Osteoporosis, which literally means porous bone, is the most commonly occurring bone disease characterized by progressive loss of normal bone density accompanied by the deterioration of its microarchitecture. It is caused by an imbalance between osteoclast-mediated bone resorption and osteoblast-mediated bone deposition, resulting in de-creased bone mass, enhanced bone fragility, and in-creased risk of fracture. In healthy individuals, osteoclast activity is primarily regulated by PTH and to a lesser degree by IL-1 and TNF. In addition, differentiation of osteoclast precursors is under the influence of M-CSF and IL-6. Fe-male hormones known as estrogens (especially estradiol) inhibit formation of these cytokines, therefore limiting the activity of osteoclasts. In postmenopausal women in whom estrogen levels are reduced, secretion of these cytokines is increased, resulting in enhanced activity of osteoclasts leading to intensified bone resorption. Osteoporosis is a disease that affects an estimated 75 million people in the United States, Europe, and Japan, including one-third of postmenopausal women and most of the elderly popula-tion. It results in more than 1.3 million fractures annually in the United States There are three general types of osteoporosis. 1. Type I primary osteoporosis occurs in post-menopausal women. Since this type appears at an earlier stage of life than type II, its long-term effect is usually more severe than osteoporosis that de-velops in the later years of life. 2. Type II primary osteoporosis occurs in elderly individuals in their seventh or eighth decade of life and is the leading cause of serious morbidity and functional loss in this age group. 3. Secondary osteoporosis develops as a result of drug therapy (i.e., corticosteroids) or disease pro-cesses that may affect bone remodeling, including malnutrition, prolonged immobilization, weightless-ness (i.e., with space travel), and metabolic bone dis-eases (i.e., hyperparathyroidism, metastatic cancers). Osteoporotic bone has normal histologic structure; however, there is less tissue mass (Fig. F8.2.1). This results in weakened bones that are more prone to fractures follow-ing even minor trauma. Femoral head and neck fractures (commonly known as hip fractures), wrist fractures, and compressed vertebrae fractures are common injuries that frequently disable and confine an elderly person to a wheelchair. Individuals suffering from fractures are at greater risk for death, not directly from the fracture, but from the complications of hospitalization because of immo-bilization and increased risk of pneumonia, pulmonary thrombosis, and embolism. Traditional treatment of individuals with osteoporosis in-cludes an improved diet with vitamin D and calcium sup-plementation and moderate exercise to help slow further bone loss. In addition to diet and exercise, pharmacologic therapy directed toward slowing down bone resorption is employed. Until recently, the treatment of choice in post-menopausal women with osteoporosis was hormone re-placement therapy with estrogen and progesterone. Estrogen is known to retard bone resorption, thereby di-minishing bone loss. The results of the Women’s Health Initiative have shown that hormone replacement therapy can indeed reduce the risk of fractures; however, it causes greater risk of adverse cardiovascular diseases as FIGURE F8.2.1 • Scanning electron micrograph of trabecular bone. a. This image shows section from the trabecular bone obtained from a vertebral body of a healthy individual. b. This specimen was obtained from a vertebral body of elderly women showing extensive signs of osteoporosis. Compare the pattern of trabecular architecture in osteoporosis with normal vertebral bone. (Courtesy of Dr. Alan Boyd). aba b continued next page chapter 8 Bone BONE FORMATION 233 intramembranous bone, with the latter occurring through the activity of the periosteal (membrane) tissue.