Epidemiology and classification of osteoporosis

Definition of Osteoporosis

The definition of osteoporosis remains difficult. Dual-energy x-ray absorptiometry is currently the “gold standard” tool for measuring bone mass, and from this, BMD can be obtained. BMD and the strength at which bones break in vitro are strongly correlated; however, BMD does not completely explain the architectural changes in bone that lead to skeletal fragility. Nonetheless, it is recognized that BMD is highly predictive of fracture risk. In 1994, an expert panel convened by the World Health Organization (WHO) established the most widely used definition that encompasses both BMD and previous fracture. It defined osteoporosis as a state in which BMD in women falls more than 2.5 standard deviations below the young adult mean. This definition, however, takes into account only deterioration in bone mineralization and does not consider any of the microarchitectural changes that may weaken bone independently of any effect on BMD. More recently, there has been a move toward assessing an individual’s absolute risk for osteoporotic fracture, an example of which is the Fracture Risk Assessment Tool (FRAX).

Classification of Osteoporosis

Osteoporosis can develop as a primary disorder or be secondary to other factors such as associated medical diseases, surgical procedures, or medications known to accelerate bone loss. It is important to note that both categories are not completely independent of each other and may on occasion be additive; for example, in individuals with primary osteoporosis, secondary causes may further aggravate the bone loss and increase the risk for fractures.

Primary osteoporosis accounts for more than 95% of cases of osteoporosis in women and 70% to 80% in men. In general, it occurs in postmenopausal women and older men; however, it rarely can be found in children and young adults with normal gonadal function and no detectable secondary cause. The pathogenesis of this type of osteoporosis remains unclear. Secondary osteoporosis accounts for fewer than 5% of cases of osteoporosis in women but up to 30% in men. Its causes are listed in Box 198.1 .

Assessment of Fracture Risk

Since 1994, osteoporosis has been defined in terms of BMD. In general, clinical development of pharmacologic agents has focused on the selection of patients on the basis of low BMD with or without prevalent vertebral deformities for inclusion into trials of efficacy. Thus guidance on whom to treat has emphasized assessment of BMD. Use of T-scores (the number of standard deviations above or below the mean for a healthy 30-year-old adult of the same sex and ethnicity as the patient) has many benefits because it is simple and widely used, is strongly correlated with risk for fractures, and can detect some high-risk patients. However, shortcomings include lack of standardization regarding which skeletal sites to study, lack of generalization to the non-White population, and the fact that it evaluates BMD as the only risk factor for fracture.

Given the increasing evidence now suggesting that T-scores alone are insufficient predictors of fracture risk, the WHO convened a scientific group to develop more accurate ways of assessing fracture risk. The use of clinical risk factors together with age and BMD increases the sensitivity of fracture prediction still further without sacrificing specificity. From this, multivariate models have been created that allow the 10-year probability of hip and other fractures to be predicted. An example of such a model is the FRAX tool developed in the United Kingdom by the WHO. Clinicians can easily input clinical data to estimate the 10-year probability of hip and major osteoporotic fractures (which includes forearm, hip, spine, and humerus fractures) in men and women between 40 and 90 years of age. The estimate can be used alone or with BMD to enhance fracture risk prediction. The 10-year probability of fracture was preferred over lifetime risk for several reasons, namely, treatments are not given for a lifetime, the 10-year interval accommodates the clinical trial experience of interventions, and the long-term prognostic value of some risk factors may decrease with time. If an individual’s life expectancy is less than 10 years, the probability produced by FRAX equals the remaining lifetime risk for fracture. In addition, the FRAX tool does not simply adjust for mortality risk based on average mortality rates for the population, but it also accommodates the fact that many risk factors that predict fracture risk also influence mortality (older age, previous fracture, low body mass index, smoking).

Using cost-effectiveness analysis, intervention thresholds for use in clinical practice within the United Kingdom concerning when to commence treatment (or perform BMD testing if not yet done) have also been added to the model. These thresholds are in accordance with recent U.K. National Osteoporosis Guideline Group guidance and are set by age and sex and based on a fracture probability equivalent to that of women with a history of a previous osteoporotic fracture. For example, the intervention threshold for treatment at the age of 50 years corresponds to a 7.5% 10-year probability of sustaining a major osteoporotic fracture. This figure rises progressively with age to 30% at the age of 80 years ( Table 198.1 ).

The FRAX model has now been calibrated to the epidemiology of 44 other countries. It is important to note that any intervention thresholds developed in one country may not be applicable to other countries. For instance, intervention thresholds have also been developed in the United States by the National Osteoporosis Foundation and suggest that persons with a 10-year risk for major osteoporotic fracture of 20% or higher or a 10-year risk for hip fracture of 3% or higher should receive pharmacologic treatment to reduce this risk.

Prevalence and Incidence

This section first discusses the prevalence of osteoporosis and then the prevalence of osteoporotic fracture. The prevalence of osteoporosis in the European Union in 2010 was estimated to be 27.6 million. Furthermore, it has been estimated that 10 million Americans older than 50 years have osteoporosis and that a further 34 million are at risk for the disease. This figure is likely to increase to more than 14 million in 2020. The prevalence of osteoporotic fracture has been evaluated in several epidemiologic studies from North America that have estimated that the remaining lifetime risk for an osteoporotic fracture is 40% in White women 50 years of age ( Table 198.2 ); the risks are 17.5% for hip fracture, 15.6% for clinically diagnosed vertebral fracture, and 16% for distal forearm fracture. Corresponding risks in men are 6%, 5%, and 2.5% (13.1% overall risk for osteoporotic fracture). Recent data from the General Practice Research Database in the United Kingdom that includes 11.3 million people (6.9% of the U.K. population) have indicated a similar risk. In women, the incidence rate of fracture increased from 54 per 10,000 per year at age 18 to 24 years to 420.4 per 10,000 per year at older than 90 years of age. A different trend is observed in men; annual fracture incidence fell from 155.3 per 10, 000 per year at age 18 to 24 years to 58.2 per 10,000 per year at age 60 to 64 years followed by a plateau and then a rise from age 75 to 79 years to an incidence of 224.8 per 10,000 per year at 90+ years ( Fig. 198.1 ). Our knowledge of the epidemiology of childhood fractures in the United Kingdom has been expanded by interrogation of the same database; at their childhood peak, the incidence of fractures (168.5 per 10,000 per year) is surpassed only at 85 years of age in women and men ( Fig. 198.2 ).

Risk Factors

Constitutional and lifestyle risk factors for low BMD are numerous. Factors that influence BMD exert their effect in two ways—through either inadequate development of peak bone mass or an excessive rate of bone loss (or a combination of the two). Genetic factors are thought to be very important in the attainment of peak bone mass; family studies have examined parent–offspring and sibling–sibling correlations in BMD and found correlation coefficients of 0.28 to 0.59. Twin studies have shown much closer concordance of bone density in monozygotic than in dizygotic twins. However, environmental factors such as hormonal status, physical activity, and calcium intake are also important in attaining peak bone mass. Environmental influences are thought to be more important than genetic factors in the determination of bone loss.

Increasing age is an important risk factor for osteoporosis. Peak bone mass is achieved in men and women by the mid-20s. It then plateaus for around 10 years before falling at a rate of 0.3% to 0.5% each year. At menopause, the rate of bone loss in women accelerates to around 3% to 5% per year for 5 to 7 years before returning to the previous rate of decline ( Fig. 198.3 ). This accounts for the increasing incidence of osteoporosis with age. Female gender is also important; men naturally have higher bone mass than women and do not have an accelerated rate of bone loss that women experience around the menopause. Other risk factors include previous fracture, maternal history of fracture, low body weight and weight loss, late age at menarche, early age at menopause, physical inactivity, low dietary calcium intake, smoking, and increased alcohol and caffeine intake. The risk of hip fracture is doubled in individuals with a maternal history of fracture. Ethnicity is another important risk factor for fracture; data from the United Kingdom recently found that age- and sex-adjusted rates of fracture were 4.7 times greater in White women compared to Black women. Protective factors for osteoporosis include greater height, weight, and muscle strength; increased dietary calcium; greater physical activity; later age at menopause; and postmenopausal estrogen use.