|
1
|
Beger C, Alves I, Carl-Innig P, Sessa M, Mohnike K, Cheung MS. Limb lengthening in individuals with achondroplasia: Analysis of an international survey. Bone 2025; 195:117462. [PMID: 40101878 DOI: 10.1016/j.bone.2025.117462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 03/08/2025] [Accepted: 03/14/2025] [Indexed: 03/20/2025]
Abstract
BACKGROUND Limb lengthening surgery is a contentious option for individuals with achondroplasia. This study aimed to assess real-world experiences, outcomes, and perspectives on limb lengthening in a multinational cohort of individuals with achondroplasia. METHODS A cross-sectional, international online survey on limb lengthening experiences and perspectives was conducted in 11 languages across 16 countries from May until July 2024. RESULTS Out of 467 responders (229 self-responders, 238 parents/caregivers), 90 (19.3 %) reported undergoing limb lengthening (LL) surgery. The mean age at first surgery was 10.5 years (SD 4.5). On average, respondents underwent 3.7 (SD 2.9) procedures, resulting in 14.5 cm (SD10.4) added and final adult height of 137.1 cm in females and 142.1 cm in males. Significant improvements were described in activities such as car driving, bathing, brushing hair, and wiping after toileting for those who underwent both arm and leg lengthening (p ≤ 0.001). Among respondents, 23 % would recommend the procedure to others and 28 % would not recommend LL. Nearly half of respondents (49 %) was uncertain about recommending LL. CONCLUSIONS This is the largest international survey on LL in achondroplasia with results highlighting some of the differences in perspectives and choices of the individual with achondroplasia and their families, providing real-world evidence of the outcomes of this intervention. While significant functional improvements were reported, a reduced percentage of respondents recommended LL intervention. The findings underscore the existence of a triad when considering limb lengthening in achondroplasia as individual choices and life experiences, socio-cultural environment and access to clinical options.
Collapse
Affiliation(s)
- Christoph Beger
- Growth Network CrescNet, Medical Faculty, Leipzig University, Leipzig, Germany
| | - Inês Alves
- ANDO Portugal, University of Évora - CHRC, Évora, Portugal.
| | | | - Marco Sessa
- Italian Association on Achondroplasia, Milan, Italy
| | - Klaus Mohnike
- Children's Hospital, Otto-von-Guericke-University, Magdeburg, Germany
| | - Moira S Cheung
- Great Ormond Street Hospital, NHS Foundation Trust, London, UK
| |
Collapse
|
|
2
|
Giorgino R, Cornacchini J, Sillmann YM, Kostyra D, Berkane Y, Peretti GM, Mangiavini L. Aesthetic lower limb lengthening techniques: a systematic review of efficacy, complications, and patient satisfaction. J Orthop Surg Res 2025; 20:415. [PMID: 40275369 DOI: 10.1186/s13018-025-05808-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2025] [Accepted: 04/10/2025] [Indexed: 04/26/2025] Open
Abstract
BACKGROUND Aesthetic limb lengthening (ALL) is a cosmetic procedure aimed at enhancing body symmetry and improving self-esteem through the gradual elongation of bones. Unlike functional limb lengthening, which addresses limb length discrepancies, ALL focuses on increasing limb length for aesthetic purposes. While functional limb lengthening has been extensively studied, a comprehensive analysis of ALL outcomes is needed. This systematic review evaluates the efficacy, complications, and patient satisfaction associated with different ALL techniques, including distraction osteogenesis and various external and internal fixation systems. METHODS A systematic search of PubMed, Embase, and Scopus was conducted up to July 2024 to identify relevant studies in English. Eligible studies included case series, cohort studies, and randomized controlled trials with at least 12 months of follow-up. Studies focusing on adult populations undergoing aesthetic limb lengthening were included. Data on limb lengthening achieved, bone healing rates, complications, and patient satisfaction were extracted and synthesized through narrative analysis. The methodological quality of studies was assessed using the MINORS criteria for non-randomized studies. RESULTS A total of 12 studies involving 760 patients were included. Most patients were male (67%), with an average age of 24.75 years. Techniques employed included the Ilizarov method, motorized internal lengthening nails (MILN), and combined methods like Lengthening And Then Nailing (LATN). The lengthening achieved ranged from 62 mm to 87 mm, with an average of 67 mm. Patient satisfaction rates ranged from 88.8 to 98%. Psychological outcomes showed improvements in body image and self-esteem. Functionally, most patients resumed normal activities with minimal joint limitations. However, common complications included infections, bone healing issues, joint deformities, and material-related complications. CONCLUSION ALL offers high patient satisfaction and psychological benefits, with patients reporting improved body image and self-esteem. Despite these positive outcomes, complications such as infections and bone healing issues remain significant. Further research with rigorous study designs is needed to improve the safety and efficacy of ALL procedures.
Collapse
Affiliation(s)
| | - Jonathan Cornacchini
- Department of Plastic and Reconstructive Surgery and Hand Surgery, Nice University Hospital, Nice, France
- Center for Engineering in Medicine and Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- Institut Universitaire Locomoteur et du Sport, Nice, France
| | - Yannick M Sillmann
- Skeletal Biology Research Center, Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Harvard School of Dental Medicine, Boston, MA, USA
- Division of Oral and Plastic Maxillofacial Surgery, University Hospital Ulm, Ulm, Germany
| | - David Kostyra
- University of Massachusetts Chan Medical School, 55 N Lake Ave, MA, 01655, Worcester, USA
| | - Yanis Berkane
- Department of Plastic, Reconstructive and Aesthetic Surgery, CHU de Rennes, University of Rennes, Rennes, France
- SITI Laboratory, Établissement Français du Sang, UMR1236, INSERM, University of Rennes, Rennes, France
| | - Giuseppe M Peretti
- IRCCS Ospedale Galeazzi Sant'Ambrogio, Milan, Italy
- Department of Biomedical Sciences for Health, University of Milan, Milan, Italy
| | - Laura Mangiavini
- IRCCS Ospedale Galeazzi Sant'Ambrogio, Milan, Italy
- Department of Biomedical Sciences for Health, University of Milan, Milan, Italy
| |
Collapse
|
|
3
|
Cheung MS, Alves I, Carl-Innig P, Eastwood D, Maghnie M, Offiah A, Paley D, Riganti S, Savarirayan R, Sessa M, Vogt B, Mohnike K. Meeting report from the 3rd ISCBH-ERN BOND Achondroplasia Workshop on Long Bone Pathology in Children with Achondroplasia, Salzburg, Austria 22nd June 2024. Bone 2025; 190:117268. [PMID: 39366536 DOI: 10.1016/j.bone.2024.117268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Revised: 09/10/2024] [Accepted: 10/01/2024] [Indexed: 10/06/2024]
Abstract
A pre-meeting workshop on Long Bone Pathology in Children with Achondroplasia was held in Salzburg, Austria at the 11th International Conference on Children's Bone Health (ICCBH) 22-25 June 2024. There remains poor understanding and awareness amongst physicians managing achondroplasia of the underlying pathophysiology, radiology, natural history and orthopaedic procedures available for long bone deformities and restrictions. The structure of the workshop consisted of presentation of the results of a multinational patient survey on views of leg lengthening in achondroplasia, lectures, a debate and an interactive round table discussion. In total 150 attendees from 71 different cities and 31 countries were in attendance.
Collapse
Affiliation(s)
- Moira S Cheung
- Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
| | - Inês Alves
- ERN BOND ePAG, ANDO Portugal, University of Évora - CHRC, Évora, Portugal
| | | | - Deborah Eastwood
- Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
| | - Mohamad Maghnie
- Pediatric Endocrinology Unit, Department of Pediatrics, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy; Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, 16132 Genoa, Italy
| | - Amaka Offiah
- Division of Clinical Medicine, University of Sheffield, Sheffield, UK
| | - Dror Paley
- Paley Orthopedic and Spine Institute, St Mary's Medical Centre, Florida Atlantic University, West Palm Beach, FL, United States of America
| | - Simone Riganti
- Pediatric Orthopedic Unit, Department of Surgery, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy
| | - Ravi Savarirayan
- Murdoch Children's Research Institute, Royal Children's Hospital, University of Melbourne, Parkville, VIC, Australia
| | - Marco Sessa
- ERN BOND ePAG, AISAC Odv Italian Association on Achondroplasia, Milan, Italy
| | - Bjoern Vogt
- Paediatric Orthopaedics, Deformity Reconstruction and Foot Surgery, University Hospital Muenster, Germany
| | - Klaus Mohnike
- Children's Hospital, Otto-von-Guericke-University, Magdeburg, Germany
| |
Collapse
|
|
4
|
García López JM, García de la Blanca JC, Martí Ciruelos R, Núñez Ligero G. Bilateral humeral lengthening and deformity correction with hexapod external fixator in an achondroplastic patient: A case report. Int J Surg Case Rep 2024; 123:110285. [PMID: 39307029 PMCID: PMC11440309 DOI: 10.1016/j.ijscr.2024.110285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Revised: 09/06/2024] [Accepted: 09/09/2024] [Indexed: 09/29/2024] Open
Abstract
INTRODUCTION AND IMPORTANCE Achondroplasia, a prevalent skeletal dysplasia, often results in limb asymmetry and functional limitations, typically managed surgically with bone lengthening techniques. CASE PRESENTATION We present the case of a 10-year-old girl with achondroplasia who underwent bilateral humeral lengthening using hexapod external fixators. The patient, previously treated for lower limb lengthening, exhibited significant upper limb shortening affecting daily activities. Surgical intervention involved two stages, employing two hexapod external fixators for precise correction and lengthening. Symmetrical lengthening of 6 cm in both humeri was achieved without major complications. Follow-up assessments revealed improved functionality and satisfactory outcomes, emphasizing the importance of addressing upper limb deformities in achondroplasia patients. CLINICAL DISCUSSION While humeral lengthening is less common than lower extremity lengthening due to historical concerns about neurovascular complications and functional implications, recent advancements highlight its potential benefits, particularly in achieving functional and aesthetic balance. CONCLUSION This case highlights the efficacy and safety of hexapod fixators in achieving multiplanar correction and functional improvement in upper limb lengthening. Further investigation should be carried out to study broader application in similar cases.
Collapse
Affiliation(s)
- José María García López
- Service of Traumatology and Orthopaedics Surgery, Hospital Universitario 12 de Octubre, Madrid, Spain
| | | | - Rafael Martí Ciruelos
- Service of Traumatology and Orthopaedics Surgery, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Guillermo Núñez Ligero
- Service of Traumatology and Orthopaedics Surgery, Hospital Universitario 12 de Octubre, Madrid, Spain
| |
Collapse
|
|
5
|
Rovira Martí P, Ginebreda Martí I, García Fontecha C. Prophylactic Intramedullary Rodding After Femoral Lengthening in Patients With Achondroplasia and Hypochondroplasia. J Pediatr Orthop 2024; 44:e249-e254. [PMID: 38084006 DOI: 10.1097/bpo.0000000000002594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2024]
Abstract
BACKGROUND Femoral fracture after femoral lengthening in patients with achondroplasia and hypochondroplasia is a frequent complication, occurring in up to 30%. The purpose of this study is to demonstrate the effectiveness of prophylactic intramedullary rodding in preventing this complication. METHODS Multicenter retrospective study involving 86 femoral lengthening procedures in 43 patients with achondroplasia or hypochondroplasia. Forty-two femora (21 patients) were prophylactically managed with intramedullary Rush rodding after external fixation removal (11 females and 10 males, mean age 14.6 years) compared with 44 femora (22 patients) without prophylactic intramedullary rodding (13 females and 9 males, mean age 15.2 years). The mean amount of lengthening in the rodding group was 13.3 cm (52.6%) with an External Fixation Index of 25.8 days/cm; in patients without rodding was 14.3 cm (61.5%) and 24.5 days/cm, respectively. RESULTS Seven cases (15.9%) without rodding developed fractures. Four of them required surgical correction due to displacement or shortening. Only 1 patient (2.4%) had fracture of the femur after prophylactic rodding, and surgery was not required. The incidence of femur fracture was significantly lower in the prophylactic rodding group compared with the nonrodding group (2.4% vs. 15.9%, respectively; P =0.034). There were no cases of infection or avascular necrosis. CONCLUSIONS Prophylactic intramedullary rodding is a safe and effective method for preventing femoral fractures after femoral lengthening in patients with achondroplasia or hypochondroplasia. LEVEL OF EVIDENCE Level III-a retrospective comparative study.
Collapse
|
|
6
|
Trofimchuk V, Dossanov B, Lozovoy V, Khmyzov S, Dossanova A, Angelov A, Pashenko A, Zhukenov O. Quality of Life in Children With Achondroplasia Undergoing Paired Limb Lengthening With an External Fixator and Modified Distraction Control: Observational Nonrandomized Study. JMIR Rehabil Assist Technol 2024; 11:e49261. [PMID: 38265860 PMCID: PMC10851121 DOI: 10.2196/49261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Revised: 09/21/2023] [Accepted: 09/29/2023] [Indexed: 01/25/2024] Open
Abstract
BACKGROUND Transosseous distraction osteosynthesis is prioritized in orthopedic care for children with achondroplasia. However, difficulties encountered during treatment and rehabilitation directly impact patients' quality of life. Using rod external fixators within a semicircular frame for osteosynthesis is less traumatic compared to spoke circular devices. Their straightforward assembly and mounting on the limb segment can help significantly reduce treatment duration, thereby improving children's quality of life during treatment and rehabilitation. OBJECTIVE This study aimed to conduct a comparative analysis of the quality of life (measured by postoperative pain syndrome, physical activity, and emotional state) among children with achondroplasia undergoing paired limb lengthening using either an external fixator with modified distraction control or a circular multiaxial system developed by the authors. METHODS This was an observational, prospective, nonrandomized, and longitudinal study with historical control. The study group consisted of 14 patients ranging from 5 to 15 (mean 7.6, SD 2.3) years old with a genetically confirmed diagnosis of achondroplasia. All patients underwent paired limb lengthening with a rod external fixator and a modified distraction control developed by the authors. A total of 28 limb segments, among them 4 (14%) humeri, 8 (29%) femurs, and 16 (57%) tibias, were lengthened in 1 round. Unpublished data from the previous study served as the control group, comprising 9 patients (18 limb segments) of the same age group (mean age at surgery 8.6, SD 2.3 years), who underwent limb lengthening surgery using a circular multiaxial system-2 (11%) humeri, 6 (33%) femurs, and 10 (56%) tibias. The Wong-Baker Faces Rating Scale was used to measure pain symptoms, while the Russified Pediatric Quality of Life (PedsQL) v4.0 questionnaire assessed quality of life. RESULTS During the latent phase (7 to 10 days after surgery), a more pronounced decrease in the indicators of physical activity and emotional state on the PedsQL v4.0 questionnaire was noted in the control group (mean 52.4, SD 4.8 versus mean 52.8, SD 5.5 points according to children's responses and their parents' responses, respectively) compared to the experimental group (mean 59.5, SD 6.8 points and mean 61.33, SD 6.5 points according to the children's responses and their parents' responses, respectively). The differences between the groups were statistically significant (P<.05 for children's responses and P<.01 for parents' responses). Importantly, 6 months after surgery, these quality-of-life indicators, as reported by children in the experimental group, averaged 70.25 (SS 4.8) points. Similarly, their parents reported a mean of 70.54 (SD 4.2) points. In the control group, the corresponding values were 69.64 (SD 5.6) and 69.35 (SD 6.2), respectively. There was no statistically significant difference between the groups. CONCLUSIONS The external fixator with modified distraction control developed by the authors provides a higher standard of living compared with the circular multiaxial system during the latency phase.
Collapse
Affiliation(s)
- Vitaliy Trofimchuk
- Department of Pediatrician Surgery, Non-Profit Joint Stock Company Astana Medical University, Astana, Kazakhstan
| | - Bolatbek Dossanov
- Department of Pediatrician Surgery, Non-Profit Joint Stock Company Astana Medical University, Astana, Kazakhstan
| | - Vassiliy Lozovoy
- Department of Pediatrician Surgery, Non-Profit Joint Stock Company Astana Medical University, Astana, Kazakhstan
| | - Sergey Khmyzov
- Department of Pathology of the Spine and Joints of Children, Sitenko Institute of Spine and Joint Pathology, Kharkiv, Ukraine
| | - Assem Dossanova
- Department of Pediatrician Surgery, Non-Profit Joint Stock Company Astana Medical University, Astana, Kazakhstan
| | - Aleksandr Angelov
- Department of Pediatrician Surgery, Non-Profit Joint Stock Company Astana Medical University, Astana, Kazakhstan
| | - Andrey Pashenko
- Department of Pathology of the Spine and Joints of Children, Sitenko Institute of Spine and Joint Pathology, Kharkiv, Ukraine
| | - Olzhas Zhukenov
- Department of Pediatrician Surgery, Non-Profit Joint Stock Company Astana Medical University, Astana, Kazakhstan
| |
Collapse
|
|
7
|
Llerena J, Rosselli P, Aragão A, Valenzuela C, Bertola D, Mendez Y, del Pino M, Calvacanti N, Thomazinho P, Pimenta JM, Cohen S, Butt T, Thomaz JC, Shediac R, Rowell R, Magalhães TS, Kim C, Fano V. Lifetime Impact Study for Achondroplasia (LISA): Findings from an observational and multinational study focused on health-related quality of life in individuals with achondroplasia in Latin America. GENETICS IN MEDICINE OPEN 2023; 2:100843. [PMID: 39669637 PMCID: PMC11613863 DOI: 10.1016/j.gimo.2023.100843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 11/13/2023] [Accepted: 11/14/2023] [Indexed: 12/14/2024]
Abstract
Purpose The multisystem clinical manifestations and complications of achondroplasia, the most common form of disproportionate short stature, can cause functional impairment and psychosocial burden. The Lifetime Impact Study for Achondroplasia (LISA), aimed to assess health-related quality of life and medical resource utilization among Latin America patients with achondroplasia. Methods Data were collected from individuals aged 3 years and above in Argentina, Brazil, and Colombia between 2018 and 2021. A total of 172 patients participated in the study. Results Children with achondroplasia reported lower scores compared with average stature children in Quality of Life in Short Stature Youth (QoLISSY) and Pediatric Quality of Life Inventory (PedsQL) questionnaires, with the greatest impact on physical and social domains. Among adolescents, a significant percentage reported pain, 10.3% experienced pain in 3 or more sites. Adults scored lower than the reference population in the EQ-5D-5L Visual Analog Score, and a considerable portion reported moderate to severe anxiety/depression, pain or discomfort, and mobility problems. The Nottingham Health Profile (NHP) revealed poor health status in terms of energy, pain, and mobility. Medical events, particularly musculoskeletal and connective tissue disorders were reported, resulting in high medical resource utilization. Conclusion Overall, the Lifetime Impact Study for Achondroplasia study provides extensive data on health-related quality of life, psychosocial impact, and health care resource utilization among individuals with achondroplasia in Latin America. The findings confirm a significant burden of illness across multiple domains for these individuals.
Collapse
Affiliation(s)
- Juan Llerena
- Instituto Fernandes Figueira, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | - Pablo Rosselli
- Fundación Cardioinfantil, Instituto de Cardiología, Bogotá, Colombia
| | - Amanda Aragão
- Instituto Fernandes Figueira, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | | | - Debora Bertola
- Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brasil
| | - Yaneth Mendez
- Fundación Cardioinfantil, Instituto de Cardiología, Bogotá, Colombia
| | - Mariana del Pino
- Hospital de Pediatría “Prof. Dr. Juan P. Garrahan,” Buenos Aires, Argentina
| | | | - Paula Thomazinho
- Instituto Fernandes Figueira, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | | | | | - Tom Butt
- BioMarin Pharmaceutical Inc, Novato, CA
| | | | | | | | | | - Chong Kim
- Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brasil
| | - Virginia Fano
- Hospital de Pediatría “Prof. Dr. Juan P. Garrahan,” Buenos Aires, Argentina
| |
Collapse
|
|
8
|
Verdoni F, Giorgino R, Virgilio C, Nannini A, Viganò M, Curci D, Peretti GM, Mangiavini L. Results and complications of bilateral limb lengthening in achondroplasia: a retrospective analysis. Front Pediatr 2023; 11:1281099. [PMID: 38027309 PMCID: PMC10655023 DOI: 10.3389/fped.2023.1281099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Accepted: 10/23/2023] [Indexed: 12/01/2023] Open
Abstract
Background Achondroplasia is one of the main causes of disharmonic dwarfism. Patients with achondroplasia might have physical and psychological limitations due to their disproportionate stature. Surgical limb lengthening is the only practical option available to achieve a stature comparable to normal population range. The purpose of this study is to analyze results and complications of our lengthening protocol. Methods A retrospective analysis was performed on 33 patients with achondroplasia (21 females and 12 males) undergoing simultaneous bilateral tibia or femur lengthening in four surgical stages from 2017 to 2021 (46 lengthening procedures, with a total of 56 tibias and 36 femurs). For each patient, patients' characteristics and antero-posterior and lateral radiographs were obtained. The following parameters were analyzed: duration of lengthening with external fixator, amount of lengthening, complications or events that influenced outcomes and the healing index (HI). Results The average tibial and femoral gain was 7.9 cm and 6.9 cm, respectively. The tibiae achieved better results than the femurs (p = 0.005). Nineteen complications were reported for 92 segments (20.7%), and the variables influencing complications were: step (p = 0.002) and fixation duration (p = 0.061). Conclusions Bilateral parallel lower limb lengthening in four surgical steps may be a viable technique in patients with achondroplasia.
Collapse
Affiliation(s)
| | - Riccardo Giorgino
- IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
- Residency Program in Orthopedics and Traumatology, University of Milan, Milan, Italy
| | - Camilla Virgilio
- Faculty of Medicine and Surgery, University of Milan, Milan, Italy
| | - Alessandra Nannini
- IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
- Residency Program in Orthopedics and Traumatology, University of Milan, Milan, Italy
| | - Marco Viganò
- IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
| | | | - Giuseppe Michele Peretti
- IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
- Department of Biomedical Sciences for Health, University of Milan, Milan, Italy
| | - Laura Mangiavini
- IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
- Department of Biomedical Sciences for Health, University of Milan, Milan, Italy
| |
Collapse
|
|
9
|
郑 学, 秦 泗, 石 磊, 郭 保, 赵 俊, 殷 海. [Preliminary study of Ilizarov technique in treatment of lower limb deformity caused by achondroplasia]. ZHONGGUO XIU FU CHONG JIAN WAI KE ZA ZHI = ZHONGGUO XIUFU CHONGJIAN WAIKE ZAZHI = CHINESE JOURNAL OF REPARATIVE AND RECONSTRUCTIVE SURGERY 2023; 37:157-161. [PMID: 36796809 PMCID: PMC9970763 DOI: 10.7507/1002-1892.202210072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Revised: 12/27/2022] [Indexed: 02/18/2023]
Abstract
Objective To investigate the surgical method and preliminary effectiveness of Ilizarov technique in the treatment of lower limb deformity caused by achondroplasia. Methods The clinical data of 38 patients with lower limb deformity caused by achondroplasia treated by Ilizarov technique between February 2014 and September 2021 were retrospectively analyzed. There were 18 males and 20 females, the age ranged from 7 to 34 years, with an average of 14.8 years. All patients presented with bilateral knee varus deformity. The preoperative varus angles was (15.2±4.2)°, and knee society score (KSS) was 61.8±7.2. Nine of these patients underwent tibia and fibula osteotomy, 29 cases underwent tibia and fibula osteotomy and bone lengthening at the same time. Full-length bearing position X-ray films of bilateral lower limbs were taken to measure the bilateral varus angles, analyze the healing index, and record the occurrence of complications. KSS score was used to evaluate the improvement of knee joint function before and after operation. Results All 38 cases were followed up 9-65 months, with an average of 26.3 months. Needle tract infection occurred in 4 cases and needle tract loosening occurred in 2 cases after operation, which were improved after symptomatic treatment such as dressing change, Kirschner wire change, and oral antibiotics, and no neurovascular injury occurred in all patients. The external fixator was worn for 3-11 months after operation, with an average of 7.6 months, and the healing index was 43-59 d/cm, with an average of 50.3 d/cm. At last follow-up, the leg was 3-10 cm longer, with an average of 5.5 cm. The varus angles was (1.5±0.2)° and the KSS score was 93.7±2.6, which significantly improved when compared with those before operation ( P<0.05). Conclusion Ilizarov technique is a safe and effective method for the treatment of short limb with genu varus deformity caused by achondroplasia, which can improve the quality of life of patients.
Collapse
Affiliation(s)
- 学建 郑
- 国家康复辅具研究中心附属康复医院矫形外科（北京 100176）Department of Orthopedic Surgery, Rehabilitation Hospital Affiliated to National Research Center for Rehabilitation AIDS, Beijing, 100176, P. R. China
| | - 泗河 秦
- 国家康复辅具研究中心附属康复医院矫形外科（北京 100176）Department of Orthopedic Surgery, Rehabilitation Hospital Affiliated to National Research Center for Rehabilitation AIDS, Beijing, 100176, P. R. China
| | - 磊 石
- 国家康复辅具研究中心附属康复医院矫形外科（北京 100176）Department of Orthopedic Surgery, Rehabilitation Hospital Affiliated to National Research Center for Rehabilitation AIDS, Beijing, 100176, P. R. China
| | - 保逢 郭
- 国家康复辅具研究中心附属康复医院矫形外科（北京 100176）Department of Orthopedic Surgery, Rehabilitation Hospital Affiliated to National Research Center for Rehabilitation AIDS, Beijing, 100176, P. R. China
| | - 俊 赵
- 国家康复辅具研究中心附属康复医院矫形外科（北京 100176）Department of Orthopedic Surgery, Rehabilitation Hospital Affiliated to National Research Center for Rehabilitation AIDS, Beijing, 100176, P. R. China
| | - 海阳 殷
- 国家康复辅具研究中心附属康复医院矫形外科（北京 100176）Department of Orthopedic Surgery, Rehabilitation Hospital Affiliated to National Research Center for Rehabilitation AIDS, Beijing, 100176, P. R. China
| |
Collapse
|
|
10
|
Balci Hİ, Anarat FB, Bayram S, Eralp L, Şen C, Kocaoğlu M. Does the technique of limb lengthening affect physeal growth in patient with achondroplasia? Comparison of the simultaneous and consecutive tibia and femur lengthening with external fixators. J Pediatr Orthop B 2023; 32:60-65. [PMID: 36125888 DOI: 10.1097/bpb.0000000000001011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
We aimed to retrospectively investigate and compare patients who underwent bilateral simultaneous and consecutive lengthening surgery of the femur and tibia in terms of the effect on physeal growth. We hypothesize that compared with the sequential lengthening technique, simultaneous lengthening of the bilateral femur and tibia affects physeal growth to a greater extent. Twenty-six patients with achondroplasia who operated in our clinic between 1995 and 2015 for limb lengthening were included in the study. Fourteen patients with bilateral lengthening of the femur and tibia at the same time were named as simultaneous bilateral lengthening (SBL). Twelve patients with bilateral lengthening of the femur and then bilateral tibia lengthening in other sections or vice versa, at a different time was named consecutive bilateral lengthening (CBL). All patients were followed until at least 18 years old. The physeal arrest was measured with predicted final length at the first visit (investigated with the multiplier method), the total amount of lengthening, and final clinical, and radiological length. Mean limb lengthening was 145 mm (48.5%) and 151 mm (46.6%) for simultaneous and consecutive groups respectively. For lower extremity length, the first group reached 527.6 mm while the expected was 447.3 mm. Considering 151 mm lengthening, the mean growth disturbance for the SBL group was 70.7 mm and for the CBL group was 47.5 mm. For total height comparing between two groups, disturbance for height was 80.5 mm and 65.4 mm, respectively. Although there was no statistical difference, simultaneous bilateral femoral and tibial lengthening has more physiological physeal disturbance effects than consecutive lengthening in patients with achondroplasia.
Collapse
Affiliation(s)
- Halil İbrahim Balci
- Department of Orthopedics and Traumatology, Istanbul Faculty of Medicine, Istanbul University
| | - Fikret Berkan Anarat
- Department of Orthopedics and Traumatology, Istanbul Faculty of Medicine, Istanbul University
| | - Serkan Bayram
- Department of Orthopedics and Traumatology, Istanbul Faculty of Medicine, Istanbul University
| | - Levent Eralp
- Department of Orthopedics and Traumatology, Istanbul Faculty of Medicine, Istanbul University (Retired)
| | - Cengiz Şen
- Department of Orthopedics and Traumatology, Istanbul Faculty of Medicine, Istanbul University
| | - Mehmet Kocaoğlu
- Department of Orthopedics and Traumatology, Unimed Center, Istanbul, Turkey
| |
Collapse
|
|
11
|
Alonso-Hernández J, Galán-Olleros M, Miranda-Gorozarri C, Egea-Gámez RM, Palazón-Quevedo Á. Two-stage Bone Lengthening With Reuse of a Single Intramedullary Telescopic Nail in Patients With Achondroplasia. J Pediatr Orthop 2022; 42:e616-e622. [PMID: 35250019 DOI: 10.1097/bpo.0000000000002133] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Patients with achondroplasia may benefit from limb-lengthening surgery with telescopic intramedullary nails (TIMNs). However, the 5-cm maximum length of the nails used in these patients in their original design may be insufficient. The aim of this research is to analyze the outcomes and complications after reusing the same TIMN for a second consecutive 5-cm lengthening in patients with achondroplasia. METHODS Retrospective study of 26 bones (16 femurs and 10 tibias) in 9 patients with achondroplasia treated for bilateral 2-stage sequential lengthening reusing the same TIMN. On completion of a first stage of 5 cm of elongation, the nail was unlocked, retracted, and re-locked; a second stage of 5 cm of distraction followed. Radiologic and clinical parameters were measured preoperatively and postoperatively, and complications were recorded. RESULTS The median age of patients at first surgery was 13.54 (12.9 to 16.3) years; 55% were males. The median preoperative height was 121 (117.5 to 127) cm, and the median healing index was 18.12 (14.5 to 32.8) and 26.96 (23.3 to 31.6) d/cm, while time to weight bearing was 185.5 (144.8 to 308.5) and 242.5 (208.5 to 293.8) days for femurs and tibias, respectively. Major complications included 3 cases of moderate ankle equinus, 2 cases of hardware failure (failure to relengthen), 2 premature consolidations, 1 common peroneal neurapraxia, and 2 valgus deformities. Femoral procedures had significantly fewer complications than tibial interventions (7 vs. 15, P=0.03), whereas patients who underwent lengthening of both the femur and tibia did not have significantly higher complication rates (14 vs. 8, P=0.6). CONCLUSIONS This study analyzes lower-limb lengthening in a series of achondroplastic patients using TIMN with the novelty of nail reuse to relengthen the bone. The complication rate found is acceptable, among which, potential damage to the internal lengthening mechanism must be considered, though this complication can usually be easily resolved. Overall, nail reuse seems advisable in cases where bone elongation is indicated, and the size and design of the nail limits the extent of lengthening. LEVEL OF EVIDENCE Level III, retrospective comparative study, before and after intervention.
Collapse
Affiliation(s)
- Javier Alonso-Hernández
- Limb Lengthening and Reconstruction Unit, Orthopaedic Surgery and Traumatology Department
- Department of Orthopaedic Surgery and Traumatology
| | | | - Carlos Miranda-Gorozarri
- Limb Lengthening and Reconstruction Unit, Orthopaedic Surgery and Traumatology Department
- Department of Orthopaedic Surgery and Traumatology
| | - Rosa M Egea-Gámez
- Department of Orthopaedic Surgery and Traumatology
- Spinal Unit, Department of Orthopaedic Surgery and Traumatology
| | - Ángel Palazón-Quevedo
- Department of Orthopaedic Surgery and Traumatology
- Hip Unit, Department of Orthopaedic Surgery and Traumatology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
| |
Collapse
|
|
12
|
Ramesh S, Zaman F, Sävendahl L, Madhuri V. Radial shockwave treatment promotes chondrogenesis in human growth plate and longitudinal bone growth in rabbits. Bone 2022; 154:116186. [PMID: 34520899 DOI: 10.1016/j.bone.2021.116186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 09/06/2021] [Accepted: 09/07/2021] [Indexed: 11/17/2022]
Abstract
OBJECTIVE The process of longitudinal bone growth occurs at the growth plate where the chondrocytes undergo apparent structural and molecular changes to promote growth. Recent reports suggest that radial shockwave treatment (rSWT) stimulates bone length in cultured fetal rat metatarsals. Therefore, we investigated if rSWT has similar growth promoting effects on cultured human growth plate fragments and addressed the same in a preclinical in vivo rabbit model by subjecting their growth plates to rSWT. METHODS Short-term effects of high-energy rSWT were evaluated in a unique model of cultured human growth plate cartilage (n = 5) wherein samples exposed to rSWT were assessed for chondrogenic markers at 24 h in comparison to unexposed samples obtained from the same limb. Local in vivo effects were studied in six-week-old rabbits who had their distal femurs exposed to four weekly sessions of rSWT at low- and high-energy levels (n = 4 each). At sacrifice, histomorphometric and immunohistochemistry analyses were performed. For effect on longitudinal growth, proximal tibiae of 22-week-old rabbits (n = 12) were asymmetrically exposed to rSWT; the contralateral side served as untreated controls. At sacrifice, the final bone length was measured. RESULTS In the ex vivo model of cultured human growth plate cartilage, rSWT exposure upregulated SOX9 and COL2A1 compared to control. In the immature rabbit model, an increased number of proliferative chondrocytes and column density was seen for both the energy levels. In the adolescent rabbits, an increase in tibial length was observed after the fourth session of high-energy rSWT and until six-weeks after rSWT compared to the untreated limb. CONCLUSIONS Our preliminary experimental results suggest that rSWT may serve as a non-invasive treatment and possibly a safe strategy to stimulate longitudinal bone growth. However, further studies are needed to assess the in vivo effects of rSWT in models of disturbed bone growth.
Collapse
Affiliation(s)
- Sowmya Ramesh
- Department of Paediatric Orthopaedics, Christian Medical College, Vellore, India; Division of Paediatric Endocrinology, Department of Women's and Children's Health, Karolinska Institutet, Solna, Sweden; Centre for Stem Cell Research, a Unit of InStem Bengaluru, Christian Medical College, Bagayam, Vellore, India.
| | - Farasat Zaman
- Division of Paediatric Endocrinology, Department of Women's and Children's Health, Karolinska Institutet, Solna, Sweden.
| | - Lars Sävendahl
- Division of Paediatric Endocrinology, Department of Women's and Children's Health, Karolinska Institutet, Solna, Sweden; Paediatric Endocrinology and Metabolism, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Solna, Sweden.
| | - Vrisha Madhuri
- Department of Paediatric Orthopaedics, Christian Medical College, Vellore, India; Centre for Stem Cell Research, a Unit of InStem Bengaluru, Christian Medical College, Bagayam, Vellore, India.
| |
Collapse
|
|
13
|
Kumble S, Savarirayan R. Emerging therapies for Achondroplasia: changing the rules of the game. Expert Opin Emerg Drugs 2021; 26:425-431. [PMID: 34758681 DOI: 10.1080/14728214.2021.2005577] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
INTRODUCTION Achondroplasia is the most common genetic cause of disproportionate short stature, affecting over 360,000 individuals. Serious complications contributing to significant morbidity in affected individuals include cranio-cervical junction compression and obstructive sleep apnoea. Current clinically available treatments are predominantly symptomatic, and associated with variable outcomes. We summarise the new precision investigational products that are currently in Phase 2 and Phase 3 clinical trials for the treatment of individuals with achondroplasia. AREAS COVERED Fibroblast growth factor receptor 3 (FGFR3), a membrane-spanning tyrosine kinase receptor, binds various fibroblast growth factors (FGF) to regulate the normal process of endochondral bone growth. Gain of FGFR3 function in individuals with achondroplasia results in inhibition of normal endochondral ossification. A greater understanding of these molecular pathways through animal models has led to the development of several targeted therapies being tested in children, which we discuss in this review. EXPERT OPINION The last decade has been game-changing in terms of new precision therapies for children with achondroplasia that have the potential to fundamentally change the natural history of this condition. The next decade will see how these therapies compare, if they might be used in combination, and evaluate the balance of their long-term benefits and harms.
Collapse
Affiliation(s)
- Smitha Kumble
- Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria Australia
| | - Ravi Savarirayan
- Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria Australia.,University of Melbourne, Parkville, Victoria, Australia
| |
Collapse
|
|
14
|
Masci G, Palmacci O, Vitiello R, Bonfiglio N, Bocchi MB, Cipolloni V, Maccauro G, Pola E. Limb lengthening with PRECICE magnetic nail in pediatric patients: A systematic review. World J Orthop 2021; 12:575-583. [PMID: 34485104 PMCID: PMC8384613 DOI: 10.5312/wjo.v12.i8.575] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 05/12/2021] [Accepted: 06/22/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Limb lengthening techniques play an increasingly important role in the pediatric orthopedic field. The principles of the osteogenesis distraction bonded traditionally with external fixators; however, the recent deployment of fully implantable systems has been able to overcome severities related to external fixators. The PRECICE® is an implantable limb lengthening intramedullary nail system that is remotely controlled and magnetically driven. AIM To review the current literature available on this matter in order to assess the PRECICE clinical and radiological outcomes and its possible complications in a population of pediatric patients undergoing limb lengthening. METHODS Only five studies met the inclusion criteria and were consequently included in the review for a total of 131 patients and 135 femurs. The clinical and radiological outcomes of interest were: the main lengthening obtained, the distraction rate, the period of time to full weight bearing, the consolidation index, and the Association for the Study and Application of Methods of Ilizarov score. RESULTS In conclusion, data collected from the articles under investigation were comparable with the exception of the consolidation index. Unfortunately, the study population was too small and the patients' follow-up was too short to make definitive conclusions. CONCLUSION This review shows that the PRECICE Nail System is still a therapeutic challenge in limb lengthening for pediatric orthopedic surgeons; however, careful pre-operative planning and an accurate surgical technique could allow the correction of more complex deformities with a low rate of complications.
Collapse
Affiliation(s)
- Giulia Masci
- Department of Orthopaedics and Traumatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome 00168, Italy
| | - Osvaldo Palmacci
- Department of Orthopaedics and Traumatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome 00168, Italy
| | - Raffaele Vitiello
- Department of Orthopaedics and Traumatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome 00168, Italy
| | - Nadia Bonfiglio
- Department of Orthopaedics and Traumatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome 00168, Italy
| | - Maria Beatrice Bocchi
- Department of Orthopaedics and Traumatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome 00168, Italy
| | - Valerio Cipolloni
- Department of Orthopaedics and Traumatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome 00168, Italy
| | - Giulio Maccauro
- Department of Orthopaedics and Traumatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome 00168, Italy
| | - Enrico Pola
- Department of Orthopaedics and Traumatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome 00168, Italy
- Policlinico di Napoli University Hospital, Università della Campania Luigi Vanvitelli School of Medicine, Napoli 80100, Italy
| |
Collapse
|
|
15
|
Dossanov B, Trofimchuk V, Lozovoy V, Khmyzov S, Dossanova A, Zhukenov O, Tuktiyeva N, Angelov A. Evaluating the results of long tubular bone distraction with an advanced rod monolateral external fixator for achondroplasia. Sci Rep 2021; 11:14727. [PMID: 34282216 PMCID: PMC8290032 DOI: 10.1038/s41598-021-94146-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 07/01/2021] [Indexed: 11/09/2022] Open
Abstract
The work aimed to evaluate the effectiveness of the developed distraction system based on the rod external monolateral fixation mechanisms by comparing it with the classical technique of long tubular bones distraction based on the circular multi-axial system. The study included patients with a genetically confirmed diagnosis of achondroplasia. The experimental group consisted of 14 patients who underwent surgical limb lengthening by the rod monolateral external fixator with a distraction system developed by the authors. The lengthening was performed on 28 segments of tubular bones. The majority of the experimental group patients achieved the lengthening value close to the planned one and the deformation correction. The fixation period was averagely 83.8 ± 3.7 days, the regenerate length was 8.5 ± 0.6 cm, and the mechanical strength of the distraction regenerate was 10.3° ± 2.18°. The rod external fixator with a control distraction system developed by the authors has small dimensions and low weight of the external supporting elements of high durability. It is reported to provide a good psychological tolerance of the treatment process and significantly outperforms the circular multi-axis system. Considering the aforementioned, the proposed apparatus can grant good orthopedic care to patients with achondroplasia.
Collapse
Affiliation(s)
- Bolatbek Dossanov
- Department of Pediatrician Surgery, NSC Astana Medical University, Nur-Sultan, Kazakhstan
| | - Vitaliy Trofimchuk
- Department of Pediatrician Surgery, NSC Astana Medical University, Nur-Sultan, Kazakhstan.
| | - Vassiliy Lozovoy
- Department of Pediatrician Surgery, NSC Astana Medical University, Nur-Sultan, Kazakhstan
| | - Sergey Khmyzov
- Department of Pathology of the Spine and Joints of Children, Sitenko Institute of Spine and Joint Pathology, Kharkiv, Ukraine
| | - Assem Dossanova
- Department of Pediatrician Surgery, NSC Astana Medical University, Nur-Sultan, Kazakhstan
| | - Olzhas Zhukenov
- Department of Pediatrician Surgery, NSC Astana Medical University, Nur-Sultan, Kazakhstan
| | - Nazym Tuktiyeva
- Department of Pediatrician Surgery and Orthopedic, NSC Semey Medical University, Semey, Kazakhstan
| | - Aleksandr Angelov
- Department of Pediatrician Surgery, NSC Astana Medical University, Nur-Sultan, Kazakhstan
| |
Collapse
|
|
16
|
Extensive Limb Lengthening for Achondroplasia and Hypochondroplasia. CHILDREN-BASEL 2021; 8:children8070540. [PMID: 34202538 PMCID: PMC8305967 DOI: 10.3390/children8070540] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 06/21/2021] [Accepted: 06/22/2021] [Indexed: 11/22/2022]
Abstract
Extensive limb lengthening (ELL) was completed in 75 patients: 66 achondroplasia and 9 hypochondroplasia. The average lengthening was 27 cm for achondroplasia (12–40 cm) and 17 cm for hypochondroplasia (range 10–25 cm). There were 48 females and 27 males. Lengthening was done either by 2-segment (14 patients; both tibias and/or both femurs) or by 4-segment lengthenings (64 patients; both femurs and tibias at the same time). Most patients also had bilateral humeral lengthening. Patients had 2 or 3 lower limb lengthenings and one humeral lengthening. Lengthenings were either juvenile-onset (31), adolescent-onset (38) or adult-onset (6). The average age at final follow-up was 26 years old (range 17–43 years). There were few permanent sequelae of complications. The most serious was one paraparesis. All patients returned to activities of normal living and only one was made worse by the surgery (paraparesis). This is the first study to show that ELL can lead to an increase of height into the normal height range. Previous studies showed mean increases of height of up to 20 cm, while this study consistently showed an average increase of 30 cm (range 15–40 cm) for juvenile-onset and mean increase of 26 cm (range 15–30 cm) for adolescent-onset. This results in low normal height at skeletal maturity for males and females. The adult-onset had a mean increase of 16.8 (range 12–22 cm). This long-term follow-up study shows that ELL can be done safely even with large lengthenings and that 4-segment lengthening may offer advantages over 2-segment lengthening. While all but the more recent cases were performed using external fixation, implantable limb lengthening promises to be an excellent alternative and perhaps an improvement.
Collapse
|
|
17
|
Wrobel W, Pach E, Ben-Skowronek I. Advantages and Disadvantages of Different Treatment Methods in Achondroplasia: A Review. Int J Mol Sci 2021; 22:ijms22115573. [PMID: 34070375 PMCID: PMC8197470 DOI: 10.3390/ijms22115573] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Revised: 05/20/2021] [Accepted: 05/22/2021] [Indexed: 02/06/2023] Open
Abstract
Achondroplasia (ACH) is a disease caused by a missense mutation in the FGFR3 (fibroblast growth factor receptor 3) gene, which is the most common cause of short stature in humans. The treatment of ACH is necessary and urgent because untreated achondroplasia has many complications, both orthopedic and neurological, which ultimately lead to disability. This review presents the current and potential pharmacological treatments for achondroplasia, highlighting the advantages and disadvantages of all the drugs that have been demonstrated in human and animal studies in different stages of clinical trials. The article includes the potential impacts of drugs on achondroplasia symptoms other than short stature, including their effects on spinal canal stenosis, the narrowing of the foramen magnum and the proportionality of body structure. Addressing these effects could significantly improve the quality of life of patients, possibly reducing the frequency and necessity of hospitalization and painful surgical procedures, which are currently the only therapeutic options used. The criteria for a good drug for achondroplasia are best met by recombinant human growth hormone at present and will potentially be met by vosoritide in the future, while the rest of the drugs are in the early stages of clinical trials.
Collapse
|
|
18
|
Abstract
PURPOSE The purpose of this study was to analyze the long-term results of humeral lengthening in achondroplastic patients and make suggestions on the most appropriate surgical technique to improve patient outcomes. METHODS Fifty-four humeral lengthening procedures performed in 27 achondroplastic patients were reviewed. Elongations were performed by means of callotasis with unilateral external fixation. Inclusion criteria were: achondroplastic patients under 17 years without prior arm operations and minimum follow-up of 36 months. RESULTS Fifty humeri in 25 patients (13 men and 12 women), aged between 9 and 17 years, met the inclusion criteria. Mean humeral lengthening was 8.82 cm (range: 5 to 10.5 cm), which represented an elongation of 54.80% (range: 46% to 63%) of the original length. The healing index was 0.91 months (range: 0.72 to 1.4 mo) per centimeter gained. Shoulder and elbow range of motion and stability were preserved in 47 limbs. Noncomplicated cases consistently experienced a significant functional improvement in the performance of activities of daily living such as putting on footwear and personal hygiene. Short-term complications included 11 pin-tract infections, 1 radial nerve neuropraxia, and 1 failure of the regenerated bone formation. None of these complications prevented from completion of treatment. Long-term complications included 2 cases of nonunion, 3 elbow flexion contractures, and 2 cases of psychological dissatisfaction, all of them in 4 patients. Factors associated with long-term complications were intraoperative fragment displacement and distal humeral osteotomy. No fractures of the regenerated bone were identified in the long term. CONCLUSIONS Callotasis with unilateral external fixation is a reliable and well-tolerated procedure for humeral lengthening in achondroplastic patients, with an acceptable complication rate. Guided fixator placement and a proximal humeral osteotomy are strongly recommended technical tips as they may help prevent complications and improve outcomes. LEVEL OF EVIDENCE Level IV-case series.
Collapse
|
|
19
|
Julien A, Perrin S, Duchamp de Lageneste O, Carvalho C, Bensidhoum M, Legeai-Mallet L, Colnot C. FGFR3 in Periosteal Cells Drives Cartilage-to-Bone Transformation in Bone Repair. Stem Cell Reports 2020; 15:955-967. [PMID: 32916123 PMCID: PMC7561512 DOI: 10.1016/j.stemcr.2020.08.005] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Revised: 08/10/2020] [Accepted: 08/11/2020] [Indexed: 12/18/2022] Open
Abstract
Most organs and tissues in the body, including bone, can repair after an injury due to the activation of endogenous adult stem/progenitor cells to replace the damaged tissue. Inherent dysfunctions of the endogenous stem/progenitor cells in skeletal repair disorders are still poorly understood. Here, we report that Fgfr3Y637C/+ over-activating mutation in Prx1-derived skeletal stem/progenitor cells leads to failure of fracture consolidation. We show that periosteal cells (PCs) carrying the Fgfr3Y637C/+ mutation can engage in osteogenic and chondrogenic lineages, but following transplantation do not undergo terminal chondrocyte hypertrophy and transformation into bone causing pseudarthrosis. Instead, Prx1Cre;Fgfr3Y637C/+ PCs give rise to fibrocartilage and fibrosis. Conversely, wild-type PCs transplanted at the fracture site of Prx1Cre;Fgfr3Y637C/+ mice allow hypertrophic cartilage transition to bone and permit fracture consolidation. The results thus highlight cartilage-to-bone transformation as a necessary step for bone repair and FGFR3 signaling within PCs as a key regulator of this transformation.
Fgfr3Y367C activating mutation in skeletal stem/progenitor cells prevents bone healing Intrinsic deficiencies in transplanted Prx1Cre;Fgfr3Y637C/+ PCs cause pseudarthrosis Prx1Cre;Fgfr3Y637C/+ PCs cannot support cartilage-to-bone transformation Wild-type PCs can rescue the Prx1Cre;Fgfr3Y637C/+ pseudarthrosis phenotype
Collapse
Affiliation(s)
- Anais Julien
- Paris University, Imagine Institute, INSERM UMR 1163, 75015, Paris, France
| | - Simon Perrin
- Paris University, Imagine Institute, INSERM UMR 1163, 75015, Paris, France
| | | | - Caroline Carvalho
- Paris University, Imagine Institute, INSERM UMR 1163, 75015, Paris, France
| | - Morad Bensidhoum
- Paris university, Laboratory of Osteoarticular Biology, Bioengineering and Bioimaging (B3OA), UMR CNRS 7052, INSERM 1271
| | - Laurence Legeai-Mallet
- Paris University, Imagine Institute, Laboratory of Molecular and Physiopathological Bases of Osteochondrodysplasia, INSERM UMR 1163, 75015, Paris, France
| | - Céline Colnot
- Paris University, Imagine Institute, INSERM UMR 1163, 75015, Paris, France.
| |
Collapse
|
|
20
|
Abstract
Limb lengthening continues to be a real challenge to both the patient and the orthopaedic surgeon. Although it is not a difficult operative problem, there is a long and exhausting postoperative commitment which can jeopardize early good results. I aim to review the history, evolution, biology, complications and current concepts of limb lengthening. Ilizarov's innovative procedure using distraction histeogenesis is the mainstay of all newly developing methods of treatment. The method of fixation is evolving rapidly from unilateral external fixator to ring fixator, computer assisted and finally lengthening intramedullary nails. The newly manufactured nails avoid many of the drawbacks of external fixation but they have their own complications. In general, the indications for limb lengthening are controversial. The indications have been extended from lower limb length inequality to upper extremity lengthening, including humeral, forearm and phalangeal lengthening. A wide range in frequency of complications is recorded in the English literature, which may reach up to 100% of cases treated. With developing experience, cosmetic lengthening has become possible using external or internal lengthening devices with an acceptable rate of problems.Level of evidence: V.
Collapse
Affiliation(s)
- Gamal A Hosny
- Benha University Hospitals, 11 Al Israa Al-Mohandeseen Street, Cairo, Egypt.
| |
Collapse
|
|
21
|
Uttarilli A, Shah H, Shukla A, Girisha KM. A review of skeletal dysplasia research in India. J Postgrad Med 2019; 64:98-103. [PMID: 29692401 PMCID: PMC5954821 DOI: 10.4103/jpgm.jpgm_527_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
We aimed to review the contributions by Indian researchers to the subspecialty of skeletal dysplasias (SDs). Literature search using specific keywords in PubMed was performed to retrieve all the published literature on SDs as on July 6, 2017. All published literature on SDs wherein at least one author was from an Indian institute was included. Publications were grouped into different categories based on the major emphasis of the research paper. Five hundred and forty publications in English language were retrieved and categorized into five different groups. The publications were categorized as reports based on: (i) phenotypes (n = 437), (ii) mutations (n = 51), (iii) novel genes (n = 9), (iv) therapeutic interventions (n = 31), and (v) reviews (n = 12). Most of the publications were single-patient case reports describing the clinical and radiological features of the patients affected with SDs (n = 352). We enlisted all the significant Indian contributions. We have also highlighted the reports in which Indians have contributed to discovery of new genes and phenotypes. This review highlights the substantial Indian contributions to SD research, which is poised to reach even greater heights given the size and structure of our population, technological advances, and expanding national and international collaborations.
Collapse
Affiliation(s)
- A Uttarilli
- Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal, Karnataka, India
| | - H Shah
- Department of Orthopedics, Kasturba Medical College, Manipal University, Manipal, Karnataka, India
| | - A Shukla
- Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal, Karnataka, India
| | - K M Girisha
- Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal, Karnataka, India
| |
Collapse
|
|
22
|
Ko KR, Shim JS, Chung CH, Kim JH. Surgical Results of Limb Lengthening at the Femur, Tibia, and Humerus in Patients with Achondroplasia. Clin Orthop Surg 2019; 11:226-232. [PMID: 31156776 PMCID: PMC6526131 DOI: 10.4055/cios.2019.11.2.226] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Revised: 11/30/2018] [Accepted: 12/07/2018] [Indexed: 01/27/2023] Open
Abstract
Background Results of limb lengthening in patients with achondroplasia were previously reported in many studies. However, the reports of comparison among the three long bones (femur, tibia, and humerus) are rare, especially for the results of crossed lengthening (lengthening of one femur and contralateral tibia followed by that of the opposite side) for the lower limbs. The purpose of this study was to report the surgical results of a series of limb lengthening in achondroplastic or hypochondroplasia patients at our institution. Methods Fifteen patients (14 with achondroplasia and 1 with hypochondroplasia) underwent lower limb lengthening of the femur (n = 32) and tibia (n = 28), and 12 of them underwent crossed lengthening. Humeral lengthening was performed in 14 patients (n = 28). The mean age at the first operation was 11.7 years, and the mean follow-up duration was 66.7 months. The healing index, consolidation period index (duration of consolidation period/gained length), and other radiographic indices were analyzed. Limb length discrepancy and hip-knee-ankle alignment in lower limbs, and the occurrence of difficulties were assessed. Results The average gain in length for the femur, tibia, and humerus was 8.3 cm, 8.5 cm, and 7.4 cm, respectively. The mean healing index was 29.6 days/cm for the femur, 29.0 days/cm for the tibia, and 27.2 days/cm for the humerus. The mean consolidation period index was 14.7 days/cm for the humerus, which was significantly lower than that in the lower limb (17.3 days/cm for the femur and 17.8 days/cm for the tibia). Of the 12 who underwent crossed lengthening, five showed limb length discrepancy ≥ 1.0 cm. Among their 24 lower limbs, three showed valgus alignment ≥ 5° and one showed varus alignment ≥ 5°. Thirty-two pin site infections and three fractures were conservatively managed. Three femoral fractures, eight equinus deformities, and four cases with premature consolidation of the fibula were surgically treated. Obstacle and true complication related to humeral lengthening were not observed. Conclusions Humeral lengthening was relatively effective and safe. Careful attention will be needed to avoid the occurrence of limb length discrepancy or malalignment in crossed lengthening.
Collapse
Affiliation(s)
- Kyung Rae Ko
- Department of Orthopedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jong Sup Shim
- Department of Orthopedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Chae Hoon Chung
- Department of Orthopedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Joo Hwan Kim
- Department of Orthopedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| |
Collapse
|
|
23
|
Changes in the range of motion of the lower limb joints during extensive tibial lengthening in achondroplasia. J Pediatr Orthop B 2018; 27:535-540. [PMID: 29878976 DOI: 10.1097/bpb.0000000000000526] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Increase in the magnitude of lengthening during the limb lengthening procedure involves a high risk of decreased range of motion (ROM) in adjacent joints. Even though patients with achondroplasia can tolerate a relatively larger amount of lengthening owing to its inherent soft-tissue laxity, they often exhibit significant joint contractures during extensive lengthening. In the present study, we evaluated temporal changes in the ROM of the hip, knee, and ankle joints throughout the treatment period in 12 limbs of six patients with achondroplasia who had undergone extensive tibial lengthening. The ROM of hip extension, knee extension, and ankle dorsiflexion were measured before distraction, at every 1-cm length gained during distraction, and at monthly intervals after the termination of distraction until the frame removal. The average amount of lengthening was 9.2±1.2 cm, corresponding to 52.8±6.8% of the original bone length. Equinus deformity of the ankle was observed in the early phase of distraction, whereas flexion contracture of the knee and hip appeared in the middle and the late phase of distraction, respectively. With dedicated physiotherapy and deliberate orthosis wearing, all of the contracture gradually resolved up to the preoperative state after the termination of distraction. This is the first report showing the development of contracture in the hip, a nonadjacent joint for the tibial lengthening.
Collapse
|
|
24
|
Özer D, Arikan Y. Alt Ekstremite Uzatma Osteotomilerinin Klinik Sonuçları. ACTA MEDICA ALANYA 2018. [DOI: 10.30565/medalanya.386818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
|
|
25
|
Uttarilli A, Shah H, Shukla A, Girisha KM. A review of skeletal dysplasia research in India. J Postgrad Med 2018; 64:98-103. [PMID: 29692401 DOI: 10.4103/jpgm.jpgm-527-17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2025] Open
Abstract
We aimed to review the contributions by Indian researchers to the subspecialty of skeletal dysplasias (SDs). Literature search using specific keywords in PubMed was performed to retrieve all the published literature on SDs as on July 6, 2017. All published literature on SDs wherein at least one author was from an Indian institute was included. Publications were grouped into different categories based on the major emphasis of the research paper. Five hundred and forty publications in English language were retrieved and categorized into five different groups. The publications were categorized as reports based on: (i) phenotypes (n = 437), (ii) mutations (n = 51), (iii) novel genes (n = 9), (iv) therapeutic interventions (n = 31), and (v) reviews (n = 12). Most of the publications were single-patient case reports describing the clinical and radiological features of the patients affected with SDs (n = 352). We enlisted all the significant Indian contributions. We have also highlighted the reports in which Indians have contributed to discovery of new genes and phenotypes. This review highlights the substantial Indian contributions to SD research, which is poised to reach even greater heights given the size and structure of our population, technological advances, and expanding national and international collaborations.
Collapse
Affiliation(s)
- A Uttarilli
- Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal, Karnataka, India
| | - H Shah
- Department of Orthopedics, Kasturba Medical College, Manipal University, Manipal, Karnataka, India
| | - A Shukla
- Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal, Karnataka, India
| | - K M Girisha
- Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal, Karnataka, India
| |
Collapse
|
|
26
|
Hamdy RC, Bernstein M, Fragomen AT, Rozbruch SR. What's New in Limb Lengthening and Deformity Correction. J Bone Joint Surg Am 2017; 99:1408-1414. [PMID: 28816903 DOI: 10.2106/jbjs.17.00464] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Reggie C Hamdy
- 1Shriners Hospital for Children, Montreal, Quebec, Canada 2Loyola University Stritch School of Medicine, Maywood, Illinois 3Hospital for Special Surgery, New York, NY
| | | | | | | |
Collapse
|