Prevention and management of osteoporosis

Epidemiology of osteoporosis: The prevalence of osteoporosis increases markedly with age in women. According to the criteria suggested by a WHO Study Group, namely a BMD 2.5 standard deviations or more below the average for the young healthy female population, by age 75 years, approximately 30% of Caucasian women would be classified as having osteoporosis, based on BMD at the femoral neck of the hip. The clinical consequences of osteoporosis are the result of fractures, the incidence of which increases as BMD decreases. Hip, forearm and vertebral fractures are most closely associated with osteoporosis although fracture risks in other bones are increased among those with osteoporosis. Hip fractures account for most of the morbidity, mortality and costs of the disease. For example, among those living independently before a hip fracture, only about half are able to do so after it. Hip fracture rates increase exponentially with age. At 80 years, a Caucasian woman has about a 3% annual risk of hip fracture. Important clinical risk factors for hip fracture include low body weight, tallness, a personal history of fracture, a family history of fracture, smoking, use of glucocorticoid steroids and physical inactivity. Genetic factors are important, although specific genes remain to be identified. Few studies of risk factors have been conducted on hip fractures in ethnic groups other than Caucasians or in men. Vertebral fractures are also strongly related to age, but even more strongly to menopause. They are also more common in women than in men, and more common among Caucasians than among African-Americans. Rates among Asians are variable but are generally midway between those in Caucasians and African-Americans. The consequences of vertebral fractures include back pain and disability, kyphosis and height loss. The risk of osteoporotic fractures in the future is greatly increased among those with vertebral fractures. Little is known about other clinical risk factors for vertebral fractures. In some countries the incidence of forearm fracture increases 10-fold in women in the 15 years following menopause, but remains fairly constant thereafter. Independently of age, the risk of fracture for postmenopausal women is about three times that for men: the lifetime fracture risk for a Caucasian woman is about 15%. Compared with Caucasians, blacks have about one-third, and Asians and Hispanics about half the risk of hip fracture. An estimated 1.7 million hip fractures occurred throughout the world in 1990. Since both world population and life expectancy are increasing, that number is expected to rise to 6.3 million by 2050. Currently, the majority of hip fractures occur in Europe and North America. However, demographic shifts over the next 50 years will lead to huge increases in the numbers of the elderly in Africa, Asia and South America. Consequently, the burden of the disease will shift from the developed to the developing countries. By 2050, 75% of the estimated 6.3 million hip fractures will occur in the developing countries. Prevention strategies suitable for these countries will therefore need to be developed and implemented. 8.2 Pathogenesis of osteoporosis and related fractures: Bone serves several important functions in the body: protection against trauma, locomotion and provision of a calcium phosphate reservoir. It is a specialized form of connective tissue composed of an organic matrix mineralized by the deposition of calcium phosphate. This gives rigidity and strength to the skeleton together with some elasticity. Morphologically, there are two forms of bone: cortical or compact, and cancellous or spongy. Bone is a living tissue, and is constantly resorbed and formed by the process known as remodelling, so that bone formation takes place not only during growth but also throughout life. Osteoblasts are the cells responsible for bone formation while osteoclasts are specialized cells that resorb bone. During growth, bone formation exceeds bone resorption. From the age of 30 to about 50 years, the amount of bone formed approximately equals the amount resorbed. From the time of the menopause in women and perhaps later in men, bone resorption exceeds bone formation. The mass of bony tissue present at any time during adult life is the difference between the amount accumulated, i.e. the so-called peak bone mass, and that lost with ageing. Pathogenetic factors favouring the osteoporotic process are those impairing bone mass accumulation during growth and those accelerating bone loss during later life. Individuals vary markedly in peak bone mass, which is mainly determined by body size. Heredity is also a determinant of peak bone mass, as are the degree of physical activity and calcium intake. The acquisition of bone mass during growth may be impaired by factors such as bed rest due to illness, and undernutrition or malnutrition, particularly when associated with low calcium and protein intakes. Several paediatric disorders impair optimal gain of bone mass. In some diseases, such as glucocorticoid excess or growth hormone deficiency, the abnormal bone mass accrual can be attributed to a change in a single hormone. In other disorders, such as anorexia nervosa and exercise-associated amenorrhoea, the cause is a combination of malnutrition and deficiency of sex steroid hormones. Severe chronic paediatric diseases requiring immunosuppressive treatment that may include glucocorticosteroids and chemotherapies or radiotherapies can adversely affect bone formation. During late adulthood, hypogonadism is a major cause of bone loss and is the main cause of postmenopausal osteoporosis. At the menopause, estrogen deficiency causes an increase in bone turnover resulting in an imbalance between bone formation and resorption. The pathophysiological mechanism involves the release in the bone marrow of cytokines, such as tumour necrosis factors and interleukins, that stimulate osteoclastic bone resorption. In men, loss of bone may be associated with low rates of bone formation rather than high rates of bone resorption, which in turn may be due to declining levels of gonadal hormones. Other endocrine diseases such as primary hyperparathyroidism, hyperthyroidism and hypercortisolism can induce bone loss. In the elderly, low calcium intake associated with a reduced endogenous production of vitamin D (vitamin D insufficiency) accelerates bone loss, probably by increasing the secretion of PTH. 8.3 Diagnosis and assessment.