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MD Consult: Books: Goldman: Cecil Medicine: Chapter 269 – OSTEONECROSIS, OSTEOSCLEROSIS/HYPEROSTOSIS, AND OTHER DISORDERS OF BONE

Goldman: Cecil Medicine, 23rd ed.

Copyright © 2007 Saunders, An Imprint of Elsevier

Chapter 269 – OSTEONECROSIS, OSTEOSCLEROSIS/HYPEROSTOSIS, AND OTHER DISORDERS OF BONE

Michael P. Whyte

   OSTEONECROSIS

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 that leads to joint destruction.

Pathobiology and Pathogenesis

Many conditions are associated with osteonecrosis ( Table 269-1 ). In adults, the most common causes are ethanol abuse and long-term glucocorticoid therapy, both of which have dose-dependent effects.


TABLE 269-1   — 
CAUSES OF ISCHEMIC NECROSIS OF CARTILAGE AND BONE

   Endocrine/metabolic

   Ethanol abuse
   Glucocorticoid therapy
   Cushing’s disease
   Diabetes mellitus
   Hyperuricemia
   Osteomalacia
   Hyperlipidemia
   Bisphosphonate therapy
   Storage diseases (e.g., Gaucher’s disease)
   Hemoglobinopathies (e.g., sickle cell disease)
   Trauma (e.g., dislocation, fracture)
   Human immunodeficiency virus infection
   Dysbaric conditions (e.g., caisson disease)
   Collagen-vascular disorders
   Irradiation
   Pancreatitis
   Organ transplantation
   Hemodialysis
   Burns
   Intravascular coagulation
   Idiopathic, familial

Skeletal infarction may 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 differ for traumatic and nontraumatic processes and for children and adults. Osteochondrosis refers to necrosis of ossification centers; more than 50 eponymic types are recorded. The susceptibility of children to osteochondrosis and its pathogenesis are poorly understood. At all ages, however, the femoral head is especially prone to infarction. Nontraumatic osteonecrosis also commonly affects the femoral condyles, distal end of the tibia, humeral head, and talus.

Clinical Manifestations

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

Diagnosis

Magnetic resonance imaging demonstrating 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 bony collapse.

Treatment

Non-weight-bearing is advisable for an affected limb. Decompression by trephine insertion is used for some sites. Arthrotomy to remove debris, transpositional osteotomy, arthroplasty, or joint replacement may be necessary.

   OSTEOSCLEROSIS/HYPEROSTOSIS

Many conditions are associated with radiographic evidence of increased bone density. Skeletal dysplasias, metabolic disturbances, and various other disorders can cause generalized or focal increases in bone mass ( Table 269-2 ). Aberrations in skeletal growth, modeling (shaping), and/or remodeling (turnover) may be at fault. Osteosclerosis refers to thickening of trabecular (spongy, cancellous) bone. Hyperostosis describes widening of cortical (compact) bone. Increases in trabecular or cortical bone or both may augment skeletal density.


TABLE 269-2   — 
DISORDERS THAT CAUSE DENSE BONES

DYSPLASIAS

   Central osteosclerosis with ectodermal dysplasia
   Craniodiaphyseal dysplasia
   Craniometaphyseal dysplasia
   Dysosteosclerosis
   Endosteal hyperostosis

   van Buchem’s disease
   Sclerosteosis
   Worth-type (LRP5 activation)
   Frontometaphyseal dysplasia
   Infantile cortical hyperostosis (Caffey’s disease)
   Juvenile Paget’s disease
   Lenz-Majewski syndrome
   Melorheostosis
   Metaphyseal dysplasia (Pyle’s disease)
   Mixed-sclerosing-bone dystrophy
   Oculodento-osseous dysplasia
   Osteodysplasia of Melnick and Needles
   Osteopathia striata
   Osteopetrosis
   Osteopoikilosis
   Progressive diaphyseal dysplasia (Engelmann’s disease)
   Pycnodysostosis
METABOLIC CONDITIONS

   Carbonic anhydrase II deficiency
   Fluorosis
   Heavy metal poisoning
   Hepatitis C–associated osteosclerosis
   Hypervitaminosis A, D
   Hyperparathyroidism, hypoparathyroidism, and pseudohypoparathyroidism
   Hypophosphatemic rickets or osteomalacia
   Milk-alkali syndrome
   Renal osteodystrophy
OTHER DISORDERS

   Axial osteomalacia
   Fibrogenesis imperfecta ossium
   High bone mass (with or without torus palatinus): LRP5 activation
   Ionizing radiation
   Lymphoma
   Mastocytosis
   Multiple myeloma
   Myelofibrosis
   Osteomyelitis
   Osteonecrosis
   Paget’s bone disease
   Sarcoidosis
   Skeletal metastases
   Tuberous sclerosis

From Whyte MP: Skeletal disorders characterized by osteosclerosis or hyper-ostosis. In Avioli LV, Krane SM (eds): Metabolic Bone Disease, 3rd ed. San Diego, Academic Press, 1998.

   Osteosclerosis

Neoplastic, hematologic, and metabolic disorders may preferentially cause sclerosis in trabecular bone because it houses marrow and remodels more rapidly than cortical bone.

   Fibrogenesis Imperfecta Ossium

Definition

This rare, sporadic condition features generalized osteopenia, but coarsening of remaining trabeculae places it among disorders of increased bone mass.

Pathobiology

The cause is unknown. Subperiosteal bone formation and collagen synthesis in nonosseous tissues seem to be normal.

Clinical Manifestations

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

Diagnosis

On radiographic study, only the skull is spared. Initially, osteopenia and a slightly abnormal appearance of trabecular bone are noted. Subsequently, the changes suggest osteomalacia. 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.

The skeletal lesion is a localized form of osteomalacia that varies considerably in severity from area to area. In diseased regions, polarized light microscopy shows collagen fibrils that lack birefringence, and electron microscopy reveals that they are thin and randomly organized.

   Hyperostosis

   Progressive Diaphyseal Dysplasia (Camurati-Engelmann Disease)

Pathobiology

Progressive diaphyseal dysplasia (Camurati-Engelmann disease) affects all races and is inherited as an autosomal dominant trait with variable penetrance. New bone formation gradually envelops both the periosteal and endosteal surfaces of long bone diaphyses. In patients with severe disease, osteosclerosis also occurs in the axial skeleton.

Mutations compromise the gene that encodes transforming growth factor-β. Osteoblast differentiation may also be deranged.

Clinical Manifestations

During childhood, limping or a broad-based and waddling gait is noted. Muscular dystrophy can be diagnosed erroneously. Severely affected individuals may have a characteristic body habitus featuring an enlarged head with prominent forehead, proptosis, and thin limbs with little subcutaneous fat or muscle mass and tender thickened bones. Cranial nerve palsies and raised intracranial pressure can occur. Some patients have hepatosplenomegaly, Raynaud’s phenomenon, and additional findings suggestive of vasculitis. 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. Femora and tibiae are most commonly affected. Metaphyses may eventually become involved. The age of onset, rate of progression, and severity are variable. Clinical, radiographic, and bone scan findings are generally concordant. Routine biochemical parameters of bone and mineral metabolism are typically normal, although serum alkaline phosphatase activity, urinary hydroxyproline levels, and the erythrocyte sedimentation rate can 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

Glucocorticoid therapy (typically a low dose of prednisone on alternate days) can relieve bone pain and may normalize skeletal histology. Bisphosphonates have sometimes been useful.

   Endosteal Hyperostosis

Pathobiology

Sclerosteosis and van Buchem’s disease, autosomal recessive disorders, are the principal types of endosteal hyperostosis. Sclerosteosis and van Buchem’s disease both map to chromosome 17q12-q21. Sclerosteosis is caused by mutations in a gene called SOST. Van Buchem’s disease involves a downstream deletion. Enhanced osteoblast activity with failure of osteoclasts to compensate for the increased bone formation seems to explain the skeletal changes.

Clinical Manifestations

Sclerosteosis (cortical hyperostosis with syndactyly) occurs primarily in Afrikaners of South Africa. Elsewhere, Dutch ancestry is also common. Gender distribution appears equal. Patients are tall and heavy beginning in childhood, have a prominent and square mandible, and have deafness and facial nerve palsy from cranial nerve entrapment. Raised intracranial pressure and headache may reflect a small cranial cavity that can shorten life expectancy. Van Buchem’s disease causes progressive asymmetrical enlargement of the jaw during puberty, but prognathism is not a feature. 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 not fragile.

Diagnosis

In sclerosteosis, the skeleton is radiographically normal in early childhood, except when bony syndactyly is present. Syndactyly is common, most often involving the index and third fingers. Progressive bony thickening widens the skull and causes prognathism. Long bones have thickened cortices. The pelvis, vertebral pedicles, ribs, and other tubular bones may become dense. Computed tomography has shown fusion of ossicles and narrowing of the internal auditory canals and cochlear aqueducts. In van Buchem’s disease, endosteal thickening homogeneously widens diaphyseal cortices and narrows medullary canals. Bones are properly modeled. Osteosclerosis involves the skull base, facial bones, vertebrae, pelvis, and ribs. Serum alkaline phosphatase activity can be increased from enhanced skeletal formation.

Treatment

Surgical decompression of narrowed foramina may alleviate cranial nerve palsies.

   Pachydermoperiostosis

Pathobiology

Pachydermoperiostosis (hypertrophic osteoarthropathy, primary or idiopathic) is an autosomal dominant disorder that features clubbing of the digits, hyperhidrosis with thickening of the skin (especially of the face), and periosteal new bone formation prominently in the distal ends of the limbs. Autosomal recessive inheritance also seems to occur. Not all patients manifest all three principal features.

The genetic defect is unknown. A controversial hypothesis suggests that initially some circulating factor acts on the vasculature to cause hyperemia and thereby alters soft tissues, but later blood flow is reduced.

Clinical Manifestations

Men seem to be more severely affected than women and blacks more commonly than whites. Symptoms typically begin during adolescence, intensify during the next decade, but then become quiescent. Arthralgia and fatigue are common. Stiffness and limited mobility occur in both the appendicular and the axial skeleton. Clubbing, with slowly progressive enlargement of the hands and feet, results in a pawlike appearance. Cutaneous changes include thickening, furrowing, pitting, and oiliness, especially of the scalp and face.

Diagnosis

Periostitis thickens the distal portions of the tibia, fibula, radius, and ulna. Clubbing is obvious, and acro-osteolysis can occur. Periosteal proliferation is exuberant, with irregular texture, and it often involves the epiphyses, whereas secondary hypertrophic osteoarthropathy (pulmonary or otherwise) typically causes a smooth and undulating periosteal reaction. Ankylosis of joints, especially in the hands and feet, may trouble older patients. Bone scanning in either condition reveals symmetrical, diffuse, regular uptake along the cortical margins of long bones, especially in the legs—the “double-stripe” sign.

Treatment

Patients with painful synovial effusions may respond to nonsteroidal anti-inflammatory drugs. Contractures or neurovascular compression by osteosclerotic lesions may require surgical intervention.

   OSTEOSCLEROSIS WITH HYPEROSTOSIS

   Osteopetrosis

Pathobiology

Osteopetrosis (marble bone disease) occurs in two major clinical forms: the autosomal recessive or “malignant” type, which kills during infancy or early childhood if it is untreated; and the autosomal dominant or “benign” type, which causes fewer problems. Other autosomal recessive types feature intermediate severity, neuronal storage disease, stillbirth, or renal tubular acidosis with cerebral calcification secondary to carbonic anhydrase II isoenzyme deficiency. Bisphosphonate-induced osteopetrosis has been reported.

Pathogenesis

The defective gene causing autosomal dominant osteopetrosis encodes a chloride channel important for osteoclast activity. Abnormalities in this gene or one that encodes a subunit of a vacuolar proton pump can also result in malignant disease. Carbonic anhydrase II deficiency is caused by deactivating mutations in the gene that encodes this isoenzyme.

Histopathologic studies show that all true forms of osteopetrosis feature profound deficiency of osteoclast action. Primary spongiosa (calcified cartilage deposited during endochondral bone formation) persists away from growth plates and constitutes the pathognomonic finding. Defective endosteal bone resorption impairs the formation of marrow space. Quiescent skeletal remodeling leads to bone fragility from diminished interconnection of osteons and from delayed conversion of immature (woven) bone to mature (compact) bone. Studies of animal models of osteopetrosis suggest that, rarely, some patients have abnormalities as distal as the marrow microenvironment that compromise osteoclast precursor cell growth and differentiation or abnormalities as proximal as bone tissue itself, with resistance to degradation. Neuronal storage disease (ceroid lipofuscin) could reflect a lysosomal defect. Deficient superoxide production (necessary for bone resorption) may also be a pathogenetic factor. Viral-like inclusions in osteoclasts are of uncertain significance.

Clinical Manifestations

Malignant osteopetrosis can first manifest during infancy as nasal “stuffiness” from underdeveloped mastoid and paranasal sinuses. Small cranial foramina may cause optic, oculomotor, or facial nerve palsy. Failure to thrive, delayed dentition, and fracture are common. Hypersplenism and recurrent infection, bruising, and bleeding reflect myelophthisis. Short stature, large head, frontal bossing, nystagmus, hepatosplenomegaly, and genu valgum are characteristic physical features. Untreated children usually die during the first decade of life of hemorrhage, pneumonia, severe anemia, or sepsis. Benign osteopetrosis occasionally causes fracture, facial palsy, deafness, mandibular osteomyelitis, bone marrow failure, impaired vision, psychomotor delay, carpal tunnel syndrome, or osteoarthritis. Carbonic anhydrase II deficiency can result in failure to thrive, fracture, developmental delay, mental subnormality, and short stature. Cerebral calcification develops during childhood, but defective skeletal modeling and osteosclerosis may correct spontaneously. Both proximal renal tubular acidosis and distal renal tubular acidosis have been described.

Diagnosis

A generalized increase in bone density is the radiographic hallmark. In severe disease, modeling defects in long bones produce an “Erlenmeyer flask” deformity ( Fig. 269-1 ). Alternating dense and lucent bands commonly occur in the metaphyses and pelvis. The cranium is usually thickened and dense, especially at the base, and the paranasal and mastoid sinuses are underpneumatized. Vertebrae may show, on lateral view, a “bone-in-bone” (endobone) configuration or end-plate sclerosis causing a “rugger jersey” appearance. Skeletal scintigraphy can disclose fractures and osteomyelitis. Magnetic resonance imaging helps the clinician to monitor the response to bone marrow transplantation because successful engraftment normalizes bone marrow signals.

FIGURE 269-1  Osteopetrosis. An anteroposterior radiograph of the distal end of the femur shows a widened metadiaphyseal region with characteristic alternating dense and lucent bands.  (From Whyte MP, Murphy WA: Osteopetrosis and other sclerosing bone disorders. In Avioli LV, Krane SM [eds]: Metabolic Bone Disease, 2nd ed. Philadelphia, WB Saunders, 1990.)

Serum levels of acid phosphatase and creatine kinase (brain isoenzyme), apparently from osteoclasts, are abnormal. In malignant osteopetrosis, hypocalcemia with secondary hyperparathyroidism and elevated serum concentrations of calcitriol can accompany radiographic changes that resemble rickets. In benign osteopetrosis, biochemical indices of mineral homeostasis are typically unremarkable, although serum parathyroid hormone levels may be increased.

Treatment

Because the origin, pathogenesis, and prognosis of the osteopetroses differ, correct classification is crucial. It may be necessary to evaluate disease progression and to study the family. For the malignant form, human leukocyte antigen (HLA)–identical bone marrow transplantation to supply functional osteoclasts has remarkably benefited some children. Calcium-deficient diets have been used but may be limited by hypocalcemia and rickets. Massive oral doses of calcitriol (1,25-dihydroxyvitamin D3), together with dietary calcium restriction (to prevent hypercalciuria/hypercalcemia) or human interferon-γ, which enhances superoxide production, have successfully stimulated osteoclast activity. Prednisone, alone or with a low-calcium, high-phosphate diet, may also be effective. Glucocorticoid therapy stabilizes pancytopenia and hepatosplenomegaly. Hyperbaric oxygenation helps in the treatment of osteomyelitis. Surgical decompression of optic and facial nerves can be beneficial. Early prenatal diagnosis, radiographically or by ultrasound, has not been successful. Mutation analysis is now useful in many affected families.

   Pycnodysostosis

Epidemiology

Pycnodysostosis is believed to have troubled the French impressionist painter Henri de Toulouse-Lautrec (1864-1901). Most descriptions have come from Europe and the United States, but the disorder seems to be especially common in Japan.

Pathobiology

This autosomal recessive condition is caused by defects in the gene that encodes cathepsin K. Diminished rates of collagen degradation and skeletal turnover are reported. In chondrocytes and osteoblasts, abnormal inclusions have been described.

Clinical Manifestations

Characteristic features seen during infancy or early childhood are disproportionate short stature, a relatively large cranium, fronto-occipital prominence, proptosis, bluish sclerae, a beaked and pointed nose, small facies and chin, an obtuse mandibular angle, a high-arched palate, and dental malocclusion with retention of primary teeth. Cranial sutures remain open. Fingers are short and clubbed from acro-osteolysis or aplasia of the terminal phalanges, and the hands are small and square. Repeated fractures cause knock-knee deformity. Mental retardation is noted in approximately 10% of patients. Adult height ranges from 4 ft 3 in to 4 ft 11 in. Life expectancy can be shortened by recurrent respiratory infections and right-sided heart failure from chronic upper airway obstruction secondary to micrognathia.

Diagnosis

Osteosclerosis is uniform, first becoming apparent in childhood and increasing with age. Skeletal modeling defects do not occur, although long bones appear to have thick cortices because of narrow medullary canals. Clavicles are gracile and hypoplastic at their lateral segments. The calvarium and base of the skull are sclerotic, orbital ridges are dense, and wormian bones are present. Serum calcium and inorganic phosphate levels and alkaline phosphatase activity are typically normal. Anemia is not a problem.

Treatment

No effective medical therapy is documented. Fractures of the long bones usually mend satisfactorily. Internal fixation of long bones is formidable because of their hardness. Tooth extraction is difficult. Osteomyelitis of the mandible may require antibiotic, surgical, and/or hyperbaric therapy.

   Hepatitis C–Associated Osteosclerosis

Rarely, achy and tender limbs develop in individuals who are infected with hepatitis C virus. Radiographic studies reveal a marked generalized increase in bone mass from osteosclerosis and hyperostosis. Disturbances in the insulin-like growth factor system may explain the enhanced bone formation. Calcitonin or bisphosphonate therapy has benefited some patients.

   FOCAL OSTEOSCLEROSIS/HYPEROSTOSIS

   Osteopoikilosis

Osteopoikilosis (“spotted bones”) is a radiologic curiosity inherited as a highly penetrant autosomal dominant trait resulting from a deactivating mutation of the LEMD3 gene. The bony lesions are asymptomatic. However, incorrect diagnosis may lead to confusion with serious conditions, including metastatic disease. Some patients have connective tissue nevi called dermatofibrosis lenticularis disseminata (i.e., Buschke-Ollendorff syndrome). Radiologically, numerous small round or oval foci of bony sclerosis appear in cancellous bone in the tarsal, carpal, pelvic, and metaepiphyseal regions of tubular bones.

   Osteopathia Striata

This autosomal dominant curiosity features linear striations in the metaphyseal regions of long bones and in the ilium. Clinically important syndromes include osteopathia striata with cranial sclerosis or with focal dermal hypoplasia (Goltz’s syndrome). Goltz’s syndrome is an X-linked recessive condition featuring widespread linear areas of dermal hypoplasia and various bony defects in the limbs of affected male patients.

   Melorheostosis

Definition

Melorheostosis causes bony changes likened to wax that has dripped down a candle. No mendelian basis for this disorder has been established. The anatomic distribution suggests a segmentary embryogenic defect.

Clinical Manifestations

Usually, monomelic involvement is noted; bilateral disease is generally asymmetrical. Cutaneous changes over affected bones are common (e.g., linear scleroderma-like areas and hypertrichosis). Soft tissue abnormalities often appear before the hyperostosis. Symptoms typically begin during childhood, with pain and stiffness the major complaints. Joints may become contracted and deformed. Leg length inequality results from soft tissue contractures and premature fusion of epiphyses. Skeletal changes seem to progress most rapidly throughout childhood. During adult life, melorheostosis may or may not gradually spread, although pain is especially common.

Diagnosis

As seen radiographically, irregular, very dense, eccentric periosteal and endosteal hyperostosis affects a single bone or several adjacent bones. The lower limbs are most commonly involved. Endosteal thickening predominates during infancy and childhood, and periosteal new bone formation is prominent during adulthood. Ectopic bone formation may occur, particularly near joints.

Treatment

Surgical correction of contractures is difficult. Recurrent deformity is common.

   Mixed-Sclerosing-Bone Dystrophy

This typically sporadic disorder features combinations of osteopoikilosis, osteopathia striata, melorheostosis, cranial sclerosis, or other skeletal defects in one individual. Patients may experience problems associated with the individual patterns of osteosclerosis or hyperostosis, such as nerve palsy with cranial sclerosis and bone pain with melorheostosis.

   OTHER DISORDERS OF BONE

   Fibrous Dysplasia

This sporadic, developmental disorder features an expansile fibrous lesion within bone. Polyostotic disease is typically seen before the age of 10 years; monostotic disease begins in adolescence or early adult life. McCune-Albright syndrome refers to a condition characterized by polyostotic fibrous dysplasia, café au lait spots ( Fig. 269-2 ), and endocrine hyperfunction.

FIGURE 269-2  McCune-Albright syndrome. Typical rough-border (“coast-of-Maine”) pigmented café au lait spots.  (From Whyte MP: Metabolic and dysplastic disorders. In Coe FL, Favus MJ [eds]: Disorders of Bone and Mineral Metabolism. New York, Raven Press, 1992.)

Pathobiology

Postzygotic mosaicism for an activating mutation in the gene that encodes the α subunit of the receptor subunit/adenylate cyclase–coupling G protein causes fibrous dysplasia and the McCune-Albright syndrome. Imperfect bone forms because mesenchymal cells do not fully differentiate to osteoblasts. Endocrinopathy generally results from end-organ hyperactivity.

Clinical Manifestations

Monostotic fibrous dysplasia is more common than polyostotic disease. The skull and long bones are affected most often. The skeletal lesions can deform bones, cause fractures, and occasionally entrap nerves. Sarcomatous degeneration is rare (incidence, <1%), but it typically occurs within the facial bones or femur and is more frequent when polyostotic disease is present. Pregnancy may reactivate previously quiescent lesions. McCune-Albright syndrome usually causes pseudoprecocious puberty in girls. Less commonly, one sees pseudoprecocious puberty in boys or thyrotoxicosis, Cushing’s disease, acromegaly, hyperprolactinemia, or hyperparathyroidism. In some patients, acquired renal phosphate wasting causes hypophosphatemic rickets or osteomalacia.

Diagnosis

As seen radiographically, in the long bones, lesions are found in either the metaphysis or the diaphysis. They are typically well defined with thin cortices and have a ground-glass appearance ( Fig. 269-3 ). Occasionally, the defects are lobulated, with trabeculated areas of radiolucency.

FIGURE 269-3  Fibrous dysplasia. A characteristic expansile lesion with a ground-glass appearance has caused thinning of the cortex in the mid-diaphysis of the fibula.  (From Whyte MP: Fibrous dysplasia. In Favus MJ [ed]: Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, 3rd ed. Philadelphia, Lippincott-Raven, 1996.)

Treatment

In patients with mild disease, bone lesions may not expand. In severe cases, individual defects can progress and new ones may appear. Spontaneous healing does not occur, but pathologic fractures generally mend well. Stress fractures, however, can be difficult to detect and treat. When the skull is involved, nerve compression may require surgical intervention. In the McCune-Albright syndrome, the aromatase inhibitor testolactone helps to control pseudoprecocious puberty in girls. Intravenous infusions of the bisphosphonate pamidronate have helped some patients.

   Hereditary Multiple Exostoses

This relatively common, highly penetrant, autosomal dominant disorder features irregular bony excrescences that protrude from expanded metaphyses. The gene defect is known in some families. Osteocartilaginous exostoses arise from growth plates and increase in size until linear growth ceases. Lesions may or may not become detached from the parent bone. Their structure is relatively unremarkable, with an outer cortex and an inner spongiosa. Disability results primarily from limb length discrepancies when linear bone growth suffers at the expense of transverse expansion. Compression of nerves, the spinal cord, or the vascular system occurs occasionally. Sarcomatous degeneration (0.5 to 2% of patients) should be suspected when an exostosis enlarges rapidly, especially during adult life.

   Enchondromatosis (Dyschondroplasia, Ollier’s Disease)

This sporadic disorder features cartilaginous masses within the trabecular bone that arise from growth plates. The condition begins in childhood with localized swelling and interferes with linear bone growth. At puberty, expansion of cartilage masses ceases, and these masses can be replaced by mature bone. Enchondromas appear radiographically as lucent defects in flat bones or in metaphyses of tubular bones, often with central calcific stippling. When enchondromatosis occurs with multiple hemangiomas (Maffucci’s syndrome), the enchondromas or hemangiomas undergo malignant transformation in approximately 15% of cases.

   Achondroplasia

Chondrodystrophies are disorders of cartilage growth that result in disproportionate short stature. Achondroplasia is the most common. A defect occurs in the gene that encodes fibroblast growth factor receptor type 3. Approximately 80% of cases are new mutations for this autosomal dominant defect, which increases in frequency with increasing paternal age. Short, tubular bones form because of abnormal endochondral ossification in the limbs. In the chondrocranium, membranous ossification is undisturbed, hence the skull vault is normal. However, the cranial base and foramen magnum are small. Lumbar lordosis is greatly exaggerated, and the spinal canal narrows from the upper to lower segments of the vertebral column. This disturbance is revealed radiographically by decreasing interpediculate distance. The head is large with frontal bossing and midface hypoplasia. The trunk is of relatively normal length, but the limbs show rhizomelic shortening, and the hands have a trident configuration. The long bones appear massive owing to their disproportionately normal width. Surprisingly, growth plates are not grossly disorganized in achondroplasia, and chondrocytes appear normal. Complications can include hydrocephalus or compression of the brain stem, spinal cord, or nerve roots. Minimal impingement by a disk or osteophyte on the small spinal canal can cause neurologic disturbances. Despite its problems, achondroplasia is compatible with good health and a normal life span.

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