Molecular foundations of the etiology and pathogenesis of Legg-Calve-Perthes disease and prospects for targeted therapy: A literature review

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Abstract

BACKGROUND: The etiology and pathogenesis of the development of Legg–Calve–Perthes disease, despite intensive research, remains not fully understood. Most studies have concluded about the multifactorial genesis of the development of hip osteochondropathy. Moreover, a complete understanding of all elements of pathogenesis leading to the manifestation and the progressive development of aseptic necrosis make it possible to develop targeted antiresorptive therapy. At present, several studies have investigated impaired functioning of signaling pathways that influence bone homeostasis during the development of Legg–Calve–Perthes disease. In addition, impaired metabolism in avascular necrosis is characterized by significant complexity and heterogeneity, which is based on aseptic inflammation associated with ischemic stress. Concepts of antiresorptive therapy were developed based on the results of studies on the pathogenesis of Legg–Calve–Perthes disease. Nevertheless, these treatment algorithms have not achieved wide practical application and require further investigation.

AIM: This study aimed to conduct a literary analysis of the molecular basis of the etiology and pathogenesis of Legg–Calve–Perthes disease and assess the prospects of therapy aimed at correcting bone homeostasis disorders.

MATERIALS AND METHODS: Data sources were PubMed, Medline, Scopus, Web of Science, and RSCI databases, without language restrictions.

RESULTS: The relationship between ischemic stress and the induction of a cytokine cascade with a predominance of the biological actions of proinflammatory cytokines, with parallel activation of intracellular regulatory networks that determine osteoresorptive processes, including due to pyroptosis, is shown. Data on the possibility of various variants of targeted antiresorptive therapy with the use of genetically engineered drugs are presented.

CONCLUSIONS: The pathogenesis of Legg–Calve–Perthes disease is characterized by significant genetic heterogeneity with the induction of various mediators of inflammation, angiogenesis, and osteogenesis, depending on the disease stage. Investigating features of impaired bone homeostasis regulation in the case of Legg–Calve–Perthes disease at the molecular and cellular level opens up opportunities for the development and clinical application of personalized therapy.

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About the authors

Nikita A. Shabaldin

Kemerovo State Medical University

Author for correspondence.
Email: shabaldin.nk@yandex.ru
ORCID iD: 0000-0001-8628-5649
SPIN-code: 6283-2581
Scopus Author ID: 57209570350

MD, PhD, Cand. Sci. (Med.), Assistant Professor

Russian Federation, Kemerovo

Andrei V. Shabaldin

Kemerovo State Medical University

Email: weit2007@yandex.ru
ORCID iD: 0000-0002-8785-7896
SPIN-code: 5281-0065

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

Russian Federation, Kemerovo

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