Clin J Gastroenterol (2008) 1:93–96 DOI 10.1007/s12328-008-0015-2
CASE REPORT
Osteonecrosis of the lateral femoral condyle in a patient with ulcerative colitis: report of a case Hiroaki Takeda Æ Shoichi Nishise Æ Shoichiro Fujishima Æ Tadahisa Fukui Æ Sayaka Otake Æ Tomohiko Orii Æ Takeshi Sato Æ Yu Sasaki Æ Sumio Kawata
Received: 25 January 2008 / Accepted: 24 April 2008 / Published online: 12 July 2008 Ó Springer 2008
Abstract Osteonecrosis is a major complication in patients with ulcerative colitis (UC). It appears most commonly in the femoral head, but sometimes occurs in the proximal humerus or femoral condyle. A 27-year-old Japanese woman presented with severe pain in the left knee in 2006. Osteonecrosis was found in the left lateral femoral condyle, and osteochondral autografting was performed. Ten and a half years prior to this episode, at the age of 17 years, she had been diagnosed as having UC, and after 18 months of medication, she had undergone total colectomy. A total prednisolone dose of 3020 mg had been administered before the operation, but the true pathogenesis—i.e. idiopathic or steroid-associated osteonecrosis— had not been determined at that time. The osteonecrosis occurred long after prednisolone therapy had been discontinued, and the total dose of prednisolone was not considered to be unusually high. In this case, osteochondral autografting was ultimately required for treatment of the osteonecrosis. However, conservative therapy is indicated for early-stage cases and should result in a good course. We report this case to draw attention to this relatively rare complication of UC and to facilitate early detection of similar lesions. Keywords Inflammatory bowel disease Osteochondral autografting Prednisolone Uveitis H. Takeda (&) Division of Endoscopy, Yamagata University Hospital, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan e-mail: [email protected] S. Nishise S. Fujishima T. Fukui S. Otake T. Orii T. Sato Y. Sasaki S. Kawata Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, Japan
Introduction Osteonecrosis is a major complication of ulcerative colitis (UC) and mostly associated with steroid therapy [1–3]. However, osteonecrosis can also have many other causes, such as trauma, alcohol intake, and collagen disease [4], which may lead to ischemic change of the arterioles, resulting in avascular osteonecrosis [2, 4]. Osteonecrosis in patients with UC appears most commonly in the femoral head and is usually bilateral, although it occasionally occurs at other bone sites, such as the proximal humerus or femoral condyle [5, 6]. We have handled a case of osteonecrosis of the lateral femoral condyle in a patient with UC. We report this relatively rare complication with the aim of alerting clinicians to its possible presence and thus expedite early detection.
Case report A 17-year-old Japanese female had visited a local hospital in 1996 because of bloody diarrhea, and UC had been diagnosed based on the results from a endoscopic examination. The symptoms had improved following the administration of oral prednisolone 30 mg/day; this drug therapy was then tapered and discontinued within 2 months of initiation. In October 1997, bloody diarrhea and abdominal pain recurred, and the patient was referred to our hospital where she was admitted and treated with intravenous prednisolone (80 mg/day) while receiving total parenteral nutrition. Her disease activity did not improve, and she developed hyperglycemia and glaucoma as side effects of the steroid treatment. A barium enema test revealed severe colitis in the entire colon, sigmoidscopy showed multiple deep ulcerations. A total colectomy was
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therefore performed. Following the surgery, the prednisolone was tapered off, and the patient returned to general good health. At this point, the cumulative lifetime prednisolone dose was calculated to be 3020 mg. In 2002, 7 years after the operation, visual disturbance occurred in her right eye. Uveitis was diagnosed and controlled by eye drops containing steroid hormone. The results of blood chemistry tests were almost normal, and the test for the presence of anti-nuclear antibody was negative. Up to 2005, the ocular symptoms were absent, and no further local steroid therapy was needed. In February 2006, the patient developed severe pain in the left knee. Plain radiography revealed a lucent focus in the left lateral femoral condyle, and stage 3 osteonecrosis was diagnosed on the basis of the Association of Research Circulation Osseous (ARCO) international classification of osteonecrosis [7] (Fig. 1). Magnetic resonance imaging (MRI) showed a distinct necrotic lesion and surrounding reactive tissue (Fig. 2). Because of pain and gait disturbance, the patient underwent osteochondral autografting to treat the lesion in June 2006, when she was 27 years old. When this report was written, the patient had undergone rehabilitation and remains in good condition.
Discussion Ischemic change of the arterioles due to various causes results in avascular osteonecrosis, but the mechanisms of osteonecrosis in patients with inflammatory bowel disease have not been clearly elucidated. Klingenstein et al. [2] Fig. 1 Plain radiograph of the left knee. A radiolucent focus is evident in the left lateral femoral condyle. The findings indicate stage 3 according to the Association Research Circulation Osseous international classification of osteonecrosis [7] and stage 3 according to the staging system for idiopathic osteonecrosis of the knee reported by Aglietti et al. [12]. a Frontal view, b lateral view
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reported that osteonecrosis in active inflammatory bowel disease could be related to disseminated intravascular coagulation in conjunction with increased intramedullary pressure caused by steroid therapy. Our patient had no episode of trauma to her knee and was not suffering from any evident collagen disease. Furthermore, the osteonecrosis occurred long after prednisolone therapy had been discontinued. However, she had actually received two courses of prednisolone therapy, and the peak dose of prednisolone was relatively high. Therefore, an association with steroid therapy can not be ruled out in this case. Another confounding factor is that the true pathogenesis— i.e., idiopathic or steroid-associated osteonecrosis—had not been determined. With regard to the incidence of osteonecrosis in inflammatory bowel disease, Vakil et al. [3] reported a figure of 4.3% (seven of 161 cases, including Crohn’s disease). In a Japanese series, femoral head osteonecrosis was reported in seven (3.6%) of 196 cases of UC [1]. At our institution, we have experienced 266 cases of UC and 68 cases of Crohn’s disease, and to date have encountered only two cases of osteonecrosis among the patients with UC. Both of these patients had a history of steroid therapy: one had bilateral femoral head osteonecrosis, and the other was the patient reported here. Osteonecrosis in patients with inflammatory bowel disease appears most commonly in the femoral head and is usually bilateral. In contrast, little information is available on sites affected by osteonecrosis. Klingenstein et al. [2] reported 23 cases of osteonecrosis associated with inflammatory bowel disease; the sites of osteonecrosis were
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Fig. 2 Magnetic resonance image of the left knee. The osteonecrosis lesion appears as a low-intensity area in both the T1- and T2-weighted images. a, b Frontal sections of the left knee, c, d sagittal sections. a, c T1, b, d T2
usually multiple, such as the hip/knee or hip/shoulder, and 67% involved the hip, 18% the knee, and 15% the shoulder. Clinical examination revealed that only four of the 23 cases involved a single osteonecrosis site, and one of the four was had a single lesion of the knee. As our patient had a single lesion in the femoral condyle, we considered this to be a relatively rare case in light of the reported incidence. Klingenstein et al. [2] suggested that comprehensive testing with MRI is indicated in all cases, even if the symptom is limited to one joint. Therefore, as it is clear that multiple joints are often involved, careful follow-up of our patient will be necessary.
There seems to be no link between the dose of steroid and the risk of osteonecrosis in steroid-related osteonecrosis in patients with inflammatory bowel disease. Vakil et al. [3] reported a mean cumulative lifetime prednisolone dose of 7 g and a mean treatment duration of 42 weeks in seven patients with inflammatory bowel disease treated with steroid. In Japan, Munakata et al. [1] reported a mean cumulative prednisolone dose of 18 g and a mean treatment duration of 64 weeks in seven cases of femoral head osteonecrosis associated with UC. It would therefore appear that most reported patients had received relatively high doses of steroids for relatively long periods. The total
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dose of prednisolone received by our patient was about 3 g, and the treatment duration was 16 weeks. If this case was steroid-related, the amount of steroid was relatively lower and the treatment duration rather shorter than those in cases reported earlier. Vakil et al. [3] discussed the occurrence of osteonecrosis in patients with inflammatory bowel disease and compared this with conditions related to other diseases. The doses and duration of steroid treatment in patients with associated osteonecrosis were considerably lower than in patients with other disease states. As mentioned at the beginning of this discussion, UC tends to form micro-thrombosis easily and may have a background of autoimmunity [2, 3]. The health of our patient was complicated by uveitis as a condition related to autoimmunity. However, no previous report has mentioned a relationship between osteonecrosis and uveitis. As uveitis is a common complication of UC, uveitis and osteonecrosis may have occurred coincidentally in our patient. Conventional X-ray imaging is not very helpful in the early stage of femoral condyle osteonecrosis [8], and the diagnosis of osteonecrosis, including stage determination, is usually based on MRI scans. The clinical course of avascular osteonecrosis varies among patients, and the natural course is not well known [9]. However, if osteonecrosis of the knee can be detected at an early stage, spontaneous regression can sometimes be expected. In some cases, conservative treatments, such as use of an insole, are effective [10]. Even in steroid-related osteonecrosis, Takao et al. [11] reported that regression can occur in some patients with early-stage disease. Therefore, cases that are diagnosed early may have a good prognosis, although surgical treatment may still be required. Unfortunately, our patient was diagnosed as stage 3 based on the ARCO international classification of osteonecrosis [7] or stage 3 based on the criteria reported by Aglietti et al. [12] and ultimately required osteochondral autografting. This case has revealed to us the necessity of making careful efforts to detect osteonecrosis at an early stage. In our patient, pain and osteonecrosis occurred 10.5 years after the onset of UC. Klingenstein et al. [2] reported that osteonecrosis occurred 3–42 years after diagnosis of inflammatory bowel disease. Thus, the period until onset of osteonecrosis varies considerably among patients, making it very difficult to detect the condition promptly at an early stage. For early detection of
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osteonecrosis, careful observation and appropriate use of MRI is recommended. In conclusion, we have reported a case of osteonecrosis in the lateral femoral condyle in a patient with UC. The clinician should be aware of this relatively rare complication and consider it during the differential diagnosis in order to facilitate early detection of the lesions. Acknowledgments We would like to thank Dr. Tamon Asano and Dr. Jun-ichi Hashimoto from the Department of Orthopedics for helpful advice.
References 1. Munakata A, Hatada Y, Yao T. Analysis of adverse effects of steroid therapy to inflammatory bowel disease. In: Annual report of the research committee of inflammatory bowel disease (in Japanese with English abstract). The Ministry of Health and Welfare of Japan. 1995; pp. 67–70. 2. Klingenstein G, Levy RN, Kornbluth A, Shah AK, Present DH. Inflammatory bowel disease-related osteonecrosis: report of a large series with a review of the literature. Aliment Pharmacol Ther. 2005;21:243–9. 3. Vakil N, Sparberg M. Steroid-related osteonecrosis in inflammatory bowel disease. Gastroenterology. 1989;96:62–7. 4. Gorczynski C, Meislin R. Osteonecrosis of the distal femur. Bull Hosp Jt Dis. 2006;63:145–52. 5. Madsen PV, Anderson G. Multifocal osteonecrosis related to steroid treatment in a patient with ulcerative colitis. Gut. 1994;35:132–4. 6. Sasaki T, Yagi T, Monji J, Yasuda K, Masuda T, Fukuzawa M, et al. Steroid-induced osteonecrosis of the femoral condyle—a clinical study of 18 knees in ten patients—(in Japanese with English abstract). Nippon Seikeigeka Gakkai Zasshi (J Jpn Orthop Assoc). 1986;60:361–72. 7. Gardeniers JM. ARCO committee on terminology and staging; Report of the committee-meeting at Santiago de Compostela. ARCO Newsl. 1993;5:79–82. 8. Ito K, Inuo-Nakayama M, Matsumoto M, Kubokawa M, Sadamoto Y, Kubo H, et al. Steroid-induced osteonecrosis in refractory ulcerative colitis. Fukuoka Igaku Zasshi. 2005;96:5– 10. 9. Lafforgue P. Pathophysiology and natural history of avascular necrosis of bone. Joint Bone Spine. 2006;73:500–7. 10. Patel DV, Breazeale NM, Behr CT, Warren RF, Wickiewicz TL, O’Brien SJ. Osteonecrosis: current clinical concepts. Knee Surg Sports Traumatol Anthrosc. 1998;6:2–11. 11. Takao M, Sugano N, Nishii T, Miki H, Yoshikawa H. Spontaneous regression of steroid-related osteonecrosis of the knees. Clin Orthop Relat Res. 2006;452:210–5. 12. Aglietti P, Insall JN, Buzzi R, Deshamps G. Idiopathic osteonecrosis of the knee: aetiology, prognosis and treatment. J Bone Joint Surg. 1983;65:588–97.
CASE REPORT
Osteonecrosis of the lateral femoral condyle in a patient with ulcerative colitis: report of a case Hiroaki Takeda Æ Shoichi Nishise Æ Shoichiro Fujishima Æ Tadahisa Fukui Æ Sayaka Otake Æ Tomohiko Orii Æ Takeshi Sato Æ Yu Sasaki Æ Sumio Kawata
Received: 25 January 2008 / Accepted: 24 April 2008 / Published online: 12 July 2008 Ó Springer 2008
Abstract Osteonecrosis is a major complication in patients with ulcerative colitis (UC). It appears most commonly in the femoral head, but sometimes occurs in the proximal humerus or femoral condyle. A 27-year-old Japanese woman presented with severe pain in the left knee in 2006. Osteonecrosis was found in the left lateral femoral condyle, and osteochondral autografting was performed. Ten and a half years prior to this episode, at the age of 17 years, she had been diagnosed as having UC, and after 18 months of medication, she had undergone total colectomy. A total prednisolone dose of 3020 mg had been administered before the operation, but the true pathogenesis—i.e. idiopathic or steroid-associated osteonecrosis— had not been determined at that time. The osteonecrosis occurred long after prednisolone therapy had been discontinued, and the total dose of prednisolone was not considered to be unusually high. In this case, osteochondral autografting was ultimately required for treatment of the osteonecrosis. However, conservative therapy is indicated for early-stage cases and should result in a good course. We report this case to draw attention to this relatively rare complication of UC and to facilitate early detection of similar lesions. Keywords Inflammatory bowel disease Osteochondral autografting Prednisolone Uveitis H. Takeda (&) Division of Endoscopy, Yamagata University Hospital, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan e-mail: [email protected] S. Nishise S. Fujishima T. Fukui S. Otake T. Orii T. Sato Y. Sasaki S. Kawata Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, Japan
Introduction Osteonecrosis is a major complication of ulcerative colitis (UC) and mostly associated with steroid therapy [1–3]. However, osteonecrosis can also have many other causes, such as trauma, alcohol intake, and collagen disease [4], which may lead to ischemic change of the arterioles, resulting in avascular osteonecrosis [2, 4]. Osteonecrosis in patients with UC appears most commonly in the femoral head and is usually bilateral, although it occasionally occurs at other bone sites, such as the proximal humerus or femoral condyle [5, 6]. We have handled a case of osteonecrosis of the lateral femoral condyle in a patient with UC. We report this relatively rare complication with the aim of alerting clinicians to its possible presence and thus expedite early detection.
Case report A 17-year-old Japanese female had visited a local hospital in 1996 because of bloody diarrhea, and UC had been diagnosed based on the results from a endoscopic examination. The symptoms had improved following the administration of oral prednisolone 30 mg/day; this drug therapy was then tapered and discontinued within 2 months of initiation. In October 1997, bloody diarrhea and abdominal pain recurred, and the patient was referred to our hospital where she was admitted and treated with intravenous prednisolone (80 mg/day) while receiving total parenteral nutrition. Her disease activity did not improve, and she developed hyperglycemia and glaucoma as side effects of the steroid treatment. A barium enema test revealed severe colitis in the entire colon, sigmoidscopy showed multiple deep ulcerations. A total colectomy was
123
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therefore performed. Following the surgery, the prednisolone was tapered off, and the patient returned to general good health. At this point, the cumulative lifetime prednisolone dose was calculated to be 3020 mg. In 2002, 7 years after the operation, visual disturbance occurred in her right eye. Uveitis was diagnosed and controlled by eye drops containing steroid hormone. The results of blood chemistry tests were almost normal, and the test for the presence of anti-nuclear antibody was negative. Up to 2005, the ocular symptoms were absent, and no further local steroid therapy was needed. In February 2006, the patient developed severe pain in the left knee. Plain radiography revealed a lucent focus in the left lateral femoral condyle, and stage 3 osteonecrosis was diagnosed on the basis of the Association of Research Circulation Osseous (ARCO) international classification of osteonecrosis [7] (Fig. 1). Magnetic resonance imaging (MRI) showed a distinct necrotic lesion and surrounding reactive tissue (Fig. 2). Because of pain and gait disturbance, the patient underwent osteochondral autografting to treat the lesion in June 2006, when she was 27 years old. When this report was written, the patient had undergone rehabilitation and remains in good condition.
Discussion Ischemic change of the arterioles due to various causes results in avascular osteonecrosis, but the mechanisms of osteonecrosis in patients with inflammatory bowel disease have not been clearly elucidated. Klingenstein et al. [2] Fig. 1 Plain radiograph of the left knee. A radiolucent focus is evident in the left lateral femoral condyle. The findings indicate stage 3 according to the Association Research Circulation Osseous international classification of osteonecrosis [7] and stage 3 according to the staging system for idiopathic osteonecrosis of the knee reported by Aglietti et al. [12]. a Frontal view, b lateral view
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reported that osteonecrosis in active inflammatory bowel disease could be related to disseminated intravascular coagulation in conjunction with increased intramedullary pressure caused by steroid therapy. Our patient had no episode of trauma to her knee and was not suffering from any evident collagen disease. Furthermore, the osteonecrosis occurred long after prednisolone therapy had been discontinued. However, she had actually received two courses of prednisolone therapy, and the peak dose of prednisolone was relatively high. Therefore, an association with steroid therapy can not be ruled out in this case. Another confounding factor is that the true pathogenesis— i.e., idiopathic or steroid-associated osteonecrosis—had not been determined. With regard to the incidence of osteonecrosis in inflammatory bowel disease, Vakil et al. [3] reported a figure of 4.3% (seven of 161 cases, including Crohn’s disease). In a Japanese series, femoral head osteonecrosis was reported in seven (3.6%) of 196 cases of UC [1]. At our institution, we have experienced 266 cases of UC and 68 cases of Crohn’s disease, and to date have encountered only two cases of osteonecrosis among the patients with UC. Both of these patients had a history of steroid therapy: one had bilateral femoral head osteonecrosis, and the other was the patient reported here. Osteonecrosis in patients with inflammatory bowel disease appears most commonly in the femoral head and is usually bilateral. In contrast, little information is available on sites affected by osteonecrosis. Klingenstein et al. [2] reported 23 cases of osteonecrosis associated with inflammatory bowel disease; the sites of osteonecrosis were
Clin J Gastroenterol (2008) 1:93–96
95
Fig. 2 Magnetic resonance image of the left knee. The osteonecrosis lesion appears as a low-intensity area in both the T1- and T2-weighted images. a, b Frontal sections of the left knee, c, d sagittal sections. a, c T1, b, d T2
usually multiple, such as the hip/knee or hip/shoulder, and 67% involved the hip, 18% the knee, and 15% the shoulder. Clinical examination revealed that only four of the 23 cases involved a single osteonecrosis site, and one of the four was had a single lesion of the knee. As our patient had a single lesion in the femoral condyle, we considered this to be a relatively rare case in light of the reported incidence. Klingenstein et al. [2] suggested that comprehensive testing with MRI is indicated in all cases, even if the symptom is limited to one joint. Therefore, as it is clear that multiple joints are often involved, careful follow-up of our patient will be necessary.
There seems to be no link between the dose of steroid and the risk of osteonecrosis in steroid-related osteonecrosis in patients with inflammatory bowel disease. Vakil et al. [3] reported a mean cumulative lifetime prednisolone dose of 7 g and a mean treatment duration of 42 weeks in seven patients with inflammatory bowel disease treated with steroid. In Japan, Munakata et al. [1] reported a mean cumulative prednisolone dose of 18 g and a mean treatment duration of 64 weeks in seven cases of femoral head osteonecrosis associated with UC. It would therefore appear that most reported patients had received relatively high doses of steroids for relatively long periods. The total
123
96
dose of prednisolone received by our patient was about 3 g, and the treatment duration was 16 weeks. If this case was steroid-related, the amount of steroid was relatively lower and the treatment duration rather shorter than those in cases reported earlier. Vakil et al. [3] discussed the occurrence of osteonecrosis in patients with inflammatory bowel disease and compared this with conditions related to other diseases. The doses and duration of steroid treatment in patients with associated osteonecrosis were considerably lower than in patients with other disease states. As mentioned at the beginning of this discussion, UC tends to form micro-thrombosis easily and may have a background of autoimmunity [2, 3]. The health of our patient was complicated by uveitis as a condition related to autoimmunity. However, no previous report has mentioned a relationship between osteonecrosis and uveitis. As uveitis is a common complication of UC, uveitis and osteonecrosis may have occurred coincidentally in our patient. Conventional X-ray imaging is not very helpful in the early stage of femoral condyle osteonecrosis [8], and the diagnosis of osteonecrosis, including stage determination, is usually based on MRI scans. The clinical course of avascular osteonecrosis varies among patients, and the natural course is not well known [9]. However, if osteonecrosis of the knee can be detected at an early stage, spontaneous regression can sometimes be expected. In some cases, conservative treatments, such as use of an insole, are effective [10]. Even in steroid-related osteonecrosis, Takao et al. [11] reported that regression can occur in some patients with early-stage disease. Therefore, cases that are diagnosed early may have a good prognosis, although surgical treatment may still be required. Unfortunately, our patient was diagnosed as stage 3 based on the ARCO international classification of osteonecrosis [7] or stage 3 based on the criteria reported by Aglietti et al. [12] and ultimately required osteochondral autografting. This case has revealed to us the necessity of making careful efforts to detect osteonecrosis at an early stage. In our patient, pain and osteonecrosis occurred 10.5 years after the onset of UC. Klingenstein et al. [2] reported that osteonecrosis occurred 3–42 years after diagnosis of inflammatory bowel disease. Thus, the period until onset of osteonecrosis varies considerably among patients, making it very difficult to detect the condition promptly at an early stage. For early detection of
123
Clin J Gastroenterol (2008) 1:93–96
osteonecrosis, careful observation and appropriate use of MRI is recommended. In conclusion, we have reported a case of osteonecrosis in the lateral femoral condyle in a patient with UC. The clinician should be aware of this relatively rare complication and consider it during the differential diagnosis in order to facilitate early detection of the lesions. Acknowledgments We would like to thank Dr. Tamon Asano and Dr. Jun-ichi Hashimoto from the Department of Orthopedics for helpful advice.
References 1. Munakata A, Hatada Y, Yao T. Analysis of adverse effects of steroid therapy to inflammatory bowel disease. In: Annual report of the research committee of inflammatory bowel disease (in Japanese with English abstract). The Ministry of Health and Welfare of Japan. 1995; pp. 67–70. 2. Klingenstein G, Levy RN, Kornbluth A, Shah AK, Present DH. Inflammatory bowel disease-related osteonecrosis: report of a large series with a review of the literature. Aliment Pharmacol Ther. 2005;21:243–9. 3. Vakil N, Sparberg M. Steroid-related osteonecrosis in inflammatory bowel disease. Gastroenterology. 1989;96:62–7. 4. Gorczynski C, Meislin R. Osteonecrosis of the distal femur. Bull Hosp Jt Dis. 2006;63:145–52. 5. Madsen PV, Anderson G. Multifocal osteonecrosis related to steroid treatment in a patient with ulcerative colitis. Gut. 1994;35:132–4. 6. Sasaki T, Yagi T, Monji J, Yasuda K, Masuda T, Fukuzawa M, et al. Steroid-induced osteonecrosis of the femoral condyle—a clinical study of 18 knees in ten patients—(in Japanese with English abstract). Nippon Seikeigeka Gakkai Zasshi (J Jpn Orthop Assoc). 1986;60:361–72. 7. Gardeniers JM. ARCO committee on terminology and staging; Report of the committee-meeting at Santiago de Compostela. ARCO Newsl. 1993;5:79–82. 8. Ito K, Inuo-Nakayama M, Matsumoto M, Kubokawa M, Sadamoto Y, Kubo H, et al. Steroid-induced osteonecrosis in refractory ulcerative colitis. Fukuoka Igaku Zasshi. 2005;96:5– 10. 9. Lafforgue P. Pathophysiology and natural history of avascular necrosis of bone. Joint Bone Spine. 2006;73:500–7. 10. Patel DV, Breazeale NM, Behr CT, Warren RF, Wickiewicz TL, O’Brien SJ. Osteonecrosis: current clinical concepts. Knee Surg Sports Traumatol Anthrosc. 1998;6:2–11. 11. Takao M, Sugano N, Nishii T, Miki H, Yoshikawa H. Spontaneous regression of steroid-related osteonecrosis of the knees. Clin Orthop Relat Res. 2006;452:210–5. 12. Aglietti P, Insall JN, Buzzi R, Deshamps G. Idiopathic osteonecrosis of the knee: aetiology, prognosis and treatment. J Bone Joint Surg. 1983;65:588–97.
