Porth's Essentials of Pathophysiology, 4e

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Musculoskeletal Function

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fractures in the weakened bones, especially those in the distal radius and the proximal femur. In contrast to osteoporosis, it is not a significant cause of hip frac- tures. There may be delayed healing and poor retention of internal fixation devices. Osteomalacia usually is accompanied by a compensatory or secondary hyper- parathyroidism stimulated by low serum calcium lev- els. Parathyroid hormone reduces renal absorption of phosphate and removes calcium from the bone. Serum calcium levels are only slightly reduced in osteomalacia. Diagnostic measures are directed toward identify- ing osteomalacia and establishing its cause. Diagnostic methods include x-ray studies, laboratory tests, bone scan, and bone biopsy. X-ray findings typical of osteo- malacia are the development of transverse lines or pseu- dofractures called Looser zones. These apparently are caused by stress fractures that are inadequately healed or by the mechanical inadequacy of penetrating nutri- ent vessels. 4 A bone biopsy may be done to confirm the diagnosis of osteomalacia in a person with nonspecific osteopenia who shows no improvement after treatment with exercise, vitamin D, and calcium. The treatment of osteomalacia is directed at the underlying cause. If the problem is nutritional, restor- ing adequate amounts of calcium and vitamin D to the diet may be sufficient. The elderly and persons with an inadequate dietary intake or sunlight exposure may require supplemental vitamin D. Supplemental vitamin D is specific for vitamin D–resistant rickets, but large doses usually are needed to overcome the resistance to calcium absorption action and to prevent renal loss of phosphate. The biologically active forms of vitamin D, 25-OH vitamin D (calciferol) or 1,25-(OH) 2 vitamin D (calcitriol), are available for use in the treatment of osteomalacia resistant to vitamin D (i.e., osteomalacia resulting from chronic liver disease and kidney failure). If osteomalacia is caused by malabsorption, the treatment is directed toward correcting the primary disease. For example, adequate replacement of pancreatic enzymes is of paramount importance in pancreatic insufficiency. In renal tubular disorders, the treatment is directed at the altered renal physiology. Rickets Rickets is a metabolic bone disorder characterized by a failure or delay in calcification of the cartilaginous growth plate in children whose epiphyses have not yet fused. 28–30 It is also manifested by widening and defor- mation of the metaphyseal regions of long bones and a delay in the mineralization of trabecular, endosteal, and periosteal bone surfaces. Rickets is not a reportable dis- ease; however, case reports and hospital records suggest that, in the United States, its incidence has been rising during the past three decades. 31 There are several forms of rickets, including nutri- tional rickets, vitamin D–dependent rickets, and vitamin D–resistant rickets. As with osteomalacia in the adult, rickets can result from kidney failure; malabsorptive syndromes such as celiac disease and cystic fibrosis; and medications such as anticonvulsants, which impair the

activation of vitamin D in the liver; and aluminum-con- taining antacids, which bind phosphorus and prevent its absorption. Etiology and Pathogenesis. Nutritional rickets results from inadequate sunlight exposure or inadequate intake of vitamin D, calcium, or phosphate. Although uncom- mon in developed countries of the world, rickets still can occur, particularly when an infant is solely breast fed, is dark skinned, or has limited exposure to sunlight. Modern conditions of dress, lifestyle, and recommenda- tions regarding sun avoidance to reduce skin cancer risk may prevent a large proportion of the population from producing adequate amounts of vitamin D. In 2003, the American Academy of Pediatrics recommended a vitamin D supplement for breast-fed infants who do not consume at least 500 mL/day of vitamin D–fortified formula/beverages and non–breast-fed infants who do not consume greater than 500 mL of vitamin D–forti- fied beverages. 31 The supplementation should start dur- ing the first 2 months of life and continue throughout childhood and adolescence. Vitamin D–dependent rickets can result from abnor- malities in the gene coding for the enzyme that con- verts inactive vitamin D to the active form of vitamin D, or from an autosomal disorder caused by mutations in the vitamin D receptor. 29 Vitamin D–resistant rick- ets involves hypophosphatemia or a decrease in serum phosphate levels, the most common form being caused by mutations of the phosphate-regulating gene on the X chromosome. 29 The gene mutation causes renal wast- ing of phosphate at the proximal tubular level of the kidney. Clinical Features. Rickets is characterized by changes in the growing bones of children with overgrowth of the epiphyseal cartilage due to inadequate provisional calci- fication and failure of the cartilage cells to disintegrate. Bones become deformed; ossification at the epiphyseal plates is delayed and disordered, resulting in widening of the epiphyseal cartilage plate. Any new bone that does grow is unmineralized. The conformation of the gross skeletal changes depends on the severity and duration of the rachitic process, and in particular on the stresses to which the individual bones are subjected. During the nonmobile stage of infancy, the head and chest undergo the greatest stresses. The skull is enlarged and soft, clo- sure of the fontanels is delayed, and the teeth are slow to develop. When an ambulating child develops rickets, deformities are likely to affect the spine, pelvis, and long bones (i.e., tibia), causing, most notably, lumbar lordo- sis and bowing of the legs (Fig. 44-3). The ends of long bones and ribs are enlarged. The thorax may be abnor- mally shaped, with prominent rib cartilage (i.e., rachitic rosary). The child usually has stunted growth, with a height sometimes far below the normal range. Weight often is not affected so that the children, many of whom present with a protruding abdomen (i.e., rachitic pot- belly), have been described as presenting a Buddha-like appearance when sitting.