2/1000 pyrs (0.1-0.9), 2.7/1000 pyrs (1.8-3.9) in the moderate risk group, and 18.4/1000 pyrs (12.4-27.2) in the high risk group. Below the age of 70 years, incidence was low in all categories, and very few individuals were considered at high risk Above the age of 70 years, the observed incidence was high in the high risk group, while in the low and moderate risk groups, the incidence remained low even over 80 years of age. In women, the age-adjusted relative risk for hip fractures was 2.5 per SD decrease in femoral neck BMD (1.8-3.6), while in men this relative risk was 3.0 per SD (1.7-5.4). In conclusion, we observed a similar relation of hip fracture with femoral neck BMD in men and women and were able to predict accurately hip fracture rates over a period of almost 4 years.

Contribution of the cortical shell of vertebrae to mechanical behaviour of the lumbar vertebrae with implications for predicting fracture risk.

In the diagnosis of osteoporosis using single energy quantitative CT (SE-QCT) on the axial skeleton, only spongy bone mineral density (BMD) is used at present. Although the density of cortical bone is also determined by most QCT methods, it is not used for evaluation. The objective of this study was to determine the extent to which the cortical bone of the lumbar vertebral bodies accounts for their load-bearing capacity and failure behaviour, and to use this information to suggest improvements in the differential diagnosis of osteoporosis. Investigations were conducted in a clinical, theoretical-numerical and biomechanical-experimental context. Cortical (BMDC) and spongy (BMDS) bone mineral density was measured by SE-QCT/85 kV on 179 patients (68 males, 111 females). These bone densities were matched with the vertebral body fractures previously determined from conventional X-rays. A finite element model was used to study the variation in structural and material parameters of the vertebral body. 19 vertebral bodies that had been removed post-mortem were available for the biomechanical-experimental investigations. Spongy and cortical bone densities were also determined by SE-QCT on these vertebral bodies. Their failure load was then measured in the axial compression test. These investigations show that, in addition to the spongiosa, the cortical shell plays an important role in the load-bearing capacity of the vertebral body. If the spongiosa is weakened due to a loss of BMD, the residual load-bearing capacity of the vertebral bodies is increasingly shouldered by the cortical bone. The lower susceptibility to fracture in men compared with women when spongy bone mineral density is reduced can thus be attributed to the lack of a reduction in cortical bone mineral density. It is recommended that the BMDC also be evaluated in future, especially in the diagnosis of bone mass losses in women, to improve the estimation of the individual fracture risk.

Ex vivo estimation of thoracolumbar vertebral body compressive strength: the relative contributions of bone densitometry and vertebral morphometry.

The estimation of vertebral fracture risk in individuals with suspected osteopenia is commonly based on measurements of lumbar spine bone density. The efficacy of vertebral size and deformity, as assessed by vertebral morphometry, in the prediction of fractures has been less studied. In an ex vivo investigation the regional relationships between vertebral size, vertebral deformity, bone density and compressive strength throughout the thoracolumbar spine were examined. In 16 vertebral columns (T1-L5) the bone mineral content (BMC) and bone mineral density (BMD) of each segment were measured using lateral projection dual-energy X-ray absorptiometry, and the vertebral cancellous density (VCD) and mid-vertebral cross-sectional area (CSA) measured using quantitative computed tomography. Vertebral body heights were determined from mid-sagittal CT scans, and vertical height ratios calculated for each segment. The failure load and failure stress of the isolated vertebral bodies were determined using a material testing device. Separate analyses were performed for the upper (T1-4), middle (T5-8) and lower (T9-12) thoracic, and lumbar (L1-5) segments. In all regions, failure load was strongly correlated with BMD (r = 0.82-0.86), moderately correlated with VCD (r = 0.60-0.71) and vertebral height (r = 0.22-0.49), and poorly correlated with the height ratios (r = 0.04-0.33). Failure stress was best predicted by BMD (r = 0.73-0.78) and VCD (r = 0.70-0.78) but was poorly correlated with all morphometric variables (r = 0.01-0.33). The segmental correlations between BMD and VCD ranged form r = 0.49 to r = 0.79. For all regions, BMD and VCD were included in the stepwise regression models for predicting failure load and failure stress. Either the mid-vertebral height or CSA were included in all the failure load models, while mid-vertebral height was included in only one of the failure stress models. The results suggest that vertebral deformity and size (as assessed by vertebral morphometry) make only a minor contribution to the prediction of vertebral strength additional to that provided by bone densitometry alone. The consistent regional relationships between variables appear to support the practice of global fracture risk assessment based on lumbar spine densitometry.

Biochemical markers in osteoporosis

Biochemical indices of skeletal turnover have been widely used as a research tool to study the natural history of osteoporosis and to assess the pharmacodynamics of drug treatments. Their promise for the future depends on whether they can be used as an adjunct in the management of individual patients. Whereas indices of both bone resorption and formation provide little value in the diagnosis of individuals with osteoporosis, they have now been shown by prospective studies to provide estimates of skeletal loss, and indeed improve the prognostic accuracy of bone mineral density to estimate fracture risk. Biochmical indices of bone resorption have proved particularly useful in assessing interventions, particularly the inhibitors of bone resorption. They might therefore be used in individuals to assess responsivity or compliance with treatment. Precision errors of many of the numbers mean that they have relatively poor predictive value in individuals, but as the specificity and precision of assays increase, the predictive value is also likely to improve.

Prophylactic replacement of Björk-Shiley convexo-concave heart valves: an easy-to-use tool to aid decision-making in individual patients.

To develop an easy-to-use tool for decision-making on prophylactic replacement of Björk-Shiley convexo-concave heart valves. Decision analysis comparing elective replacement with observation. Referral centres for patients with artificial heart valves. Quantitative estimates were obtained from a follow up study conducted in The Netherlands, including 2303 patients with a mean follow up of 6.6 years and from recently published studies. Elective valve replacement with a new artificial heart valve. Loss of life-expectancy. A simple graph was constructed to present the loss of life-expectancy caused by strut fracture for combinations of basal life-expectancy (life-expectancy without strut fracture) and lethal fracture risk (strut fracture risk multiplied by lethality of fracture). This loss can be compared directly with the loss of life-expectancy caused by surgical mortality. This quantitative approach takes into account individual patient characteristics, such as age, gender, cardiac comorbidity, and position of the valve, but the final estimation of surgical mortality also requires clinical judgement. The calculations can be made easily by hand or with a simple computer application. This decision support tool enables the direct estimation of the gain or loss of life-expectancy that is likely with replacement of a Björk-Shiley convexo-concave heart valve. It can be used to evaluate individual patients as well as groups of patients, and allows for easy incorporation of revisions of fracture risk estimates.

Densitometric studies of the tensile strength of the proximal femur

The prognostic assessment of the fracture resistance of the proximal femur is of great importance to the age related increasing incidence of femur neck fractures. This is particularly important in sport for the elderly. The statistical relationship between the osteodensitometrically determined bone density and the risk of a femur neck fracture has been shown in epidemiological studies, whereby the determination of bone density at the proximal femur has provided the most precise predictive results. The present investigation determines the direct relationship between bone density and fracture resistance. Twenty isolated femurs were investigated with the DPX-L-system (Lunar) to measure the bone density in three different areas of the metaphysia as well as important morphometric parameters. Subsequently the femora were fractured in a special device which also recorded the forces required for fracture. The statistical analysis showed a high correlation between the fracture forces and the bone density of the femur neck and trochanter regions. This was true to a lesser extent in the Ward triangle. No significant correlation was found to the morphometric parameters. Quite different forces with considerably greater amplitudes can occur in falls. These may also be absorbed by different structures such as muscle tissue, and, therefore not act directly upon the femur neck. Despite these limitations the determination of bone density appears to permit the individual estimation of fracture risk of the femur neck.

Effect of prefracture versus postfracture dietary assessment on hip fracture risk estimates.

Dietary factors are presumed to have influence on bone mass and hence fracture susceptibility. Most information in this respect is based on retrospective assessment of previous dietary habits. In a population-based case-control study nested within a cohort, we collected dietary information both before and after a first hip fracture. Thus it was possible to study reported changes in dietary habits, intentional as well as unintentional, among hip fracture patients after a first hip fracture and to compare postfracture with prefracture dietary information. More than 65 000 women born 1914-1948 in two counties in central Sweden completed a food frequency questionnaire regarding their usual current dietary habits, before attending a mammographic screening between the years 1987 and 1990. Subsequently 123 of them sustained a first hip fracture and were defined as cases in the present study. For every case, one control, individually matched by age and county of residence, was selected from the cohort. A second identical food frequency questionnaire was mailed to both cases and controls on average 2 years after the hip fracture event. In total 98 case/control pairs could be included in the analysis. The association between diet and hip fracture was evaluated and the results from the two dietary assessments were contrasted. Women who themselves claimed that they had not changed their diet in recent years were analysed separately. The hip fracture cases, compared with the controls, had reduced their reported dietary intake of dairy products after the fracture. Apparently this was not intentional since this effect was more pronounced among those cases who claimed that their diet was unchanged. The changes were most apparent among the younger cases with a more recent hip fracture and with a body mass index above the median. Half of the cases, more than twice the frequency in controls, who were initially classified as having high intake of dairy products were classified as having low intake (<800 mg calcium/day) after the hip fracture. This also lowered, in fact reversed, the relative risk estimates of hip fracture both for intake of dairy products and calcium. Crude odds ratios of highest quartile of intake versus lowest, changed from 3.0 to 0.6 for dairy products and from 2.6 to 0.9 for calcium. No other foods or nutrients displayed such notable differences between the two surveys. We conclude that the use of current and retrospective dietary information after a hip fracture can lead to a differential misclassification in dietary studies and to biased estimates of hip fracture risk as compared with prospectively collected dietary information.

When should bone density measurements be repeated?

We calculated how long to wait before repeating bone mineral density (BMD) measurements to reassess fracture risk. Correlation results from serial measurements of 495 postmenopausal Japanese-American women were used to estimate 95% confidence intervals (CI) for future BMD. After 7 years of follow-up, BMD correlations with the initial measurement ranged between 0.81 and 0.94, depending on age group and measurement site. In this analysis, the period between measurements was defined as the time required for the lower 95% CI to fall below the BMD value corresponding to doubling of fracture risk. Progressive bone loss causes fracture risk to double after 10 years, on average. However, the 95% CIs indicate that a second BMD measurement will detect risk doubling after only 2 or 3 years for some women. For untreated, early postmenopausal women, the period between measurements was approximately 2-5 years for the radius and 4-6 years for the calcaneus, depending on the initial BMD level. The period was approximately 1 year longer for women age 60 and older. Treatments that halve the bone loss rate would increase the period by 1-3 years. In the absence of a second measurement of BMD, the CI will continue to expand with time, corresponding to a wider range in risk between individuals, and a greater proportion of women will be at increased fracture risk. Obtaining a second BMD measurement pinpoints the patient's status within the precision of the measurement. We conclude that repeated BMD measurements will provide a more accurate estimate of fracture risk than a single, baseline measurement.

Single-leg strut fractures in explanted Björk-Shiley valves

A retrospective follow-up study in the Netherlands on the risk of fracture of Björk-Shiley convexo-concave valves concluded that prophylactic replacement is advisable for certain groups of patients. We have examined valves explanted from twenty-two patients because they met epidemiological criteria for reoperation, with or without the presence of moderate cardiac impairment, or because there were other cardiac complaints not related to the valve. No information was available before explanation to suggest a valve defect. All patients survived their operations. Of the twenty-four valves, seven (29% [95% CI 13-52]) had fracture of one of the legs of the outlet strut (single-leg strut fracture [SLF]). Two other valves had features that suggested fatigue defects. As in the previous study, 70 degrees valves had the highest risk of SLF (five of sixteen, two aortic and three mitral). However, two of eight 60 degrees valves (both aortic) also had SLF. Current hazard calculations and explanation recommendations may need to be revised. Since several of the defective valves were welded by the same person, knowledge of manufacturing details may help in estimation of fracture risk for an individual patient.

Fracture prediction models for osteoporosis prevention

Fracture prediction models have been developed that can estimate an individual's cumulative or lifetime fracture risk on the basis of bone mineral measurements and other factors. Examples illustrate how estimates of cumulative fracture risk might be influenced by initial age and level of bone mass, as well as by anticipated bone loss rate. New data regarding bone loss rates, fracture costs, and fracture risk factors should be incorporated to improve the accuracy of existing models. Such models could then be used for cost-benefit analysis to explore optimal treatment strategies.

Colles' fracture and bone density of the ultradistal radius.

To determine whether Colles' fracture, generally considered a manifestation of postmenopausal osteoporosis, is associated with a decrease in bone density at the site of fracture, we measured bone mineral density of the ultradistal radius (UDR-BMD) by single-photon absorptiometry with computer-assisted image processing. In 119 normal women (ages 22-92 years), UDR-BMD decreased by 17% between ages 30 and 75 years. From UDR-BMD measurements in these normal women and in 40 women (ages 53-80 years) with Colles' fracture alone, a population-based analysis was made to estimate fracture risk at different values of UDR-BMD. Colles' fracture was uncommon at UDR-BMD greater than 0.40 g/cm2 (the "fracture threshold"). As bone density decreased below this level, fractures became more frequent (a "gradient of risk").

Fracture prevalence and bone mineral mass in osteoporosis measured with computed tomography and dual energy photon absorptiometry.

In 174 adults presenting with backache, bone densitometry was performed on the lumbar spine, both femoral necks, and one femoral shaft employing dual energy photon absorptiometry (DPA); in 112 of these, densitometry was undertaken on L4 using single energy quantitative computer assisted tomography (CT). Radiographs of the spine were obtained in all patients and those with known or suspected malignant disease were excluded. The subjects were divided into two groups according to the presence (n = 128) or absence (n = 44) of signs of vertebral collapse or compression. The predictive value of the densitometric results for the presence of vertebral fractures was calculated and used as an estimate of fracture risk. While CT showed somewhat higher predictive values than DPA of the spine or combinations of DPA results from spine and femoral necks, the difference was not significant. It is concluded that with both CT and DPA the probability of the presence or absence of fracture can be raised to 75-80% when the probability prior to the investigation is 50% and when the threshold values of the measurements are chosen so that their sensitivity and specificity are about equal.

Methods and application of bone densitometry in clinical diagnosis.

With the awareness of osteoporosis as a major health problem for an aging population, there is great interest in early recognition and treatment of abnormal bone loss. Effective prevention of bone loss has to occur prior to the occurrence of irreparable damage. Standard radiographic procedures are not sensitive enough for the task. Therefore, a number of alternative procedures to estimate bone loss have been developed over the years, ranging from efforts to quantitate information obtained from radiographic images to sophisticated procedures such as neutron activation analysis or procedures based on the Compton scatter phenomenon. Only two procedures, photon absorptiometry and computed tomography (CT), have emerged as applicable for routine clinical use. In photon absorptiometry the entire bone mineral (cortical and trabecular bone) of a specific skeletal site is measured. CT allows measuring of bone mineral of trabecular or cortical bone alone. Normally, bone mass reaches a maximum in the third decade and then continuously declines. This age-related bone loss is greater in women in whom an accelerated rate of loss occurs at the menopause. When bone density reaches a critical fracture threshold, skeletal fractures occur (spine, hip, and distal long bones). The age at which this critical fracture threshold is reached depends on the maximal bone mass achieved in early adulthood and the rate of loss with increasing age. With the exception of NaF, present-day therapeutic efforts only retard or prevent bone loss but do not significantly add bone mineral to the skeleton. Recognition of high-risk groups and early treatment are therefore required. Absorptiometry, and probably in the future CT, also permit the measuring of bone mineral at sites of fracture with sufficient accuracy and precision to allow an early detection of lower than normal (for age and sex) bone mass, estimating fracture risk, and monitoring of the rate of bone loss by repeated measurements. An operational diagnosis of osteoporosis based on fracture risk has also been attempted from bone mineral measurements. And last, the effect of a drug regimen used to prevent or decrease bone loss can be monitored with these procedures.

Fracture risk estimation for Swedish earthquakes

For Swedish earthquakes, the average magnitude increases gently with the focal depth, whereas the seismic wave energy exhibits significant maxima at 15, 23 and 28 km depth. The earthquake fracture risk is estimated to be about 10 −6 for an underground storage facility in a carefully selected site.