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

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Abstract

BACKGROUND: Despite studies on various issues of distraction osteosynthesis, many morphological aspects of this problem are still insufficiently studied and remained debatable.

AIM: To determine the features of the reparative activity of the regenerate and analyze the content of some osteotropic growth factors in children with achondroplasia.

MATERIALS AND METHODS: Growth factors were determined in serum and blood plasma using equipment from Thermo Fisher (USA). Factor concentrations were determined using ELISA kits: PDGF-AA (R&D Systems, USA), PDGF-BB (R&D Systems, USA), IGF-1 (Immunodiagnostic systems, USA), IGF-2 (Mediagnost, Germany), TGF-β1 (eBioscience, USA), and TGF-β2 (eBioscience, USA). The structural state of the tibial regenerate was determined using by ultrasonography (HITACHI, Japan). Patients with achondroplasia aged 9–12 years (n = 32) were examined at the beginning of distraction (10–20 days), in the middle of distraction (21–40 days), and at the end of distraction (41–63 days).

RESULTS: The ultrasound method showed the dynamic formation of the structural state of the distraction regenerate at the studied stages of distraction. At the same stages of distraction, the concentration of osteotropic growth factors was assessed.

CONCLUSIONS: The serum content of osteotropic growth factors in the blood of children with achondroplasia differs from age-normative values. Growth factors that play a key role in osteogenesis, IGF-1, BMP-4, TGF-β1, and TGF-β2 were reduced, whereas the expressions of IGF-2 and BMP-6 were compensatory increased. At the end of the distraction period, the values of all studied growth factors exceeded the initial values, regardless of their preoperative values and their dynamics at the stages of distraction. The assessment of the dynamics of the concentration of osteotropic growth factors in the blood of patients with achondroplasia during the distraction period and natural growth period indicate the presence of a commonality of processes during the distraction period and prenatal growth of the tibia. Our comprehensive ultrasound study of the structural state of the distraction regenerate of the tibia and biochemical studies of growth factors in the blood of patients with achondroplasia at the age of 9–12 years made it possible to identify the features of reparative osteogenesis of the distraction regenerate of the tibia and the physiological effect of osteotropic growth factors from the viewpoint of the process of reparative regeneration.

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About the authors

Svetlana N. Lyneva

Ilizarov National Medical Research Centre for Traumatology and Orthopedics

Author for correspondence.
Email: luneva_s@mail.ru
ORCID iD: 0000-0002-0578-1964
SPIN-code: 9572-2655
Scopus Author ID: 26024323300
ResearcherId: R-4032-2018

PhD, Dr. Sci. (Biol.), Professor

Russian Federation, Kurgan

Tatyana I. Menschchikova

Ilizarov National Medical Research Centre for Traumatology and Orthopedics

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

PhD, Dr. Sci. (Biol.)

Russian Federation, Kurgan

Anna M. Aranovich

Ilizarov National Medical Research Centre for Traumatology and Orthopedics

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

MD, PhD, Dr. Sci. (Med.), Professor

Russian Federation, Kurgan

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Supplementary files

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2. Fig. 1. Sonograms of the regenerates of the tibia of patient Z., 12 years old. Achondroplasia, short stature. The distraction period was 9 days, bilocal elongation, and the total elongation was 1.78 cm: a, diagram of the regenerate structure; b, width of the echopositive zone of the proximal regenerate of 0.90 cm, the acoustic density of the regenerate was 95 c.u., and the acoustic density of the structures was 101 c.u.; c, width of the echopositive zone of the distal regenerate of 0.80 cm. The acoustic density of the regenerate was 89 c.u., and the acoustic density of the structures was 101 c.u. c.u., conditional units

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3. Fig. 2. Sonograms of the regenerates of the tibia of patient Z., 12 years old. Achondroplasia, short stature. The distraction period was 20 days, bilocal elongation, and the total elongation was 4.0 cm: a, diagram of the regenerate structure; b, the width of the echopositive zone of the proximal regenerate was 2.2 cm, the acoustic density of the regenerate was 110 c.u., and the acoustic density of the bone trabeculae was 147 c.u.; c, the width of the echopositive zone of the distal regenerate was 1.80 cm, the acoustic density of the regenerate was 93.2 c.u., and the acoustic density of the bone trabeculae was 67 c.u. c.u., conditional units

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4. Fig. 3. Sonograms of the regenerates of the tibia of patient I., 10 years old. Achondroplasia, short stature. The distraction period was 38 days, bilocal elongation, and the total elongation was 7.0 cm: a, diagram of the regenerate structure; b, width of the echopositive zone of the proximal regenerate of 5.0 cm, the acoustic density of the regenerate was 118 c.u., and the acoustic density of the bone trabeculae was 150 c.u.; c, the width of the echopositive zone of the distal regenerate was 1.80 cm, the acoustic density of the regenerate was 112 c.u, and the acoustic density of the bone trabeculae was 145 c.u. c.u., conditional units

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5. Fig. 4. Sonograms of the regenerates of the tibia of patient I., 10 years old. Achondroplasia, short stature. The distraction period was 55 days, bilocal elongation, and the total elongation was 9.0 cm: a, diagram of the regenerate structure; b, the width of the echopositive zone of the proximal regenerate was 30 cm, the acoustic density of the regenerate was 119 c.u., and the acoustic density of the bone trabeculae was 182 c.u.; c, the distal regenerate is visualized in the form of a ladle, and the acoustic density of the regenerate was 128 c.u. c.u., conditional units

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6. Fig. 5. Sonogram of the distraction regenerate of the tibia of patient I., 10 years old. In the duplex scanning mode, vascular branches of various diameters from 0.5 mm to 2.5 mm are developed. Peripheral indices; PI = 1.10, RI = 0.67; and PI = 1.52, RI = 0.75

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7. Fig. 6. Sonogram of the distraction regenerate of the tibia of patient V., 10 years old. Achondroplasia, short stature. Bilocal elongation. The total elongation was 9 cm (proximal regenerate, 5 cm; distal regenerate, 4 cm). The reparative activity was reduced, and hypoechoic cyst-like foci of various sizes are visualized in the intermediary zone

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Copyright (c) 2022 Lyneva S.N., Menschchikova T.I., Aranovich A.M.

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