http://informahealthcare.com/mor ISSN 1439-7595 (print), 1439-7609 (online) Mod Rheumatol, 2015; 25(2): 278–281 © 2014 Japan College of Rheumatology DOI: 10.3109/14397595.2014.932038
ORIGINAL ARTICLE
Epidemiology of nontraumatic osteonecrosis of the femoral head in Japan Kazuma Ikeuchi, Yukiharu Hasegawa, Taisuke Seki, Yasuhiko Takegami, Takafumi Amano, and Naoki Ishiguro Nagoya University Hospital, Nagoya University Graduate School of Medicine, Nagoya, Japan Abstract
Keywords
Objectives. To elucidate the epidemiology of nontraumatic osteonecrosis of the femoral head (ONFH), and to estimate the annual incidence rate in Japan. Methods. We examined, over the course of 3 years, personal records and radiographic images from the national registry of documents used for the study of nontraumatic ONFH in patients in Aichi Prefecture, Japan (population: 7.4 million). Those patients not meeting the diagnostic criteria according to the Japanese Investigation Committee for nontraumatic ONFH were excluded from this study. Results. A total of 285 out of the 327 patients who applied for the national registration of nontraumatic ONFH during the 3-year study met the diagnostic criteria for personal records, radiographic images, and magnetic resonance images. Forty-two patients (12.8%) were not considered to have nontraumatic ONFH. The mean age of patients was 50.4 years, and the male-female ratio was 2.1:1. Nontraumatic ONFH was steroid-induced in 135 cases (47.4%), alcohol-associated in 87 cases (30.5%), steroid-induced and alcohol- associated in 14 cases (4.9%), and idiopathic in 49 cases (17.2%). Conclusions. The age-adjusted annual incidence of nontraumatic ONFH in Aichi Prefecture was estimated at 138.5 patients.Thus the annual incidence rate in Japan (population 128 million) was 1.91/100,000.
Epidemiology, Femoral head, Incidence rate, Nontraumatic osteonecrosis
Introduction Nontraumatic osteonecrosis of the femoral head (ONFH) occurs frequently in young, active individuals. If femoral head collapse progresses, it can lead to secondary degenerative osteoarthritis, causing pain and difficulty in walking [1–3]. The causes and risk factors for nontraumatic ONFH have been investigated in many studies [4–11], but they remain controversial. Advances in magnetic resonance imaging (MRI) have had a significant impact, allowing early detection of abnormalities and diagnosis of the condition [12–15]. Good long-term outcomes of various surgical treatments, including femoral osteotomies and total hip arthroplasty, have also been reported [16–24], and strategies from diagnosis to treatment have been standardized [25]. In Japan, patients with diseases that are the target of Specified Disease Treatment Research Programs can receive medical subsidy (medical care- bearing public expenses) to covering almost the entire cost of their medical treatment. In 1992, nontraumatic ONFH was designated by the Ministry of Health, Labor, and Welfare as an intractable disease. Patients with nontraumatic ONFH can receive medical subsidy under the Specified Disease Treatment Research Program, provided they register with their own prefectural local authority using the personal questionnaire described by an orthopedic surgeon. The registration data this system provides Correspondence to: Kazuma Ikeuchi, Department of Orthopedics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi Prefecture, Japan. Tel: 052-741-2111. Fax: 052-744-2260. E-mail: [email protected]
History Received 24 March 2014 Accepted 3 June 2014 Published online 16 July 2014
has enabled estimation of the incidence of nontraumatic ONFH in Japanese people, and the prevalence rate based on nationwide surveys [26–28]. However, patient registration is only based purely on the personal questionnaire, and the individuals responsible for reviewing the documents do not evaluate radiographic images. Aichi Prefecture is the only prefecture in Japan where the senior authors (YH, TS) strictly assessed the criteria for nontraumatic ONFH based on both the personal questionnaire for the second query, and radiographic and MR images. Reviewing only the personal questionnaire for the second query could lead to conditions that are not nontraumatic ONFH, such as osteoarthritis of the hip and subchondral insufficiency fracture of the femoral head [29] to be misdiagnosed as nontraumatic ONFH, resulting in a possible overestimation of the number of patients with nontraumatic ONFH. Furthermore, specified diseases without nontraumatic ONFH may include systemic lupus erythematosus (SLE) and idiopathic thrombocytopenic purpura. In cases where medical subsidy is received based on registration as a specified disease such as SLE even when steroid-induced ONFH is present, the patient is probably receiving treatment without registration of nontraumatic ONFH, which could lead to the underestimation of the number of patients with nontraumatic ONFH. The primary objective of this study was to assess newly registered patients with nontraumatic ONFH in Aichi Prefecture, Japan. The second objective was to ascertain the number of underestimated cases of steroid-induced ONFH. The third objective was to estimate the incidence of nontraumatic ONFH in both Aichi Prefecture and Japan.
DOI 10.3109/14397595.2014.932038
Patients and methods Between August 2010 and July 2013, patients newly registered with the Specified Disease Treatment Research Program with nontraumatic ONFH in Aichi Prefecture, Japan, were surveyed retrospectively. The population of Aichi Prefecture was 7.41 million in 2011. The diagnostic criteria were in accordance with those proposed by the Japanese Investigation Committee [30,31]. Evaluation was based not only on personal records, but also on plain radiographs and MR images. Any patient not meeting the diagnostic criteria for nontraumatic ONFH was excluded by the senior authors (YH, TS) and members of the Japanese Investigation Committee, from the incidence of nontraumatic ONFH. The personal questionnaire for the second query included the following information: age, sex, symptom onset, presence of diagnostic criteria, disease type and stage, absence of exclusion criteria, treatment methods, disease caused by steroid use, quantity and duration of steroid use, volume of alcohol consumption, and consumption period. The diagnostic criteria were: 1) collapse of the femoral head without joint-space narrowing or acetabular abnormality on radiography (including crescent sign); 2) demarcating sclerosis in the femoral head without joint space narrowing or acetabular abnormality; 3) “cold in hot” on bone scintigraphy; 4) low-intensity band on T1-weighted images (band-like pattern); 5) trabecular and marrow necrosis on histology. Nontraumatic femoral head osteonecrosis was diagnosed in any patient meeting two or more of the five criteria. Disease stage and type categorization were based on categories proposed by the Research Committee on Idiopathic Osteonecrosis of the Femoral Head in Japan [30]. Disease type categorization was based on the proportion of the necrotized area covered by the weight-bearing part, based on findings on radiographs and/or MR images, and patients were divided thereby into the four categories of type A, type B, type C-1, and type C-2 [30]. We excluded patients who registered more than 2 years after the onset of hip pain. However, some patients did not complain of severe hip pain. Therefore, stage 4 patients were included. The first study used personal records, including the age at registration, sex, radiograph evaluation, MR image evaluation, bone scintigraphy results, and histopathological results of patients with nontraumatic ONFH. The second study involved a survey of the specified disease registration conditions of all 895 cases of nontraumatic femoral head osteonecrosis registered in our university hospital, based on their medical records. Patients undergoing treatment for nontraumatic ONFH induced by steroids administered for a specified disease were studied. The medical condition that was registered with the specified disease registration program for each patient attending the hospital for both conditions was also surveyed. The third study involved the calculation of the age-adjusted incidence rate of patients with nontraumatic ONFH in Japan using registration data in Aichi Prefecture. Both authors (KI, YH) provided statistical analysis. The epidemiological research of such patients with nontraumatic ONFH in Aichi Prefecture was approved by the review board of our hospital.
Epidemiology of nontraumatic ONFH in Japan 279 Table 1. 42 Cases that required differential diagnosis with nontraumatic ONFH. Osteoarthritis of the hip Subchondral insufficiency fracture of the femoral head Trauma Unknown arthritis Epiphyseal dysplasia of the hip Rheumatoid arthritis Post total hip arthroplasty Transient osteoporosis of the hip Hematologic disease Total
23 8 3 3 1 1 1 1 1 42
ONFH, osteonecrosis of the femoral head.
fracture of the femoral head in 8 patients, and traumatic ONFH in 3 patients. A total of 285 patients were newly diagnosed with nontraumatic ONFH. The number of patients diagnosed with nontraumatic ONFH was 88 in the first year of the study, 97 in the second year, and 100 in the last year. There were no significant differences in the annual incidence between the 3 years (p ⫽ 0.821). The mean age of newly diagnosed nontraumatic ONFH patients was 50.4 ⫾ 14.5 years (192 men, mean age: 49.4 ⫾ 13.7; 93 women, mean age: 52.5 ⫾ 15.9), with a male-female ratio of 2.1:1 (Figure 1). Of the 285 patients, 224 (78.6%) who underwent plain radiography showed femoral head collapse, and 245 (86.0%) showed demarcating sclerosis. Of the 266 patients who underwent MRI, 260 (97.7 %) showed a low-intensity band in the femoral head on T1-weighted images. Of the 29 patients who underwent bone scintigraphy, 23 (79.3%) showed “cold in hot,” and 6 (85.7%) out of 7 patients who underwent histopathological examination fulfilled all five categories of diagnostic criteria. Nontraumatic ONFH was steroid- induced in 135 cases (47.4%), alcohol- associated in 87 cases (30.5%), both steroid-induced and alcohol- associated in 14 cases (4.9%) and idiopathic in 49 cases (17.2%) (Table 2). The underlying disorders in patients with steroid-induced ONFH included systemic lupuserythematosus (SLE) in 24 patients, nephrotic syndrome in 13, dermatological disease in 9, and idiopathic thrombocytopenic purpura in 8 patients. In 31 (30.7%) out of 101 patients with steroid-induced ONFH, the specified disease was also the cause of the condition. Among the 31 patients who received treatment at our university hospital for both steroid- induced ONFH and the specified disease causing ONFH, 18 had SLE, and 4 had idiopathic thrombocytopenic purpura. In 6 of these 31 patients, the specified disease was registered along with nontraumatic ONFH, whereas 3 patients had registered only
Results A total of 327 patients with nontraumatic ONFH were registered during the study. All patients (100%) underwent radiographic examination, and 304 (93.0%) underwent MRI. Thirty patients (9.2%) were examined using bone scintigraphy. Seven patients (2.1%) underwent pathological examination. The senior authors (YH, TS) strictly confirmed that 42 of the cases were not nontraumatic ONFH (Table 1). Differential diagnoses included osteoarthritis of the hip in 23 patients, subchondral insufficiency
Figure 1. Age distribution of the newly registered nontraumatic osteonecrosis of the femoral head.
280
K. Ikeuchi et al.
Mod Rheumatol, 2015; 25(2): 278–281
Table 2. Distribution of potential causative factors. Steroid-induced Alcohol- associated Both Neither
All patients (%) 47.4 30.5 4.9 17.2
Male (%) 39.6 40.1 5.2 15.1
Female (%) 63.4 10.8 4.3 21.5
the nontraumatic ONFH, and 13 patients had registered only the specified disease. In 9 cases, neither condition was registered by the patient. Based on this investigation, only 9 (29.0%) of the 31 cases of steroid-induced ONFH caused by a specified disease had been registered. The authors estimated the annual incidence rate of nontraumatic ONFH based on the assumption that the risk of nontraumatic ONFH is the same for the residents of Aichi Prefecture as it is in the rest of Japan. A diagnosis of nontraumatic ONFH was made in 285 patients in Aichi Prefecture during the 3-year study period, which gave a registration frequency adjusted for age of 1.31/100,000. Of these, a specified disease was the cause of the nontraumatic ONFH in 52 (18.2 %) patients. Therefore, assuming that the registration rate of specified diseases is the same among patients at our university hospital as it is throughout Aichi Prefecture, we believe that 130.5 cases were underestimated during the 3-year period. Adding these underestimated cases gives a total incidence of 415.5 new cases of nontraumatic ONFH during the 3-year period. Based on these data, the incidence of newly registered nontraumatic ONFH in one year in Aichi Prefecture (population: 7.41 million) is estimated at 138.5 cases, and the incidence of newly registered nontraumatic ONFH cases in the Japanese population (population: 128 million) is 2446 cases, giving an incidence rate of 1.91/100,000.
Discussions Few reports on the national incidence and epidemiology of nontraumatic ONFH have been published to date in Japan. Several reports have described various causes and incidences of steroid-induced ONFH [32–37]. Kang et al. estimated the number of patients with the disease to be 14,103 cases each year in Korea, based on data from health insurance claim records [28]. This figure gives an incidence rate of 28.91/100,000 in the Korean population (approximately 48.00 million in 2010). This incidence rate is almost the same as that in prefectures in Japan with a high prevalence of this condition. Many reports considered patient records that may have included concomitant conditions such as osteoarthritis of the hip or subchondral insufficiency fracture. In Japan, Fukushima et al. estimated that there are 11,400 cases of nontraumatic ONFH and 2,200 cases of new nontraumatic ONFH registrations each year, based on a nationwide only documentation survey [27]. In Fukuoka Prefecture (population: 5.0 million), the incidence rate for nontraumatic ONFH is 2.51/100,000 [26]. In this study, the authors estimated the number of nontraumatic ONFH cases to be 2,446, and the incidence rate to be 1.91/100,000. National data shows that a total of 14,812 cases of nontraumatic ONFH were registered in Japan in 2011 [38]. The registration frequency in Aichi Prefecture is 8.04/100,000, whereas it was almost double in the Fukuoka Prefecture at 15.24/100,000. The prefecture with the highest rate of registration was Okayama Prefecture, at 23.03/100,000, and the prefecture with the lowest registration rate was Mie Prefecture, at 6.50/100,000. There was a difference of almost 3.5 between the lowest and the highest registration frequency. The correlation coefficient for the number of specified diseases other than nontraumatic ONFH registered within this distribution is 0.53, demonstrating regional difference (Figure 2). In regions with large numbers of specified disease
Figure 2. All application frequency of the nontraumatic ONFH according to the each prefecture. Aichi prefecture (∗), Fukuoka prefecture (arrow).
registrations, there were also higher numbers of nontraumatic ONFH cases registered. The new registration frequency in Fukuoka Prefecture was reported as 2.51/100,000 [26]. In this study, after adjustment for age, the new registration frequency was reduced by approximately 50% to 1.31/100,000. Considering all registered cases in the national registration data [38], the proportion of newly registered patients was found to be 16.3% in Aichi Prefecture and 16.5% in Fukuoka Prefecture. If we assume that approximately 16.4% of all registered patients are new registrations, we can estimate that there are approximately 2429 new cases in Japan, giving an incidence rate of 1.90/100,000. This result is the same as the incidence rate for Aichi Prefecture. In this study, the authors reviewed both personal records and radiographic images for a more accurate diagnosis. Reviewing documents alone could probably lead to the overestimation of the incidence of nontraumatic ONFH. Yamamoto et al. also report that in 11.1% of patients diagnosed with ONFH who subsequently underwent surgery, the condition was in fact shown to be subchondral insufficiency fracture of the femoral head [39]. In this study, 42 cases (12.8%) were not nontraumatic ONFH. However, the authors found that most of the misdiagnosed patients (23 patients) were those with osteoarthritis of the hip. Subchondral insufficiency fracture of the femoral head was misdiagnosed in 8 patients. Both osteoarthritis of the hip and subchondral insufficiency fractures should be differentiated from nontraumatic ONFH. Considering that some patients with ONFH may remain unregistered, there is a strong possibility that the occurrence frequency is being underestimated. For example, in this study, only 9 (29.0%) out of 31 cases of ONFH caused by steroid use for a specified disease had registered their nontraumatic ONFH. This study had several limitations. First, it was carried out only in one prefecture of Japan. For this reason, the number of cases was small. Second, the survey period was short; if surveying of both patient written records and radiographic images by specialized doctors can be carried out over a longer period, this will allow estimation of a more accurate incidence rate in the future. Third, the lack of national registration of patients with nontraumatic ONFH is an important factor in underestimating the annual incidence. For the significant contribution of this underestimation (the actual number of underestimated cases is 768.4/year), our study provides strong and compelling evidence for evaluating this important matter.
Epidemiology of nontraumatic ONFH in Japan 281
DOI 10.3109/14397595.2014.932038
In conclusion, we estimated the annual number of nontraumatic ONFH in Aichi Prefecture at 138.5 patients. Thus the annual incidence rate in Japan (population 128 million) was 1.91/100,000.
18.
Acknowledgments
19.
The senior authors (Y. Hasegawa and T. Seki) have received funding from a research grant for the Research on Idiopathic Osteonecrosis of the Femoral Head and the Research on Epidemiology of Intractable Diseases from the Ministry of Health, Labor and Welfare of Japan.
20.
Conflict of interest N. Ishiguro has received research funding from Takeda, MitsubishiTanabe, Astellas, Chugai, Abbott, Bristol-Myers Squibb, Eisai, Daiichi Sankyo Company Ltd,Janssen, Kaken and Pfizer and has served on speaker bureaus for Daiichi Sankyo Company Ltd, Takeda Pharmaceutical Co Ltd, Hisamitsu Pharmaceutical Co Inc, Otsuka Pharmaceutical Co Ltd, Taisho Toyama Pharmaceutical Co Ltd, Kaken Pharmaceutical Co Ltd, Eisai Co Ltd, Janssen Pharmaceutical K.K, Bristol-Myers Squibb, Abbott Japan, Chugai Pharmaceutical Co Ltd, Mitsubishi Tanabe Pharmaceutical, UCB Japan, Astellas Pharma Inc., and Pfizer Japan Inc.
References 1. Jergesen HE, Khan AS. The natural history of untreated asymptomatic hips in patients who have non-traumatic osteonecrosis. J Bone Joint Surg Am. 1997;79(3):359–63. 2. Ohzono K, Saito M, Takaoka K, Ono K, Saito S, Nishina T, Kadowaki T. Natural history of nontraumatic avascular necrosis of the femoral head. J Bone Joint Surg Br. 1991;73(1):68–72. 3. Ito H, Matsuno T, Omizu N, Aoki Y, Minami A. Mid-term prognosis of non-traumatic osteonecrosis of the femoral head. J Bone Joint Surg Br. 2003;85(6):796–801. 4. Glueck CJ, Freiberg R, Tracy T, Stroop D, Wang P. Thrombophilia and hypofibrinolysis. Clin Orthop Relat Res. 1997;334:43–56. 5. Kerachian MA, Séguin C, Harvey EJ. Glucocorticoids in osteonecrosis of the femoral head: a new understanding of the mechanisms of action. J Steroid Biochem Mol Biol. 2009;114(3–5):121–8. 6. Lee JS, Koo KH, Ha YC, Koh KK, Kim SJ, Kim JR, et al. Role of thrombotic and fibrinolytic disorders in osteonecrosis of the femoral head. Clin Orthop Relat Res. 2003;417:270–6. 7. Hungerford DS, Zizic TM. Alcoholism associated ischemic necrosis of the femoral head: Early diagnosis and treatment. Clin Orthop Relat Res. 1978;130:144–53. 8. Mankin HJ. Nontraumatic necrosis of bone (osteonecrosis). N Engl J Med. 1992;326(22):1473–9. 9. Mont MA, Hungerford DS. Non-traumatic avascular necrosis of the femoral head. J Bone Joint Surg Am. 1995;77(3):459–74. 10. Hirota Y, Hirohata T, Fukuda K, Mori M, Yanagawa H, Ohno Y, Sugioka Y. Association of alcohol intake, cigarette smoking, and occupational status with the risk of idiopathic osteonecrosis of the femoral head. Am J Epidemiol. 1993;137(5):530–8. 11. Takahashi S, Fukushima W, Kubo T, Iwamoto Y, Hirota Y, Nakamura H. Pronounced risk of nontraumatic osteonecrosis of the femoral head among cigarette smokers who have never used oral corticosteroids: a multicenter case-control study in Japan. J Orthop Sci. 2012;17(6):730–6. 12. Mitchell MD, Kundel HL, Steinberg ME, Kressel HY, Alavi A, Axel L. Avascular necrosis of the hip: comparison of MR, CT, and scintigraphy. AJR Am J Roentgenol.1986;147(1):67–71. 13. Sakamoto M, Shimizu K, Iida S, Akita T, Moriya H, Nawata Y. Osteonecrosis of the femoral head: a prospective study with MRI. J Bone Joint Surg Br. 1997;79(2):213–9. 14. Malizos KN, Karantanas AH, Varitimidis SE, Dailiana ZH, Bargiotas K, Maris T. Osteonecrosis of the femoral head: etiology, imaging and treatment. Eur J Radiol. 2007;63(1):16–28. 15. Nagasawa K, Tada Y, Koarada S, Horiuchi T, Tsukamoto H, Murai K, et al. Very early development of steroid-associated osteonecrosis of femoral head in systemic lupus erythematosus: prospective study by MRI. Lupus. 2005;14(5):385–90. 16. Mont MA, Carbone JJ, Fairbank AC. Core decompression versus nonoperative management for osteonecrosis of the hip. Clin Orthop Relat Res. 1996;324:169–78. 17. Sugioka Y, Hotokebuchi T, Tsutsui H. Transtrochanteric anterior rotational osteotomy for idiopathic and steroid-induced necrosis of the
21. 22.
23.
24. 25. 26. 27. 28. 29. 30. 31. 32.
33. 34.
35. 36.
37.
38. 39.
femoral head. Indication and long term results. Clin Orthop Relat Res. 1992;277:111–20. Atsumi T, Muraki M, Yoshihara S, Kajihara T. Posterior rotational osteotomy for the treatment of femoral head osteonecrosis. Arch Orthop Trauma Surg. 1999;119(7–8):388–93. Hasegawa Y, Iwata H, Torii S, Iwase T, Kawamoto K, Iwasada S. Vascularized pedicle bone-grafting for nontraumatic avascular necrosis of the femoral head. A 5- to 11-year follow-up. Arch Orthop Trauma Surg. 1997;116(5):251–8. Hasegawa Y, Sakano S, Iwase T, Iwasada S, Torii S, Iwata H. Pedicle bone grafting versus transtrochanteric rotational osteotomy for avascular necrosis of the femoral head. J Bone Joint Surg Br. 2003;85(2):191–8. Sakano S, Hasegawa Y, Torii Y, Kawasaki M, Ishiguro N. Curved intertrochanteric varus osteotomy for osteonecrosis of the femoral head. J Bone Joint Surg Br. 2004;86(3):359–65. Solarino G, Piazzolla A, Notarnicola A, Moretti L, Tafuri S, De Giorgi S, Moretti B. Long-term results of 32-mm alumina-onalumina THA for avascular necrosis of the femoral head. J Orthop Traumatol. 2012;13(1):21–7. Gangji V, De Maertelaer V, Hauzeur JP. Autologous bone marrow cell implantation in the treatment of non-traumatic osteonecrosis of the femoral head: Five year follow-up of a prospective controlled study. Bone. 2011;49(5):1005–9. Lee SB, Sugano N, Nakata K, Matsui M, Ohzono K. Comparison between bipolar hemiarthroplasty and THA for osteonecrosis of the femoral head. Clin Orthop Relat Res. 2004;424:161–5. Mont MA, Jones LC, Hungerford DS. Nontraumatic osteonecrosis of the femoral head: ten years later. J Bone Joint Surg Am. 2006;88(5):1117–32. Yamaguchi R, Yamamoto T, Motomura G, Ikemura S, Iwamoto Y. Incidence of nontraumatic osteonecrosis of the femoral head in the Japanese population. Arthritis Rheum. 2011;63(10):3169–73. Fukushima W, Fujioka M, Kubo T, Tamakoshi A, Nagai M, Hirota Y. Nationwide epidemiologic survey of idiopathic osteonecrosis of the femoral head. Clin Orthop Relat Res. 2010;468(10):2715–24. Kang JS, Park S, Song JH, Jung YY, Cho MR, Rhyu KH. Prevalence of osteonecrosis of the femoral head: a nationwide epidemiologic analysis in Korea. J Arthroplasty. 2009;24(8):1178–83. Yamamoto T, Bullough PG. Subchondral insufficiency fracture of the femoral head: a differential diagnosis in acute onset of coxarthrosis in the elderly. Arthritis Rheum. 1999;42(12):2719–23. Sugano N, Atsumi T, Ohzono K, Kubo T, Hotokebuchi T, Takaoka K. The 2001 revised criteria for diagnosis, classification, and staging of idiopathic osteonecrosis of the femoral head. J Orthop Sci. 2002;7(5):601–5. Sugano N, Kubo T, Takaoka K, Ohzono K, Hotokebuchi T, Matsumoto T, et al. Diagnostic criteria for non-traumatic osteonecrosis of the femoral head. A multicenter study. J Bone Joint Surg Br. 1999;81(4):590–595. Oinuma K, Harada Y, Nawata Y, Takabayashi K, Abe I, Kamikawa K, Moriya H. Osteonecrosis in patients with systemic lupus erythematosus develops very early after starting high dose corticosteroid treatment. Ann Rheum Dis. 2001;60(12):1145–8. Gladman DD, Chaudhry-Ahluwalia V, Ibañez D, Bogoch E, Urowitz MB. Outcomes of symptomatic osteonecrosis in 95 patients with systemic lupus erythematosus. J Rheumatol. 2001;28(10):2226–9. Kubo T, Yamazoe S, Sugano N, Fujioka M, Naruse S, Yoshimura N, Hirasawa Y. Initial MRI findings of non-traumatic osteonecrosis of the femoral head in renal allograft recipients. Magn Reson Imaging. 1997;15(9):1017–23. Torii Y, Hasegawa Y, Kubo T, Kodera Y, Minami S, Morishita Y, et al. Osteonecrosis of the femoral head after allogeneic bone marrow transplantation. Clin Orthop Relat Res. 2001;382: 124–32. Yildirim ZK, Büyükavci M, Eren S, Orbak Z, Sahin A, Karakelleoğlu C. Late side effects of high-dose steroid therapy on skeletal system in children with idiopathic thrombocytopenic purpura. J Pediatr Hematol Oncol. 2008;30(10):749–753. Shigemura T, Nakamura J, Kishida S, Harada Y, Ohtori S, Kamikawa K, et al. Incidence of osteonecrosis associated with corticosteroid therapy among different underlying diseases: prospective MRI study. Rheumatology (Oxford). 2011;50(11):2023–8. Ministry of Health, Labour and Welfare. Japan Intractable Diseases Information Center. Health administration reported case. [Statistics Japan] URL: http://www.nanbyou.or.jp/ [accessed 2014-01-15] Yamamoto T, Iwamoto Y, Schneider R, Bullough PG. Histopathological prevalence of subchondral insufficiency fracture of the femoral head. Ann Rheum Dis. 2008;67(2):150–3.
Copyright of Modern Rheumatology (Informa Healthcare) is the property of Informa Healthcare and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
ORIGINAL ARTICLE
Epidemiology of nontraumatic osteonecrosis of the femoral head in Japan Kazuma Ikeuchi, Yukiharu Hasegawa, Taisuke Seki, Yasuhiko Takegami, Takafumi Amano, and Naoki Ishiguro Nagoya University Hospital, Nagoya University Graduate School of Medicine, Nagoya, Japan Abstract
Keywords
Objectives. To elucidate the epidemiology of nontraumatic osteonecrosis of the femoral head (ONFH), and to estimate the annual incidence rate in Japan. Methods. We examined, over the course of 3 years, personal records and radiographic images from the national registry of documents used for the study of nontraumatic ONFH in patients in Aichi Prefecture, Japan (population: 7.4 million). Those patients not meeting the diagnostic criteria according to the Japanese Investigation Committee for nontraumatic ONFH were excluded from this study. Results. A total of 285 out of the 327 patients who applied for the national registration of nontraumatic ONFH during the 3-year study met the diagnostic criteria for personal records, radiographic images, and magnetic resonance images. Forty-two patients (12.8%) were not considered to have nontraumatic ONFH. The mean age of patients was 50.4 years, and the male-female ratio was 2.1:1. Nontraumatic ONFH was steroid-induced in 135 cases (47.4%), alcohol-associated in 87 cases (30.5%), steroid-induced and alcohol- associated in 14 cases (4.9%), and idiopathic in 49 cases (17.2%). Conclusions. The age-adjusted annual incidence of nontraumatic ONFH in Aichi Prefecture was estimated at 138.5 patients.Thus the annual incidence rate in Japan (population 128 million) was 1.91/100,000.
Epidemiology, Femoral head, Incidence rate, Nontraumatic osteonecrosis
Introduction Nontraumatic osteonecrosis of the femoral head (ONFH) occurs frequently in young, active individuals. If femoral head collapse progresses, it can lead to secondary degenerative osteoarthritis, causing pain and difficulty in walking [1–3]. The causes and risk factors for nontraumatic ONFH have been investigated in many studies [4–11], but they remain controversial. Advances in magnetic resonance imaging (MRI) have had a significant impact, allowing early detection of abnormalities and diagnosis of the condition [12–15]. Good long-term outcomes of various surgical treatments, including femoral osteotomies and total hip arthroplasty, have also been reported [16–24], and strategies from diagnosis to treatment have been standardized [25]. In Japan, patients with diseases that are the target of Specified Disease Treatment Research Programs can receive medical subsidy (medical care- bearing public expenses) to covering almost the entire cost of their medical treatment. In 1992, nontraumatic ONFH was designated by the Ministry of Health, Labor, and Welfare as an intractable disease. Patients with nontraumatic ONFH can receive medical subsidy under the Specified Disease Treatment Research Program, provided they register with their own prefectural local authority using the personal questionnaire described by an orthopedic surgeon. The registration data this system provides Correspondence to: Kazuma Ikeuchi, Department of Orthopedics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi Prefecture, Japan. Tel: 052-741-2111. Fax: 052-744-2260. E-mail: [email protected]
History Received 24 March 2014 Accepted 3 June 2014 Published online 16 July 2014
has enabled estimation of the incidence of nontraumatic ONFH in Japanese people, and the prevalence rate based on nationwide surveys [26–28]. However, patient registration is only based purely on the personal questionnaire, and the individuals responsible for reviewing the documents do not evaluate radiographic images. Aichi Prefecture is the only prefecture in Japan where the senior authors (YH, TS) strictly assessed the criteria for nontraumatic ONFH based on both the personal questionnaire for the second query, and radiographic and MR images. Reviewing only the personal questionnaire for the second query could lead to conditions that are not nontraumatic ONFH, such as osteoarthritis of the hip and subchondral insufficiency fracture of the femoral head [29] to be misdiagnosed as nontraumatic ONFH, resulting in a possible overestimation of the number of patients with nontraumatic ONFH. Furthermore, specified diseases without nontraumatic ONFH may include systemic lupus erythematosus (SLE) and idiopathic thrombocytopenic purpura. In cases where medical subsidy is received based on registration as a specified disease such as SLE even when steroid-induced ONFH is present, the patient is probably receiving treatment without registration of nontraumatic ONFH, which could lead to the underestimation of the number of patients with nontraumatic ONFH. The primary objective of this study was to assess newly registered patients with nontraumatic ONFH in Aichi Prefecture, Japan. The second objective was to ascertain the number of underestimated cases of steroid-induced ONFH. The third objective was to estimate the incidence of nontraumatic ONFH in both Aichi Prefecture and Japan.
DOI 10.3109/14397595.2014.932038
Patients and methods Between August 2010 and July 2013, patients newly registered with the Specified Disease Treatment Research Program with nontraumatic ONFH in Aichi Prefecture, Japan, were surveyed retrospectively. The population of Aichi Prefecture was 7.41 million in 2011. The diagnostic criteria were in accordance with those proposed by the Japanese Investigation Committee [30,31]. Evaluation was based not only on personal records, but also on plain radiographs and MR images. Any patient not meeting the diagnostic criteria for nontraumatic ONFH was excluded by the senior authors (YH, TS) and members of the Japanese Investigation Committee, from the incidence of nontraumatic ONFH. The personal questionnaire for the second query included the following information: age, sex, symptom onset, presence of diagnostic criteria, disease type and stage, absence of exclusion criteria, treatment methods, disease caused by steroid use, quantity and duration of steroid use, volume of alcohol consumption, and consumption period. The diagnostic criteria were: 1) collapse of the femoral head without joint-space narrowing or acetabular abnormality on radiography (including crescent sign); 2) demarcating sclerosis in the femoral head without joint space narrowing or acetabular abnormality; 3) “cold in hot” on bone scintigraphy; 4) low-intensity band on T1-weighted images (band-like pattern); 5) trabecular and marrow necrosis on histology. Nontraumatic femoral head osteonecrosis was diagnosed in any patient meeting two or more of the five criteria. Disease stage and type categorization were based on categories proposed by the Research Committee on Idiopathic Osteonecrosis of the Femoral Head in Japan [30]. Disease type categorization was based on the proportion of the necrotized area covered by the weight-bearing part, based on findings on radiographs and/or MR images, and patients were divided thereby into the four categories of type A, type B, type C-1, and type C-2 [30]. We excluded patients who registered more than 2 years after the onset of hip pain. However, some patients did not complain of severe hip pain. Therefore, stage 4 patients were included. The first study used personal records, including the age at registration, sex, radiograph evaluation, MR image evaluation, bone scintigraphy results, and histopathological results of patients with nontraumatic ONFH. The second study involved a survey of the specified disease registration conditions of all 895 cases of nontraumatic femoral head osteonecrosis registered in our university hospital, based on their medical records. Patients undergoing treatment for nontraumatic ONFH induced by steroids administered for a specified disease were studied. The medical condition that was registered with the specified disease registration program for each patient attending the hospital for both conditions was also surveyed. The third study involved the calculation of the age-adjusted incidence rate of patients with nontraumatic ONFH in Japan using registration data in Aichi Prefecture. Both authors (KI, YH) provided statistical analysis. The epidemiological research of such patients with nontraumatic ONFH in Aichi Prefecture was approved by the review board of our hospital.
Epidemiology of nontraumatic ONFH in Japan 279 Table 1. 42 Cases that required differential diagnosis with nontraumatic ONFH. Osteoarthritis of the hip Subchondral insufficiency fracture of the femoral head Trauma Unknown arthritis Epiphyseal dysplasia of the hip Rheumatoid arthritis Post total hip arthroplasty Transient osteoporosis of the hip Hematologic disease Total
23 8 3 3 1 1 1 1 1 42
ONFH, osteonecrosis of the femoral head.
fracture of the femoral head in 8 patients, and traumatic ONFH in 3 patients. A total of 285 patients were newly diagnosed with nontraumatic ONFH. The number of patients diagnosed with nontraumatic ONFH was 88 in the first year of the study, 97 in the second year, and 100 in the last year. There were no significant differences in the annual incidence between the 3 years (p ⫽ 0.821). The mean age of newly diagnosed nontraumatic ONFH patients was 50.4 ⫾ 14.5 years (192 men, mean age: 49.4 ⫾ 13.7; 93 women, mean age: 52.5 ⫾ 15.9), with a male-female ratio of 2.1:1 (Figure 1). Of the 285 patients, 224 (78.6%) who underwent plain radiography showed femoral head collapse, and 245 (86.0%) showed demarcating sclerosis. Of the 266 patients who underwent MRI, 260 (97.7 %) showed a low-intensity band in the femoral head on T1-weighted images. Of the 29 patients who underwent bone scintigraphy, 23 (79.3%) showed “cold in hot,” and 6 (85.7%) out of 7 patients who underwent histopathological examination fulfilled all five categories of diagnostic criteria. Nontraumatic ONFH was steroid- induced in 135 cases (47.4%), alcohol- associated in 87 cases (30.5%), both steroid-induced and alcohol- associated in 14 cases (4.9%) and idiopathic in 49 cases (17.2%) (Table 2). The underlying disorders in patients with steroid-induced ONFH included systemic lupuserythematosus (SLE) in 24 patients, nephrotic syndrome in 13, dermatological disease in 9, and idiopathic thrombocytopenic purpura in 8 patients. In 31 (30.7%) out of 101 patients with steroid-induced ONFH, the specified disease was also the cause of the condition. Among the 31 patients who received treatment at our university hospital for both steroid- induced ONFH and the specified disease causing ONFH, 18 had SLE, and 4 had idiopathic thrombocytopenic purpura. In 6 of these 31 patients, the specified disease was registered along with nontraumatic ONFH, whereas 3 patients had registered only
Results A total of 327 patients with nontraumatic ONFH were registered during the study. All patients (100%) underwent radiographic examination, and 304 (93.0%) underwent MRI. Thirty patients (9.2%) were examined using bone scintigraphy. Seven patients (2.1%) underwent pathological examination. The senior authors (YH, TS) strictly confirmed that 42 of the cases were not nontraumatic ONFH (Table 1). Differential diagnoses included osteoarthritis of the hip in 23 patients, subchondral insufficiency
Figure 1. Age distribution of the newly registered nontraumatic osteonecrosis of the femoral head.
280
K. Ikeuchi et al.
Mod Rheumatol, 2015; 25(2): 278–281
Table 2. Distribution of potential causative factors. Steroid-induced Alcohol- associated Both Neither
All patients (%) 47.4 30.5 4.9 17.2
Male (%) 39.6 40.1 5.2 15.1
Female (%) 63.4 10.8 4.3 21.5
the nontraumatic ONFH, and 13 patients had registered only the specified disease. In 9 cases, neither condition was registered by the patient. Based on this investigation, only 9 (29.0%) of the 31 cases of steroid-induced ONFH caused by a specified disease had been registered. The authors estimated the annual incidence rate of nontraumatic ONFH based on the assumption that the risk of nontraumatic ONFH is the same for the residents of Aichi Prefecture as it is in the rest of Japan. A diagnosis of nontraumatic ONFH was made in 285 patients in Aichi Prefecture during the 3-year study period, which gave a registration frequency adjusted for age of 1.31/100,000. Of these, a specified disease was the cause of the nontraumatic ONFH in 52 (18.2 %) patients. Therefore, assuming that the registration rate of specified diseases is the same among patients at our university hospital as it is throughout Aichi Prefecture, we believe that 130.5 cases were underestimated during the 3-year period. Adding these underestimated cases gives a total incidence of 415.5 new cases of nontraumatic ONFH during the 3-year period. Based on these data, the incidence of newly registered nontraumatic ONFH in one year in Aichi Prefecture (population: 7.41 million) is estimated at 138.5 cases, and the incidence of newly registered nontraumatic ONFH cases in the Japanese population (population: 128 million) is 2446 cases, giving an incidence rate of 1.91/100,000.
Discussions Few reports on the national incidence and epidemiology of nontraumatic ONFH have been published to date in Japan. Several reports have described various causes and incidences of steroid-induced ONFH [32–37]. Kang et al. estimated the number of patients with the disease to be 14,103 cases each year in Korea, based on data from health insurance claim records [28]. This figure gives an incidence rate of 28.91/100,000 in the Korean population (approximately 48.00 million in 2010). This incidence rate is almost the same as that in prefectures in Japan with a high prevalence of this condition. Many reports considered patient records that may have included concomitant conditions such as osteoarthritis of the hip or subchondral insufficiency fracture. In Japan, Fukushima et al. estimated that there are 11,400 cases of nontraumatic ONFH and 2,200 cases of new nontraumatic ONFH registrations each year, based on a nationwide only documentation survey [27]. In Fukuoka Prefecture (population: 5.0 million), the incidence rate for nontraumatic ONFH is 2.51/100,000 [26]. In this study, the authors estimated the number of nontraumatic ONFH cases to be 2,446, and the incidence rate to be 1.91/100,000. National data shows that a total of 14,812 cases of nontraumatic ONFH were registered in Japan in 2011 [38]. The registration frequency in Aichi Prefecture is 8.04/100,000, whereas it was almost double in the Fukuoka Prefecture at 15.24/100,000. The prefecture with the highest rate of registration was Okayama Prefecture, at 23.03/100,000, and the prefecture with the lowest registration rate was Mie Prefecture, at 6.50/100,000. There was a difference of almost 3.5 between the lowest and the highest registration frequency. The correlation coefficient for the number of specified diseases other than nontraumatic ONFH registered within this distribution is 0.53, demonstrating regional difference (Figure 2). In regions with large numbers of specified disease
Figure 2. All application frequency of the nontraumatic ONFH according to the each prefecture. Aichi prefecture (∗), Fukuoka prefecture (arrow).
registrations, there were also higher numbers of nontraumatic ONFH cases registered. The new registration frequency in Fukuoka Prefecture was reported as 2.51/100,000 [26]. In this study, after adjustment for age, the new registration frequency was reduced by approximately 50% to 1.31/100,000. Considering all registered cases in the national registration data [38], the proportion of newly registered patients was found to be 16.3% in Aichi Prefecture and 16.5% in Fukuoka Prefecture. If we assume that approximately 16.4% of all registered patients are new registrations, we can estimate that there are approximately 2429 new cases in Japan, giving an incidence rate of 1.90/100,000. This result is the same as the incidence rate for Aichi Prefecture. In this study, the authors reviewed both personal records and radiographic images for a more accurate diagnosis. Reviewing documents alone could probably lead to the overestimation of the incidence of nontraumatic ONFH. Yamamoto et al. also report that in 11.1% of patients diagnosed with ONFH who subsequently underwent surgery, the condition was in fact shown to be subchondral insufficiency fracture of the femoral head [39]. In this study, 42 cases (12.8%) were not nontraumatic ONFH. However, the authors found that most of the misdiagnosed patients (23 patients) were those with osteoarthritis of the hip. Subchondral insufficiency fracture of the femoral head was misdiagnosed in 8 patients. Both osteoarthritis of the hip and subchondral insufficiency fractures should be differentiated from nontraumatic ONFH. Considering that some patients with ONFH may remain unregistered, there is a strong possibility that the occurrence frequency is being underestimated. For example, in this study, only 9 (29.0%) out of 31 cases of ONFH caused by steroid use for a specified disease had registered their nontraumatic ONFH. This study had several limitations. First, it was carried out only in one prefecture of Japan. For this reason, the number of cases was small. Second, the survey period was short; if surveying of both patient written records and radiographic images by specialized doctors can be carried out over a longer period, this will allow estimation of a more accurate incidence rate in the future. Third, the lack of national registration of patients with nontraumatic ONFH is an important factor in underestimating the annual incidence. For the significant contribution of this underestimation (the actual number of underestimated cases is 768.4/year), our study provides strong and compelling evidence for evaluating this important matter.
Epidemiology of nontraumatic ONFH in Japan 281
DOI 10.3109/14397595.2014.932038
In conclusion, we estimated the annual number of nontraumatic ONFH in Aichi Prefecture at 138.5 patients. Thus the annual incidence rate in Japan (population 128 million) was 1.91/100,000.
18.
Acknowledgments
19.
The senior authors (Y. Hasegawa and T. Seki) have received funding from a research grant for the Research on Idiopathic Osteonecrosis of the Femoral Head and the Research on Epidemiology of Intractable Diseases from the Ministry of Health, Labor and Welfare of Japan.
20.
Conflict of interest N. Ishiguro has received research funding from Takeda, MitsubishiTanabe, Astellas, Chugai, Abbott, Bristol-Myers Squibb, Eisai, Daiichi Sankyo Company Ltd,Janssen, Kaken and Pfizer and has served on speaker bureaus for Daiichi Sankyo Company Ltd, Takeda Pharmaceutical Co Ltd, Hisamitsu Pharmaceutical Co Inc, Otsuka Pharmaceutical Co Ltd, Taisho Toyama Pharmaceutical Co Ltd, Kaken Pharmaceutical Co Ltd, Eisai Co Ltd, Janssen Pharmaceutical K.K, Bristol-Myers Squibb, Abbott Japan, Chugai Pharmaceutical Co Ltd, Mitsubishi Tanabe Pharmaceutical, UCB Japan, Astellas Pharma Inc., and Pfizer Japan Inc.
References 1. Jergesen HE, Khan AS. The natural history of untreated asymptomatic hips in patients who have non-traumatic osteonecrosis. J Bone Joint Surg Am. 1997;79(3):359–63. 2. Ohzono K, Saito M, Takaoka K, Ono K, Saito S, Nishina T, Kadowaki T. Natural history of nontraumatic avascular necrosis of the femoral head. J Bone Joint Surg Br. 1991;73(1):68–72. 3. Ito H, Matsuno T, Omizu N, Aoki Y, Minami A. Mid-term prognosis of non-traumatic osteonecrosis of the femoral head. J Bone Joint Surg Br. 2003;85(6):796–801. 4. Glueck CJ, Freiberg R, Tracy T, Stroop D, Wang P. Thrombophilia and hypofibrinolysis. Clin Orthop Relat Res. 1997;334:43–56. 5. Kerachian MA, Séguin C, Harvey EJ. Glucocorticoids in osteonecrosis of the femoral head: a new understanding of the mechanisms of action. J Steroid Biochem Mol Biol. 2009;114(3–5):121–8. 6. Lee JS, Koo KH, Ha YC, Koh KK, Kim SJ, Kim JR, et al. Role of thrombotic and fibrinolytic disorders in osteonecrosis of the femoral head. Clin Orthop Relat Res. 2003;417:270–6. 7. Hungerford DS, Zizic TM. Alcoholism associated ischemic necrosis of the femoral head: Early diagnosis and treatment. Clin Orthop Relat Res. 1978;130:144–53. 8. Mankin HJ. Nontraumatic necrosis of bone (osteonecrosis). N Engl J Med. 1992;326(22):1473–9. 9. Mont MA, Hungerford DS. Non-traumatic avascular necrosis of the femoral head. J Bone Joint Surg Am. 1995;77(3):459–74. 10. Hirota Y, Hirohata T, Fukuda K, Mori M, Yanagawa H, Ohno Y, Sugioka Y. Association of alcohol intake, cigarette smoking, and occupational status with the risk of idiopathic osteonecrosis of the femoral head. Am J Epidemiol. 1993;137(5):530–8. 11. Takahashi S, Fukushima W, Kubo T, Iwamoto Y, Hirota Y, Nakamura H. Pronounced risk of nontraumatic osteonecrosis of the femoral head among cigarette smokers who have never used oral corticosteroids: a multicenter case-control study in Japan. J Orthop Sci. 2012;17(6):730–6. 12. Mitchell MD, Kundel HL, Steinberg ME, Kressel HY, Alavi A, Axel L. Avascular necrosis of the hip: comparison of MR, CT, and scintigraphy. AJR Am J Roentgenol.1986;147(1):67–71. 13. Sakamoto M, Shimizu K, Iida S, Akita T, Moriya H, Nawata Y. Osteonecrosis of the femoral head: a prospective study with MRI. J Bone Joint Surg Br. 1997;79(2):213–9. 14. Malizos KN, Karantanas AH, Varitimidis SE, Dailiana ZH, Bargiotas K, Maris T. Osteonecrosis of the femoral head: etiology, imaging and treatment. Eur J Radiol. 2007;63(1):16–28. 15. Nagasawa K, Tada Y, Koarada S, Horiuchi T, Tsukamoto H, Murai K, et al. Very early development of steroid-associated osteonecrosis of femoral head in systemic lupus erythematosus: prospective study by MRI. Lupus. 2005;14(5):385–90. 16. Mont MA, Carbone JJ, Fairbank AC. Core decompression versus nonoperative management for osteonecrosis of the hip. Clin Orthop Relat Res. 1996;324:169–78. 17. Sugioka Y, Hotokebuchi T, Tsutsui H. Transtrochanteric anterior rotational osteotomy for idiopathic and steroid-induced necrosis of the
21. 22.
23.
24. 25. 26. 27. 28. 29. 30. 31. 32.
33. 34.
35. 36.
37.
38. 39.
femoral head. Indication and long term results. Clin Orthop Relat Res. 1992;277:111–20. Atsumi T, Muraki M, Yoshihara S, Kajihara T. Posterior rotational osteotomy for the treatment of femoral head osteonecrosis. Arch Orthop Trauma Surg. 1999;119(7–8):388–93. Hasegawa Y, Iwata H, Torii S, Iwase T, Kawamoto K, Iwasada S. Vascularized pedicle bone-grafting for nontraumatic avascular necrosis of the femoral head. A 5- to 11-year follow-up. Arch Orthop Trauma Surg. 1997;116(5):251–8. Hasegawa Y, Sakano S, Iwase T, Iwasada S, Torii S, Iwata H. Pedicle bone grafting versus transtrochanteric rotational osteotomy for avascular necrosis of the femoral head. J Bone Joint Surg Br. 2003;85(2):191–8. Sakano S, Hasegawa Y, Torii Y, Kawasaki M, Ishiguro N. Curved intertrochanteric varus osteotomy for osteonecrosis of the femoral head. J Bone Joint Surg Br. 2004;86(3):359–65. Solarino G, Piazzolla A, Notarnicola A, Moretti L, Tafuri S, De Giorgi S, Moretti B. Long-term results of 32-mm alumina-onalumina THA for avascular necrosis of the femoral head. J Orthop Traumatol. 2012;13(1):21–7. Gangji V, De Maertelaer V, Hauzeur JP. Autologous bone marrow cell implantation in the treatment of non-traumatic osteonecrosis of the femoral head: Five year follow-up of a prospective controlled study. Bone. 2011;49(5):1005–9. Lee SB, Sugano N, Nakata K, Matsui M, Ohzono K. Comparison between bipolar hemiarthroplasty and THA for osteonecrosis of the femoral head. Clin Orthop Relat Res. 2004;424:161–5. Mont MA, Jones LC, Hungerford DS. Nontraumatic osteonecrosis of the femoral head: ten years later. J Bone Joint Surg Am. 2006;88(5):1117–32. Yamaguchi R, Yamamoto T, Motomura G, Ikemura S, Iwamoto Y. Incidence of nontraumatic osteonecrosis of the femoral head in the Japanese population. Arthritis Rheum. 2011;63(10):3169–73. Fukushima W, Fujioka M, Kubo T, Tamakoshi A, Nagai M, Hirota Y. Nationwide epidemiologic survey of idiopathic osteonecrosis of the femoral head. Clin Orthop Relat Res. 2010;468(10):2715–24. Kang JS, Park S, Song JH, Jung YY, Cho MR, Rhyu KH. Prevalence of osteonecrosis of the femoral head: a nationwide epidemiologic analysis in Korea. J Arthroplasty. 2009;24(8):1178–83. Yamamoto T, Bullough PG. Subchondral insufficiency fracture of the femoral head: a differential diagnosis in acute onset of coxarthrosis in the elderly. Arthritis Rheum. 1999;42(12):2719–23. Sugano N, Atsumi T, Ohzono K, Kubo T, Hotokebuchi T, Takaoka K. The 2001 revised criteria for diagnosis, classification, and staging of idiopathic osteonecrosis of the femoral head. J Orthop Sci. 2002;7(5):601–5. Sugano N, Kubo T, Takaoka K, Ohzono K, Hotokebuchi T, Matsumoto T, et al. Diagnostic criteria for non-traumatic osteonecrosis of the femoral head. A multicenter study. J Bone Joint Surg Br. 1999;81(4):590–595. Oinuma K, Harada Y, Nawata Y, Takabayashi K, Abe I, Kamikawa K, Moriya H. Osteonecrosis in patients with systemic lupus erythematosus develops very early after starting high dose corticosteroid treatment. Ann Rheum Dis. 2001;60(12):1145–8. Gladman DD, Chaudhry-Ahluwalia V, Ibañez D, Bogoch E, Urowitz MB. Outcomes of symptomatic osteonecrosis in 95 patients with systemic lupus erythematosus. J Rheumatol. 2001;28(10):2226–9. Kubo T, Yamazoe S, Sugano N, Fujioka M, Naruse S, Yoshimura N, Hirasawa Y. Initial MRI findings of non-traumatic osteonecrosis of the femoral head in renal allograft recipients. Magn Reson Imaging. 1997;15(9):1017–23. Torii Y, Hasegawa Y, Kubo T, Kodera Y, Minami S, Morishita Y, et al. Osteonecrosis of the femoral head after allogeneic bone marrow transplantation. Clin Orthop Relat Res. 2001;382: 124–32. Yildirim ZK, Büyükavci M, Eren S, Orbak Z, Sahin A, Karakelleoğlu C. Late side effects of high-dose steroid therapy on skeletal system in children with idiopathic thrombocytopenic purpura. J Pediatr Hematol Oncol. 2008;30(10):749–753. Shigemura T, Nakamura J, Kishida S, Harada Y, Ohtori S, Kamikawa K, et al. Incidence of osteonecrosis associated with corticosteroid therapy among different underlying diseases: prospective MRI study. Rheumatology (Oxford). 2011;50(11):2023–8. Ministry of Health, Labour and Welfare. Japan Intractable Diseases Information Center. Health administration reported case. [Statistics Japan] URL: http://www.nanbyou.or.jp/ [accessed 2014-01-15] Yamamoto T, Iwamoto Y, Schneider R, Bullough PG. Histopathological prevalence of subchondral insufficiency fracture of the femoral head. Ann Rheum Dis. 2008;67(2):150–3.
Copyright of Modern Rheumatology (Informa Healthcare) is the property of Informa Healthcare and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
