How to heal what we cannot see? Medicine faces illnesses, injuries or ailments on a daily basis which cannot be directly observed. In all those cases, it’s necessary to find the tools to learn about the ailment degree, and to perform the proper follow up of the injury recovery process itself since it is vital to know in which stage we are, and what we have to do not to relapse. Currently, we have two main alternatives. On one side, we have all the technologies for medical imaging which can show at bare sight what is going on within our bodies. On the other side, there are biomarkers.

Biological Markers

A biomarker is a biological molecule whose presence or absence (as well as its proportion) could serve as an indicator of physiopathology or of a recovery process. At a sports medicine level, the usual thing is these markers show the degree of an injury as well as the pace of the recovery process which should be regularly monitored. For example, the state of a damaged tissue in a tendinopathy. Biomarkers are agents involved in the occurrence of an injury and in its recovery process as well. The correct identification of the cells that take part in these processes is vital to improve current clinical interventions.

For example, in pathogenesis of tendinopathy its common to have an inflammatory response which will cause, among other things, interleukin concentration increase in blood, a type of cytokine or tiny proteins directly related to that inflammation (proteins that can also be measured as growth factors such as tumour necrosis (TNF-α) which stimulates the acute stage of inflammation).  Besides, after the damage there will appear stem cells that will work on the reconstruction of the tissue and at the same time, they will take part in healing. Measuring any of those molecules will serve as an indicator of the state of such injury.

Besides, with the development of omics and its multidisciplinary study of the interaction among genes, proteins or metabolites, bioinformatics analysis has also permitted the identification of potentially relevant genes in illnesses and ailments of any kind. In the case of tendinopathies, currently, a small amount of this type of molecules involved in the regulation of an early phase are known. However, there are studies [1] which start to discover possible candidates for this type of processes, such as MACROD1, a gene thought to be important in the appearance and development of tendinopathy. Getting to identify candidate genes with the aim of an early diagnosis and treatment using these technologies is a revolution in the biomarkers field.

An Image Is Worth A Thousand Data Pieces 

Biomarkers have proven to have a higher efficiency when detecting the tendinopathy state, but they are not useful when the professional’s interest is to see the recovery process as such. As it is a dynamic aspect of injury, there is the need for techniques that facilitate a proper follow up of a changing period as articulation healing. The tools that have proven the best outcomes are the medical imaging ones.

Magnetic resonance (MRI) or ultrasounds allow you to see the internal architecture of a tendon or muscle. This allows professionals to observe, for example, fibre alignment or any structural change caused by the injury, and this ultimately facilitates diagnosis of any ailments as well as monitoring the efficiency of a treatment and warning of possible risks during recovery. 

However, depending on our needs, the use of these traditional imaging techniques could be limited. A clear example of this is found in the study published about arthralgia (AIA) or joint pain in the Journal of Clinical Medicine [2] in February 2022.  This type of ailment provokes joint pain, myalgia, or joint stiffness, and in previous studies echography (ultrasounds) were used to try to find a relationship between the image and the AIA symptoms. The inconsistency arising from relating the data made researchers explore a new type of a more sophisticated imaging technique which achieved better outcomes. 

MR elastography is a novel imaging technique used to measure tendon stiffness using shear waves in a focused ultrasound. These waves travel slowly and attenuate when they make contact with the tissues.That variation in their propagation speed depending on the tissue they go through allow to obtain its correlation with tissue elasticity. This allows us to know, in tendinopathy cases, if stiffness of the damaged tendon has varied: the greater the speed, the less elastic the tendons. 

There is still a long way ahead in the monitoring of the different phases of an injury. Identifying biomarkers that can offer true, precise and reliable information and which can also adapt to changing circumstances of a recovery process should be the main objective of the investigations in the coming years. Only in this way the efficiency of treatments will continue to grow. And with it, athletes’ and society’s health will improve too.

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 952981.

Bibliography:

[1] Zhu Yx, Huang Jq, Ming Yy, Zhuang Z., Xia H. (2021). Screening of key biomarkers of tendinopathy based on bioinformatics and machine learning algorithms. PLoS ONE 16(10): e0259475.

[2] Martinez, J.A., Taljanovic, M.S., Nuncio Zuniga, A.A., Wertheim, B.C., Roe, D.J., Ehsani, S., Jiralerspong, S., Segar, J., Chalasani, P. (2022). Feasibility Trial to Evaluate Tendon Stiffness Obtained from Shear Wave Elastography Imaging as a Biomarker of Aromatase Inhibitor-Induced Arthralgias. J. Clin. Med. 11, 1067.