Biological options in avn

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Biological options in avn

  1. 1. Biological options in AVNfemur Dr. Sushil Paudel
  2. 2.  Avascular necrosis (also osteonecrosis,bone infarction,aseptic necrosis,ischemic bone necrosis,and AVN) Disease where there is cellular deathof bone components due tointerruption of the blood supply
  3. 3.  The LEV enters the femoral head within a 1-cm-wide zone between the cartilage of the femoralhead and the cortical bone of the femoralneck. Supply the lateral and central thirds of thefemoral head When patent, the artery of the ligamentumteres (ALT) supplies the medial third of thefemoral head
  4. 4.  Etiology and pathophysiology
  5. 5.  AVN : areas of dead trabecular bone andmarrow extending to involve the subchondralplate. Anterolateral aspect of the femoral head, theprincipal weightbearing region typicallyinvolved, but any region of the femoral headmay be involved. Involved segment usually never fullyrevascularizes, and collapse of the femoralhead usually occurs
  6. 6.  Elderly persons at decreased risk Fat cells become smaller, space between fatcells fills with a loose reticulum and mucoid fluid,which are resistant AVN. Condition is termed gelatinous marrow. Even in the presence of increasedintramedullary pressure, interstitial fluid escapesinto the blood vessels, leaving the spaces free toabsorb additional fluid.
  7. 7.  Clinical picture nonspecific Presenting symptom unilateral hip pain, whichmay be followed by a limp and a decreasedrange of motion (ROM). Young adults between the ages of 30 and 40most frequently affected Bilateral in more than 50% of patients
  8. 8. Sequelae of avascular necrosis Minimal AVN - If the vascular area is small and isnot adjacent to an articular surface, the patientmay be asymptomatic; healing may occurspontaneously, or the disease may remainundetected or be discovered incidentallyduring workup for other conditions.
  9. 9.  More severe AVN : repair begins at the interfacebetween viable bone and necrotic bone. Dead bone reabsorbed only partially. Reactive and reparative bone laid down on deadtrabeculae, resulting in a sclerotic margin ofthickened trabeculae within an advancing front ofhyperemia, inflammation, bone resorption, andfibrosis. Incomplete resorption of dead bone has a mixedsclerotic and cystic appearance on radiographs.Necrosis and repair are ongoing in various stages ofevolution within a single lesion.
  10. 10.  Mechanical failure - In the subchondral regionmicrofractures do not heal Progression of the microfractures results in adiffuse subchondral fracture, seenradiographically as the crescent sign Following subchondral fracture and progressiveweightbearing, collapse of the articularcartilage occurs Continued fracture, necrosis, and furtherweightbearing may progress to degenerativejoint disease (DJD) and joint dissolution
  11. 11. IMAGING MODALITIES AP and lateral radiographs of both hips Initially within normal limits because it takes aperiod of weeks to months after the initiatingevent for changes to appear on radiographs The first changes to be noted are areas ofradiolucency and sclerosis within the femoralhead, usually in the anterior superior quadrant
  12. 12.  If osteonecrosis suspected despite normal-appearing plain radiographs, MRI of both hipsshould be obtained because more than 50% ofcases are bilateral
  13. 13. MRI Help guide interventional procedures such ascore decompression, Demonstrate response of the femoral head totreatment Noninvasive means of evaluating articularcartilage congruity Sequential evaluation of asymptomatic lesionsundetectable on plain radiographs.
  14. 14. I DDPlain film radiographs Malignancy Osteomyelitis Transient osteoporosis of the hip Bone sarcoma Advanced Degenerative joint disease Insufficiency fractures Epiphyseal dysplasia Bone metastases
  15. 15. Bone scintigrams Infection Plasma cell myeloma Skeletal metastasis Hemangioma Radiation therapy Arthritis Sympathetic dystrophy Bone marrow edema syndrome Bone metastases
  16. 16. CT scans Degenerative disease Insufficiency fracture Malignancy Infection Plasma cell myeloma Bone metastases
  17. 17. MRIs Transient osteoporosis of the hip Transient bone marrow syndrome Bone bruise Epiphyseal stress fracture Infection Infiltrative neoplasm Insufficiency fracture Bone metastases
  18. 18. Ficat and Arlet Radiographic StagingSystem for AVN Stage 0 (preclinical and preradiologic) Avascular necrosis (AVN) can be suggestedonly if it has already been diagnosed in thecontralateral hip.
  19. 19.  Stage 1 (preradiologic)Defined by normal findings on radiographs andpositive findings on MRI or bone scintigraphy. Early resorptive stage, Late in this stage, plain radiographs may showminimal osteoporosis and/or blurring and poordefinition of the bony trabeculae
  20. 20.  Stage 2 (reparative) Demineralization evident; first manifestation ofthe reparative stage, represents resorption ofdead bone, and may be generalized or patchyor appear in the form of small cysts within thefemoral head
  21. 21. Anteroposterior view of thepelvis in a patient withbilateral avascular necrosisof the femoral head. Mildflattening to the superioraspect of the right femoralhead (open arrow)indicates stage 3 disease.The left femoral head has anormal contour, indicatingstage 2 disease.
  22. 22. Stage 3 (early collapse of the femoralhead ) Linear subcortical lucency, representing a fracture line,present immediately beneath the articular cortex andmay extend into the articular cartilage at thesuperolateral aspect of the femoral head. Crescent sign ; best demonstrated on a frogleg view Subarticular cortex remain attached to the cartilageand is separated from the underlying femur by soft tissue,termed the eggshell sign. The femoral head initially preserves its roundappearance, but later, it demonstrates collapse,indicated by joint-space widening.
  23. 23. Frogleg lateral view of the right hip in a patient with avascular necrosis shows thecrescent sign, indicating subchondral fracture.
  24. 24. Stage 4 (progressive degenerative disease) Further flattening of the femoral head with lossof its smooth convex contour Ultimately, the superior femoral fragment,representing the articular surface and theimmediate subchondral bone becomeseparated from the underlying femoral head ordepressed and compacted into the femoralhead. Fragments of bone and cartilage may separatefrom the underlying femur, become loosebodies.
  25. 25.  Severe collapse anddestruction of the femoralhead leads to progressivedegenerative jointdisease (DJD) with joint-space narrowing,marginal osteophyteformation, andsubchondral cystformation
  26. 26. Steinberg et als Staging System for AVN Steinberg et al proposed a 6-stage classificationsystem based on that of Ficat and Arlet andincluded radiologic clinical classificationfindings
  27. 27.  Stage 0 - both preclinical and preradiologic,identified when imaging is performed to evaluateAVN in the contralateral hip or to exclude otherdiseases. Abnormal MRI findings, normalradiographic findings, and normal bone scanfindings Stage 1 - normal radiographic findings or minimaldemineralization or blurred trabeculae,Pain in theanterior groin or thigh ,Limited ROM in the hip Stage 2 - Osteoporosis, groin pain, and mottledsclerotic and/or cystic area
  28. 28.  Stage 3 - crescent sign (subchondral fracture) ,pain with subchondral fracture activity, and nofemoral head flattening Stage 4 - marked collapse and fractureinvolving the articular surface, Segmentalflattening, pain with femoral head activity, noacetabular involvement, and normal joint space Stage 5 - joint space narrowing, resting pain,and acetabular degeneration (DJD)
  29. 29.  AVN Classification per Central Avascular SegmentSignal Alterations
  30. 30. Class A - Central osteonecrotic focus signal analogous to that of fat arenoted. Increased signal is demonstrated on T1WIs, and intermediate tohigh signal is demonstrated on T2WIs
  31. 31. Class B - The presence of central osteonecrotic focus signal analogous to that of blood is observed. Increasedsignal is demonstrated on both T1WIs and T2WIs
  32. 32. Class C - Central osteonecrotic focus signal analogous to that of fluid is present. Decreased signal isdemonstrated on T1WIs, and increased signal is demonstrated on T2WIs
  33. 33.  Class D - The presence of central osteonecroticfocus signal analogous to that of fibrous tissue isnoted. Decreased signal is demonstrated onboth T1WIs and T2WIs
  34. 34. University of PennsylvaniaSystem
  35. 35.  To determine the most appropriate treatment,consider the following aspects: age of the patient, stage of the disease (early orlate),location and amount of boneaffected (small or large area),underlying causeof AVN (with ongoing causes such ascorticosteroid or alcohol use, treatment may notwork unless use of the substance is stopped)
  36. 36. Conservative management Restricted weight-bearing Pharmacological agentslipid-lowering drugs, anticoagulants,vasodilators, and bisphosphonates External, biophysical, nonoperative modalitiesPulsed electromagnetic field stimulationExtracorporeal shockwave therapyhyperbaric oxygen (HBO)
  37. 37. Restricted weight-bearing Advised with the expectation of preventing femoralhead collapse during the healing Only 5 studies with reference to weight bearing astreatment modality Factors related to resolution : early, asymptomaticdisease (ARCO stage I) and small lesion size (amodified index of necrotic extent of < 25). Hernigou et al, observed that clinical andradiographic signs of the disease in asymptomatichips with a very small asymptomatic lesion progressmore slowly than do signs in hips with a largesymptomatic stage-II lesion
  38. 38.  Agarwal et al studied 60 patients with AVN of the hip (100 hips ). Allpatients were treated with alendronate 10 mg/day (or 70 mg/week)along with 500-1000 mg of daily calcium and vitamin D supplements,and were advised to avoid weight-bearing. NSAIDs and analgesicswere permitted as needed and were recorded. CONCLUSION: Alendronate reduces pain, improves function and retards AVNprogression. Early surgical intervention can be avoided in mostpatients.Rheumatology (Oxford) 2005 Efficacy of alendronate, a bisphosphonate, in the treatment of AVN ofthe hip. A prospective open-label study. Agarwala S, Jain D Joshi VR,Sule A P. D. Hinduja Hospital, Mahim, Mumbai 400 016, India.
  39. 39. Operative intervention 1. Core decompression 2. Core decompression with bone graftingPhemister type fibular graftingCancellous iliac bone graftingMeyer’s Quardatus femoris muscle graftingSartorious muscle pedicle graftingTensor fascia lata pedicle graftingGluteus medius pedicle graftingVascularized muscle pedicle bone grafting
  40. 40.  3. Osteotomy 4. Surface arthroplasty 5. Total hip arthroplasty
  41. 41. Core decompression 2 methods of core decompression: large-diameter trephines and small-diameter drills. Themost common method, the 8 to 10-mmtrephine, is completed under fluoroscopy withthe core track either being left open or filled inwith bone graft
  42. 42.  Complications e.g., articular cartilage damageand subchondral fractures associated with thelarge-diameter technique, Kim et al. developed the multiple small-diameter core decompression technique. In their initial cohort of patients treated with thistechnique, they reported a lower rate ofcollapse (14.3%) as compared with the ratereported with the traditional trephine method Kim SY, Kim DH, Park IH, Park BC, Kim PT, Ihn JC. Multiple drilling compared withstandard core decompression for the treatment of osteonecrosis of the femoralhead [abstract]. J Bone Joint Surg Br. 2004;
  43. 43. After core decompression
  44. 44.  Stulberg et al. compared core decompressionalone with conservative treatment in aprospective, randomized study of 55hips. Onthe basis of Harris hip scores, operativetreatment was successful in approximately 70%of hips with Ficat Stage-I, II, or III osteonecrosis. Incontrast, nonoperative treatment was successfulfor 20% of hips with Ficat Stage-I disease, 0% withStage-II,and 10% with Stage-III Stulberg BN, Davis AW, Bayer TW, Levine M,Easley K. Osteonecrosis of the femoral head.Aprospective randomized treatment protocol Clin Orthop.
  45. 45.  Smith et al. reviewed twelve articles, publishedbetween 1979 and 1991, that included a total of702 hips with an average duration of followup ofthirty-eight months. Using the University ofPennsylvania staging system, they reported asuccessful result in 78% of the Ficat Stage-I hips,62% of the Stage-II hips, and 41% of the Stage- IIIhips. Smith SW, Fehring TK, Griffin WL, Beaver WB.Core decompression of theosteonecrotic femoral head. J Bone Joint Surg Am
  46. 46.  USE OF OSTEOINDUCTIVE SUBSTANCES ALONGWITH CORE DECOMPRESSION
  47. 47.  Mont et al used a modified trapdoor techniqueand bone morphogenetic protein enriched bonegraft substitute through a window at the femoralhead-neck junction in 23 patients. Successful clinical results (a Harris hip score of 80points or greater and no additional procedures) in18 of 21 hips (86%) at a minimum follow up of 36months (mean, 48 months; range, 36–55 months) Extensive dissection required and, technically moredifficult than a standard core decompression Mont MA, Etienne G, Ragland PS. Outcome of nonvascularized bone graftingfor osteonecrosis of the femoral head. Clin Orthop Relat Res. 2003
  48. 48. Lieberman et all retrospectively evaluated 15 patients (17 hips) withAVN hip treated with core decompression combined with anallogeneic, antigen-extracted, autolyzed fibula allograft and 50 mgof partially purified human bone morphogenetic protein andnoncollagenous proteins Clinical success in 14 of 15 hips (93%; 13 patients) with Stage IIAdisease. 3 of 17 hips had radiographic progress and converted to total hipreplacements. Only 1of seven hips with 50% or less involvement of the femoral headdeveloped radiographic progression of the femoral head No radiographic progression in the 3 hips with less than 1/3involvement of the weight bearing surface of the femoral head. Concluded further evaluation of the potential efficacy of bonemorphogenetic protein required in randomized trials.Treatment of osteonecrosis of the femoral head with core decompression and human bone morphogenetic protein.Lieberman JR
  49. 49.  Mesenchymal stem cells (MSC) from adult bonemarrow are multipotent that can differentiateinto fibroblastic, osteogenic, myogenic,adipogenic and reticular cells.These cells mayalso provide a potential therapy for bone repair Procedure of autologous stem celltransplantation has been standardized with theguidelines that these should be instilled inconcentration of 2X106 stem cells in non-traumatic pre-collapse stage of avascularnecrosis femur head.
  50. 50.  Effectiveness of bone marrow mononuclear cellsrelated to the availability of stem cells endowedwith osteogenic properties Injected marrow stromal cells secrete angiogeniccytokines, resulting in increased angiogenesis Bone marrow contains the bone morphogeneticproteins such as BMP-2 Supplementation of bone marrow stromal cellscultures with FGF-2 resulted in prolonged lifespan ofbone marrow stromal cells to more than 70doublings and maintained their differentiationpotential accompanied by an increase of theirtelomerase size
  51. 51. Yan et al treated 44 hips in 28 patients with AVN at early stageby percutaneous multiple holes decompression followed byautologous BMCs infusion. Autologous BMCs wereconcentrated from bone marrow that was taken from theposterior iliac crest of the patient. Patients were followed up atleast 2 years. The results were determined by the changes inthe Harris hip score and the progression in the radiograghicstages. They concluded ercutaneous multiple holes decompressioncombined with autologous BMCs is a new way to treatavascular necrosis of the femoral head. Treatment of osteonecrosis of the femoral head by percutaneousdecompression and autologous bone marrow mononuclear cell infusion.Yan ZQ, Chen YSLi , Yang Y Huo JZ Chen ZR Shi JHGe JB Source Department ofOrthopaedics, Zhongshan Hospital of Fudan University, Shanghai 200032,China. healthbone@zshospital.net
  52. 52.  Valerie et al studied the implantation of autologous bone-marrow mononuclear cells in a necrotic lesion of the femoralhead along with core decompression. After twenty-four months, significant reduction in pain (p =0.021) and in joint symptoms within the bone-marrow-graftgroup Implantation of autologous bone-marrow mononuclear cellsappears to be a safe and effective treatment for early stagesof osteonecrosis of the femoral head. Treatment of Osteonecrosis of the Femoral Head with Implantation of Autologous Bone-Marrow CellsValérie Gangji, MD1; Jean-Philippe Hauzeur, MD, PhD J Bone Joint Surg Am. 2005
  53. 53.  Deltro et al, published their experience in 8 patientswhere they assessed the efficacy and safety ofautologous bone-marrow mononuclear cells (BMMC)implantation in necrotic lesions of the femoral head inpatients with sickle cell disease. After 8 months, 7 of the eight patients reportedimprovement from symptoms Concluded autologous bone-marrow mononuclear cellsimplantation is a safe and effective treatment for earlystages of femoral head osteonecrosis in patients withsickle cell disease Daltro GC, Fortuna VA, Salvino de Araújo SA, FerrazLessa PI, SobrinhoUA, Borojevic R. Femoral head necrosis treatment with autologousstem cells in sickle cell disease. Acta Orthop Bras. 2008;
  54. 54.  Use of a tantalum implant reported in 2 studies Tantalum is a light metal that has a high yield to stress. Inthese studies, porous tantalum rods used to potentiallyallow bone growth to occur while providing support.While the short-term results in these studies comparedfavorably to other core decompression techniqueslonger follow-up is needed to more fully assess theefficacy of this procedure. Tsao AK, Roberson JR, Christie MJ, Dore DD, Heck DA, Robertson DD, Poggie RA.Biomechanical and clinical evaluations of a porous tantalum implant for thetreatment of early-stage osteonecrosis. J Bone Joint Surg Am. 2005;87 Suppl 2: 22-7.8722 2005 Veillette CJ, Mehdian H, Schemitsch EH, McKee MD. Survivorship analysis andradiographic outcome following tantalum rod insertion for osteonecrosis of thefemoral head. J Bone Joint Surg Am. 2006;88 Suppl 3: 48-55.8848 2006
  55. 55.  Bone-grafting procedures can be divided intotwo general categories: non-vascularized andvascularized
  56. 56.  3 approaches to introduce bone graft into thefemoral head a core tract window in the femoral neck (a ―lightbulb‖procedure) a ―trapdoor‖ made through the articularcartilage in the femoral head
  57. 57.  Cortical strut-grafting, a procedure popularizedby Phemister, Boettcher et al., and Bonfiglio etal. not commonly used today Technique involves the removal of an 8 to 10-mm-diameter cylindrical core of bone from thefemoral head and neck. This core tract is thenfilled with cortical strut grafts harvested from theilium,fibula, or tibia. Postoperatively,protected weight-bearing forthree to six months
  58. 58. Grafting using an intact fibular allograft
  59. 59. Lightbulb procedure The term lightbulb procedure introduced byRosenwasser et al. Cortical window lifted from the femoral head-neckjunction, cancellous bone graft from the iliac crestused to fill the defect in the femoral head aftercomplete evacuationof the necrotic bone. In their series, thirteen of fifteen hips wereasymptomatic at a mean of twelve years (range,ten to fifteen years) Rosenwasser MP, Garino JP, Kiernan HA, MichelsenCB. Long termfollowup of thorough debridement and cancellous bone graftingofthe femoral head for avascular necrosis. ClinOrthop. 1994
  60. 60. Trapdoor
  61. 61. Muscle pedicle grafting
  62. 62.  Meyers (1978) reported that fresh autologousiliac bone chips combined with a muscle-pedicle bone graft gave good results in stages 1and 2 necrosis, but was unsatisfactory in stages3 and 4.
  63. 63. Technique for performing muscle-pedicle bonegrafting to the femoral head, modified after Meyerset al
  64. 64.  Baksi(1991) reported his results at 3 to 12 years(mean, 7 years) follow-up in treating 61 patients(68 hips) with a variety of muscle pedicle bonegrafts. Tensor fascia lata anteriorly and the quadratusfemoris posteriorly preferred. As many as 83% of the patients, obtained goodor excellent results at follow-up.Baksi DP. Treatment of osteonecrosis of the femoral head by drilling andmuscle-pedicle bone grafting. J Bone Joint Surg Br. 1991;
  65. 65. Vascularized fibular grafting
  66. 66.  The rationale for management of osteonecrosis ofthe femoral head with a free vascularized fibulargraft based on five principles: (1) decompression of the femoral head, (2) removal of the necrotic bone, (3) replacement with fresh autogenous cancellousbone, (4) support of the subchondral bone with a viable strong bone strut, (5) revascularization and osteogenesis of thefemoral head.
  67. 67.  INDICATIONS: Symptomatic patients younger than fifty years ofage with stage- II, III, or IV Patients younger than 20 of age who havestage-V disease and a good range of motion ofthe hip
  68. 68. A 15-cm incision is made on the lateral aspect of the leg between thelateral and posteriorcompartments. The incision is begun 10 cm distal to the fibular head (PF)and ends10 cm proximal to the tip of the lateral malleolus (LM).
  69. 69. The yellow arrow is pointing to the anterior intermuscular septum. The black arrow ispointing to the fibula, on which a small cuff of muscle and periosteum has beenpreserved—the so-called marbleizing technique
  70. 70. The interosseous membrane (IOM) is divided with a specially designedright-angle Beaverblade (white arrow). The close proximity of the deep peroneal nerve andanterior tibial artery(black arrow) can be seen in this photograph
  71. 71. The fibular osteotomy is performed once the pediclehas been isolated distally and proximallyand protected with malleable retractors
  72. 72. The proximal stump of the peroneal artery is ligated with the hemostaticclips (arrow) justas it branches from the posterior tibial artery, ensuring at least a 4 to 5-cmpedicle
  73. 73. Cancellous bone harvested from the greater trochantericarea is inserted into the cavity formedby removal of the necrotic bone. The fibulargraft is inserted into the core tract and stabilizedwith a 0.62-mm Kirschner wire (K). Theperoneal veins and artery are anastomosed tothe ascending branches of the lateral femoralcircumflex artery (LFCA) and vein
  74. 74.  Urbaniak reviewed the results in 1523 hips treated with a freevascularizedfibular graft for osteonecrosis between 1979 and October1, 2000 Best results obtained in the patients who had had no collapse of thesubchondral bone or articularcartilage preoperatively. Of the hips that had not had preoperative subchondral or articularcollapse, 91% had a successful result after six months to twenty-twoyears of follow-up. If collapse had been present, the success rate was 85%, and if therehad also been joint-space narrowing, it was 65% Urbaniak JR, Coogan PG, Gunneson EB, Hunley JA. Treatment of osteonecrosis of thefemoral head with free vascularized fibular grafting. A long-term follow-up study of onehundred and three hips. J Bone Joint SurgAm. 1995
  75. 75. Vascularized iliac crestgrafting
  76. 76. OSTEOTOMY To rotate the necrotic or collapsing segment ofthe hip out of the weight bearing zone,replacing it with a segment of articular cartilageof the femoral head supported by healthyviable bone. In addition to the biomechanical effect,osteotomy reduce venous hypertension anddecrease intramedullary pressure.
  77. 77.  Utilized for both pre- and postcollapse lesions, butnot be performed if there is acetabular involvement Work best when the lesions are small or mediumsized with a combined necrotic angle of less than200° or with less than 30% of femoral headinvolvement. For varus osteotomies, there should be at least 20° ofthe superolateral femoral head not involved withdisease, because this area of cartilage will beshifted into weight bearing after the osteotomy.
  78. 78.  Valgus osteotomy requires normal bone andcartilage in the central or medial aspect of thehead. Extension can be added when the necroticsegment is posterior Flexion can be added if the lesion is anterior
  79. 79.  The angular measurements of the lesion on theAP and lateral radiographs are added togetherto give the “combined necrotic angle,―as described by Kerboul et al. (From Kerboul M,Thomine J, Postel M, Merle DAubigné R. TheConservative Surgical Treatment of IdiopathicAseptic Necrosis of the Femoral Head. J BoneJoint Surg Br 1974
  80. 80. Radiographs of a hip that underwent a varusosteotomy for osteonecrosis
  81. 81.  Rotational osteotomy indicated in early tointermediate stages in which the acetabularcartilage is relatively unaffected Must be sufficient normal bone and cartilage inthe femoral head so that after rotation theintact segment occupies at least 36% of theweight-bearing surface of the acetabulum. Contraindications include whole-head necrosis,significant degenerative changes in the femoralhead or acetabulum, and poor general health
  82. 82. Rotational Osteotomies In 1973, Sugioka reported transtrochantericanterior rotation osteotomy More than 500 of these procedures wereperformed since 1972, and Sugiokas results,especially in hips treated before significantfemoral head collapse, were quite gratifying Unfortunately, these results could not beconsistently duplicated by other investigators
  83. 83. Schematic of the Sugioka transtrochantericrotational osteotomy of the femoral head.
  84. 84. Transposition of necrotic focus of femoral head anteroinferiorlyaway from weight-bearing area as a result of anterior rotation ofthe femoral head. (A) before rotation and (B) after rotation. (FromSugioka Y, Mohtai M. Osteonecrosis of the Femoral Head
  85. 85.  Zhang et alExperimentenly injected intravenous bonemarrow mesenchymal cells in rabbit and resultsrevealed intravenously implanted MSCs couldmigrate into the femoral head of hosts, andespecially migrate directionally and survive in thenecrotic femoral heads. Thus, it is feasible andsafe to treat femoral head necrosis by intravenoustransplantation of allogeneic MSCs Intravenous transplantation of allogeneic bone marrow mesenchymal stemcells and its directional migration to the necrotic femoral head Zhang-hua LiInternational Journal of Medical Sciences 2011
  86. 86.  Total hip replacement is recommended forpatients over the age of fifty years who haveany degree of symptomatic osteonecrosis orpatients over the age of forty years who haveadvancedstage-IV disease or involvement of>50% of the femoral head with limited hipmotion.

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