Image Quiz

A Fifty-three-Year-Old Woman with Osteoarthritis of the Knees (continued)

Answer: Benign autosomal-dominant osteopetrosis (adult osteopetrosis).


Fig. 1-A
Fig. 1-B		 Figs. 1-A and 1-B Anteroposterior (Fig. 1-A) and lateral (Fig. 1-B) radiographs of the right knee, showing a subtle but diffuse increase in bone density, cortical thickening, and patchy areas of sclerosis within the medullary cavity of the distal part of the femur and proximal part of the tibia. The medial compartment of the knee joint demonstrates narrowing, and there are medial peripheral osteophytes on the distal part of the femur and proximal part of the tibia. There is also loss of articular cartilage at the patellofemoral articulation. No soft-tissue calcification is detected.

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Fig. 2		 Fig. 2 Lateral radiograph of the chest, demonstrating sharply defined thick bands of sclerosis of the vertebral end plates and sclerotic islands in multiple vertebral bodies (bone-within-bone appearance).

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Fig. 3		 Fig. 3 Axial fat-suppressed T2-weighted magnetic resonance image of the right tibia, revealing circumferential thickening of low-signal cortical bones and low-signal foci in the central portion of the medullary cavity (asterisk), which appear darker than adjacent bone marrow (arrowhead).

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Discussion

Osteopetrosis is an inherited disorder characterized by defective osteoclast resorption that leads to universally hard but brittle bone1. The disorder has been named Albers-Schönberg disease or the so-called "marble bone disease"2,3. Osteopetrosis markedly compromises the body's ability to acidify the Howship lacuna and to resorb bone and calcified cartilage. This results in generalized osseous sclerosis.

There are three forms of osteopetrosis: malignant autosomal recessive, intermediate autosomal recessive, and benign autosomal dominant. The malignant form typically presents within the first year of life. Osseous overgrowth of the marrow spaces results in decreased hematopoiesis, leading to myelophthisic anemia and subsequent hepatosplenomegaly4. Most patients do not survive past their first decade5. The intermediate form of osteopetrosis shares many features of the malignant counterpart; however, it is less severe and has a delayed onset. Most patients survive into adulthood. Fractures are common in the first decade. Patients may have hematologic abnormalities as well as symptoms from a compression of cranial nerves. The benign autosomal dominant form, adult osteopetrosis, is the most common type of osteopetrosis. It usually presents with pathologic fractures that may occur at any age. Although most patients are diagnosed after their first fracture, 40% of them are asymptomatic6.

Osteopetrosis can be suspected in a patient with a history of multiple fractures. Fractures typically occur in the appendicular skeleton, most commonly in the proximal part of the femur as well as in the femoral shaft and upper extremities. These fractures may result from minimal trauma due to the pathologic nature of the bone. Because the abnormally osteopetrotic bone is most easily subjected to tensile stress, most fractures occur at right angles to the cortex. Although the adult form of osteopetrosis is an autosomal dominant disorder, in some kindred, generations are skipped. Thus, the patient may be the only affected individual in the family.

The diagnosis of osteopetrosis can be confirmed by radiographic imaging. The degree of radiographic expression is quite variable and ranges from asymptomatic incidentally discovered adult dense skeletons to the morbidly abnormal skeleton in the fulminant infantile form of the disease. The radiographic findings of adult osteopetrosis include generalized sclerosis, sclerotic foci within the bones, and vertebral end-plate thickening6 (Fig. 2). Thickening of cortical and cancellous bones accounts for characteristic opacity in the radiographs of patients with osteopetrosis. Sclerotic foci within the bones (endobone or bone-within-bone) are a result of failed resorption of primary spongiosa7 (Fig. 3). The histologic features of osteopetrotic bone reveal no abnormal appearance on examination under light microscopy; however, electron microscopy demonstrates missed ruffled borders, indicating dysfunctional osteoclasts8,9. Densitometry values of the vertebral bodies are four to five times greater in osteopetrotic patients than they are in normal control subjects10.

The knee radiographs of our patient demonstrated subtle but abnormal generalized sclerosis of the bone. There was no soft-tissue calcification, and the involved long bones were not enlarged or deformed. These findings are consistent with a diagnosis of metabolic bone disease, sclerotic bone dysplasia, or neoplasm11. A differential diagnosis is shown in Table I.

TABLE I Differential Diagnosis of Sclerotic Bone11

Bone tumor

  • Metastatic tumor
  • Hodgkin disease
  • Leukemia or lymphoma
  • Myelofibrosis

Metabolic bone disease

  • Paget disease
  • Renal osteodystrophy
  • Parathyroid-related diseases
  • Hypervitaminosis (A and D)
  • Hormone-related bone diseases (e.g., cretinism, pheochromocytoma)

Sclerosing bone dysplasia

  • Osteopetrosis
  • Osteopoikilosis
  • Osteopathic striata
  • Melorheostosis
  • Hypertrophic pulmonary osteoarthropathy

A review of the chest radiograph (Fig. 2) showed bands of sclerosis involving the vertebral end plates. A magnetic resonance image (Fig. 3) confirmed abnormal diffuse circumferential cortical thickening of the femur and tibia with endobones in the medullary cavity. Neither the history nor the physical examination of our patient suggested renal insufficiency, parathyroid disease, or underlying neoplasm. Although there are only a limited number of reported cases of patients with osteopetrosis who have undergone total joint arthroplasty, previous studies demonstrated that adult patients with osteopetrosis and coexisting osteoarthritis of the hip or knee can be managed successfully with total joint arthroplasty12-17. The follow-up time in these studies, however, is relatively short (range, six months to six years).

Because of the presence of extremely hard but brittle bones, orthopaedic surgical procedures are difficult and may pose additional risks of complications. Therefore, preoperative detection of the underlying disorder is important. Orthopaedic surgeons should be alert for the possibility of adult osteopetrosis when abnormally dense and sclerotic bone is detected on preoperative radiographs. Further investigations, including blood chemistry tests (serum levels of calcium, phosphate, and parathyroid hormone; and renal function tests) and radiographic imaging at other sites, such as the chest or skull, should be performed in order to exclude other potential disorders and to confirm the diagnosis.

*The authors did not receive any outside funding or grants in support of their research for or preparation of this work. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.

References

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