Chris De Laet

Predictive Value of BMD for Hip and Other Fractures.

The relationship between BMD and fracture risk was estimated in a meta‐analysis of data from 12 cohort studies of ∼39,000 men and women. Low hip BMD was an important predictor of fracture risk. The prediction of hip fracture with hip BMD also depended on age and z score.

Assessment of fracture risk.

The diagnosis of osteoporosis is based on the measurement of bone mineral density (BMD). There are a number of clinical risk factors that provide information on fracture risk over and above that given by BMD. The assessment of fracture risk thus needs to be distinguished from diagnosis to take account of the independent value of the clinical risk factors. These include age, a prior fragility fracture, a parental history of hip fracture, smoking, use of systemic corticosteroids, excess alcohol intake and rheumatoid arthritis. The independent contribution of these risk factors can be integrated by the calculation of fracture probability with or without the use of BMD. Treatment can then be offered to those identified to have a fracture probability greater than an intervention threshold.

A meta-analysis of prior corticosteroid use and fracture risk

The relationship between use of corticosteroids and fracture risk was estimated in a meta‐analysis of data from seven cohort studies of ∼42,000 men and women. Current and past use of corticosteroids was an important predictor of fracture risk that was independent of prior fracture and BMD.

International Variations in Hip Fracture Probabilities: Implications for Risk Assessment

It is recommended that intervention thresholds should be based on absolute fracture risk, but there is a large variation in hip fracture incidence from different regions of the world. The aim of this study was to examine heterogeneity of hip fracture probability in different regions from recent estimates of hip fracture incidence and mortality to adjust intervention thresholds. Ten‐year probabilities of hip fracture were computed in men and women at 10‐year intervals from the age of 50 years and lifetime risks at the age of 50 years from the hazard functions of hip fracture and death. Lifetime risk at the age of 50 years varied from 1% in women from Turkey to 28.5% in women from Sweden. High lifetime risks in women were associated with high lifetime risks in men (r = 0.83). There also were significant correlations of 10‐year risk at any age between men and women. Ten‐year probability was standardized to that of men and women from Sweden (set at 1.0). There was a 15‐fold range in 10‐year probability from 1.24 in Norway to 0.08 in Chile. Countries were categorized by 10‐year probabilities comprising very high risk (Norway, Iceland, Sweden, Denmark, and the United States), high risk (China [Taiwan {TW}], Germany, Switzerland, Finland, Greece, Canada, The Netherlands, Hungary, Singapore, Italy, United Kingdom, Kuwait, Australia, and Portugal), medium risk (China [Hong Kong {HK}], France, Japan, Spain, Argentina, and China), and low risk (Turkey, Korea, Venezuela, and Chile). The categorization of hip fracture probabilities can be used to adjust intervention thresholds based on age, sex, and relative risk from a reference population such as Sweden.

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 (≥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.

The incidence of vertebral fractures in men and women: the Rotterdam Study.

Vertebral fractures are considered the most common fractures in osteoporosis. Nevertheless, little is known about the epidemiology of these fractures, especially in men. Therefore, the incidence of vertebral fractures was studied in 3469 men and women from the Rotterdam Study. Spinal radiographs were obtained at baseline and again after a mean follow‐up of 6.3 years. The follow‐up radiographs were scored for vertebral fractures using the McCloskey‐Kanis assessment method. Whenever a vertebral fracture was detected, the radiograph was compared with the baseline radiograph. If this fracture was not already present at baseline, it was considered an incident fracture. The incidence increased strongly with age, ranging from 7.8/1000 person years (PY) at ages 55‐65 years to 19.6/1000 PY at ages over 75 years for women, and 5.2‐9.3/1000 PY for men, respectively. Analyses repeated in strata of presence or absence of prevalent vertebral fractures showed that both in men and in women, the increase in incidence with age was almost exclusively observed in subjects with one or more prevalent fractures present at baseline. For both genders, the incidence of vertebral fractures doubled per SD decrease in lumbar spine or femoral neck bone mineral density (BMD). This study shows that overall, the incidence of vertebral fractures is higher in women than in men. In both genders, the incidence increases with age. Furthermore, the presence of a prevalent vertebral fracture and a low BMD are strong independent predictors of incident vertebral fractures in men and women.

Excess mortality after hospitalisation for vertebral fracture

An excess mortality is well described after vertebral fracture. Deaths are in part related to co-morbidity, but could also be due to the fracture event itself, either directly or indirectly. The aim of this study was to examine the quantum and pattern of mortality following vertebral fracture. We identified 16,051 men and women aged 50 years or more with a vertebral fracture that required hospitalization in 28.8 million person years from the patient register of Sweden. Mortality after vertebral fracture was examined using Poisson models applied to fracture patients and compared to that of the general population. At all ages, the risk of death was markedly increased immediately after the event. After a short period of declining risk, the risk increased with age at a rate that was higher than that of the general population and comparable to that 1 year after hip fracture. The latter function was assumed to be due to deaths related to co-morbidity and the residuum assumed to be due to the vertebral fracture. Causally related deaths comprised 28% of all deaths associated with vertebral fracture (depending on age). We conclude that a minority of deaths following hospitalization for vertebral fracture are attributable to the fracture itself under the assumptions we used.

Blood Pressure in Adulthood and Life Expectancy With Cardiovascular Disease in Men and Women: Life Course Analysis

Limited information exists about the consequences of hypertension during adulthood on residual life expectancy with cardiovascular disease. We aimed to analyze the life course of people with high blood pressure levels at age 50 in terms of total life expectancy and life expectancy with and without cardiovascular disease compared with normotensives. We constructed multistate life tables for cardiovascular disease, myocardial infarction, and stroke using data from 3128 participants of the Framingham Heart Study who had their 50th birthday while enrolled in the study. For the life table calculations, we used hazard ratios for 3 transitions (healthy to death, healthy to disease, and disease to death) by categories of blood pressure level and adjusted by age, sex, and confounders. Irrespective of sex, 50-year-old hypertensives compared with normotensives had a shorter life expectancy, a shorter life expectancy free of cardiovascular disease, myocardial infarction, and stroke, and a longer life expectancy lived with these diseases. Normotensive men (22% of men) survived 7.2 years (95% confidence interval, 5.6 to 9.0) longer without cardiovascular disease compared with hypertensives and spent 2.1 (0.9 to 3.4) fewer years of life with cardiovascular disease. Similar differences were observed in women. Compared with hypertensives, total life expectancy was 5.1 and 4.9 years longer for normotensive men and women, respectively. Increased blood pressure in adulthood is associated with large reductions in life expectancy and more years lived with cardiovascular disease. This effect is larger than estimated previously and affects both sexes similarly. Our findings underline the tremendous importance of preventing high blood pressure and its consequences in the population.

Risk factors for incident vertebral fractures in men and women: the Rotterdam Study.

Low BMD and prevalent vertebral fractures are known risk factors for incident vertebral fractures. In 3001 men and women from the Rotterdam Study, prevalent nonvertebral fractures, early menopause, current smoking, and walking aid use were also strong risk factors for incident vertebral fractures.

Femoral neck BMD is a strong predictor of hip fracture susceptibility in elderly men and women because it detects cortical bone instability: The Rotterdam Study

We studied HSA measurements in relation to hip fracture risk in 4806 individuals (2740 women). Hip fractures (n = 147) occurred at the same absolute levels of bone instability in both sexes. Cortical instability (propensity of thinner cortices in wide diameters to buckle) explains why hip fracture risk at different BMD levels is the same across sexes.