Controlled longitudinal bone growth by temporary tension band plating

Transcription

1 CHILDREN S ORTHOPAEDICS Controlled longitudinal bone growth by temporary tension band plating AN EXPERIMENTAL STUDY M. Gottliebsen, B. Møller-Madsen, H. Stødkilde- Jørgensen, O. Rahbek From Aarhus University Hospital, Aarhus, Denmark Permanent growth arrest of the longer bone is an option in the treatment of minor leglength discrepancies. The use of a tension band plating technique to produce a temporary epiphysiodesis is appealing as it avoids the need for accurate timing of the procedure in relation to remaining growth. We performed an animal study to establish if control of growth in a long bone is possible with tension band plating. Animals (pigs) were randomised to temporary epiphysiodesis on either the right or left tibia. Implants were removed after ten weeks. Both tibiae were examined using MRI at baseline, and after ten and 15 weeks. The median interphyseal distance was significantly shorter on the treated tibiae after both ten weeks (p = 0.04) and 15 weeks (p = 0.04). On T 1 -weighted images the metaphyseal water content was significantly reduced after ten weeks on the treated side (p = 0.04) but returned to values comparable with the untreated side at 15 weeks (p = 0.14). Return of growth was observed in all animals after removal of implants. Temporary epiphysiodesis can be obtained using tension band plating. The technique is not yet in common clinical practice but might avoid the need for the accurate timing of epiphysiodesis. Cite this article: Bone Joint J 2013;95-B: M. Gottliebsen, MD, PhD, Specialist Registrar in Orthopaedics B. Møller-Madsen, MD, DMSci, Consultant Orthopaedic Surgeon, Professor O. Rahbek, MD, PhD, Consultant Orthopaedic Surgeon, Associate Professor Aarhus University Hospital, Department of Children s Orthopaedics, Nørrebrogade 44, 8000 Aarhus C, Denmark. H. Stødkilde-Jørgensen, MD, DMSci, Professor Aarhus University Hospital, MR-Research Centre, Brendstrupgaardsvej 100, 8200 Aarhus N, Denmark. Correspondence should be sent to Mr M. Gottliebsen; martin.gottliebsen@gmail.com 2013 The British Editorial Society of Bone & Joint Surgery doi: / x.95b $2.00 Bone Joint J 2013;95-B: Received 8 February 2012; Accepted after revision 7 February 2013 Leg-length discrepancy (LLD) can give rise to disturbances of gait, cause pain in the lower limbs and lumbar spine, and affect the quality of life. 1,2 With a moderate discrepancy of between 2 cm and 5 cm, equalisation of leg length is often achieved by inducing growth arrest in one or more of the long bones using epiphysiodesis. This technique was introduced in 1933 by Phemister 3 who obtained fusion of the growth plate by cutting a rectangular block of bone containing metaphysis, physis and epiphysis, and re-inserting it in a reversed position so that the physis was interrupted. This procedure had disadvantages, including a prolonged post-operative recovery. More recently, Canale, Russell and Holcomb 4 popularised a minimally invasive technique in which the physis is destroyed by the repeated passage of a drill. 5-7 Growth arrest may also be achieved using percutaneous transphyseal screws. 8 All techniques need careful pre-operative planning that often involves many radiographs. In 1949, Blount and Clarke 9 first described bilateral stapling of the epiphyseal plate as a method to control growth. Problems included failure of hardware and an unpredictable outcome. Stapling of the proximal tibia can lead to a varus deformity; and loosening of the staples is a common complication. 10,11 Guided growth using a tension band plating technique is widely used to correct angular deformities by partial epiphysiodesis. 12 This technique uses an extraperiosteal plate fixed by one screw on each side of the growth plate. The screws are not rigidly fixed in the plate and can angulate progressively during treatment. The prospect of using this technique to control long bone growth is appealing as it is minimally invasive and carries a low risk of hardware failure compared with staples. 13 Furthermore, correct timing may not be as important because growth is believed to resume after removal of the plate. MR imaging has previously been used to evaluate the effect of epiphysiodesis in both clinical and experimental studies. 14,15 We designed an experimental study in a large animal model in order to investigate whether growth can be controlled in a long bone using a tension band plating technique. We aimed to show that temporary epiphysiodesis can be obtained using this technique and that growth would resume after removal of implants. Materials and Methods Five ten-week-old skeletally immature Danish domestic pigs were chosen for the study. They VOL. 95-B, No. 6, JUNE

2 856 M. GOTTLIEBSEN, B. MØLLER-MADSEN, H. STØDKILDE-JØRGENSEN, O. RAHBEK Week 0 Anaesthesia Surgery (temporary epiphysiodesis) Week 10 Anaesthesia Surgery (implant removal) MRI Week 15 Anaesthesia MRI Fig. 2 Fig. 1 Diagram showing temporary epiphysiodesis with medial and lateral tension band platings on proximal tibia. had a mean weight of 39.6 kg (38.3 to 40.0) at the start of the experiment. The experimental protocol was in accordance with Danish Animal Research guidelines and had ethical approval. We expected a mean increase in interphyseal distance of 10 mm after intervention when the control side is compared with the treated side. In our animal model the length of the tibia would be about 130 mm at surgery and a mean difference in interphyseal distance of 10 mm would correspond to 7.6% of the tibial length, which we believe has clinical relevance. Estimated standard deviation of the differences was 5 mm. The desired power was 80% and α = When performing the sample size calculation analysis using parametric tests (a paired t-test) was planned. This gives a study population of four individuals. As a Wilcoxon signed-rank test was likely to be used (as normality can only be assessed with difficulty in a small population) 15% were added to the number, and five animals were thus included in the study. A paired randomised design was used with the animal as its own control. The right proximal tibia was randomly allocated to either temporary epiphysiodesis (Fig. 1) or no treatment. The left proximal tibia received the opposite treatment. The plates and screws were removed after ten weeks. The resumption of growth was then studied for five additional weeks (Fig. 2). After intramuscular premedication with 5 mg/kg S-ketamine (ketaminol; Pfizer, Berlin, Germany) and 0.5 mg/kg midazolam (Dormicum; Hameln Pharmaceuticals, Hameln, Germany) intravenous (IV) access was obtained and general anaesthesia was induced with 0.5 mg/kg intravenous (IV) etomidate (Hypnomidate; Janssen-Cilag, Beerse, Belgium). The pigs were intubated and anaesthesia Flowchart showing treatments and assessments across the follow-up. was maintained with 5 mg/kg/hour IV propofol (Fresenius Kabi AB, Uppsala, Sweden) and mg/kg/hour fentanyl (Haldid; Janssen-Cilag, Beerse, Belgium). Streptocillin (0.1 ml per kg weight; benzylpenicillin 200 mg and dihydrostreptomycin 250 mg/ml; both Boehringer Ingelheim, Copenhagen, Denmark) was administered intramuscularly before incision and every morning for the following three days and 2 mg/kg/day intramuscular flunixin (Finadyne Vet.; Intervet International B.V., Boxmeer, the Netherlands) was given for three days post-operatively as analgesia. At baseline a MR scan was performed and this was followed by index surgery; small longitudinal incisions were made over the medial and lateral aspects of the proximal tibia on the intervention side. Tension band plating implants (eight-plates, 12 mm; Orthofix, McKinney, Texas) were placed extraperiosteally across the physis on both medial and lateral sides, guided by 1.6 mm diameter pins drilled into the epiphysis and metaphysis from the medial and lateral sides under fluoroscopic control. The plates were secured with 24 mm cannulated screws (Orthofix) in the epiphysis and metaphysis. The wounds were closed and the soft tissues infiltrated with 20 ml Marcaine (5 mg bupivacaine and mg adrenaline per ml; AstraZeneca, London, United Kingdom). After ten weeks further radiographs were obtained. When the implants were removed, the incisions, wound closure and post-operative pain management were identical to the initial procedure. A second MR scan was performed whilst the animal was still anaesthetised. A third scan of both tibiae was performed under anaesthetic 15 weeks after the initial operation. The animal was then killed with 50 mg/kg pentobarbital. The tibiae were harvested and frozen at -25 C (Fig. 2). The MR scans were obtained using a Siemens Magnetom Avento 1.5 Tesla scanner to run the following four multiple-slice (25 coronal images) sequences on both tibiae using an 11 cm diameter surface coil applied to the proximal tibiae, as follows: THE BONE & JOINT JOURNAL

3 CONTROLLED LONGITUDINAL BONE GROWTH BY TEMPORARY TENSION BAND PLATING 857 Table I. Median values of interphyseal distance (mm) and median differences (mm) on T 1 whole tibia MRI (CI, confidence interval) Median interphyseal distance (95% CI) Timepoint Intervention (n = 5) Control (n = 5) Median difference (95% CI) p-value Week (108.9 to 112.7) (109.1 to 109.8) -0.4 (-0.9 to 0.2) 0.50 Week (125.8 to 129.1) (136.2 to 140.3) 11.3 (10.4 to 12.2) 0.04 Week (137.4 to 140.1) (146.2 to 150.1) 8.9 (8.3 to 9.5) High resolution T-weighted (echo time 20 ms, repetition time 800 ms, slice thickness 3 mm, echo train length 1, number of averages 2, field of view (FoV) mm and resolution pixels). 2. Water content estimation T 1 -weighted (echo time 1.61 ms, repetition time 15 ms, slice thickness 4 mm, echo train length 1, number of averages 3, FoV mm and resolution pixels). 3. T 2 -weighted (echo time 41 ms, repetition time 2000 ms, slice thickness 3 mm, echo train length 7, number of averages 2, FoV mm and resolution pixels). 4. T 1 -weighted sequence of the whole tibia (echo time 20 ms, repetition time 800 ms, slice thickness 3 mm, echo train length 1, number of averages 2, FoV mm and resolution pixels). During the imaging process the animal was kept anaesthetised and ventilated. In order to avoid artefacts from the implants the scans were performed immediately after removal of the plates and screws at ten weeks and before death at 15 weeks. The information on the Dicom images was removed before processing. However, because traces can be seen on the images, complete blinding could not be assured. The distance between the proximal and distal physes (sequence 4) was measured using Siemens software (syngo-fastview; Siemens AG, Berlin, Germany). In slice 14 and 15 of each tibia the distance was measured at three fixed positions (medial, central and lateral). Spatial identical regions of interests (ROIs) were applied to slice 14 and 15 on short echo time T 1 -weighted images (sequence 2) and mean pixel values calculated using software developed at our institution (SisWin; Aarhus University Hospital, Aarhus, Denmark). Mean values between the slides were used for statistical analysis. The status of the proximal tibial growth plate cartilage was assessed on images from both scanning sessions (sequences 1 and 3). Repeatability was estimated by performing double measurements on all slices. The intraclass correlation coefficient (ICC) for measurements of interphyseal distance and metaphyseal water content combined was 0.96 and 0.98, respectively. ICC coefficients > 80% can in general be viewed as good reliability. Statistical analysis. Non-parametric statistics were used to analyse data as normal distribution could not be assured with only five pairs of data available. ICC coefficients were calculated for measurements obtained at ten weeks and at the end of the experiment. Wilcoxon signed-ranks tests were used to test for differences between the control and intervention side. p-values < 0.05 were considered to be significant. Median values with non-parametric 95% confidence intervals (CI) were used. The Intercooled Stata 12.1 (StataCorp, College Station, Texas) statistical analysis package was used for statistical computations. Results There were no significant differences in the interphyseal distances before treatment (p = 0.50). Temporary epiphysiodesis resulted in a significant shortening of the distance between the proximal and distal physes in all treated tibiae compared with the control side (Table I). This was the case at both ten and 15 weeks, indicating that no rebound effect took place after removal of implants. Changes in metaphyseal water content in the proximal tibia were observed and quantified on short echo time T 1 sequences after epiphysiodesis. No significant difference in water content was evident at baseline between the treated and control tibiae (Fig. 3, Table II). After removal of implants there was a significant change in signal intensity in the metaphysis on the treated side compared with the control side (Fig. 4). After a further five weeks the water content in the metaphysis appeared similar to that of the control side (Fig. 5). At ten weeks, the mean pixel values were significantly reduced in the metaphysis on the treated side compared with the control side (Table II). Five weeks later these values were similar to those on the control side, indicating that the metaphyseal water content had returned to normal (Table II). We examined the physis on T 1 - and T 2 -weighted images to detect any injury to the growth plate. No cartilage damage or bony bridges were observed in any of the treated animals. All animals tolerated the procedures well and were walking and eating two hours after surgery. No implant failure, infection or wound problems were observed. We were unable to perform the final MR scanning on one animal while alive because of technical problems. After the animal was killed the tibiae were harvested and immediately scanned again using the same sequences as in all other imaging sessions. Discussion Using tension band plating we were able to perform a reversible epiphysiodesis in an animal model. The median interphyseal distance was significantly longer in control proximal tibiae compared to those subjected to temporary epiphysiodesis. This difference in interphyseal length was still evident five weeks after removal of implants. We did not observe rebound growth after removal of the implants VOL. 95-B, No. 6, JUNE 2013

4 858 M. GOTTLIEBSEN, B. MØLLER-MADSEN, H. STØDKILDE-JØRGENSEN, O. RAHBEK Table II. Median pixel values and median differences from regions of interest on water estimation T 1 -weighted MRI (CI, confidence interval) Median pixel values (95% CI) Timepoint Intervention (n = 5) Control (n = 5) Median difference (95% CI) p-value Week (959 to 1204) 1144 (1087 to 1200) 28 (-42 to 98) 0.69 Week (424 to 547) 964 (902 to 1024) 420 (354 to 486) 0.04 Week (737 to 1092) 768 (705 to 830) -160 (-268 to 52) 0.14 Fig. 3 Fluoroscopic images showing temporary epiphysiodesis with tension band plating at a) week 0, immediately post-operatively, and b) after ten weeks before removal of hardware. but acknowledge that five weeks of follow-up might be too short a period to document this. The results in these animals may not readily be transferred into clinical practice. Skeletally immature Danish domestic pigs were chosen because of advantages compared with studies in rodents; we were able to use commercially available implants and the bones have a size that corresponds to that of the growing child. The proximal tibia of the pig has previously been used to study epiphysiodesis with both staples and tension band plating Our institution has strict regulations against any contact with animals that can transfer Creutzfeldt Jakob disease, and therefore sheep or goats could not be used as models even though they have faster longitudinal bone growth. As seen in Table I growth does not stop completely after tension band plating. A radiostereometric study on the effect of epiphysiodesis showed that some remaining growth in the arrested physis could be expected. 19 However, we did not experience any cases of implant failure or loosening and therefore continued growth at the proximal tibial physis seems unlikely. The observed increase in interphyseal distance during temporary epiphysiodesis is most likely to be the result of growth in the distal tibia, which is believed to contribute about 50% of overall growth in the human tibia. The exact contribution to bone growth of the physis in the distal tibia of pigs is unknown. Documentation of the safety and efficiency of reversible temporary epiphysiodesis is limited to retrospective clinical studies and only one experimental study. One study reported that temporary epiphysiodesis with staples in the distal femur appeared to be safe, but staples placed bilaterally in the proximal tibia risked inducing an angulating deformity. 10 Loosening of staples appears to be a problem. 11 The effect of bilateral stapling of the proximal tibia has been investigated in an animal study on rabbits. 20 In six out of ten animals in whom irreversible growth arrest was induced, the growth plate still appeared to be in continuity and no bony bridges were seen. Prolonged temporary epiphysiodesis using implants may therefore lead to permanent growth arrest. In clinical practice many surgeons stick to the two year rule that states that it is safe to leave staples over a physis for up to two years in a growing child. THE BONE & JOINT JOURNAL

5 CONTROLLED LONGITUDINAL BONE GROWTH BY TEMPORARY TENSION BAND PLATING 859 Fig. 4 T1-weighted MR images at ten weeks of control (left) and tension band plating knees (right) immediately after removal of implants. White arrow marks trace after metaphyseal screw. Fig. 5 T1-weighted MR images at 15 weeks of control (left) and tension band plating knees (right) immediately after removal of implants. White arrow marks trace after metaphyseal screw. This rule originates from the 1949 paper by Blount and Clarke,9 who cite a personal communication from Phemister. MRI has previously been used to investigate the effect of epiphysiodesis on the growth plate and surrounding bone in rabbits.15 The detection of changes in solid biomaterials such as bone using short, or even ultra-short, echo time MRI have been investigated by various authors This has proved useful as a non-invasive method to study biochemical or metabolic changes in tissue. In bone marrow, water content and lipid signals are of particular interest. We used a modern clinical MR scanner to examine the effect of temporary epiphysiodesis with tension band plating. This was possible because MRI was performed either before surgery or after removal of hardware to avoid artefacts. Using short echo time T1 sequences VOL. 95-B, No. 6, JUNE 2013 changes in metaphyseal signal intensity were observed that corresponded to the induced growth arrest (Fig. 5). These changes disappeared five weeks after removal of implants. The median values from metaphyseal T1 ROIs appear to correlate with changes in growth in the treated physis (Table II). However, this way of assessing MRI information has not previously been reported and more studies are needed to validate the correlation between measurements of water content and bone growth. We believe that this technique might be used to detect disturbances of growth. The clinical application of these findings is yet to be investigated. To our knowledge this is the first paper that reports on the use of the tension band plating technique to obtain temporary reversible epiphysiodesis. Introduction of this technique into clinical practice may enable correction of LLD

6 860 M. GOTTLIEBSEN, B. MØLLER-MADSEN, H. STØDKILDE-JØRGENSEN, O. RAHBEK by epiphysiodesis in a safe manner at all ages during growth. Careful timing of epiphysiodesis may not be crucial and the indications for treatment of LLD could change. The question of possible rebound growth needs to be addressed in future studies. The study was supported by grants from The Danish Rheumatism Association, The Central Denmark Region and Institute of Clinical Medicine, Aarhus University. No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. This article was primary edited by M. Paterson and first-proof edited by J. Scott. References 1. Friend L, Widmann RF. Advances in management of limb length discrepancy and lower limb deformity. Curr Opin Pediatr 2008;20: Vitale MA, Choe JC, Sesko AM, et al. The effect of limb length discrepancy on health-related quality of life: is the 2 cm rule appropriate? J Pediatr Orthop B 2006;15: Phemister DB. Operative arrestment of longitudinal growth of bones in the treatment of deformities. J Bone Joint Surg [Am] 1933;15-A: Canale ST, Russell TA, Holcomb RL. Percutaneous epiphysiodesis: experimental study and preliminary clinical results. J Pediatr Orthop 1986;6: Ramseier LE, Sukthankar A, Exner GU. Minimal invasive epiphysiodesis using a modified Canale -technique for correction of angular deformities and limb leg length discrepancies. J Child Orthop 2009;3: Inan M, Chan G, Littleton AG, Kubiak P, Bowen JR. Efficacy and safety of percutaneous epiphysiodesis. J Pediatr Orthop 2008;28: Surdam JW, Morris CD, DeWeese JD, Drvaric DM. Leg length inequality and epiphysiodesis: review of 96 cases. J Pediatr Orthop 2003;23: Metaizeau JP, Wong-Chung J, Bertrand H, Pasquier P. Percutaneous epiphysiodesis using transphyseal screws (PETS). J Pediatr Orthop 1998;18: Blount WP, Clarke GR. Control of bone growth by epiphyseal stapling: a preliminary report. J Bone Joint Surg [Am] 1949;31-A: Gorman TM, Vanderwerff R, Pond M, MacWilliams B, Santora SD. Mechanical axis following staple epiphysiodesis for limb-length inequality. J Bone Joint Surg [Am] 2009;91-A: Raab P, Wild A, Seller K, Krauspe R. Correction of length discrepancies and angular deformities of the leg by Blount s epiphyseal stapling. Eur J Pediatr 2001;160: Stevens PM. Guided growth for angular correction: a preliminary series using a tension band plate. J Pediatr Orthop 2007;27: Burghardt RD, Herzenberg JE, Standard SC, Paley D. Temporary hemiepiphyseal arrest using a screw and plate device to treat knee and ankle deformities in children: a preliminary report. J Child Orthop 2008;2: Synder M, Harcke HT, Bowen JR, Caro PA. Evaluation of physeal behavior in response to epiphyseodesis with the use of serial magnetic resonance imaging. J Bone Joint Surg [Am] 1994;76-A: Synder M, Harcke HT, Conard K, Bowen JR. Experimental epiphysiodesis: magnetic resonance imaging evaluation with histopathologic correlation. Int Orthop 2001;25: Karbowski A, Camps L, Matthiass HH. Metaphyseal aspects of stapling. An experimental study in pigs. Arch Orthop Trauma Surg 1989;108: Herwig J, Schmidt A, Matthiab HH, Kleemann H, Buddecke E. Biochemical events during stapling of the proximal tibial epiphyseal plate in pigs. Clin Orthop Relat Res 1987;218: Kanellopoulos AD, Mavrogenis AF, Dovris D, et al. Temporary hemiepiphysiodesis with blount staples and eight-plates in pigs. Orthopedics 2011; Lauge-Pedersen H, Hagglund G, Johnsson R. Radiostereometric analysis for monitoring percutaneous physiodesis: a preliminary study. J Bone Joint Surg [Br] 2006;88-B: Christensen NO. Growth arrest by stapling: an experimental study of longitudinal bone growth and morphology of the growth region. Acta Orthop Scand Suppl 1973; Anumula S, Wehrli SL, Magland J, Wright AC, Wehrli FW. Ultra-short echotime MRI detects changes in bone mineralization and water content in OVX rat bone in response to alendronate treatment. Bone 2010;46: Li X, Ma BC, Bolbos RI, et al. Quantitative assessment of bone marrow edema-like lesion and overlying cartilage in knees with osteoarthritis and anterior cruciate ligament tear using MR imaging and spectroscopic imaging at 3 Tesla. J Magn Reson Imaging 2008;28: Bae WC, Chen PC, Chung CB, et al. Quantitative ultrashort echo time (UTE) MRI of human cortical bone: correlation with porosity and biomechanical properties. J Bone Miner Res 2012;27: THE BONE & JOINT JOURNAL