The Journal of Bone and Joint Surgery (American). 2008;90:366-374.
doi:10.2106/JBJS.G.00774
© 2008 The Journal of Bone and Joint Surgery, Inc.
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Proximal Tibial Osteochondromas in Patients with Fibrodysplasia Ossificans Progressiva

Gregory K. Deirmengian, MD1, Nader M. Hebela, MD1, Michael O'Connell, PhD2, David L. Glaser, MD1, Eileen M. Shore, PhD3 and Frederick S. Kaplan, MD1

1 Department of Orthopaedic Surgery, The University of Pennsylvania School of Medicine, Silverstein-2, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104. E-mail address for F.S. Kaplan: frederick.kaplan{at}uphs.upenn.edu
2 Laboratory of Immunology, National Institutes of Health, 5600 Nathan Shock Drive, Room 4B16, Baltimore, MD 21224
3 Department of Orthopaedic Surgery, The University of Pennsylvania School of Medicine, 424 Stemmler Hall, 36th and Hamilton Walk, Philadelphia, PA 19104
Investigation performed at The Center for Research in Fibrodysplasia Ossificans Progressiva and Related Disorders, and the Departments of Orthopaedic Surgery, Genetics, and Medicine, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants in excess of $10,000 from the International Fibrodysplasia Ossificans Progressiva Association, the Ian Cali Endowment, the Whitney Weldon Endowment, the Isaac & Rose Nassau Professorship of Orthopaedic Molecular Medicine, and the National Institutes of Health (R01-AR41916). 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.

Background: Fibrodysplasia ossificans progressiva is a rare autosomal dominant disorder characterized by congenital malformation of the great toes and by progressive heterotopic ossification of skeletal muscle and soft connective tissues. The disorder is caused by a recurrent missense mutation in the glycine-serine activation domain of activin A receptor type I, a bone morphogenetic protein (BMP) type-I receptor, in all classically affected individuals. Osteochondromas of the proximal part of the tibia are benign osteochondral neoplasms or orthotopic lesions of skeletal remodeling associated with dysregulated BMP signaling and have been considered an atypical feature of fibrodysplasia ossificans progressiva, but they may be underdiagnosed because of their often asymptomatic nature. The purpose of the present study was to determine the prevalence and characteristics of proximal tibial osteochondromas in individuals who have fibrodysplasia ossificans progressiva.

Methods: Over a period of thirty months, we evaluated all patients with new and established fibrodysplasia ossificans progressiva for the presence of proximal tibial osteochondromas on the basis of medical history, physical examination, and radiographic studies. We quantified the prevalence of osteochondromas and characterized the types of osteochondromas to identify relevant trends.

Results: Ninety-six patients (including fifty-two female patients and forty-four male patients) with fibrodysplasia ossificans progressiva were evaluated on the basis of a history and physical examination. Plain radiographs were available for sixty-seven patients. Ninety percent of all patients had osteochondroma of the proximal part of the tibia. These lesions usually were asymptomatic, most commonly were bilateral, and typically were located at the pes anserinus. Seventy-five percent of the lesions were pedunculated, and 25% were sessile.

Conclusions: Proximal tibial osteochondromas are a common phenotypic feature of fibrodysplasia ossificans progressiva, a finding that expands the recognized consequences of recurrent activating mutations in activin A receptor type I to include not only congenital skeletal malformations and heterotopic skeletogenesis but also benign osteochondral neoplasms or orthotopic lesions of skeletal modeling. The present study provides insight into the genetic basis of osteochondroma formation in patients with fibrodysplasia ossificans progressiva and possibly into that of more common conditions in which these lesions occur.


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Proximal tibial exostosis and fibrodysplasia ossificans progressiva
Shigeru Ehara, M.D.
JBJS Online, 13 Mar 2008 [Full text]