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Osteonecrosis has rarely been reported in patients with inflammatory bowel disease, either during or after corticosteroid therapy6,7,8,9. In addition, other treatments for this disease have been implicated in the pathogenesis of osteonecrosis, including parenteral nutrition, especially with lipid emulsions7. In the two patients described in this report, osteonecrosis developed in both hips in the absence of any history of corticosteroid use. Although rare, osteonecrosis appears to be another skeletal complication associated with inflammatory bowel disease rather than a complication of its treatment.
Case Reports
Patient 1
Patient 1 was a 38-year-old man with Crohn's disease who was first seen at University Hospital in August 1991 for fever and recurrent perianal sepsis. In July 1989, an ischiorectal abscess was incised and drained at another hospital; a biopsy of the tissues did not show granuloma or tumor10. At that time, because of a five-year history of diarrhea (up to six to seven bowel movements daily) and an estimated weight loss of 20 kg, further studies were performed. Serum iron, calcium, folic acid, and vitamin B12 concentrations were normal. Fecal cultures (including cultures for yersinia species)11 and studies for parasites were negative. Colonoscopy showed segmental superficial and deep serpentine ulcers, mucosal swelling, erythema, friability, and pseudopolyps in the transverse and descending colon, with a normal ascending colon and rectum. Endoscopic examination of the ileum revealed hyperemia but no ulceration. Multiple ileal and colonic biopsies revealed severe but patchy inflammatory changes with no granulomas. The distribution of the inflammatory process was most consistent with a diagnosis of Crohn's disease of the ileum and colon. Upper gastrointestinal endoscopy and biopsies revealed focal gastritis (without helicobacter species) and nonspecific duodenitis. No granulomas were seen12. Barium radiographs of the upper gastrointestinal tract were normal, but radiographs of the colon showed changes characteristic of Crohn's disease.
The patient also had a four-year history of right hip pain that worsened with walking and was associated with morning stiffness. Slight tenderness of the right hip was noted during his initial evaluation in 1989; his right leg was externally rotated, with a restricted range of motion in both legs, more on the right side. There was no history of trauma or alcohol consumption. Radiographs of both hips in July 1989 revealed changes typical of avascular necrosis in the left hip and gross destruction of the right hip (Figure 1A). In addition, there was radiographic evidence of sacroiliitis and early ankylosing spondylitis.
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Patient 2
Patient 2 was a 23-year-old man with Crohn's disease who was hospitalized in September 1985 because of abdominal pain and diarrhea but no weight loss. He had been hospitalized in 1971 and 1981 for polyarthritis involving his knees, ankles, and wrists. Treatment with aspirin (Entrophen) led to symptomatic improvement both times. In 1981, radiographs of the pelvis, hips, hands, and feet were normal except for poor definition of the sacroiliac-joint margins. A radionuclide bone scan showed increased uptake in both sacroiliac joints. Because of some diarrhea, barium radiographs of the upper and lower gastrointestinal tracts were obtained and showed changes characteristic of Crohn's disease involving the distal ileum and transverse colon. Since 1981, the patient had been treated with 4 g of sulfasalazine daily and supplements of iron and folic acid.
In September 1985, abdominal examination revealed tenderness in the right lower quadrant. An anal fistula was present. Sigmoidoscopy showed multiple discrete aphthous ulcers; a rectal biopsy showed active inflammation but no granulomas. Laboratory studies revealed a hemoglobin level of 10.7 g per deciliter, a white-cell count of 11,600 per cubic millimeter, and an erythrocyte sedimentation rate of 82 mm per hour. Tests for rheumatoid factor and antinuclear antibodies were negative. HLA typing was negative for HLA-B27. Blood and fecal cultures, including cultures for yersinia species, and studies for parasites were negative. Abdominal ultrasonography revealed no abscess. Barium radiographic studies showed changes in the distal ileum and transverse colon similar to those recorded in 1981, as well as narrowing of the distal descending colon. The sacroiliac-joint margins were poorly defined, and there was irregular demineralization of the right and left femoral heads (Figure 2). Some hip pain was present, particularly on the right side. There was no history of corticosteroid use, trauma, or alcohol use. Because of the patient's gastrointestinal symptoms, he was treated with a low-residue diet and 750 mg of metronidazole daily orally.
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Discussion
Osteonecrosis is a disorder of unknown pathogenesis that has been associated with multiple disorders, as well as trauma and chronic alcoholism, and may affect multiple regions of bone1. A relation with corticosteroid therapy was first described more than 30 years ago2,3. Osteonecrosis related to corticosteroid therapy has been described in both renal-transplant recipients and patients with systemic lupus erythematosus1,5. The estimated prevalence of osteonecrosis in these groups of patients ranges from 1 to 20 percent in the former and 5 to 40 percent in the latter. In other conditions treated with corticosteroids, however, the prevalence of osteonecrosis is too low to be associated with confidence with corticosteroids.
There are four reports of patients with inflammatory bowel disease and osteonecrosis6,7,8,9. In 1971, Brom et al.6 described a 27-year-old woman with Crohn's disease, periostitis, arthritis, and aseptic necrosis of both humeral heads. Although the patient had been treated with intravenous and oral corticosteroids, the authors believed that the bone changes were due to Crohn's disease and not to corticosteroid therapy, because of the concomitant periostitis and apparently atypical distribution of the osteonecrosis, which involved the humeral heads and the lower femur, but not the hip joints. Shapiro et al.7 described two girls, 14 and 16 years of age, and one 16-year-old boy with Crohn's ileocolitis and multifocal osteonecrosis. All three patients had received intravenous corticosteroid therapy as well as parenteral nutrition with infused lipids for four to six weeks; once remission was achieved, the corticosteroids were gradually discontinued. Since congenital hyperlipidemia in rabbits13 and hyperlipidemia in humans have been associated with osteonecrosis, the authors hypothesized that the combination of lipid infusion and corticosteroids might be additive in the setting of Crohn's disease, because both these factors could increase serum lipid levels, leading to fat embolism and altered diffusion of oxygen to metabolically active bone tissue14 and ultimately to bone ischemia and necrosis. Vakil and Sparberg8 described 7 patients with osteonecrosis (5 with ulcerative colitis and 2 with Crohn's disease) in a group of 161 patients with inflammatory bowel disease treated with corticosteroids. Osteonecrosis developed in all seven patients within six months after the initiation of corticosteroid therapy. This result was consistent with the observations of Cruess,4 who reported that corticosteroid-associated osteonecrosis occurred within six to eight months after the initiation of therapy, whereas osteopenic complications occurred two to three years later. In contrast, Culp et al.9 reported the occurrence of lunate and femoral-head osteonecrosis in a 46-year-old man with Crohn's disease two years after a one-month course of prednisone at a daily dose of 7.5 mg. Given the very frequent use of corticosteroids in patients with inflammatory bowel disease, this rarity of published reports describing osteonecrosis in patients with the disorder may reflect only a disincentive to publish reports of corticosteroid-related osteonecrosis. The experience with our two patients indicates, however, that osteonecrosis may occur in patients with inflammatory bowel disease who have not received any corticosteroid therapy.
Source Information
From the Department of Medicine (Gastroenterology), University Hospital and University of British Columbia, Vancouver.
Address reprint requests to Dr. Freeman at ACU F-137, University Hospital (UBC Site), 2211 Wesbrook Mall, Vancouver, BC V6T 1W5, Canada.
References
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Related Letters:
Osteonecrosis of the Femoral Heads in Inflammatory Bowel Disease
Stiles R. G., Carpenter W. A., Tigges S., Goffin E., Devuyst O., Freeman H. J.
Extract |
Full Text
N Engl J Med 1994;
330:791-792, Mar 17, 1994.
Correspondence
This article has been cited by other articles:
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