Available Findings Fail to Provide Strong Evidence of the Role of Bone Morphogenic Protein-2 in Femoral Head Osteonecrosis

Document Type : CURRENT CONCEPTS REVIEW

Authors

1 Massachusetts General Hospital at Harvard Medical School, Boston, USA Orthopedic Research Center, Department of Orthopedic Surgery, Mashhad University of Medical Science, Mashhad, Iran

2 Rothman Orthopedic at Thomas Jefferson University, Philadelphia, PA, USA

3 Royal London Hospital, London, UK

Abstract

Despite widespread research on non-traumatic femoral head osteonecrosis (FHON), there is no consensus about preventative treatment options. Insufficient blood supply and increased intra-osseous pressure are the initiating events in the majority of cases. BMPs are growth factors that belong to the transforming growth factor β (TGFβ) superfamily. Two specific formulations of BMPs have already been approved by the FDA: 1. BMP-2 (Infused, Medtronic) for the treatment of tibial open fractures and spinal fusion; 2. BMP-7 (OP-1, Stryker) in the setting of long bone non-unions. To our knowledge there is no published work reviewing the utility of BMP-2 in the setting of FHON.
Online databases (EMBASE, Cochrane, MEDLINE and PubMed) for literature relating to the use of BMP-2 in the treatment of FHON on 2nd June 2017. Animal studies: A total of 169 animal subjects with induced FHON were treated with BMP-2 in all the included in vivo studies.
Improved histological parameters, areas of revascularization, areas of new bone formation and osteoid deposition were seen in all studies. The number of osteoclasts decreased post operatively, in the ibandronate and BMP-2 group. Human studies: In combination, 96 human hips were treated in two studies utilizing BMP-2 and mean follow-up was at least five years. Success rate of BMP-2 was above 80 % (based on Harris score and WOMAC score) in both studies. Both are level III studies.
The present review of animal and clinical studies could not find well-designed prospective comparable studies with large sample size and preliminary evidence is not sufficient to supports the utilization of BMP-2, and its impact on the midterm outcomes of FHON. Level of evidence: III

Keywords

Main Subjects

References

1. Ma Y, Wang T, Liao J, Gu H, Lin X, Jiang Q, et al. Efficacy
of autologous bone marrow buffy coat grafting
combined with core decompression in pa-tients with
avascular necrosis of femoral head: a prospective,
double-blinded, randomized, controlled study. Stem
Cell Res Ther. 2014; 5(5):115.
2. Mankin H. Non traumatic necrosis of bone
(osteonecrosis). N Engl J Med.1992; 326(22).1473-9.
3. MontMA, Marulanda GA, Seyler TM, Plate JF, Delanois
RE. Core decom-pression and nonvascularized
bone grafting for the treatment of early stage
osteonecrosis of the femoral head. Instr Course Lect.
2007; 56: 213-20.
4. Peyvandi M, Mazloomi M, Garadaghi M, Parsa A,
Nassab H, Kachooei A, et al. Clinical trial on femoral
head osteonecrosis: simple core decompression vs.
core decompression and fibular allo-graft placement.
J Am Sci. 2014; 10:74-7.
5. Gao Y, Zhang C. Cytotherapy of osteonecrosis of
the femoral head: a mini review. Int Orthop. 2010;
34(6):779-82.
6. Papanna M, Saldanha K, Kurian B, Fernandes J, Jones
S. The use of re-combinant morphogenic protein-
2(rhBMP-2) in children undergoing revision surgery
for persistent non-union. Strategies Trauma Limb
Reconstr. 2016; 11(1):53-8.
7. Mont MA, Cherian JJ, Sierra RJ, Jones LC, Lieberman
JR. Nontraumatic Osteonecrosis of the femoral head:
where do we stand today?: a ten-year up-date. J Bone
Joint Surg Am. 2015; 97(19):1604-27.
8. Deckers MM, van Bezooijen RL, van der Horst G,
Hoogendam J, van Der Bent C, Papapoulos SE,
et al. Bone morphogenetic proteins stimulate
angiogenesis through osteoblast-derived vascular 
endothelial growth factor A. En-docrinology. 2002;
143(4):1545-53
9. Chen D, Zhao M, Mundy G. Bone morphogenetic
proteins. Growth Factors. 2004; 22(4):233-41.
10. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA
Group. Preferred reporting items for systematic
reviews and meta-analyses: the PRISMA state-ment.
Int J Surg. 2010; 8(5):336-41.
11. Slim K, Nini E, Forestier D, Kwiatkowski F, Panis Y,
Chipponi J. Meth-odological index for non‐randomized
studies (MINORS): development and val-idation of a
new instrument. ANZ J Surg. 2003; 73(9):712-6.
12. Sackett D. Rules of evidence and clinical
recommendations on the use of antithrombotic
agents. Chest. 1986; 95(2 Suppl):2S-4.
13. Kim HKW, Su PH, Qiu YS. Histopathologic changes in
growth-plate carti-lage following ischemic necrosis
of the capital femoral epiphysis—An experi-mental
investigation in immature pigs. J Bone Joint Surg Am.
2001; 83(5):688–97.
14. Cheng T, Murphy C, Cantrill L, Mikulec K, Carpenter
C, Schindeler A, et al. Local delivery of recombinant
human bone morphogenetic proteins and
bisphosphonate via sucrose acetate isobutyrate can
prevent femoral head col-lapse in Legg-Calve-Perthes
disease: a pilot study in pigs. Int Orthop. 2014;
38(7):1527-33.
15. Zhou L, Yoon S, Jang K, Moon Y, Wagle S, Lee K, et al.
COMP-angiopoietin1 potentiates the effects of bone
morphogenic protein-2 on ischemic necrosis of the
femoral head in rats. PLoS One. 2014; 9(10):e110593.
16. Vandermeer JS, Kamiya N, Aya-ay J, Garces A, Browne
R, Kim HK. Lo-cal administration of ibandronate
and bone morphogenetic protein-2 after is-chemic 
osteonecrosis of the immature femoral head: a
combined therapy that stimulates bone formation
and decreases femoral head deformity. J Bone Joint
Surg Am. 2011; 93(10):905-13.
17. Aruwajoye O, Aswath P, Kim H. Material properties of
bone in the femo-ral head treated with ibandronate
and BMP-2 following ischemic osteonecrosis. J Orthop
Res. 2017; 35(7):1453-60.
18. Ma XW, Cui DP, Zhao DW. Vascular endothelial growth
factor/bone mor-phogenetic protein-2 bone marrow
combined modification of the mesenchymal stem
cells to repair the avascular necrosis of the femoral
head. Int J Clin Exp Med. 2015; 8(9):15528-34.
19. Sun W, Li Z, Gao F, Shi Z, Zhang Q, Guo W. Recombinant
human bone morphogenetic protein-2 in debridement
and impacted bone graft for the treatment of femoral
head osteonecrosis. PLoS One. 2014; 9(6):e100424.
20. 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.
21. Korompilias AV, Beris AE, Lykissas MG, Kostas-
Agnantis IP, Soucacos PN. Femoral head osteonecrosis:
why choose free vascularized fibula grafting.
Microsurgery. 2011; 31(3): 223-8.
22. Gruber R, Mayer C, Schulz W, Graninger W, Peterlik M,
Watzek G, et al. Stimulatory effects of cartilage-derived
morphogenetic proteins 1 and 2 on os-teogenic diff
erentiation of bone marrow stromal cells. Cytokine.
2000, 12(11):1630-8.
23. Mont MA, Jones LC, Einhorn TA, Hungerford DS, Reddi
AH. Osteonecro-sis of the femoral head. Potential
treatment with growth and diff erentiation factors.
Clin Orthop Relat Res. 1998; (355 Suppl):S314-35.
24. Tsumaki N, Tanaka K, Arikawa-Hirasawa E, Nakase T,
Kimura T, Thom-as JT, et al. Role of CDMP-1 in skeletal
morphogenesis: promotion of mesenchymal cell
recruitment and chondrocyte diff erentiation. J Cell
Biol. 1999; 144(1):161-73.
25. Reddi AH. Cartilage morphogenetic proteins: role in
joint development, homoeostasis, and regeneration.
Ann Rheum Dis. 2003; 62:73-8.
26. Yamaguchi A, Ishizuya T, Kintou N, Wada Y, Katagiri T,
Wozney JM, et al. Effects of BMP-2, BMP-4, and BMP-
6 on osteoblastic differentiation of bone marrowderived
stromal cell lines, ST2 and MC3T3-G2/PA6.
Biochem Biophys Res Commun. 1996; 220(2):366-71.
27. Mont MA, Etienne G, Ragland PS. Outcome of
nonvascularized bone graft-ing for osteonecrosis
of the femoral head. Clin Orthop Relat Res. 2003;
417:84-92.
28. Simank HG, Manggold J, Sebald W, Ries R, Richter W,
Ewerbeck V, et al. Bone morphogenetic protein-2 and
growth and diff erentiation factor-5 en-hance the
healing of necrotic bone in a sheep model. Growth
Factors. 2001; 19(4):247-57.
29. Calori GM, Mazza E, Colombo A, Mazzola S, Colombo
M. Core decom-pression and biotechnologies in the
treatment of avascular necrosis of the fem-oral head.
EFORT Open Reviews. 2017; 2(2):41-50.
The Archives of Bone and Joint Surgery
Volume 8, Issue 1
January 2020
Pages 5-10

Files

History

  • Receive Date: 10 March 2018
  • Revise Date: 07 August 2019
  • Accept Date: 18 August 2019

Share

How to cite

Statistics