Porth's Essentials of Pathophysiology, 4e

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Disorders of the Skeletal System: Metabolic and Rheumatic Disorders

C h a p t e r 4 4

diminishing the expression of osteoprotegerin (OPG) (see Chapter 42, Understanding Bone Remodeling). Compensatory osteoblastic activity and new bone for- mation occurs, but does not keep pace with the bone that is lost. Male sex hormone deficiency may contribute to age- related bone loss in men, although the effect is not of the same magnitude as that caused by estrogen deficiency. Unlike women, men do not have a midlife loss of sex hormone production. 12,13 Another factor that provides relative protection for men is the fact that they achieve 8% to 10% more peak bone mass than women. 13 Although androgens have long been assumed to be criti- cal for growth and maintenance of the male skeleton, it has recently been suggested that estrogens obtained from peripheral conversion of testicular and adrenal hormone precursors may be even more important than androgens in the maintenance of bone mass in men. Age-related changes in bone density occur in all indi- viduals and contribute to the development of osteopo- rosis in both sexes. Age-related changes in bone cells and matrix have a strong impact on bone metabolism. Osteoblasts from elderly persons have reduced replica- tive and biosynthetic potential compared with those of younger persons. Growth factors that stimulate osteo- blastic activity also lose their potential over time. The end result is a skeleton that has decreased ability to make bone. Reduced physical activity increases the rate of bone loss because mechanical forces are important stimuli for normal bone remodeling. Thus, the decreased physical activity that often accompanies aging may also contribute to the loss of bone mass in the elderly. Secondary osteoporosis is associated with many conditions, including endocrine disorders, malabsorp- tion disorders, malignancies, alcoholism, and certain medications. 14 Persons with endocrine disorders such as hyperthyroidism, hyperparathyroidism, Cushing syn- drome, or diabetes mellitus are at high risk for devel- opment of osteoporosis. 15 Hyperthyroidism causes an acceleration of bone turnover. Some malignancies (e.g., multiple myeloma) secrete osteoclast-activating factor, causing significant bone loss. Alcohol is a direct inhibi- tor of osteoblasts and may also inhibit calcium absorp- tion. Corticosteroid use is the most common cause of drug-related osteoporosis, and long-term corticosteroid use in the treatment of disorders such as rheumatoid arthritis and chronic obstructive lung disease is associ- ated with a high rate of fractures. 16 The prolonged use of aluminum-containing antacids, which increase calcium excretion, and anticonvulsants, which impair vitamin D production, may also contribute to bone loss. Persons with human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) who are being treated with antiretroviral therapy may develop a decrease in bone density and signs of osteopenia and osteoporosis. 17 Several groups of children and adolescents are at par- ticular risk for decreased bone mass, including prema- ture infants and those with low birth weight who have lower-than-expected bone mass in the early weeks of life, and children who require treatment with corticosteroid

drugs (e.g., those with childhood inflammatory diseases and transplant recipients). 18 Children with cystic fibro- sis often have impaired gastrointestinal function that reduces the absorption of calcium and other nutrients, and many also require the frequent use of corticosteroid drugs. Premature osteoporosis is increasingly being seen in female athletes due to an increased prevalence of eating disorders and amenorrhea. 19 It most frequently affects women engaged in endurance sports, such as running and swimming; in activities where appearance is impor- tant, such as figure skating, diving, and gymnastics; or in sports with weight restrictions, such as horse racing, martial arts, and rowing. The female athlete triad refers to a pattern of disordered eating that leads to amenor- rhea and eventually osteoporosis. Poor nutrition, com- bined with intense training, can decrease the critical body fat–to–muscle ratio needed for normal menses and estrogen production by the ovary. The decreased levels of estrogen combined with the lack of calcium and vita- min D from dietary deficiencies result in a loss of bone density and increased risk for fractures. There is a con- cern that athletes with low BMD will be at increased risk for fractures during their competitive years. It is unclear whether osteoporosis induced by amenorrhea is reversible. Data are emerging that even having only one or two elements of the triad greatly increases the risk of these women for long-term morbidity. 19 Clinical Features Osteoporotic changes occur in the diaphysis and metaphysis of bone. 3,4 There is loss of trabeculae from cancellous bone and thinning of the cortex to such an extent that minimal stress causes fractures. The changes that occur with osteoporosis have been explained by two distinct disease processes: postmenopausal, or age- related, osteoporosis. In postmenopausal women, the increase in osteoclastic activity affects mainly bones or portions of bone that have increased surface area, such as the cancellous compartment of the vertebral bodies. The osteoporotic trabeculae become thinned and lose their interconnections, leading to microfractures and eventual vertebral collapse. In senile osteoporosis, the osteoporotic cortex is thinned by subperiosteal and end- osteal resorption and the haversian systems are widened. In severe cases, the haversian systems are so enlarged that the cortex resembles cancellous bone 4 (Fig. 44-1). Hip fractures, which are seen later in life, are more com- monly associated with senile osteoporosis. Clinical Manifestations. Osteoporosis is usually a silent disorder. Often, the first manifestations of the dis- order are those that accompany a skeletal fracture—a vertebral compression fracture or fracture of the hip, pelvis, humerus, or other bones (Fig. 44-2). Fractures are typically sudden in onset and may be caused by a fall, sudden movement, lifting, jumping, or even cough- ing. Hip fractures occur mainly in persons over age 65. Wedging and collapse of vertebrae cause a loss of height in the vertebral column and kyphosis, a condition