C De Laet

Ten Year Probabilities of Osteoporotic Fractures According to BMD and Diagnostic Thresholds

Abstract: The objectives of the present study were to estimate 10 year probabilities of osteoporotic fractures in men and women according to age and bone mineral density (BMD) at the femoral neck. Risks were computed from the incidence of a first hip, distal forearm, proximal humerus and symptomatic vertebral fracture from patient records in Malmo¨, Sweden and future mortality rates for each year of age from Poisson models using the Swedish patient register and statistical year book. Fracture probability was computed using the Swedish population and cut-off values for T-scores based on the NHANES III female population. We assumed that the risk of fracture increased with decreasing BMD as assessed by meta-analysis in independent studies. The 10-year probability of any fracture was determined from the proportion of individuals fracture-free from the age of 45 years. With the exception of forearm fractures in men, 10 year probabilities increased with age and T-score. In the case of hip and spine fractures, fracture probabilities for any age with low BMD were similar between men and women. The effect of age on risk independently of BMD suggests that intervention thresholds should not be at a fixed T-score but vary according to absolute probabilities. Intervention thresholds based on hip BMD T-scores are similar between sexes.

Long-term risk of osteoporotic fracture in Malmö.

Abstract: The objectives of the present study were to estimate long-term risks of osteoporotic fractures. The incidence of hip, distal forearm, proximal humerus and vertebral fracture were obtained from patient records in Malmo¨, Sweden. Vertebral fractures were confined to those coming to clinical attention, either as an inpatient or an outpatient case. Patient records were examined to exclude individuals with prior fractures at the same site. Future mortality rates were computed for each year of age from Poisson models using the Swedish Patient Register and the Statistical Year Book. The incidence and lifetime risk of any fracture were determined from the proportion of individuals fracture-free from the age of 45 years. Lifetime risk of shoulder, forearm, hip and spine fracture were 13.3%, 21.5%, 23.3% and 15.4% respectively in women at the age of 45 years. Corresponding values for men at the age of 45 years were 4.4%, 5.2%, 11.2% and 8.6%. The risk of any of these fractures was 47.3% and 23.8% in women and men respectively. Remaining lifetime risk was stable with age for hip fracture, but decreased by 20–30% by the age of 70 years in the case of other fractures. Ten and 15 year risks for all types of fractures increased with age until the age of 80 years, when they approached lifetime risks because of the competing probabilities of fracture and death. We conclude that fractures of the hip and spine carry higher risks than fractures at other sites, and that lifetime risks of fracture of the hip in particular have been underestimated.

Smoking and fracture risk: a meta-analysis.

Smoking is widely considered a risk factor for future fracture. The aim of this study was to quantify this risk on an international basis and to explore the relationship of this risk with age, sex and bone mineral density (BMD). We studied 59,232 men and women (74% female) from ten prospective cohorts comprising EVOS/EPOS, DOES, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, Hiroshima and two cohorts from Gothenburg. Cohorts were followed for a total of 250,000 person-years. The effect of current or past smoking, on the risk of any fracture, any osteoporotic fracture and hip fracture alone was examined using a Poisson model for each sex from each cohort. Covariates examined were age, sex and BMD. The results of the different studies were merged using the weighted β-coefficients. Current smoking was associated with a significantly increased risk of any fracture compared to non-smokers (RR=1.25; 95% Confidence Interval (CI)=1.15–1.36). Risk ratio (RR) was adjusted marginally downward when account was taken of BMD, but it remained significantly increased (RR=1.13). For an osteoporotic fracture, the risk was marginally higher (RR=1.29; 95% CI=1.13–1.28). The highest risk was observed for hip fracture (RR=1.84; 95% CI=1.52–2.22), but this was also somewhat lower after adjustment for BMD (RR=1.60; 95% CI=1.27–2.02). Risk ratios were significantly higher in men than in women for all fractures and for osteoporotic fractures, but not for hip fracture. Low BMD accounted for only 23% of the smoking-related risk of hip fracture. Adjustment for body mass index had a small downward effect on risk for all fracture outcomes. For osteoporotic fracture, the risk ratio increased with age, but decreased with age for hip fracture. A smoking history was associated with a significantly increased risk of fracture compared with individuals with no smoking history, but the risk ratios were lower than for current smoking. We conclude that a history of smoking results in fracture risk that is substantially greater than that explained by measurement of BMD. Its validation on an international basis permits the use of this risk factor in case finding strategies.

The burden of osteoporotic fractures: a method for setting intervention thresholds.

Abstract: The aim of this study was to assess the relationship between morbidity from hip fracture and that from other osteoporotic fractures by age and sex based on the population of Sweden. Osteoporotic fractures were designated as those associated with low bone mineral density (BMD) and those that increased in incidence with age after the age of 50 years. Severity of fractures was weighted according to their morbidity using utility values based on those derived by the National Osteoporosis Foundation. Morbidity from fractures other than hip fracture was converted to hip fracture equivalents according to their disutility weights. Excess morbidity was 3.34 and 4.75 in men and women at the age of 50 years, i.e. the morbidity associated with osteoporotic fractures was 3–5 times that accounted for by hip fracture. Excess moribidity decreased with age to approximately 1.25 between the ages of 85 and 89 years. On the assumption that the age- and sex-specific pattern of fractures due to osteoporosis is similar in different communities, the computation of excess morbidity can be utilized to determine the total morbidity from osteoporotic fractures from knowledge of hip fracture rates alone. Such data can be used to weight probabilities of hip fracture in different countries in order to take into account the morbidity from fractures other than hip fracture, and to modify intervention thresholds based on hip fracture risk alone. If, for example, a 10-year probability of hip fracture of 10% was considered an intervention threshold, this would be exceeded in women with osteoporosis aged 65 years and more, but when weighted for other osteoporotic fractures would be exceeded in all women (and men) with osteoporosis.

The components of excess mortality after hip fracture

A high excess mortality is well described after hip fracture. Deaths are in part related to comorbidity and in part due directly or indirectly to the hip fracture event itself (causally related deaths). The aim of this study was to examine the quantum and pattern of mortality following hip fracture. We studied 160,000 hip fractures in men and women aged 50 years or more, in 28.8 million person-years from the patient register of Sweden, using Poisson models applied to hip fracture patients and the general population. At all ages the risk of death was markedly increased compared with population values immediately after the event. Mortality subsequently decreased over a period of 6 months, but thereafter remained higher than that of the general population. The latter function was assumed to account for deaths related to comorbidity and the residuum assumed to be due to the hip fracture. Causally related deaths comprised 17-32% of all deaths associated with hip fracture (depending on age) and accounted for more than 1.5% of all deaths in the population aged 50 years or more. Hip fracture was a more common cause for mortality than pancreatic or stomach cancer. Thus, interventions that decreased hip fracture rate by, say, 50% would avoid 0.75% or more of all deaths.

Bone density and risk of hip fracture in men and women: cross sectional analysis

Abstract Objective: To determine the relative contribution of decline in bone density to the increase in risk of hip fracture with age in men and women. Design: Incidence data of hip fracture from the general population were combined with the bone density distribution in a sample from the same population and with a risk estimate of low bone density known from literature. Setting: The Netherlands. Subjects: All people with a hospital admission for a hip fracture in 1993, and bone density measured in a sample of 5814 men and women aged 55 years and over in a district of Rotterdam. Main outcome measure: One year cumulative risk of hip fracture by age, sex, and bone density measured at the femoral neck. Results: A quarter of all hip fractures occurred in men. Men reached the same incidence as women at five years older. Controlled for age, the risk of hip fracture by bone density was similar in men and women. The risk of hip fracture increased 13-fold from age 60 to 80; decrease in bone density associated with age contributed 1.9 (95% confidence interval 1.5 to 2.4) in women and 1.6 (1.3 to 1.8) in men. Conclusions: The risk of hip fracture by age and bone density is similar in men and women. The decrease in bone density associated with age makes a limited contribution to the exponential increase of the risk of hip fracture with age. Key messages The risk of hip fracture increases exponentially with age in both men and women Men have about the same risk of hip fracture five years later than women The risk of hip fracture by age and bone density is similar in men and women The difference in age specific incidence is explained completely by the different bone density in men and women The contribution of decline in bone density to the exponential increase in risk of hip fracture with age is relatively small

Risk of hip fracture according to the World Health Organization criteria for osteopenia and osteoporosis.

The risk of hip fracture is commonly expressed as a relative risk. The aim of this study was to examine the utility of relative risks of hip fracture in men and women using World Health Organization (WHO) diagnostic criteria for low bone mass and osteoporosis. Reference data for bone mineral density (BMD) at the femoral neck, from the third National Health and Nutrition Examination Survey (NHANES III), were applied to the population of Sweden. Relative risks (RRs) were calculated from the known relationship between BMD at the femoral neck and hip fracture risk. The apparent prevalence of low bone mass and osteoporosis depended on the segment of the young population chosen for reference ranges. Using a reference derived from women aged 20-29 years, the prevalence of osteoporosis was 21.2% in women between the ages of 50 and 84 years and 6.3% in men. The RRs associated with osteoporosis depended markedly on the risk comparison. For example, in men or women aged 50 years, the RR of hip fracture in those with osteoporosis compared to those without osteoporosis was 7.4 and 6.1, respectively. The RR of those at the threshold value for osteoporosis compared to those with an average value for BMD at that age was 6.6 and 4.6 in men and women, respectively. RRs were lower comparing those at the threshold value compared to the risk of the general population at that age (4.2 and 2.9, respectively). When RR was expressed in relation to the population risk rather than to the risk at the average value for BMD, RR decreased at all ages by 37%. Such adjustments are required for risk assessment in individuals and for the combined use of different risk factors. Because the average T score at each age decreased with age, the RR of hip fracture at any age decreased with advancing age in the presence of osteoporosis. The decrease in relative risk with age is, however, associated with an increase in absolute risk. Thus, for clinical use, the expression of absolute risks may be preferred to relative risks.

A new approach to the development of assessment guidelines for osteoporosis

The diagnosis of osteoporosis is made from the measurement of BMD. DXA at the hip is the appropriate diagnostic site. Current clinical guidelines follow the principle that BMD measurements are indicated in individuals with risk factors for fracture and that treatment is recommended in those with a BMD below a critical value. In some countries reimbursement for the costs of treatment depend upon such thresholds for BMD. In Europe the critical value corresponds to a T-score of-2.5 SD, whereas in the USA less stringent criteria are used. It is evident, however, that fracture risk at any given T-score varies markedly according to age and other risk factors. This has led to the view that interventions should be targeted to those at high risk, irrespective of a fixed BMD threshold. In this sense, BMD is utlized as a risk assessment, since in many instances intervention thresholds will be less stringent than the diagnostic threshold. Thus, intervention thresholds need to differ from diagnostic thresholds and be based on fracture probabilities. A 10-year fracture probability appears to be an appropriate time frame. There are a number of problems to be overcome in the development of assessment guidelines. They need to take account of not only the risk of hip fracture but also that of other fractures which contribute significantly to morbidity, particularly in younger individuals. A promising approach is to weight fracture probabilities according to the disutility incurred compared with hip fracture probability. Account also needs to be taken of the large geographic variation in fracture probabilities worldwide. A further challenge for the future will be to identify risk factors that predict fracture with high validity in different regions of the world and their independent contributions, so that models of risk prediction can be constructed and ultimately validated in independent cohorts.

Fracture risk following an osteoporotic fracture

The aim of this study was to examine the pattern of fracture risk following a prior fracture at the spine, shoulder or hip. We studied 1918 patients with fractures at these sites identified from the Department of Radiology in Malmo who were followed for 5 years. Poisson regression was used to compute fracture rates immediately after the initial fracture and at 5 years thereafter in men and women aged 60 or 80 years. Immediate fracture risk was higher than that of the general population, more markedly so at the age of 60 than at 80 years. At the age of 60 years, the risk of hip, forearm and spine fractures were significantly increased following a prior spine, hip or shoulder fracture in men. A similar pattern was seen in women, except that the increase in risk of forearm fracture following a spine or hip fracture was not statistically significant. The incidence of further fractures at the shoulder, spine or hip fell with time after the first fracture, a fall that was significant for all fractures after a shoulder fracture, hip fracture after a spine fracture, and hip and spine fractures after a hip fracture. We conclude that the risk of a subsequent fracture immediately after an osteoporotic fracture is highest immediately after the event. This provides a rationale for very early intervention immediately after fractures to avoid recurrent fractures.

Ten-year risk of osteoporotic fracture and the effect of risk factors on screening strategies.

Bone mineral density (BMD) measurements are widely used to estimate the risk of osteoporotic fractures. In addition, many other risk factors have been identified, some of which are known to add to the risk independently of BMD measurements. The combination of BMD with such risk factors increases the gradient of risk/standard deviation (SD) than that achieved by BMD alone. In this paper, we report the fracture probabilities according to age, gender, and relative risk, and have investigated the effects of changes in the gradient of risk for osteoporotic fractures on the sensitivity and specificity of assessments, modeled on the population of Sweden. Ten-year risks of hip, clinical vertebral, forearm, or proximal humeral fracture were computed with increments in gradient of risk that varied from 1.5 to 6.0 per SD change in skeletal risk. The identification of high-risk groups had little effect on the specificity of assessments, but increased the sensitivity over a wide range of assumptions. The inclusion of all four fracture types had little effect on sensitivity, but increased the positive predictive value of the test. Positive predictive value also increased with age, so that values greater than 50% were obtained testing women at the age of 65 years with modest gradient of risk of 2.0-2.5/SD when small segments of the population were targeted (0.5-5%). Screening of women to direct intervention at the age of 65 years and targeting 25% of the population could save up to 23% of all fractures in women over the next 10 years by the use of multiple tests with a moderate gradient of risk (RR = 2.0/SD). Such gradients might be achieved with the use of multiple risk factors to identify patients at risk.