Hypertrophic Osteoarthropathy on Bone Scintigraphy

DISCUSSION

Hypertrophic osteoarthropathy is a syndrome characterized by abnormal proliferation of the skin and osseous tissue at the distal extremities. Clinical features include digital clubbing, periostosis (excessive bone formation or subperiosteal new bone formation) of tubular bones, and synovial effusions. Periostosis is usually accompanied by pain on palpation of the involved area (1).

On ^99mTc-methylene diphosphonate bone scintigraphy, the differential diagnosis of hypertrophic osteoarthropathy includes normal variants (the lateral cortices of the tibiae often show symmetric linear uptake); shin splints, which can appear similar to hypertrophic osteoarthropathy but are confined to the tibiae; and chronic venous insufficiency, which can cause symmetric periosteal uptake, usually confined to the lower extremities below the knees. Bone scintigraphy typically demonstrates a symmetric linear increase in tracer accumulation along the diaphyseal and metaphyseal surfaces of long bones (the railroad-track pattern). In addition to being used for diagnosis, bone scintigraphy can be used to evaluate the response to therapy, as scintigraphic findings can resolve after treatment of the underlying secondary cause.

The primary form of hypertrophic osteoarthropathy is not associated with any other medical disorders. The secondary form is usually associated with lung cancer, pulmonary infections (abscess, tuberculosis, fungal infection, and pneumocystis pneumonia), chronic obstructive pulmonary disease, cystic fibrosis, and right-to-left cardiac shunts and may be seen less often in other conditions (e.g., Hodgkin lymphoma, sarcoidosis, and cirrhosis). Among patients with lung cancer, hypertrophic osteoarthropathy is associated most frequently with adenocarcinoma and least frequently with small cell carcinoma (1). Rarely, arterial vascular prosthesis infections may be associated with hypertrophic osteoarthropathy (2). Bone scintigraphy is a sensitive way to detect involvement.

The exact mechanism of hypertrophic osteoarthropathy is unclear. Currently there are 2 known pathways: neurogenic and humoral. In the neurogenic pathway, diseased organs innervated by the vagus nerve may induce a neural reflex leading to vasodilatation and increased blood flow to the extremities (3). The humoral pathway involves localized activation of the platelet–endothelial cells, with the subsequent release of fibroblast growth factors (e.g., platelet-derived growth factor) (4). The frequent association with lung disease raises the possibility that circulatory bypass of the lung may play an important role. Another hypothesis involves tumor production and release into the circulation of a factor (one possible candidate is vascular endothelial growth factor) that promotes features of hypertrophic osteoarthropathy such as vascular proliferation, edema formation, and new bone formation (4).

Treatment with nonsteroidal antiinflammatory or other analgesic medications may significantly relieve symptoms. Removal of lung cancer or treatment of the other causes of hypertrophic osteoarthropathy may cause the clinical manifestations to regress in many patients but is not always effective. In patients with refractory disease, bisphosphonates, including pamidronate (5) and zoledronic acid, have been found to be highly effective.