Biological options in avn

1. Biological options in AVN femur Dr. Sushil Paudel

2. Avascular necrosis (also osteonecrosis , bone infarction , aseptic necrosis , ischemic bone necrosis ,and AVN ) Disease where there is cellular death of bone components due to interruption of the blood supply

3. The LEV enters the femoral head within a 1-cm-wide zone between the cartilage of the femoral head and the cortical bone of the femoral neck. Supply the lateral and central thirds of the femoral head When patent, the artery of the ligamentum teres (ALT) supplies the medial third of the femoral head

4. Etiology and pathophysiology

5. AVN : areas of dead trabecular bone and marrow extending to involve the subchondral plate. Anterolateral aspect of the femoral head, the principal weightbearing region typically involved, but any region of the femoral head may be involved. Involved segment usually never fully revascularizes , and collapse of the femoral head usually occurs

6. Elderly persons at decreased risk Fat cells become smaller, space between fat cells fills with a loose reticulum and mucoid fluid, which are resistant AVN. Condition is termed gelatinous marrow . Even in the presence of increased intramedullary pressure, interstitial fluid escapes into the blood vessels, leaving the spaces free to absorb additional fluid.

7. Clinical picture nonspecific Presenting symptom unilateral hip pain, which may be followed by a limp and a decreased range of motion (ROM). Young adults between the ages of 30 and 40 most frequently affected Bilateral in more than 50% of patients

8. Sequelae of avascular necrosis Minimal AVN - If the vascular area is small and is not adjacent to an articular surface, the patient may be asymptomatic; healing may occur spontaneously, or the disease may remain undetected or be discovered incidentally during workup for other conditions.

9. More severe AVN : repair begins at the interface between viable bone and necrotic bone . Dead bone reabsorbed only partially . Reactive and reparative bone laid down on dead trabeculae , resulting in a sclerotic margin of thickened trabeculae within an advancing front of hyperemia, inflammation, bone resorption , and fibrosis. Incomplete resorption of dead bone has a mixed sclerotic and cystic appearance on radiographs. Necrosis and repair are ongoing in various stages of evolution within a single lesion.

10. Mechanical failure - In the subchondral region microfractures do not heal Progression of the microfractures results in a diffuse subchondral fracture, seen radiographically as the crescent sign Following subchondral fracture and progressive weightbearing , collapse of the articular cartilage occurs Continued fracture, necrosis, and further weightbearing may progress to degenerative joint disease (DJD) and joint dissolution

11. IMAGING MODALITIES AP and lateral radiographs of both hips Initially within normal limits because it takes a period of weeks to months after the initiating event for changes to appear on radiographs The first changes to be noted are areas of radiolucency and sclerosis within the femoral head, usually in the anterior superior quadrant

12. If osteonecrosis suspected despite normal-appearing plain radiographs, MRI of both hips should be obtained because more than 50% of cases are bilateral

13. MRI Help guide interventional procedures such as core decompression, Demonstrate response of the femoral head to treatment Noninvasive means of evaluating articular cartilage congruity Sequential evaluation of asymptomatic lesions undetectable on plain radiographs.

14. I DD Plain film radiographs Malignancy Osteomyelitis Transient osteoporosis of the hip Bone sarcoma Advanced Degenerative joint disease Insufficiency fractures Epiphyseal dysplasia Bone metastases

15. Bone scintigrams Infection Plasma cell myeloma Skeletal metastasis Hemangioma Radiation therapy Arthritis Sympathetic dystrophy Bone marrow edema syndrome Bone metastases

16. CT scans Degenerative disease Insufficiency fracture Malignancy Infection Plasma cell myeloma Bone metastases

17. MRIs Transient osteoporosis of the hip Transient bone marrow syndrome Bone bruise Epiphyseal stress fracture Infection Infiltrative neoplasm Insufficiency fracture Bone metastases

18. Ficat and Arlet Radiographic Staging System for AVN Stage 0 (preclinical and preradiologic ) Avascular necrosis (AVN) can be suggested only if it has already been diagnosed in the contralateral hip.

19. Stage 1 ( preradiologic ) Defined by normal findings on radiographs and positive findings on MRI or bone scintigraphy . Early resorptive stage, Late in this stage, plain radiographs may show minimal osteoporosis and/or blurring and poor definition of the bony trabeculae

20. Stage 2 ( reparative) Demineralization evident ; first manifestation of the reparative stage, represents resorption of dead bone, and may be generalized or patchy or appear in the form of small cysts within the femoral head

21. Anteroposterior view of the pelvis in a patient with bilateral avascular necrosis of the femoral head. Mild flattening to the superior aspect of the right femoral head (open arrow) indicates stage 3 disease. The left femoral head has a normal contour, indicating stage 2 disease.

22. Stage 3 (early collapse of the femoral head ) Linear subcortical lucency , representing a fracture line, present immediately beneath the articular cortex and may extend into the articular cartilage at the superolateral aspect of the femoral head . Crescent sign ; best demonstrated on a frogleg view Subarticular cortex remain attached to the cartilage and is separated from the underlying femur by soft tissue, termed the eggshell sign. The femoral head initially preserves its round appearance, but later, it demonstrates collapse, indicated by joint-space widening .

23. Frogleg lateral view of the right hip in a patient with avascular necrosis shows the crescent sign, indicating subchondral fracture .

24. Stage 4 (progressive degenerative disease) Further flattening of the femoral head with loss of its smooth convex contour Ultimately , the superior femoral fragment, representing the articular surface and the immediate subchondral bone become separated from the underlying femoral head or depressed and compacted into the femoral head . Fragments of bone and cartilage may separate from the underlying femur, become loose bodies.

25. Severe collapse and destruction of the femoral head leads to progressive degenerative joint disease (DJD) with joint-space narrowing, marginal osteophyte formation, and subchondral cyst formation

26. Steinberg et al's Staging System for AVN Steinberg et al proposed a 6-stage classification system based on that of Ficat and Arlet and included radiologic clinical classification findings

27. Stage 0   - both preclinical and preradiologic , identified when imaging is performed to evaluate AVN in the contralateral hip or to exclude other diseases. Abnormal MRI findings, normal radiographic findings, and normal bone scan findings Stage 1  - normal radiographic findings or minimal demineralization or blurred trabeculae,Pain in the anterior groin or thigh ,Limited ROM in the hip Stage 2   - Osteoporosis, groin pain, and mottled sclerotic and/or cystic area

28. Stage 3  - crescent sign ( subchondral fracture) , pain with subchondral fracture activity, and no femoral head flattening Stage 4  - marked collapse and fracture involving the articular surface, Segmental flattening, pain with femoral head activity, no acetabular involvement, and normal joint space Stage 5  - joint space narrowing, resting pain, and acetabular degeneration (DJD)

29. AVN Classification per Central Avascular Segment Signal Alterations

30. Class A  - Central osteonecrotic focus signal analogous to that of fat are noted. Increased signal is demonstrated on T1WIs, and intermediate to high signal is demonstrated on T2WIs

31. Class B  - The presence of central osteonecrotic focus signal analogous to that of blood is observed. Increased signal is demonstrated on both T1WIs and T2WIs

32. Class C  - Central osteonecrotic focus signal analogous to that of fluid is present. Decreased signal is demonstrated on T1WIs, and increased signal is demonstrated on T2WIs

33. Class D  - The presence of central osteonecrotic focus signal analogous to that of fibrous tissue is noted. Decreased signal is demonstrated on both T1WIs and T2WIs

34. University of Pennsylvania System

35. To determine the most appropriate treatment, consider the following aspects: age of the patient, stage of the disease  (early or late), location and amount of bone affected  (small or large area), underlying cause of AVN  (with ongoing causes such as corticosteroid or alcohol use, treatment may not work unless use of the substance is stopped)

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. Restricted weight-bearing Advised with the expectation of preventing femoral head collapse during the healing Only 5 studies with reference to weight bearing as treatment modality Factors related to resolution : early, asymptomatic disease (ARCO stage I) and small lesion size (a modified index of necrotic extent of < 25). Hernigou et al , observed that clinical and radiographic signs of the disease in asymptomatic hips with a very small asymptomatic lesion progress more slowly than do signs in hips with a large symptomatic stage-II lesion

38. Agarwal et al studied 60 patients with AVN of the hip (100 hips ). All patients 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 analgesics were permitted as needed and were recorded. CONCLUSION: Alendronate reduces pain, improves function and retards AVN progression. Early surgical intervention can be avoided in most patients. Rheumatology (Oxford) 2005 Efficacy of alendronate , a bisphosphonate , in the treatment of AVN of the hip. A prospective open-label study. Agarwala S, Jain D Joshi VR, Sule A P. D. Hinduja Hospital, Mahim , Mumbai 400 016, India.

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. 3. Osteotomy 4. Surface arthroplasty 5. Total hip arthroplasty

41. Core decompression 2 methods of core decompression: large-diameter trephines and small-diameter drills. The most common method, the 8 to 10-mm trephine, is completed under fluoroscopy with the core track either being left open or filled in with bone graft

42. Complications e.g., articular cartilage damage and subchondral fractures associated with the large-diameter technique, Kim et al. developed the multiple small-diameter core decompression technique. In their initial cohort of patients treated with this technique, they reported a lower rate of collapse (14.3%) as compared with the rate reported with the traditional trephine method Kim SY, Kim DH, Park IH, Park BC, Kim PT, Ihn JC. Multiple drilling compared with standard core decompression for the treatment of osteonecrosis of the femoral head [abstract]. J Bone Joint Surg Br. 2004;

43. After core decompression

44. Stulberg et al. compared core decompression alone with conservative treatment in a prospective, randomized study of 55hips. On the basis of Harris hip scores, operative treatment was successful in approximately 70% of hips with Ficat Stage-I, II, or III osteonecrosis . In contrast, nonoperative treatment was successful for 20% of hips with Ficat Stage-I disease, 0% with Stage- II,and 10% with Stage-III Stulberg BN, Davis AW, Bayer TW, Levine M,Easley K. Osteonecrosis of the femoral head.A prospective randomized treatment protocol Clin Orthop .

45. Smith et al. reviewed twelve articles, published between 1979 and 1991, that included a total of 702 hips with an average duration of followup of thirty-eight months. Using the University of Pennsylvania staging system, they reported a successful result in 78% of the Ficat Stage-I hips, 62% of the Stage-II hips, and 41% of the Stage- III hips. Smith SW, Fehring TK, Griffin WL, Beaver WB.Core decompression of the osteonecrotic femoral head. J Bone Joint Surg Am

46. USE OF OSTEOINDUCTIVE SUBSTANCES ALONG WITH CORE DECOMPRESSION

47. Mont et al used a modified trapdoor technique and bone morphogenetic protein enriched bone graft substitute through a window at the femoral head-neck junction in 23 patients. Successful clinical results (a Harris hip score of 80 points or greater and no additional procedures) in 18 of 21 hips (86%) at a minimum follow up of 36 months (mean, 48 months; range, 36–55 months) Extensive dissection required and, technically more difficult than a standard core decompression Mont MA, Etienne G, Ragland PS. Outcome of nonvascularized bone grafting for osteonecrosis of the femoral head. Clin Orthop Relat Res. 2003

48. Lieberman et all retrospectively evaluated 15 patients (17 hips) with AVN hip treated with core decompression combined with an allogeneic , antigen-extracted, autolyzed fibula allograft and 50 mg of partially purified human bone morphogenetic protein and noncollagenous proteins Clinical success in 14 of 15 hips (93%; 13 patients) with Stage IIA disease. 3 of 17 hips had radiographic progress and converted to total hip replacements. Only 1of seven hips with 50% or less involvement of the femoral head developed radiographic progression of the femoral head No radiographic progression in the 3 hips with less than 1/3 involvement of the weight bearing surface of the femoral head. Concluded further evaluation of the potential efficacy of bone morphogenetic protein required in randomized trials. Treatment of osteonecrosis of the femoral head with core decompression and human bone morphogenetic protein. Lieberman JR

49. Mesenchymal stem cells (MSC) from adult bone marrow are multipotent that can differentiate into fibroblastic, osteogenic , myogenic , adipogenic and reticular cells.These cells may also provide a potential therapy for bone repair Procedure of autologous stem cell transplantation has been standardized with the guidelines that these should be instilled in concentration of 2X10 6 stem cells in non-traumatic pre-collapse stage of avascular necrosis femur head.

50. Effectiveness of bone marrow mononuclear cells related to the availability of stem cells endowed with osteogenic properties Injected marrow stromal cells secrete angiogenic cytokines, resulting in increased angiogenesis Bone marrow contains the bone morphogenetic proteins such as BMP-2 Supplementation of bone marrow stromal cells cultures with FGF-2 resulted in prolonged lifespan of bone marrow stromal cells to more than 70 doublings and maintained their differentiation potential accompanied by an increase of their telomerase size

51. Yan et al treated 44 hips in 28 patients with AVN at early stage by percutaneous multiple holes decompression followed by autologous BMCs infusion. Autologous BMCs were concentrated from bone marrow that was taken from the posterior iliac crest of the patient. Patients were followed up at least 2 years. The results were determined by the changes in the Harris hip score and the progression in the radiograghic stages. They concluded ercutaneous multiple holes decompression combined with autologous BMCs is a new way to treat avascular necrosis of the femoral head. Treatment of osteonecrosis of the femoral head by percutaneous decompression and autologous bone marrow mononuclear cell infusion. Yan ZQ, Chen YSLi , Yang Y Huo JZ Chen ZR Shi JHGe JB Source Department of Orthopaedics , Zhongshan Hospital of Fudan University, Shanghai 200032, China. [email protected]

52. Valerie et al studied the implantation of autologous bone-marrow mononuclear cells in a necrotic lesion of the femoral head along with core decompression. After twenty-four months, significant reduction in pain (p = 0.021) and in joint symptoms within the bone-marrow-graft group Implantation of autologous bone-marrow mononuclear cells appears to be a safe and effective treatment for early stages of osteonecrosis of the femoral head. Treatment of Osteonecrosis of the Femoral Head with Implantation of Autologous Bone-Marrow Cells Valérie Gangji , MD 1 ; Jean-Philippe Hauzeur , MD, PhD J Bone Joint Surg Am.  2005

53. Deltro et al , published their experience in 8 patients where they assessed the efficacy and safety of autologous bone-marrow mononuclear cells (BMMC) implantation in necrotic lesions of the femoral head in patients with sickle cell disease. After 8 months, 7 of the eight patients reported improvement from symptoms Concluded autologous bone-marrow mononuclear cells implantation is a safe and effective treatment for early stages of femoral head osteonecrosis in patients with sickle cell disease Daltro GC, Fortuna VA, Salvino de Araújo SA, FerrazLessa PI, Sobrinho UA, Borojevic R. Femoral head necrosis treatment with autologous stem cells in sickle cell disease. Acta Orthop Bras. 2008;

54. Use of a tantalum implant reported in 2 studies Tantalum is a light metal that has a high yield to stress. In these studies, porous tantalum rods used to potentially allow bone growth to occur while providing support. While the short-term results in these studies compared favorably to other core decompression techniques longer follow-up is needed to more fully assess the efficacy 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 the treatment 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 and radiographic outcome following tantalum rod insertion for osteonecrosis of the femoral head. J Bone Joint Surg Am. 2006;88 Suppl 3: 48-55.8848  2006  

55. Bone-grafting procedures can be divided into two general categories: non- vascularized and vascularized

56. 3 approaches to introduce bone graft into the femoral head a core tract window in the femoral neck (a “ lightbulb ” procedure) a “trapdoor” made through the articular cartilage in the femoral head

57. Cortical strut-grafting, a procedure popularized by Phemister , Boettcher et al., and Bonfiglio et al. not commonly used today Technique involves the removal of an 8 to 10-mm-diameter cylindrical core of bone from the femoral head and neck. This core tract is then filled with cortical strut grafts harvested from the ilium,fibula , or tibia. Postoperatively,protected weight-bearing for three to six months

58. Grafting using an intact fibular allograft

59. Lightbulb procedure The term lightbulb procedure introduced by Rosenwasser et al. Cortical window lifted from the femoral head-neck junction, cancellous bone graft from the iliac crest used to fill the defect in the femoral head after complete evacuationof the necrotic bone. In their series, thirteen of fifteen hips were asymptomatic at a mean of twelve years (range, ten to fifteen years) Rosenwasser MP, Garino JP, Kiernan HA, MichelsenCB . Long term followup of thorough debridement and cancellous bone grafting ofthe femoral head for avascular necrosis. ClinOrthop . 1994

60. Trapdoor

61. Muscle pedicle grafting

62. Meyers (1978) reported that fresh autologous iliac bone chips combined with a muscle-pedicle bone graft gave good results in stages 1 and 2 necrosis, but was unsatisfactory in stages 3 and 4.

63. Technique for performing muscle-pedicle bone grafting to the femoral head, modified after Meyers et al

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 bone grafts. Tensor fascia lata anteriorly and the quadratus femoris posteriorly preferred. As many as 83% of the patients, obtained good or excellent results at follow-up. Baksi DP. Treatment of osteonecrosis of the femoral head by drilling and muscle-pedicle bone grafting. J Bone Joint Surg Br. 1991;

65. Vascularized fibular grafting

66. The rationale for management of osteonecrosis of the femoral head with a free vascularized fibular graft based on five principles: (1) decompression of the femoral head, (2) removal of the necrotic bone, (3) replacement with fresh autogenous cancellous bone, (4) support of the subchondral bone with a viable strong bone strut, (5) revascularization and osteogenesis of the femoral head.

67. INDICATIONS: Symptomatic patients younger than fifty years of age with stage- II, III, or IV Patients younger than 20 of age who have stage-V disease and a good range of motion of the hip

68. A 15-cm incision is made on the lateral aspect of the leg between the lateral and posterior compartments. The incision is begun 10 cm distal to the fibular head (PF) and ends 10 cm proximal to the tip of the lateral malleolus (LM).

69. The yellow arrow is pointing to the anterior intermuscular septum. The black arrow is pointing to the fibula, on which a small cuff of muscle and periosteum has been preserved— the so-called marbleizing technique

70. The interosseous membrane (IOM) is divided with a specially designed right-angle Beaver blade (white arrow). The close proximity of the deep peroneal nerve and anterior tibial artery (black arrow) can be seen in this photograph

71. The fibular osteotomy is performed once the pedicle has been isolated distally and proximally and protected with malleable retractors

72. The proximal stump of the peroneal artery is ligated with the hemostatic clips (arrow) just as it branches from the posterior tibial artery, ensuring at least a 4 to 5-cm pedicle

73. Cancellous bone harvested from the greater trochanteric area is inserted into the cavity formed by removal of the necrotic bone. The fibular graft is inserted into the core tract and stabilized with a 0.62-mm Kirschner wire (K). The peroneal veins and artery are anastomosed to the ascending branches of the lateral femoral circumflex artery (LFCA) and vein

74. Urbaniak reviewed the results in 1523 hips treated with a free vascularizedfibular graft for osteonecrosis between 1979 and October 1, 2000 Best results obtained in the patients who had had no collapse of the subchondral bone or articularcartilage preoperatively. Of the hips that had not had preoperative subchondral or articular collapse, 91% had a successful result after six months to twenty-two years of follow-up. If collapse had been present, the success rate was 85%, and if there had also been joint-space narrowing, it was 65% Urbaniak JR, Coogan PG, Gunneson EB, Hunley JA. Treatment of osteonecrosis of the femoral head with free vascularized fibular grafting. A long-term follow-up study of one hundred and three hips. J Bone Joint SurgAm . 1995

75. Vascularized iliac crest grafting

76. OSTEOTOMY To rotate the necrotic or collapsing segment of the hip out of the weight bearing zone, replacing it with a segment of articular cartilage of the femoral head supported by healthy viable bone. In addition to the biomechanical effect, osteotomy reduce venous hypertension and decrease intramedullary pressure.

77. Utilized for both pre- and postcollapse lesions, but not be performed if there is acetabular involvement Work best when the lesions are small or medium sized with a combined necrotic angle of less than 200° or with less than 30% of femoral head involvement. For varus osteotomies , there should be at least 20° of the superolateral femoral head not involved with disease, because this area of cartilage will be shifted into weight bearing after the osteotomy .

78. Valgus osteotomy requires normal bone and cartilage in the central or medial aspect of the head. Extension can be added when the necrotic segment is posterior Flexion can be added if the lesion is anterior

79. The angular measurements of the lesion on the AP and lateral radiographs are added together to give the “combined necrotic angle,â € as described by Kerboul et al. (From Kerboul M, Thomine J, Postel M, Merle D'Aubignà © R. The Conservative Surgical Treatment of Idiopathic Aseptic Necrosis of the Femoral Head. J Bone Joint Surg Br 1974

80. Radiographs of a hip that underwent a varus osteotomy for osteonecrosis

81. Rotational osteotomy indicated in early to intermediate stages in which the acetabular cartilage is relatively unaffected Must be sufficient normal bone and cartilage in the femoral head so that after rotation the intact segment occupies at least 36% of the weight-bearing surface of the acetabulum . Contraindications include whole-head necrosis, significant degenerative changes in the femoral head or acetabulum , and poor general health

82. Rotational Osteotomies In 1973, Sugioka reported transtrochanteric anterior rotation osteotomy More than 500 of these procedures were performed since 1972, and Sugioka's results, especially in hips treated before significant femoral head collapse, were quite gratifying Unfortunately, these results could not be consistently duplicated by other investigators

83. Schematic of the Sugioka transtrochanteric rotational osteotomy of the femoral head.

84. Transposition of necrotic focus of femoral head anteroinferiorly away from weight-bearing area as a result of anterior rotation of the femoral head. (A) before rotation and (B) after rotation. (From Sugioka Y, Mohtai M. Osteonecrosis of the Femoral Head

85. Zhang et al Experimentenly injected intravenous bone marrow mesenchymal cells in rabbit and results revealed intravenously implanted MSCs could migrate into the femoral head of hosts, and especially migrate directionally and survive in the necrotic femoral heads. Thus, it is feasible and safe to treat femoral head necrosis by intravenous transplantation of allogeneic MSCs Intravenous transplantation of allogeneic bone marrow mesenchymal stem cells and its directional migration to the necrotic femoral head Zhang- hua Li International Journal of Medical Sciences 2011

86. Total hip replacement is recommended for patients over the age of fifty years who have any degree of symptomatic osteonecrosis or patients over the age of forty years who have advancedstage -IV disease or involvement of >50% of the femoral head with limited hip motion.