THE DILEMMA OF AVASCULAR NECROSIS

steonecrosis refers to the in situ death of bone, with the femoral head being the site most commonly affected. (AVN) of the femoral head is a common entity with approximately 20,000 new cases reported each year. AVN is the underlying diagnosis in as many as 10% of 500,000 total hip arthroplasties performed in the United States. A significant percentage of these hip arthroplasties are done in individuals in their late 30s and early 40s. To orthopaedic surgeons, however, early osteonecrosis of the femoral head often is silent or presents with nonspecific clinical finding, similarly early radiographic finding of the disease also may be inconspicious and as such, they may impose a challenge for clinicians and radiologists. The dilemma of this disease is that many surgeons and workers in its field find difficulties and confusion in selecting the appropriate approach to understand or to select the most acceptable methods or way regarding the aetiology, pathogenesis, classification and the most effective options of treatment. Here is this review articles we try to clarify or to nearly approximate the most widely acceptable methods of different treatment modalities. In addition to reviewing the pathology and some other related problems. The term avascular (AVN), osteonecrosis implies that a segment of bone has lost its blood supply so that the cellular elements die with it. The phrase “aseptic necrosis” indicates that infection generally plays no part in the process. Avascular necrosis has long appears as a distinctive feature in a number of nontraumatic disorders. Sites which are peculiarly vulnerable to ischemic necrosis are the femoral head, the femoral condyles, the head of humerus, the capitulum, proximal part of the scuphiod, talus, patella and the vertebra. The anatomic coarse and the nature of the blood vessels, with the characteristic histological structures of the blood vessels in this area probably give a good Correspondence to: Dr. Mohammed H. Kubba Department of Orthopaedic Surgery, Basrah General Hospital, Basrah; IRAQ. O Leading Article


Introduction
steonecrosis refers to the in situ death of bone, with the femoral head being the site most commonly affected.(AVN) of the femoral head is a common entity with approximately 20,000 new cases reported each year.AVN is the underlying diagnosis in as many as 10% of 500,000 total hip arthroplasties performed in the United States.A significant percentage of these hip arthroplasties are done in individuals in their late 30s and early 40s.To orthopaedic surgeons, however, early osteonecrosis of the femoral head often is silent or presents with nonspecific clinical finding, similarly early radiographic finding of the disease also may be inconspicious and as such, they may impose a challenge for clinicians and radiologists.The dilemma of this disease is that many surgeons and workers in its field find difficulties and confusion in selecting the appropriate approach to understand or to select the most acceptable methods or way regarding the aetiology, pathogenesis, classification and the most effective options of treatment.
Here is this review articles we try to clarify or to nearly approximate the most widely acceptable methods of different treatment modalities.In addition to reviewing the pathology and some other related problems.The term avascular (AVN), osteonecrosis implies that a segment of bone has lost its blood supply so that the cellular elements die with it.The phrase "aseptic necrosis" indicates that infection generally plays no part in the process.
Avascular necrosis has long appears as a distinctive feature in a number of nontraumatic disorders.Sites which are peculiarly vulnerable to ischemic necrosis are the femoral head, the femoral condyles, the head of humerus, the capitulum, proximal part of the scuphiod, talus, patella and the vertebra.The anatomic coarse and the nature of the blood vessels, with the characteristic histological structures of the blood vessels in this area probably give a good explanation to the development of (AVN) 3 .The subarticular regions of the bone lie at the most distant part of the bone's vascular territory.The subcondral trabecule are supplied by endratrioles system with limited collateral connection and lastly the vascular sinusoid which nourish the marrow and bone cells, unlike arterial capillaries, have no adventilial layer and their patency is determined by the volume and pressure of the surrounding marrow tissue, which itself is encased in unyielding bone.The system functions essentially as a closed compartment within which one element can expand only at the expense of the others.

Pathophysiology
Ischemia results in death of haemopoietic tissue within 6-12 hours; the asteoclast, osteoblasts and osteocytes die within 12-48 hours, and if bone marrow fat in 2-5 days.At the bone ends, cartilage receives nutrition from synovial fluid, cartilage and subcrtilaginous bone are not therefore necessarily affected 4 .Revascularization is seen at the livedead marrow interface.The necrotic zone is invaded by capillaries, fibroblast and macrophages.Fibrous tissue replaces dead marrow and in turn may calcify, new osteotrabeculae lay down fresh woven bone to replace the devilalized trabeculae.This advancing front of neovascularization and ossification has been termed "creeping substitution" 45 .Reparative new bone formation proceeds slowly and probably does not advance for more than 8-10 mm into the necrotic zone.With time structural failure begins to occur in the most heavily stressed part of the necrotic segment.Moreover, until very late the articular cartilage retains its thickness and viability.
In the final stages, fregmentation of the necrotic bone leads to progressive deformity and distraction of the joint surface.The segmental ischemic necrosis rarely increases, indeed, occasionally they even disappear 50 .

Pathogenesis
The pathogenesis of (AVN) still is unknown despite numerous studies.Various hypothesis have suggested concerning the pathophysiologic mechanisms underlying the disease including fat embolism, intra-vascular coagulation and intraosseous stress.These theories are for the most part not mutually exclusive.But rather may be thought of as being mutually supportive in most cases 51 .The process of (AVN) can be indicated in at least four different ways: 1-Severance of the local blood supply.

4-
Compression of capillaries and sinusoid by marrow swelling.
Ischemia in the majority of cases is due to combination of several of these factors 3 .
In traumatic (AVN) the vascular anatomy in particularly important.In fractures, or lesser injuries, also sometime result in subchondral necrosis.
Impact injuries and osteoarticular fractures at any of the convex articular surfaces behave in the same way and often develop localized ischemic changes.
Various mechanisms leading to capillary thrombosis have been demonstrated in patients with non-traumatic (AVN).Over 80% of cases are associated with high-dosage corticosteroid medication or alcohol abuse (or both, acting cumulatively).These conditions give rise to hyperlipidaemia and fatty degeneration of the liver.At the level of the bone, high dosage corticosteroid administration and alcohol over-use cause fat cell swelling in the marrow, there is a demonstrable rise in intraosseous pressure and contrast venography shows slowing of venous blood flow in the bone.Jones (1994) has favoured the idea that fat embolism plays a part, given rise to capillary endothelial damage, platelet aggregation and thrombosis 28 .
Glueck and colleagues observed that patients with very early non-traumatic (AVN) should undergo laboratory test for coagulopathies 24 .
Sickle-cell disease is a genetic disorder in which the red cell contain abnormal haemoglobin (Hbs).In deoxygentated blood there is increased aggregation of the haemoglobin molecules and distraction of the red cells, which become somewhat sickle -shaped.Chronic haemolytic anaemia and the tendency to clamping of the sickle-shaped cells, which results in, diminished capillary flow and recurrent episodes of intracapillary thrombosis 3 .
Secondary changes such as trabecular coarsening, infarction of the marrow, periostitis and osetonecrosis are common.
In Gaucher's disease a specific enzyme results in the abnormal storage of glucocerberoside in macrophayes of the RE system.The effects are seen shiefly in the liver, spleen and bone marrow, where the large polyhedral (Gaucher cells) accumulate.Bone complications are common and osteonecrosis is among the worst of them.
Bone ischemia is usually attributed to the increase in medullary cell volume and sinusoidal compression.In radiation necrosis unlike the common form of ischemic necrosis it is more diffuse and the effect is more variable.Marrow and bone cells die, but for months or even years there may be no structural change in the bone, a striking feature is the absence of repair and remodelling.
In dysbaric osteonecrosis a generalized embolic phenomena and intracapillary coagulation occurs.Prlonged compression may also cause swelling of marrow fat cells and decrease intramedullary blood flow, possibly due to oxygen toxicity 46 .
The main conditions associated with non traumatic osteonecrosis includes

Classification of (AVN)
A number of systems for the classification of (AVN) of the femoral head had been proposed The most widely used system is that of Ficat and Arlet This system was modified by Hungerford and Lennox to include stage O (an asymptomatic hip with evidence of osteonecrosis on MRI) 26 .
Steinberg et al. 53 later expanded this system to include six stages, with the important addition of quantification of the involvement of the femoral head.
Marcus et al, 34 in 1973, also described a six staging system, which included both radiographic changes and clinical signs and symptoms.
In 1987, the Japanese investigation committee 41 for intractable disease, avascular necrosis of the femoral head, developed a classification system that incorporates the size and location of the lesion and has been found, by several authors, to help to predict the outcome.
According to this system, type-A lesions are medial and rarely progress.Type-B lesions are central and there is intermediate progression, and type-C lesions demonstrate lateral involvement of the head and have the worse prognosis.
Finally, the association research circulation osseous (ARCO) 7 recently proposed a new international classification system.That system represents an attempt to incorporate features of the classification system of Ficat and Arlet, to quantify the involvement as described by Steinberg et al, and to determine the anatomical location of involvement as proposed by the Japanese investigation committee.
The proposed pittsburgh classification 43 , is based on three major parameters: 1-Magnetic resonance imaging (MRI) 2-Structure of the femoral head and, 3-Contour of the femoral head as seen on plain radiographs.The three-stage classification is proposed as an easy and reproducible system that will allow a more uniform assessment of outcome.

Investigation
In many cases of (AVN) the history is important to suggest the underlying causes.A known episode of trauma, an occupation and a family background of Gaucher's disease or sickle cell disease.
There may be a record of high dosage corticosteroid administration.Alcohol, corticosteroids, immunosuppressions and cytotoxic drugs either singly or in combination are the commonest causes of non-traumatic (AVN) 3 .
It has been suggested that patients with very early traumatic osteonecrosis should undergo laboratory test for coagulopathies.
In cases of suspected SLE, antiphospholipid antibodies may be measured.
In early (AVN) both the intramedullary pressure and the response to saline injection may increase three or four fold.
Venous stasis can also be demonstrated by venography after injection of radioopaque medium in to the bone 63 .Uchio et al. study the angiokinematic factor of (AVN) the early results of the study suggest that disturbed venous drainage and increase intraosseous pressure might be important factor in the pathogenesis of (AVN).
Because typical radiographic finding of AVN most commonly appears relatively late in the disease process, that is, after the onset of clinical manifestation, radiographs may lack sensitivity in detecting early disease 49 .
Small lesions may not be detected on conventional radiographs because they may be obscured by the abnormally mineralized underlying bone 49 .
With the advert of more sophisticated imaging modalities, including radionuclide bone scintigraphy, computed tomography (CT), and magnetic resonance imaging (MRI), substantial gains in the diagnosis of osteoneurosis on early, pre collapse stages have been achieved 4,36 .
In the clinical setting, imaging is considered a valuable tool for providing an early and definitive identification of the osteonerotic lesion, evaluating its type and extent, determining prognosis, and monitoring the effect of treatmen differential diagnosis particularly challenging cases with an atypical initial presentation.Moreover, characterization of the infarcted segment, in terms of identification of its precise location in relation to the weight bearing surface of the femoral head 40 , accurate quantification of its extent, and evaluation of collapse are extremely important parameter influencing the choice of conservative or operative treatment.
Although the diagnostic role of bone scintigraphy with technetium labeleddiphosphonates in AVN has not been well defined, it is generally accepted that the detection of cold lesion is highly sensitive for early disease indicating devascularization of the femoral head 9,49 .However, because of its capability to detect bone marrow abnormalities, MRI has been described to detect osteonecrosis of the femoral head with a sensitivity approaching 100% 30,35 .In this regard, MRI has been found to be effective in evaluating osteonecrosis where conventional radiography and bone scintigraph are negative or equivocal.

Treatment
.More recently a course of hyperbaric oxygen treatment is effective in the treatment of idiopathic stage -I (AVN).It may be used in conjunction with core decompression, fenestration and drilling or other forms of orthopaedic intervention 47 .During the early 1960s Arlet and Ficat 5 performed core biopsies in order to examine the pathological changes taken place in femoral head.This procedure frequently produce immediate relief of preoperative pain, and it was felt that this was because of decompression of the increased intraosseous pressure which found to be present in the femoral head used as therapeutic rather than as a diagnostic procedure and was referred as core decompression.
Initially, Ficat 20 as well as Hungerford and Lennox 26 reported high rates of success with use of this procedure.However, their results have not been duplicated by other investigators and enthusiasm for core decompression has recently waned.1n 1980, after experiencing poor results treating patients with (AVN) conservatively Steinberg 54 and colleagues began to perform a modified type of core decompression with supplemental cancellous bone graft.
It was shown that is properly performed to procedure had an extremely low incidence of complication and was effective in treating patients with earlier stages of (AVN) as compared with patients who were treated nonoperatively or patients who received symptomatic treatment.

Osteotomy techniques
In an effort to improve the prognosis of patients with (AVN), several surgical procedure have been proposed with the aim of slowing down the progress of degenerative changes.Various osteotomy techniques have been proposed to remove the necrotic area, which is usually located in the antero-superior part of the femoral head, out of the weight bearing zone.However, the most effective type of osteotomy is still contraversial because osteotomies have been propsed on approximately every plane, each with its own rationale.Sugioka stated that the best results were obtained when the osteotmy was performed during the early stage of necrosis or in extensive lesions in the absence of advanced collapse 59 .More specifically, of patient characteristics, young patient have been reported to be the best candidates for intertrochanteric osteotomy with upper age limits generally around 45 year 20,33 .Patients with Ficat stage III lesion or late stage II can be treated successfully with intertrochantric osteotomy.The operation has to be avoided if there is poor patient compliance and if the patient is not highly motivated to accept a lengthy disability period.However, intertrochantric osteotomy should be avoided in patients with underlying metabolic disease or in patients with systemic conditions treated with chemotherapy or corticosteroids.

Free vascularized fibular graft
An appealing to maintain available femoral head without violating the joint capsule in free vascularized fibular grafting (FVFG).
In most of the types of free vascularized fibular graft procedures two teams of surgeons worked simultaneously.One team isolated the middle 1/3 of the contralateral fibula and the other team working of the hip region.Harvesting the fibula according to the method of Gilbert technique.The placement of the fibula to the head of the femur is done either by direct approach, intra capsular, or by extra capsular placement of the fibular graft.The technique of intra capsular involve the total excision of the necrosed bone then replaced by autogenous cancellous bone associated with a bone vascularized graft taken from the contralateral fibula.The articular cartilage that normally remains preserved for a long time during the natural history of the disease is protected and used to cover the grafted area.The extra capsular placement of vascularized fibular graft in the subchondral region of the femoral head is widely accepted method for treating patient with (AVN).The rationale for its use includes; the femoral head is decompressed, necrotic bone is removed, frish autogenous concellous and vascularized cortical bone grafts are added, and new bon formation that fuses with the affected subcondral bone is induced, this prevent will collapse of the articular cartilage 4,18,53,61 .Urbaniak and colleagues have remained leader in the field of osteonecrosis during the course of its study.During the procedure the femoral head is decompressed, which may interrupt the cycle of ischemia and intraosseous hypertension that is thought to contribute to the disease.The necrotic bone is then excised, possibly by removing the obstacle to revascularization, the defect then is filled with osteoinductive concellous graft and a viable cortical strut to support the subchondral surface.A period of limited weight bearing protects the healing construct 15 .The loannina technique uses serial CT scan of the proximal femur to identify the configuration of the femur and the size, location, and configuration of the lesion with a computer-aided design and computer aided manufacturing process.Optimal graft placement is determined and a guide wire canal is drilled in patient-specific aming device.The aiming device resulted in good placement of the fibular graft in 89% of the patients studied to date.Beris and Soucacos et al. 8 present the loannina technique.The goal of this technique was to optimize the length and position of the fibular graft in the necrotic defect, and to diminish the x ray exposure and preparation time.To data, there is still no agreement on the best surgical method for preserving the hip in adult with (AVN) of the femoral head.In general, either free vascularized fibula transplants or vascularized iliac creast transplants are used.The insertion of corticospongious iliac creast transplant prefused by the circumflex ilium profunda artery in the femoral head places a high quality autogenous bone transplant in a weak host bed.And lastly this type of vascularized graft lack the need for vessel anastomosis 16 .Although retention of the femoral head is accepted as the goal of early treatment, methods for treating osteonecrosis of the femoral head remain controversial.Once-end-stage osteonecrosis has developed with collapse of the femoral head, total hip arthroplasty has become the accepted means for surgical management of pain and restoration of function 64 .

Discussion
In many cases of (AVN) an underlaying disorder will be obvious from the history: a known episode of trauma, is a more obvious cause an occupation such as deep-sea diving or working under compressed air, a family backgraound of Gaucher's disease or sickle cell disease.
Drugs use such as corticosteroid, immunosuppresive and cytoxic either singly or in combination are the commonest cause of non-traumatic osteonecrosis.The threshold depends not only on the total intake but also on the time over the intake, and the presence of associated disorder which in themselves may predispose to osteonecrosis 3 .
Accumulative dose of 2000mg of predinsolone equivalent administration over several years is less likely to cause (AVN) than the same dose given over a period of months.
It is important to bear in mind that multiple causative agent have an additive effect for the development of (AVN) 57 .
The threshold dose for alcohol is equally vague, base on the known dose relationship of alcohol-induced fatty degeneration of the liver, it may be around 150mg of ethanol per day, for men and considerably less for woman.
Steroid treatment produce a hyperlipidemic state that often leads to osteoporosis, however, at least 1/3 of the cases of (AVN) have been associated with steroid treatment 44 .
There is no clear relationship to etiology was observed except in patient exposed to combination of steroids and alcohol in whom the prognosis seemed to be somewhat worse 52 .
Given the unpredictable natural history of (AVN) that usually progresses to structural failure, it is conceivable that early diagnosis is crucial in selecting the appropriate treatment options that eventually may halt the evolutionary and debilitating course of this disease.
To orthopaedic surgeon, however early (AVN) of the femoral head often is silent or present with non-specific clinical finding 60 .
Thornhill et al. 13 their result stress the importance of distinguishing between patient who have sclerotic changes only, they demonstrated that patients who do not have cystic changes or collapse of the femoral head are most likely to benefit from core decompression.We see that the proposed classification by Pittsburgh has excellent agreement and is anticipated to be more helpful in comparing methods of treatment in multicentre studies 43 .
Given that many theories regarding the pathogenesis of (AVN) of the femoral head have been proposed, it is not surprising that a wide variety of treatment options have been advocated for this disease.These modalities have included non-operative measures, electrical stimulation, hyperbaric oxygen therapy, statin drug therapy, corrective osteotomy, vascularized and nonvascularized bone graft, core decompression with and without bone graft, arthrodesis and endoprosthetic replacement.
Each patient should be evaluated preoperatively on the basis of medical history, associated risk factors, the results of physical examination antroposterior and lateral radiographs, technetium-99 bone scan and MRI.
It is generally agreed that without specific treatment the majority of clinically diagnosed cases will progress to collapse of the femoral head and the head require some form of arthroplasty if the initial treatment consisted of nonoperative measures only 38,52,53 .
There is general agreement in the literature that core decompression is most effective in the earlier stages of the disease, however, the overall rate of success of this procedure for the treatment of non-traumatic osteonecrosis has varied widely from as low as 17% to as high as 89% 17,37,56 .It is effective in hips treated prior to collapse, especially in those with smaller lesion.Among the advantages are the following, it is a procedure with long time of experience (30 years), it is relatively simple and requires no special equipment, it is a short procedure with little blood loss and if done carefully, the complication rate is extremely low and protected weight bearing is required for only 6-12 weeks and finally it can be done bilaterally.
The major disadvantage of core decompression is that it is not as effective as we would like it to be especially in treating hip with larger lesions or in those after collapse has already began.However, even in this group results are better than with conservative management.
The result of core decompression is limited to the stage I and stage IIA of the sclesotic type, where as the result is limited in cases of stage IIA (cystic type).
Mont and Hungerford 37 reported that radiolucented or cystic area on plain radiographs represent regions of resroption of bone and corresponded to the fibrous or granulation tissue seen in histological section.
Similarly, osteosclerotic changes bordering the necrotic area corresponded histological in section 54 to the region of repair with newly formed bone laid on dead trabeculae.
For this reason Thornhill et al. in their study believe that preservation of the joint should be the goal of treatment of early stage of non traumatic (AVN), furthermore they found that both a rapid onset of symptoms and the use of corticosteriod are independently associated with poor outcome.
Steinberg M. 55 after performing 406 procedures perform a modified type of core decompression with a supplemental cancellous bone graft taken from the intertrochanteric area.They concluded that, compared to nonoperative or symp-tomatic managemnet, core decompression with or without a cancellous bone graft was a safe and effective procedure for treatment of early stages of AVN.
Recently there has been increasing interest in free vascularized fibular grafting (FVFG), and some of the reports cited indicate that it may be one of the most effective treatment, especially after femoral head collapse.FVFG with this procedure is applied to patient younger than 40 years who have stage II of stage III osteonecrosis with good spherically of the femoral head and a healthy shell of cartilage 29 .
Other studies indicate that equal or nearly equal results can be obtained with simpler procedure such as nonvascularized tibia or fibular 9,12 allograft or with cancellous grafting 21,48 .
The major disadvantage of this procedure are associated with the need to harvest the patient own fibula and perform to microvascular anastomosis.
In a recent comparison between core decompression and (FVFG) it was found that the increased morbidity of the FVFG is justified by the associated delay in or prevention of articular collapse in hip with stage II or III disease (FVFG) is an appealing alternative to all of the other mentioned methods of treatment.During the procedure the femoral head is decompressed, which may interrupt the cycle of ischemia and intra osseous hypertension that is thought to contribute to the disease.
The necrotic bone is then is excised, possibly removing the obstacle to revascularization.
The defect then is filled with osteoinductive cancellous graft and available strut to support the subcondral surface.A period of limited weightbearing protect the healing construct 15 .
Vascularized iliac creast transplant is another salvage procedure for the AVN of the head of the femur in which the necessity for microvascular surgery is omitted 15 .
Osteotomies of the femur and acetabulum have been recommended as a way to unload the necrotic segment of the femoral head and redirect weight bearing through a more viable area.
Sugioka et al. reported excellent results with their technique of rotational osteotomy, however, similar success rates have not achieve elsewhere.
Patient with ficat stage II lesions or late stage II lesions can be treated successfully with intertrochanteric osteotomy.
In term of pathogenesis, idiopathic avascular necrosis represents the best indication.However, intertrochanteric osteotomy should be avoided in patient with underlying metabolic disease or in patients with a systemic condition who have been treated with chemotherapy or corticosteroid 20 .
Different types of electrical stimulation, both alone and supplement to operative procedures, have been used to treat (AVN).Promising results have been reported with the use of pulsing electromagnatic field 1,2,27 .
There is great deal of controversy about the recommended treatment of so called silent or esymptomatic hip with early stage osteonecrosis.Some authors emphasized the importance of long-term follow-up in order to determine the true rates of radiographic and clinical progression 10,32 .