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Treatment of osteonecrosis of the femoral head: Combination of operation and multiple cellular mediators
Medical Hypotheses (2007) 68, 502–505
http://intl.elsevierhealth.com/journals/mehy
Treatment of osteonecrosis of the femoral head: Combination of operation and multiple cellular mediators q Benxiang Yuan, Zude Liu
*
Department of Orthopaedics, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200 001, China Received 31 July 2006; accepted 1 August 2006
Summary The goal in the treatment of osteonecrosis of the femoral head is to preserve, not replace, the femoral head. Although many methods have been proposed, none has proved completely satisfactory. Cellular mediators as a supplement to bone grafting and decompression is an attractive approach to this problem because it combines the desirable features of other procedures, each of which has shown a certain degree of effectiveness in stimulating bone growth and repair. Basic and clinical researches have shown the efficacy of various cellular mediators (bone morphogenetic proteins, interleukins, angiogenic growth factors, etc.) in healing bone defects. The potential application of these cellular mediators to other musculoskeletal conditions, including osteonecrosis of the femoral head, only recently has been explored. The surgical alternatives may include core decompression, osteotomy, nonvascularized, and vascularized bone grafting, which might be enhanced with the use of cellular mediators. At least three of these factors are potential candidates as therapeutic modalities: cytokines, bone morphogenetic proteins, and angiogenic factors. Therefore, we hypothesized that the combination of operation and multiple cellular mediators is an attractive method to preserve the femoral head for the therapy of osteonecrosis of the femoral head. c 2006 Elsevier Ltd. All rights reserved.
Introduction Osteonecrosis of the femoral head is a devastating disease usually leading to hip joint destruction in the third through fifth decades of life (average age, 36 years). Unfortunately, the results of arthroplasty in these patients have been less than satis-
q
This work has not been presented at any meeting yet. * Corresponding author. Tel.: +86 21 53882102. E-mail addresses: [email protected] (B. Yuan), liuzude@ gmail.com (Z. Liu).
factory, with failure rates ranging from 10% to 50% at follow-up that averages 5 years. Despite continued improvement in the design and technique of hip arthroplasty, it is unlikely that prosthetic hips will last more than the 40 years life expectancy for these patients [1,2]. Thus, in this group of active young patients, it is important to delay a hip replacement as long as possible with treatments that will not compromise any subsequent possibilities for a hip arthroplasty. Success rates of hip salvaging procedures show considerable variation, with disparities in methods
0306-9877/$ - see front matter c 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.mehy.2006.08.024
Treatment of osteonecrosis of the femoral head by multiple centers. Nonsurgical methods include pharmacologic agents and electrical stimulation. Surgical methods include core decompression, nonvascularized bone grafting, vascularized bone grafting, and osteotomies. But none of these procedures is universally effective [3–8]. Basic and clinical researches have shown the efficacy of various cellular mediators, such as bone morphogenetic proteins (BMP), interleukins, angiogenic growth factors, in healing bone defects [9–11]. This new era of cellular mediators biology may be applied to the treatment of numerous musculoskeletal conditions, including reconstructive surgery and traumatology, as an alternative or adjunct to bone grafts. Therefore, we hypothesized that the combination of operation with multiple steoinductive and osteoconductive agents is an attractive method to preserve the femoral head for the therapy of osteonecrosis of the femoral head.
Overview of cellular mediators The future in the prevention and treatment of osteonecrosis likely will involve the use of biologic substances or their recombinants, such as growth factors and cytokines. Bone formation and regeneration are complex processes involving the interactions of numerous cells with local and systemic regulation factors. These regulators include cellular mediators, cytokines, hormones, and extracellular components of the matrix. Clearly, bone formation can be stimulated by bone morphogenetic proteins and certain cytokines. Bone resorption also can be modulated, stimulated, or repressed by numerous other cytokines. In addition, neovascularization and neural growth can be enhanced. During the past decade, there has been an explosive increase in the number of growth factors and other cytokines that have been identified and characterized. At least three of these groups are potential candidates as therapeutic modalities in the treatment of osteonecrosis: (1) cytokines (including interleukins, tumor necrosis factors, and signaling molecules such as FGFs, PDGF, IGFs, TGF[beta]s); (2) bone morphogenetic proteins; and (3) angiogenic factors.
Cytokines There are several alternative approaches to cytokine therapy for the treatment of osteonecrosis. The ideal cytokine treatment might stimulate an enhanced rate of creeping substitution over the
503 existing dead bone [12]. Addition of proosteoblastic factors could stimulate bone formation, or bone resorption could be inhibited by the addition of an osteoclastic inhibitor such as IL4 or INF[gamma]. Another approach to modifying osteoclastic activity would involve reducing the synthesis or activity of osteoclastic activation factors directly or indirectly. For example, addition of purified receptors for one of the proosteoclastic cytokines might modify the response by generating competition between the injected substance and the membrane bound receptors. Alternatively, an antagonist could be used for one or more of the osteoclastic stimulating cytokines to bind the soluble cytokine(s) involved in the pathologic process.
Bone morphogenetic proteins Bone morphogenetic proteins are a family of proteins with shown osteogenic potential. This group of proteins has the capacity to promote osteogenesis at nonosseous sites [13]. Bone morphogenetic proteins may be useful adjuncts in the treatments of osteonecrosis because of their pleiotropic effects such as stimulation of new bone formation, neovascularization, and promotion of articular cartilage repair. Research using bone morphogenetic protein to stimulate bone formation is more advanced than other research using cellular mediators.
Angiogenic factors A characteristic feature of osteonecrosis is that the bone lesion is avascular. One possible approach to the treatment of this disease would involve stimulating angiogenesis. Angiogenesis, also called neovascularization, involves several steps including degradation of the existing basement membrane and recruitment of endothelial cells. These steps are likely to be controlled by soluble angiogenic factors. Such factors may include angiogenin, prostaglandin E2, FGF[alpha] and FGF[beta], angiogenic lipid fraction, IL1, and TNF[alpha]. Fibroblast growth factors have been shown to promote the growth of mesodermal cells such as vascular endothelial cells and fibroblasts. They also have been shown to stimulate angiogenesis when given in small (nanogram) amounts [14]. Interleukin 1 and TNF[alpha] have been shown to promote neovascularization in the rabbit cornea. This effect occurs even though TNF[alpha] inhibits endothelial cell proliferation in vitro [15]. Another factor, angiogenin, stimulates neovascularization. This protein has been isolated and
504 sequenced, but its mode of action is unknown. It may cause the release of other factors that in turn stimulate angiogenesis directly.
Operative treatment aimed at preserving the femoral head Because osteonecrosis treated with arthroplasty produces poor results, much focus has been on modalities aimed at femoral head preservation. The efficacy of these methods varies depending on the stage and extent of the disease. It appears that treatment methods seeking to alter the early stages (before femoral head collapse) are the most successful. All four categories of surgical treatment directed toward preserving the femoral head (core decompression, nonvascularized, and vascularized bone grafting) possibly could be enhanced with the use of adjuvant cytokines.
Core decompression The use of core decompression with or without bone grafting has been the subject of numerous reports. Its use remains controversial, as its reported efficacy in early stages of the disease ranges from 30% to 40%, to more than 90% [16–18]. Large series of these procedures report 70% to 90% head salvage in follow-ups ranging from 5 to 10 years [19]. A review of the literature found 24 reports analyzing 1206 hips, with Stages I, II, and III disease according to the Ficat and Arlet classification, treated by core decompression with or without cancellous bone grafting [20]. Overall, there was a 63.5% clinical success rate (range, 33–95%), and 63% of the hips showed no radiographic evidence of disease progression. At a mean follow-up of 30 months (range, 6–114 months), 23% required a total hip replacement or salvage procedure. The use of bone morphogenetic proteins or various other cytokines as osteoinductive agents might have a role if delivered to the femoral head at the time of core decompression. The core tract lends itself to being filled with a matrix containing bone morphogenetic proteins or other cellular mediator. For those who use the combination of core and bone, grafting, proosteogenic mediators could be added to the bone graft material before insertion into the tract.
Nonvascularized bone grafting Cortical bone grafts are used to provide structural support to the subchondral bone and articular car-
Yuan and Liu tilage to prevent collapse during repair. Autogenous graft from healthy areas replaces dead bone and can be remodeled, promoting healing. This includes multiple surgical approaches and types of grafts. The simplest to use are those of Phemister, in which cortical strut grafts of ilium, fibula, or tibia are placed through a cored track [21,22]. Bonfiglio initially reported a 70% success rate at 6 years with these strut grafts [23]. Buckley et al. reported 90% excellent results with a core decompression combined with autografts at a mean 8 year follow-up for early stage osteonecrosis in asymptomatic patients [24]. Ganz [25] were the first to mention the technique of cancellous grafting through a window in the femoral neck. Rosenwasser et al. [26] combined complete evacuation of the femoral head in the femur with replacement by cancellous iliac crest bone. They had 87% excellent results in 15 patients at a 12 year mean follow-up. Additional refinements of this method and the use of adjuvant growth factors may make the results more efficacious. The cellular mediators can be added easily to the autogenous bone graft without modifying the procedure substantially. The biologic effects of these agents might improve the healing response of these grafted femoral heads by enhancing incorporation of these grafts and promoting remodeling. Likewise, any of the bone grafting techniques may become more useful in treatment of osteonecrosis as methods to enhance bone growth through the use of cytokines become part of orthopedics practice. The enhancement of healing could shorten the period of restricted weightbearing, ensure better compliance, and lead to more successful outcomes.
Summary Cellular mediators can be used as adjuncts to bone grafting for any of the surgical procedures used in the attempt to save the hip: core decompression, osteotomy, nonvascularized, and vascularized bone grafting. The cellular mediators have pleiotropic effects that possibly could address the specific problems associated with osteonecrosis: ischemia, increased intraosseous pressure, bone deterioration, subchondral collapse, and articular cartilage damage. So we hypothesized that the combination of operation and multiple cellular mediators is an attractive method to preserve the femoral head for the therapy of osteonecrosis of the femoral head.
Treatment of osteonecrosis of the femoral head
Acknowledgments This work should be attributed to the Department of Orthopaedics, Renji Hospital, Shanghai Jiao Tong University, School of Medicine. Support was provided solely from institutional and departmental sources.
References [1] Mont MA, Jones LC, Hungerford DS. Nontraumatic osteonecrosis of the femoral head: ten years later. J Bone Joint Surg Am 2006;88:1117–32. [2] Wu LD, Jin LB, Yan SG, Yang QS, Dai XS, Wang XH. Total hip arthroplasty with cementless cups and femoral head autografts for patients with hip dysplasia and osteoarthritis. Chin J Traumatol 2004;7:280–5. [3] Zhao D, Xu D, Wang W, Cui X. Iliac graft vascularization for femoral head osteonecrosis. Clin Orthop Relat Res 2006;442:171–9. [4] Yen CY, Tu YK, Ma CH, Yu SW, Kao FC, Lee MS. Osteonecrosis of the femoral head: comparison of clinical results for vascularized iliac and fibula bone grafting. J Reconstr Microsurg 2006;22:21–4. [5] Fornasier VL, Battaglia DM. Finding the unexpected: pathological examination of surgically resected femoral heads. Skeletal Radiol 2005;34:321–8. [6] Lai KA, Shen WJ, Yang CY, Shao CJ, Hsu JT, Lin RM. The use of alendronate to prevent early collapse of the femoral head in patients with nontraumatic osteonecrosis. A randomized clinical study. J Bone Joint Surg Am 2005;87:2155–9. [7] Berend KR, Gunneson EE, Urbaniak JR. Free vascularized fibular grafting for the treatment of postcollapse osteonecrosis of the femoral head. J Bone Joint Surg Am A 2003;85:987–93. [8] Rijnen WH, Gardeniers JW, Buma P, Yamano K, Slooff TJ, Schreurs BW. Treatment of femoral head osteonecrosis using bone impaction grafting. Clin Orthop Relat Res 2003:74–83. [9] Southwood LL, Frisbie DD, Kawcak CE, Ghivizzani SC, Evans CH, McIlwraith CW. Evaluation of Ad-BMP-2 for enhancing fracture healing in an infected defect fracture rabbit model. J Orthop Res 2004;22:66–72. [10] Stilgren LS, Abrahamsen B, Abdallah BM, Jorgensen NR. The cytokine system of bone tissue. Ugeskr Laeger 2005;167: 874–8. [11] Niyibizi C, Baltzer A, Lattermann C, et al. Potential role for gene therapy in the enhancement of fracture healing. Clin Orthop Relat Res 1998:S148–53.
505 [12] Kaneyama K, Segami N, Sato J, Nishimura M, Yoshimura H. Interleukin-6 family of cytokines as biochemical markers of osseous changes in the temporomandibular joint disorders. Br J Oral Maxillofac Surg 2004;42:246–50. [13] Jones AL, Bucholz RW, Bosse MJ, et al. Recombinant human BMP-2 and allograft compared with autogenous bone graft for reconstruction of diaphyseal tibial fractures with cortical defects. A randomized, controlled trial. J Bone Joint Surg Am 2006;88:1431–41. [14] Alexandrakis MG, Passam FH, Pappa CA, et al. Relation between bone marrow angiogenesis and serum levels of angiogenin in patients with myelodysplastic syndromes. Leuk Res 2005;29:41–6. [15] Winet H, Bao JY, Moffat R. A control model for tibial cortex neovascularization in the bone chamber. J Bone Miner Res 1990;5:19–30. [16] 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 2004:139–45. [17] Steinberg ME. Core decompression of the femoral head for avascular necrosis: indications and results. Can J Surg 1995;38(Suppl. 1):S18–24. [18] Chen CH, Chang JK, Huang KY, Hung SH, Lin GT, Lin SY. Core decompression for osteonecrosis of the femoral head at pre-collapse stage. Kaohsiung J Med Sci 2000;16:76–82. [19] Steinberg ME, Larcom PG, Strafford B, et al. Core decompression with bone grafting for osteonecrosis of the femoral head. Clin Orthop Relat Res 2001:71–8. [20] Mont MA, Carbone JJ, Fairbank AC. Core decompression versus nonoperative management for osteonecrosis of the hip. Clin Orthop Relat Res 1996:169–78. [21] Mont MA, Etienne G, Ragland PS. Outcome of nonvascularized bone grafting for osteonecrosis of the femoral head. Clin Orthop Relat Res 2003:84–92. [22] LeCroy CM, Rizzo M, Gunneson EE, Urbaniak JR. Free vascularized fibular bone grafting in the management of femoral neck nonunion in patients younger than fifty years. J Orthop Trauma 2002;16:464–72. [23] Smith KR, Bonfiglio M, Montgomery WJ. Non-traumatic necrosis of the femoral head treated with tibial bone-grafting. A follow-up note. J Bone Joint Surg Am 1980;62:845–7. [24] Buckley PD, Gearen PF, Petty RW. Structural bone-grafting for early atraumatic avascular necrosis of the femoral head. J Bone Joint Surg Am 1991;73:1357–64. [25] Ganz R, Jakob RP. Segmental avascular necrosis of the femoral head: flexion osteotomy combined with cancellous bone grafting of the lesion. Orthopade 1980;9:265–77 [author’s transl]. [26] Rosenwasser MP, Garino JP, Kiernan HA, Michelsen CB. Long term followup of thorough debridement and cancellous bone grafting of the femoral head for avascular necrosis. Clin Orthop Relat Res 1994:17–27.
http://intl.elsevierhealth.com/journals/mehy
Treatment of osteonecrosis of the femoral head: Combination of operation and multiple cellular mediators q Benxiang Yuan, Zude Liu
*
Department of Orthopaedics, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200 001, China Received 31 July 2006; accepted 1 August 2006
Summary The goal in the treatment of osteonecrosis of the femoral head is to preserve, not replace, the femoral head. Although many methods have been proposed, none has proved completely satisfactory. Cellular mediators as a supplement to bone grafting and decompression is an attractive approach to this problem because it combines the desirable features of other procedures, each of which has shown a certain degree of effectiveness in stimulating bone growth and repair. Basic and clinical researches have shown the efficacy of various cellular mediators (bone morphogenetic proteins, interleukins, angiogenic growth factors, etc.) in healing bone defects. The potential application of these cellular mediators to other musculoskeletal conditions, including osteonecrosis of the femoral head, only recently has been explored. The surgical alternatives may include core decompression, osteotomy, nonvascularized, and vascularized bone grafting, which might be enhanced with the use of cellular mediators. At least three of these factors are potential candidates as therapeutic modalities: cytokines, bone morphogenetic proteins, and angiogenic factors. Therefore, we hypothesized that the combination of operation and multiple cellular mediators is an attractive method to preserve the femoral head for the therapy of osteonecrosis of the femoral head. c 2006 Elsevier Ltd. All rights reserved.
Introduction Osteonecrosis of the femoral head is a devastating disease usually leading to hip joint destruction in the third through fifth decades of life (average age, 36 years). Unfortunately, the results of arthroplasty in these patients have been less than satis-
q
This work has not been presented at any meeting yet. * Corresponding author. Tel.: +86 21 53882102. E-mail addresses: [email protected] (B. Yuan), liuzude@ gmail.com (Z. Liu).
factory, with failure rates ranging from 10% to 50% at follow-up that averages 5 years. Despite continued improvement in the design and technique of hip arthroplasty, it is unlikely that prosthetic hips will last more than the 40 years life expectancy for these patients [1,2]. Thus, in this group of active young patients, it is important to delay a hip replacement as long as possible with treatments that will not compromise any subsequent possibilities for a hip arthroplasty. Success rates of hip salvaging procedures show considerable variation, with disparities in methods
0306-9877/$ - see front matter c 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.mehy.2006.08.024
Treatment of osteonecrosis of the femoral head by multiple centers. Nonsurgical methods include pharmacologic agents and electrical stimulation. Surgical methods include core decompression, nonvascularized bone grafting, vascularized bone grafting, and osteotomies. But none of these procedures is universally effective [3–8]. Basic and clinical researches have shown the efficacy of various cellular mediators, such as bone morphogenetic proteins (BMP), interleukins, angiogenic growth factors, in healing bone defects [9–11]. This new era of cellular mediators biology may be applied to the treatment of numerous musculoskeletal conditions, including reconstructive surgery and traumatology, as an alternative or adjunct to bone grafts. Therefore, we hypothesized that the combination of operation with multiple steoinductive and osteoconductive agents is an attractive method to preserve the femoral head for the therapy of osteonecrosis of the femoral head.
Overview of cellular mediators The future in the prevention and treatment of osteonecrosis likely will involve the use of biologic substances or their recombinants, such as growth factors and cytokines. Bone formation and regeneration are complex processes involving the interactions of numerous cells with local and systemic regulation factors. These regulators include cellular mediators, cytokines, hormones, and extracellular components of the matrix. Clearly, bone formation can be stimulated by bone morphogenetic proteins and certain cytokines. Bone resorption also can be modulated, stimulated, or repressed by numerous other cytokines. In addition, neovascularization and neural growth can be enhanced. During the past decade, there has been an explosive increase in the number of growth factors and other cytokines that have been identified and characterized. At least three of these groups are potential candidates as therapeutic modalities in the treatment of osteonecrosis: (1) cytokines (including interleukins, tumor necrosis factors, and signaling molecules such as FGFs, PDGF, IGFs, TGF[beta]s); (2) bone morphogenetic proteins; and (3) angiogenic factors.
Cytokines There are several alternative approaches to cytokine therapy for the treatment of osteonecrosis. The ideal cytokine treatment might stimulate an enhanced rate of creeping substitution over the
503 existing dead bone [12]. Addition of proosteoblastic factors could stimulate bone formation, or bone resorption could be inhibited by the addition of an osteoclastic inhibitor such as IL4 or INF[gamma]. Another approach to modifying osteoclastic activity would involve reducing the synthesis or activity of osteoclastic activation factors directly or indirectly. For example, addition of purified receptors for one of the proosteoclastic cytokines might modify the response by generating competition between the injected substance and the membrane bound receptors. Alternatively, an antagonist could be used for one or more of the osteoclastic stimulating cytokines to bind the soluble cytokine(s) involved in the pathologic process.
Bone morphogenetic proteins Bone morphogenetic proteins are a family of proteins with shown osteogenic potential. This group of proteins has the capacity to promote osteogenesis at nonosseous sites [13]. Bone morphogenetic proteins may be useful adjuncts in the treatments of osteonecrosis because of their pleiotropic effects such as stimulation of new bone formation, neovascularization, and promotion of articular cartilage repair. Research using bone morphogenetic protein to stimulate bone formation is more advanced than other research using cellular mediators.
Angiogenic factors A characteristic feature of osteonecrosis is that the bone lesion is avascular. One possible approach to the treatment of this disease would involve stimulating angiogenesis. Angiogenesis, also called neovascularization, involves several steps including degradation of the existing basement membrane and recruitment of endothelial cells. These steps are likely to be controlled by soluble angiogenic factors. Such factors may include angiogenin, prostaglandin E2, FGF[alpha] and FGF[beta], angiogenic lipid fraction, IL1, and TNF[alpha]. Fibroblast growth factors have been shown to promote the growth of mesodermal cells such as vascular endothelial cells and fibroblasts. They also have been shown to stimulate angiogenesis when given in small (nanogram) amounts [14]. Interleukin 1 and TNF[alpha] have been shown to promote neovascularization in the rabbit cornea. This effect occurs even though TNF[alpha] inhibits endothelial cell proliferation in vitro [15]. Another factor, angiogenin, stimulates neovascularization. This protein has been isolated and
504 sequenced, but its mode of action is unknown. It may cause the release of other factors that in turn stimulate angiogenesis directly.
Operative treatment aimed at preserving the femoral head Because osteonecrosis treated with arthroplasty produces poor results, much focus has been on modalities aimed at femoral head preservation. The efficacy of these methods varies depending on the stage and extent of the disease. It appears that treatment methods seeking to alter the early stages (before femoral head collapse) are the most successful. All four categories of surgical treatment directed toward preserving the femoral head (core decompression, nonvascularized, and vascularized bone grafting) possibly could be enhanced with the use of adjuvant cytokines.
Core decompression The use of core decompression with or without bone grafting has been the subject of numerous reports. Its use remains controversial, as its reported efficacy in early stages of the disease ranges from 30% to 40%, to more than 90% [16–18]. Large series of these procedures report 70% to 90% head salvage in follow-ups ranging from 5 to 10 years [19]. A review of the literature found 24 reports analyzing 1206 hips, with Stages I, II, and III disease according to the Ficat and Arlet classification, treated by core decompression with or without cancellous bone grafting [20]. Overall, there was a 63.5% clinical success rate (range, 33–95%), and 63% of the hips showed no radiographic evidence of disease progression. At a mean follow-up of 30 months (range, 6–114 months), 23% required a total hip replacement or salvage procedure. The use of bone morphogenetic proteins or various other cytokines as osteoinductive agents might have a role if delivered to the femoral head at the time of core decompression. The core tract lends itself to being filled with a matrix containing bone morphogenetic proteins or other cellular mediator. For those who use the combination of core and bone, grafting, proosteogenic mediators could be added to the bone graft material before insertion into the tract.
Nonvascularized bone grafting Cortical bone grafts are used to provide structural support to the subchondral bone and articular car-
Yuan and Liu tilage to prevent collapse during repair. Autogenous graft from healthy areas replaces dead bone and can be remodeled, promoting healing. This includes multiple surgical approaches and types of grafts. The simplest to use are those of Phemister, in which cortical strut grafts of ilium, fibula, or tibia are placed through a cored track [21,22]. Bonfiglio initially reported a 70% success rate at 6 years with these strut grafts [23]. Buckley et al. reported 90% excellent results with a core decompression combined with autografts at a mean 8 year follow-up for early stage osteonecrosis in asymptomatic patients [24]. Ganz [25] were the first to mention the technique of cancellous grafting through a window in the femoral neck. Rosenwasser et al. [26] combined complete evacuation of the femoral head in the femur with replacement by cancellous iliac crest bone. They had 87% excellent results in 15 patients at a 12 year mean follow-up. Additional refinements of this method and the use of adjuvant growth factors may make the results more efficacious. The cellular mediators can be added easily to the autogenous bone graft without modifying the procedure substantially. The biologic effects of these agents might improve the healing response of these grafted femoral heads by enhancing incorporation of these grafts and promoting remodeling. Likewise, any of the bone grafting techniques may become more useful in treatment of osteonecrosis as methods to enhance bone growth through the use of cytokines become part of orthopedics practice. The enhancement of healing could shorten the period of restricted weightbearing, ensure better compliance, and lead to more successful outcomes.
Summary Cellular mediators can be used as adjuncts to bone grafting for any of the surgical procedures used in the attempt to save the hip: core decompression, osteotomy, nonvascularized, and vascularized bone grafting. The cellular mediators have pleiotropic effects that possibly could address the specific problems associated with osteonecrosis: ischemia, increased intraosseous pressure, bone deterioration, subchondral collapse, and articular cartilage damage. So we hypothesized that the combination of operation and multiple cellular mediators is an attractive method to preserve the femoral head for the therapy of osteonecrosis of the femoral head.
Treatment of osteonecrosis of the femoral head
Acknowledgments This work should be attributed to the Department of Orthopaedics, Renji Hospital, Shanghai Jiao Tong University, School of Medicine. Support was provided solely from institutional and departmental sources.
References [1] Mont MA, Jones LC, Hungerford DS. Nontraumatic osteonecrosis of the femoral head: ten years later. J Bone Joint Surg Am 2006;88:1117–32. [2] Wu LD, Jin LB, Yan SG, Yang QS, Dai XS, Wang XH. Total hip arthroplasty with cementless cups and femoral head autografts for patients with hip dysplasia and osteoarthritis. Chin J Traumatol 2004;7:280–5. [3] Zhao D, Xu D, Wang W, Cui X. Iliac graft vascularization for femoral head osteonecrosis. Clin Orthop Relat Res 2006;442:171–9. [4] Yen CY, Tu YK, Ma CH, Yu SW, Kao FC, Lee MS. Osteonecrosis of the femoral head: comparison of clinical results for vascularized iliac and fibula bone grafting. J Reconstr Microsurg 2006;22:21–4. [5] Fornasier VL, Battaglia DM. Finding the unexpected: pathological examination of surgically resected femoral heads. Skeletal Radiol 2005;34:321–8. [6] Lai KA, Shen WJ, Yang CY, Shao CJ, Hsu JT, Lin RM. The use of alendronate to prevent early collapse of the femoral head in patients with nontraumatic osteonecrosis. A randomized clinical study. J Bone Joint Surg Am 2005;87:2155–9. [7] Berend KR, Gunneson EE, Urbaniak JR. Free vascularized fibular grafting for the treatment of postcollapse osteonecrosis of the femoral head. J Bone Joint Surg Am A 2003;85:987–93. [8] Rijnen WH, Gardeniers JW, Buma P, Yamano K, Slooff TJ, Schreurs BW. Treatment of femoral head osteonecrosis using bone impaction grafting. Clin Orthop Relat Res 2003:74–83. [9] Southwood LL, Frisbie DD, Kawcak CE, Ghivizzani SC, Evans CH, McIlwraith CW. Evaluation of Ad-BMP-2 for enhancing fracture healing in an infected defect fracture rabbit model. J Orthop Res 2004;22:66–72. [10] Stilgren LS, Abrahamsen B, Abdallah BM, Jorgensen NR. The cytokine system of bone tissue. Ugeskr Laeger 2005;167: 874–8. [11] Niyibizi C, Baltzer A, Lattermann C, et al. Potential role for gene therapy in the enhancement of fracture healing. Clin Orthop Relat Res 1998:S148–53.
505 [12] Kaneyama K, Segami N, Sato J, Nishimura M, Yoshimura H. Interleukin-6 family of cytokines as biochemical markers of osseous changes in the temporomandibular joint disorders. Br J Oral Maxillofac Surg 2004;42:246–50. [13] Jones AL, Bucholz RW, Bosse MJ, et al. Recombinant human BMP-2 and allograft compared with autogenous bone graft for reconstruction of diaphyseal tibial fractures with cortical defects. A randomized, controlled trial. J Bone Joint Surg Am 2006;88:1431–41. [14] Alexandrakis MG, Passam FH, Pappa CA, et al. Relation between bone marrow angiogenesis and serum levels of angiogenin in patients with myelodysplastic syndromes. Leuk Res 2005;29:41–6. [15] Winet H, Bao JY, Moffat R. A control model for tibial cortex neovascularization in the bone chamber. J Bone Miner Res 1990;5:19–30. [16] 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 2004:139–45. [17] Steinberg ME. Core decompression of the femoral head for avascular necrosis: indications and results. Can J Surg 1995;38(Suppl. 1):S18–24. [18] Chen CH, Chang JK, Huang KY, Hung SH, Lin GT, Lin SY. Core decompression for osteonecrosis of the femoral head at pre-collapse stage. Kaohsiung J Med Sci 2000;16:76–82. [19] Steinberg ME, Larcom PG, Strafford B, et al. Core decompression with bone grafting for osteonecrosis of the femoral head. Clin Orthop Relat Res 2001:71–8. [20] Mont MA, Carbone JJ, Fairbank AC. Core decompression versus nonoperative management for osteonecrosis of the hip. Clin Orthop Relat Res 1996:169–78. [21] Mont MA, Etienne G, Ragland PS. Outcome of nonvascularized bone grafting for osteonecrosis of the femoral head. Clin Orthop Relat Res 2003:84–92. [22] LeCroy CM, Rizzo M, Gunneson EE, Urbaniak JR. Free vascularized fibular bone grafting in the management of femoral neck nonunion in patients younger than fifty years. J Orthop Trauma 2002;16:464–72. [23] Smith KR, Bonfiglio M, Montgomery WJ. Non-traumatic necrosis of the femoral head treated with tibial bone-grafting. A follow-up note. J Bone Joint Surg Am 1980;62:845–7. [24] Buckley PD, Gearen PF, Petty RW. Structural bone-grafting for early atraumatic avascular necrosis of the femoral head. J Bone Joint Surg Am 1991;73:1357–64. [25] Ganz R, Jakob RP. Segmental avascular necrosis of the femoral head: flexion osteotomy combined with cancellous bone grafting of the lesion. Orthopade 1980;9:265–77 [author’s transl]. [26] Rosenwasser MP, Garino JP, Kiernan HA, Michelsen CB. Long term followup of thorough debridement and cancellous bone grafting of the femoral head for avascular necrosis. Clin Orthop Relat Res 1994:17–27.