Multiple drilling combined with simvastatin versus multiple drilling alone for the treatment of avascular osteonecrosis of the femoral head: 3-year follow-up study

Multiple small-diameter drilling was performed by one of us (Zhenfeng Yuan) between April 2011 and June 2012 in 39 patients (64 hips) at the same institution for the treatment of non-traumatic osteonecrosis of the femoral head. Of these patients, 21 (34 hips) received simvastatin after the procedure. Eighteen patients (30 hips) who refused subsequent treatment with simvastatin were taken as controls. Patients in the MD group underwent core decompression with multiple small-diameter drilling. Patients in the SIM group underwent multiple drilling combined with oral simvastatin, 20 mg per day for 12 months beginning on the day after the drilling procedure. In the MD group, two patients (four hips) were lost to follow-up; therefore, 16 patients (26 hips) were available for study. In the SIM group, one patient (two hips) was lost to follow-up; therefore, 20 patients (32 hips) were available for study (Fig. 1). Observations were truncated 36 months postoperatively to permit statistical comparison between the two groups. This study was approved by the ethics committee of Liaocheng People’s Hospital and informed consent was obtained from all individual participants included in the study.

Osteonecrosis of the femoral head was diagnosed if magnetic resonance imaging (MRI) (coronal and sagittal) revealed the following: belt-shaped or circular low intensity signals surrounded by high intensity signals in the outer area on short tau inversion; or a high intensity area surrounded by belt-shaped or circular low intensity signals within the femoral head on T1-weighted images [24]. The patients were classified according to the ARCO system [25]. Patients were eligible for inclusion in the study if they were older than 18 years, had hip pain and had ARCO stage I, II or IIIA ANFH. Patients were excluded from the study if they had ARCO stage IIIB, IIIC or IV ANFH. The procedure was not performed on patients older than 60 years.

The largest anteroposterior diameter of the head (R), the longest anteroposterior length of the necrotic lesion (A) and the longest mediolateral length of the necrotic lesion (B) were measured on axial slices on MRI. The extent of the necrotic portion was calculated by the equation: percentage of necrotic lesion = {(A × B)/R²} × 100. This method has a more acceptable accuracy and is reasonably repeatable compared with other methods [26]. All hips were assessed using this method, with necrotic portions greater than 30 % considered large lesions, 15–30 % medium lesions and less than 15 % small lesions. The location of the necrotic lesion was classified as A, B, C1 or C2 according to the classification developed by the Specific Disease Investigation Committee under the auspices of the Japanese Ministry of Health, Labor and Welfare [27]. Three experienced radiologists reviewed all MRI scans and plain radiographs together in a blinded fashion.

Patients were followed-up 1, 3, 6, 9, 12, 24 and 36 months after the procedure. In addition, they received a follow-up visit whenever they were unwell. Follow-up took the form of outpatient visits. Examinations included joint pain, function and range of motion. HHS and VAS pain score were recorded. Plain radiographs (anteroposterior and frog lateral view) and MRI scans of both hips were obtained at scheduled follow-up times. The primary outcomes of the study were clinical and radiological failure. Clinical failure was defined as HHS < 75 points or a requirement for subsequent hip surgery such as bone grafting, osteotomy or hip replacement. New occurrence of collapse or increased collapse of greater than 2 mm on plain radiographs during follow-up was defined as radiological failure [28, 29].

For the drilling procedure, patients were placed in the supine position on a fracture table. A C-arm fluoroscope was draped with a sterile sleeve and positioned over the hip region to enable an anteroposterior view. After the position of the femoral head had been marked and the hip draped, a 3.0 mm Steinman pin was inserted percutaneously under fluoroscopic guidance. The pin was inserted into the femoral head at the site of the lesion. Anteroposterior and lateral fluoroscopic views were necessary while advancing the pin to ensure that it remained in the medullary canal of the femoral neck. Depending on lesion size, each femoral head was drilled three to six times. The wound was closed using a simple bandage without suture.

Patients who had undergone unilateral drilling were advised to use two crutches when walking for 6 weeks after the procedure. Two crutches when walking for 12 weeks were advised for patients who had undergone a bilateral procedure. Patients were allowed to engage in physical activities and sports 12 months after surgery. No further rehabilitation program was implemented [28].

Statistical analysis of the data was performed using SPSS version 18.0 for Windows (IBM, Armonk, NY, USA). Baseline characteristics were presented using descriptive statistics. The chi-square test was used to compare nominal data. The t-test or Mann–Whitney U test was used to compare metric data. Univariate analyses were performed using the chi-square test. Variables with a P value of less than 0.10 on univariate analysis were entered into multivariate analysis. Causes of ANFH were also entered into multivariate analysis. Multivariate analysis was performed using a logistic proportional hazards regression model. Because of the multicollinearity between ARCO stage and lesion size, models were fitted using the forward conditional procedure. All statistical assessments were two-sided and evaluated at the 0.05 level of statistical significance.

1. Musso ES, Mitchell SN, Schink-Ascani M, Bassett CA. Results of conservative management of osteonecrosis of the femoral head. A retrospective review. Clin Orthop Relat Res. 1986;207:209–15.Google Scholar
2. Martin JR, Houdek MT, Sierra RJ. Use of concentrated bone marrow aspirate and platelet rich plasma during minimally invasive decompression of the femoral head in the treatment of osteonecrosis. Croat Med J. 2013;54(3):219–24.View ArticlePubMedPubMed CentralGoogle Scholar
3. Markel DC, Miskovsky C, Sculco TP, Pellicci PM, Salvati EA. Core decompression for osteonecrosis of the femoral head. Clin Orthop Relat Res. 1996;323:226–33.View ArticleGoogle Scholar
4. Moya-Angeler J, Gianakos AL, Villa JC, Ni A, Lane JM. Current concepts on osteonecrosis of the femoral head. World J Orthop. 2015;6(8):590–601.View ArticlePubMedPubMed CentralGoogle Scholar
5. Scully SP, Aaron RK, Urbaniak JR. Survival analysis of hips treated with core decompression or vascularized fibular grafting because of avascular necrosis. J Bone Joint Surg Am. 1998;80(9):1270–5.View ArticlePubMedGoogle Scholar
6. Song WS, Yoo JJ, Kim YM, Kim HJ. Results of multiple drilling compared with those of conventional methods of core decompression. Clin Orthop Relat Res. 2007;454:139–46.View ArticlePubMedGoogle Scholar
7. Rastogi S, Sankineani SR, Nag HL, Mohanty S, Shivanand G, Marimuthu K, Kumar R, Rijal L. Intralesional autologous mesenchymal stem cells in management of osteonecrosis of femur: a preliminary study. Musculoskelet Surg. 2013;97(3):223–8.View ArticlePubMedGoogle Scholar
8. Bozic KJ, Zurakowski D, Thornhill TS. Survivorship analysis of hips treated with core decompression for nontraumatic osteonecrosis of the femoral head. J Bone Joint Surg Am. 1999;81(2):200–9.View ArticlePubMedGoogle Scholar
9. Mihalko WM, Balos L, Santilli M, Mindell ER. Osteonecrosis after powered core decompression. Clin Orthop Relat Res. 2003;412:77–83.View ArticleGoogle Scholar
10. Mont MA, Carbone JJ, Fairbank AC. Core decompression versus nonoperative management for osteonecrosis of the hip. Clin Orthop Relat Res. 1996;324:169–78.View ArticleGoogle Scholar
11. Calori GM, Mazza E, Colombo M, Mazzola S, Mineo GV, Giannoudis PV. Treatment of AVN using the induction chamber technique and a biological-based approach: indications and clinical results. Injury. 2014;45(2):369–73.View ArticlePubMedGoogle Scholar
12. Kim SY, Kim DH, Park IH. Multiple drilling compared with core decompression for the treatment of osteonecrosis of the femoral head. J Bone Joint Surg Am. 2004;86B(Suppl):149.Google Scholar
13. Pritchett JW. Statin therapy decreases the risk of osteonecrosis in patients receiving steroids. Clin Orthop Relat Res. 2001;386:173–8.View ArticleGoogle Scholar
14. Nishida K, Yamamoto T, Motomura G, Jingushi S, Iwamoto Y. Pitavastatin may reduce risk of steroid-induced osteonecrosis in rabbits: a preliminary histological study. Clin Orthop Relat Res. 2008;466(5):1054–8.View ArticlePubMedPubMed CentralGoogle Scholar
15. Ajmal M, Matas AJ, Kuskowski M, Cheng EY. Does statin usage reduce the risk of corticosteroid-related osteonecrosis in renal transplant population? Orthop Clin North Am. 2009;40(2):235–9.View ArticlePubMedPubMed CentralGoogle Scholar
16. Jiang Y, Zhang Y, Zhang H, Zhu B, Li P, Lu C, Xu Y, Chen W, Lin N. Pravastatin prevents steroid-induced osteonecrosis in rats by suppressing PPARgamma expression and activating Wnt signaling pathway. Exp Biol Med (Maywood). 2014;239(3):347–55.View ArticleGoogle Scholar
17. Mundy G, Garrett R, Harris S, Chan J, Chen D, Rossini G, Boyce B, Zhao M, Gutierrez G. Stimulation of bone formation in vitro and in rodents by statins. Science. 1999;286(5446):1946–9.View ArticlePubMedGoogle Scholar
18. Sugiyama M, Kodama T, Konishi K, Abe K, Asami S, Oikawa S. Compactin and simvastatin, but not pravastatin, induce bone morphogenetic protein-2 in human osteosarcoma cells. Biochem Biophys Res Commun. 2000;271(3):688–92.View ArticlePubMedGoogle Scholar
19. Ahn KS, Sethi G, Chaturvedi MM, Aggarwal BB. Simvastatin, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, suppresses osteoclastogenesis induced by receptor activator of nuclear factor-kappaB ligand through modulation of NF-kappaB pathway. Int J Cancer. 2008;123(8):1733–40.View ArticlePubMedGoogle Scholar
20. Ayukawa Y, Yasukawa E, Moriyama Y, Ogino Y, Wada H, Atsuta I, Koyano K. Local application of statin promotes bone repair through the suppression of osteoclasts and the enhancement of osteoblasts at bone-healing sites in rats. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;107(3):336–42.View ArticlePubMedGoogle Scholar
21. Bauer DC, Mundy GR, Jamal SA, Black DM, Cauley JA, Ensrud KE, van der Klift M, Pols HA. Use of statins and fracture: results of 4 prospective studies and cumulative meta-analysis of observational studies and controlled trials. Arch Intern Med. 2004;164(2):146–52.View ArticlePubMedGoogle Scholar
22. Edwards CJ, Hart DJ, Spector TD. Oral statins and increased bone-mineral density in postmenopausal women. Lancet. 2000;355(9222):2218–9.View ArticlePubMedGoogle Scholar
23. Chan MH, Mak TW, Chiu RW, Chow CC, Chan IH, Lam CW. Simvastatin increases serum osteocalcin concentration in patients treated for hypercholesterolaemia. J Clin Endocrinol Metab. 2001;86(9):4556–9.View ArticlePubMedGoogle Scholar
24. 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(1):125–33.Google Scholar
25. ARCO Committee on Terminology and Staging. In: Schoutens AAJ, Gardeniers JWM, Hughes SPF, editors. Bone circulation and vascularization in normal and pathological conditions. New York, NY: Plenum Press; 1993. p. 375–80.Google Scholar
26. Kim YM, Ahn JH, Kang HS, Kim HJ. Estimation of the extent of osteonecrosis of the femoral head using MRI. J Bone Joint Surg (Br). 1998;80(6):954–8.View ArticleGoogle Scholar
27. Sugano N, Atsumi T, Ohzono K, Kubo T, Hotokebuchi T, Takaoka K. The 2001 revised criteria for diagnosis, classification, and staging of idiopathic osteonecrosis of the femoral head. J Orthop Sci. 2002;7(5):601–5.View ArticlePubMedGoogle Scholar
28. Lee MS, Hsieh PH, Chang YH, Chan YS, Agrawal S, Ueng SW. Elevated intraosseous pressure in the intertrochanteric region is associated with poorer results in osteonecrosis of the femoral head treated by multiple drilling. J Bone Joint Surg (Br). 2008;90(7):852–7.View ArticleGoogle Scholar
29. Kang P, Pei F, Shen B, Zhou Z, Yang J. Are the results of multiple drilling and alendronate for osteonecrosis of the femoral head better than those of multiple drilling? A pilot study. Joint Bone Spine. 2012;79(1):67–72.View ArticlePubMedGoogle Scholar
30. Yang P, Bian C, Huang X, Shi A, Wang C, Wang K. Core decompression in combination with nano-hydroxyapatite/polyamide 66 rod for the treatment of osteonecrosis of the femoral head. Arch Orthop Trauma Surg. 2014;134(1):103–12.View ArticlePubMedGoogle Scholar
31. Mont MA, Ragland PS, Etienne G. Core decompression of the femoral head for osteonecrosis using percutaneous multiple small-diameter drilling. Clin Orthop Relat Res. 2004;429:131–8.View ArticleGoogle Scholar
32. Lim YW, Kim YS, Lee JW, Kwon SY. Stem cell implantation for osteonecrosis of the femoral head. Exp Mol Med. 2013;45:e61.View ArticlePubMedPubMed CentralGoogle Scholar
33. Nozaki Y, Kumagai K, Miyata N, Niwa M. Pravastatin reduces steroid-induced osteonecrosis of the femoral head in SHRSP rats. Acta Orthop. 2012;83(1):87–92.View ArticlePubMedPubMed CentralGoogle Scholar
34. Pengde K, Fuxing P, Bin S, Jing Y, Jingqiu C. Lovastatin inhibits adipogenesis and prevents osteonecrosis in steroid-treated rabbits. Joint Bone Spine. 2008;75(6):696–701.View ArticlePubMedGoogle Scholar
35. Jadhav SB, Jain GK. Statins and osteoporosis: new role for old drugs. J Pharm Pharmacol. 2006;58(1):3–18.View ArticlePubMedGoogle Scholar
36. Sato T, Morita I, Murota S. Involvement of cholesterol in osteoclast-like cell formation via cellular fusion. Bone. 1998;23(2):135–40.View ArticlePubMedGoogle Scholar
37. Hughes A, Rogers MJ, Idris AI, Crockett JC. A comparison between the effects of hydrophobic and hydrophilic statins on osteoclast function in vitro and ovariectomy-induced bone loss in vivo. Calcif Tissue Int. 2007;81(5):403–13.View ArticlePubMedGoogle Scholar
38. Takenaka M, Hirade K, Tanabe K, Akamatsu S, Dohi S, Matsuno H, Kozawa O. Simvastatin stimulates VEGF release via p44/p42 MAP kinase in vascular smooth muscle cells. Biochem Biophys Res Commun. 2003;301(1):198–203.View ArticlePubMedGoogle Scholar
39. 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.PubMedGoogle Scholar
40. Mont MA, Fairbank AC, Petri M, Hungerford DS. Core decompression for osteonecrosis of the femoral head in systemic lupus erythematosus. Clin Orthop Relat Res. 1997;334:91–7.Google Scholar
41. Tikiz C, Tikiz H, Taneli F, Gumuser G, Tuzun C. Effects of simvastatin on bone mineral density and remodeling parameters in postmenopausal osteopenic subjects: 1-year follow-up study. Clin Rheumatol. 2005;24(5):447–52.View ArticlePubMedGoogle Scholar