Biological therapies for the treatment of early stage pre-collapse osteonecrosis of the femoral head
Keywords:
osteonecrosis, femoral head, core decompression, cell therapy, stem cellsAbstract
The pathogenetic mechanism for non-traumatic osteonecrosis of the femoral head (ONFH) remains elusive. It is known, that an important part of the underlying pathology in ON is cell deficiency, hence, it is rational to consider the use of cell-based treatments to supplement more established surgical interventions. This chapter will focus surgically on Core Decompression (CD) and discuss a number of its technical advancements and variations. It will also focus on cell-based therapies that attempt to improve simple CD outcomes and argue their variability and safety.
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References
1. Lieberman JR, Berry DJ, Mont MA et al. Osteonecrosis of the hip: management in the 21st century. Instr Course Lect 2003; 52: 337–55.
2. Mont MA, Zywiel MG, Marker DR et al. The natural history of untreated asymptomatic osteonecrosis of the femoral head: a systematic literature review. J Bone Joint Surg Am 2010; 92:2165–70.
3. Piuzzi NS, Chahla J, Schrock JB et al. Evidence for the use of cell based therapy for the treatment of osteonecrosis of the femoral head: a systematic review of the literature. J Arthroplasty 2017;32: 1698–708.
4. Chughtai M, Piuzzi NS, Khlopas A et al. An evidence-based guide to the treatment of osteonecrosis of the femoral head. Bone Joint J 2017; 99-B: 1267–79.
5. Mont MA, Cherian JJ, Sierra RJ et al. Nontraumatic osteonecrosis of the femoral head: where do we stand today? A ten-year update. J Bone Joint Surg 2015; 97: 1604–27.
6. McGrory BJ, York SC, Iorio R et al. Current practices 283 of AAHKS members in the treatment of adult osteonecrosis of the femoral head. J Bone Joint Surg Am 2007; 89: 1194–204.
7. Cornell CN, Salvati EA, Pellicci PM. Long-term follow-up of total hip replacement in patients with osteonecrosis. Orthop Clin North Am 1985; 16: 757–69.
8. Chandler HP, Reineck FT, Wixson RL et al. Total hip replacement in patients younger than thirty years old: a five-year follow up study. J Bone Joint Surg Am 1981; 63: 1426–34.
9. Issa K, Pivec R, Kapadia BH et al. Osteonecrosis of the femoral head. The total hip replacement solution. Bone Joint J 2013;95-B: 46–50.
10. De Kam DC, Busch VJ, Veth RP, Schreurs BW. Total hip arthroplasties in young patients under 50 years: limited evidence for current trends. A descriptive literature review. Hip Int 2011 Sep-Oct; 21: 518–25.
11. Hernigou P, Manicom O, Poignard A et al. Core decompression with marrow stem cells. Oper Tech Orthop 2004; 14: 68–74.
12. Papakostidis C, Tosounidis TH, Jones E et al. The role of “cell therapy” in osteonecrosis of the femoral head. A systematic review of the literature and meta-analysis of 7 studies. Acta Orthop 2016 Feb; 87: 72–8.
13. Mont MA, Jones LC, Hungerford DS. Nontraumatic osteonecrosis of the femoral head: ten years later. J Bone Joint Surg Am 2006; 88: 1117–32.
14. Marker DR, Seyler TM, Ulrich SD et al. Do modern techniques improve core Decompression outcomes for hip osteonecrosis? Clin Orthop Relat Res 2008; 466: 1093–103.
15. Petrigliano FA, Lieberman JR. Osteonecrosis of the hip: novel approaches to evaluation and treatment. Clin Orthop Relat Res2007; 465: 53–62.
16. Papavasiliou A, Yercan HS, Koukoulias N. The role of hip arthroscopy in the management of osteonecrosis. J Hip Preserv Surg 2014; 1: 56–61.
17. Mont MA, Etienne G, Ragland PS. Outcome of non-vascularized bone grafting for osteonecrosis of the femoral head. Clin Orthop Relat Res 2003; 417: 84–92.
18. Papavasiliou AV, Triantafyllopoulos I, Paxinos O, Tsoukas D, Kostantoulakis C. The role of cell therapies and hip arthroscopy in the management of osteonecrosis: an update. J Hip Preserv Surg. 2018 Jun 14;5(3):202-208.
19. Karantanas AH. Accuracy and limitations of diagnostic methods for avascular necrosis of the hip.Expert Opin Med Diagn. 2013 Mar;7(2):179-87
20. Jones LC, Hungerford DS. Osteonecrosis: etiology, diagnosis, and treatment. Curr Opin Rheumatol 2004; 16: 443–9.
21. Suh KT, Kim SW, Roh HL et al. Decreased osteogenic differentiation of mesenchymal stem cells in alcohol-induced osteonecrosis. Clin Orthop Relat Res 2005; (431): 220–5.
22. Cui Q, Wang Y, Saleh KJ et al. Alcohol-induced adipogenesis in a cloned bone-marrow stem cell. J Bone Joint Surg Am 2006; 88:148–54.
23. Drescher W, Bunger MH, Weigert K et al. Methylprednisolone enhances contraction of porcine femoral head epiphyseal arteries. Clin Orthop Relat Res 2004; 423: 112–7.
24. Drescher W, Li H, Lundgaard A et al. Endothelin1-induced femoral head epiphyseal artery constriction is enhanced by long-term corticosteroid treatment. J Bone Joint Surg Am 2006; 88: 173–9.
25. Yin L, Li YB, Wang YS. Dexamethasone-induced adipogenesis in primary marrow stromal cell cultures: mechanism of steroid induced osteonecrosis. Chin Med J 2006; 119: 581–8.
26. Lee JS, Roh HL, Kim CH et al. Alterations in the differentiation ability of mesenchymal stem cells in patients with nontraumatic osteonecrosis of the femoral head: comparative analysis according to the risk factor. J Orthop Res 2006; 24: 604–9.
27. Wang GJ, Cui Q. The pathogenesis of steroid-induced osteonecrosis and the effect of lipid-clearing agents on this mechanism. In: JR Urbaniak, JP Jones (eds). Osteonecrosis: Etiology, Diagnosis, and Treatment. Rosemont, IL: American Academy of Orthopaedic Surgeons, 1997, 159–66.
28. Wang GJ, Cui Q, Balian G. The pathogenesis and prevention of steroid induced osteonecrosis. Clin Orthop Relat Res 2000; 370: 295–310.
29. Hernigou P, Beaujean F. Abnormalities in the bone marrow of the iliac crest in patients who have osteonecrosis secondary to corticosteroid therapy or alcohol abuse. J Bone Joint Surg Am1997; 79: 1047–53.
30. Hernigou P, Beaujean F, Lambotte JC. Decrease in the mesenchymal stem-cell pool in the proximal femur in corticosteroid induced osteonecrosis. J Bone Joint Surg Br 1999; 81: 349–55.
31. Hernigou P, Trousselier M, Roubineau F et al. Stem cell therapy for the treatment of hip osteonecrosis: a 30-year review of progress. Clin Orthop Surg 2016 Mar; 8: 1–8.
32. Bianco P, Riminucci M, Gronthos S et al. Bone marrow stromal stem cells: nature, biology, and potential applications. Stem Cells 2001; 19: 180–92.
33. Conway EM, Collen D, Carmeliet P. Molecular mechanisms of blood vessel growth. Cardiovasc Res 2001; 49: 507–21.
34. Murphy MB, Moncivais K, Caplan AI. Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine. Exp Mol Med 2013; 45: e54.
35. Gangji V, De Maertelaer V, Hauzeur JP. Autologous bone marrow cell implantation in the treatment of non-traumatic osteonecrosis of the femoral head: five year follow-up of a prospective controlled study. Bone 2011; 49: 1005–9.
36. Yan Z, Hang D, Guo C, Chen Z. Fate of mesenchymal stem cells transplanted to osteonecrosis of femoral head. J Orthop Res 2009;27: 442–6.
37. Alshameeri Z, McCaskie A. The role of orthobiologics in hip preservation surgery. J Hip Preserv Surg 2015 Dec; 2: 339–54.
38. Hernigou P, Beaujean F. Treatment of osteonecrosis with autologous bone marrow grafting. Clin Orthop Relat Res 2002; 405:14–23.
39. Hernigou P, Poignard A, Zilber S et al. Cell therapy of hip osteonecrosis with autologous bone marrow grafting. Indian J Orthop 2009; 43: 40–5.
40. Sen RK, Tripathy SK, Aggarwal S et al. Early results of core decompression and autologous bone marrow mononuclear cells instillation in femoral head osteonecrosis. A randomized control study. J Arthroplasty 2012; 27: 679–86.
41. Hernigou P, Homma Y, Flouzat Lachaniette CH et al. Benefits of small volume and small syringe for bone marrow aspirations of mesenchymal stem cells. Int Orthop 2013; 37: 2279–87.
42. Liu Y, Liu S, Su X. Core decompression and implantation of bone marrow mononuclear cells with porous hydroxylapatite composite filler for the treatment of osteonecrosis of the femoral head. Arch Orthop Trauma Surg 2013; 133: 125–33.
43. Lim YW, Kim YS, Lee JW, Kwon SY. Stem cell implantation for osteonecrosis of the femoral head. Exp Mol Med 2013; 45: e61.
44. Ma Y, Wang T, Liao J et al. Efficacy of autologous bone marrow buffy coat grafting combined with core decompression in patients with avascular necrosis of femoral head: a prospective, double blinded, randomized, controlled study. Stem Cell Res Ther 2014;5: 115.
45. Pepke W, Kasten P, Beckmann N et al. Core decompression and autologous bone marrow concentrate for treatment of femoral head osteonecrosis: a randomized prospective study. Orthop Rev 2016; 8: 6162.
46. Rastogi S, Sankineani SR, Nag HL et al. Intralesional autologous mesenchymal stem cells in management of osteonecrosis of femur: a preliminary study. Musculoskelet Surg 2013; 97: 223–8.
47. Tabatabaee RM, Saberi S, Parvizi J et al. Combining concentrated autologous bone marrow stem cells injection with core decompression improves outcome for patients with early-stage osteonecrosis of the femoral head: a comparative study. J Arthroplasty 2015; 30: 11–5.
48. Yamasaki T, Yasunaga Y, Ishikawa M et al. Bone-marrow derived mononuclear cells with a porous hydroxyapatite scaffold for the treatment of osteonecrosis of the femoral head: a preliminary study. J Bone Joint Surg Br 2010; 92: 337–41.
49. Zhao D, Cui D, Wang B et al. Treatment of early stage osteonecrosis of the femoral head with autologous implantation of bone marrow-derived and cultured mesenchymal stem cells. Bone 2012; 50: 325–30.
50. Houdek MT, Wyles CC, Martin JR et al. Stem cell treatment for avascular necrosis of the femoral head: current perspectives. StemCells Cloning 2014; 7: 65–70.
51. Mao Q, Jin H, Liao F et al. The efficacy of targeted intra-arterial delivery of concentrated autologous bone marrow containing mononuclear cells in the treatment of osteonecrosis of the femoral head: a five-year follow-up study. Bone 2013; 57: 509–16.
52. Mao Q, Wang W, Xu T et al. Combination treatment of biomechanical support and targeted intra-arterial infusion of peripheral blood stem cells mobilized by granulocyte-colony stimulating The role of cell therapies and hip arthroscopy in the management of osteonecrosis _ 207 factor for the osteonecrosis of the femoral head: a randomized controlled clinical trial. J Bone Miner Res 2015; 30: 647–56.
53. Lieberman JR, Conduah A, Urist MR. Treatment of osteonecrosis of the femoral head with core decompression and human bone morphogenetic protein. Clin Orthop Relat Res 2004; 429:139–45.
54. Seyler TM, Marker DR, Ulrich SD et al. Nonvascularized bone grafting defers joint arthroplasty in hip osteonecrosis. Clin Orthop Relat Res 2008; 466: 1125–32.
55. Sun W, li Z, Gao f et al. Recombinant human bone morphogenetic protein-2 in debridement and impacted bone graft for the treatment of femoral head osteonecrosis. PLoS One 2014; 9: e100424.
56. Guadilla J, Fiz N, Andia I, Sanchez M. Arthroscopic management and platelet-rich plasma therapy for avascular necrosis of the hip. Knee Surg Sports Traumatol Arthrosc 2012; 20: 393–8.
57. Hernigou P, Lambotte JC. Bilateral hip osteonecrosis: influence of hip size on outcome. Ann Rheum Dis 2000; 59: 817–21.
58. Hernigou P, Lambotte JC. Volumetric analysis of osteonecrosis of the femur: anatomical correlation using MRI. J Bone Joint Surg Br 2001; 83: 672–5.
59. Andriolo L, Merli G, Tobar C, Altamura SA, Kon E, Filardo G. Regenerative therapies increase survivorship of avascular necrosis of the femoral head: a systematic review and meta-analysis. Int Orthop. 2018 Jul;42(7):1689-1704
60. Larson E, Jones LC, Goodman SB, Koo KH, Cui Q. Early-stage osteonecrosis of the femoral head: where are we and where are we going in year 2018? Int Orthop. 2018 Jul;42(7):1723-1728.
2. Mont MA, Zywiel MG, Marker DR et al. The natural history of untreated asymptomatic osteonecrosis of the femoral head: a systematic literature review. J Bone Joint Surg Am 2010; 92:2165–70.
3. Piuzzi NS, Chahla J, Schrock JB et al. Evidence for the use of cell based therapy for the treatment of osteonecrosis of the femoral head: a systematic review of the literature. J Arthroplasty 2017;32: 1698–708.
4. Chughtai M, Piuzzi NS, Khlopas A et al. An evidence-based guide to the treatment of osteonecrosis of the femoral head. Bone Joint J 2017; 99-B: 1267–79.
5. Mont MA, Cherian JJ, Sierra RJ et al. Nontraumatic osteonecrosis of the femoral head: where do we stand today? A ten-year update. J Bone Joint Surg 2015; 97: 1604–27.
6. McGrory BJ, York SC, Iorio R et al. Current practices 283 of AAHKS members in the treatment of adult osteonecrosis of the femoral head. J Bone Joint Surg Am 2007; 89: 1194–204.
7. Cornell CN, Salvati EA, Pellicci PM. Long-term follow-up of total hip replacement in patients with osteonecrosis. Orthop Clin North Am 1985; 16: 757–69.
8. Chandler HP, Reineck FT, Wixson RL et al. Total hip replacement in patients younger than thirty years old: a five-year follow up study. J Bone Joint Surg Am 1981; 63: 1426–34.
9. Issa K, Pivec R, Kapadia BH et al. Osteonecrosis of the femoral head. The total hip replacement solution. Bone Joint J 2013;95-B: 46–50.
10. De Kam DC, Busch VJ, Veth RP, Schreurs BW. Total hip arthroplasties in young patients under 50 years: limited evidence for current trends. A descriptive literature review. Hip Int 2011 Sep-Oct; 21: 518–25.
11. Hernigou P, Manicom O, Poignard A et al. Core decompression with marrow stem cells. Oper Tech Orthop 2004; 14: 68–74.
12. Papakostidis C, Tosounidis TH, Jones E et al. The role of “cell therapy” in osteonecrosis of the femoral head. A systematic review of the literature and meta-analysis of 7 studies. Acta Orthop 2016 Feb; 87: 72–8.
13. Mont MA, Jones LC, Hungerford DS. Nontraumatic osteonecrosis of the femoral head: ten years later. J Bone Joint Surg Am 2006; 88: 1117–32.
14. Marker DR, Seyler TM, Ulrich SD et al. Do modern techniques improve core Decompression outcomes for hip osteonecrosis? Clin Orthop Relat Res 2008; 466: 1093–103.
15. Petrigliano FA, Lieberman JR. Osteonecrosis of the hip: novel approaches to evaluation and treatment. Clin Orthop Relat Res2007; 465: 53–62.
16. Papavasiliou A, Yercan HS, Koukoulias N. The role of hip arthroscopy in the management of osteonecrosis. J Hip Preserv Surg 2014; 1: 56–61.
17. Mont MA, Etienne G, Ragland PS. Outcome of non-vascularized bone grafting for osteonecrosis of the femoral head. Clin Orthop Relat Res 2003; 417: 84–92.
18. Papavasiliou AV, Triantafyllopoulos I, Paxinos O, Tsoukas D, Kostantoulakis C. The role of cell therapies and hip arthroscopy in the management of osteonecrosis: an update. J Hip Preserv Surg. 2018 Jun 14;5(3):202-208.
19. Karantanas AH. Accuracy and limitations of diagnostic methods for avascular necrosis of the hip.Expert Opin Med Diagn. 2013 Mar;7(2):179-87
20. Jones LC, Hungerford DS. Osteonecrosis: etiology, diagnosis, and treatment. Curr Opin Rheumatol 2004; 16: 443–9.
21. Suh KT, Kim SW, Roh HL et al. Decreased osteogenic differentiation of mesenchymal stem cells in alcohol-induced osteonecrosis. Clin Orthop Relat Res 2005; (431): 220–5.
22. Cui Q, Wang Y, Saleh KJ et al. Alcohol-induced adipogenesis in a cloned bone-marrow stem cell. J Bone Joint Surg Am 2006; 88:148–54.
23. Drescher W, Bunger MH, Weigert K et al. Methylprednisolone enhances contraction of porcine femoral head epiphyseal arteries. Clin Orthop Relat Res 2004; 423: 112–7.
24. Drescher W, Li H, Lundgaard A et al. Endothelin1-induced femoral head epiphyseal artery constriction is enhanced by long-term corticosteroid treatment. J Bone Joint Surg Am 2006; 88: 173–9.
25. Yin L, Li YB, Wang YS. Dexamethasone-induced adipogenesis in primary marrow stromal cell cultures: mechanism of steroid induced osteonecrosis. Chin Med J 2006; 119: 581–8.
26. Lee JS, Roh HL, Kim CH et al. Alterations in the differentiation ability of mesenchymal stem cells in patients with nontraumatic osteonecrosis of the femoral head: comparative analysis according to the risk factor. J Orthop Res 2006; 24: 604–9.
27. Wang GJ, Cui Q. The pathogenesis of steroid-induced osteonecrosis and the effect of lipid-clearing agents on this mechanism. In: JR Urbaniak, JP Jones (eds). Osteonecrosis: Etiology, Diagnosis, and Treatment. Rosemont, IL: American Academy of Orthopaedic Surgeons, 1997, 159–66.
28. Wang GJ, Cui Q, Balian G. The pathogenesis and prevention of steroid induced osteonecrosis. Clin Orthop Relat Res 2000; 370: 295–310.
29. Hernigou P, Beaujean F. Abnormalities in the bone marrow of the iliac crest in patients who have osteonecrosis secondary to corticosteroid therapy or alcohol abuse. J Bone Joint Surg Am1997; 79: 1047–53.
30. Hernigou P, Beaujean F, Lambotte JC. Decrease in the mesenchymal stem-cell pool in the proximal femur in corticosteroid induced osteonecrosis. J Bone Joint Surg Br 1999; 81: 349–55.
31. Hernigou P, Trousselier M, Roubineau F et al. Stem cell therapy for the treatment of hip osteonecrosis: a 30-year review of progress. Clin Orthop Surg 2016 Mar; 8: 1–8.
32. Bianco P, Riminucci M, Gronthos S et al. Bone marrow stromal stem cells: nature, biology, and potential applications. Stem Cells 2001; 19: 180–92.
33. Conway EM, Collen D, Carmeliet P. Molecular mechanisms of blood vessel growth. Cardiovasc Res 2001; 49: 507–21.
34. Murphy MB, Moncivais K, Caplan AI. Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine. Exp Mol Med 2013; 45: e54.
35. Gangji V, De Maertelaer V, Hauzeur JP. Autologous bone marrow cell implantation in the treatment of non-traumatic osteonecrosis of the femoral head: five year follow-up of a prospective controlled study. Bone 2011; 49: 1005–9.
36. Yan Z, Hang D, Guo C, Chen Z. Fate of mesenchymal stem cells transplanted to osteonecrosis of femoral head. J Orthop Res 2009;27: 442–6.
37. Alshameeri Z, McCaskie A. The role of orthobiologics in hip preservation surgery. J Hip Preserv Surg 2015 Dec; 2: 339–54.
38. Hernigou P, Beaujean F. Treatment of osteonecrosis with autologous bone marrow grafting. Clin Orthop Relat Res 2002; 405:14–23.
39. Hernigou P, Poignard A, Zilber S et al. Cell therapy of hip osteonecrosis with autologous bone marrow grafting. Indian J Orthop 2009; 43: 40–5.
40. Sen RK, Tripathy SK, Aggarwal S et al. Early results of core decompression and autologous bone marrow mononuclear cells instillation in femoral head osteonecrosis. A randomized control study. J Arthroplasty 2012; 27: 679–86.
41. Hernigou P, Homma Y, Flouzat Lachaniette CH et al. Benefits of small volume and small syringe for bone marrow aspirations of mesenchymal stem cells. Int Orthop 2013; 37: 2279–87.
42. Liu Y, Liu S, Su X. Core decompression and implantation of bone marrow mononuclear cells with porous hydroxylapatite composite filler for the treatment of osteonecrosis of the femoral head. Arch Orthop Trauma Surg 2013; 133: 125–33.
43. Lim YW, Kim YS, Lee JW, Kwon SY. Stem cell implantation for osteonecrosis of the femoral head. Exp Mol Med 2013; 45: e61.
44. Ma Y, Wang T, Liao J et al. Efficacy of autologous bone marrow buffy coat grafting combined with core decompression in patients with avascular necrosis of femoral head: a prospective, double blinded, randomized, controlled study. Stem Cell Res Ther 2014;5: 115.
45. Pepke W, Kasten P, Beckmann N et al. Core decompression and autologous bone marrow concentrate for treatment of femoral head osteonecrosis: a randomized prospective study. Orthop Rev 2016; 8: 6162.
46. Rastogi S, Sankineani SR, Nag HL et al. Intralesional autologous mesenchymal stem cells in management of osteonecrosis of femur: a preliminary study. Musculoskelet Surg 2013; 97: 223–8.
47. Tabatabaee RM, Saberi S, Parvizi J et al. Combining concentrated autologous bone marrow stem cells injection with core decompression improves outcome for patients with early-stage osteonecrosis of the femoral head: a comparative study. J Arthroplasty 2015; 30: 11–5.
48. Yamasaki T, Yasunaga Y, Ishikawa M et al. Bone-marrow derived mononuclear cells with a porous hydroxyapatite scaffold for the treatment of osteonecrosis of the femoral head: a preliminary study. J Bone Joint Surg Br 2010; 92: 337–41.
49. Zhao D, Cui D, Wang B et al. Treatment of early stage osteonecrosis of the femoral head with autologous implantation of bone marrow-derived and cultured mesenchymal stem cells. Bone 2012; 50: 325–30.
50. Houdek MT, Wyles CC, Martin JR et al. Stem cell treatment for avascular necrosis of the femoral head: current perspectives. StemCells Cloning 2014; 7: 65–70.
51. Mao Q, Jin H, Liao F et al. The efficacy of targeted intra-arterial delivery of concentrated autologous bone marrow containing mononuclear cells in the treatment of osteonecrosis of the femoral head: a five-year follow-up study. Bone 2013; 57: 509–16.
52. Mao Q, Wang W, Xu T et al. Combination treatment of biomechanical support and targeted intra-arterial infusion of peripheral blood stem cells mobilized by granulocyte-colony stimulating The role of cell therapies and hip arthroscopy in the management of osteonecrosis _ 207 factor for the osteonecrosis of the femoral head: a randomized controlled clinical trial. J Bone Miner Res 2015; 30: 647–56.
53. Lieberman JR, Conduah A, Urist MR. Treatment of osteonecrosis of the femoral head with core decompression and human bone morphogenetic protein. Clin Orthop Relat Res 2004; 429:139–45.
54. Seyler TM, Marker DR, Ulrich SD et al. Nonvascularized bone grafting defers joint arthroplasty in hip osteonecrosis. Clin Orthop Relat Res 2008; 466: 1125–32.
55. Sun W, li Z, Gao f et al. Recombinant human bone morphogenetic protein-2 in debridement and impacted bone graft for the treatment of femoral head osteonecrosis. PLoS One 2014; 9: e100424.
56. Guadilla J, Fiz N, Andia I, Sanchez M. Arthroscopic management and platelet-rich plasma therapy for avascular necrosis of the hip. Knee Surg Sports Traumatol Arthrosc 2012; 20: 393–8.
57. Hernigou P, Lambotte JC. Bilateral hip osteonecrosis: influence of hip size on outcome. Ann Rheum Dis 2000; 59: 817–21.
58. Hernigou P, Lambotte JC. Volumetric analysis of osteonecrosis of the femur: anatomical correlation using MRI. J Bone Joint Surg Br 2001; 83: 672–5.
59. Andriolo L, Merli G, Tobar C, Altamura SA, Kon E, Filardo G. Regenerative therapies increase survivorship of avascular necrosis of the femoral head: a systematic review and meta-analysis. Int Orthop. 2018 Jul;42(7):1689-1704
60. Larson E, Jones LC, Goodman SB, Koo KH, Cui Q. Early-stage osteonecrosis of the femoral head: where are we and where are we going in year 2018? Int Orthop. 2018 Jul;42(7):1723-1728.
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2020-03-24
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