The Accordian Maneuver & the Effects of Compression Loading on Delayed Regenerate Bone Formation in Cases of Limb Lengthening

Asim M Makhdom, M.D, MSc Adrian Sever Cartaleanu, M.D, Sebastian Rendon, M.D, Isabelle Villemure, ing, Ph.D., & Reggie C. Hamdy, MB, ChB, MSc, FRCSC


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Introduction

Distraction osteogenesis (DO) is a surgical technique used worldwide to treat a broad variety of musculoskeletal and craniofacial conditions, including correction of angular deformities or management of bone defects secondary to infection, trauma, or tumor via limb lengthening or segmental bone transport (Ilizarov 1990; Birch and Samchukov 2004). This technique was popularized by Ilizarov in the early 1950s who demonstrated that when controlled gradual distraction is applied to the two ends of a bone following a low energy osteotomy, new bone will form in the distracted gap (Ilizarov 1990). Its principle is based on the intrinsic capacity of the bone to regenerate under a controlled mechanical environment and is considered the best type of in vivo bone tissue engineering technique (Makhdom and Hamdy 2013). Both the rate and rhythm of distraction are vital to the quality of the regenerate bone. DO consists of three phases.

The first is the latency period (5 to 7 days), which immediately follows the osteotomy and during which no distraction is applied. This phase is characterized by a process similar to fracture healing, involving an intense local inflammatory reaction. This inflammatory response enables local recruitment and proliferation of mesenchymal stem cells, fibroblasts, and osteoprogenitor cells as well as capillary invasion. The second phase is the distraction phase in which gradual and distraction forces are applied, typically with an external fixator, until the desired lengthening is achieved (typically at rate of 1 mm of lengthening per day). During this phase, the mechanical forces of distraction are transduced into cellular events that lead to new bone formation. The third phase is the consolidation phase in which there is no distraction. However, the external fixator is maintained until the newly formed bone in the distracted gap becomes mechanically strong enough to withstand mechanical stresses without the fixator (every one centimeter of lengthening requires at least one month of consolidation) (Hamdy et al. 2012).

Although DO is associated with satisfactory outcomes in most cases, absent or delayed callus formation in the distraction gap may occur. This could lead to significant morbidities, as the fixator needs to be kept in place for an extended period of time until the bone is completely consolidated. Consequently, unfavorable psychological impact, increased pin tract infections, persistent pain and increased risk of osteopenia might be encountered (Eldridge and Bell 1991; Garcia-Cimbrelo et al. 1992; Velazquez et al. 1993). In some cases, subsequent surgical interventions might be required (Eldridge and Bell 1991; Velazquez et al. 1993; Birch and Samchukov 2004). Numerous techniques have been described in the management of poor regenerate in cases of DO, including systemic administration of pharmaceutical agents such as bisphosphonates, local exogenous administration of growth factors (GFs) such as BMPs, bone marrow cells (BMC), and the use of externally applied low-intensity pulsed ultrasound (LIPU) and pulsed electromagnetic fields (PEMF) (Aronson 1994; Eyres et al. 1996; Gebauer and Correll 2005; Sabharwal 2011; Makhdom and Hamdy 2013).

There are several modalities where the use of compressive forces in the context of DO could be used in order to accelerate bone formation in the distracted gap, and these include early and increasing weight bearing on the operated limb, dynamization of the fixator, overdistraction and then shortening and alternating cycles of distraction and compression (Mora 2006; Claes et al. 2008; Hamdy et al. 2012). This last technique – the accordion maneuver – has originally been described by Ilizarov in order accelerate bone regeneration in DO (Ilizarov 1990). However, despite several reports in the English literature on the successful use of this technique in the management of poor regenerate, they are mostly anecdotal without a detailed description of this maneuver (Greenwald et al. 2000; Laursen et al. 2000; Simpson and Kenwright 2000; Mofid et al. 2002; Loboa et al. 2005; Krishnan et al. 2006; Mori et al. 2006; Vidyadhara and Rao 2007; Madhusudhan et al. 2008; El-Sayed et al. 2010).

The aim of this study is to report our experience with the accordion maneuver in a small series of cases with absent or delayed bone formation during DO and to provide a detailed description of this technique, as performed in our center. We also present a review of the literature regarding the use of alternating cycles of distraction and compression in cases of DO, non-unions and fractures in both human and animal studies.

Patients & Methods

After approval from our local institutional review board, we retrospectively reviewed all patients who underwent straight lower limb lengthening at our institution between 1997 and 2012. The demographic data, clinical course and imaging information, diagnosis, surgery, lengthening details, and complications were all collected from the medical record system. Sixty-five patients (forty-one males and twenty-four females, M:F=1.7:1) underwent 72 interventions (35 on right side, 37 on left side), in which 72 bone segments were lengthened (44 femora and 28 tibiae). The mean age at initial surgery was 12.4 years (range, 3.5 – 20.5 years) and the patients were followed-up for an average of 2.38 years (range, 0.5 – 7.42 years). Seventy-eight percent of these patients underwent correction for congenital problems. Patients' diagnosis, surgery information, distraction details, and complications are summarized in (Table 1 ). In all patients, a low energy osteotomy was performed by creating multiple small drill holes at the site of osteotomy followed by completion of the osteotomy with an osteotome. Immediate weight bearing as tolerated was initiated in all patients with intense physiotherapy. Distraction was started after a mean latency period of 5.87 days (range, 4 – 11 days). Sequential weekly x-rays were performed to assess the bone formation in the distraction gap and the results of lengthening. In most cases the distraction was initiated at a rate of 1 mm per day and a rhythm of four times 0.25 mm increments per day. However, rate and rhythm were sometimes irregular and were correlated with the radiographic appearance and progression of the callus. The specific indication for using the accordion maneuver was an absent or delayed callus formation in the distraction gap, judged radiographically. The accordion maneuver consisted in alternating distraction with compression as follows: distraction (0.25 mm) in the morning, then compression (0.25 mm) in the afternoon, followed by distraction (0.25 mm) in the evening, resulting in an overall daily lengthening of 0.25 mm.

Results

The decision to apply the accordion maneuver was taken during initial distraction when imaging has shown absent or significantly delayed callus formation in the distraction gap. This was the case of tibiae in four patients (6.15%) of the 65 investigated. Their mean age was 16.5 years (range, 10 to 20 years). After lengthening initiation, their x-rays showed an absent or very timid bone regenerate in the distraction gap (Figure 1A ). In these four cases, the accordion maneuver was applied at a mean of 4.5 weeks after surgery (range, 3 – 7 weeks), which corresponds to a mean of 3.62 weeks (range, 2 – 6 weeks) after initiation of the distraction phase. The accordion maneuver was carried out on a daily basis, alternating distraction with compression three times per day, for an average of 6.75 weeks, as previously described. The total distraction period (the routine distraction period + the accordion maneuver period) was of an average of 12.5 weeks (range, 11 – 14 weeks) to obtain a mean lengthening of 3.92 cm (range 3– 5 cm). The residual limb length discrepancy was on average 1.12 cm (range, 0.7 – 2 cm). A mean healing index of 75.38 days/cm was noted. Details on clinical and accordion maneuver details are provided in (Table 2 ).

Favorable progression of the bone regenerate was noted after an average of 5.3 weeks (range, 4 – 6 weeks) after starting the accordion maneuver in three out of four patients (Figure 1B ). These patients continued to have full bone consolidation in the distraction gap. However, in one patient (case no.3), infection has complicated the course and there was absent bone formation after using the accordion maneuver (Figure 2A ). Antibiotic treatment, additional bone grafting and administration of bone morphogenetic protein-7 (OP-1) ultimately resulted in bone union for this patient (Figure 2B ).

Discussion

Several host related, local and iatrogenic causes can lead to poor bone regenerate during DO (Sabharwal 2011). These include systemic illness, infection, immunosuppression, poor tissue envelope, exposure to radiation, instability of the external fixator, suboptimal osteotomy technique and rapid distraction rate (Sabharwal 2011). We were unable to identify any of these risk factors in 3 out of the 4 patients with poor regenerate and the application of the accordion maneuver in these 3 patients resulted in successful bone regeneration in the distracted gap, while, in the fourth patient (case no.3), the accordion maneuver failed to stimulate the regenerative process. We believe this is most likely due to the presence of underlying infection. This emphasizes the importance of identifying all risk factors that may lead to a poor regenerate in DO before the use of the accordion technique. However, a firm conclusion can be made when a larger sample size is studied. A review of the English literature revealed several clinical studies in humans reporting the use of the accordion technique in cases with poor regenerate bone formation in DO, the majority of them with positive outcome. However, the description of the alternate compression - distraction regimen in these studies is anecdotal and lacks details as of when, how and for how long this technique is applied (Table 3 )(Tsuchiya et al. 1997; Simpson and Kenwright 2000; El-Mowafi et al. 2005; Krishnan et al. 2006; Vidyadhara and Rao 2007; El-Sayed et al. 2010; Iacobellis et al. 2010; Hatzokos et al. 2011; Kawoosa et al. 2003).

The accordion maneuver has also been used clinically to stimulate bone formation in the context of fracture healing. Similar to its reported use in DO, most of these studies also reported positive outcome, however still with poor description of the technique (Table 4 ) (Laursen et al. 2000; Kulkarni 2004; Inan et al. 2005; Madhusudhan et al. 2008; Chand et al. 2010). Interestingly, only experimental studies performed in animals have provided details of this technique. Mofid et al. showed that daily sequential compression and distraction for 3 weeks during the consolidation phase at rate of 1mm/day increased significantly the bone formation when compared to the control group in mandibular DO in rabbit model (Mofid et al. 2002). Claes et al. investigated the effect of temporary distraction and compression on bone regeneration in fracture healing (Claes et al. 2008). The authors noted higher bone formation in the treatment group when compared with the control group. On the other hand, Greenwald et al. used a rat mandibular DO model and reported that there were no differences histologically and radiographically between a groups of rats with distraction/compression protocol versus a control group with standard DO technique (Greenwald et al. 2000). We could not explain why these negative results were obtained, except that the regimen used by these authors was not an accordion technique with alternating cycles of distraction and compression, but rather 5 days of distraction followed by 2 days of compression. However, taken together, both clinical and experimental studies demonstrated the positive role of accordion maneuver in acceleration of bone regeneration in the context of both fracture healing and DO. However, the rate and rhythm of the accordion technique varied between experimental studies and were not available in the clinical studies, therefore, it is difficult to conclude which accordion regimen gives the best results.

From a mechanistic approach, it would be interesting to understand why the addition of compressive forces to those of distraction in cases of DO (the accordion technique) may lead to successful stimulation of bone formation in the distracted gap. It is well known that the mechanical environment plays a major role in bone formation (osteogenesis and chondrogenesis) and that bones adapt to the mechanical loads they are subjected to in terms of modeling , remodeling and regeneration (Wolff's law).(Huang and Ogawa 2010). Interestingly, experimental studies showed that dynamic compression have greater bone remodeling than static compression (Saxon et al. 2005). One explanation is that the skeleton requires "time-off" from mechanical loading as bone cells desensitize promptly from the mechanical stimulation, and resensitization must happen before the cell can transduce any prospective mechanical loads into biochemical signals (Robling et al. 2002). In DO, mechanical loads can take the form of compressive, tensile (distraction) or shear forces. Not all these forces have equal effect on bone formation. It has been demonstrated that the application of various types of loads may have different effects on the differentiation of mesenchymal stem cells and may ultimately decide the fate of progenitor cells exposed to these loads: osteogenic versus chondrogenic fate. Compressive forces may lead to fibrogenesis, osteogenesis and intramembranous bone formation, while distraction forces may lead to chondrogenesis and endochondral bone formation (Figure 3 ) (Amir et al. July 2009). In the context of standard technique of DO, most of the forces generated during the lengthening process are believed to be tensile forces. The addition of outside compressive forces during the lengthening process has been reported to be beneficial for bone formation, whether in the form of weight bearing, compression after overdistraction, dynamization of the fixator or, as mentioned by the accordion maneuver(Ilizarov 1990). All these have been shown to be beneficial for regenerate bone formation in the distracted gap. In the only study that we were able to find, directly comparing the effects of compression versus distraction, Hente et al. observed that the amount of periosteal callus formation was up to 25 times greater on the compression side when compared to the distraction side in an experimental model of tibial fractures, using a specially designed external fixator (Hente et al. 2004). This may explain the positive effect of adding "compression" during the accordion maneuver.

At the molecular level, numerous studies have analyzed the expression of various cytokines, growth factors and other molecules in the context of DO (Lewinson et al. 2003; Tong et al. 2003; Rhee and Buchman 2005; Makhdom and Hamdy 2013). However, to the best of our knowledge, no study directly analyzed the molecular changes as a result of application the accordion technique and compared these changes to standard distraction protocols without compression. Thus, at the molecular level, the mechanism of action of the accordion technique remains largely unknown. All the above mentioned studies lead us to believe that the addition of compressive forces in the context of DO could have a positive effect in the stimulation of regenerate bone in the distracted gap. However, how frequent these compressive forces should be applied in order to provide optimal results, for how long and when during the lengthening process? All these remain unanswered questions.

Conclusion

We believe that, in our small series, the accordion regimen described in this study may be successful in triggering the osteogenic potential of a poor regenerate, thus avoiding more invasive surgical procedures. The literature showed that the accordion maneuver is a successful approach to trigger bone healing. However, details of how and when to apply this combination of distraction/compression forces were lacking. Further research in the form of multi-institutional clinical as well as experimental studies is needed in order to optimize the use of the accordion technique as a non-invasive and non-pharmaceutical method to stimulate bone formation, not only in the context of DO but also in other bony pathologies with poor bone formation. Finally, our future understanding of mechanotransduction in DO might extend the indications of the accordion maneuver to be used not only in cases of poor regenerate, but also during standard lengthening procedures to accelerate bone regeneration.

References:

  • Amir,L.R.,V. Everts and A.L.J.J.Bronckers (July 2009). Bone regeneration during distraction osteogenesis. Odontology 97(2): 63-75.
  • Aronson,J. (1994). Experimental and clinical experience with distraction osteogenesis. Cleft Palate Craniofac J 31(6): 473-481; discussion 481-472.
  • Birch, J. G. and M. L. Samchukov (2004). Use of the Ilizarov method to correct lower limb deformities in children and adolescents. J Am Acad Orthop Surg 12(3): 144-154.
  • Chand, P., R. L. Shrestha, B. R. KC, et al. (2010). Managing Difficult Fractures due to Ballistic Trauma with Ilizarov Ring Fixation. Medical Journal of Shree Birendra Hospital 9(1).
  • Claes, L., P. Augat, S. Schorlemmer, et al. (2008). Temporary distraction and compression of a diaphyseal osteotomy accelerates bone healing. J Orthop Res 26(6): 772-777.
  • El-Mowafi, H., B. Elalfi and K. Wasfi (2005). Functional outcome following treatment of segmental skeletal defects of the forearm bones by Ilizarov application. Acta Orthop Belg 71(2): 157-162.
  • El-Sayed, M. M., J. Correll and K. Pohlig (2010). Limb sparing reconstructive surgery and Ilizarov lengthening in fibular hemimelia of Achterman-Kalamchi type II patients. J Pediatr Orthop B 19(1): 55-60.
  • Eldridge, J. C. and D. F. Bell (1991). Problems with substantial limb lengthening. Orthop Clin North Am 22(4): 625-631.
  • Eyres, K. S., M. Saleh and J. A. Kanis (1996). Effect of pulsed electromagnetic fields on bone formation and bone loss during limb lengthening. Bone 18(6): 505-509.
  • Garcia-Cimbrelo, E., B. Olsen, M. Ruiz-Yague, et al. (1992). Ilizarov technique. Results and difficulties. Clin Orthop Relat Res (283): 116-123.
  • Gebauer, D. and J. Correll (2005). Pulsed low-intensity ultrasound:a new salvage procedure for delayed unions and nonunions after leg lengthening in children. J Pediatr Orthop 25(6): 750-754.
  • Greenwald, J. A., J. S.Luchs, B. J. Mehrara, et al. (2000). Pumping the regenerate: an evaluation of oscillating distraction osteogenesis in the rodent mandible. Ann Plast Surg 44(5): 516-521.
  • Hamdy, R., J. Rendon and M. Tabrizian (2012). Distraction Osteogenesis and its Challenges in Bone Regeneration. Bone Regeneration. T. H. Rijeka, Intech. 1: 177-204.
  • Hatzokos, I., S. I. Stavridis, E. Iosifidou, et al. (2011). Autologous bone marrow grafting combined with demineralized bone matrix improves consolidation of docking site after distraction osteogenesis. J Bone Joint Surg Am93(7): 671-678.
  • Hente, R., B. Fuchtmeier, U. Schlegel, et al. (2004). The influence of cyclic compression and distraction on the healing of experimental tibial fractures. J Orthop Res 22(4): 709-715.
  • Huang, C. and R. Ogawa (2010). Mechanotransduction in bone repair and regeneration. FASEB J 24(10): 3625-3632.
  • Iacobellis, C., A. Berizzi and R. Aldegheri (2010). Bone transport using the Ilizarov method: a review of complications in 100 consecutive cases. Strategies Trauma Limb Reconstr 5(1): 17-22.
  • Ilizarov, G. A. (1990). Clinical application of the tension-stress effect for limb lengthening. Clin Orthop Relat Res (250): 8-26.
  • Inan, M., S. Karaoglu, F. Cilli, et al. (2005). Treatment of femoral nonunions by using cyclic compression and distraction. Clin Orthop Relat Res (436): 222-228.
  • Kawoosa, A. A., S. Majid, M. R. Mir, et al. (2003). Results of tibial lengthening by Ilizarov technique. Indian J Orthop 37(7).
  • Krishnan, A., C. Pamecha and J. J. Patwa (2006). Modified Ilizarov technique for infected nonunion of the femur: the principle of distraction-compression osteogenesis. J Orthop Surg (Hong Kong) 14(3): 265-272.
  • Kulkarni, G. S. (2004). Principles and practice of deformity correction. Indian J Orthop 38: 191-198.
  • Laursen,M.B.,P.Lass and K. S. Christensen (2000). Ilizarov treatment of tibial nonunions results in 16 cases. Acta Orthop Belg 66(3): 279- 285.
  • Lewinson, D., A. Rachmiel, S. Rihani-Bisharat, et al. (2003). Stimulation of Fos- and Jun-related genes during distraction osteogenesis. J Histochem Cytochem 51(9): 1161-1168.
  • Loboa, E. G., T. D. Fang, D. W. Parker, et al. (2005). Mechanobiology of mandibular distraction osteogenesis: finite element analyses with a rat model. J Orthop Res 23(3): 663-670.
  • Madhusudhan, T. R., B. Ramesh, K. Manjunath, et al. (2008). Outcomes of Ilizarov ring fixation in recalcitrant infected tibial non-unions - a prospective study. J Trauma Manag Outcomes 2(1): 6.
  • Makhdom, A. M. and R. C. Hamdy (2013). The Role of Growth Factors on Acceleration of Bone Regeneration during Distraction Osteogenesis. Tissue Eng Part B Rev. Mofid, M. M., N. Inoue, A. Atabey, et al. (2002). Callus stimulation in distraction osteogenesis. Plast Reconstr Surg 109(5): 1621-1629.
  • Mora, R. (2006). Diagnosis and treatment with compression-distraction technioques. Non-union of the long bones. Italia, Springer-Verlag: p.173.
  • Mori, S., M. Akagi, A. Kikuyama, et al. (2006). Axial shortening during distraction osteogenesis leads to enhanced bone formation in a rabbit model through the HIF-1alpha/vascular endothelial growth factor system. J Orthop Res 24(4): 653-663.
  • Rhee, S. T. and S. R. Buchman (2005). Colocalization of c-Src (pp60src) and bone morphogenetic protein 2/4 expression during mandibular distraction osteogenesis: in vivo evidence of their role within an integrin-mediated mechanotransduction pathway. Ann Plast Surg 55(2): 207-215.
  • Robling, A. G., F. M. Hinant, D. B. Burr, et al. (2002). Improved bone structure and strength after long-term mechanical loading is greatest if loading is separated into short bouts. J Bone Miner Res 17(8): 1545-1554.
  • Sabharwal, S. (2011). Enhancement of bone formation during distraction osteogenesis: pediatric applications. J Am Acad Orthop Surg 19(2): 101-111.
  • Saxon, L. K., A. G. Robling, I. Alam, et al. (2005). Mechanosensitivity of the rat skeleton decreases after a long period of loading, but is improved with time off. Bone 36(3): 454-464.
  • Simpson, A. H. and J. Kenwright (2000). Fracture after distraction osteogenesis. J Bone Joint Surg Br 82(5): 659-665.
  • Tong, L., S. R. Buchman, M. A. Ignelzi, Jr., et al. (2003). Focal adhesion kinase expression during mandibular distraction osteogenesis: evidence for mechanotransduction. Plast Reconstr Surg 111(1): 211- 222; discussion 223-214.
  • Tsuchiya, H., K. Tomita, K. Minematsu, et al. (1997). Limb salvage using distraction osteogenesis. A classification of the technique. J Bone Joint Surg Br 79(3): 403-411.
  • Velazquez, R. J., D. F. Bell, P. F. Armstrong, et al. (1993). Complications of use of the Ilizarov technique in the correction of limb deformities in children. J Bone Joint Surg Am 75(8): 1148-1156.
  • Vidyadhara, S. and S. K. Rao (2007). A novel approach to juxta-articular aggressive and recurrent giant cell tumours: resection arthrodesis using bone transport over an intramedullary nail. Int Orthop 31(2): 179-184.