1. What is osteoporosis and what are its consequences?
Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture. Bone strength reflects the integration of two main features: bone density and bone quality. Bone density is expressed as grams of mineral per area or volume and in any given individual is determined by peak bone mass and amount of bone loss. Bone quality refers to architecture, turnover, damage accumulation (e.g., microfractures) and mineralization. A fracture occurs when a failure-inducing force (e.g., trauma) is applied to osteoporotic bone. Thus, osteoporosis is a significant risk factor for fracture, and a distinction between risk factors that affect bone metabolism and risk factors for fracture must be made.
It is important to acknowledge a common misperception that osteoporosis is always the result of bone loss. Bone loss commonly occurs as men and women age; however, an individual who does not reach optimal (i.e., peak) bone mass during childhood and adolescence may develop osteoporosis without the occurrence of accelerated bone loss. Hence sub-optimal bone growth in childhood and adolescence is as important as bone loss to the development of osteoporosis.
Currently there is no accurate measure of overall bone strength. Bone mineral density (BMD) is frequently used as a proxy measure and accounts for approximately 70 percent of bone strength. The World Health Organization (WHO) operationally defines osteoporosis as bone density 2.5 standard deviations below the mean for young white adult women. It is not clear how to apply this diagnostic criterion to men, children, and across ethnic groups. Because of the difficulty in accurate measurement and standardization between instruments and sites, controversy exists among experts regarding the continued use of this diagnostic criterion.
Osteoporosis can be further characterized as either primary or secondary. Primary osteoporosis can occur in both genders at all ages but often follows menopause in women and occurs later in life in men. In contrast, secondary osteoporosis is a result of medications, other conditions, or diseases. Examples include glucocorticoid-induced osteoporosis, hypogonadism, and celiac disease.
The consequences of osteoporosis include the financial, physical, and psychosocial, which significantly affect the individual as well as the family and community. An osteoporotic fracture is a tragic outcome of a traumatic event in the presence of compromised bone strength, and its incidence is increased by various other risk factors. Traumatic events can range from high-impact falls to normal lifting and bending. The incidence of fracture is high in individuals with osteoporosis and increases with age. The probability that a 50-year-old will have a hip fracture during his or her lifetime is 14 percent for a white female and 5 to 6 percent for a white male. The risk for African Americans is much lower at 6 percent and 3 percent for 50-year-old women and men, respectively. Osteoporotic fractures, particularly vertebral fractures, can be associated with chronic disabling pain. Nearly one-third of patients with hip fractures are discharged to nursing homes within the year following a fracture. Notably, one in five patients is no longer living 1 year after sustaining an osteoporotic hip fracture. Hip and vertebral fractures are a problem for women in their late 70s and 80s, wrist fractures are a problem in the late 50s to early 70s, and all other fractures (e.g., pelvic and rib) are a problem throughout postmenopausal years. The impact of osteoporosis on other body systems, such as gastrointestinal, respiratory, genitourinary, and craniofacial, is acknowledged, but reliable prevalence rates are unknown.
Hip fracture has a profound impact on quality of life, as evidenced by findings that 80 percent of women older than 75 years preferred death to a bad hip fracture resulting in nursing home placement. However, little data exist on the relationship between fractures and psychological and social well-being. Other quality-of-life issues include adverse effects on physical health (impact of skeletal deformity) and financial resources. An osteoporotic fracture is associated with increased difficulty in activities of daily life, as only one-third of fracture patients regain pre-fracture level of function and one-third require nursing home placement. Fear, anxiety, and depression are frequently reported in women with established osteoporosis and such consequences are likely under-addressed when considering the overall impact of this condition.
Direct financial expenditures for treatment of osteoporotic fracture are estimated at $10 to $15 billion annually. A majority of these estimated costs are due to in-patient care but do not include the costs of treatment for individuals without a history of fractures, nor do they include the indirect costs of lost wages or productivity of either the individual or the caregiver. More needs to be learned about these indirect costs, which are considerable. Consequently, these figures significantly underestimate the true costs of osteoporosis.
2. How do risks vary among different segments of the population?
The prevalence of osteoporosis, and incidence of fracture, vary by gender and race/ethnicity. White postmenopausal women experience almost three-quarters of hip fractures and have the highest age-adjusted fracture incidence. Most of the information regarding diagnosis and treatment is derived from research on this population. However, women of other age, racial, and ethnic groups, and men and children, are also affected. Much of the difference in fracture rates among these groups appears to be explained by differences in peak bone mass and rate of bone loss; however, differences in bone geometry, frequency of falls, and prevalence of other risk factors appear to play a role as well.
Both men and women experience an age-related decline in BMD starting in midlife. Women experience more rapid bone loss in the early years following menopause, which places them at earlier risk for fractures. In men, hypogonadism is also an important risk factor. Men and perimenopausal women with osteoporosis more commonly have secondary causes for the bone loss than do postmenopausal women.
African American women have higher bone mineral density than white non-Hispanic women throughout life, and experience lower hip fracture rates. Some Japanese women have lower peak BMD than white non-Hispanic women, but have a lower hip fracture rate; the reasons for which are not fully understood. Mexican American women have bone densities intermediate between those of white non-Hispanic women and African American women. Limited available information on Native American women suggests they have lower BMD than white non-Hispanic women.
Risks associated with low bone density are supported by good evidence, including large prospective studies. Predictors of low bone mass include female gender, increased age, estrogen deficiency, white race, low weight and body mass index (BMI), family history of osteoporosis, smoking, and history of prior fracture. Use of alcohol and caffeine-containing beverages is inconsistently associated with decreased bone mass. In contrast, some measures of physical function and activity have been associated with increased bone mass, including grip strength and current exercise. Levels of exercise in childhood and adolescence have an inconsistent relationship to BMD later in life. Late menarche, early menopause, and low endogenous estrogen levels are also associated with low BMD in several studies.
Although low BMD has been established as an important predictor of future fracture risk, the results of many studies indicate that clinical risk factors related to risk of fall also serve as important predictors of fracture. Fracture risk has been consistently associated with a history of falls, low physical function such as slow gait speed and decreased quadriceps strength, impaired cognition, impaired vision, and the presence of environmental hazards (e.g., throw rugs). Increased risk of a fracture with a fall includes a fall to the side and attributes of bone geometry, such as tallness, hip axis, and femur length. Some risks for fracture, such as age, a low BMI, and low levels of physical activity, probably affect fracture incidence through their effects on both bone density and propensity to fall and inability to absorb impact.
Results of studies of persons with osteoporotic fractures have led to the development of models of risk prediction, which incorporate clinical risk factors along with BMD measurements. Results from the Study of Osteoporotic Fractures (SOF), a large longitudinal study of postmenopausal, white non-Hispanic women, suggest that clinical risk factors can contribute greatly to fracture risk assessment. In this study, 14 clinical risk factors predictive of fracture were identified. The presence of five or more of these factors increased the rate of hip fracture for women in the highest tertile of BMD from 1.1 per 1,000 woman-years to 9.9 per 1,000 woman-years. Women in the lowest tertile of BMD with no other risk factors had a hip fracture rate of 2.6 per 1,000 woman-years as compared with 27.3 per 1,000 woman-years with five or more risk factors present. A second model, derived from the Rotterdam study, predicted hip fractures using a smaller number of variables, including gender, age, height, weight, use of a walking aid, and current smoking. However, these models have not been validated in a population different from that in which they were derived.
A large number of medical disorders are associated with osteoporosis and increased fracture risk. These can be organized into several categories: genetic disorders, hypogonadal states, endocrine disorders, gastrointestinal diseases, hematologic disorders, connective tissue disease, nutritional deficiencies, drugs, and a variety of other common serious chronic systemic disorders, such as congestive heart failure, end-stage renal disease, and alcoholism.
The distribution of the most common causes appears to differ by demographic group. Among men, 30 to 60 percent of osteoporosis is associated with secondary causes; with hypogonadism, glucocorticoids, and alcoholism the most common. In perimenopausal women, more than 50 percent is associated with secondary causes, and the most common causes are hypoestrogenemia, glucocorticoids, thyroid hormone excess, and anticonvulsant therapy. In postmenopausal women, the prevalence of secondary conditions is thought to be much lower, but the actual proportion is not known. In one study, hypercalciuria, hyperparathyroidism, and malabsorption were identified in a group of white postmenopausal osteoporotic women who had no history of conditions that cause bone loss. These data suggest that additional testing of white postmenopausal women with osteoporosis may be indicated, but an appropriate or cost-effective evaluation strategy has not been determined.
Glucocorticoid use is the most common form of drug-related osteoporosis, and its long-term administration for disorders such as rheumatoid arthritis and chronic obstructive pulmonary disease is associated with a high rate of fracture. For example, in one study, a group of patients treated with 10 mg of prednisone for 20 weeks experienced an 8 percent loss of BMD in the spine. Some experts suggest that any patient who receives orally administered glucocorticoids (such as Prednisone) in a dose of 5 mg or more for longer than 2 months is at high risk for excessive bone loss.
People who have undergone organ transplant are at high risk for osteoporosis due to a variety of factors, including pretransplant organ failure and use of glucocorticoids after transplantation.
Hyperthyroidism is a well-described risk factor for osteoporosis. In addition, some studies have suggested that women taking thyroid replacement may also be at increased risk for excess bone loss, suggesting that careful regulation of thyroid replacement is important.
Several groups of children and adolescents may be at risk for compromised bone health. Premature and low birth weight infants have lower-than-expected bone mass in the first few months of life, but the long-term implications are unknown.
Glucocorticoids are now commonly used for the treatment of a variety of common childhood inflammatory diseases, and the bone effects of this treatment need to be considered when steroid use is required chronically. The long-term effects on bone health of intermittent courses of systemic steroids or the chronic use of inhaled steroids, as are often used in asthma, are not well described.
Cystic fibrosis, celiac disease, and inflammatory bowel disease are examples of conditions associated with malabsorption and resultant osteopenia in some individuals. The osteoporosis of cystic fibrosis is also related to the frequent need for corticosteroids as well as to other undefined factors.
Hypogonadal states, characterized clinically by delayed menarche, oligomenorrhea, or amenorrhea, are relatively common in adolescent girls and young women. Settings in which these occur include strenuous athletic training, emotional stress, and low body weight. Failure to achieve peak bone mass, bone loss, and increased fracture rates have been shown in this group. Anorexia nervosa deserves special mention. Although hypogonadism is an important feature of the clinical picture, the profound undernutrition and nutrition-related factors are also critical. This latter point is evidenced, in part, by the failure of estrogen replacement to correct the bone loss.
- Residents of Long-Term Care Facilities
Residents of nursing homes and other long-term care facilities are at particularly high risk of fracture. Most have low BMD and a high prevalence of other risk factors for fracture, including advanced age, poor physical function, low muscle strength, decreased cognition and high rates of dementia, poor nutrition, and, often, use of multiple medications.
3. What factors are involved in building and maintaining skeletal health throughout life?
Growth in bone size and strength occurs during childhood, but bone accumulation is not completed until the third decade of life, after the cessation of linear growth. The bone mass attained early in life is perhaps the most important determinant of life-long skeletal health. Individuals with the highest peak bone mass after adolescence have the greatest protective advantage when the inexorable declines in bone density associated with increasing age, illness, and diminished sex-steroid production take their toll. Bone mass may be related not only to osteoporosis and fragility later in life but also to fractures in childhood and adolescence. Genetic factors exert a strong and perhaps predominant influence on peak bone mass, but physiological, environmental, and modifiable lifestyle factors can also play a significant role. Among these are adequate nutrition and body weight, exposure to sex hormones at puberty, and physical activity. Thus, maximizing bone mass early in life presents a critical opportunity to reduce the impact of bone loss related to aging. Childhood is also a critical time for the development of lifestyle habits conducive to maintaining good bone-health throughout life. Cigarette smoking, which usually starts in adolescence, may have a deleterious effect on achieving bone mass.
Good nutrition is essential for normal growth. A balanced diet, adequate calories, and appropriate nutrients are the foundation for development of all tissues, including bone. Adequate and appropriate nutrition is important for all individuals, but not all follow a diet that is optimal for bone health. Supplementation of calcium and vitamin D may be necessary. In particular, excessive pursuit of thinness may affect adequate nutrition and bone health.
Calcium is the specific nutrient most important for attaining peak bone mass and for preventing and treating osteoporosis. Sufficient data exist to recommend specific dietary calcium intakes at various stages of life. Although the Institute of Medicine recommends calcium intakes of 800 mg/day for children ages 3 to 8 and 1,300 mg/day for children and adolescents ages 9 to 17, only about 25 percent of boys and 10 percent of girls ages 9 to 17 are estimated to meet these recommendations. Factors contributing to low calcium intakes are restriction of dairy products, a generally low level of fruit and vegetable consumption, and a high intake of low calcium beverages such as sodas. For older adults, calcium intake should be maintained at 1,000 to 1,500 mg/day, yet only about 50 to 60 percent of this population meets this recommendation.
Vitamin D is required for optimal calcium absorption and thus is also important for bone health. Most infants and young children in the United States have adequate vitamin D intake because of supplementation and fortification of milk. During adolescence, when consumption of dairy products decreases, vitamin D intake is less likely to be adequate, and this may adversely affect calcium absorption. A recommended vitamin D intake of 400 to 600 IU/day has been established for adults.
Other nutrients have been evaluated for their relation to bone health. High dietary protein, caffeine, phosphorus, and sodium can adversely affect calcium balance, but their effects appear not to be important in individuals with adequate calcium intakes.
Regular physical activity has numerous health benefits for individuals of all ages. The specific effects of physical activity on bone health have been investigated in randomized clinical trials and observational studies. There is strong evidence that physical activity early in life contributes to higher peak bone mass. Some evidence indicates that resistance and high impact exercise are likely the most beneficial. Exercise during the middle years of life has numerous health benefits, but there are few studies on the effects of exercise on BMD. Exercise during the later years, in the presence of adequate calcium and vitamin D intake, probably has a modest effect on slowing the decline in BMD. It is clear that exercise late in life, even beyond 90 years of age, can increase muscle mass and strength twofold or more in frail individuals. There is convincing evidence that exercise in elderly persons also improves function and delays loss of independence and thus contributes to quality of life. Randomized clinical trials of exercise have been shown to reduce the risk of falls by approximately 25 percent, but there is no experimental evidence that exercise affects fracture rates. It also is possible that regular exercisers might fall differently and thereby reduce the risk of fracture due to falls, but this hypothesis requires testing.
Sex steroids secreted during puberty substantially increase BMD and peak bone mass. Gonadal steroids influence skeletal health throughout life in both women and men. In adolescents and young women, sustained production of estrogens is essential for the maintenance of bone mass. Reduction in estrogen production with menopause is the major cause of loss of BMD during later life. Timing of menarche, absent or infrequent menstrual cycles, and the timing of menopause influence both the attainment of peak bone mass and the preservation of BMD. Testosterone production in adolescent boys and men is similarly important in achieving and maintaining maximal bone mass. Estrogens have also been implicated in the growth and maturation of the male skeleton. Pathologic delay in the onset of puberty is a risk factor for diminished bone mass in men. Disorders that result in hypogonadism in adult men result in osteoporosis.
- Growth Hormone and Body Composition
Growth hormone and insulin-like growth factor-I, which are maximally secreted during puberty, continue to play a role in the acquisition and maintenance of bone mass and the determination of body composition into adulthood. Growth hormone deficiency is associated with a decrease in BMD. Children and youth with low BMI are likely to attain lower-than-average peak bone mass. Although there is a direct association between BMI and bone mass throughout the adult years, it is not known whether the association between body composition and bone mass is due to hormones, nutritional factors, higher impact during weight-bearing activities, or other factors. There are several observational studies of fractures in older persons that show an inverse relationship between fracture rates and BMI.
Source: National Institutes of Health
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