The term osteopenia refers to decreased bone mass, while osteoporosis is defined as osteopenia that is severe enough to significantly increase the risk of fracture. Radiographically, osteoporosis is considered bone mass at least 2.5 standard deviations below mean peak bone mass, whereas osteopenia is 1 to 2.5 standard deviations below the mean. The disorder may be localized or generalized (involving the entire skeleton). Although osteoporosis can be secondary to endocrine disorders (e.g., hyperthyroidism), gastrointestinal disorders (e.g., malnutrition), or drugs (e.g., corticosteroids), most osteoporosis is primary.
The most common forms of osteoporosis are the senile and postmenopausal types. The following discussion relates largely to these forms of osteoporosis.
Peak bone mass is achieved during young adulthood. Its magnitude is influenced by hereditary factors, especially polymorphisms in the genes that influence bone metabolism (discussed later). Physical activity, muscle strength, diet, and hormonal state also make important contributions. After maximal skeletal mass is attained, bone turnover continues with a net deficit in bone formation resulting in an average loss of 0.7% of bone mass per year. Although much remains unknown, discoveries in the molecular biology of bone formation and resorption have provided new insights into the pathogenesis of osteoporosis (
Fig. 21.5 • Age-related changes. Osteoblasts from older individuals have reduced proliferative and biosynthetic potential and reduced response to growth factors compared to osteoblasts in younger individuals. The net result is a diminished capacity to make bone. This form of osteoporosis, known as senile osteoporosis, is categorized as a low-turnover osteoporosis.
• Increased IL-1, IL-6, TNF levels
Increased expression of RANK, RANKL • Increased osteoclast activity • Decreased replicative activity of osteoprogenitor cells • Decreased synthetic activity of osteoblasts • Decreased biologic activity of matrix-bound growth factors • Reduced physical activity PEAK BONE MASS
Fig.21.5Pathophysiologyofpostmenopausalandsenileosteoporosis(seetext).
Reduced physical activity. The decreased physical activity that is associated with normal aging contributes to senile osteoporosis. Mechanical forces stimulate normal bone remodeling as evidenced by bone loss in an immobilized or paralyzed extremity. The type of exercise is important, as load magnitude influences bone density more than the number of load cycles. Thus, resistance exercises such as weight training are more effective stimuli for increasing bone mass than repetitive endurance activities such as bicycling.
Genetic factors. Single gene defects (e.g., LRP5 mutations) account for only a small fraction of osteoporosis cases. Polymorphisms in other genes have been linked to osteoporosis by genome-wide association studies, in particular genes in the Wnt signaling pathway.
Calcium nutritional state. Adolescents (particularly girls) tend to have low dietary calcium intake, a factor that restricts peak bone mass. Calcium deficiency, increased PTH concentrations, and reduced levels of vitamin D also may play a role in the development of senile osteoporosis.