Osteonecrosis after renal transplantation

Jon J. P. Warner, Sumner Karas, Thomas S. Thornhill

9 Osteonecrosis After Renal Transplantation

The term renal osteodystrophy, as classically used to describe the musculoskeletal manifestations of uraemia, included osteoporosis, osteitis fibrosa cystica, osteomalacia, osteosclerosis and metastatic calcification. The advent of maintenance haemodialysis and renal transplantation has altered the clinical, metabolic and radiographic disorders that constitute this syndrome." Perhaps the best example of this change has been the condition of non-traumatic osteonecrosis (NON) of the femoral head seen in association with renal transplantation. This type of osteonecrosis frequently occurs in young, otherwise healthy patients with monoarticular disease who are at high risk of loosening of the prosthesis following total hip arthroplasty, 16 although the incidence of the condition following kidney transplantation has decreased in recent years in association with better control of phosphate levels, increased calcium concentration in the dialysis bath, and improved metabolic status at the time of transplantation. 4l,42,6l,70,74,77 However, NON still occurs in approximately 6 percent of renal recipients and remains a major diagnostic and therapeutic dilemma in orthopaedics. 13,2I,22.24,27,43,45,89,92,99.102.103,1I5 The term osteonecrosis is preferred to avascular necrosis where there is loss of arterial supply to the femoral head. 39,67,68,73 The term osteonecrosis, where this aetiology is less clear, more aptly describes a series of biologic events which culminate in the death of cellular elements within the femoral head. Although susceptibility of the femoral head may be related to its marginal single inflow-outflow vascular system and the clinical outcome in the untreated state being progressive collapse of the femoral head,13,21 the aetiology and pathophysiology of osteonecrosis remains co ntroversial.2.19,20,22,25,28,30,31,33-35,39,40,45-52,55,57-59,60,73,76,77,83,90,91,104,107,109,112 In general, NON occurs most frequently in patients treated with high dose corticosteroids for systemic illnesses such as chronic renal failure and systemic lupus erythematosis, although numerous clinical conditions have also been identified as risk factors (Fig.9-1). The patients are typically less than 50 years of age and the incidence of bilateral involvement of the hips approaches 80 percent. 50,100,1l5 Assuming the transplant functions well, one is dealing with a young, active patient population subjected to the problems associated with chronic steroid use as well as

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178 I.

AVASCULAR (TRAUMATIC) OSTEONECROSIS OF THE FEMORAL HEAD subcapital fracture hip dislocation

II. IDIOPATHIC OSTEONECROSIS glucocorticoids Steroid therapy Cushing's syndrome Systemic lupus erythematosis Haemaglobinopathies S-S, SoC, others Metabolic disorders Gout Gaucher's disease Alcoholism Pancreatitis Fat embolism Dysbarism true idiopathic"Chandler's Disease"

Figure 9-1. Classification of Osteonecrosis of the Femoral Head. From Kenzora lE, Glimcher Ml: Osteonecrosis, in Kelly WN, Harris ED, Ruddy S, Sledge CB (eds): Textbook of Rheumatology, Philadelphia, \V.B. Saunders Co., 1981, pp. 1755-1777.

occasional steroid pulses to treat acute rejection episodes. Steroid-induced osteoporosis plus immunosuppression from combined use of prednisone, azathioprine. and cyclosporin may increase susceptibility of the femoral head to cellular necrosis. If the transplant fails. the patient returns to dialysis when he is subjected to additional problems of renal osteodystrophy; this may be additive in accelerating femoral head collapse.

AETIOLOGY

The aetiology of NON is unknown, but it has been suggested to be multifactorial and not a single event.f" The first step in early diagnosis is recognition of any of the recognized risk factors in the patient (Fig. 9-1). Transplant patients have at least two significant risk factors, corticosteroid treatment and renal bone disease. The former appears to be the essential element; in fact, it is quite rare for patients with uraemia on long-term dialysis to develop NON in the absence of steroid treatment.f Thus, the causes of NON in renal transplant patients include bone disease associated with chronic renal failure (secondary hyperparathyroidism, osteomalacia, osteoporosis). corticosteroid immunosuppression. and perhaps other unidentified factors. 67,7o Mechanistically it would appear that systemic illness renders osteogenic cells more vulnerable; with the additive effects of corticosteroids to accumulated cell stress. osteonecrosis results.f?

Stage

Clinical feature

Radiographic signs

OX w ithout core biop sy

Haemodyn amics

Scintogram

+ ++

reduced uptake ? increased uptake

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probable

or NI.

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Early

o

Preclinical I Preradiographic

IIA Before flatten ing of head or sequest rum formation liB Trans it ion

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0 0 Normal joint lin e Normal head contour NI. trabecul ae or osteoporosis Diffuse poro sis. sclerosi s. or cysts - NI. joint line NI. head contour Flattening Crescent sign

Broken con tour of head; sequest rum ; NI. joint space "out of round " Flattened contour Decreased joint space; Collaps e of head

+

im possi ble im possible

Figure 9-2. Ficat Classificat ion of Non-traumatic Osteonecrosis. From Ficat RP: Review Art icle- Idiopathic bone necrosis of the femoral head . J Bone Jo int Surg 67B:3-9, 1985.

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Figure 9·3a. The earliest reliable radiographic sign of NON is the crescent sign, a pathognomonic, radiolucent, subchondral line parallelling the articular surface.

Figure 9·3b. Despite core decompression, 24 months later the femoral head has collapsed and is now in Ficat Stage III disease. Arrow shows area of femoral head collapse.

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DIAGNOSTIC APPROACH Clinical and experimental work supports the assertion that the most important factor in effective treatment of transplant related NON is early diagnosis. 28,47,50,105,115 The average time interval from renal transplantation to the onset of hip symptoms is 10 months, and the vast majority of patients have had perioperative or postoperative 'pulse' steroids,61,74,115 Symptoms usually preceed radiographic manifestations of the disease by several months; and by the time X-ray changes are evident, the prognosis is poor for survival of a normal hip joint. 70,91,108 The first step in diagnosis is a high index of suspicion in patients who develop hip pain of unclear aetiology in the setting of steroid treatment. The diagnostic approach may then include radiographic examination, bone scanning, magnetic resonance imaging (MRI), and 'functional bone investigation' (FBI) by manometric testing and venography.28,50

Radiographic Classification The Ficat System" classifies NON based on the radiographic progression of disease from normal appearance (Stages 0 and I) to sclerocystic involvement of the femoral head (Stage IIA), subchondral collapse or 'crescent sign' (Stage liB), and finally, collapse or 'out-of-round' and frank arthritis of the hip joint (Stages III and IV) (Fig. 9-2). The prognostic significance is that progression to Stage lIB with a crescent sign on X-ray, implies subchondral collapse of bone and loss of architectural integrity of the femoral head (Fig. 9-3); procedures which attempt to preserve the femoral head wiII fail in stages beyond Ficat lIB. The goal should be detection of disease in the preclinical (Ficat 0) stage or the pre radiographic (Ficat I) stage (Fig. 9-4). Evidence suggests that these patients wiII respond to core decompression, a femoral head saving technique to be discussed below. The Steinberg classification'?' was developed in 1984 as a quantitative modification of the Ficat system; it employs methods of point counting, planimetry, and concentric circles to measure the degree of femoral head involvement, permitting more sensitive and precise monitoring of disease progression (Fig. 9-5).

Bone Scan Prior to development of a crescent sign (Ficat lIB), the diagnosis of NON may be difficult and is based on the patient's history of risk factors, symptoms, and an X-ray picture of sclerocystic femoral head involvement (Ficat lIA). Symptoms usually antedate the earliest radiographic changes by several months, and often occur as long as 12 months after transplant.'? Patients in preclinical (Ficat 0) or preradiographic (Ficat I) stages of disease are very difficult to detect; however, a patient with proven NON on one side has an 80 percent chance of developing contralateral disease. Radionuclide bone scanning may be helpful though not diagnostic. The earliest diagnostic finding is photopenia of the femoral head, a manifestation of ischaemia and infarction!'! (Fig. 9-4). As the repair process progresses, the femoral head demonstrates a 'hot' scan 104 , I06, 1I5 (Fig. 9·6). In the best situation, scintigraphy may

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Figure 9·4a. The right hip (upper) is normal, and the left hip (lower) is Ficat Stage I disease (Pre-radiographic). be sensitive but non_specific;14.1l».I06.115 in addition, the high incidence of bilateral involvement and previous hip replacement surgery may make it difficult to interpret this test. The false negative rate in most recent studies has been reported to range from IO to 52 percent. II,48,49,1l»,I07,1I5 Current indications for use of technetium-99 bone scanning is unexplained hip pain in a patient with normal radiographs who is at risk for NON.

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..

Figure 9-4b. Technetium-99 bone scan demonstrates photopenia of the left femoral head. Normal roentgenogram; normal bone scan Normal roentgenogram; abnormal bone scan Sclerosis and/or cyst formation in femoral head A) mild « 20%1 B) moderate (20-40%1 C) severe (>40%) Stage III Subchondral collapse (crescent signl without flattening A) mild « 15%) B) moderate (15-30%) C) severe (>30%) Flattening of head without joint narrowing Stage IV Al mild «14% of surface & <2mm depression) B) moderate (15-30% of surface of 2-4 mm depression) CI severe (> 30% of surface of > 4 mm depression) Flattening of head with joint narrowing Stage V A) mild (determined as for B) moderate stage IV, plus estimate C) severe of acetabular involvement Stage VI Advanced degenerative changes of hip joint - For sclerocystic changes: Point counting on a grid determines percent involvement of head. - For crescent sign: Planimetric assessment is performed on AP and lateral X-rays. - For articular flattening: Concentric circles are used to assess percent of head flattening. Stage 0 Stage I Stage II

Figure 9-5. Steinberg Classification for Non-traumatic Osteonecrosis. From Steinberg ME, Brighton CT, Hayken GD, Tooze SE, Steinberg DR: Early results in treatment of avascular necrosis of the femoral head with electrical stimulation. Orth Clin N Am 15(1):163-175, 1984.

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Figure 9·6a. In this patient the left side is normal, and the right side shows Ficat Stage IIA disease.

Figure 9-6b. The bone scan shows increased uptake on the right side compared with the normal pattern on the left.

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Figure 9-7a. Manometric and venographic studies. A special trochar is inserted percutaneously through the greater trochanter and manometric and venographic studies are then performed in order to assess bone marrow pressure and venous outflow.

Figure 9·7b. Biplane image intensification is used to confirm the position of the trephine for removal of a core of bone from the femoral head and neck. The trephine is directed up into the lesion in the anterolateral portion of the femoral head.

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Magnetic Resonance Imaging Early clinical experience with MRI has revealed that it is the most sensitive technique for detection of early NON.4-l·5~.8~-88 In the less advanced course of the disease, MRI reflects primarily metabolic and cellular derangements in the marrow, with ingrowth of vascularized mesenchymal tissue during the subsequent repair process,37-39 As these changes occur during the preclinical (Ficat 0) and preradiographic (Ficat I) stages, treatment may be instituted prior to disturbance of travecular architecture while the disease is still at the cellular level and theoretically reversible. The classic appearance of NON on MRI is a dark segment in the femoral head, surrounded by a peripheral high intensity rim on T1 imaging. Recent studies by MitcheIl8~-86 have suggested that the radiographic appearance of the os teo necrotic lesion on Tl imaging may be a prognostic factor in determining the fate of the femoral head, with a central dark area of low intensity being a poor prognostic sign while a higher intensity lesion may be more favourable.

Functional Bone Investigation and Core Decompression The rationale for functional bone investigation (FBI) and core decompression (CD) is predicated on the assumption that the femoral head behaves as a closed compartment with blockage of osseous microcirculation resulting in increased bone marrow

Intramedullary pressure OSTEONECROSIS"

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Marrow oedema Fibrosis Figure 9-8. In NON-associated with steroids, hypertrophy of intraosseous adipocytes and fat cell emboli have been implicated as factors associated with obstruction of venous outflow at the sinusoidalleveI. The result is an elevation of venous outflow resistance, bone marrow pressure, and a progressive ischaemia. A vicious cycle develops: This consists of intraosseous hypertension secondary to increased venous outflow resistance, which leads to progressive ischaemia that causes marrow oedema and fibrosis, and a further reduction in venous outflow, leading to more ischaemia, and eventually to necrosis of marrow and osseous cellular elements. Core decompression is thought to function by decompression of this developing compartment syndrome and interruption of this vicious cycle of progressive ischaemia.

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pressure (BMP). As BMP increases relative to mean arterial pressure, a relative decrease in femoral head perfusion pressure occurs, resulting in decreased perfusion with progressive ischaemia and eventual necrosis of all the cellular elements 28,48.50.8I,82,106,1I9 (Fig. 9-9). Normal BMP is taken to be less than or equal to 30 mm mercury.v-'? Core decompression is the technique of removal of a core of bone from the involved femoral head, and is believed to work in a manner analogous to fascial decompression for compression neuropathy or muscle compartmental syndrome" (Fig. 9-7). The procedure also allows definitive diagnosis since it provides tissue from the femoral head for pathologic determination of osteonecrosis.

PATHOPHYSIOLOGY OF NON Biology of necrosis - The Infarction Theory was originally suggested by Chandler as 'coronary disease of the hip' .15 A variety of circumstances such as mechanical interruption, fat emboli,19,23.31-34.40.46,59,6O and interruption of blood supply (lateral retinacular vessels) to the anterolateral segment of the femoral head might lead !o infarction of the femoral head. However, recent experimental and clinical observations have led to alternate interpretations; it is now commonly believed that NON is the product of accumulated insults at the cellular level, and not an instantaneous event. 68 The Progressive Ischemia Theory was originally proposed by Ficat and Arlet,2S-30 B M P Gauge

Adipocytes

Cortical Bone Trabecular Bone

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Venous Outflow

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Figure 9-9. Starling mechanism of decreased intraosseous blood flow. Closed compartment. Vessels and sinusoids function as thin-walled, flexible tubes within the cortex which acts as a rigid canister. Decreased venous outflow and elevated bone marrow pressure may occur as a result of increased volume within the marrow, or from any process which obstructs circulation at the sinusoidal level. For example, intramedullary lipocyte hypertrophy (corticosteroids) proliferation of reticuloendothelial cells (Gaucher's disease), nitrogen bubble emboli (Caisson's disease). Ischaemia of all the cellular elements results, and further extravasation of fluid into the extravascular spaces may further impede microcirculation and enhance ischaemia.

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DISEASE

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Figure 9·10. Accumulation cell stress. The cause of idiopathic osteonecrosis is multifactorial and rarely a single instantaneous, or sudden event. Anatomic location (vascular supply to the femoral head), systemic disease (renal failure), and steroids (cytotoxicity and indirect vascular effects) are the key elements which are additive in femoral head necrosis. Accumulated cell stress or sickness progresses and eventually becomes irreversible, and necrosis results. From Kenzora JE, Glimcher MJ: Accumulated cell stress: The multifactorial etiology of idiopathic osteonecrosis. Ortho Clin N Am 16(4):669-679, 1985. then by Hungerford.f"?' This explanation of the pathophysiology of NON is based on the observations that bone functions like a Starling resistor.81,82,89 Ficat states that the common denominator is blockage of the osseous microcirculation with resultant intramedullary fibrosis, and that this develops into a vicious cycle due to the compartmental nature of bone-" (Fig. 9·8). It is believed that any condition which increases BMP will predispose the femoral head to NON28,50,103 (Fig. 9-10).

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The association between prolonged corticosteroid administration and elevated BMP has been decided in many studies,23.32.3S,4 8 .so. s3 .s ~ .JI) .1I~ and several investigators have demonstrated reduced femoral head blood flow associated with elevated BMP in the setting of chronic corticosteroid treatment. f10.f11 Intramedullary lipocyte hypertrophy has been observed in these hips, and has been implicated as a mechanism of compressing the intraosseous microcirculation." Ficat and others believe that preclinical (Stage 0) and preradiographic (Stage 1) disease, and early disease prior to subchondral collapse (lIA), may be reversible by core decompression which alleviates venous hypertension, decreases elevated BMP, and thus prevents ischaemia from progressing to necrosis of cells within the femoral head.14·1s.so

THE ROLE OF CORTICOSTEROIDS Multiple investigations have analysed the effects of steroids on bone. Corticosteroids routinely produce osteoporosis when administered over a prolonged period to experimental animals2J.34.SJ but do not produce osteonecros is in otherwise healthy subjects . Others, however, have observed random and focal loss of osteocytes in femoral heads of an imals receiving chronic high doses of corticosteroids.22.2J.H.4o.89.loo.lIs subch ondr al r esorpt ion With r evas cutariz at ion

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B. Figure 9-11. Development of subchondral collapse. A: Following necrosis of a segment of bone, there is proportionately greater osteoclastic response at the subchondral bone plate and this weakens the structural integrity of this area. B: The high concentration of shear forces here results in eventual subchondral collapse ('crescent sign' or Ficat Stage lIB). Appositional new bone formation occurs to a varying degree in the underlying trabecular bone of the cancellous portion of the femoral head, and this corresponds to the sclerosis seen on X-ray. C: However, osteoclastic resorption outpaces osteoblastic new bone formation in the subchondral area and fracture of this relatively weakened area results in flattening of the femoral head (Ficat Stage III) . D: Involvement of the acetabular side of the joint results from incongruity of the femoral head, and frank osteoarthritis is the end result.

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More recent studies using the electron microscope have demonstrated progressive ultrastructural degeneration of osteocytes secondary to gradual accumulation of intracellular lipids. 62-65 It appears that corticosteroids exert a direct cytotoxic effect on osteocytes, rendering these cells less resistant to stresses of local ischaemia or added metabolic insults. The precise biologic mechanisms of this cell toxicity are unknown, but at high levels corticosteroids impair metabolism of cell membranes and ribonucleic acid. 67 Corticosteroids may also affect blood flow within the femoral head indirectly through mechanisms which increase BMP and reduce perfusion pressure, analogous to a compartment syndrome (Fig. 9_9).8,29,30,51,78,94,114 Other proposed mechanisms for elevated BMP have included lipocyte hypertrophy within the marrow,89,113,114 aberrations in lipid metabolism 45,46,53,62-M,78,89,97,109,1I4 or fat emboli occluding intraosseous microcirculation at the subchondral level.22,23,32-34,46,53,57,58,60,97,114 Glimcher and Kenzora have proposed the Accumulative Cell Stress Hypothesis of NON.37-39,67,68,70 They define cell stress as the relative state of illness or dysfunction of the cells within the femoral head; the aetiology is believed to be multifactorial. The major variables appear to be anatomic locations, systemic illness, and corticosteroids (Fig. 9-10). The theory postulates that bone cells become more stressed in a cumulative fashion. During the development of chronic renal failure, for instance, multiple metabolic bone disorders include secondary hyperparathyroidism, osteomalacia, and osteoporosis. As the condition progresses and the patients require chronic haemodialysis, the bone disease worsens. Individuals who then receive renal transplants require continuous immunosuppression, including steroids. The anatomic location of cells within the femoral head places them at risk for ischaemia due to the single inflow-outflow vascular anatomy of this region, while corticosteroids provide the final stress to already dysfunctional cells, and produce irreversible changes. The result is death of all marrow and bone forming cells in the femoral head.

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Figure 9-12a. This patient has Ficat Stage IIA disease with (sclerotic predominant) a greater degree of sclerotic new bone formation in the femoral head.

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Figure 9-12b. In this patient with Ficat Stage IIA (cystic predominant) there is a greater degree of cystic involvement of the femoral head and relatively little sclerotic new bone formation. This may represent less active bone formation in response to ischaemia and necrosis; and cystic predominant IIA disease may prognostically be less favourable than sclerotic predominant IlA disease with regard to core decompression. This may be due to the scaffolding effect of new bone against collapse of the necrotic portion of the femoral head.

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Figure 9-12c. The anterolateral area of both femoral heads demonstrates an avascular (cold) segment surrounded by a (hot) area of increased bone turnover.

EVENTS FOLLOWING NECROSIS

Following cell necrosis within the femoral head, regardless of aetiology, a series of biological events occur which result in repair and new bone formation. There appears to be two separate processes occurring in cancellous bone and the cortical bone of the subchondral plate (Fig. 9-11). In the cancellous bone, there is invasion and

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Ficat Hungerford Warner

82 18 12

6 11 17

FfCAT STAGE (#Hips) IIA & liB Failure (%)

51 23 16

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69

Figure 9-13. Comparison of results of core decompression of the femoral head. From Ficat RP, Arlet J: The syndrome of bone and ischemia, in Ischemia and Necrosis of Bone, Hungerford DS (ed): New York, William & Wilkins, 1980, pp. 77-102. replacement of necrotic marrow between dead trabeculae by proliferating capillaries and undifferentiated mesenchymal marrow cells from living bone. Through the process of dedifferentiation, new osteoblasts are formed from mesenchymal cells and woven bone is laid down upon dead trabeculae. This results in an increased mass of bone per unit volume of tissue and leads to a local increase in bone density, this is perceived as sclerosis radiologically and classified by Ficat as Stage IIA disease (Fig. 9-12). In the subchondral area, dense cortical bone is replaced by the process of creeping substitution, which favours osetoclastic resorption of the dead bone at a rate exceeding osteoblastic new bone formation. This results in a net decrease in the mass of bone in the subchondral area of the femoral head." The inequality of repair between cancellous bone of the femoral head and cortical bone of the subchondral area, renders the femoral head susceptible to fracture in the subchondral region. With normal physiologic loading of the hip, sites of high load are concentrated at the antero-lateral portion of the femoral head; thus, a subchondral fracture may occur in this weakened portion of the head. The radiographic picture seen is Ficat Stage lIB, or 'crescent sign' (Fig. 9-3); at this stage the disease process as become irreversible and leads to eventual femoral head collapse, joint incongruity, and eventual arthritic changes.

TREATMENT OPTIONS Prophylactic Treatment Since 1975, there has been a marked decrease in the incidence of NON associated with transplantation to only 1-2 percent of patients.61.67-7o.74 It appears that this decreased incidence is related to prevention of underlying renal bone disease by changing pretransplant dialysis protocols and decreasing maintenance steroid doses after engraftment.sl-s" The esential changes in dialysis include increasing ionized calcium levels in the dialysate and increasing oral calcium supplementation so that calciurri intake via diet and medication is greater than 1 g/day. Additional changes in medical management comprise administration of dihydrotachysterol (0.125-0.5 mg/day), multivitamins, and oral phosphate binders in the form of aluminium-containing antacids. These changes have had the combined effect of producing healthier bone tissues with a decreased exposure to cellular toxins," though reports of aluminium induced osteomalacia of bone have raised concerns about this newer form of therapy.

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CONSERVATIVE MANAGEMENT Non -traumatic osteonecrosis associated with chronic renal failure and steroid treatment is a progressive disea se leading to inevitable femoral head involvement and collapse. There is no role for conservative treatment by non-weight bearing with crutches due to the overwhelming (>90 percent) failure rate. 90,I05 Similarly, hip arthrodesis is a poor choice since this disease is bilateral in as many as 80 percent of ind ividuals. and bilateral hip arthrodesis leads to a poor functional result . 66,m

TREATMENT PRIOR TO COLLAPSE (STAGES 0, I, IIA) Core Decompression The principle of core decompression is to interrupt the effects of progressive ischaemia of the femoral head . The technique involves driling through the lat eral femoral cortex and removing an 8 mm core of bone. It is theoretically applicable in the ischaemic phase of disease prior to frank osteonecrosis or only after a moderate amount of necrosis . The rationale for the technique is based on the assumption tliat the femoral head functions as a 'Starling resistor' (Fig. 9-9), as it is modelled as a rigid canister through which thin-walled, flexible tubes (vascular channels) pass, It is believed that while driving pressure (mean arterial pressure) remains constant, an increase in pre ssure (BMP) within this rigid, osseous canister but outside the flexible tubes, causes a proportionate decrease in flow (perfusion pre ssure).20,28,29.47-S0,I03.106,1I2.1I3.1l7 The resulting intraosseous hypertension has been attributed to microvenous stasis secondary to an increased volume of marrow adipocytes,20 .23.112-114 intraosseous lipid microemboli,I3,21,23,31 ,32,35 and local vasculitis. 20,23 ,32 The progressive ischaemia theory is based on a continuing rise in interosseous pressure which can be directly assessed using a pressure transducer and indirectly by measuring compliance within the compartment or by injecting a contrast agent into the interosseous space. Manometries consisting of initial measurement of BMP and a stress test (response of bone to injection of saline), and venography, are used to assess haemodynamic changes within the femoral head of patients with the presumptive diagnosis of NON (Fig. 9-7). Abnormal findings include an initial BMP greater than 30 mm mercury, a stress test where BMP fails to return to within 10 mm mercury above baseline 5 min after injection of 5 cc of saline, and venography which demonstrates diaphyseal reflux, poor metaphyseal run-off, or residual pooling of dye after 5 min . Core decompression is performed on all patients with abnormal manometries or venography. An 8 mm trephine is inserted through the greater trochanter, and using biplane image intensification, it is guided up into the osteonecrotic segment (Fig.9-7). Patients are kept non-weightbearing on crutches for 6 weeks following the procedure. The best results have been in individuals with Ficat Stage 0 (preclinical), Stage I (preradiographic), and Stage IIA (sclerocystic) disease. The first clinical studies by Ficat and Hungerford were very promising with a reported success rate of 80-90 percent. 28,48,SO More recent studies have suggested the usefulness of th is procedure in the earlier stages of disease, although clinical results have not been

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as dramatic.IOJ.I07.1l5 This may be due to detection bias as a result of more sensitive and objective methods of measurement provided by the Steinberg scale of radiographic assessment (Fig. 9-5). Recent studies have raised many questions about the rationale and theory behind core decornpresslon.t v-!" Elevated BMP has been observed in the setting of degenerative osteoarthritis; therefore, it is possible that the elevated BMP which has been observed in NON may be an epiphenomenon rather than a causative factor as is commonly believed by those who recommend the core decompression procedure.I.J9.55.69.7S,81 A recent study of patients with predominantly steroidassociation NON, failed to demonstrate a reliable association of elevated BMP and abnormal venograms with NON;lls moreover, it was observed that all patients who did well following core decompression had significantly lower BMP than those who failed the procedure. A recent animal study observed a significant osteocyte loss without elevation of BMP in rabbits treated with high dose steroids.l'f These observations suggest that core decompression may work by mechanisms other than decompression, and that NON is purely the result of an ischaemic insult. An alternative theory is that core decompression stimulates a more active and rapid osteoblastic new bone formation in the subchondral area of the femoral'head, and that this new bone formation may keep pace with the osteoclastic resorption occurring during the revascularization and healing process. The end result would be a scaffolding effect against femoral head collapse while healing occurred. This hypothesis is supported by a recent observation that patients with Ficat Stage IIA disease with a greater degree of sclerosis of the femoral head, had a more favourable outcome following core decompression than did those with a greater proportion of cystic involvement of the femoral head (Fig. 9-12). Unfortunately, patients with renal bone disease and steroid-associated NON represent the poorest group following core decompression. The marked osteoporosis which occurs in these patients may predispose to rapid collapse of the weakened subchondral bone after core decompression; and it is likely that osteoblastic cells subjected to chronic steroids and metabolic bone disease associated with chronic renal failure, are less able to respond to the demand for new bone formation following femoral head necrosis.68,7~

BONE GRAFTING Some investigators believe that core decompression may be only partially effective, or that this procedure may actually hasten femoral head collapse in osteoporotic individuals. A study by Penix and associates" using finite element analysis concluded that removal of a core of bone from the femoral head increases compressive forces just medial to the core tract by 80 percent. It has been suggested that following core decompression insertion of a long piece of cortical bone (either a fibular or tibial strut) would increase the success of the procedure by resisting shear forces which lead to subchondral collapse through the necrotic portion of the femoral head. Other than the biomechanical advantages,7-1O.77.98 addition of a cortical bone strut appears to have little biologic rationale. Though there is much evidence that autogenous bone grafts can enhance bone repair in fracture healing and fusion procedures, there is currently

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no evidence that a cortical bone strut hastens healing across the necrotic segment of the femoral head. Penix and associates," however, have shown that a properly inserted strut will reduce the magnitude of shear stresses that initiate subchondral fracture. Because of the questionable biologic advantages of a cortical strut, other investigators have reasoned that cancellous bone grafting or vascularized pedical bone grafting will have a greater healing potential due to the much higher percentage of marrow and osteogenic cells surviving within the living graft materiaI. 79,s O. IOI.1I0 Unfortunately, most of vascularized grafts are composed of weaker cancellous bone and so the biomechanical advantage of this procedure is lost.

ElECTRICAL STIMULATION Electrical stimulation is another technique which has been suggested in the treatment of NON. This recommendation is based on its proven effectiveness in stimulating new bone formation in healing of fracture non-unions.3-6.36.99 Several preliminary studies have demonstrated encouraging results in use of externally applied electrical fields without surgery.26.103.116 More recent studies have sought to combine the theoretical biomechanical and biologic advantages of core decompression and bone grafting with the technique of direct current electrical stimulation'P'rt'" (Fig. 9-14).

ELECTRODE COILED AROUND GRAFT

POWER SOURCE ( SUBCUTANEOUS) Figure 9-14. Schematic drawing of the operative procedure for combination bone grafting and electrical stimulation. Note the three decompression channels into the avascular area and the bone grafts in place, the more proximal one with the cathode coiled about it. From Steinberg MD, Brighton CT, Hayken MD, Tooze SE, Steinberg DR: Electrical stimulation in the treatment of osteonecrosis of the femoral head-A l-year follow-up. Ortho Clin N Amer 16(4):747-756, 1985.

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These studies have been unable to demonstrate a significant benefit from the addition of electrical stimulation; however, most of the patients who underwent the procedure had already progressed beyond Ficat Stage lIB (crescent sign) disease, so it is not surprising that these hips failed the procedure. In addition, the insertion of a cortical or cancellous bone strut with an electrical stimulation apparatus is a technically demanding procedure. This is because there is no biomechanical advantage if the graft/stimulation construct is not inserted far enough into the subchondral osteonecrotic segment to reduce shearing forces. Successof this technique would be contingent on optimal graft placement in a patient with early NON (Stages O,I,lIA). Results in such a patient are still unknown.

TREATMENT FOLLOWING COLLASPE (IIB /II /IV)

Biplanar Intertrochanteric Osteotomy Biplane intertrochanteric osteotomy is an attractive technique for treatment of NON with a minimal to moderate degree of femoral head collapse. 96,108,11I Its advantage

Figure 15a. This patient has Ficat Stage III disease with femoral head collapse involving the anterolateral segment.

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Figure 9-1Sb. Biplane intertrochanteric valgus-flexion osteotomy was performed in order to rotate the involved portion of the anterolateral segment out from under the weight-bearing portion of the femoral head. This patient is now bearing weight on the more normal part of the femoral head which was not involved with the necrotic process. is that the procedure preserves the femoral head, and is therefore a more desirable treatment alternati ve for younger patients (less th an 60 years of age), since th ese individuals are poor candidates for prosthetic replacement of the hip joint ." The procedure a tt empts to preserve the femoral head by delivering the osteonecrotic segment from the weight bearing portion of the hip or by containing it within the weight bearing dome (Fig. 9-15). This decreases the probability of further collapse of the femoral head by reducing the compressive forces on the weakened necrotic segment while the healing process is completed. Wa gner and Baur have reported an 85.5 percent success rate in 83 hips undergoing this procedure. The minimum follow-up in this group was 5 years.'!' Preliminary experience at our institution since 1982 has consisted of ten intertrochanteric osteotomies." The lon gest follow-up has been 3 years, and all patients continue to ha ve excellent symptomatic relief without radiographic evidence of progressive femoral head collapse.

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The limitations of this procedure are the extent of the necrotic segment of the femoral head, the presence of osteoarthritic involvement of the entire hip joint, and the technically demanding nature of the procedure.

BIPOLAR HEMIARTHROPLASTY AND TOTAL HIP ARTHROPLASTY Hemiarthroplasty or bipolar hip replacement are procedures which replace the collapsed femoral head with artificial components. These have been suggested as useful techniques for NON with femoral head collapse where there is no significant destruction of the acetabular cartilage of the hip joint (Ficat Stage 111).66 Total hip arthroplasty has been the suggested treatment for NON with significant destruction of the acetabular cartilage in addition to collapse of the femoral head (Ficat Stage IV).12,17,7I,93 In this case, cartilage destruction extends to the acetabular side of the joint and therefore both the femoral head and acetabulum are replaced. Though many studies have suggested that renal failure patient with NON do well with these arthroplasty procedures,12,17,7l,93 recent long-term studies have observed a failure rate up to four times that of patients with osteoarthritis who undergo these procedures'P-" (Fig. 9-16). During a 12-year period (1970-1982) 34 patients underwent 53 cemented total hip arthroplasties for advanced NON at the Brigham and Women's Hospital. The average length of follow-up was 8.3 years and the mean age of the patients was 36 years.

Figure 9-16. Failure after total hip replacement in a patient with renal failure on chronic steroid treatment. On the left side the femoral component has fractured out of the weakened osteoporotic femoral shaft and the acetabular component is loose. On the right side the acetabulum and femur are both radiographically loose.

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There was a 29 percent incidence of early postoperative complications which included three wound haematomas, three transient sciatic nerve palsies, one pulmonary embolus, one postoperative cholecystitis requiring surgery, and one fatal myocardial infarction. Late complications were significant in both number and magnitude. There was a 66 percent incidence which included 21 hips that became loose both clinically and radiographically (17 hips have been revised to date), three hips with radiographic evidence of loosening, three hips which developed late haematogenous sepsis, a 53 percent incidence of heterotopic ossification with significant (grade III) heterotopic bone in eight hips, and seven postoperative hip dislocations. There are numerous factors which suggest that this population is at higher risk for complications as compared with groups of patients undergoing total hip arthroplasty for osteoarthritis. First, one is dealing with a young, active patient population susceptible to increased risks of component loosening due to their higher activity level than older patients with osteoarthritis.I" The higher incidence of loosening is also probably due to the presence of renal bone disease (osteoporosis, osteomalacia, and secondary hyperparathyroidism) and its effects on bone healing and remodelling. This is supported by our observation of increased component loosening rate in patients with failed renal transplants compared with those whose transplants continued to function. The high incidence of late sepsis may be explained by chronic immunosuppression. The increased numbers of postoperative dislocations is probably multifactorial, with predisposing factors including a relative laxity of capsule and soft tissues in the young patients who are more active than older patients with total hip arthroplasties. The higher rate of heterotopic ossification may be due to altered calcium metabolism in patients receiving steroids; it may also be due to moderate elevations in the calcium-phosphorous product and active bone formation following restoration of 1,25 dihydroxycholycalciferol production by the renal allograft.

TREATMENT OPTIONS

IIA

(SCLEROTIC)

IIA

(CYSTIC)

us

III

IV

• CORE DECOMPRESSION

.ANGULATION OSTEOTOMY

• BONE GRAFTING

.ROTATIONAL OSTEOTOMY ISujiokal

• ELECTRICAL STIMULATION? ?

• ENDOPROSTHESIS

·T.H.R.

Figure 9-17. Treatment options for non-traumatic osteonecrosis of the femoral head.

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Many investigators have recommended noncemented, porous coated total hip arthroplasty components as an alternative to conventional cemented total hip components, based on the theoretical advantage of a lower loosening rate due to direct bony ingrowth into the cornponents.s" Though this appears to be the case in many instances, it would seem that biologic fixation may not be suitable as an alternative in these patients who have difficulty mounting and maintaining the bony response necessary for component fixation without cernent.s'

CONCLUSIONS Our current treatment protocol for NON is core decompression for Ficat Stages 0, I, IIA (sclerotic-predominant) disease, angulation intertrochanteric osteotomy for Ficat Stages IIA (cystic-predominant), III, and IV disease if the segment of the femoral head is not too extensively involved (based on the AP and lateral radiographs, CT scan, and more recently MRI), bipolar hemiarthroplasty for Ficat III disease not amenable to osteotomy, and total hip arthroplasty (cemented) for patients with Ficat IV disease (Fig. 9-17). It should be remembered that patients with NON associated with chronic renal failure and chronic steroid treatment represent the prognostically least favourable group with regard to all of these procedures. The factors which seem to be responsible for this high failure rate are: 1) younger age and higher activity level; 2) pre-existent renal bone disease with reduced healing potential of bone; 3) immunosuppression, particularly with steroids; and 4) greater degree of soft tissue laxity.

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