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Review Article

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Hip Pelvis 2023; 35(3): 147-156

Published online September 30, 2023

https://doi.org/10.5371/hp.2023.35.3.147

© The Korean Hip Society

Updating Osteonecrosis of the Femoral Head

Young-Seung Ko, MD* , Joo Hyung Ha, MD† , Jung-Wee Park, MD* , Young-Kyun Lee, MD* , Tae-Young Kim, MD‡ , Kyung-Hoi Koo, MD*,§

Author Affiliations
Department of Orthopaedic Surgery, Seoul National University Bundang Hospital, Seongnam, Korea*
Department of Orthopaedic Surgery, Gumdan Top General Hospital, Incheon, Korea†
Department of Orthopaedic Surgery, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea‡
Kay Joint Center at Cheil Orthopaedic Hospital, Seoul, Korea§

Correspondence to : Tae-Young Kim, MD
(https://orcid.org/0000-0003-2028-0460)
Department of Orthopaedic Surgery, Konkuk University Medical Center, Konkuk University School of Medicine, 120-1 Neungdongro, Gwangjin-gu, Seoul 05030, Korea
TEL: +82-2-2030-8146
E-mail: syty-chan@hanmail.net

Young-Seung Ko and Joo Hyung Ha contributed equally to this study as co-first authors.

Received: January 27, 2023; Revised: June 16, 2023; Accepted: June 16, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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Osteonecrosis of the femoral head (ONFH), a condition characterized by the presence of a necrotic bone lesion in the femoral head, is caused by a disruption in the blood supply. Its occurrence is more common in young and middle-aged adults and it is the main reason for performance of total hip arthroplasty in this age group. Its incidence is increasing along with increased use of glucocorticoids for management of adjuvant therapy for treatment of leukemia as well as organ transplantation and other myelogenous diseases. Current information on etiology and pathogenesis, as well as natural history, stage system, and treatments is provided in this review. A description of the Association Research Circulation Osseous (ARCO) criteria for classification of glucocorticoids- and alcohol-associated ONFH, 2019 ARCO staging system, and 2021 ARCO classification using computed tomography for the early stages of ONFH is also provided.

Keywords Femur head necrosis, Etiology, Pathogenesis, Staging, Classification

INTRODUCTION

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Osteonecrosis of the femoral head (ONFH), a condition characterized by the presence of a necrotic bone lesion in the femoral head, is caused by a disruption in the blood supply1). The incidence of ONFH is increasing worldwide, particularly among young and middle-aged individuals2,3,4,5). In the United States alone, the estimated annual occurrence of ONFH is approximately 15,000 to 20,000 new cases2,6). Similar trends have been reported in East Asian countries including Japan, and China, where significant numbers of individuals are affected by this condition4,5,6,7). In South Korea, more than 10,000 new cases of ONFH have been reported annually7,8).

Trauma, such as a displaced fracture of the femoral neck or hip dislocation, can damage local blood vessels and compromise the supply of blood to the femoral head, leading to development of ONFH9). In addition, non-traumatic risk factors associated with ONFH include the use of corticosteroids, excessive consumption of alcohol and tobacco, certain medical conditions such as sickle cell disease and systemic lupus erythematosus (SLE), as well as factors such as organ transplantation, HIV (human immunodeficiency virus) infection, coagulation disorders, genetic factors, Caisson disease (divers), myeloproliferative diseases, and radiation necrosis9,10,11,12,13,14).

Once ONFH has developed, the size and location of the necrotic portion are critical in determining the risk of femoral head collapse2,15). The prognosis may be better for small lesions, which sometimes remain stable without progressing, while progression to collapse is more likely with larger lesions involving the weight-bearing area of the femoral head, leading to development of secondary arthritis of the hip16,17,18,19).

Accurate evaluation and classification of the size and location of the necrotic lesions is important to the process of making appropriate decisions regarding treatment. Lesions that differ in size may require different treatment approaches with the aim of preserving the femoral head and preventing collapse. Accurate assessment of the necrotic portion can be helpful in determining the optimal treatment strategy for each individual case, with the aim of preventing further deterioration and preserving hip joint function15,20,21,22).

In this review, we have updated current information on the etiology and pathogenesis of the disease, criteria for classification of alcohol and glucocorticoid associated ONFH, staging system, classification for early-stage ONFH, and treatments.

ETIOLOGY

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Caisson disease, dysbaric ONFH in divers, was first reported in 195223). The association of glucocorticoid use and ONFH was reported in 195724). Bone necrosis in patients with sickle cell disease was reported in the 1950s25). Excessive alcohol use had been recognized as a risk factor for ONFH by the 1960s26). Since 1990, association of hypofibrinolysis, thrombophilia, and impaired angiogenesis due to abnormal enzymes and various polymorphisms with ONFH has been reported26,27). Involvement of protein S and protein C deficiencies27,28,29,30), presence of antiphospholipid antibodies31,32), mutations in the factor V Leiden or the prothrombin 20210A gene33), polymorphisms of the plasminogen activator inhibitor-1 gene (PAI-1)34,35), and diminished activity of 5,10-methylenetetrahydrofolate reductase (MTHFR) in hypofibrinolysis/hypercoagulability has been reported35). An association of polymorphisms of vascular endothelial growth factor (VEGF) and polymorphism in the endothelial nitric oxide synthase gene with impaired angiogenesis has been reported21,36,37,38,39).

In addition, smoking, pelvic radiation therapy, non-glucocorticoid chemotherapeutics, HIV infection, rheumatic disease, Gaucher’s disease, SLE, and pancreatitis have also been reported as associated conditions or risk factors for ONFH40).

In 2019, a Delphi survey was conducted by Association Research Circulation Osseous (ARCO) in order to develop criteria for classification of alcohol-associated and glucocorticoid-associated ONFH. The ARCO criteria for classification of alcohol-associated ONFH were as follows: (1) patients must have a history of alcohol consumption >400 mL/week (320 g/week, any alcoholic drink); (2) diagnosis of ONFH must occur within one year after consuming this amount of alcohol; and (3) patients must not have any risk factors other than alcohol abuse11). The ARCO criteria for classification of glucocorticoid-associated ONFH were as follows: (1) patients must have taken glucocorticoids that totaled more than 2 g of prednisolone or its equivalent in the previous three months; (2) diagnosis of osteonecrosis must occur within two years of glucocorticoid usage; and (3) other than glucocorticoids, patients should have no other risk factors10).

PATHOGENESIS

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The pathogenesis of ONFH is complex and research is ongoing. However, over the past three decades, knowledge of the pathophysiology of the disease has shown significant advancement, and various consensuses have been reached.

First, ONFH has a multi-factorial etiology involving exposure to risk factors and genetic predispositions. Reciprocal interaction and cooperation occurs among these elements in the pathogenesis9,12,41). This genetic predisposition explains why the condition affects some users of glucocorticoids and alcoholics while it may not affect others. Second, the first event of ischemia occurs in the marrow space, not inside the vessel. Third, the process of pathogenesis involves (1) bone marrow necrosis and death of osteocytes, (2) a fibrovascular healing process in the area surrounding the necrotic marrow zone, (3) fracture and collapse of an osteonecrotic lesion, and (4) secondary osteoarthritis of the hip9,12,41).

A reliable model of the pathophysiology of non-traumatic ONFH was presented by ARCO in 20199). Mesenchymal stem cells differentiating to adipocytes are stimulated by glucocorticoids and alcohol, leading to activation of intracellular synthesis of lipids and induction of adipocyte hypertrophy 42,43, 44). An increase in the number and volume of marrow fat cells results in intraosseous hypertension in the femoral head, which causes squeezing of the venous sinusoids and intravascular coagulation. This leads to restriction of arterial blood flow, resulting in ischemic alternations in the femoral head. Marrow adipocytes die within two days of developing ischemia. The ischemia is usually recovered by thrombolysis and angiogenesis, and the presence of lesions does not lead to irreversible necrosis. However, in cases of ischemia that is sustained for two to five days, osteocytes die and vanish completely within 2-4 weeks, leaving a sequestrum. Because gradual replacement of dead bone with new bone does not occur, a foreign body reaction occurs in the area surrounding the sequestrum, resulting in the formation of fibrovascular tissue that encapsulates the lesion. Histologic criteria for ONFH include marrow necrosis, osteocyte death, and encapsulating fibrovascular tissue. Advancement of the ischemic lesion is determined by the restoration of vascular perfusion. Restoration of vascular perfusion is hindered by hypercoagulability/hypo-fibrinolysis genetic predispositions and/or hypoangiogenesis (Fig. 1)9,12,41).

NATURAL HISTORY ACCORDING TO SIZE AND LOCATION OF OSTEONECROSIS

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The fate of ONFH is largely determined by the size and location of osteonecrosis. The risk of femoral head collapse is influenced by the size and location of the necrotic portion. Even without medical or surgical treatment, collapse of small lesions seldom occurs, whereas progression of large lesions is more likely, leading to collapse of the femoral head16,18,19). Once ONFH has developed, the size of the necrotic lesion remains stable and does not increase regardless of the progression of the disease45). This means that expansion or enlargement of the necrotic portion does not occur over time during the disease course. Thus, measurement of the size of osteonecrosis should be performed prior to planning treatment for ONFH patients, and small osteonecrosis lesions should not be treated. Therefore, cautious assessment based on the size of the necrosis and the predicted course of the condition is necessary for determining the most appropriate treatment approach for each individual.

ARCO STAGING

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The first ARCO ONFH staging system was developed in 1994. However, it had been reported that progression of a stage 0 lesion: marrow necrosis with viable osteocytes to definite osteonecrosis does not occur41). Thus, the ONFH staging system was updated by ARCO in 2019. In the 2019 revised version of the staging system, stage III was divided into two parts: early IIIA and late IIIB based on a head depression depth of 2 mm, sub-classification of size and location was not included, and stage 0 was removed (Fig. 2, Table 1)46).

ARCO CLASSIFICATION OF SIZE AND LOCATION OF NECROSIS IN EARLY STAGE ONFH

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Various systems for classification of ONFH have been introduced in order to characterize the extent and location of osteonecrosis. There are currently three classification systems that are frequently employed, Japanese Investigation Committee (JIC) classification, Steinberg classification, and modified Kerboul classification.

However, there is no consensus regarding which method is universally acknowledged. Development of a unified system for classifying the amount and location of osteonecrosis was required. A novel system for classification of necrotic size and location in the early stage of ONFH (pre-collapse) was developed by ARCO in 2021. Using that classification, necrotic lesions were classified into three types: type 1 is a small lesion, where the lateral necrotic margin is medial to the apex of the femoral head; type 2 is a medium-sized lesion, with the lateral necrotic margin located between the apex of the femoral head and the lateral acetabular edge; and type 3 is a large lesion, which extends outside the lateral acetabular edge (Fig. 3). The 2021 ARCO classification is considered highly reliable and valid and use of this method as a unified system for classification of ONFH in the early stages is recommended by ARCO47).

TREATMENTS

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Determining the treatment approach for ONFH is based on the size and location of the necrotic lesion, as well as the risk of progression to femoral head collapse. It should be noted that progression to collapse does not often occur with small lesions even without medical or surgical intervention, whereas progressive deterioration is more likely to occur with larger lesions16,18,19). The extent of the necrotic portion is typically established during the ischemic attack, so that once ONFH has developed, the size of the lesion remains constant regardless of disease progression stage45). Consequently, evaluating the size of the necrotic portion prior to initiating treatment is essential, and caution should be exercised in determining the effectiveness of specific treatment modalities, with consideration for the varying natural courses based on the size and location of the necrotic lesion.

1. Medical Treatments

Several pharmacological agents including enoxaparin, statins, bisphosphonates, iloprost, and acetylsalicylic acid have been evaluated for their potential to slow down or reverse the progression of ONFH48,49,50,51,52,53,54). However, it is important to note that the effectiveness of these agents has not been conclusively proven based on high-level evidence20). In addition, many of these pharmacological interventions have shown an association with adverse reactions or side effects.

Consequently, there is currently no recommended pharmacological approach for the prevention or treatment of ONFH. Conduct of additional research and clinical trials will be required in order to verify the efficacy and safety of potential pharmacological interventions for treatment of this condition.

2. Core Decompression and Bone Marrow Aspirate Concentration

Core decompression (CD), a surgical technique, is commonly used in the early stages of ONFH, with the aim of preventing collapse of the femoral head and potentially reversing the disease progression. However, results regarding the efficacy of CD have been inconsistent, leading to questions about its effectiveness55). In recent years, use of the combination of CD with bone marrow aspirate concentration (BMAC) therapy as a potential improvement has been evaluated. Earlier studies suggested that enhanced treatment outcomes could be achieved with the addition of cell therapy through BMAC56,57,58,59,60,61). However, more recent studies have reported no significant differences in outcomes between CD with BMAC and CD alone. In addition, high rates of progression have been observed in large lesions with use of both CD and BMAC therapies62,63,64). The effectiveness of BMAC remains controversial and further research will be required in order to clarify its role in the treatment of ONFH.

3. Osteotomies

Several procedures for osteotomy of the proximal femur have been introduced in the effort to preserve osteonecrotic hips. These procedures involve relocating the necrotic portion from the weight-bearing dome to a non-weight-bearing region. Certain factors, including the patient’s age (under 40 years), body mass index (below 24 kg/m2), stage of the disease (ARCO stage 3A or 3B)16,18,46,65), and size of the necrotic portion (medium-sized lesion), should be considered when selecting candidates for osteotomy. These criteria can be helpful in identifying suitable candidates for osteotomy procedures.

Among these types of osteotomy, transtrochanteric curved varus osteotomy (TCVO) and transtrochanteric rotational osteotomy (TRO) have been predominantly performed in Japan and South Korea66). A study conducted by Lee et al.67) in 2017 compared the outcomes of 91 TROs and 65 TCVOs. According to the results, various aspects of TCVO were found to be superior to those of TRO. Shorter operation times, less blood loss, lower rates of postoperative collapse, decreased osteoarthritic changes (20% vs. 37.4%), and a lower rate of conversion to total hip arthroplasty (THA) (10.8% vs. 16.5%) were obtained with use of TCVO. Based on these findings, TCVO was recommended as the preferred option over TRO.

4. Vascularized Bone Grafts

The technique of vascularized fibular grafting was initially introduced by Judet et al.68) in 1980 and later gained popularity through the work of Urbaniak et al.69) and Yoo et al.70). Another approach, vascularized iliac bone grafting with a pedicle of the iliac circumflex artery, has also been favored due to its proximity to the femoral head and the absence of microsurgical anastomosis71). However, despite their potential benefits, vascularized bone graft procedures have been criticized for their technical complexities and associated donor site morbidities. As a result, use of these procedures is currently limited to a select few specialized centers worldwide where they are performed by experienced surgeons.

5. Resurfacing Arthroplasty

Hip resurfacing arthroplasty (HRA) is regarded as an alternative to THA, particularly in younger patients who wish to maintain high levels of activity after surgery72,73). HRA involves the removal of the damaged surface of the femoral head and the placement of a metal cap, while preserving the femoral neck. Use of this technique enables the preservation of more bone stock compared to THA, which involves the complete removal and replacement of the femoral head.

The potential for improved range of motion and function is a main advantage of HRA compared to THA. The preservation of the femoral neck with use of HRA allows for a more natural anatomy and can potentially reduce the risk of dislocation. In addition, use of HRA with the larger femoral head size can result in enhanced stability and contribute to better hip kinematics.

However, the risk of complications specific to HRA, such as femoral neck fractures and issues related to metal-on-metal bearing surfaces, including metal ion release and adverse local tissue reactions, may be increased74,75,76). Careful discussion of these factors with the patient is required, and their individual suitability for HRA should be thoroughly evaluated. The use of HRA in the treatment of ONFH has declined significantly as a result of these concerns and complications.

6. THA Using Highly Cross-Linked Polyethylene Liners

The use of more durable bearing materials has gained traction in response to concerns over excessive wear rates and osteolysis associated with conventional polyethylene bearings in young patients77). Highly cross-linked polyethylene (HXLPE), with enhanced wear resistance, has rapidly replaced conventional polyethylene in many cases. The crosslinking process involves exposing the polyethylene to ionizing radiation during manufacturing, which increases the number of crosslinks and reduces wear. Current crosslinking techniques utilize gamma-rays instead of electron beam irradiation, followed by annealing or remelting of the polyethylene78).

HXLPE can be combined with either cobalt chromium or ceramic femoral heads. Promising clinical and radiological results have been reported from short-term and mid-term follow-up studies on the use of HXLPE liners in patients with ONFH79,80). In addition, recent long-term follow-up studies have reported a good survival rate for THA with HXLPE liners81,82,83). Conduct of additional research and long-term studies will be necessary in order to evaluate the durability and longevity of HXLPE.

7. THA Using Ceramic-on-Ceramic Bearings

The lowest wear rates have been reported for ceramic-on-ceramic (CoC) bearings compared to other bearing materials77). However, the use of CoC bearings is associated with specific complications. The implementation of these bearings has led to concerns regarding fractures of ceramic components as well as audible squeaking noises84,85).

Despite these potential complications, several studies have reported promising outcomes at mid-term and long-term follow-up with use of CoC THA in patients with ONFH86,87,88,89,90). Favorable results in terms of wear reduction and improved longevity have been reported with the use of CoC bearings. A further decrease in the incidence of ceramic fractures as well as enhanced performance of CoC THA is expected with the introduction of newer ceramic materials, such as the delta ceramic91).

However, it is important to note that there is still no knowledge regarding the long-term outcomes of CoC THA for treatment of ONFH. Continued research and conduct of long-term studies will be necessary for evaluation of the durability, complications, and overall success of CoC bearings in the treatment of ONFH.

SUMMARY

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Exposure to risk factors and genetic predispositions can influence the development of ONFH. The size and location of the osteonecrosis is the primary factor influencing the rapidity of disease progression. The size of osteonecrosis is determined during the initial ischemic episode and is not altered. Advancement of small lesions of osteonecrosis does not occur even without intervention, therefore they do not require therapy, whereas most large lesions result in collapse of the femoral head. Medical or surgical treatment may be required for painful ONFH hips with medium-to-large sized lesions. During the last five years, ARCO developed criteria for classification of glucocorticoid-and alcohol-associated osteonecrosis, revised the system for staging ONFH, and developed a system for classification of size/location for early stage ONFH. ARCO has recommended the use of these new systems as unified classification and staging systems. Small lesions in ONFH do not progress and therefore treatment is typically not required. Medical or surgical interventions may be helpful in management of medium-sized to large lesions with accompanying pain. Proven efficacy has not been demonstrated for pharmacological treatments. CD combined with BMAC therapy may not be effective in treatment of large lesions and conduct of additional research will be required. The decision to perform osteotomy should be the result of a selective process. Selective consideration and deliberation are required for HRA. Despite promising outcomes of THA with HXLPE or CoC bearings in the short to medium term, results from long-term follow-up are still anticipated.

CONFLICTS OF INTEREST

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CONFLICT OF INTEREST: Young-Kyun Lee has been an editorial board member since January 2023, but had no role in the decision to publish this article. No other potential conflict of interest relevant to this article was reported.

FIGURES

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Fig. 1.

Summary of the pathophysiology of non-traumatic osteonecrosis of the femoral head.


Fig. 2.

The 2019 ARCO (Association Research Circulation Osseous) staging system for osteonecrosis of the femoral head. (A) Stage I. (B) Stage II. (C) Stage IIIA. (D) Stage IIIB. (E) Stage IV.


Fig. 3.

The 2021 ARCO (Association Research Circulation Osseous) classification for osteonecrosis of the femoral head in the early stages (computed tomography-based): (A) Type 1 is a small lesion that is restricted medial to the apex of the femoral head; (B) Type 2 is a medium-sized lesion where the lateral margin of the necrotic portion is located between the apex of the femoral head and the lateral edge of the acetabulum; and (C) Type 3 is a large lesion that extends laterally to the lateral edge of the acetabulum.


TABLES

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Table 1. The 2019 Revised ARCO Staging for Osteonecrosis of the Femoral Head

ARCO stageImage findings
IX-ray: normal
MRI: low-signal band on T1-weighted MRI
IIX-ray: abnormal
MRI: abnormal
IIISubchondral fracture on X-ray or CT
IIIA (early)Femoral head depression≤2 mm
IIIB (late)Femoral head depression >2 mm
IVX-ray: osteoarthritis

ARCO: Association Research Circulation Osseous, MRI: magnetic resonance imaging, CT: computed tomography.

REFERENCES

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  1. Arlet J. Nontraumatic avascular necrosis of the femoral head. Past, present, and future. Clin Orthop Relat Res 1992;:12-21.
  2. Mont MA, Cherian JJ, Sierra RJ, Jones LC, Lieberman JR. Nontraumatic osteonecrosis of the femoral head: where do we stand today? A ten-year update. J Bone Joint Surg Am 2015;97:1604-1627.
    Pubmed CrossRef
  3. Park JW, Won SH, Moon SY, Lee YK, Ha YC, Koo KH. Burden and future projection of revision Total hip Arthroplasty in South Korea. BMC Musculoskelet Disord 2021;22:375.
    Pubmed CrossRef
  4. van der Jagt D, Mokete L, Pietrzak J, Zalavras CG, Lieberman JR. Osteonecrosis of the femoral head: evaluation and treatment. J Am Acad Orthop Surg 2015;23:69-70.
    Pubmed CrossRef
  5. 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;63:3169-3173.
    Pubmed CrossRef
  6. Moya-Angeler J, Gianakos AL, Villa JC, Ni A, Lane JM. Current concepts on osteonecrosis of the femoral head. World J Orthop 2015;6:590-601.
    Pubmed CrossRef
  7. 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;24:1178-1183.
    Pubmed CrossRef
  8. Park JW, Kim HS, Park S, Kim SH, Lee YK, Koo KH. Trends in surgical treatment of femoral head osteonecrosis in South Korea: an analysis using nationwide claims database. Clin Orthop Surg 2022;14:500-506.
    Pubmed CrossRef
  9. Cui Q, Jo WL, Koo KH, et al. ARCO consensus on the pathogenesis of non-traumatic osteonecrosis of the femoral head. J Korean Med Sci 2021;36:e65.
    Pubmed CrossRef
  10. Yoon BH, Jones LC, Chen CH, et al. Etiologic classification criteria of ARCO on femoral head osteonecrosis part 1: glucocorticoid-associated osteonecrosis. J Arthroplasty 2019;34:163-168.e1.
    Pubmed CrossRef
  11. Yoon BH, Jones LC, Chen CH, et al. Etiologic classification criteria of ARCO on femoral head osteonecrosis part 2: alcohol-associated osteonecrosis. J Arthroplasty 2019;34:169-174.e1.
    Pubmed CrossRef
  12. Seamon J, Keller T, Saleh J, Cui Q. The pathogenesis of nontraumatic osteonecrosis. Arthritis 2012;2012:601763.
    Pubmed CrossRef
  13. Mont MA, Salem HS, Piuzzi NS, Goodman SB, Jones LC. Nontraumatic osteonecrosis of the femoral head: where do we stand today?: a 5-year update. J Bone Joint Surg Am 2020;102:1084-1099.
    Pubmed CrossRef
  14. Ikeuchi K, Hasegawa Y, Seki T, Takegami Y, Amano T, Ishiguro N. Epidemiology of nontraumatic osteonecrosis of the femoral head in Japan. Mod Rheumatol 2015;25:278-281.
    Pubmed CrossRef
  15. Karantanas AH. Accuracy and limitations of diagnostic methods for avascular necrosis of the hip. Expert Opin Med Diagn 2013;7:179-187.
    Pubmed CrossRef
  16. Ha YC, Jung WH, Kim JR, Seong NH, Kim SY, Koo KH. Prediction of collapse in femoral head osteonecrosis: a modified Kerboul method with use of magnetic resonance images. J Bone Joint Surg Am 2006;88 Suppl 3:35-40.
    CrossRef
  17. Kim YM, Ahn JH, Kang HS, Kim HJ. Estimation of the extent of osteonecrosis of the femoral head using MRI. J Bone Joint Surg Br 1998;80:954-958.
    Pubmed CrossRef
  18. 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;7:601-605.
    Pubmed CrossRef
  19. Steinberg ME, Hayken GD, Steinberg DR. A quantitative system for staging avascular necrosis. J Bone Joint Surg Br 1995;77:34-41.
    Pubmed CrossRef
  20. Lee YJ, Cui Q, Koo KH. Is there a role of pharmacological treatments in the prevention or treatment of osteonecrosis of the femoral head?: a systematic review. J Bone Metab 2019;26:13-18.
    Pubmed CrossRef
  21. Hines JT, Jo WL, Cui Q, et al. Osteonecrosis of the femoral head: an updated review of ARCO on pathogenesis, staging and treatment. J Korean Med Sci 2021;36:e177.
    Pubmed CrossRef
  22. Lee YK, Lee B, Parvizi J, Ha YC, Koo KH. Which osteotomy for osteonecrosis of the femoral head and which patient for the osteotomy?. Clin Orthop Surg 2019;11:137-141.
    Pubmed CrossRef
  23. Dale T. Bone necrosis in divers; caisson disease. Acta Chir Scand 1952;104:153-156.
    Pubmed
  24. Ravault PP, Lejeune E, Colomb D, Fries D. [Osteonecrosis of the femur head associated with corticotherapy]. Rev Rhum Mal Osteoartic 1962;29:546-550
    Pubmed
  25. Chung SM, Ralston EL. Necrosis of the femoral head associated with sickle-cell anemia and its genetic variants. A review of the literature and study of thirteen cases. J Bone Joint Surg Am 1969;51:33-58.
    Pubmed
  26. Arlet J, Franck JL, Nghiem L, Solera ML, de Graeve J. [Multiple bone necroses and familial type I hyperlipemia. Apropos of a case report]. Rev Rhum Mal Osteoartic 1983;50:149-153
    Pubmed
  27. Pierre-Jacques H, Glueck CJ, Mont MA, Hungerford DS. Familial heterozygous protein-S deficiency in a patient who had multifocal osteonecrosis. A case report. J Bone Joint Surg Am 1997;79:1079-1084.
    Pubmed CrossRef
  28. Glueck CJ, Freiberg R, Tracy T, Stroop D, Wang P. Thrombophilia and hypofibrinolysis: pathophysiologies of osteonecrosis. Clin Orthop Relat Res 1997;:43-56.
    Pubmed
  29. Jones LC, Mont MA, Le TB, et al. Procoagulants and osteonecrosis. J Rheumatol 2003;30:783-791.
    Pubmed
  30. Zalavras CG, Vartholomatos G, Dokou E, Malizos KN. Genetic background of osteonecrosis: associated with thrombophilic mutations?. Clin Orthop Relat Res 2004;:251-255.
  31. Korompilias AV, Gilkeson GS, Ortel TL, Seaber AV, Urbaniak JR. Anticardiolipin antibodies and osteonecrosis of the femoral head. Clin Orthop Relat Res 1997;:174-180.
  32. Seleznick MJ, Silveira LH, Espinoza LR. Avascular necrosis associated with anticardiolipin antibodies. J Rheumatol 1991;18:1416-1417.
    Pubmed
  33. Björkman A, Svensson PJ, Hillarp A, Burtscher IM, Rünow A, Benoni G. Factor V leiden and prothrombin gene mutation: risk factors for osteonecrosis of the femoral head in adults. Clin Orthop Relat Res 2004;:168-172.
  34. Glueck CJ, Fontaine RN, Gruppo R, et al. The plasminogen activator inhibitor-1 gene, hypofibrinolysis, and osteonecrosis. Clin Orthop Relat Res 1999;:133-146.
    Pubmed CrossRef
  35. Glueck CJ, Freiberg RA, Fontaine RN, Tracy T, Wang P. Hypofibrinolysis, thrombophilia, osteonecrosis. Clin Orthop Relat Res 2001;:19-33.
    Pubmed CrossRef
  36. Glueck CJ, Freiberg RA, Boppana S, Wang P. Thrombophilia, hypofibrinolysis, the eNOS T-786C polymorphism, and multifocal osteonecrosis. J Bone Joint Surg Am 2008;90:2220-2229.
    Pubmed CrossRef
  37. Kim T, Hong JM, Lee J, et al. Promoter polymorphisms of the vascular endothelial growth factor gene is associated with an osteonecrosis of the femoral head in the Korean population. Osteoarthritis Cartilage 2008;16:287-291.
    Pubmed CrossRef
  38. Koo KH, Lee JS, Lee YJ, Kim KJ, Yoo JJ, Kim HJ. Endothelial nitric oxide synthase gene polymorphisms in patients with nontraumatic femoral head osteonecrosis. J Orthop Res 2006;24:1722-1728.
    Pubmed CrossRef
  39. Lee YJ, Lee JS, Kang EH, et al. Vascular endothelial growth factor polymorphisms in patients with steroid-induced femoral head osteonecrosis. J Orthop Res 2012;30:21-27.
    Pubmed CrossRef
  40. Koo KH, Mont MA, Jones LC. Osteonecrosis: Springer Berlin, 2014; 2014. p. 59-139.
  41. Koo KH, Jeong ST, Jones JP. Borderline necrosis of the femoral head. Clin Orthop Relat Res 1999;:158-165.
  42. Cui Q, Wang GJ, Balian G. Steroid-induced adipogenesis in a pluripotential cell line from bone marrow. J Bone Joint Surg Am 1997;79:1054-1063.
    Pubmed CrossRef
  43. Cui Q, Wang Y, Saleh KJ, Wang GJ, Balian G. Alcohol-induced adipogenesis in a cloned bone-marrow stem cell. J Bone Joint Surg Am 2006;88 Suppl 3:148-154.
    CrossRef
  44. Wang GJ, Sweet DE, Reger SI, Thompson RC. Fat-cell changes as a mechanism of avascular necrosis of the femoral head in cortisone-treated rabbits. J Bone Joint Surg Am 1977;59:729-735.
    Pubmed
  45. Koo KH, Ahn IO, Kim R, et al. Bone marrow edema and associated pain in early stage osteonecrosis of the femoral head: prospective study with serial MR images. Radiology 1999;213:715-722.
    Pubmed CrossRef
  46. Yoon BH, Mont MA, Koo KH, et al. The 2019 revised version of Association Research Circulation Osseous staging system of osteonecrosis of the femoral head. J Arthroplasty 2020;35:933-940.
    Pubmed CrossRef
  47. Koo KH, Mont MA, Cui Q, et al. The 2021 Association Research Circulation Osseous classification for early-stage osteonecrosis of the femoral head to computed tomography-based study. J Arthroplasty 2022;37:1074-1082.
    Pubmed CrossRef
  48. Ajmal M, Matas AJ, Kuskowski M, Cheng EY. Does statin usage reduce the risk of corticosteroid-related osteonecrosis in renal transplant population?. Orthop Clin North Am 2009;40:235-239.
    Pubmed CrossRef
  49. Glueck CJ, Freiberg RA, Sieve L, Wang P. Enoxaparin prevents progression of stages I and II osteonecrosis of the hip. Clin Orthop Relat Res 2005;:164-170.
    CrossRef
  50. Glueck CJ, Freiberg RA, Wissman R, Wang P. Long term anticoagulation (4-16 years) stops progression of idiopathic hip osteonecrosis associated with familial thrombophilia. Adv Orthop 2015;2015:138382.
    Pubmed CrossRef
  51. Pengde K, Fuxing P, Bin S, Jing Y, Jingqiu C. Lovastatin inhibits adipogenesis and prevents osteonecrosis in steroid-treated rabbits. Joint Bone Spine 2008;75:696-701.
    Pubmed CrossRef
  52. Pritchett JW. Statin therapy decreases the risk of osteonecrosis in patients receiving steroids. Clin Orthop Relat Res 2001;:173-178.
    CrossRef
  53. Lai KA, Shen WJ, Yang CY, Shao CJ, Hsu JT, Lin RM. The use of alendronate to prevent early collapse of the femoral head in patients with nontraumatic osteonecrosis. A randomized clinical study. J Bone Joint Surg Am 2005;87:2155-2159.
    Pubmed
  54. Lee YK, Ha YC, Cho YJ, et al. Does zoledronate prevent femoral head collapse from osteonecrosis? A prospective, randomized, open-label, multicenter study. J Bone Joint Surg Am 2015;97:1142-1148.
    Pubmed CrossRef
  55. Yoon BH, Lee YK, Kim KC, Ha YC, Koo KH. No differences in the efficacy among various core decompression modalities and non-operative treatment: a network meta-analysis. Int Orthop 2018;42:2737-2743.
    Pubmed CrossRef
  56. Hernigou P, Dubory A, Homma Y, et al. Cell therapy versus simultaneous contralateral decompression in symptomatic corticosteroid osteonecrosis: a thirty year follow-up prospective randomized study of one hundred and twenty five adult patients. Int Orthop 2018;42:1639-1649.
    Pubmed CrossRef
  57. Kang JS, Suh YJ, Moon KH, et al. Clinical efficiency of bone marrow mesenchymal stem cell implantation for osteonecrosis of the femoral head: a matched pair control study with simple core decompression. Stem Cell Res Ther 2018;9:274.
    Pubmed CrossRef
  58. Li X, Xu X, Wu W. Comparison of bone marrow mesenchymal stem cells and core decompression in treatment of osteonecrosis of the femoral head: a meta-analysis. Int J Clin Exp Pathol 2014;7:5024-5030.
    Pubmed
  59. Ma Y, Wang T, Liao J, et al. Efficacy of autologous bone marrow buffy coat grafting combined with core decompression in patients with avascular necrosis of femoral head: a prospective, double-blinded, randomized, controlled study. Stem Cell Res Ther 2014;5:115.
    Pubmed CrossRef
  60. Sen RK, Tripathy SK, Aggarwal S, Marwaha N, Sharma RR, Khandelwal N. Early results of core decompression and autologous bone marrow mononuclear cells instillation in femoral head osteonecrosis: a randomized control study. J Arthroplasty 2012;27:679-686.
    Pubmed CrossRef
  61. Zhao D, Cui D, Wang B, et al. Treatment of early stage osteonecrosis of the femoral head with autologous implantation of bone marrow-derived and cultured mesenchymal stem cells. Bone 2012;50:325-330.
    Pubmed CrossRef
  62. Lim YW, Kim YS, Lee JW, Kwon SY. Stem cell implantation for osteonecrosis of the femoral head. Exp Mol Med 2013;45:e61.
    Pubmed CrossRef
  63. Nally FJ, Zanotti G, Buttaro MA, et al. THA conversion rate comparing decompression alone, with autologous bone graft or stem cells in osteonecrosis. Hip Int 2018;28:189-193
    Pubmed CrossRef
  64. Pepke W, Kasten P, Beckmann NA, Janicki P, Egermann M. Core decompression and autologous bone marrow concentrate for treatment of femoral head osteonecrosis: a randomized prospective study. Orthop Rev (Pavia) 2016;8:6162.
    Pubmed CrossRef
  65. Ha YC, Kim HJ, Kim SY, Kim KC, Lee YK, Koo KH. Effects of age and body mass index on the results of transtrochanteric rotational osteotomy for femoral head osteonecrosis. J Bone Joint Surg Am 2010;92:314-321.
    Pubmed CrossRef
  66. Sugioka Y. Transtrochanteric anterior rotational osteotomy of the femoral head in the treatment of osteonecrosis affecting the hip: a new osteotomy operation. Clin Orthop Relat Res 1978;:191-201.
  67. Lee YK, Park CH, Ha YC, Kim DY, Lyu SH, Koo KH. Comparison of surgical parameters and results between curved varus osteotomy and rotational osteotomy for osteonecrosis of the femoral head. Clin Orthop Surg 2017;9:160-168.
    Pubmed CrossRef
  68. Judet J, Judet H, Gilbert A. [Trial revascularization of the femur head with a pediculed fibular transplant]. Rev Chir Orthop Reparatrice Appar Mot 1980;66 Suppl 2:65
    Pubmed
  69. Urbaniak JR, Coogan PG, Gunneson EB, Nunley JA. Treatment of osteonecrosis of the femoral head with free vascularized fibular grafting. A long-term follow-up study of one hundred and three hips. J Bone Joint Surg Am 1995;77:681-694.
    Pubmed CrossRef
  70. Yoo MC, Chung DW, Hahn CS. Free vascularized fibula grafting for the treatment of osteonecrosis of the femoral head. Clin Orthop Relat Res 1992;:128-138.
  71. Zhao D, Xu D, Wang W, Cui X. Iliac graft vascularization for femoral head osteonecrosis. Clin Orthop Relat Res 2006;442:171-179.
    Pubmed CrossRef
  72. Amstutz HC, Le Duff MJ. Current status of hemi-resurfacing arthroplasty for osteonecrosis of the hip: a 27-year experience. Orthop Clin North Am 2009;40:275-282.
    Pubmed CrossRef
  73. De Smet KA, Van Der Straeten C, Van Orsouw M, Doubi R, Backers K, Grammatopoulos G. Revisions of metal-on-metal hip resurfacing: lessons learned and improved outcome. Orthop Clin North Am 2011;42:Array-269.
    Pubmed CrossRef
  74. Zustin J, Sauter G, Morlock MM, Rüther W, Amling M. Association of osteonecrosis and failure of hip resurfacing arthroplasty. Clin Orthop Relat Res 2010;468:756-761.
    Pubmed CrossRef
  75. Junnila M, Seppänen M, Mokka J, et al. Adverse reaction to metal debris after Birmingham Hip Resurfacing arthroplasty. Acta Orthop 2015;86:345-350.
    Pubmed CrossRef
  76. Matharu GS, Berryman F, Judge A, et al. Blood metal ion thresholds to identify patients with metal-on-metal hip implants at risk of adverse reactions to metal debris: an external multicenter validation study of Birmingham Hip Resurfacing and Corail-Pinnacle implants. J Bone Joint Surg Am 2017;99:1532-1539.
    Pubmed CrossRef
  77. Kamath AF, Prieto H, Lewallen DG. Alternative bearings in total hip arthroplasty in the young patient. Orthop Clin North Am 2013;44:451-462.
    Pubmed CrossRef
  78. Muratoglu OK, Bragdon CR, O’Connor DO, Jasty M, Harris WH. A novel method of cross-linking ultra-high-molecular-weight polyethylene to improve wear, reduce oxidation, and retain mechanical properties. Recipient of the 1999 HAP Paul Award. J Arthroplasty 2001;16:149-160.
    Pubmed CrossRef
  79. Min BW, Lee KJ, Song KS, Bae KC, Cho CH. Highly cross-linked polyethylene in total hip arthroplasty for osteonecrosis of the femoral head: a minimum 5-year follow-up study. J Arthroplasty 2013;28:526-530.
    Pubmed CrossRef
  80. Kim YH, Choi Y, Kim JS. Cementless total hip arthroplasty with alumina-on-highly cross-linked polyethylene bearing in young patients with femoral head osteonecrosis. J Arthroplasty 2011;26:218-223.
    Pubmed CrossRef
  81. Youngman TR, Verhotz DR, Layon DR, et al. Mean 16-year results of total hip arthroplasty with alumina ceramic femoral heads on highly cross-linked polyethylene in patients 50 years or less. J Arthroplasty 25 Apr 20232023.
    CrossRef
  82. Bryan AJ, Calkins TE, Karas V, Culvern C, Nam D, Della Valle CJ. Primary total hip arthroplasty in patients less than 50 years of age at a mean of 16 years: highly crosslinked polyethylene significantly reduces the risk of revision. J Arthroplasty 2019;34:S238-S241.
    Pubmed CrossRef
  83. Rames RD, Stambough JB, Pashos GE, Maloney WJ, Martell JM, Clohisy JC. Fifteen-year results of total hip arthroplasty with cobalt-chromium femoral heads on highly cross-linked polyethylene in patients 50 years and less. J Arthroplasty 2019;34:1143-1149.
    Pubmed CrossRef
  84. Koo KH, Ha YC, Jung WH, Kim SR, Yoo JJ, Kim HJ. Isolated fracture of the ceramic head after third-generation alumina-on-alumina total hip arthroplasty. J Bone Joint Surg Am 2008;90:329-336.
    Pubmed CrossRef
  85. Lee YK, Ha YC, Yoo JI, Jo WL, Kim KC, Koo KH. Mid-term results of the BIOLOX delta ceramic-on-ceramic total hip arthroplasty. Bone Joint J 2017;99-B:741-748.
    Pubmed CrossRef
  86. Park YS, Park SJ, Lim SJ. Ten-year results after cementless THA with a sandwich-type alumina ceramic bearing. Orthopedics 2010;33:796.
    Pubmed CrossRef
  87. Baek SH, Kim SY. Cementless total hip arthroplasty with alumina bearings in patients younger than fifty with femoral head osteonecrosis. J Bone Joint Surg Am 2008;90:1314-1320.
    Pubmed CrossRef
  88. Kang BJ, Ha YC, Ham DW, Hwang SC, Lee YK, Koo KH. Third-generation alumina-on-alumina total hip arthroplasty: 14 to 16-year follow-up study. J Arthroplasty 2015;30:411-415.
    Pubmed CrossRef
  89. Park JW, Ko YS, Lee YK, Ha YC, Koo KH. Ten to 13-year results of delta ceramic-on-ceramic total hip arthroplasty in patients less than 30 years old. J Bone Joint Surg Am 2023;105:789-796.
    Pubmed CrossRef
  90. Kim YH, Park JW, Jang YS, Kim EJ. Long-term results (minimum of 20 years) of a pure proximal-loading metaphyseal-fitting anatomic cementless stem without distal stem fixation in hip arthroplasty. J Arthroplasty 2023;38:743-750.
    Pubmed CrossRef
  91. Konan S, Alazzawi S, Yoon BH, Cha YH, Koo KH. A focused update on preventing ceramic fractures in hip arthroplasty: is the ‘cup’ half full?. Bone Joint J 2019;101-B:897-901.
    Pubmed CrossRef

Article

Review Article

Hip Pelvis 2023; 35(3): 147-156

Published online September 30, 2023 https://doi.org/10.5371/hp.2023.35.3.147

Copyright © The Korean Hip Society.

Updating Osteonecrosis of the Femoral Head

Young-Seung Ko, MD* , Joo Hyung Ha, MD† , Jung-Wee Park, MD* , Young-Kyun Lee, MD* , Tae-Young Kim, MD‡ , Kyung-Hoi Koo, MD*,§

Department of Orthopaedic Surgery, Seoul National University Bundang Hospital, Seongnam, Korea*
Department of Orthopaedic Surgery, Gumdan Top General Hospital, Incheon, Korea†
Department of Orthopaedic Surgery, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea‡
Kay Joint Center at Cheil Orthopaedic Hospital, Seoul, Korea§

Correspondence to:Tae-Young Kim, MD
(https://orcid.org/0000-0003-2028-0460)
Department of Orthopaedic Surgery, Konkuk University Medical Center, Konkuk University School of Medicine, 120-1 Neungdongro, Gwangjin-gu, Seoul 05030, Korea
TEL: +82-2-2030-8146
E-mail: syty-chan@hanmail.net

Young-Seung Ko and Joo Hyung Ha contributed equally to this study as co-first authors.

Received: January 27, 2023; Revised: June 16, 2023; Accepted: June 16, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Osteonecrosis of the femoral head (ONFH), a condition characterized by the presence of a necrotic bone lesion in the femoral head, is caused by a disruption in the blood supply. Its occurrence is more common in young and middle-aged adults and it is the main reason for performance of total hip arthroplasty in this age group. Its incidence is increasing along with increased use of glucocorticoids for management of adjuvant therapy for treatment of leukemia as well as organ transplantation and other myelogenous diseases. Current information on etiology and pathogenesis, as well as natural history, stage system, and treatments is provided in this review. A description of the Association Research Circulation Osseous (ARCO) criteria for classification of glucocorticoids- and alcohol-associated ONFH, 2019 ARCO staging system, and 2021 ARCO classification using computed tomography for the early stages of ONFH is also provided.

Keywords: Femur head necrosis, Etiology, Pathogenesis, Staging, Classification

INTRODUCTION

Osteonecrosis of the femoral head (ONFH), a condition characterized by the presence of a necrotic bone lesion in the femoral head, is caused by a disruption in the blood supply1). The incidence of ONFH is increasing worldwide, particularly among young and middle-aged individuals2,3,4,5). In the United States alone, the estimated annual occurrence of ONFH is approximately 15,000 to 20,000 new cases2,6). Similar trends have been reported in East Asian countries including Japan, and China, where significant numbers of individuals are affected by this condition4,5,6,7). In South Korea, more than 10,000 new cases of ONFH have been reported annually7,8).

Trauma, such as a displaced fracture of the femoral neck or hip dislocation, can damage local blood vessels and compromise the supply of blood to the femoral head, leading to development of ONFH9). In addition, non-traumatic risk factors associated with ONFH include the use of corticosteroids, excessive consumption of alcohol and tobacco, certain medical conditions such as sickle cell disease and systemic lupus erythematosus (SLE), as well as factors such as organ transplantation, HIV (human immunodeficiency virus) infection, coagulation disorders, genetic factors, Caisson disease (divers), myeloproliferative diseases, and radiation necrosis9,10,11,12,13,14).

Once ONFH has developed, the size and location of the necrotic portion are critical in determining the risk of femoral head collapse2,15). The prognosis may be better for small lesions, which sometimes remain stable without progressing, while progression to collapse is more likely with larger lesions involving the weight-bearing area of the femoral head, leading to development of secondary arthritis of the hip16,17,18,19).

Accurate evaluation and classification of the size and location of the necrotic lesions is important to the process of making appropriate decisions regarding treatment. Lesions that differ in size may require different treatment approaches with the aim of preserving the femoral head and preventing collapse. Accurate assessment of the necrotic portion can be helpful in determining the optimal treatment strategy for each individual case, with the aim of preventing further deterioration and preserving hip joint function15,20,21,22).

In this review, we have updated current information on the etiology and pathogenesis of the disease, criteria for classification of alcohol and glucocorticoid associated ONFH, staging system, classification for early-stage ONFH, and treatments.

ETIOLOGY

Caisson disease, dysbaric ONFH in divers, was first reported in 195223). The association of glucocorticoid use and ONFH was reported in 195724). Bone necrosis in patients with sickle cell disease was reported in the 1950s25). Excessive alcohol use had been recognized as a risk factor for ONFH by the 1960s26). Since 1990, association of hypofibrinolysis, thrombophilia, and impaired angiogenesis due to abnormal enzymes and various polymorphisms with ONFH has been reported26,27). Involvement of protein S and protein C deficiencies27,28,29,30), presence of antiphospholipid antibodies31,32), mutations in the factor V Leiden or the prothrombin 20210A gene33), polymorphisms of the plasminogen activator inhibitor-1 gene (PAI-1)34,35), and diminished activity of 5,10-methylenetetrahydrofolate reductase (MTHFR) in hypofibrinolysis/hypercoagulability has been reported35). An association of polymorphisms of vascular endothelial growth factor (VEGF) and polymorphism in the endothelial nitric oxide synthase gene with impaired angiogenesis has been reported21,36,37,38,39).

In addition, smoking, pelvic radiation therapy, non-glucocorticoid chemotherapeutics, HIV infection, rheumatic disease, Gaucher’s disease, SLE, and pancreatitis have also been reported as associated conditions or risk factors for ONFH40).

In 2019, a Delphi survey was conducted by Association Research Circulation Osseous (ARCO) in order to develop criteria for classification of alcohol-associated and glucocorticoid-associated ONFH. The ARCO criteria for classification of alcohol-associated ONFH were as follows: (1) patients must have a history of alcohol consumption >400 mL/week (320 g/week, any alcoholic drink); (2) diagnosis of ONFH must occur within one year after consuming this amount of alcohol; and (3) patients must not have any risk factors other than alcohol abuse11). The ARCO criteria for classification of glucocorticoid-associated ONFH were as follows: (1) patients must have taken glucocorticoids that totaled more than 2 g of prednisolone or its equivalent in the previous three months; (2) diagnosis of osteonecrosis must occur within two years of glucocorticoid usage; and (3) other than glucocorticoids, patients should have no other risk factors10).

PATHOGENESIS

The pathogenesis of ONFH is complex and research is ongoing. However, over the past three decades, knowledge of the pathophysiology of the disease has shown significant advancement, and various consensuses have been reached.

First, ONFH has a multi-factorial etiology involving exposure to risk factors and genetic predispositions. Reciprocal interaction and cooperation occurs among these elements in the pathogenesis9,12,41). This genetic predisposition explains why the condition affects some users of glucocorticoids and alcoholics while it may not affect others. Second, the first event of ischemia occurs in the marrow space, not inside the vessel. Third, the process of pathogenesis involves (1) bone marrow necrosis and death of osteocytes, (2) a fibrovascular healing process in the area surrounding the necrotic marrow zone, (3) fracture and collapse of an osteonecrotic lesion, and (4) secondary osteoarthritis of the hip9,12,41).

A reliable model of the pathophysiology of non-traumatic ONFH was presented by ARCO in 20199). Mesenchymal stem cells differentiating to adipocytes are stimulated by glucocorticoids and alcohol, leading to activation of intracellular synthesis of lipids and induction of adipocyte hypertrophy 42,43, 44). An increase in the number and volume of marrow fat cells results in intraosseous hypertension in the femoral head, which causes squeezing of the venous sinusoids and intravascular coagulation. This leads to restriction of arterial blood flow, resulting in ischemic alternations in the femoral head. Marrow adipocytes die within two days of developing ischemia. The ischemia is usually recovered by thrombolysis and angiogenesis, and the presence of lesions does not lead to irreversible necrosis. However, in cases of ischemia that is sustained for two to five days, osteocytes die and vanish completely within 2-4 weeks, leaving a sequestrum. Because gradual replacement of dead bone with new bone does not occur, a foreign body reaction occurs in the area surrounding the sequestrum, resulting in the formation of fibrovascular tissue that encapsulates the lesion. Histologic criteria for ONFH include marrow necrosis, osteocyte death, and encapsulating fibrovascular tissue. Advancement of the ischemic lesion is determined by the restoration of vascular perfusion. Restoration of vascular perfusion is hindered by hypercoagulability/hypo-fibrinolysis genetic predispositions and/or hypoangiogenesis (Fig. 1)9,12,41).

NATURAL HISTORY ACCORDING TO SIZE AND LOCATION OF OSTEONECROSIS

The fate of ONFH is largely determined by the size and location of osteonecrosis. The risk of femoral head collapse is influenced by the size and location of the necrotic portion. Even without medical or surgical treatment, collapse of small lesions seldom occurs, whereas progression of large lesions is more likely, leading to collapse of the femoral head16,18,19). Once ONFH has developed, the size of the necrotic lesion remains stable and does not increase regardless of the progression of the disease45). This means that expansion or enlargement of the necrotic portion does not occur over time during the disease course. Thus, measurement of the size of osteonecrosis should be performed prior to planning treatment for ONFH patients, and small osteonecrosis lesions should not be treated. Therefore, cautious assessment based on the size of the necrosis and the predicted course of the condition is necessary for determining the most appropriate treatment approach for each individual.

ARCO STAGING

The first ARCO ONFH staging system was developed in 1994. However, it had been reported that progression of a stage 0 lesion: marrow necrosis with viable osteocytes to definite osteonecrosis does not occur41). Thus, the ONFH staging system was updated by ARCO in 2019. In the 2019 revised version of the staging system, stage III was divided into two parts: early IIIA and late IIIB based on a head depression depth of 2 mm, sub-classification of size and location was not included, and stage 0 was removed (Fig. 2, Table 1)46).

ARCO CLASSIFICATION OF SIZE AND LOCATION OF NECROSIS IN EARLY STAGE ONFH

Various systems for classification of ONFH have been introduced in order to characterize the extent and location of osteonecrosis. There are currently three classification systems that are frequently employed, Japanese Investigation Committee (JIC) classification, Steinberg classification, and modified Kerboul classification.

However, there is no consensus regarding which method is universally acknowledged. Development of a unified system for classifying the amount and location of osteonecrosis was required. A novel system for classification of necrotic size and location in the early stage of ONFH (pre-collapse) was developed by ARCO in 2021. Using that classification, necrotic lesions were classified into three types: type 1 is a small lesion, where the lateral necrotic margin is medial to the apex of the femoral head; type 2 is a medium-sized lesion, with the lateral necrotic margin located between the apex of the femoral head and the lateral acetabular edge; and type 3 is a large lesion, which extends outside the lateral acetabular edge (Fig. 3). The 2021 ARCO classification is considered highly reliable and valid and use of this method as a unified system for classification of ONFH in the early stages is recommended by ARCO47).

TREATMENTS

Determining the treatment approach for ONFH is based on the size and location of the necrotic lesion, as well as the risk of progression to femoral head collapse. It should be noted that progression to collapse does not often occur with small lesions even without medical or surgical intervention, whereas progressive deterioration is more likely to occur with larger lesions16,18,19). The extent of the necrotic portion is typically established during the ischemic attack, so that once ONFH has developed, the size of the lesion remains constant regardless of disease progression stage45). Consequently, evaluating the size of the necrotic portion prior to initiating treatment is essential, and caution should be exercised in determining the effectiveness of specific treatment modalities, with consideration for the varying natural courses based on the size and location of the necrotic lesion.

1. Medical Treatments

Several pharmacological agents including enoxaparin, statins, bisphosphonates, iloprost, and acetylsalicylic acid have been evaluated for their potential to slow down or reverse the progression of ONFH48,49,50,51,52,53,54). However, it is important to note that the effectiveness of these agents has not been conclusively proven based on high-level evidence20). In addition, many of these pharmacological interventions have shown an association with adverse reactions or side effects.

Consequently, there is currently no recommended pharmacological approach for the prevention or treatment of ONFH. Conduct of additional research and clinical trials will be required in order to verify the efficacy and safety of potential pharmacological interventions for treatment of this condition.

2. Core Decompression and Bone Marrow Aspirate Concentration

Core decompression (CD), a surgical technique, is commonly used in the early stages of ONFH, with the aim of preventing collapse of the femoral head and potentially reversing the disease progression. However, results regarding the efficacy of CD have been inconsistent, leading to questions about its effectiveness55). In recent years, use of the combination of CD with bone marrow aspirate concentration (BMAC) therapy as a potential improvement has been evaluated. Earlier studies suggested that enhanced treatment outcomes could be achieved with the addition of cell therapy through BMAC56,57,58,59,60,61). However, more recent studies have reported no significant differences in outcomes between CD with BMAC and CD alone. In addition, high rates of progression have been observed in large lesions with use of both CD and BMAC therapies62,63,64). The effectiveness of BMAC remains controversial and further research will be required in order to clarify its role in the treatment of ONFH.

3. Osteotomies

Several procedures for osteotomy of the proximal femur have been introduced in the effort to preserve osteonecrotic hips. These procedures involve relocating the necrotic portion from the weight-bearing dome to a non-weight-bearing region. Certain factors, including the patient’s age (under 40 years), body mass index (below 24 kg/m2), stage of the disease (ARCO stage 3A or 3B)16,18,46,65), and size of the necrotic portion (medium-sized lesion), should be considered when selecting candidates for osteotomy. These criteria can be helpful in identifying suitable candidates for osteotomy procedures.

Among these types of osteotomy, transtrochanteric curved varus osteotomy (TCVO) and transtrochanteric rotational osteotomy (TRO) have been predominantly performed in Japan and South Korea66). A study conducted by Lee et al.67) in 2017 compared the outcomes of 91 TROs and 65 TCVOs. According to the results, various aspects of TCVO were found to be superior to those of TRO. Shorter operation times, less blood loss, lower rates of postoperative collapse, decreased osteoarthritic changes (20% vs. 37.4%), and a lower rate of conversion to total hip arthroplasty (THA) (10.8% vs. 16.5%) were obtained with use of TCVO. Based on these findings, TCVO was recommended as the preferred option over TRO.

4. Vascularized Bone Grafts

The technique of vascularized fibular grafting was initially introduced by Judet et al.68) in 1980 and later gained popularity through the work of Urbaniak et al.69) and Yoo et al.70). Another approach, vascularized iliac bone grafting with a pedicle of the iliac circumflex artery, has also been favored due to its proximity to the femoral head and the absence of microsurgical anastomosis71). However, despite their potential benefits, vascularized bone graft procedures have been criticized for their technical complexities and associated donor site morbidities. As a result, use of these procedures is currently limited to a select few specialized centers worldwide where they are performed by experienced surgeons.

5. Resurfacing Arthroplasty

Hip resurfacing arthroplasty (HRA) is regarded as an alternative to THA, particularly in younger patients who wish to maintain high levels of activity after surgery72,73). HRA involves the removal of the damaged surface of the femoral head and the placement of a metal cap, while preserving the femoral neck. Use of this technique enables the preservation of more bone stock compared to THA, which involves the complete removal and replacement of the femoral head.

The potential for improved range of motion and function is a main advantage of HRA compared to THA. The preservation of the femoral neck with use of HRA allows for a more natural anatomy and can potentially reduce the risk of dislocation. In addition, use of HRA with the larger femoral head size can result in enhanced stability and contribute to better hip kinematics.

However, the risk of complications specific to HRA, such as femoral neck fractures and issues related to metal-on-metal bearing surfaces, including metal ion release and adverse local tissue reactions, may be increased74,75,76). Careful discussion of these factors with the patient is required, and their individual suitability for HRA should be thoroughly evaluated. The use of HRA in the treatment of ONFH has declined significantly as a result of these concerns and complications.

6. THA Using Highly Cross-Linked Polyethylene Liners

The use of more durable bearing materials has gained traction in response to concerns over excessive wear rates and osteolysis associated with conventional polyethylene bearings in young patients77). Highly cross-linked polyethylene (HXLPE), with enhanced wear resistance, has rapidly replaced conventional polyethylene in many cases. The crosslinking process involves exposing the polyethylene to ionizing radiation during manufacturing, which increases the number of crosslinks and reduces wear. Current crosslinking techniques utilize gamma-rays instead of electron beam irradiation, followed by annealing or remelting of the polyethylene78).

HXLPE can be combined with either cobalt chromium or ceramic femoral heads. Promising clinical and radiological results have been reported from short-term and mid-term follow-up studies on the use of HXLPE liners in patients with ONFH79,80). In addition, recent long-term follow-up studies have reported a good survival rate for THA with HXLPE liners81,82,83). Conduct of additional research and long-term studies will be necessary in order to evaluate the durability and longevity of HXLPE.

7. THA Using Ceramic-on-Ceramic Bearings

The lowest wear rates have been reported for ceramic-on-ceramic (CoC) bearings compared to other bearing materials77). However, the use of CoC bearings is associated with specific complications. The implementation of these bearings has led to concerns regarding fractures of ceramic components as well as audible squeaking noises84,85).

Despite these potential complications, several studies have reported promising outcomes at mid-term and long-term follow-up with use of CoC THA in patients with ONFH86,87,88,89,90). Favorable results in terms of wear reduction and improved longevity have been reported with the use of CoC bearings. A further decrease in the incidence of ceramic fractures as well as enhanced performance of CoC THA is expected with the introduction of newer ceramic materials, such as the delta ceramic91).

However, it is important to note that there is still no knowledge regarding the long-term outcomes of CoC THA for treatment of ONFH. Continued research and conduct of long-term studies will be necessary for evaluation of the durability, complications, and overall success of CoC bearings in the treatment of ONFH.

SUMMARY

Exposure to risk factors and genetic predispositions can influence the development of ONFH. The size and location of the osteonecrosis is the primary factor influencing the rapidity of disease progression. The size of osteonecrosis is determined during the initial ischemic episode and is not altered. Advancement of small lesions of osteonecrosis does not occur even without intervention, therefore they do not require therapy, whereas most large lesions result in collapse of the femoral head. Medical or surgical treatment may be required for painful ONFH hips with medium-to-large sized lesions. During the last five years, ARCO developed criteria for classification of glucocorticoid-and alcohol-associated osteonecrosis, revised the system for staging ONFH, and developed a system for classification of size/location for early stage ONFH. ARCO has recommended the use of these new systems as unified classification and staging systems. Small lesions in ONFH do not progress and therefore treatment is typically not required. Medical or surgical interventions may be helpful in management of medium-sized to large lesions with accompanying pain. Proven efficacy has not been demonstrated for pharmacological treatments. CD combined with BMAC therapy may not be effective in treatment of large lesions and conduct of additional research will be required. The decision to perform osteotomy should be the result of a selective process. Selective consideration and deliberation are required for HRA. Despite promising outcomes of THA with HXLPE or CoC bearings in the short to medium term, results from long-term follow-up are still anticipated.

CONFLICTS OF INTEREST

CONFLICT OF INTEREST: Young-Kyun Lee has been an editorial board member since January 2023, but had no role in the decision to publish this article. No other potential conflict of interest relevant to this article was reported.

Fig 1.

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Figure 1.

Summary of the pathophysiology of non-traumatic osteonecrosis of the femoral head.

Hip & Pelvis 2023; 35: 147-156https://doi.org/10.5371/hp.2023.35.3.147

Fig 2.

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Figure 2.

The 2019 ARCO (Association Research Circulation Osseous) staging system for osteonecrosis of the femoral head. (A) Stage I. (B) Stage II. (C) Stage IIIA. (D) Stage IIIB. (E) Stage IV.

Hip & Pelvis 2023; 35: 147-156https://doi.org/10.5371/hp.2023.35.3.147

Fig 3.

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Figure 3.

The 2021 ARCO (Association Research Circulation Osseous) classification for osteonecrosis of the femoral head in the early stages (computed tomography-based): (A) Type 1 is a small lesion that is restricted medial to the apex of the femoral head; (B) Type 2 is a medium-sized lesion where the lateral margin of the necrotic portion is located between the apex of the femoral head and the lateral edge of the acetabulum; and (C) Type 3 is a large lesion that extends laterally to the lateral edge of the acetabulum.

Hip & Pelvis 2023; 35: 147-156https://doi.org/10.5371/hp.2023.35.3.147

Table 1 . The 2019 Revised ARCO Staging for Osteonecrosis of the Femoral Head.

ARCO stageImage findings
IX-ray: normal
MRI: low-signal band on T1-weighted MRI
IIX-ray: abnormal
MRI: abnormal
IIISubchondral fracture on X-ray or CT
IIIA (early)Femoral head depression≤2 mm
IIIB (late)Femoral head depression >2 mm
IVX-ray: osteoarthritis

ARCO: Association Research Circulation Osseous, MRI: magnetic resonance imaging, CT: computed tomography..

References

  1. Arlet J. Nontraumatic avascular necrosis of the femoral head. Past, present, and future. Clin Orthop Relat Res 1992;:12-21.
  2. Mont MA, Cherian JJ, Sierra RJ, Jones LC, Lieberman JR. Nontraumatic osteonecrosis of the femoral head: where do we stand today? A ten-year update. J Bone Joint Surg Am 2015;97:1604-1627.
    Pubmed CrossRef
  3. Park JW, Won SH, Moon SY, Lee YK, Ha YC, Koo KH. Burden and future projection of revision Total hip Arthroplasty in South Korea. BMC Musculoskelet Disord 2021;22:375.
    Pubmed CrossRef
  4. van der Jagt D, Mokete L, Pietrzak J, Zalavras CG, Lieberman JR. Osteonecrosis of the femoral head: evaluation and treatment. J Am Acad Orthop Surg 2015;23:69-70.
    Pubmed CrossRef
  5. 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;63:3169-3173.
    Pubmed CrossRef
  6. Moya-Angeler J, Gianakos AL, Villa JC, Ni A, Lane JM. Current concepts on osteonecrosis of the femoral head. World J Orthop 2015;6:590-601.
    Pubmed CrossRef
  7. 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;24:1178-1183.
    Pubmed CrossRef
  8. Park JW, Kim HS, Park S, Kim SH, Lee YK, Koo KH. Trends in surgical treatment of femoral head osteonecrosis in South Korea: an analysis using nationwide claims database. Clin Orthop Surg 2022;14:500-506.
    Pubmed CrossRef
  9. Cui Q, Jo WL, Koo KH, et al. ARCO consensus on the pathogenesis of non-traumatic osteonecrosis of the femoral head. J Korean Med Sci 2021;36:e65.
    Pubmed CrossRef
  10. Yoon BH, Jones LC, Chen CH, et al. Etiologic classification criteria of ARCO on femoral head osteonecrosis part 1: glucocorticoid-associated osteonecrosis. J Arthroplasty 2019;34:163-168.e1.
    Pubmed CrossRef
  11. Yoon BH, Jones LC, Chen CH, et al. Etiologic classification criteria of ARCO on femoral head osteonecrosis part 2: alcohol-associated osteonecrosis. J Arthroplasty 2019;34:169-174.e1.
    Pubmed CrossRef
  12. Seamon J, Keller T, Saleh J, Cui Q. The pathogenesis of nontraumatic osteonecrosis. Arthritis 2012;2012:601763.
    Pubmed CrossRef
  13. Mont MA, Salem HS, Piuzzi NS, Goodman SB, Jones LC. Nontraumatic osteonecrosis of the femoral head: where do we stand today?: a 5-year update. J Bone Joint Surg Am 2020;102:1084-1099.
    Pubmed CrossRef
  14. Ikeuchi K, Hasegawa Y, Seki T, Takegami Y, Amano T, Ishiguro N. Epidemiology of nontraumatic osteonecrosis of the femoral head in Japan. Mod Rheumatol 2015;25:278-281.
    Pubmed CrossRef
  15. Karantanas AH. Accuracy and limitations of diagnostic methods for avascular necrosis of the hip. Expert Opin Med Diagn 2013;7:179-187.
    Pubmed CrossRef
  16. Ha YC, Jung WH, Kim JR, Seong NH, Kim SY, Koo KH. Prediction of collapse in femoral head osteonecrosis: a modified Kerboul method with use of magnetic resonance images. J Bone Joint Surg Am 2006;88 Suppl 3:35-40.
    CrossRef
  17. Kim YM, Ahn JH, Kang HS, Kim HJ. Estimation of the extent of osteonecrosis of the femoral head using MRI. J Bone Joint Surg Br 1998;80:954-958.
    Pubmed CrossRef
  18. 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;7:601-605.
    Pubmed CrossRef
  19. Steinberg ME, Hayken GD, Steinberg DR. A quantitative system for staging avascular necrosis. J Bone Joint Surg Br 1995;77:34-41.
    Pubmed CrossRef
  20. Lee YJ, Cui Q, Koo KH. Is there a role of pharmacological treatments in the prevention or treatment of osteonecrosis of the femoral head?: a systematic review. J Bone Metab 2019;26:13-18.
    Pubmed CrossRef
  21. Hines JT, Jo WL, Cui Q, et al. Osteonecrosis of the femoral head: an updated review of ARCO on pathogenesis, staging and treatment. J Korean Med Sci 2021;36:e177.
    Pubmed CrossRef
  22. Lee YK, Lee B, Parvizi J, Ha YC, Koo KH. Which osteotomy for osteonecrosis of the femoral head and which patient for the osteotomy?. Clin Orthop Surg 2019;11:137-141.
    Pubmed CrossRef
  23. Dale T. Bone necrosis in divers; caisson disease. Acta Chir Scand 1952;104:153-156.
    Pubmed
  24. Ravault PP, Lejeune E, Colomb D, Fries D. [Osteonecrosis of the femur head associated with corticotherapy]. Rev Rhum Mal Osteoartic 1962;29:546-550
    Pubmed
  25. Chung SM, Ralston EL. Necrosis of the femoral head associated with sickle-cell anemia and its genetic variants. A review of the literature and study of thirteen cases. J Bone Joint Surg Am 1969;51:33-58.
    Pubmed
  26. Arlet J, Franck JL, Nghiem L, Solera ML, de Graeve J. [Multiple bone necroses and familial type I hyperlipemia. Apropos of a case report]. Rev Rhum Mal Osteoartic 1983;50:149-153
    Pubmed
  27. Pierre-Jacques H, Glueck CJ, Mont MA, Hungerford DS. Familial heterozygous protein-S deficiency in a patient who had multifocal osteonecrosis. A case report. J Bone Joint Surg Am 1997;79:1079-1084.
    Pubmed CrossRef
  28. Glueck CJ, Freiberg R, Tracy T, Stroop D, Wang P. Thrombophilia and hypofibrinolysis: pathophysiologies of osteonecrosis. Clin Orthop Relat Res 1997;:43-56.
    Pubmed
  29. Jones LC, Mont MA, Le TB, et al. Procoagulants and osteonecrosis. J Rheumatol 2003;30:783-791.
    Pubmed
  30. Zalavras CG, Vartholomatos G, Dokou E, Malizos KN. Genetic background of osteonecrosis: associated with thrombophilic mutations?. Clin Orthop Relat Res 2004;:251-255.
  31. Korompilias AV, Gilkeson GS, Ortel TL, Seaber AV, Urbaniak JR. Anticardiolipin antibodies and osteonecrosis of the femoral head. Clin Orthop Relat Res 1997;:174-180.
  32. Seleznick MJ, Silveira LH, Espinoza LR. Avascular necrosis associated with anticardiolipin antibodies. J Rheumatol 1991;18:1416-1417.
    Pubmed
  33. Björkman A, Svensson PJ, Hillarp A, Burtscher IM, Rünow A, Benoni G. Factor V leiden and prothrombin gene mutation: risk factors for osteonecrosis of the femoral head in adults. Clin Orthop Relat Res 2004;:168-172.
  34. Glueck CJ, Fontaine RN, Gruppo R, et al. The plasminogen activator inhibitor-1 gene, hypofibrinolysis, and osteonecrosis. Clin Orthop Relat Res 1999;:133-146.
    Pubmed CrossRef
  35. Glueck CJ, Freiberg RA, Fontaine RN, Tracy T, Wang P. Hypofibrinolysis, thrombophilia, osteonecrosis. Clin Orthop Relat Res 2001;:19-33.
    Pubmed CrossRef
  36. Glueck CJ, Freiberg RA, Boppana S, Wang P. Thrombophilia, hypofibrinolysis, the eNOS T-786C polymorphism, and multifocal osteonecrosis. J Bone Joint Surg Am 2008;90:2220-2229.
    Pubmed CrossRef
  37. Kim T, Hong JM, Lee J, et al. Promoter polymorphisms of the vascular endothelial growth factor gene is associated with an osteonecrosis of the femoral head in the Korean population. Osteoarthritis Cartilage 2008;16:287-291.
    Pubmed CrossRef
  38. Koo KH, Lee JS, Lee YJ, Kim KJ, Yoo JJ, Kim HJ. Endothelial nitric oxide synthase gene polymorphisms in patients with nontraumatic femoral head osteonecrosis. J Orthop Res 2006;24:1722-1728.
    Pubmed CrossRef
  39. Lee YJ, Lee JS, Kang EH, et al. Vascular endothelial growth factor polymorphisms in patients with steroid-induced femoral head osteonecrosis. J Orthop Res 2012;30:21-27.
    Pubmed CrossRef
  40. Koo KH, Mont MA, Jones LC. Osteonecrosis: Springer Berlin, 2014; 2014. p. 59-139.
  41. Koo KH, Jeong ST, Jones JP. Borderline necrosis of the femoral head. Clin Orthop Relat Res 1999;:158-165.
  42. Cui Q, Wang GJ, Balian G. Steroid-induced adipogenesis in a pluripotential cell line from bone marrow. J Bone Joint Surg Am 1997;79:1054-1063.
    Pubmed CrossRef
  43. Cui Q, Wang Y, Saleh KJ, Wang GJ, Balian G. Alcohol-induced adipogenesis in a cloned bone-marrow stem cell. J Bone Joint Surg Am 2006;88 Suppl 3:148-154.
    CrossRef
  44. Wang GJ, Sweet DE, Reger SI, Thompson RC. Fat-cell changes as a mechanism of avascular necrosis of the femoral head in cortisone-treated rabbits. J Bone Joint Surg Am 1977;59:729-735.
    Pubmed
  45. Koo KH, Ahn IO, Kim R, et al. Bone marrow edema and associated pain in early stage osteonecrosis of the femoral head: prospective study with serial MR images. Radiology 1999;213:715-722.
    Pubmed CrossRef
  46. Yoon BH, Mont MA, Koo KH, et al. The 2019 revised version of Association Research Circulation Osseous staging system of osteonecrosis of the femoral head. J Arthroplasty 2020;35:933-940.
    Pubmed CrossRef
  47. Koo KH, Mont MA, Cui Q, et al. The 2021 Association Research Circulation Osseous classification for early-stage osteonecrosis of the femoral head to computed tomography-based study. J Arthroplasty 2022;37:1074-1082.
    Pubmed CrossRef
  48. Ajmal M, Matas AJ, Kuskowski M, Cheng EY. Does statin usage reduce the risk of corticosteroid-related osteonecrosis in renal transplant population?. Orthop Clin North Am 2009;40:235-239.
    Pubmed CrossRef
  49. Glueck CJ, Freiberg RA, Sieve L, Wang P. Enoxaparin prevents progression of stages I and II osteonecrosis of the hip. Clin Orthop Relat Res 2005;:164-170.
    CrossRef
  50. Glueck CJ, Freiberg RA, Wissman R, Wang P. Long term anticoagulation (4-16 years) stops progression of idiopathic hip osteonecrosis associated with familial thrombophilia. Adv Orthop 2015;2015:138382.
    Pubmed CrossRef
  51. Pengde K, Fuxing P, Bin S, Jing Y, Jingqiu C. Lovastatin inhibits adipogenesis and prevents osteonecrosis in steroid-treated rabbits. Joint Bone Spine 2008;75:696-701.
    Pubmed CrossRef
  52. Pritchett JW. Statin therapy decreases the risk of osteonecrosis in patients receiving steroids. Clin Orthop Relat Res 2001;:173-178.
    CrossRef
  53. Lai KA, Shen WJ, Yang CY, Shao CJ, Hsu JT, Lin RM. The use of alendronate to prevent early collapse of the femoral head in patients with nontraumatic osteonecrosis. A randomized clinical study. J Bone Joint Surg Am 2005;87:2155-2159.
    Pubmed
  54. Lee YK, Ha YC, Cho YJ, et al. Does zoledronate prevent femoral head collapse from osteonecrosis? A prospective, randomized, open-label, multicenter study. J Bone Joint Surg Am 2015;97:1142-1148.
    Pubmed CrossRef
  55. Yoon BH, Lee YK, Kim KC, Ha YC, Koo KH. No differences in the efficacy among various core decompression modalities and non-operative treatment: a network meta-analysis. Int Orthop 2018;42:2737-2743.
    Pubmed CrossRef
  56. Hernigou P, Dubory A, Homma Y, et al. Cell therapy versus simultaneous contralateral decompression in symptomatic corticosteroid osteonecrosis: a thirty year follow-up prospective randomized study of one hundred and twenty five adult patients. Int Orthop 2018;42:1639-1649.
    Pubmed CrossRef
  57. Kang JS, Suh YJ, Moon KH, et al. Clinical efficiency of bone marrow mesenchymal stem cell implantation for osteonecrosis of the femoral head: a matched pair control study with simple core decompression. Stem Cell Res Ther 2018;9:274.
    Pubmed CrossRef
  58. Li X, Xu X, Wu W. Comparison of bone marrow mesenchymal stem cells and core decompression in treatment of osteonecrosis of the femoral head: a meta-analysis. Int J Clin Exp Pathol 2014;7:5024-5030.
    Pubmed
  59. Ma Y, Wang T, Liao J, et al. Efficacy of autologous bone marrow buffy coat grafting combined with core decompression in patients with avascular necrosis of femoral head: a prospective, double-blinded, randomized, controlled study. Stem Cell Res Ther 2014;5:115.
    Pubmed CrossRef
  60. Sen RK, Tripathy SK, Aggarwal S, Marwaha N, Sharma RR, Khandelwal N. Early results of core decompression and autologous bone marrow mononuclear cells instillation in femoral head osteonecrosis: a randomized control study. J Arthroplasty 2012;27:679-686.
    Pubmed CrossRef
  61. Zhao D, Cui D, Wang B, et al. Treatment of early stage osteonecrosis of the femoral head with autologous implantation of bone marrow-derived and cultured mesenchymal stem cells. Bone 2012;50:325-330.
    Pubmed CrossRef
  62. Lim YW, Kim YS, Lee JW, Kwon SY. Stem cell implantation for osteonecrosis of the femoral head. Exp Mol Med 2013;45:e61.
    Pubmed CrossRef
  63. Nally FJ, Zanotti G, Buttaro MA, et al. THA conversion rate comparing decompression alone, with autologous bone graft or stem cells in osteonecrosis. Hip Int 2018;28:189-193
    Pubmed CrossRef
  64. Pepke W, Kasten P, Beckmann NA, Janicki P, Egermann M. Core decompression and autologous bone marrow concentrate for treatment of femoral head osteonecrosis: a randomized prospective study. Orthop Rev (Pavia) 2016;8:6162.
    Pubmed CrossRef
  65. Ha YC, Kim HJ, Kim SY, Kim KC, Lee YK, Koo KH. Effects of age and body mass index on the results of transtrochanteric rotational osteotomy for femoral head osteonecrosis. J Bone Joint Surg Am 2010;92:314-321.
    Pubmed CrossRef
  66. Sugioka Y. Transtrochanteric anterior rotational osteotomy of the femoral head in the treatment of osteonecrosis affecting the hip: a new osteotomy operation. Clin Orthop Relat Res 1978;:191-201.
  67. Lee YK, Park CH, Ha YC, Kim DY, Lyu SH, Koo KH. Comparison of surgical parameters and results between curved varus osteotomy and rotational osteotomy for osteonecrosis of the femoral head. Clin Orthop Surg 2017;9:160-168.
    Pubmed CrossRef
  68. Judet J, Judet H, Gilbert A. [Trial revascularization of the femur head with a pediculed fibular transplant]. Rev Chir Orthop Reparatrice Appar Mot 1980;66 Suppl 2:65
    Pubmed
  69. Urbaniak JR, Coogan PG, Gunneson EB, Nunley JA. Treatment of osteonecrosis of the femoral head with free vascularized fibular grafting. A long-term follow-up study of one hundred and three hips. J Bone Joint Surg Am 1995;77:681-694.
    Pubmed CrossRef
  70. Yoo MC, Chung DW, Hahn CS. Free vascularized fibula grafting for the treatment of osteonecrosis of the femoral head. Clin Orthop Relat Res 1992;:128-138.
  71. Zhao D, Xu D, Wang W, Cui X. Iliac graft vascularization for femoral head osteonecrosis. Clin Orthop Relat Res 2006;442:171-179.
    Pubmed CrossRef
  72. Amstutz HC, Le Duff MJ. Current status of hemi-resurfacing arthroplasty for osteonecrosis of the hip: a 27-year experience. Orthop Clin North Am 2009;40:275-282.
    Pubmed CrossRef
  73. De Smet KA, Van Der Straeten C, Van Orsouw M, Doubi R, Backers K, Grammatopoulos G. Revisions of metal-on-metal hip resurfacing: lessons learned and improved outcome. Orthop Clin North Am 2011;42:Array-269.
    Pubmed CrossRef
  74. Zustin J, Sauter G, Morlock MM, Rüther W, Amling M. Association of osteonecrosis and failure of hip resurfacing arthroplasty. Clin Orthop Relat Res 2010;468:756-761.
    Pubmed CrossRef
  75. Junnila M, Seppänen M, Mokka J, et al. Adverse reaction to metal debris after Birmingham Hip Resurfacing arthroplasty. Acta Orthop 2015;86:345-350.
    Pubmed CrossRef
  76. Matharu GS, Berryman F, Judge A, et al. Blood metal ion thresholds to identify patients with metal-on-metal hip implants at risk of adverse reactions to metal debris: an external multicenter validation study of Birmingham Hip Resurfacing and Corail-Pinnacle implants. J Bone Joint Surg Am 2017;99:1532-1539.
    Pubmed CrossRef
  77. Kamath AF, Prieto H, Lewallen DG. Alternative bearings in total hip arthroplasty in the young patient. Orthop Clin North Am 2013;44:451-462.
    Pubmed CrossRef
  78. Muratoglu OK, Bragdon CR, O’Connor DO, Jasty M, Harris WH. A novel method of cross-linking ultra-high-molecular-weight polyethylene to improve wear, reduce oxidation, and retain mechanical properties. Recipient of the 1999 HAP Paul Award. J Arthroplasty 2001;16:149-160.
    Pubmed CrossRef
  79. Min BW, Lee KJ, Song KS, Bae KC, Cho CH. Highly cross-linked polyethylene in total hip arthroplasty for osteonecrosis of the femoral head: a minimum 5-year follow-up study. J Arthroplasty 2013;28:526-530.
    Pubmed CrossRef
  80. Kim YH, Choi Y, Kim JS. Cementless total hip arthroplasty with alumina-on-highly cross-linked polyethylene bearing in young patients with femoral head osteonecrosis. J Arthroplasty 2011;26:218-223.
    Pubmed CrossRef
  81. Youngman TR, Verhotz DR, Layon DR, et al. Mean 16-year results of total hip arthroplasty with alumina ceramic femoral heads on highly cross-linked polyethylene in patients 50 years or less. J Arthroplasty 25 Apr 20232023.
    CrossRef
  82. Bryan AJ, Calkins TE, Karas V, Culvern C, Nam D, Della Valle CJ. Primary total hip arthroplasty in patients less than 50 years of age at a mean of 16 years: highly crosslinked polyethylene significantly reduces the risk of revision. J Arthroplasty 2019;34:S238-S241.
    Pubmed CrossRef
  83. Rames RD, Stambough JB, Pashos GE, Maloney WJ, Martell JM, Clohisy JC. Fifteen-year results of total hip arthroplasty with cobalt-chromium femoral heads on highly cross-linked polyethylene in patients 50 years and less. J Arthroplasty 2019;34:1143-1149.
    Pubmed CrossRef
  84. Koo KH, Ha YC, Jung WH, Kim SR, Yoo JJ, Kim HJ. Isolated fracture of the ceramic head after third-generation alumina-on-alumina total hip arthroplasty. J Bone Joint Surg Am 2008;90:329-336.
    Pubmed CrossRef
  85. Lee YK, Ha YC, Yoo JI, Jo WL, Kim KC, Koo KH. Mid-term results of the BIOLOX delta ceramic-on-ceramic total hip arthroplasty. Bone Joint J 2017;99-B:741-748.
    Pubmed CrossRef
  86. Park YS, Park SJ, Lim SJ. Ten-year results after cementless THA with a sandwich-type alumina ceramic bearing. Orthopedics 2010;33:796.
    Pubmed CrossRef
  87. Baek SH, Kim SY. Cementless total hip arthroplasty with alumina bearings in patients younger than fifty with femoral head osteonecrosis. J Bone Joint Surg Am 2008;90:1314-1320.
    Pubmed CrossRef
  88. Kang BJ, Ha YC, Ham DW, Hwang SC, Lee YK, Koo KH. Third-generation alumina-on-alumina total hip arthroplasty: 14 to 16-year follow-up study. J Arthroplasty 2015;30:411-415.
    Pubmed CrossRef
  89. Park JW, Ko YS, Lee YK, Ha YC, Koo KH. Ten to 13-year results of delta ceramic-on-ceramic total hip arthroplasty in patients less than 30 years old. J Bone Joint Surg Am 2023;105:789-796.
    Pubmed CrossRef
  90. Kim YH, Park JW, Jang YS, Kim EJ. Long-term results (minimum of 20 years) of a pure proximal-loading metaphyseal-fitting anatomic cementless stem without distal stem fixation in hip arthroplasty. J Arthroplasty 2023;38:743-750.
    Pubmed CrossRef
  91. Konan S, Alazzawi S, Yoon BH, Cha YH, Koo KH. A focused update on preventing ceramic fractures in hip arthroplasty: is the ‘cup’ half full?. Bone Joint J 2019;101-B:897-901.
    Pubmed CrossRef

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