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Gomez-Barrena, EnriqueAuthor

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May 13, 2024
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Association between Bone Turnover Markers and Fracture Healing in Long Bone Non-Union: A Systematic Review

Publicated to:Journal of Clinical Medicine. 13 (8): - 2024-01-01 13(8), DOI: 10.3390/jcm13082333

Authors: Perut, Francesca; Roncuzzi, Laura; Gomez-Barrena, Enrique; Baldini, Nicola

Affiliations

Hosp Univ La Paz, IdiPAZ, Dept Orthoped Surg & Traumatol, Madrid 28046, Spain - Author
IRCCS Ist Ortoped Rizzoli, Biomed Sci & Technol & Nanobiotechnol Lab, I-40136 Bologna, Italy - Author
Univ Autonoma Madrid, Fac Med, Madrid 28029, Spain - Author
Univ Bologna, Dept Biomed & Neuromotor Sci, I-40136 Bologna, Italy - Author

Abstract

Background: Fracture healing is a very complex and well-orchestrated regenerative process involving many cell types and molecular pathways. Despite the high efficiency of this process, unsatisfying healing outcomes, such as non-union, occur for approximately 5-10% of long bone fractures. Although there is an obvious need to identify markers to monitor the healing process and to predict a potential failure in callus formation to heal the fracture, circulating bone turnover markers' (BTMs) utility as biomarkers in association with radiographic and clinical examination still lacks evidence so far. Methods: A systematic review on the association between BTMs changes and fracture healing in long bone non-union was performed following PRISMA guidelines. The research papers were identified via the PubMed, Cochrane, Cinahl, Web of Science, Scopus, and Embase databases. Studies in which the failure of fracture healing was associated with osteoporosis or genetic disorders were not included. Results: A total of 172 studies were collected and, given the inclusion criteria, 14 manuscripts were included in this review. Changes in circulating BTMs levels were detected during the healing process and across groups (healed vs. non-union patients and healthy vs. patients with non-union). However, we found high heterogeneity in patients' characteristics (fracture site, gender, and age) and in sample scheduling, which made it impossible to perform a meta-analysis. Conclusions: Clinical findings and radiographic features remain the two important components of non-union diagnosis so far. We suggest improving blood sample standardization and clinical data collection in future research to lay the foundations for the effective use of BTMs as tools for diagnosing non-union.

Keywords

BiomarkersBone turnover markersChallengesCtxDelayed unionFracture healingManagementNon-unionOsteocalcinPrognosticRisk

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Journal of Clinical Medicine due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2024 there are still no calculated indicators, but in 2023, it was in position 59/329, thus managing to position itself as a Q1 (Primer Cuartil), in the category Medicine, General & Internal.

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-18:

  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 16 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

    It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

    • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

    Leadership analysis of institutional authors

    This work has been carried out with international collaboration, specifically with researchers from: Italy.