Ultrasound Criteria of Reparative Osteogenesis in the Distraction Regenerate of the Femur in Patients Aged 9–12 Years With Achondroplasia Undergoing Cross-Lengthening of the Femur and Contralateral Tibia

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Abstract

BACKGROUND: The relevance of longitudinal assessment of reparative osteogenesis is shown by the fact that the maturation of the femoral regenerate defines the timing of initiating contralateral tibial lengthening and overall hospital stay duration.

AIM: This study aimed to identify ultrasound criteria of reparative osteogenesis in the femoral distraction regenerate that allow for the initiation of surgical treatment on the contralateral tibia in patients with achondroplasia.

METHODS: Patients with achondroplasia aged 9–12 years (n = 37) were examined; at age 6–7 years, they had undergone the first stage of treatment, namely, bilateral tibial lengthening. At the second stage of treatment, femoral lengthening was performed first, followed by contralateral tibial lengthening. Femoral lengthening was achieved using double corticotomy. The distraction period lasted 63 ± 3 days, with a length gain of 6.5 ± 0.5 cm. Ultrasound (AVISUS Hitachi, Japan) of the bone regenerate was performed at days 7, 20, 30, and 60 after the start of distraction and then once monthly during fixation. Statistical analysis was conducted using variation statistics for small samples. Significance was set at p ≤ 0.05; differences were tested using the Wilcoxon W-test.

RESULTS: During distraction, the number and size of linear echodense fragments in the intermediate zone of the regenerate increased. A growth zone in the central part of the regenerate was preserved in the form of a weakly mineralized layer with acoustic density of 65–85 AU to maintain distraction. Ultrasound by the end of the distraction period revealed narrowing of the echopositive zone of the regenerate, a decrease in connective tissue layers, and filling of the intermediate zone. At the beginning of the fixation period, the acoustic density of the fragments and regenerate reached 198 ± 9.0 and 158 ± 4.5 AU (p ≤ 0.05 vs. baseline), respectively, due to active mineralization, indicating the possibility of moderate physical loading of the limb and proceeding with surgery of the contralateral tibia.

CONCLUSION: The ultrasound criteria of reparative osteogenesis in the femoral distraction regenerate that allow for the initiation of contralateral tibial lengthening in patients aged 9–12 years with achondroplasia include the following: the formation of characteristic zonal structure of the regenerate throughout the distraction period; absence of focal lesions in all visualized regenerate zones; a 50% increase in acoustic density of the regenerate by the end of distraction vs. the baseline; and a decrease in the echopositive zone width by the beginning of fixation to 45%–48% of the achieved lengthening.

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About the authors

Tatyana I. Menshchikova

National Ilizarov Medical Research Center for Traumatology and Orthopedics

Author for correspondence.
Email: tat-mench@mail.ru
ORCID iD: 0000-0002-5244-7539
SPIN-code: 2820-9120

Dr. Sci. (Biology)

Russian Federation, Kurgan

Anna M. Aranovich

National Ilizarov Medical Research Center for Traumatology and Orthopedics

Email: aranovich_anna@mail.ru
ORCID iD: 0000-0002-7806-7083
SPIN-code: 7277-6339

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Kurgan

References

  1. Pauli RM. Achondroplasia: a comprehensive clinical review. Orphanet J Rare Dis. 2019;14(1):1. doi: 10.1186/s13023-018-0972-6 EDN: UDCAAA
  2. Harris R, Patton JT. Achondroplasia and thanatophoric dwarfism in the newborn. Clin Genet. 1971;2(2):61–72. doi: 10.1111/j.1399-0004.1971.tb00257.x
  3. Horton WA, Hall JG, Hecht JT. Achondroplasia. Lancet. 2007;370(9582):162–172. doi: 10.1016/S0140-6736(07)61090-3
  4. 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 EDN: JCDLDK
  5. Murton MC, Drane ELA, Goff-Leggett DM, et al. Burden and treatment of achondroplasia: a systematic literature review. Adv Ther. 2023;40(9):3639–3680. doi: 10.1007/s12325-023-02549-3 EDN: DRPJTM
  6. 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 EDN: PVUYPN
  7. Legare JM. Achondroplasia. In: Adam MP, Feldman J, Mirzaa GM, et al., eds. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025.
  8. Tofts L, Ireland P, Tate T, et al. Consensus guidelines for the use of vosoritide in children with achondroplasia in Australia. Children. 2024;11(7):789. doi: 10.3390/children11070789 EDN: HABXJM
  9. Biosse Duplan M, Dambroise E, Estibals V, et al. An Fgfr3-activating mutation in immature murine osteoblasts affects the appendicular and craniofacial skeleton. Dis Model Mech. 2021;14(4):dmm048272. doi: 10.1242/dmm.048272 EDN: QAUISF
  10. Shirley ED, Ain MC. Achondroplasia: manifestations and treatment. J Am Acad Orthop Surg. 2009;17(4):231–241. doi: 10.5435/00124635-200904000-00004
  11. 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 EDN: ETOWJP
  12. Hoover-Fong J, Scott CI, Jones MC. Health supervision for people with achondroplasia. Pediatrics. 2020;145(6):e20201010. doi: 10.1542/peds.2020-1010
  13. Pfeiffer KM, Brod M, Smith A, et al. Assessing physical symptoms, daily functioning, and well-being in children with achondroplasia. Am J Med Genet A. 2021;185(1):33–45. doi: 10.1002/ajmg.a.61903 EDN: JZBTGI
  14. Sommer R, Blömeke J, Dabs M, et al. An ICF-CY-based approach to assessing self- and observer-reported functioning in young persons with achondroplasia-development of the pilot version of the Achondroplasia Personal Life Experience Scale (APLES). Disabil Rehabil. 2017;39(24):2499–2503. doi: 10.1080/09638288.2016.1226969
  15. Unger S, Bonafé L, Gouze E. Current care and investigational therapies in achondroplasia. Curr Osteoporos Rep. 2017;15(2):53–60. doi: 10.1007/s11914-017-0347-2 EDN: CDHGLC
  16. Popkov AV. Akhondroplaziya: rukovodstvo dlya vrachei. Popkov AV, Shevtsov VI, eds. Moscow: Meditsina; 2001. 352 p. (In Russ.)
  17. 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. doi: 10.7507/1002-1892.202210072
  18. Chilbule SK, Dutt V, Madhuri V. Limb lengthening in achondroplasia. Indian J Orthop. 2016;50(4):397–405. doi: 10.4103/0019-5413.185604 EDN: DQXUGB
  19. Shevtsov VI, Leonchuk SS. Stimulation of distraction osteogenesis during limb lengthening: our concept. Traumatology and Orthopedics of Russia. 2021;27(1):75–85. doi: 10.21823/2311-2905-2021-27-1-75-85 EDN: ZALXJW
  20. 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 EDN: YBFUZO
  21. Novikov KI, Klintsov EV, Klimov OV, et al. Failed distractional bone regeneration as a complication of distraction osteosynthesis: risk factors, preventive diagnosis, treatment. Orthopaedic Genius. 2024;30(1):134–141. doi: 10.18019/1028-4427-2024-30-1-134-141 EDN: EZRBEC
  22. Aranovich AM, Stogov MV, Tushina NV, et al. C-reactive protein as a prognostic marker of distraction osteogenesis disorders. Preliminary results. Orthopaedic Genius. 2020;26(3):382–384. doi: 10.18019/1028-4427-2020-26-3-382-384 EDN: COTQQA
  23. Aranovich AM, Stogov MV, Kireeva EF, et al. Prediction and control of the distraction osteogenesis course. Analytical review. Orthopaedic Genius. 2019;25(3):400–406. doi: 10.18019/1028-4427-2019-25-3-400-406 EDN: VZHOMN
  24. Bayram S, Yıldırım AM, Eralp L, et al. The relationship between limb lengthening rate and callus quality in patients with achondroplasia. Indian J Orthop. 2022;56(11):1891–1896. doi: 10.1007/s43465-022-00694-5 EDN: TIYFKQ
  25. Puseva ME, Lebedinskii VI, Mikhailov IN, et al. Complex characteristic of forearm distraction regenerated bone experimentally. Orthopaedic Genius. 2013;(4):84–90. EDN: RPWODD
  26. Maffulli N, Hughes T, Fixsen JA. Ultrasonographic monitoring of limb lengthening. J Bone Joint Surg Br. 1992;74(1):130–132. doi: 10.1302/0301-620X.74B1.1732241
  27. Ciminari R, Galletti S, Pelotti P, Donzelly O. Ultrasound-radiographic correlations of the various phases of bone regeneration in secondary limb lengthening: an investigation protocol. Giornale Ital Ortoped Traumatol. 1991;17(3):141–142. (In Italian.)
  28. Hupperts R, Pfeil J, Kaps HP. Ultrasound follow-up of bone lengthening osteotomy. Z Orthop Ihre Grenzgeb. 1990;128(1):90–95. (In German.) doi: 10.1055/s-2008-1039867
  29. Menshchikova TI, Aranovich AM. Tibial lengthening in achondroplasia patients aged 6–9 years as the first stage of growth correction. Orthopaedic Genius. 2021;27(3):366–371. doi: 10.18019/1028-4427-2021-27-3-366-371 EDN: RQVSDS
  30. Luneva SN, Menshchikova TI, Aranovich AM. Features of the reparative osteogenesis of the distraction of the tibial regenerate and osteotropic growth factors in patients with achondroplasia at the age of 9–12 years. Pediatric Traumatology Orthopaedics and Reconstructive Surgery. 2022;10(3):223–234. doi: 10.17816/PTORS108618 EDN: WHEOFF
  31. Aborin SA, Gorevanov EA, Popkov DA, et al. Zonal change of the optical density of regenerated bone and femur in lengthening of congenitally shortened femur using the technique of bifocal distraction osteosynthesis. Orthopaedic Genius. 2003;(1):68–71. EDN: PFTDNJ
  32. Novikov KI, Klimov OV, Novikova OS. The roentgenologic characteristic features of distraction regenerated bone formation for the monofocal and bifocal variant of femoral lengthening in patients with achondroplasia. Orthopaedic Genius. 2007;(4):16–20. EDN: JHKHEH
  33. Shevtsov VI, Bakhlykov YN. Morphological characteristics of the “growth zone” of tibial distraction regenerate in experiment. Bulletin of Tyumen State University. 2004;(3):123–127.
  34. Popkov AV, Popkov DA, Irianov YM, et al. Stimulation of bone tissue reparative regeneration for shaft fractures (an experimental study). International Journal of Applied and Fundamental Research. 2014;(9-1):82–88. (In Russ.)
  35. Irianov YM, Gorbach EN, Petrovskaya NV. Quantitative assessment of the periosteal blood supply of canine tibial diaphysis for leg lengthening using the method of distraction osteosynthesis. Morphological Newsletter. 2007;(1-2):57–60. EDN: MJCMKJ
  36. Larionov AA, Kochetkov YS, Desiatnichenko KS, et al. Experimental grounds for stimulation of formation and reorganization of distraction regenerated bone. Orthopaedic Genius. 2000;(1). (In Russ.)
  37. Shevtsov VI, Irianov YM, Irianova TY. The effect of distraction on the shape-forming processes of regenerating bone tissue. Orthopaedic Genius. 2005;(4):77–80. (In Russ.) EDN: LDGXNN
  38. Novikov KI, Komarova ES, Kolesnikov SV, et al. Evolution of tactical approaches to eliminating limb length discrepancy. Orthopaedic Genius. 2024;30(2):301–308. doi: 10.18019/1028-4427-2024-30-2-301-308 EDN: RPAGRV

Supplementary files

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2. Fig. 1. Sequence of limb segment lengthening in patients with achondroplasia aged 9–12 years: a — at stage I, simultaneous lengthening of both legs is performed; b — at stage II, the femur is lengthened, and then the contralateral leg is lengthened.

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3. Fig. 2. Sonogram of the distraction regenerate of the right femur of patient B., 8 years old. Diagnosis: achondroplasia, condition after lengthening of both tibias. Stage II. The period of femur distraction is 7 days, the amount of lengthening is 7 mm. Fragments are 0.9–1.1 mm in size; the width of the visualized zone of the regenerate is 7 mm, the depth of ultrasound penetration is 24 mm; the acoustic density of the regenerate is 85 conventional units.

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4. Fig. 3. The same patient. Stage II. The period of femur distraction is 20 days, the amount of lengthening is 20 mm. Fragments are 1.4–2.2 mm in size; the width of the visualized zone of the regenerate is 20.2 mm, the depth of ultrasound penetration is 23 mm; the acoustic density of the fragments is 118–120 conventional units. The acoustic density of the regenerate is 101 conventional units.

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5. Fig. 4. The same patient. Stage II. The femur distraction period is 30 days, the elongation value is 30 mm. Fragments are 3.4–4.1 mm in size; the width of the visualized regenerate zone is 30.5 mm, the ultrasound penetration depth is 17.5 mm; the acoustic density of the fragments is 140–158 conventional units; the acoustic density of the regenerate is 111 conventional units.

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6. Fig. 5. The same patient. Stage II. End of the femur distraction period (60 days), elongation value — 6.0 cm. Fragments measuring 7.4–8.2 mm; width of the visualized regenerate zone — 30.5 mm, ultrasound penetration depth — 17.5 mm; acoustic density of fragments — 162–171 conventional units; acoustic density of regenerate — 135 conventional units.

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7. Fig. 6. Sonogram of the distraction regenerate of the right femur of patient K., 12 years old. Stage II. The femur fixation period is 30 days. Fragments are up to 8.7 mm in size; the width of the visualized regenerate zone is 20.7–23.7 mm, the ultrasound penetration depth is 10 mm; Acoustic density of fragments — 198 conventional units; acoustic density of regenerate — 136 conventional units.

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8. Fig. 7. Sonogram of the distraction regenerate of the right femur of patient K., 12 years old. Stage II. Femoral fixation period 60 days. Acoustic density of the forming cortical plate — 185 conventional units; the width of the visualized regenerate zone is 15 mm, the depth of ultrasound penetration is 8.5 mm.

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