Asymptomatic Osteonecrosis

Should It Be Treated?

Abstract

Currently, there is no consensus regarding the treatment of precollapse osteonecrosis, particularly for asymptomatic osteonecrosis. With approximately 10,000 to 20,000 new cases of osteonecrosis a year, no single surgeon or center has the kind of experience that is able to address the most important questions concerning this disease. The literature strongly documents that symptoms of osteonecrosis will progress. Although the literature also supports the progression of asymptomatic osteonecrosis to symptomatic osteonecrosis on to collapse, that support is less convincing. Progression is proportional to lesion size, with small lesions (< 15% of femoral head involvement by volume) unlikely to progress. Although the results of core decompression have been somewhat controversial, the weight of the literature supports both the efficacy and safety of the procedure. The decision to treat osteonecrosis with core decompression is primarily based upon lesion size and stage of disease and does not necessarily depend on whether the patient is symptomatic. As large lesions (> 30% of the femoral head) are less likely to be successfully treated by core decompression and small lesions (< 15% of the femoral head) are less likely to progress, asymptomatic lesions within these ranges can be observed. The literature supports the position that moderately sized lesions (15-30% of the femoral head) should be treated by core decompression (with or without bone grafting).

The true prevalence of nontraumatic osteonecrosis of the femoral head is unknown, but because most patients with osteonecrosis have a total hip arthroplasty (THA), the number of cases can be approximated by knowing the number of THAs done for osteonecrosis. Large published series of THAs are remarkably consistent, with a diagnosis of osteonecrosis in 8 to 12% of the cases.³⁴ Assuming that an average of 10% of all THAs involve osteonecrosis, it is reasonable to assume that there are 10,000 to 20,000 new cases each year in the United States.^34,53 Another remarkably consistent statistic across series of osteonecrosis is that the disease presents at an average age of mid to late thirties.^2,7,22,34,53 At our institution, 25% of osteonecrosis patients are younger than 25 years.^7,13 This lends a sense of urgency to discover effective treatments to preserve the femoral head, stabilize the disease, and delay THA. Although most patients already have advanced disease at the time of presentation to an orthopaedist, an MRI of a patient with a symptomatic hip sometimes detects an asymptomatic lesion on the contralateral side.

There also is considerable disagreement about which preservative treatment is appropriate for a particular stage of the disease, and there is a considerable nihilism about any preservative treatment.^{6,28,33,34,43} Many physicians are telling patients with early disease to come back when their symptoms justify THA. Much of the medical literature regarding the natural history and surgical treatment of the disease concerns symptomatic osteonecrosis.^{6,7,12,28,36,38,41} The purpose of this study is to define which cases of asymptomatic osteonecrosis should be treated surgically and to provide evidence to support treatment by core decompression.

Natural History

Historically, it generally was accepted that osteonecrosis progressed through a number of distinct stages, ultimately resulting in destruction of the articulating surface of the affected joint.^{9,13,32,34,49,51} As a result, various staging systems have been developed to characterize the progression of this disease.^{8-10,30,38,40,44,48} All the systems describe a disease that evolves from an initial lesion or infarct usually located in the weightbearing portion of the femoral head, followed by an attempt at repair of this lesion with the development of a hypervascular and sclerotic area surrounding the lesion. Then subchondral collapse occurs, which in turn affects the overlying cartilage and finally results in incongruity of the articulating surface. Only recently has evidence been reported that some lesions do not progress clinically or radiologically.^16,17,24,42

Progression can refer to either clinical progression or radiologic progression. Clinical progression involves either development of pain or intensification of pain. Radiographic progression is based on observation of specific features seen on radiographs, such as sclerosis or subchondral fracture. It is clear that clinical and radiologic progression must be interrelated, but exactly how they are interrelated is under debate.

There is no consensus regarding the origin of pain associated with osteonecrosis. Some investigators propose that the pain is associated with increased intraosseous pressure and edema^8,9,13,20; others propose that pain is correlated with radiographic evidence of collapse in the early followup.³⁶ Additionally confounding this issue is the fact that asymptomatic osteonecrosis does exist. Progression of asymptomatic osteonecrosis could refer to either development of pain or progression of the lesion to subchondral collapse. This issue is important because it impacts the decision to treat asymptomatic osteonecrosis and, if so, how it should be treated.

Our appreciation of the natural history of the earliest stages of the disease, whether symptomatic or not, has been limited. Before the availability of MRIs, little was known about the preradiologic stage of the disease, particularly in regard to lesion size. For atraumatic osteonecrosis, the cause and time of onset of the disease is unknown. Traditionally, a diagnosis of osteonecrosis was made using radiographs or the histologic findings of core specimens. Ficat et al⁹ and Hungerford and Zizic¹³ have suggested that elevated intraosseous pressure and abnormal venograms were pathognomic for early osteonecrosis. However, with the advent of the noninvasive MRI, an earlier diagnosis of osteonecrosis became achievable. It was now possible to easily detect the crescent sign and nonradiologic bony changes, such as increased edema. As a result, it became easier to diagnose the asymptomatic case, because many asymptomatic cases also are not apparent radiologically.

Most of what we know about the natural history of osteonecrosis, regardless of whether it is symptomatic, comes from the study of screening at-risk patients, studying the contralateral side in patients presenting with advanced disease, or studying patients in whom attempts at treating the disease (such as with simple protected weightbearing) have failed. Although there are limitations to each of these types of studies, a generalized picture of how the disease behaves has evolved.

Several authors of studies on at-risk patient populations address the issue of onset and progression.^{2,19,22,24,39,42,51} Koo et al²² studied 138 patients treated with corticosteroids for various reasons with no evidence of preexisting osteonecrosis. Twenty-two patients developed ARCO Stage I osteonecrosis within 16 months of onset of treatment. Kopecky et al,²⁴ in a study of 104 renal transplantation patients, reported that 14 patients developed osteonecrosis 1 to 13 months after the onset of steroid therapy. Sakamoto et al⁴² reported that 17 of 48 patients (31 hips) developed osteonecrosis 2 to 6 months after first receiving corticosteroids for various autoimmune-related disorders. In a retrospective study of 60 patients with systemic lupus erythematosis (SLE) and corticosteroid therapy, Sugano et al⁵¹ observed that 9 patients (16 hips) developed osteonecrosis within 9 months to 18 years (mean, 3 years). In another study of osteonecrosis 66 patients with SLE receiving corticosteroid therapy, Aranow et al² detected 11 asymptomatic hips in 8 patients. All remained asymptomatic for 1 year. Most of these studies showed that osteonecrosis, if it is occurs at all, develops within 1 to 2 years of the onset of corticosteroid therapy. The rate of development for osteonecrosis associated with other risk factors remains to be determined.

Any study done before MRI scans were used to diagnose osteonecrosis that attempts to assess the natural history of the asymptomatic side of osteonecrosis must deal with the dilemma of the asymptomatic radiologically negative side of osteonecrosis. For example, Jergesen and Khan¹⁷ reported on 106 patients with osteonecrosis in which an asymptomatic side was noted in 45 patients. Of these 45 asymptomatic hips, 22 had radiographic evidence of osteonecrosis and 23 did not. Three hips in the xray-positive group had prophylactic core decompression. Of the remaining 19 xray-positive patients, 3 collapsed. However, 14 of 19 (74%) of the remaining xray-positive patients became symptomatic during the followup period. Of the 23 xray-negative patients, 3 hips collapsed. Because it is impossible to know how many of the xray-negative patients actually had osteonecrosis, the author’s conclusion that asymptomatic osteonecrosis rarely progresses must be questioned.

Reports have indicated that progression to collapse occurs within 1 to 5 years after the onset of symptoms.^1,5,15,29,32 Nonetheless, a small yet definite number of patients may not progress to another radiologic stage or to collapse.^{17,21,32,37,42,44} Jergesen and Khan¹⁷ found that 5 of 19 asymptomatic radiologically positive patients remained pain free for 71 months to 149 months of followup. Meyers³² reported one case of Stage II (Marcus classification system) osteonecrosis that did not change for 10 years, and another case (Stage IV osteonecrosis with minimal collapse) with complete resolution of pain after nonweightbearing for 2 years. Several investigators have shown that the lesions of some individuals may decrease in size over time.^16,24,42 In fact, pain and MRI changes may disappear completely in some patients. Niishi et al³⁶ reported 15 hips (14 patients) with cessation of collapse, and 10 hips (9 patients) where the patients became asymptomatic. Using MRI to study 25 hips in 14 renal allograft patients, Kopecky et al²⁴ observed that the lesions in 7 hips in 5 asymptomatic patients regressed in size or disappeared. Based on this evidence, it is important to determine the type of patient who may be at risk to progress.

There are a number of factors including stage of the disease, size of lesion, and location of lesion that may influence the rate of progression of osteonecrosis. In 1993, Takatori et al⁵² observed a relationship between the size of the osteonecrotic lesion and collapse. None of the small, medial anterosuperior lesions collapsed, whereas 14 of 17 of the larger lesions collapsed. Shimizu et al⁴⁴ noted that hips in which the lesion involved 25% of the diameter of the head and involved at least 67% of the major weightbearing area were more likely to collapse (17 of 23 hips; 74%). In their study, survival rates for hips diagnosed as Ficat Stage I were better than for Ficat Stage II. Aaron et al¹ also noted that the percentage of those with clinical progression increased with increasing radiologic stage of the disease. In contrast, they found that hips diagnosed with Ficat Stage I disease had evidence of a more rapid radiographic progression than did hips classified as Ficat Stage II and Stage III (p = 0.005). There was a trend for Stage II lesions showing 0-mm to 1-mm of collapse to progress in younger patients at a slower rate than in older patients with Stage II lesions. Using MRI, Nishii et al³⁷ studied 65 hips in 47 patients with a diagnosis of osteonecrosis of the femoral head without radiologic evidence of collapse. Thirty-three hips collapsed, whereas 32 hips did not collapse over the 2 to 3 years of this study. The lesion size in the collapsed group (43.4% ± 22.2) was larger than the lesion size in the group of hips that did not collapse (18.8% ± 14.4; p < 0.001). Nishii et al³⁷ noted that 6% (1/16) of the A lesions (volume < 15%), 42% (8/19) of the B lesions (15-30% involvement), and 80% (24/30) of the C lesions (volume > 30%) collapsed. The hips that did not collapse generally were classified at an earlier stage of the disease (most were ARCO Stage 1). In the nine A and B lesions that collapsed, collapse was more likely when the lesion was located at the anterosuperior portion of the femoral head. Koo and Kim²¹ reported collapse in 97% (28/29 hips) of the medium (34 to 66, index of necrotic extent) and large lesions (67 to 100, index of necrotic extent) within 12 months of diagnosis as compared to only one of eight hips (12.5%) with smaller lesions (≤33, index of necrotic extent) at 15 months. Sugano et al⁵¹ reported no radiologic changes in the six patients with the smaller more medial Type A lesions (Japanese System) whereas, in the eight patients with the larger Type C lesions, 6 hips in 4 went on to collapse.

There are several limitations of previous publications concerning early osteonecrosis. Routine radiographic examination may not detect the subtle changes seen with early stage disease, such as fracture of the articular surface at the periphery of the necrotic area or the beginning of a crescent sign.³² Magnetic resonance images were not used routinely to screen for early osteonecrosis until the late 1980s, and many cases of preradiologic osteonecrosis may have gone unrecognized. It even has been questioned whether MRI scans are sensitive enough to screen for ON.¹⁷ Another confounding variable is trying to study the natural history of this disease in patients with different etiologic risk factors. Changes associated with these risk factors such as alterations in corticosteroid therapy or abstaining from alcohol possibly could influence the impact of that risk factor on the natural history of the disease. Several studies have evaluated the asymptomatic leg of a patient diagnosed with osteonecrosis in the contralateral leg. However, it is unclear as to whether the natural history of bilateral or multifocal disease is identical to that of unilateral disease. Many studies have implied that their findings in conservatively treated patients (ie limited weightbearing) can be extrapolated to the untreated patient. However, it is possible that conservative treatment impeded the rate of progression of the disease in some patients.

Treatment

Joint-preserving procedures used for the early stage of symptomatic osteonecrosis have included nonoperative measures (protective weightbearing and analgesics), core decompression with and without bone grafting, vascularized bone grafting, nonvascularized bone grafting (eg, trap door, lightbulb procedures) and osteotomies. Because of the morbidity associated with vascularized bone grafts, nonvascularized bone grafting and osteotomies, these procedures have not been considered for treatment of asymptomatic patients. To address the possible surgical treatment of asymptomatic osteonecrosis, we need to appreciate the effectiveness of nonoperative treatment and core decompression in the treatment of early-stage symptomatic osteonecrosis.

Protective weightbearing (with analgesics) is ineffective in delaying collapse. In a review of 21 publications in which the results of nonoperative treatment were reported, Mont et al³³ reported that only 182 of 819 hips (22.7%) with a mean followup of 34 months (range, 20 months-10 years) had satisfactory clinical results. For Ficat Stage I diagnoses, the hip survival rate improved to 35%. Patterson et al⁴¹ reported poor results in 79% of hips (19 of 24 hips) who had received conservative treatment. Musso et al³⁵ reported that 94% of hips had unsatisfactory results, with 76% requiring arthroplasty by 16 months. Stulberg⁴⁹ and Stulberg et al⁵⁰ calculated a median survival time of 11 months with a survival rate of almost 20% by 60 months for Ficat Stage I hips. Koo et al ²³reported similar results for early stage disease (Steinberg Stage I) with a median time to failure of 15 months and a survival rate of 33% (4 of 12 hips).

Since it was first introduced, there has been controversy surrounding the use of core decompression for the treatment of osteonecrosis. During a routine diagnostic core-biopsy procedure, Arlet and Ficat³ noted that the diseased hips had an elevated intraosseous pressure and that the procedure resulted in a decompression of the affected joint. Concerns were raised revolving around what pathophysiologic mechanisms were involved and whether the procedure was safe. Although the first concern remains under debate because of our lack of knowledge about the pathogenesis of this disease, concerns about significant fracture rates have mostly not been borne out. Although high complication rates (fracture, infection) have been reported in a few publications,^6,12 the experience of the majority of authors is that the complication rate is extremely low^3,7-9,13,33

Several publications report on survival analyses involving core decompression for the treatment of osteonecrosis. Stulberg et al⁵⁰ found survival rates exceeding 70% (Ficat Stage I), 71% (Ficat Stage II), and 73% (Ficat Stage III) at 60 months followup. The median survival rate for Stage I disease was greater than 27 months. In the series with the longest followup, Fairbank et al⁷ reported a survival rate of 92% at 5 years, 52% at 10 years, 30% at 15 years, and 2% at 20 years. With regard to Ficat Stage I disease, the success rates were 100% (5 years), 96% (10 years) and 90% (15 years). In a study of early stage disease (Ficat Stages I, IIA, IIB), Iorio et al¹⁵ found clinical and radiographic success rates of 76% and 72% respectively at 1 year, 52% and 61% at 2 years, and 44% and 37% at 5 years. The survival rates were improved in patients with good bone stock and patients who weighed less than 79.4 kg. Simank et al⁴⁵ reported success rates of 82% after 2 years, 57% after 4 years, and 50% after 6 years for early stage disease (Steinberg Stages 0-II). There was a trend of inferior results with extensive lesions. In contrast, both Koo et al²³ and Scully et al⁴³ had lower success rates at 3 years for all patients included in their studies. Koo et al²³ reported a survival rate of less than 25% for early stage disease. Scully et al⁴³ reported a survival rate of less than 70% for Stage II and approximately 40% for Stage III disease. However, they noted that core decompression was effective in the treatment of Ficat Stage I disease, with none of the eight hips treated with core decompression requiring THA.

There are six articles^{6,12,23,25,28,43} that are cited frequently in the literature as showing the ineffectiveness of core decompression to treat osteonecrosis. In 1986, Camp and Colwell⁶ reported that 11 of 18 (60%) early stage hips went on to collapse. Concerns about this study include the high complication rate (fractures, a broken trephine, and the inadvertent use of the trephine into the joint), the fact that 40 procedures were done by 13 different surgeons, and the fact that that a nonstandard technique was used. Hopson and Siverhus¹² found 12 of 20 hips with Ficat Stages I or II required additional intervention at an average time of 9.2 months because of progression of pain (n = 1), progression of pain and radiographic changes (n = 10), and fracture through the tract (n = 1). They observed that eight hips did not progress at their latest followup (46.8 months, 15-67 months). Arlet and Ficat³ objected to Hobson and Silverhus’ use of the words “considerable morbidity” because they reported one fracture in the 21 procedures and Arlet and Ficat’s experience had been only one fracture in more than 500 procedures at that time. Learmonth et al²⁸ reported that core decompression was ineffective for either Ficat Stage I osteonecrosis [7 of 12 hips (58%) clinical and 9 of 12 hips (75%) radiologic deterioration] or Ficat Stage II osteonecrosis [22 of 29 hips (76%) clinical and 25 of 29 hips (86%) radiologic deterioration]. However, the coring procedure used by Learmonth and colleagues involved the breaching of the subchondral bone and the successful biopsy was described as “capped proximally with articular cartilage,”²⁸ a modification of the procedure not advocated for core decompression. Kristensen et al²⁵ reported that only five of 18 patients with Ficat Stage I disease had pain relief lasting more than 1 year. As stated previously, Scully et al⁴³ found better survival rates of hips after vascularized fibular grafting, compared with core decompression alone. Although their study frequently is viewed as one against the use of core decompression, the survival rates were 100% (8 of 8 hips) for Ficat Stage I and 65% (28 of 43 hips) for Stage II disease at greater than 4 years of followup. One key criticism of most of these studies is that the lesion size was not evaluated, which we now know influences the outcome of this procedure.

Koo et al²³ reported on 37 hips in 33 patients with Steinberg Stage I (22 hips), Stage II (11 hips), or Stage III (four hips) disease. Only cases of early osteonecrosis without radiologic evidence of collapse were included. Failure was defined as collapse on xray greater than or equal to 2 mm. The core decompression procedure involved filling the defect with cancellous bone graft. They observed that 14 of 18 hips (78%) that had core decompression collapsed. Although one of the collapsed hips failed at 3 years, thirteen collapsed within one year of the core decompression. However, five of the 18 cases were successful with a mean followup of 33.6 years (range, 27 to 39 months). There was a 30% survival rate for Steinberg Stage I up to about three years of followup.

Several investigators^{4,11,21,26,47} have reported a relationship between lesion size and the probability of a successful outcome for core decompression. In general, the smaller the lesion, the greater the probability for success. In 1990, Beltran et al⁴ found that hips with large lesions (> 50% involvement) were more likely to collapse (13/15 hips; 87%) than hips with small lesions (< 25% involvement) (no cases of collapse in eight hips). In the medium-sized lesions (25%-50% involvement), the results were more variable, with three of seven femoral heads collapsing. Lafforgue et al²⁶ reported similar findings, concluding that osteonecrotic hips with lesions involving more than 45% of the weightbearing femoral cortex had fewer successful results than hips with lesions with less than 45% of weightbearing involvement. Koo and Kim²¹ found that although only one of eight hips with small Grade A lesions (≤ 33, index of necrosis) collapsed, almost all of the larger lesions [21 of 22 hips with Grade B lesions (34-66, index of necrosis); seven of seven hips with Grade C lesions (67-100, index of necrosis)] collapsed. Steinberg et al⁴⁷ found that, in addition to lesion size, stage of disease also influenced the outcome. None (0 of 3 hips) of the Type A (< 15% of femoral head involvement by volume) Stage I lesions progressed, whereas some degree of radiographic progression was seen in all other hips studied (n = 70), including the Type A, Stage II lesions (n = 11). Total hip replacement was required more frequently (19 of 59 hips; 32%) in the moderate (15-30% of the femoral head) and large lesions (> 30% of the femoral head) as compared to the small lesions (1 of 14 hips; 7%) at a followup between 2 and 6 years. Holman et al¹¹ also reported better outcomes in patients with less than 21% femoral head involvement compared with patients with larger lesions. In contrast to the previously cited investigators, Lavernia and Sierra²⁷ did not find a correlation between extent of femoral head involvement and survival rates for core decompression. However, failure was defined as reoperation (total hip arthroplasty), which may not be a sensitive measure of progression. Most of the studies support that lesion size seems to be the most important factor affecting the outcome of the natural history or treatment outcome for osteonecrosis. None of the studies previously mentioned address the concept of treating asymptomatic osteonecrosis. Therefore, a careful analysis of lesion size with MRI analysis after nonoperative treatment or core decompression is vital.

In discussing the effectiveness of a treatment, most studies have used radiographic progression or clinical progression as the outcome. Studies that have used progression to arthroplasty have been criticized for the associated factors that also may contribute to making decision to treat osteonecrosis of the femoral head. However, little attention has been given to the delay in progression of osteonecrosis or the delay to treat this disease. With the risks and benefits associated with core decompression, an impedance in the rate of progression compared with the natural history of this disease should be an acceptable outcome. However, what is an acceptable delay: 2 years, 3 years, or 5 years?

Risk and Benefit Analysis

In the preceding sections we have provided the evidence that many, if not most, cases of osteonecrosis of the femoral head will progress to collapse and that treatment is effective in delaying THA, if not permanently preserving the femoral head. However, all treatments are not equal. Although it may be true that free-vascularized bone grafting or intertrochanteric osteotomy have an equivalent or even a higher success rate than core decompression for early stage osteonecrosis,^43,46 it also is true that there is a greater morbidity, a higher complication rate, and a greater negative impact on THA for these procedures. In assessing the risk and benefit ratio for a particular patient, several aspects of the patient and the disease come into play. The age of the patient determines the importance of success. Preservation of the femoral head is more important for a 25-year-old than a 55-year-old because of the current anticipated longevity of THR. Size of the lesion is also important. The larger the lesion, the less likely any treatment will be successful. In contrast, small central lesions are not likely to progress. Whole head lesions probably cannot be prevented from collapsing. Patient comorbidities enter into the equation. Patients should be seen in terms of probable longevity, as well as potential level of activity. A sedentary individual is a more satisfactory candidate for THA than a highly active one.

Recommendations for Treatment

Based on what is known about osteonecrosis (and being mindful that there is much that is not known), the authors propose that asymptomatic osteonecrosis should be treated with core decompression (with or without bone graft) in an attempt to mitigate the anticipated progression of the disease. There are several exceptions to this recommendation. Occasionally, very large asymptomatic lesions of the contralateral hip will be discovered on MRI for evaluation of a symptomatic side (Fig 1C). These lesions are greater than 260°, as measured on the Kerboul angle¹⁸ (the sum of the angles of involvement measured from the center of the head on both AP and lateral xrays). The evidence is so strong that conservative treatment is ineffective for large asymptomatic lesions that preservative treatment cannot be recommended. Also, very small lesions (Fig 1A), particularly those that appear in the central portion of the weightbearing cone, can simply be observed because these lesions may not progress. Asymptomatic lesions in patients who would be otherwise prime candidates for THA (> 55 years old) can also be observed. In patients between the ages of 30 and 50 years with lesions in the moderate size range (Kerboul angle, 120°-180°) (Fig 1B),^21,37,51 we think that it is reasonable to treat these patients with core decompression (with or without bone grafting). The evidence for this treatment recommendation is admittedly circumstantial, but the risks of treatment are small and the consequences of progression are substantial.

Fig 1.: A-C. (A) Small central osteonecrosis lesion (left hip), unlikely to progress by virtue of both size and location, is shown. (B) Large symptomatic hip lesion (left) with early collapsing moderate sized asymptomatic lesion in the weightbearing area of the right hip is shown. The right sided lesion is likely to progress. (C) The left hip lesion is painful and shows early collapse. Although the right hip lesion has not collapsed, it involves the whole femoral head. Therefore, prophylactic intervention is not indicated.