Applied Radiology

Dr. Ly is with the Department of Radiology and Nuclear Medicine, Wilford Hall Medical Center, San Antonio, TX.

The skeletal system is dynamic --a center for many important physiologic processes, including red blood cell production and calcium and phosphorus metabolism. Maintenance of physiologic homeostasis requires an adequate supply of minerals, hormones, and vitamins. Metabolic bone diseases are characterized by disruption of the normal physiologic activity of bones. Although some metabolic bone processes are congenital and are detected early in life, others are acquired and may not be detected until later in adulthood. Despite the recent technological advances in computed tomography (CT) and magnetic resonance (MR) imaging, conventional radiography remains the primary imaging modality for the evaluation of metabolic bone disease. This article will review some of the more common metabolic bone processes seen at our institution.

Osteoporosis

Osteoporosis is defined as decreased bone mass (with normal matrix mineralization) of the involved bone caused by either a deficiency of osteoid production or an increased resorption of bone. The illness may be characterized as follows: diffuse, as in the elderly female who is not on hormone replacement therapy; regional, involving a portion of the skeleton; or localized, eg, following extremity disuse after cast placement for stabilization of a fracture (Figure 1). The most frequent sites of involvement are the spine, pelvis, and periarticular regions of the appendicular skeleton. The spine is typically one of the earliest sites to manifest with osteoporotic changes, which include osteopenia, anterior wedging, cortical thinning with endplate preservation, and biconcave vertebral bodies. ¹

Rickets and osteomalacia

Faulty mineralization or calcification of bone matrix is termed rickets in children and osteomalacia in adults. Patients usually present with nonspecific pain, weakness, and bone deformities. Numerous causes include dietary deficiencies of vitamin D or calcium, renal disease, enzymatic defects, liver disease, and inadequate absorption of calcium or phosphorus. ² Radiographic features include osteopenia, widened physes of the long bones, and flaring or cupping of the metaphysis (Figure 2). ³ Long-standing disease leads to osseous softening, giving a bowed appearance, which is most commonly seen in the tibia and femur. Findings in the pelvis include protrusio acetabuli and coxa vera. The majority of patients respond to vitamin D therapy and calcium supplementation, if indicated.

Paget's disease

Paget's disease is a condition of uncertain pathogenesis that is characterized by disorganized bone remodeling and that predominantly affects Caucasians or Northern Europeans. Histologically, a mosaic appearance of osseous formation is typical. Three phases of the disease have been described. ⁴ The acute or hot phase is seen radiographically as a radiolucent area that has been described as "flame-shaped" when involving a long bone and is termed osteoporosis circumscripta when the radiolucency contains geographic margins and involves the skull. The mixed blastic-lytic phase, in which increasing osteoblastic activity (evidenced by increasing sclerosis) coexists with the ongoing osteoclastic activity, results in bone with a mixed sclerotic and lytic appearance. It is during this middle phase that trabecular coarsening, cortical thickening, and generalized bony enlargement occur. The cool or quiescent phase, in which smoldering osteoblastic activity remains, is manifested by dense sclerosis of the affected bone (Figure 3). Complications of Paget's disease include pathologic fractures and, rarely, sarcomatous degeneration. ⁵

Calcium pyrophosphate dihydrate deposition disease

Calcium pyrophosphate dihydrate deposition disease (CPPD) is a disorder characterized by calcium pyrophosphate crystal deposition within articular cartilage (ie, knee menisci, triangular fibrocartilage of the wrist, symphysis pubis), synovium, tendons, capsule, and ligaments (Figure 4). ⁶ This disease of calcium metabolism is associated with a classic triad of findings: cartilage calcification, pain, and joint destruction. Other than by anatomic location, the joint destruction of CPPD is difficult to distinguish from that of osteoarthritis. Calcium pyrophosphate dihydrate deposition disease is frequently associated with gout, hemochromatosis, and hyperparathyroidism.

Hemochromatosis arthropathy

Hemochromatosis is a rare disorder characterized pathologically by tissue damage secondary to excessive iron deposition. Associated morbidity can be significant, as commonly affected organs include the heart, liver, pancreas, skin, and joints. The arthritis of hemochromatosis is insidious in onset and may occur at any stage during the course of the disease, rarely preceding the other clinical features. Although hemochromatosis arthropathy superficially resembles degenerative joint disease--also showing joint space narrowing, subchondral sclerosis, and osteophytosis--the distribution of findings (metacarpophalangeal joints, wrists, elbows, and glenohumeral articulations) distinguishes it from osteoarthritis. ⁷ Abnormalities are particularly frequent in the second and third metacarpophalangeal joints, and peculiar hook-like osteophytes on the radial aspect of the metacarpal heads are characteristic (Figure 5). ⁸ Furthermore, there is symmetric loss of joint space, which is unusual for osteoarthritis. The loss of joint space is associated with subchondral bony eburnation and cyst formation. Currently, the most effective treatment is vigorous phlebotomy. Death is certain if the disease goes untreated.

Hemophilic arthropathy

Hemophilia A is a sex-linked deficiency or abnormality of a plasma protein called factor VIII (FVIII), ⁹ which is seen in 1 of 5000 male births. Symptoms typically begin in childhood in association with hemorrhage after minor trauma and increase through adolescence. The initial episode of intra-articular bleeding is accompanied by joint effusion. With recurrent small bleeds or after a large bleed, periarticular osteoporosis and regional soft-tissue swelling are commonly seen. In adolescents, the hyperemic joint may lead to localized accelerated growth and limb length discrepancies. Eventually, osseous irregularity and erosion develop, accompanied by subchondral cystic change (Figure 6). Synovial effusions are common and may appear radiodense due to hemosiderin deposition. As osseous erosions continue, joint space narrowing is seen with progressive and symmetric cartilaginous destruction. Eventually, complete obliteration of the joint space occurs, and secondary degenerative signs, such as osteophytosis and eburnation, develop. With chronic disease, muscle atrophy and joint contractures may develop. Treatment for hemophilia typically involves some form of factor replacement, depending on the severity of the disease. The pain and swelling associated with joint injuries can be treated with conservative measures.

Hurler's syndrome

Hurler's syndrome is one of the autosomal-recessive mucopolysaccharidoses and is caused by a deficiency of the alpha-L-iduronidase enzyme, resulting in excessive accumulation of muco-polysaccharides. ¹⁰ Clinical manifestations include mental retardation, corneal clouding, and organomegaly of the heart, spleen, and liver. A common radiographic finding seen on the lateral view is an oval-shaped vertebral body with rounded vertebral end plates. Moreover, there frequently is a dorsolumbar gibbous deformity with a bony projection extending off the anteroinferior aspect of the vertebral body (Figure 7). Other findings include osteopenia and an abnormally configured pelvis.

Osteogenesis imperfecta

This hereditary disorder is the result of abnormal type I collagen metabolism (quality or quantity, defect in bone matrix), producing a congenital form of osteoporosis. Osteogenesis imperfecta is characterized by early hearing loss, blue sclera, osteoporosis, bone fragility, and defective dentition. Two forms have been described, congenital (10%) and tarda (90%). ¹¹ In general, the congenital form is much more severe and is characterized by multiple fractures at birth. Only 20% of those with the tarda form will have fractures at birth. Radiologic findings usually include a thinned cortex, osteoporosis, and osseous deformities (Figure 8). The main differential consideration is nonaccidental trauma.

Sickle cell disease

The most common hemoglobinopathy, sickle cell disease, occurs primarily in African Americans and people of Mediterranean descent. ¹² It affects the skeleton by either causing marrow hyperplasia, which replaces the marrow and trabecular bone, ¹ or results in infarction of marrow and bone. ² The most frequently affected bones are the long bones, skull, and spine. Radiographic findings usually appear 10 to 14 days after infarction and include a permeative medullary pattern, periosteal new bone formation, and osteopenia. Chronic disease is manifested by sclerosis and cortical thickening. Humeral or femoral head avascular necrosis can occur and results in a patchy, sclerotic pattern and head flattening in later stages (Figure 9). Other findings may include diploic widening, fish vertebrae, and ischemic dactylitis. ³

Hypertrophic pulmonary osteoarthropathy

Hypertrophic pulmonary osteoarthropathy is a chronic proliferative disease characterized by clubbing of the fingers and toes, synovitis, and painful periostitis of long and tubular bones. The exact mechanism is unknown. This disease is a manifestation of pulmonary disease and is often associated with bronchogenic carcinoma. Radiographic findings include periosteal new bone involving the diaphysis of the tibia, fibula, radius, ulna, humerus, femur, and other long and tubular bones (Figure 10). ¹³ The differential diagnosis includes primary osteoarthropathy, thyroid acropachy, and venous stasis.

Beta-thalassemia

This hereditary disease in patients of Mediterranean descent is characterized by deficient production of beta-hemoglobin chains and can result in a chronic microcytic anemia. In an attempt to compensate for the anemia, the marrow activity increases significantly, thereby producing the characteristic radiographic changes. Long and tubular bones have an expanded appearance and can be associated with cortical thinning and trabecular coarsening (Figure 11). Calvarial changes include dipoploic expansion with a "hair-on-end" appearance to the skull trabeculae. Moreover, there is widening and flattening of the vertebral body, resulting in vertebral plana. The ribs are osteopenic and widened, with an occasional "rib-within-rib" appearance. Extramedullary hematopoiesis is common, manifesting as a soft-tissue, paraspinal mass. ¹⁴

Conclusion

Metabolic bone disease is often detected or suggested on conventional radiography. This article has briefly reviewed a variety of metabolic processes with osseous manifestations, including osteoporosis, rickets/osteomalacia, Paget's disease, CPPD, hemochromatosis arthropathy, hemophilic arthropathy, Hurler's syndrome, osteogenesis imperfecta, sickle cell disease, hypertrophic pulmonary arthropathy, and beta-thalassemia. Familiarization with the characteristic radiographic findings of these entities is important for effective diagnosis and treatment. AR