Correspondence

Osteonecrosis of the Femoral Heads in Inflammatory Bowel Disease

N Engl J Med 1994; 330:791-792March 17, 1994

Article

To the Editor:

The Brief Report by Freeman and Kwan (Oct. 28 issue)1 describes presumed osteonecrosis in two patients with inflammatory bowel disease who had not received glucocorticoid therapy. We believe that the radiographic diagnosis is in error. In both patients, the radiographs show uniform diffuse narrowing of the joint space in both hips, with maintenance of the normal contour of the femoral heads in the early radiographs. This pattern is consistent with an inflammatory arthropathy and is not consistent with osteonecrosis as the primary disease. Osteonecrosis is a primary bone problem (infarction) that results in radiographic sclerosis and lucency and then in collapse of the femoral head, causing the loss of its normal contour. The collapse may be followed by secondary osteoarthritis with narrowing of the joint space. The radiographs in both patients clearly show loss of joint space but an intact, normally contoured femoral head.

The central question is whether the disease process in these patients' hips was a primary joint problem (arthropathy) or a primary bone infarction (primary osteonecrosis). We think the term “osteonecrosis” should be reserved for cases of primary bone infarction. This should be distinguished from a primary joint process that leads to cartilage loss first and thus to early narrowing of the joint space. The joint process may cause secondary osteonecrosis in the underlying subchondral bone.

Freeman and Kwan1 report that both patients had sacroiliitis and radiographic changes characteristic of ankylosing spondylitis. This combination has a well-known association with inflammatory bowel disease2 and is also termed “enteropathic spondyloarthropathy.” The radiographic features are identical to those of ankylosing spondylitis.

In summary, we believe that the patients in this report had inflammatory arthropathy associated with inflammatory bowel disease (enteropathic spondyloarthropathy) and that the osteonecrosis seen pathologically was a secondary phenomenon caused by the primary hip arthropathy.

Richard G. Stiles, M.D.
Walter A. Carpenter, Ph.D., M.D.
Stefan Tigges, M.D.
Emory Clinic, Atlanta, GA 30322

2 References

1
Freeman HJ, Kwan WCP. Non-corticosteroid-associated osteonecrosis of the femoral heads in two patients with inflammatory bowel disease. N Engl J Med 1993;329:1314-1316
Full Text | Web of Science | Medline

2
Enteropathic arthropathies. In: Resnick D, Niwayama G, eds. Diagnosis of bone and joint disorders. 2nd ed. Vol. 2. Philadelphia: W.B. Saunders, 1988:1218-51.

To the Editor:

Freeman and Kwan describe two patients with inflammatory bowel disease (Crohn's disease) who had prolonged hip pain and eventual osteonecrosis of the femoral heads that was unexplained. We believe that two conditions associated with this disease -- hypercoagulability and malabsorption-related osteopenia -- might have contributed to the osteonecrosis.

Fibrin microclots have been detected in the circulation of patients with Crohn's disease. Such clots may lead to osteonecrosis by progressively occluding epiphyseal capillaries,1 since the blood supply to the femoral heads is known to be precariously collateralized2. Did the authors consider the possibility of an associated coagulopathy in Patient 1, who had thrombocytosis and recurrent sepsis? The existence of procoagulant activity has been demonstrated in patients with Crohn's disease, including hyperviscosity, increased generation of thromboplastin, hyperfibrinogenemia, and thrombocytosis,3 and hypercoagulability can also occur during sepsis1. Hypercoagulability in Crohn's disease may also result from malabsorption-induced depletion of vitamin K and an attendant deficiency in protein C and protein S3.

Bone demineralization has been reported to predispose patients with Crohn's disease and malabsorption to fatigue fractures4. Such demineralization was noted in Patient 2 four years after the initial evaluation for Crohn's disease. We wonder whether this patient had calcium or vitamin D deficiency with secondary hyperparathyroidism or hypogonadism, each a possible factor in osteopenia, independent of glucocorticoid therapy5.

The interesting observations of Freeman and Kwan could thus be accounted for by two disorders known to be associated with Crohn's disease.

Eric Goffin, M.D.
Olivier Devuyst, M.D.
St. Luc Academic Hospital, B-1200 Brussels, Belgium

5 References

1
Jones JP Jr. Fat embolism, intravascular coagulation, and osteonecrosis. Clin Orthop 1993;292:294-308
Web of Science | Medline

2
Mankin HJ. Nontraumatic necrosis of bone (osteonecrosis). N Engl J Med 1992;326:1473-1479
Full Text | Web of Science | Medline

3
Talbot RW, Heppell J, Dozois RR, Beart RW Jr. Vascular complications of inflammatory bowel disease. Mayo Clin Proc 1986;61:140-145
Web of Science | Medline

4
Gravallese EM, Kantrowitz FG. Arthritic manifestations of inflammatory bowel disease. Am J Gastroenterol 1988;83:703-709
Web of Science | Medline

5
Ryde SJ, Clements D, Evans WD, et al. Total body calcium in patients with inflammatory bowel disease: a longitudinal study. Clin Sci 1991;80:319-324
Web of Science | Medline

Author/Editor Response

Dr. Freeman replies:

To the Editor: The comments of both groups emphasize the potential difficulties in interpreting the earliest radiographic changes and making an initial diagnosis in patients with inflammatory bowel disease and osteonecrosis as well as the need to explore further the pathogenesis of osteonecrosis in these patients. As described in our report and in the earlier report by Brom et al.,1 an enteropathic spondyloarthropathy may be an important factor predisposing patients to osteonecrosis. Newer imaging methods, such as magnetic resonance imaging, may permit the identification of the earliest radiologic changes of osteonecrosis and precisely clarify the sequence of changes in patients with inflammatory bowel disease. Clearly, additional studies are needed to elucidate the effects of this inflammatory disease process, including studies focused on alterations in immunologic mediators and their effects on bone and cartilage, changes in the coagulation cascade that might cause vascular occlusion and bone infarction, as well as alterations in calcium and mineral metabolism that might further increase the risk of bone fracture.

Hugh J. Freeman, M.D.
University of British Columbia, Vancouver, BC V6T 1Z3, Canada

1 References

1
Brom B, Bank S, Marks IN, Cobb JJ. Periostitis, aseptic necrosis, and arthritis occurring in a patient with Crohn's disease. Gastroenterology 1971;60:1106-1109
Web of Science | Medline

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