Comparison between upper and lower limb lengthening in patients with achondroplasia

GENERAL ORTHOPAEDICS Comparison between upper and lower limb lengthening in patients with achondroplasia A RETROSPECTIVE STUDY S-J. Kim, M. V. Agashe, S-H. Song, H-J. Choi, H. Lee, H-R. Song From Korea University Guro Hospital, Seoul, Korea Lengthening of the humerus is now an established technique. We compared the complications of humeral lengthening with those of femoral lengthening and investigated whether or not the callus formation in the humerus proceeds at a higher rate than that in the femur. A total of 24 humeral and 24 femoral lengthenings were performed on 12 patients with achondroplasia. We measured the pixel value ratio (PVR) of the lengthened area on radiographs and each radiograph was analysed for the shape, type and density of the callus. The quality of life (QOL) of the patients after humeral lengthening was compared with that prior to surgery. The complication rate per segment of humerus and femur was 0.87% and 1.37%, respectively. In the humerus the PVR was significantly higher than that of the femur. Lower limbs were associated with an increased incidence of concave, lateral and central callus shapes. Humeral lengthening had a lower complication rate than lower-limb lengthening, and QOL increased significantly after humeral lengthening. Callus formation in the humerus during the distraction period proceeded at a significantly higher rate than that in the femur. These findings indicate that humeral lengthening has an important role in the management of patients with achondroplasia. S-J. Kim, MD, Orthopaedic Surgeon M. V. Agashe, MD, Orthopaedic Surgeon S-H. Song, MD, Orthopaedic Surgeon H. Lee, MD, Research fellow H-R. Song, MD, PhD, Orthopaedic Surgeon Korea University Guro Hospital, Institute for Rare Diseases and Department of Orthopaedic Surgery, 80 Gurodong, Guro-gu, Seoul 152-703, Korea. H-J. Choi, MS, Medical Student Dartmouth Medical School, 1 Rope Ferry Road, Hanover, New Hampshire 03755-1404, USA. Correspondence should be sent to Professor H-R. Song; e-mail: songhae@korea.ac.kr 2012 British Editorial Society of Bone and Joint Surgery doi:10.1302/0301-620x.94b1. 27567 $2.00 J Bone Joint Surg Br 2012;94-B:128 33. Received 13 May 2011; Accepted after revision 9 September 2011 Distraction osteogenesis using an external fixator is now the standard technique for limb lengthening. 1,2 Lengthening of the humerus has been performed less frequently than lengthening of the femur and tibia, 3 and there are relatively few reports of humeral lengthening in the literature. 3,4 This may be due to the perception that the risks associated with the procedure outweigh the possible advantages. Tanaka et al 5 recently reported that callus formation in the humerus during the distraction period of lengthening proceeded at a significantly faster rate than in the tibia. De Bastiani et al 6 reported that the healing index in humeral lengthening was lower than that in femoral and tibial lengthening. Although corrections of deformity and upper limb lengthening have been described in several series, 7-9 to our knowledge there has been no study that has compared the callus formation and complications of humeral lengthening with those of femoral lengthening in the same patients. It is essential to be able to measure callus maturation and corticalisation during distraction osteogenesis in order to assess progress. Quantitative methods such as bone scans, CT and dual energy x-ray absorptiometry (DEXA) are sensitive but expensive. The pixel value ratio (PVR) using PACS (Picture Archiving Communication System) is a simple and cost-effective investigation tool. Serial radiological assessment using a classification such as that of Li et al 10 is also helpful. We have previously reported the relationship between PVR and bone regeneration fracture. 11 We have also suggested that careful radiological assessment of the patterns of callus formation is a useful method for the evaluation and monitoring of regenerate bone. 12 Using these methods, we wished to investigate the difference in callus maturation between humeral lengthening and femoral lengthening. We reviewed a series of patients with achondroplasia who underwent humeral and femoral lengthening to compare callus formation, complications and quality of life following lengthening of the lower and upper limbs. Patients and Methods We undertook a retrospective study on 48 segments (24 humeral and 24 femoral) in 12 patients with achondroplasia. All had bilateral lower-limb lengthening two to three years before bilateral humeral lengthening. Their mean age at the time of the initial surgery was 128 THE JOURNAL OF BONE AND JOINT SURGERY

COMPARISON BETWEEN UPPER AND LOWER LIMB LENGTHENING IN PATIENTS WITH ACHONDROPLASIA 129 11.8 years (6.2 to 19.8). There were six males and six females. The mean follow-up after surgery was 4.5 years (0.8 to 6.8). Only patients with complete medical records and radiographs were included in the study. A total of six patients had been excluded: two with incomplete records, one with systemic disease, one with previous injury, one with previous surgery and one with a brain tumour. Operative technique for humeral and femoral lengthening. All surgery was performed by the senior author (HRS). Monolateral external fixators (U&I, Seoul, Korea) were used in all cases. Two or three Schanz screws were inserted perpendicular to the anatomical axis in the proximal and distal sections of the humerus or the femur, and the fixator was attached. After incising the periosteum longitudinally a transverse osteotomy was performed in the mid-diaphyseal region using multiple drill-holes. Post-operative care. Lengthening was commenced after seven days at a rate of 1 mm/day (0.25 mm every six hours). The rate was subsequently adjusted according to the morphology of the callus on radiographs. After the completion of lengthening the fixator was removed when three of four cortices had shown satisfactory corticalisation. A cast was applied after removal of the fixator, and was retained for four to six weeks. The records were reviewed to determine the clinical outcome and complications. At each visit the range of movement at the relevant joints was recorded and the presence of pin-site infection, angulation or translation of the osteotomy site and any other complications. Evaluation. All the radiographs were studied by three observers (HRS, SJK, MA). The PVR was measured on the digital radiographs using StarPACS PiView (Star 5.0.6.1 software, Infinitt Co. Ltd, Seoul, Korea). The pixel value was measured with the pixel lens included in the tools of the PACS. The pixel value of the regeneration area was calculated from nine cortical and medullary readings on both anteroposterior and lateral views. One reading was taken at the centre of the callus, and the other two at the midpoint between the centre of the callus and the osteotomised ends both proximally and distally (Fig. 1). The mean of the resulting 18 values (nine in each of the two views) was used for further evaluation of callus stiffness. In order to measure the pixel value of the proximal and distal ends, three readings were taken (one in each cortex and one in the medulla) at a point midway between the osteotomy and the proximal or distal fixation in both anteroposterior and lateral views. 13 Care was taken to avoid any metal from fixation pins. The PVR of the regenerate was calculated using the following formula: PVR = [(pixel value of the proximal segment + pixel value of the distal segment) / 2] / pixel value of the regenerate. The stage of corticalisation was determined by the PVR, a value of 1 indicating corticalisation of the regenerate. The radiological features of distraction osteogenesis were classified with regard to shape and type on the basis of the Li classification 10 (Tables I and II). The shape was based Fig. 1 Pixel value assessment; the pixel value of the regeneration area was calculated from three cortical and three medullary readings each. One point is marked at the centre of the callus, and the other two at the midpoint of the centre and the osteotomised ends proximally and distally. For measuring the pixel value of the proximal end, three points were marked in each cortex and medulla at the midpoint of the osteotomised end and the proximal fixator. Points marked on the radiographs are where pixel values were taken. Note the nine points in the regeneration area and the three points in the proximal segment. on the width of the callus compared to the original osteotomy site. The type was based on four patterns of osteogenesis (sparse, homogeneous, heterogeneous and lucent) and three densities (low, intermediate and normal). The density was judged relative to the adjacent soft tissues and cortex. The shape, type and density were analysed in three different segments. Follow-up. At each annual follow-up patients were examined by the senior author (HRS) and complications or sequelae were recorded. They also completed two validated quality of life (QOL) questionnaires, the Short-Form 36 (SF-36) 14 and the Rosenberg self-esteem questionnaire. 15 The QOL scores before and after humeral lengthening were analysed retrospectively. Statistical analysis. Differences in external fixator index (EFI) and healing index (HI) were assessed by an independent two-sample t-test and one-way analysis of variance (ANOVA) with Tukey s honestly significant difference (HSD) post-hoc test. The results were based on two-tailed tests. Statistical differences for PVR and callus features were analysed using repeated measures analysis of variance (RMANOVA). PVR and callus features were tested for concurrence and reproducibility by inter-observer studies. Intraobserver studies were not carried out. The differences in the VOL. 94-B, No. 1, JANUARY 2012

130 S-J. KIM, M. V. AGASHE, S-H. SONG, H-J. CHOI, H. LEE, H-R. SONG Table I. Classification of callus by shape as proposed by Li et al 10 Shape Fusiform Cylindrical Concave Lateral Central Description Regenerate wider than the original bone Regenerate of same width as the original bone Regenerate narrower than the original bone Regenerate mainly on one side of the distraction gap Regenerate is a thin pillar Table II. Classification of callus by type as proposed by Li et al 10 Type Low density Intermediate density Normal density Sparse Type 1 (soft) Type 5 (half tone) Homogeneous Type 2 (stripe) Type 6 (uniform) Type 9 (solid) Heterogeneous Type 3 (speckle) Type 7 (irregular) Type 10 (cyst defects) Lucent Type 4 (adjacent) Type 8 (sawtooth) SF-36 and Rosenberg self-esteem scores before and after humeral lengthening were analysed using the two-tailed t- test. A p-value < 0.05 was considered to be significant. Results The mean gain in length in the humerus was 9.8 cm (7.3 to 14.9) and in the femur was 10.2 cm (7.9 to 12.6). The mean lengthening percentage (LP) was 38.4% (30% to 53%) in the humerus and 35.2% (29% to 42%) in the femur. The mean healing index (HI) was 31.1 days/cm (14 to 60) in the humerus and 34.4 days/cm (17 to 80) in the femur. The mean external fixator index (EFI) was 29.1 days/cm (20 to 75) in the humerus and 33.4 days/cm (21 to 84) in the femur. The complication rate per segment of humerus and femur was respectively 0.87% and 1.37% (Table III). Complications. The planned lengthening was achieved in every case. There was no nonunion or other major complication. Most problems in the humeral segments were due to pin-site infection (in 11 (46%)), but these resolved with local treatment and oral antibiotics. Two patients developed temporary elbow flexion contractures of 20 and 35, respectively; however, they resolved following physiotherapy with a return of a full range of movement. One patient had a radial nerve neurapraxia that resolved within two months. One humeral re-fracture occurred after removal of the fixator but united following immobilisation in a brace. Overall, varus angulation at the osteotomy site occurred in four segments (16%), with a mean angulation of 6.5 (0 to 39 ) at the final follow-up (Fig. 2). In humeral lengthening there were only two segments (8%) of joint complications and five segments (20%) bony complications. Relatively more complications occurred in femoral lengthening. Pin-site infection occurred in 13 segments (54%), joint complications occurred in ten segments (41%) and bony complications occurred in ten segments (41%). A flexion contracture of the hip was the most frequent joint Table III. Summary of results showing the amount of lengthening, lengthening percentages, healing index, external fixator index and complications per segment before and after humeral lengthening Parameter Humerus Femur Mean lengthening (cm) (SD, range) Mean lengthening percentage (SD, range) Mean healing index (days/cm) (SD, range) Mean external fixator index (days/cm) (SD, range) Complication rate per segment (%) 9.8 (1.4) (7.3 to 14.9) 38.4% (2.5) (30% to 53%) 31.1 (15.1) (14 to 60) 29.1 (13.2) (20 to 75) 10.21 (1.5) (7.9 to 12.6) 35.2% (21.1) (29% to 42%) 34.4 (20) (17 to 80) 33.4 (19.8) (21 to 84) p-value complication and re-fracture was the most common bony complication. A flexion contracture of > 30 occurred in seven (29%) patients; they underwent intramuscular recession of the rectus femoris, sartorius and iliopsoas muscles and physiotherapy and the mean flexion contracture was 5.5 (0 to 11 ) at final follow-up. Callus features. The PVR at the regenerate of each bone increased during the distraction period. A PVR of 1.0 at the regenerate was achieved first in the humerus. The mean PVR at 28 weeks was 1.021 (SD 0.11) and 0.995 (SD 0.15) in the humerus and femur, respectively. The mean PVR in the humerus was significantly higher than that in the femur (p < 0.05) (Fig. 3). In the 24 lengthened humeral segments there were six heterogeneous, 18 homogeneous and no lucent pathways during the consolidation period, whereas in the 24 femoral segments there were 13 heterogeneous, nine homogeneous and two lucent pathways. In the humerus there were ten cylindrical, 12 fusiform and two concave shapes, whereas in the femur there were six cylindrical, four fusiform, seven concave, six lateral and one central shape. Homogeneous, fusiform and cylindrical shapes were more prominent in the humerus than in the femur (p < 0.05). The inter-observer agreement among the three observers of PVR was fair, with a correlation coefficient between 0.7710 and 0.9660 and a 95% confidence interval (CI) between 0.3585 and 0.9855. With regard to callus feature, the correlation coefficient was between 0.3685 and 0.9695 and the 95% CI between 0.0450 and 0.9854. Quality of life. The patients with humeral lengthening and prior lower limb lengthening scored higher in the Rosenberg self-esteem questionnaire (mean 23.16, SD 1.5) than those with femoral lengthening only (mean 21.1, SD 1.1). The difference in self-esteem scores between the patients before and after humeral lengthening was significant (p = 0.0007). The SF-36 questionnaire also showed significant improvement after bilateral humeral lengthening (p = 0.0368 for the physical component summary, p = 0.0013 for the mental component summary and p = 0.0083 for the total score) (Table IV). 0.2 0.061 0.005 0.002 0.87 1.37 0.0001 THE JOURNAL OF BONE AND JOINT SURGERY

COMPARISON BETWEEN UPPER AND LOWER LIMB LENGTHENING IN PATIENTS WITH ACHONDROPLASIA 131 Fig. 2a Fig. 2b Radiographs of an 18-year-old male a) immediately post-operatively and b) at the last follow-up (one year after operation), showing severe varus deformity after lengthening. PVR 1.05 1.03 1.01 0.99 0.97 0.95 0.93 0.91 0.89 0.87 0.85 4 8 12 16 20 24 28 Time (weeks) Humerus Femur Fig. 3 Serial graph of the pixel value ratio (PVR) measurements for the humerus and femur during the lengthening period. Discussion Limb lengthening is a complex procedure and has a high complication rate. The limb must be lengthened safely without causing deterioration in function. In the lower limb there seems to be an increasing number of complications when the lengthening exceeds 20%. 16 This phenomenon does not occur in the humerus. In our study, the mean lengthening was 38.4% in the humerus and 35.2% in the femur. We were able to perform extensive lengthening because bone healing is known to be good 17 in achondroplastic patients, who tolerate lengthening well because of ligament and soft tissue laxity, and their muscle length exceeds their bone length before lengthening. 18 Previously, Tanaka et al 5 reported that the humerus shows significantly faster bony reconstruction than the tibia. However, they reviewed only six humeral segments and compared callus in the humerus with callus in six femoral and eight tibial segments. In our study, we reviewed 24 humeral segments and compared callus formation with 24 femoral segments in the same patients. Furthermore, we were able to determine the rate of callus formation by measuring the serial PVR for 28 weeks instead of a single estimate of bone mineral apparent density (BMAD). The PVR has recently been validated as an objective evaluation of mineralisation in the lengthening zone. 19-21 It is a cheap, cost-effective and sensitive parameter for measuring callus stiffness. However, to our knowledge, no previous study has used serial PVR measurement and callus pattern analysis in cases of humeral lengthening. We found that the regenerate zone of the humerus showed a higher mean PVR than that of the femur. This is because callus formation in the humerus during distraction proceeds at a higher rate than in the femur. Tanaka et al 5 reported that there was no significant difference in callus formation in the humerus and femur at eight weeks. We found that the mean PVR of the femur was similar to that of the humerus up to 20 weeks, but showed a significant difference after 20 weeks. This is probably associated with the complications of femoral lengthening, such as refracture, callus subsidence and angulation of the osteotomy VOL. 94-B, No. 1, JANUARY 2012

132 S-J. KIM, M. V. AGASHE, S-H. SONG, H-J. CHOI, H. LEE, H-R. SONG Table IV. Results of the Short-Form 36 (SF-36) and the Rosenberg selfesteem questionnaires (PCS, physical component summary; MCS, mental component summary; TCS, total component summary; SD, standard deviation; SEM, standard error) Outcome measure Before humeral lengthening After humeral lengthening p-value * SF-36 (PCS) 0.0368 Mean 40.3 54.9 SEM 4.72 4.61 SD 16.3 16 SF-36 (MCS) 0.0013 Mean 46.8 66.3 SEM 4.34 3.02 SD 15 10.5 SF-36 (TCS) 0.0083 Mean 45.2 62 SEM 4.7 3.4 SD 16.3 11.8 Rosenberg questionnaire 0.0007 Mean 21.08 23.16 SEM 1 1.5 SD 0.29 0.44 * two-tailed t-test site during weight-bearing. Singh et al 11 reported that homogeneous pathways showed the most favourable outcomes during lengthening. In addition, there is usually a gradual reduction in the width of the regenerate bone as distraction continues, so that by the end of the distraction phase most regenerate bone has a fusiform shape. This is associated with a more rapid bone healing index. 22 In our series there were more homogeneous pathways in the humerus than in the lower limbs during lengthening. The shape of the callus was more likely to be fusiform or cylindrical in the humerus than in the femur. The occurrence of these particular shapes and healing patterns can be used clinically to alert the surgeon to potential problems. By monitoring the healing progress in this way adverse conditions can be detected early, enabling corrective interventions. Premature consolidation may be an indication of a high rate of bone formation during the lengthening process. 7 In our study there were two premature consolidations in the 24 bilateral humeral lengthenings, but none in the femoral lengthenings. Fewer complications have been found in lengthening of the humerus than in lengthening of the femur. We found a flexion contracture in two elbows (8%), but interruption of the lengthening procedure was not necessary. These contractures resolved following removal of the fixator. More joint complications, however, occurred in femoral lengthening, and patients needed soft-tissue release to improve the range of movement. This may be due to a lower EFI in the humeral lengthenings than in the femoral lengthenings. We believe that re-fractures and angulation deformities are more frequent in femoral than in humeral lengthening because the former are weight-bearing segments. We had only one (4%) re-fracture of the new regenerated bone in 24 humeral segments after removal of the fixator, whereas there were five (21%) re-fractures in the femoral lengthenings. Lee et al 23 reported two (10%) re-fractures in 19 humeral lengthenings and Hosny 24 reported two (12%) in 16 humeral lengthenings. The incidence of re-fractures in our series was thus less than in other studies. We suggest that the risk of re-fracture can be minimised by careful analysis of the regenerate during healing. We have previously recommended temporary cessation of distraction and the application of gradual compression when concave, lateral or central callus shapes appear in the regenerate bone, until satisfactory regenerate with fusiform callus develops. 12 Some of the dissatisfaction expressed by patients with a lengthened lower limb may be attributed to the effects of upper- and lower-limb mismatch. 25,26 Someone with short arms and lengthened lower limbs will have difficulty in donning and removing socks, shoes or underwear. Our series shows that in terms of QOL, humeral lengthening is a good option for patients with achondroplasia. The patients with humeral lengthening scored well in both the SF-36 and the Rosenberg self-esteem questionnaires. Hence, lengthening of both upper and lower limbs averted the disappointing outcomes that arise from lower limb lengthening alone. Our study has some limitations. The number of patients was small; however, achondroplasia is uncommon, with an incidence of 1 in 25 000 to 40 000 people, 27 and hence even this number is significant. There is also an area of potential bias in the selection of patients. One prerequisite for limb lengthening surgery in achondroplasia is a strongly motivated patient with carers who have understood the benefits and risks of the surgery. It is possible that these patients will experience a better quality of life owing to an enhanced perception of their wellbeing as a result of their surgery. Another limitation is the fact that the rate of distraction was varied according to the morphology of the callus, and this may have some effect on the PVR. However, we feel that this may not be significant, as it was validated in the senior author s previous study. 13,19 In conclusion, humeral lengthening is a safe procedure with a relatively lower complication rate than in the femur. The callus formation in the humerus during the distraction period proceeds at a significantly higher rate than in the femur. Quality of life is significantly improved as a result of humeral lengthening after a previous femoral lengthening. These findings confirm that lengthening of the humerus using a monolateral external fixator in patients with achondroplasia is a reliable and safe technique. Supplementary material A table detailing a summary of complications and their management is available with the electronic version of this article on our website www.jbjs.org.uk THE JOURNAL OF BONE AND JOINT SURGERY

COMPARISON BETWEEN UPPER AND LOWER LIMB LENGTHENING IN PATIENTS WITH ACHONDROPLASIA 133 This study was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (A110416). 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. References 1. Sun XT, Easwar TR, Manesh S, et al. Complications and outcome of tibial lengthening using the Ilizarov method with or without a supplementary intramedullary nail: a case-matched comparative study. J Bone Joint Surg [Br] 2011;93-B:782 787. 2. Aston WJ, Calder PR, Baker D, Hartley J, Hill RA. Lengthening of the congenital short femur using the Ilizarov technique: a single-surgeon series. J Bone Joint Surg [Br] 2009;91-B:962 967. 3. Kiss S, Pap K, Vizkelety T, Terebessy T, Balla M, Szoke G. The humerus is the best place for bone lengthening. Int Orthop 2008;32-3:385 388. 4. Liu T, Zhang X, Li Z, Zeng W, Peng D, Sun C. Callus distraction for humeral nonunion with bone loss and limb shortening caused by chronic osteomyelitis. J Bone Joint Surg [Br] 2008;90-B:795 800. 5. Tanaka K, Nakamura K, Matsushita T, et al. Callus formation in the humerus compared with the femur and tibia during limb lengthening. Arch Orthop Trauma Surg 1998;117:262 264. 6. De Bastiani G, Aldegheri R, Renzi-Brivio L, Trivella G. Limb lengthening by callus distraction (callotasis). J Pediatr Orthop 1987;7:129 134. 7. Cattaneo R, Catagni MA, Guerreschi F. Applications of the Ilizarov method in the humerus: lengthenings and nonunions. Hand Clin 1993;9:729 739. 8. Poul J, Svebis M. Results of lengthening 20 humeri. Acta Chir Orthop Traumatol Cech 2001;68:289 293 (in Czech). 9. Tetsworth K, Krome J, Paley D. Lengthening and deformity correction of the upper extremity by the Ilizarov technique. Orthop Clin North Am 1991;22:689 713. 10. Li R, Saleh M, Yang L, Coulton L. Radiographic classification of osteogenesis during bone distraction. J Orthop Res 2006;24:339 347. 11. Singh S, Song HR, Venkatesh KP, et al. Analysis of callus pattern of tibia lengthening in achondroplasia and a novel method of regeneration assessment using pixel values. Skeletal Radiol 2010;39:261 266. 12. Venkatesh KP, Modi HN, Devmurari K, et al. Femoral lengthening in achondroplasia. J Bone Joint Surg [Br] 2009;91-B:1612 1617. 13. Hazra S, Song HR, Biswal S, et al. Quantitative assessment of mineralization in distraction osteogenesis. Skeletal Radiol 2008;37:843 847. 14. Jenkinson C, Wright L, Coulter A. Criterion validity and reliability of the SF-36 in a population sample. Qual Life Res 1994;3:7 12. 15. Rosenberg M. Society and the adolescent self-image. Princeton University Press: Princeton, 1965. 16. Yun AG, Severino R, Reinker K. Attempted limb lengthening beyond twenty percent of the initial bone length: results and complications. J Pediatr Orthop 2000;20:151 159. 17. Yasui N, Kawabata H, Kojimoto H, et al. Lengthening of the lower limbs in patients with achondroplasia and hypochondroplasia. Clin Orthop 1997;344:298 306. 18. Paley D. Current techniques of limb lengthening. J Pediatr Orthop 1988;8:73 92. 19. Zhao L, Fan Q, Venkatesh KP, Park MS, Song HR. Objective guidelines for removing an external fixator after tibial lengthening using pixel value ratio: a pilot study. Clin Orthop 2009;467:3321 3326. 20. Babatunde OM, Fragomen AT, Rozbruch SR. Noninvasive quantitative assessment of bone healing after distraction osteogenesis. HSS J 2009:Epub. 21. Shim JS, Chung KH, Ahn JM. Value of measuring bone density serial changes on a picture archiving and communication system (PACS) monitor in distraction osteogenesis. Orthopedics 2002;25:1269 1272. 22. Catagni M. Imaging techniques: the radiographic classification of bone regenerate during distraction. In: Maiocchi AB, Aronson J, eds. Operative principles of Ilizarov. London: Williams and Wilkins, 1991;53 57. 23. Lee FY, Schoeb JS, Yu J, Christiansen BD, Dick HM. Operative lengthening of the humerus: indications, benefits, and complications. J Pediatr Orthop 2005;25:613 616. 24. Hosny GA. Unilateral humeral lengthening in children and adolescents. J Pediatr Orthop B 2005;14:439 443. 25. Aldegheri R, Dall'Oca C. Limb lengthening in short stature patients. J Pediatr Orthop B 2001;10:238 247. 26. Kashiwagi N, Suzuki S, Seto Y, Futami T. Bilateral humeral lengthening in achondroplasia. Clin Orthop 2001;391:251 257. 27. Takken T, van Bergen MW, Sakkers RJ, Helders PJ, Engelbert RH. Cardiopulmonary exercise capacity, muscle strength, and physical activity in children and adolescents with achondroplasia. J Pediatr 2007;150:26 30. VOL. 94-B, No. 1, JANUARY 2012