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33 fortunately it is usually self limited it tends to

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33Fortunately, it is usually self-limited. It tends to occur in middle-aged men and women in their late second or third trimester of pregnancy.33It is characterized by bone marrow edema, seen on magnetic resonance imaging (MRI), and areas of localized bone demineralization are seen on plain radiographs. Treatment is primarily symptomatic and the condition usually resolves spontaneously over 3 to 6 months, withno long-term adverse effects.Classic regional osteoporosis is associated with disuse or immobilization of a limb because of fractures, motor paralysis, or bone or joint inflammation (see Fig. 45.14). A negative calcium balance develops early and continues throughout the period of immobilization. After 8 weeks of immobilization, significant osteoporosis is present, although it may develop earlier in persons
younger than 20 years or older than 50 years. A uniform distribution of osteoporosis also has been observed in astronauts and in individuals treated with air suspension therapy as a result of weightlessness and lack of mechanical strain.Pathophysiology.Whatever the cause, osteoporosis develops when the remodeling cycle—the process of bone resorption and bone formation—is disrupted, leading to an imbalance in the coupling process. The explosion of new information in the field of bone biology has led to new understanding of the roles of hormones, growth and signaling factors, and cellular biology in osteoporosis. Although hormonal influences remain important in maintaining bone health, genetic factors and the role of oxidative stress are receiving increased attention as critical determinants of bone homeostasis.25,28Reactive oxygen species (ROSs) are normal byproducts of aerobic metabolism, and although they can cause cell damage, at levels below which they cause oxidative stress (OS),ROSs serve as signaling molecules for many cell types, including osteocytes, osteoblasts, and osteoclasts. When excess ROSs accumulate, OS occurs and can result in loss of bone mass and bone strength.28The osteoclast differentiation pathway is directed by a series of processes that include proliferation, differentiation, fusion, and activation. These processes are controlled by hormones,cytokines, and paracrine stromal-cell microenvironment interactions. Thus the intercellular communication in bone and the key molecular regulators are necessary for bone homeostasis. Certain transcription factors, known as Forkhead box (FoxO), help protect against the effects of OS by preventing excess accumulation of ROS and regulating certain genes that affect DNA repair and cell life span. FoxOs help remove damaged and abnormal cells by inducing apoptosis.28Interleukins (IL-1, IL-4, IL-6, IL-7, IL-11, IL-17), tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-β), prostaglandin E2, and hormones interact to control osteoclasts34(Fig. 45.11). Normal bone homeostasis is dependent on the balance between the cytokine receptor activator of nuclear factor κβ ligand (RANKL), its receptor RANK, and its

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