Current Orthopaedics (2008) 22, 349e358

ava i lab le at www.sc ienced i rec t . com

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HIP

Osteonecrosis of the femoral head: Part2d Options for treatment

Samuel J. Parsons a,*, Niall Steele b

a North Staffordshire Royal Infirmary, University Hospital of North Staffordshire NHS Trust, Princes Road,Hartshill, Stoke on Trent ST54 7LN, United Kingdomb Robert Jones and Agnes Hunt Hospital, Gobowen, Oswestry, Shropshire SY10 7AG, United Kingdom

KEYWORDSOsteonecrosis;Hip;Treatment

* Corresponding author.E-mail addresses: samuelparsons@

niallsteele@rjah.nhs.uk (N. Steele).

0268-0890/$ - see front matter ª 200doi:10.1016/j.cuor.2008.07.009

Summary

The management of osteonecrosis of the hip is evolving but remains challenging. As the patientsare typically younger, it remains imperative to preserve the femoral head for as long as ispossible. When arthroplasty is indicated, the need for longevity of implants and bearing surfacesis paramount. Developments in bone biology, the use of appropriate pharmacology, improvedimplant design, better bearing surfaces and appropriate choice of implant fixation should allimprove the historically poorer results seen with arthroplasty in osteonecrosis patients.ª 2008 Elsevier Ltd. All rights reserved.

Introduction

The natural history of avascular necrosis/osteonecrosis is ofgradual progression with subchondral fracture of thefemoral head leading to collapse and ultimately osteoar-thritis of the hip joint. Steinberg et al reported thatprogression occurred in 92% of 48 hips that had under gonenon-operative management.1 Many factors affect treat-ment decisions, i.e. disease stage, the presence ofcollapse, acetabular involvement, size and site of thelesion.

Treatment ranges from purely symptomatic therapy,through joint preserving procedures for early precollapse

hotmail.co.uk (S.J. Parsons),

8 Elsevier Ltd. All rights reserved

lesions up to varying forms of arthroplasty for later stagedisease.

Pre-collapse disease has a better prognosis and mayrequire less invasive intervention, but once collapse hasoccurred treatment options become more limited andinvasive intervention becomes more likely.

Non-operative management seeks to eliminate riskfactors and optimise any exacerbating conditions. Surgicaltreatments range from core decompression (with orwithout bone grafting), osteotomy, hemi-resurfacing, fullre-surfacing, hemi-arthroplasty, and total hip arthroplasty.Disease diagnosed in the pre-collapse state may beamenable to newer non-operative treatments, but thestage at which specific interventions may be successful isnot yet known. Research into the pathology and risk factorsmay lead to targeted therapies, such as the use of growthfactors and specific drug treatments, which are likely tobecome increasingly important but surgical management iscurrently the norm.

.

350 S.J. Parsons, N. Steele

Non-surgical treatment

As small pre-collapse lesions may have a more favourableprognosis, taking much longer to become symptomatic andmay even resolve; some authors have suggested observa-tion as being appropriate management for early and smalllesions. Cheng et al reported the spontaneous resolution ofvery small lesions in 3 of 13 asymptomatic hips in organtransplant patients taking steroids. It took between sevenand eleven months for early resolution to appear on MRIand 19 to 44 months to completely resolve.2 During thehealing period the hips were completely asymptomatic andthe patients received no treatment for their osteonecrosis.All three patients had ARCO stage one disease, i.e. smalllesions with a necrotic index of less than 21, and headinvolvement of less than 30%. Hernigou et al, looked at 40patients over a ten-year period with very small asymp-tomatic lesions, diagnosed when investigating the contra-lateral hip.3 The lesions all had a volume of <5 cm3

involving <10% of the volume of the femoral head. By tenyears 88% had become symptomatic and 73% eventuallycollapsed. Thus they stressed the need for prolongedfollow-up of even the smallest lesions.

Non-weight bearing

Non-weight bearing has been thought to slow diseaseprogression by allowing the off-loaded necrotic bone toheal. Initially patients would non-weight bear, withprogression to full weight bearing as symptoms and signssettled. This would be followed by clinical and radiologicalfollow up at six weekly intervals until the pain subsidedcompletely. Typically protected weight bearing fora minimum of 3e6 months would be necessary before toreturning a patient to full weight bearing without aids.

A meta analysis, by Mont et al, of protected weightbearing in 819 patients demonstrated a failure rate of >80%at a mean of 34 months. Restricted weight bearing forosteonecrosis of the hip cannot be recommended asa routine treatment4 but may have a role for patients withvery limited disease or those not fit for surgery.

Pharmacological agents

As the aetiology of osteonecrosis is multi-factorial, anddrugs will only act on one part of the aetiological pathway,the role of pharmacological agents for treatment iscurrently very limited. However, there are powerful drugswhich affect conditions that may play a part in the patho-physiology of the disease; drugs directed toward treatingthese conditions may prove to have a profound effect, i.e.lipid lowering drugs in hyperlipidaemia, anticoagulants withthrombotic conditions. As the aetiology is further under-stood it can be anticipated that medical management maybe able to arrest development of the osteonecrotic headand induce healing prior to femoral head collapse.

Low molecular weight heparins

Hypofibrinolysis (a reduced ability to lyse thrombi) andthrombophilia (an increased tendency to form thrombi)

have been found to be patho-aetiologic in the developmentof osteonecrosis, in both idiopathic and secondary osteo-necrosis.5 Patients with idiopathic osteonecrosis oftendemonstrate heritable hypofibrinolysis via mutation of thePAI-1 gene5 and increased thrombophilia due increasedexpression of the MTHFR gene or low levels of protein S.6

These conditions may lead to blocked venous drainage witha consequent increase in intra-osseous pressure andreduced arterial flow; effectively a compartment syndromeof bone.

Treatment of the underlying coagulation disorders mayarrest or delay the progression of the osteonecrosis, andanticoagulation with warfarin or LMW heparin, if started inthe early stages of osteonecrosis before collapse, may alsoresult in improvement of the condition.6

In addition to correcting any underlying coagulationdisorder, LMW heparin may also have direct effects on theprogression or healing of osteonecrotic segments. In a studyusing a vessel deprived osteonecrosis model in rat femoralheads, Norman et al noted decreased residual necroticbone and articular cartilage degeneration in those animalstreated with low molecular weight heparin. It was believedto increase osteoclastic bone resorption and angiogenesiswhile inhibiting the inflammatory response.7

Bisphosphonates (See Annex A)

Bisphosphonates are used in many conditions where boneresorption is important. In conditions such as osteoporosis,Paget’s and fibrous dysplasia they have been shown toreduce fracture risk, to improve bone mineral density, andshow reduced bone turnover metabolites, leading toradiographic improvement in the lesions of both Paget’sand fibrous dysplasia.

The rationale for the use of bisphosphonates in AVN isthat prevention of resorption of necrotic bone during thereparative revascularisation phase would prevent structuralfailure.

Disease modelling in animals has shown that bisphosph-onates can be safely used to prevent revascularisation andresorption of necrotic bone.

In a bone chamber model in rats the resorption ofnecrotic bone was prevented with alendronate, while beingalmost completely resorbed in controls. The authorsconcluded that systemic alendronate prevented resorptionof the necrotic bone during revascularisation.8

A pig model of Legg-Calve-Perthes disease (ischaemicnecrosis of capital epiphysis followed by resorption ofnecrotic bone then collapse) has also shown promisingresults using ibandronate.9 However this study used largedoses of bisphosphonates, which in one arm of the studywere started prior to the ischaemic insult.

There have been a number of human studies. Lai et al,randomised 40 patients with Steinberg II or III non-trau-matic osteonecrosis and a necrotic area of >30% (class C),into two groups of 2010 comparing alendronate withplacebo. The patients were followed up for minimumperiod of 24 months with plain film, MRI and Harris hipscores. In the control group 20 of the 25 hips worsened,shown by an increase in Steinberg grade. 19 had collapsedby final follow-up but in the alendronate group only four ofthe 29 hips had progressed one or more Steinberg stage at

Osteonecrosis of the femoral head 351

follow-up (p< 0.001). The pre-study Harris hip score was67.6 in control group, and 65.7 in the alendronate group.Post-study, the scores fell to 49.2 in the control group andincreased to 74.4 in the alendronate group. While theyshowed an improvement in both disease progression andsymptom relief, the authors observed that no evidence ofreduction or resolution of the necrotic area was shown byimaging, raising the question as to what will happen to thisnecrotic bone in the longer term.

A larger study by Agarwala et al of 60 patients, with 100osteonecrotic hips11 compared alendronate either 10 mgonce daily or 70 mg once weekly. This led to markedimprovements in pain and disability scores, standing andwalking times, and an increased range of movement of thehip. Radiological progression, seen on plain x-ray, by oneFicat and Arlet grade was seen in 14% at one year, 28% attwo years and 54% in those with more than two years followup. They felt that whilst bisphosphonates did not lead toa cure, they did significantly retard the progress of thecondition with improved range of movement, a reduction inbone oedema and joint effusion, good pain relief anda subsequent reduced requirement for analgesia, anddelayed requirement for surgery.

Nishii et al also used alendronate, in 33 hips in 22patients with osteonecrosis.12 14 patients (20 hips) received5 mg daily with 8 patients (13 hips) as controls. After 12months, collapse occurred in 6 of the 13 control group,compared with 1 of the 20 alendronate group. Thealendronate group had less worsening of their hip pain(p Z 0.003) compared to the control group. It is difficult tocompare this study with others, the patients weren’trandomised, the follow up period was short, it involvedsmall numbers of patients, and staged the lesions using anunfamiliar grading system, but combined with the previousstudies it does give additional support for the use ofbisphosphonates in early stage osteonecrosis. However, thedoses required and duration of therapy are yet to be clearlyestablished. The long-term effect of these drugs, many ofwhich have an extremely long half-life, on normal bonehomeostasis and turnover also merits caution.

Statins

Statins inhibit HMG-CoA reductase, this enzyme normallycatalyses the last step in cholesterol synthesis. These drugsreduce serum Low Density Lipo-protein (LDL) activity andreduce the entry of LDL into the circulation.

Steroids induce hyperlipidaemia that predisposes toosteonecrosis. Increased serum lipids are found in 60e85%of patients with osteonecrosis.

Two mechanisms are thought to lead to steroid inducedosteonecrosis:

� the accumulation of fat in the rigid marrow cavitycausing an intra-osseous compartment syndrome� the differentiation of osteoprogenitor cells along an

adipocyte lineage, so reducing the number of cellsavailable for repair and remodelling of necrotic bone.

Affecting either of these steps could be expected toreduce the risk of osteonecrosis.

Lovastatin both lowers serum lipid levels, and counter-acts steroid induced adipogenesis in bone marrow stromalcells.13

Cui et al demonstrated the effectiveness of statinsfor treating steroid induced adipogenesis in both multipo-tential bone marrow cell line and full animal model.14 In ananimal model none given both Lovastatin and steroiddeveloped osteonecrosis. They also showed that while bonemass in steroid treated chickens decreases significantly, itwas preserved in animals treated with steroids andconcomitant Lovastatin. They concluded that statins mini-mise the effect of steroids on fat cell accumulation in themarrow while maintaining the osteoblastic phenotype topreserve the normal microenvironment of bone marrow andthus prevent the development of osteonecrosis.15

Pritchett found that statins were effective in humansreceiving steroids. In 284 steroid treated patients, followedfor a minimum of five years, only 1% receiving concomitantstatin therapy developed osteonecrosis, against an expec-ted incidence of 3e20%.16 Of the three patients that diddevelop osteonecrosis, it occurred after at least five yearsof steroid treatment. Their recommendation was tocommence patients on statins prior to commencing steroidtherapy, to protect against the risk of both osteoporosis andosteonecrosis.

Other treatment options

Extra-corporeal shock wave therapy has been found to bemore effective than core decompression and fibular graft-ing, leading to regression of some small lesions and givingpain relief,17 the mechanism is felt to be secondary tomicro-fracture caused by the shock waves. Animal studieshave suggested that shock waves may actually cause anincrease in neovascularisation and the expression ofangiogenic growth factors.

The use of hyperbaric oxygen (HBO) has also been shownto be useful. HBO improves oxygenation, reducing oedema,and induces angioneogenesis; these changes causea reduction in intra-osseous pressure and improvement inmicrocirculation. Reis et al in a study involving 16 hips in 12patients, all with Steinberg stage 1 disease, gave eachpatient 100 consecutive days of HBO, which involvedbreathing 100% oxygen via a mask at 2e2.4 atmospherespressure for 90 minutes. Though the follow-up period ispoorly defined they reported that 13 of the 16 femoralheads subsequently appeared normal on MRI after thistreatment.18

Surgical treatment options

Initially surgery is intended to preserve the joint, with moreadvanced disease or greater involvement where preserva-tion of the joint is not possible, joint replacement proce-dures becomes the mainstay of surgical management.

Core decompression

Originally described in 1964 by Ficat and Arlet19 coredecompression is currently the most widely used procedurein the early stages of osteonecrosis of the femoral head.

Figure 1 Approaches to the femoral head, articular surfacetrapdoor or ‘light bulb’ via the base of the femoral neck.

352 S.J. Parsons, N. Steele

Originally it was used to obtain histological samples to aiddiagnosis of patients with hip pain. The procedure involvedremoving a central core of 8e10 mm with a hollow biopsytrephine followed by venography to confirm an abnormalpattern of blood flow within the femoral head. Bonemarrow pressure was measured and found to be consis-tently elevated in patients with osteonecrosis. Theprocedure also gave pain relief which was what lead to itsuse therapeutically rather than purely a diagnosticprocedure.

Decompressing the rigid intra-osseous chamber of thefemoral head aims to reduce intra-osseous pressure, sorestoring or improving vascular flow to prevent furtherischaemic episodes and progressive bone infarction. It hasbeen suggested that core decompression enhances theprocess of creeping substitution of the necrotic area bystimulating an angiogenic response in the drilled channels.

The usual surgical technique is to drill a single 8e10 mmcore into the necrotic lesion. Recently Mont et al20 useda multiple drill hole technique with a 3.2 mm pin reporting80% successful results for stage one disease (Harris hipscore of >80 and no further surgery). Many authors combinecore decompression with bone grafting, either vascularisedor non-vascularised, to enhance bone formation and reducethe risk of proximal femoral fracture.

There have been many studies looking at whether coredecompression alters the natural history of osteonecrosis.Comparison is difficult as there are many differences instudy design, patient selection, classification of necroticlesion, imaging techniques used and surgical proceduresperformed. In particular, early studies did not benefit fromadvanced imaging techniques to analyse the size andlocation of the necrotic lesions. Some have reportedimprovement with decompression, others have not. Ameta-analysis of outcome following core decompression of1206 hips shows the best results are seen with early stagedisease, 84% of Ficat stage-I, and 65% of Ficat stage-II hada successful result,4 but once collapse has occurred resultsbecome very much worse.

A retrospective review by Smith et al21 showsa substantially worse result in the presence of collapse ofthe femoral head preoperatively. Looking at 114 hips theynoted a marked decrease in satisfactory results whena crescent sign was present. The success rate for Ficatstage-I hips was 81%, but for Ficat stage-III disease of whichthere were 19 hips, the success rate was 0% with all hipsrequiring further surgery following core decompression.

Steinberg,22 applying his classification retrospectively,assessed 297 hips in 205 patients who had received coredecompression and cancellous bone grafting into the coretract followed for two years. He felt that the site and stageof the lesion influenced the results of core decompression.Total hip arthroplasty was required in 22% of the stage I andII hips with small area of involvement (stage IA and IIA, lessthan 15% head involvement). In contrast 39% of the stage-Ihips and 40% of the stage-II hips with involvement of �15%of the head (stage IB, IIB and IIC) eventually required totalhip arthroplasty.

Core decompression seems to be more effective thanpurely symptomatic treatment. It should be performed inearly stage hips and before there is any evidence ofcollapse. As it will not restore femoral head sphericity or

remove the collapsed segment from the weight bearingarea. Its use in Ficat stage III/IV disease should probably beconfined to those who are unfit or unwilling to accept moreextensive surgical procedures.

Obviously any contributory factors should be addressedif possible, particularly as patients who continue steroidtherapy after decompression have a worse prognosis.

Results are very much better in patients when decom-pression is combined with a grafting procedure, e.g. cor-tico-cancellous bone grafting, bone marrow aspirate, withor without Bone Morphogenetic Proteins (BMP’s). Additionalpost decompression procedures, such as direct currentstimulation and capacitance coupling probably add verylittle to long-term survival of the hip.

Bone grafting

Bone grafting procedures offer many advantages for thetreatment of pre-collapse lesions and early post collapseosteonecrosis of the femoral head, when the articularcartilage is not damaged. It allows decompression andremoval of necrotic bone, can provide structural support,act as scaffolding for repair and allow remodelling of sub-chondral bone.

Introducing graft via the core decompression tract waspopularised by Phemister.23 After removing an 8e10 mmcore, the tract is filled with cortical strut grafts taken fromthe ilium, fibula or tibia.

Bone graft can also be introduced through a corticalwindow in the femoral neck. This was originally performedin conjunction with an osteotomy by Ganz and Buchler.24

The term ‘light bulb’ procedure was introduced by Rose-nwasser et al.25 Cancellous bone graft harvested from theiliac crest is used to fill the defect in the femoral head aftercomplete evacuation of the necrotic bone. In their series 13of 15 hips, with stage II/III disease, were asymptomatic ata mean of 12 years (Fig. 1).

Another approach to bone grafting the femoral head isvia a trapdoor through the articular cartilage of thefemoral head, as first described by Merle d’Aubigne.26

Figure 2 Trapdoor grafting.

Osteonecrosis of the femoral head 353

After an arthrotomy the hip is dislocated anteriorly, thecollapsed segment is exposed via a 2 cm-square flap raisedfrom the chondral surface of the head (Fig. 2). Thenecrotic segment is removed with curettes and burrs. Thevoid is then filled with iliac crest bone graft with or withoutgraft expanders.

Mont et al27 reported on 24 Ficat stage III and 6 stage IVhips, treated using this method. With an average follow upof 56 months, 73% had good to excellent results. The 8 hipswith fair to poor results had Kerboul angles greater than 200degrees (Fig. 3), indicating the limitations and difficultiesof the technique in restoring femoral head sphericity inlarger lesions.

There is no consensus regarding the indications for non-vascularised bone grafting. While the proponents recom-mend grafting for hips with less 2 mm of femoral headdepression or in those where core decompression has failedwith no acetabular involvement, techniques requiring

Figure 3 Kerboul angle, provid

extensive dissection or dislocation of the hip and theelevation of flaps of cartilage may jeopardise an alreadytenuous blood supply to the femoral head. Combined withadjuvant therapies such as autologous bone marrow and theaddition of growth factors, bone grafting may yield betterresults in the longer term, especially in early stage disease.

Bone marrow

Augmenting other treatment methods with bone marrowmay be of benefit. A small pilot study looked at the effectof autologous bone marrow injection into the necrotic areaafter 3 mm core decompression. The authors compareda treatment group of 10 hips with ARCO grade I/II(pre-collapse) who underwent core decompression andimplantation of autologous bone marrow cells harvested atthe time of the decompression with 8 control hips, withsame stage disease that had core decompression alone. The

es a measure of lesion size.

354 S.J. Parsons, N. Steele

outcomes measures used were VAS pain scores, WOMACscore, lequesne index and an assessment of the volume ofthe necrotic lesion. After 24 months follow up the treat-ment group had statistically significant reductions in VAS(p Z 0.021), and joint symptoms. In the control group 5 ofthe 8 hips progressed to stage III (crescent sign), but onlyone in the treatment group (p Z 0.016). Two in the controlgroup underwent total hip replacement in the follow-upperiod, whilst none in the treatment group did. The volumeof the necrotic lesion in the treatment group as a propor-tion of the whole femoral head decreased from an averageof 15.6% to 10.1% at 24 months, in the control group it wentfrom 16.7% to 20.6% over the same period. The authors feltthat the effectiveness of the bone marrow might be due toosteogenic stem cells giving additional repair capacity, andthe angiogenic cytokines secreted by marrow stromal cellscausing increased angiogenesis and subsequent improve-ment in osteogenesis.28

A similar study29 in 189 hips followed for five to ten yearsfollowing decompression and implantation of autologousiliac crest bone marrow, reported successful outcomes(defined as avoidance of hip replacement) in 136 (94%) of145 hips that operated on before collapse, but only in 19(43%) of 44 hips that had been operated on after femoralhead collapse.

Bone morphogenetic proteins

Bone morphogenetic proteins (BMPs) have been used as anadjunct to grafting procedures, to promote angiogenesis orto activate bone formation. Recombinant Human BMP-2(rhBMP-2) is a growth and differentiation factor that stimu-lates mesenchymal cells to differentiate into bone or carti-lage forming cells. As surrounding mesenchymal cellsinfiltrate an area implanted with rhBMP-2, bone or cartilageis formed and vascular invasion is noted to occur. While usedup until now mainly for fracture treatment, rhBMP-2 hasbeen used to enhance healing after core decompression. Ina study of 24 patients with FICAT I or II osteonecrosis receivedrhBMP-2 mixed with autologous blood clot at core decom-pression. The incidence of disease progression at 2 years waslower in the rhBMP group than in controls (46% vs. 58%) andfewer patients required THR (25% vs. 47%). However eightpatients did develop heterotopic bone formation.30

BMP-7 (osteogenic protein-1, OP-1) has also been eval-uated as an adjunct to femoral head preserving procedures.To replicate osteonecrosis treated via a trap doorapproach, Mont et al31 created a femoral head defectmodel in 34 dogs. After elevating the articular flap, in onearm of the study, the bone defect was filled with bone graftwith OP-1, and in the other arm graft alone was used.Compared with femoral defects that were not grafted,those grafted with or with out OP-1 consistently healed.However those with OP-1 healed sooner, the one-monthpost procedure histologic appearance of the OP-1 groupwas comparable to the 3-month appearance of thosetreated with bone graft alone.

Fibular bone grafting

As originally described by Phemister23 tibial bone strutswere inserted though two core tracts drilled into the

femoral neck. The technique evolved to use the patient’sipsilateral fibula, harvested at the time as the coredecompression and inserted into a single core tractdirected toward the necrotic lesion. Microvascular surgicaltechniques allow the bone to be harvested on a vascularpedicle, the intention being to prevent collapse of thefemoral head and to enhance vascularisation. The tech-nique involves decompression of the femoral head, withsequentially larger reamers. Then necrotic bone is removedand replaced with autogenous iliac crest cancellous bonegraft. The fibular bone strut supports the subchondralbone, allowing revascularisation and osteogenesis of thefemoral head.

It involves harvesting a section of ipsilateral fibula withits peroneal artery and two veins which is placed up thecore tract to within 3e5 mm of the subchondral bone andheld with a K wire. The pedicle is then anastomosed to theascending branches of the lateral circumflex femoralvessels.

Reported results vary. Urbaniak32 reporting on 103 hipsin 89 patients and showed a statistically significantincrease in Harris hip scores with vascularised grafting.After a minimum follow-up of five years 31 hips hadrequired conversion to total hip arthroplasty. Whencompared to core decompression alone, the results arebetter. Kane et al,33 treated 39 hips with decompression ora free vascularised graft, followed for 2e5 years. Coredecompression alone was successful (defined as no furthersurgery) in 8 of 19 hips (42%), whereas treatment with thefree graft was successful in 16 of 20 hips (80%).

Comparing vascularised with non-vascularised grafts, theformer perform better. Plakseychuk et al (Z),34 comparedtwo groups of fifty patients. They used Kaplan-Meier survi-vorship analysis for stage I/II disease, with collapse as theend point. After seven years follow-up 86% of hips with vas-cularised graft had not collapsed, compared with 30% for thenon-vascularised group. 70% of the vascularised graft grouphad a significant improvement in Harris hip score, against 36%of the non-vascularised group. Radiographic signs of diseaseprogression were noted in 24% of the vascularised group andin 72% of the non-vascularised graft group. Non-vascularisedgrafting was also noted to have poorer results for steroid andalcohol associated osteonecrosis.

Whilst some of the results are good, it is a complexprocedure microvascular expertise not available to allunits. Rates of donor site morbidity are as high as 20%,(motor weakness, ankle discomfort and sensory abnormal-ities in the lower limb). Additionally there is a small risk ofproximal femoral fracture due to the size of core tract forthe graft insertion and the graft also leads to a markedchange in the bone stock of the proximal femoral neck andcalcar, making subsequent arthroplasty more difficult.

Osteotomy

Various osteotomies have been proposed to rotate thenecrotic or collapsing segment of the hip out of the weightbearing zone, replacing it with a segment of articularcartilage of the femoral head supported by healthy viablebone. In addition to the biomechanical effect, osteotomymay also reduce venous hypertension and decrease intra-medullary pressure.

Osteonecrosis of the femoral head 355

Two main types have been described:

1. Trans-trochanteric rotational2. Intertrochanteric varus or valgus osteotomy (usually

combined with either flexion or extension).

Osteotomy is used rarely, but does have a place in themanagement of the symptomatic younger patients (<45years). It is best suited to patients not being treated withlong term steroids, with minimal osteoarthritic changes,with no loss of joint space or acetabular involvement anda small combined necrotic angle (Kerboul angle).

While Sugioka et al35 reported good to excellent resultsafter trans-trochanteric anterior rotational osteotomies,others have not reproduced the results of this difficultprocedure.

The major concern with osteotomy arises when under-taking a subsequent joint replacement; problems removingmetal work removal, broken screws, and fractures have allbeen reported.

Limited femoral resurfacing

Resurfacing of the femoral head with cement fixation wasfirst performed in the early 1980’s in young active patientsas a means of preserving bone stock to permit laterconversion to total hip arthroplasty with minimal morbidity.The procedure represented an evolution of the SmithPetersen mold arthroplasty.

Langlais et al36 reviewed the x-ray appearance of 86 cuparthroplasties, assessed the tolerance of the acetabulum tothe cup. At mean follow up of 6.5 years, 85% had good toexcellent results. Congruence between the acetabulum andthe cup was the one factor predicting good outcome. Andthe importance of precision fitting of the cup to thehealthiest region of acetabular cartilage, whether periph-eral or central, was stressed, as when this was achievedprotrusio complications were non-existent.

Hungerford et al,37 reported a series of 33 femoral headresurfacing for stage III/IV disease. 91% survived 5 years,and 70% for 10 years. The failures, 13 hips, underwent totalhip arthroplasty after a mean interval of sixty months withgood results. Failure was secondary to persistent painarising from acetabular cartilage wear. They felt that hemi-resurfacing was a useful interim procedure in hips thatcould only otherwise be treated by total hip arthroplasty.

Beaule et al, followed 37 hemi-resurfaced hips for anaverage of 6.5 years (2e18 years) and reported good toexcellent results (Harris and UCLA hip scores) in 79% and59% at five and ten years respectively.38 At operation theacetabular cartilage was graded and photographed. Fromthis they concluded that a longer duration of preoperativesymptoms was associated with a greater degree of degen-erative change in acetabular cartilage, and that suchpatients required earlier revision to total joint arthroplasty.

Thus a good outcome from hemi-resurfacing requires goodquality acetabular cartilage and an accurately sized femoralhead component. If these can’t be achieved then the patientmay be better served with a total joint replacement. Oneother factor of note is that whilst the pain relief offered byhemi-resurfacing can be good, it is not as predictable as thatseen with conventional total joint replacement.

Full resurfacing arthroplasty

Total articular resurfacing arthroplasty (TARA), was intro-duced by Townley.39 This involved replacing a limitedportion of the femoral head and a thin cemented poly-ethylene acetabular component. It had high rates offailure, the large sliding distances combined with thinpolyethylene led to rapid acetabular wear, subsequentosteolysis and early implant failure.

The renaissance of large head, metal on metal bearingsurfaces has seen resurfacing become an increasinglypopular choice for younger patients with end stagearthritis. However the use of these devices for osteone-crotic hips has led to some concerns regarding the vascularinsult to the femoral head. However this mode of failurewas not seen with hemi-resurfacing for osteonecrosis andfemoral failure did not occur; analysis of 25 femoral headsup to 12 years after hemi-resurfacing of the hip showedthat osteonecrosis is not induced by this procedure,40 thefailures that are seen with hemi-resurfacing are usually dueto continued erosion of acetabular cartilage.

Revell et al,41 reported a single surgeon series ofresurfacing of 73 hips in 60 patients. The Ficat stages wereadvanced in the majority of patients (2 stage II, 25 stage III,46 stage IV). The patients average age was 43 years, andthe average follow up was 6.1 years.2e12 All operationswere performed via a posterior approach. The criteria forresurfacing either pre or intraoperatively were:

1. Less than 35% necrosis2. Head neck junction integrity preserved3. Good remaining bone stock providing a stable founda-

tion for femoral component post reaming.

Any patient not meeting these criteria was not felt tobe suitable for a resurfacing arthroplasty. They reported93.2% survival rate at 6.1 years, with five failures, butexpressed concerns that the femoral component survivalmight be at risk in patients with on-going alcohol exposureor steroid use. They felt that with late stage disease,patients entered a relatively stable phase from a vascularperspective but in a potentially less stable mechanicalenvironment.

Mont et al, reported a matched group of 42 hips usinglarge head metal on metal resurfacing with a mean followup of 41 months. The osteonecrotic group had 94.5%survival rate of implant at final follow up, compared with95.2% for osteoarthritic patients,42 similar results are seenboth groups of patients.

These results suggest that resurfacing in the hands ofexperienced arthroplasty surgeons provides good short-term outcome with preservation of proximal femoral bonestock. In common with the results for young osteoarthriticpatients only longer term follow up will show if the goodearly results will be maintained.

Total hip arthroplasty

The underlying diagnosis of osteonecrosis appears to havean impact on implant durability which may account forconflicting results for arthroplasty in such patients. The

Figure 4 Pyrophosphate and Bisphosphonate structure.

Figure 5 Table of bisphosphonates. RP is a measure ofrelative potency, demonstrating the effect of R2 side chainmodification.

356 S.J. Parsons, N. Steele

femoral bone quality is often poor, there may be continuingdefective bone mineral metabolism, in a hip that is sub-jected to continuing insults. In particular, patients withsickle cell disease, systemic lupus erythematosus, post-renal transplant and on-going alcohol abuse seem to farepoorly. Additionally this patient group are younger and aremore active, all factors affecting implant longevity. Thepoor early results for total joint arthroplasty were welldemonstrated in a matched comparison between total hiparthroplasties performed for osteonecrosis and osteoar-thritis, by Ortiguera et al.43 This involved 188 hips withcemented Charnley stems, followed up for 17.8 years(range 10e25 years) and showed poorer results in osteo-necrotic patients. Overall revision rates for osteonecrosisand osteoarthritis were not significantly different, but inpatients younger than 50 years, the revision rate in osteo-necrosis (50%) was significantly higher than that in anyother group. Similarly, the mechanical failure rate inosteonecrosis was significantly greater in the patientsyounger than 50. Also dislocations occurred morefrequently in the osteonecrosis group (10%) than in theosteoarthritis group (1%).

Comparing total hip arthroplasty using third generationcementing techniques with second generation uncementedhip replacement, Kim et al reported very encouragingresults with a 98% survival at 12 years follow-up, theseexcellent results were however in a very selected patientgroup that may not be truly representative.44

Mont et al, in a single surgeon series of young patients(mean age 38 years) using an uncemented prosthesisshowed good early results. They compared 52 osteonecrotichips with 52 osteoarthritic hips. Short term results over fouryears showed that revision free survivorship was compa-rable between the groups. This group did use a combinationof bearing surfaces some with metal on HXLPE, and someceramic on ceramic.45

The use of contemporary cementing techniques oruncemented components combined with improved bearingsurfaces that reduce wear can all be expected to lead toimproved longevity of implants. Coupled with the largerhead combinations made possible by hard on hard bearingsurfaces, this should reduce the increased dislocation risk.

These factors are showing promise and will hopefullylead to better survival of joint replacements used in thisdemanding of all patient groups.

Annex A e Biphosphonates

Bisphosphonates are synthetic metabolically stableanalogues of inorganic pyrophosphate in which the PeOePbond has been replaced with a non-hydrolysable PeCePbond. The diphosphate configuration of both PeOeP andPeCeP contributes to a three-dimensional structurecapable of binding divalent ions such as calcium and is thebasis for their bone targeting properties. Whereas the PeOeP bond is rapidly metabolised, the PeCeP bond ofbisphosphonates is not metabolised so there is considerablelongevity of these compounds after administration (Fig. 4).

The mode of action of these compounds depends ontheir chemical structure, which can be grouped intonitrogen containing and non-nitrogen containingcompounds.

The older bisphosphonates (etidronate, clodronate)possess simple non-nitrogen side chains (R1 and R2, seeFig. 4) and are metabolised to non-hydrolysable analoguesof ATP. Bisphosphonate binds to mineral in bone exposed byosteoclastic activity (normal or pathological). Osteoclastshave a high endocytic activity in the later stages of thebone remodelling cycle and resorb both the bone and thebound bisphosphonate or the ATP analogue. These cyto-toxic analogues accumulate intracellularly leading to inhi-bition of osteoclast function and premature apoptosis.

Modifying the R2 side chain has led to the developmentof agents with very much higher anti-resorptive activity(Fig. 5). These agents containing amino/primary aminegroups are the nitrogen containing bisphosphonates, forexample Risedronate and Alendronate.

They exert their effect by inhibiting the parts of themevalonate pathway. This is the biosynthetic pathway forcholesterol production that is also targeted by certainstatins.

Certain cholesterol precursors are made via this pathway.They transfer their respective lipid component, onto thecysteine residue of a protein, in a process known as proteinprenylation. The same process forms GTPase. It is this processthat nitrogen containing bisphosphonates inhibit. Leading toa loss of GTPase prenylation this in turn causes a loss ofosteoclast regulation, including control of cell morphology,disruption of integrin signalling, altered membrane proteintrafficking, loss of membrane ruffling and disruption of cyto-skeleton then ultimately induction of apoptosis.

Osteonecrosis of the femoral head 357

It is a common misconception that the mechanism ofaction of bisphosphonates is specific to the osteoclast.This is not the case; the mevalonate pathway is presentin many cell types. As the osteoclast is in direct contactwith the bone surface during resorption they are exposedto very high concentrations of these compounds and assuch are the most affected. Other cells exposed to highconcentrations of bisphosphonates in cell culture havealso shown problems with protein prenylation, though theclinical relevance of this observation is unclear at thepresent time.

Acknowledgements

Andrew and Alan in Medical illustration, RJAH, Oswestry.

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