Biomarker Targets for Stress Fracture Surveillance and Intervention in Military Personnel: A Scoping Review

Musculoskeletal injuries (MSKIs) are the most common cause of medical discharge from military service, with most directly attributable to physical training and arduous occupational tasks. MSKIs affect (but not limited to) muscles, bones, joints, tendons, ligaments, and/or cartilage. A high proportion of military MSKIs are overuse injuries occurring in the lower limbs. Because of the impact of MSKIs on personnel and the organization, it is imperative that methods of identifying at risk personnel are developed, refined, and implemented. Biomarkers are used within clinical and research settings as indicators or surrogate measures of damage to target tissue. Furthermore, biomarkers can offer an objective insight into MSKIs risk rather relying on self-report methods, which are often reported too late. Numerous risk factors for MSKIs have been identified, several of which represent modifiable health behaviors and therefore may provide targets for intervention. The potential effects of these behaviors on biomarkers may provide a means of identifying those at increased risk or susceptibility to MSKIs, informing early intervention. This review aimed to identify specific and sensitive biomarkers of bone and soft-tissue damage/injury and examines potential associations between biomarker and modifiable health behaviors.

A scoping review was undertaken to assess published evidence of current biomarkers used to assess tissue damage, and potential mechanisms by which changes in health behaviors may ameliorate bone/soft-tissue injuries, within military populations. Following the PRISMA ScR guidelines, relevant literature was identified in peer-reviewed journals that met the following criteria: (1) healthy adults aged between 16 and 60 years with/without work-related MSKIs/disorders; (2) population included military personnel or athletes; (3) studies reporting associations between biomarker of bone or soft-tissue health/injury and presence of bone/soft-tissue injury or medical imaging; (4) study is written in English (Abstract or Structured Summary).

A total of 2,973 articles were identified from the initial database search and, after removing duplicates, 2,291 studies were screened. Among these, 33 publications met the eligibility criteria and included in analyses. The review encompasses studies published from 2003 onwards. Most studies were observational prospective cohort studies. The most prevalent biomarker associated with variables of MSKIs, particularly stress fracture risk, was vitamin D (or substrate of vitamin D), which was analyzed in 22 of the identified studies.

This review highlights a range of potential biomarkers for use in military populations, however, it also demonstrates that these biomarkers are often assessed within sub-optimal study designs and often only in relation to stress fracture occurrence. This could have contributed to limited significant associations between biomarker concentration and MSKIs outcomes. The most commonly used biomarker of bone health was vitamin D. The review highlights the importance of contextual factors such as seasonality, sleep status, training load, and smoking status, which can influence biomarker concentrations. Thus, the importance of standardizing biomarker sample collection methods and analyses, as well as measuring other factors affecting biomarker concentrations is discussed. Some studies directly assessed associations between biomarker concentrations and MSKIs outcomes, these were often not the primary purpose of the studies reviewed.