Osteonecrosis, Osteosclerosis/Hyperostosis, and Other Disorders of Bone

Definition

Osteonecrosis (aseptic, avascular, or ischemic necrosis of bone) refers to skeletal infarction. Bone infarcts may be asymptomatic, cause self-limited discomfort, or engender painful collapse of subarticular bone and resulting joint destruction.

Epidemiology and Pathobiology

Many conditions are associated with osteonecrosis ( Table 229-1 ). In adults, the most common causes are prior hip fracture, osteomyelitis ( Chapter 251 ), renal dialysis ( Chapter 117 ), ethanol abuse ( Chapter 364 ), and long-term glucocorticoid therapy ( Chapter 28 ).

Skeletal infarction can result from blood vessel destruction (e.g., joint dislocation, fracture), obstruction (e.g., thromboemboli, sickle cell disease, fat emboli, caisson disease), or, hypothetically, compression from local expansion of fatty tissue (e.g., ethanol abuse, glucocorticoid treatment, diabetes mellitus). However, symptoms may not occur unless, weeks later, resorption of dead bone during skeletal repair leads to pathologic fracture. Certain skeletal sites (often subarticular) are predisposed to osteonecrosis, but the locations differ for traumatic compared with nontraumatic processes. Osteochondrosis refers to necrosis of ossification centers. At all ages, however, the femoral head is especially prone to infarction. Nontraumatic osteonecrosis commonly affects the humeral head, femoral condyles, distal end of the tibia, and talus. Although the pathogenesis is uncertain, administration of potent bone antiresorptive agents, especially to patients with malignant disease, and antiangiogenic agents has been associated with osteonecrosis of the jaw ( Fig. 229-1 ). Other drugs less commonly associated with osteonecrosis of the jaw include lenalidomide, corticosteroids, taxanes, letrozole, and methotrexate.

Clinical Manifestations

Pain occurs acutely if there is skeletal collapse. Chronic arthralgia results from desquamated necrotic tissue and articular destruction.

Diagnosis

Magnetic resonance imaging that demonstrates bone marrow edema is especially sensitive for detecting early osteonecrosis. Bone scintigraphy discloses skeletal reconstitution with or without fracture. Relatively late in the pathologic process, radiographs first show patchy areas of osteopenia and osteosclerosis that reflect skeletal repair. A linear subchondral radiolucency (crescent sign) indicates bone collapse.

Treatment

Fibrogenesis Imperfecta Ossium

This rare, usually sporadic condition features generalized osteopenia, but coarsening of the remaining trabeculae places it among the disorders that manifest osteosclerosis. The cause is unknown, but it is possibly genetic. Subperiosteal bone formation and collagen synthesis in nonosseous tissues seem to be normal.

Clinical Manifestations

Intractable skeletal pain typically begins gradually during middle age or later and then rapidly increases, with a debilitating course and eventual immobility. Spontaneous fractures are a prominent complication. Physical examination reveals marked bone tenderness.

Diagnosis and Treatment

On radiography, only the skull is spared. Initially, osteopenia and a slightly abnormal appearance of trabecular bone are noted. The skeletal lesion is a localized form of osteomalacia ( Chapter 226 ) that varies considerably in severity from area to area.

Corticomedullary junctions become indistinct as compact bone is replaced by an abnormal cancellous pattern. Generalized osteopenia causes the remaining spongy bone to appear coarse and dense in a fishnet pattern of mixed lytic and sclerotic areas. Alkaline phosphatase activity in serum is increased. Therapy with recombinant growth hormone under expert guidance may provide short-term benefit.

Progressive Diaphyseal Dysplasia (Camurati-Engelmann Disease)

Progressive diaphyseal dysplasia, which affects all races, is inherited as an autosomal dominant trait with variable expressivity. New bone formation gradually envelops both the periosteal and endosteal surfaces of long bone diaphyses. In patients with severe disease, osteosclerosis also affects the axial skeleton.

Mutations alter the gene that encodes transforming growth factor-β1. The differentiation of osteoclasts may be deranged.

Clinical Manifestations

During childhood, limping or a broad-based, waddling gait is noted. Muscular dystrophy can be diagnosed erroneously. Severely affected individuals may have a characteristic body habitus featuring an enlarged head with a prominent forehead, proptosis, and thin limbs with little subcutaneous fat or muscle mass as well as tender, thickened bones. Cranial nerve palsies and raised intracranial pressure can occur. Some patients have hepatosplenomegaly and Raynaud phenomenon. Symptoms may remit after puberty.

Diagnosis

Irregular hyperostosis of the diaphyses of the major long bones slowly develops as a result of periosteal and endosteal new bone formation. The femur and tibia are most commonly affected. Metaphyses may be involved. The age at onset, rate of progression, and severity are variable. Clinical, radiographic, and bone scan findings are generally concordant. Serum alkaline phosphatase activity, biochemical markers of skeletal turnover, and erythrocyte sedimentation rate may be elevated. Histopathologic study reveals newly formed woven bone that matures and becomes incorporated into cortical bone. Electron microscopy of muscle may show myopathic changes and vascular abnormalities.

Treatment

Endosteal Hyperostosis

Sclerosteosis types 1 and 2 and van Buchem disease are rare autosomal recessive disorders and the most severe forms of endosteal hyperostosis. Sclerosteosis is caused by deactivating mutations in genes SOST and LRP4 . Van Buchem disease involves a deletion downstream of an SOST enhancer. Increased osteoblastic activity from impaired sclerostin action, with failure of osteoclasts to compensate for the increased bone formation, leads to the skeletal changes.

Clinical Manifestations

Sclerosteosis (generalized hyperostosis with syndactyly) affects primarily people of Dutch ancestry. The gender distribution appears equal. Patients are tall and heavy beginning in childhood, with a prominent, square mandible. Raised intracranial pressure and headache may reflect a diminishing cranial cavity that shortens life expectancy. Van Buchem disease causes progressive asymmetrical enlargement of the jaw during puberty. Patients may be symptom free, or, beginning as early as infancy, they may have recurrent facial nerve palsy, deafness, and optic atrophy from narrowing of cranial foramina. Long bones may hurt with applied pressure but are strong.