Ultrasound evaluation of the tibial graft structure during fixation with the Ilizarov device in patients with achondroplasia

Abstract

BACKGROUND: Bone regeneration during fixation needs to be evaluated due to clinical measures taken to prevent possible complications, such as evaluation of the correct segment axis, verification of the equality of the extended and contralateral segments (with repeated lengthening), maintenance of fixation rigidity, functional control of the load on the operated limb, and the patient’s motor activity. All of these factors have a direct impact on the structure and maturation of the distraction graft and readiness for device removal. It is relevant to study the proximal graft in bilocal treatment based on the greatest elongation (5.5 [5.0; 6.0] cm) compared to the distal graft. Proximal graft maturation affects the timing of device removal.

AIM: The aim was to evaluate the structure of the tibial distraction graft in achondroplasia patients of different ages during the fixation period.

MATERIALS AND METHODS: AVISUS Hitachi (Japan) was used for ultrasound scanning with a 7.5 MHz linear sensor. The graft was evaluated using standard programs. The study included achondroplasia patients aged 6–9 years (group I, n = 15) and 10–15 years (group II, n = 15). The study was conducted at 5, 30, 60, and 90 days (with repeated limb lengthening) from the start of the fixation period. In group I of monolocal tibial lengthening, the elongation was 6.5 [6; 7] cm. For bilocal leg lengthening in groups I and II, the proximal graft elongation was 5.5 [5.0; 6.0] cm, and the distal graft elongation was 2.5 [2.0; 3.0] cm.

RESULT: In groups I and II, a favorable course of osteogenesis was observed, with typical stages of graft formation. Group II showed slower development of typical structures, resulting in longer fixation times. Therefore, the fixation time was 55 ± 5 days (p ≤ 0.05) in group I and 63 ± 3 days (p ≤ 0.05) in group II (in case of favorable progression). The exception was 1 patient (out of 10 patients with repeated leg lengthening), who developed a hypoechoic cyst-like lesion in the graft midzone during distraction. The time to cortical plate formation increased to 85 ± 5 days (p ≤ 0.05).

CONCLUSIONS: Ultrasound evaluation of tibial distraction regeneration during fixation showed that the activity of reparative osteogenesis during this period corresponds to the activity of reparative osteogenesis during distraction. Although it is not possible to fully visualize elongation achieved during fixation due to the formation of echo-dense fragments at the ends of the parent bone, ultrasound scanning allows evaluation of changes in graft filling, vascularization, and graft readiness for removal of the external fixation device.

Keywords

achondroplasia / bone graft ultrasound / fixation / osteogenesis / leg lengthening

References

[1] Richette P, Bardin T, Stheneur C. Achondroplasia: from genotype to phenotype. Joint Bone Spine. 2008;75(2):125–130. doi: 10.1016/j.jbspin.2007.06.007

[2] Richette P., Bardin T., Stheneur C. Achondroplasia: from genotype to phenotype // Joint Bone Spine. 2008. Vol. 75, N 2. P. 125–130. doi: 10.1016/j.jbspin.2007.06.007

[3] Legare JM. Achondroplasia. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1152/

[4] Legare J.M. Achondroplasia. In: Adam M.P., Feldman J., Mirzaa G.M., et al., editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle, 1993–2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1152/

[5] Pauli RM. Achondroplasia: a comprehensive clinical review. Orphanet J Rare Dis. 2019;14(1):1. doi: 10.1186/s13023-018-0972-6

[6] Pauli R.M. Achondroplasia: a comprehensive clinical review // Orphanet J. Rare Dis. 2019. Vol. 14, N 1. P. 1. doi: 10.1186/s13023-018-0972-6

[7] Foreman PK, van Kessel F, van Hoorn R, et al. Birth prevalence of achondroplasia: a systematic literature review and meta-analysis. Am J Med Genet A. 2020;182(10):2297–2316. doi: 10.1002/ajmg.a.61787

[8] Foreman P.K., van Kessel F., van Hoorn R, et al. Birth prevalence of achondroplasia: a systematic literature review and meta-analysis // Am J Med Genet A. 2020. Vol. 182, N 10. P. 2297–2316. doi: 10.1002/ajmg.a.61787

[9] Matsushita M, Esaki R, Mishima K, et al. Clinical dosage of meclozine promotes longitudinal bone growth, bone volume, and trabecular bone quality in transgenic mice with achondroplasia. Sci Rep. 2017;7(1):7371. doi: 10.1038/s41598-017-07044-8

[10] Matsushita M., Esaki R., Mishima K., et al. Clinical dosage of meclozine promotes longitudinal bone growth, bone volume, and trabecular bone quality in transgenic mice with achondroplasia // Sci Rep. 2017. Vol. 7, N 1. P. 7371. doi: 10.1038/s41598-017-07044-8

[11] Bonafe L, Cormier-Daire V, Hall C, et al. Nosology and classification of genetic skeletal disorders: 2015 revision. Am J Med Genet A. 2015;167A(12):2869–2892. doi: 10.1002/ajmg.a.37365

[12] Bonafe L., Cormier-Daire V., Hall C., et al. Nosology and classification of genetic skeletal disorders: 2015 revision // Am J Med Genet A. 2015. Vol. 167A, N 12. P. 2869–2892. doi: 10.1002/ajmg.a.37365

[13] Coi A, Santoro M, Garne E, et al. Epidemiology of achondroplasia: a population-based study in Europe. Am J Med Genet A. 2019;179(9):1791–1798. doi: 10.1002/ajmg.a.61289

[14] Coi A., Santoro M., Garne E., et al. Epidemiology of achondroplasia: a population-based study in Europe // Am J Med Genet A. 2019. Vol. 179, N 9. P. 1791–1798. doi: 10.1002/ajmg.a.61289

[15] Wang Y, Liu Z, Liu Z, et al. Advances in research on and diagnosis and treatment of achondroplasia in China. Intractable Rare Dis Res. 2013;2(2):45–50. doi: 10.5582/irdr.2013.v2.2.45

[16] Wang Y., Liu Z., Liu Z., et al. Advances in research on and diagnosis and treatment of achondroplasia in China // Intractable Rare Dis Res. 2013. Vol. 2, N 2. P. 45–50. doi: 10.5582/irdr.2013.v2.2.45

[17] Couser NL, Pande CK, Turcott CM, et al. Mild achondroplasia/hypochondroplasia with acanthosis nigricans, normal development, and a p.Ser348Cys FGFR3 mutation. Am J Med Genet A. 2017;173(4):1097–1101. doi: 10.1002/ajmg.a.38141

[18] Couser N.L., Pande C.K., Turcott C.M., et al. Mild achondroplasia/hypochondroplasia with acanthosis nigricans, normal development, and a p.Ser348Cys FGFR3 mutation // Am J Med Genet A. 2017. Vol. 173, N 4. P. 1097–1101. doi: 10.1002/ajmg.a.38141

[19] Wrobel W, Pach E, Ben-Skowronek I. Advantages and disadvantages of different treatment methods in achondroplasia: a review. Int J Mol Sci. 2021;22(11):5573. doi: 10.3390/ijms22115573.

[20] Wrobel W., Pach E., Ben-Skowronek I. Advantages and disadvantages of different treatment methods in achondroplasia: a review // Int J Mol Sci. 2021. Vol. 22, N 11. P. 5573. doi: 10.3390/ijms22115573

[21] Duggan S. Vosoritide: first approval. Drugs. 2021;81(17):2057–2062. doi: 10.1007/s40265-021-01623-w

[22] Duggan S. Vosoritide: first approval // Drugs. 2021. Vol. 81, N 17. P. 2057–2062. doi: 10.1007/s40265-021-01623-w

[23] Wendt DJ, Dvorak-Ewell M, Bullens S, et al. Neutral endopeptidase-resistant C-type natriuretic peptide variant represents a new therapeutic approach for treatment of fibroblast growth factor receptor 3-related dwarfism. J Pharmacol Exp Ther. 2015;353(1):132–149. doi: 10.1124/jpet.114.218560

[24] Wendt D.J., Dvorak-Ewell M., Bullens S., et al. Neutral endopeptidase-resistant C-type natriuretic peptide variant represents a new therapeutic approach for treatment of fibroblast growth factor receptor 3-related dwarfism // J Pharmacol Exp Ther. 2015. Vol. 353, N 1. P. 132–149. doi: 10.1124/jpet.114.218560

[25] Paton DM. Efficacy of vosoritide in the treatment of achondroplasia. Drugs Today (Barc). 2022;58(9):451–456. doi: 10.1358/dot.2022.58.9.3422313

[26] Paton D.M. Efficacy of vosoritide in the treatment of achondroplasia // Drugs Today (Barc). 2022. Vol. 58, N 9. P. 451–456. doi: 10.1358/dot.2022.58.9.3422313

[27] Savarirayan R, Tofts L, Irving M, et al. Once-daily, subcutaneous vosoritide therapy in children with achondroplasia: a randomised, double-blind, phase 3, placebo-controlled, multicentre trial. Lancet. 2020;396(10252):684–692. doi: 10.1016/S0140-6736(20)31541-5

[28] Savarirayan R., Tofts L., Irving M., et al. Once-daily, subcutaneous vosoritide therapy in children with achondroplasia: a randomised, double-blind, phase 3, placebo-controlled, multicentre trial // Lancet. 2020. Vol. 396, N 10252. P. 684–692. doi: 10.1016/S0140-6736(20)31541-5

[29] Savarirayan R, Irving M, Maixner W, et al. Rationale, design, and methods of a randomized, controlled, open-label clinical trial with open-label extension to investigate the safety of vosoritide in infants, and young children with achondroplasia at risk of requiring cervicomedullary decompression surgery. Sci Prog. 2021;104(1):368504211003782. doi: 10.1177/00368504211003782

[30] Savarirayan R., Irving M., Maixner W., et al. Rationale, design, and methods of a randomized, controlled, open-label clinical trial with open-label extension to investigate the safety of vosoritide in infants, and young children with achondroplasia at risk of requiring cervicomedullary decompression surgery // Sci Prog. 2021. Vol. 104, N 1. ID: 368504211003782. doi: 10.1177/00368504211003782

[31] Foreman PK, van Kessel F, van Hoorn R, et al. Birth prevalence of achondroplasia: a systematic literature review and meta-analysis. Am J Med Genet A. 2020;182(10):2297–2316. doi: 10.1002/ajmg.a.61787

[32] Foreman P.K., van Kessel F., van Hoorn R., et al. Birth prevalence of achondroplasia: a systematic literature review and meta-analysis // Am J Med Genet A. 2020. Vol. 182, N 10. P. 2297–2316. doi: 10.1002/ajmg.a.61787

[33] Popkov AV, Shevtsov VI, Dzhanbakhishov GSO. Achondroplasia: a guide for doctors. Moscow: Medicine; 2001. 352 p. (In Russ.) EDN: UHZIDG

[34] Попкова А.В., Шевцова В.И., Джанбахишов Г.С.О., и др. Ахондроплазия: руководство для врачей. Москва: Медицина, 2001. 352 с. EDN: UHZIDG

[35] Zheng X, Qin S, Shi L, et al. Preliminary study of Ilizarov technique in treatment of lower limb deformity caused by achondroplasia. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2023;37(2):157–161. (In Chin.) doi: 10.7507/1002-1892.202210072

[36] Zheng X., Qin S., Shi L., et al. Preliminary study of Ilizarov technique in treatment of lower limb deformity caused by achondroplasia // Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2023. Vol. 37, N 2. P. 157–161. (In Chin.) doi: 10.7507/1002-1892.202210072

[37] Donaldson J, Aftab S, Bradish C. Achondroplasia and limb lengthening: Results in a UK cohort and review of the literature. J Orthop. 2015;12(1):31–34. doi: 10.1016/j.jor.2015.01.001

[38] Donaldson J., Aftab S., Bradish C. Achondroplasia and limb lengthening: Results in a UK cohort and review of the literature // J Orthop. 2015. Vol. 12, N 1. P. 31–34. doi: 10.1016/j.jor.2015.01.001

[39] Aranovich AM, Gofman FF, Korkin AY, et al. Surgical rehabilitation of patients with systemic skeletal diseases. In: XII All-Russian congress of traumatologists and orthopedists. Collection of abstracts. Saint Petersburg: Saint Petersburg Public Organization “Man and His Health”, 2022. P. 37–38. (In Russ.) EDN: MZZFEG

[40] Аранович А.М., Гофман Ф.Ф., Коркин А.Я., и др. Хирургическая реабилитация больных с системными заболеваниями скелета. В кн: XII Всероссийский съезд травматологов-ортопедов. Сборник тезисов. Санкт-Петербург: Санкт-Петербургская общественная организация «Человек и его здоровье», 2022. С. 37–38. EDN: MZZFEG

[41] Luneva SN, Menshchikova TI, Aranovich AM. Features of reparative osteogenesis of distraction regenerate of the tibia and the content of some osteotropic growth factors in patients with achondroplasia aged 9–12 years. Pediatric Orthopedics, Traumatology and Reconstructive Surgery. 2022;10(3):223–234. EDN: WHEOFF doi: 10.17816/PTORS108618

[42] Лунева С.Н., Менщикова Т.И., Аранович А.М. Особенности репаративного остеогенеза дистракционного регенерата большеберцовой кости и содержание некоторых остеотропных факторов роста у больных ахондроплазией в возрасте 9–12 лет // Ортопедия, травматология и восстановительная хирургия детского возраста. 2022. Т. 10. № 3. С. 223–234. EDN: WHEOFF doi: 10.17816/PTORS108618

[43] Menshchikova TI, Aranovich AM. Lengthening of the shins in patients with achondroplasia 6–9 years old as the first stage of growth correction. Genius of Orthopedics. 2021;27(3):366–371. EDN: RQVSDS doi: 10.18019/1028-4427-2021-27-3-366-371

[44] Менщикова Т.И., Аранович А.М. Удлинение голеней у больных ахондроплазией 6–9 лет как первый этап коррекции роста // Гений ортопедии. 2021. Т. 27, № 3. С. 366–371. EDN: RQVSDS doi: 10.18019/1028-4427-2021-27-3-366-371

[45] Chirkova AM, Silantyeva TA, Erofeev SA, et al. Histomorphometric features of distraction regenerates formed after disruption of the integrity of the tibia in various ways. In: Danilov RK, editor. Fundamental and applied problems of histology. Histogenesis and tissue regeneration. Proceedings of a scientific conference. Saint Petersburg: Kirov Military Medical Academy; 2004. P. 137–139. (In Russ.)

[46] Чиркова А.М., Силантьева Т.А., Ерофеев С.А., и др. Гистоморфометрические особенности дистракционных регенератов, формирующихся после нарушения целостности большеберцовой кости различными способами. В кн.: Фундаментальные и прикладные проблемы гистологии. Гистогенез и регенерация тканей. Материалы научной конференции / под ред. Р.К. Данилова. Санкт-Петербург: Военно-медицинская академия им. С.М. Кирова, 2004. С. 137–139.

[47] Onoprienko GA, Voloshin VP. Microcirculation and regeneration of bone tissue: theoretical and clinical aspects. Moscow: Binom. Laboratory of knowledge; 2017. 184 p. (In Russ.)

[48] Оноприенко Г.А., Волошин В.П. Микроциркуляция и регенерация костной ткани: теоретические и клинические аспекты. Москва: Бином. Лаборатория знаний, 2017. 184 с.