A 49-Year-Old Man With Pain at the Site of a Previous Fracture

Maria Romanova, MD


January 14, 2016


Osteopetrosis (marble bone disease) is a rare hereditary disorder of diminished osteoclast function characterized by deficient bone resorption.[1] In this patient, the plain radiograph of the right femur shows a marked, diffuse increase in the density of the osseous structures, and evidence of refracture is noted through the proximal mid-diaphyseal/subtrochanteric region (Figure 1). A similar pattern, with increased bone density (which gives the bones a very bright appearance), is noted on the radiograph of the pelvis (Figure 2).

Figure 1.

Figure 2.

Figure 3.

A review of past radiographs of the cervical spine (Figure 3) reveals diffusely increased density of all osseous structures, with a "sandwich" appearance (presence of an extreme and uniform increase in radiographic density at the superior and inferior margins) of the upper vertebrae (ie, C2-C4), and a healed posterior spinous process fracture of the sixth and seventh cervical vertebra.

As a consequence of deficient bone resorption resulting from diminished osteoclast function, bone modeling and remodeling are impaired in osteopetrosis. Defective bone turnover results in skeletal fragility, despite the increase in bone mass. The condition is a heterogeneous disorder encompassing different molecular lesions (more than 14, some with human homologues, have been identified in the murine model) and a wide range of clinical features in its phenotypic manifestation in affected individuals.[1]

In humans, three distinct forms of the disease account for most cases of osteopetrosis; these forms, based on age and clinical features, are adult-onset, infantile, and intermediate. The adult-onset form (benign osteopetrosis, also called "Albers-Schönberg disease") is inherited in an autosomal dominant pattern and is often recognized only incidentally. In most cases, it is due to an autosomal dominant single gene mutation of the chloride channel 7 (CLC7) gene, which is involved in a regulatory pathway for bone remodeling. Homozygous mutations of this gene are one cause of the severe infantile form of the disease. Typically, no evidence of bone marrow failure is found.

Approximately 50% of patients with infantile osteopetrosis are asymptomatic. The diagnosis is often made incidentally (usually in late adolescence) because radiologic abnormalities start appearing in childhood in the setting of fractures sustained by the individual, or it is made as a result of the development of osteomyelitis, especially of the mandible. In other patients, the diagnosis may be made earlier in life, on the basis of the family history.

The term "benign" is a misnomer. Bony defects are common and include neuropathies caused by cranial nerve entrapment, with specific problems, including deafness and facial palsy. Carpal tunnel syndrome and osteoarthritis also occur. The bones are fragile and may fracture easily;[2] approximately 40% of patients have recurrent fractures. Bone marrow function is not compromised.[1]

Other manifestations include vision impairment caused by retinal degeneration and psychomotor retardation. In benign osteopetrosis, laboratory data may reveal elevated alkaline phosphatase levels, as well as elevated levels of acid phosphatase and creatinine kinase caused by increased release from defective osteoclasts.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: