Overview
Lower extremity bone stress injury (BSI) is a common overuse injury in athletes and typically requires 4-12 weeks rehabilitation time, provided the injury does not require surgery. Current BSI treatment strategies include cessation of load-bearing sporting activities, consideration for crutches and/or immobilization, pain management, and a gradual return to activities until symptoms resolve. Premature return to sport can result in risk of complications and reinjury of the healing BSI. Moreover, our prior work reported that 1/3 of women with a tibial BSI will sustain at least one additional BSI within one year, indicating that current return to sport guidelines may be inadequate. However, there are no gold standard or validated clinical, functional or imaging outcomes that are consistently used to assess BSI healing and guide return to sport. In this prospective observational study, the investigators will enroll male and female athletes with a diagnosed BSI. The investigators will utilize diagnostic imaging, blood samples, and questionnaires to identify primary and secondary outcomes for assessing BSI healing in runners. Our long-term goal is to identify whether biomarkers, health and lifestyle factors, and training patterns associated with future BSI have the potential to inform and improve BSI treatment.
Description
Bone stress injuries (BSIs) result from the accumulation of repetitive skeletal loading that exceeds the bone's capacity for repair. Although magnetic resonance imaging (MRI) is commonly used to diagnose and grade BSIs, there is no accepted standard for determining when an injury has healed sufficiently for an athlete to resume running or unrestricted sport. Previous studies have used measures such as pain-free hopping, pain-free running, completion of a return-to-run program, medical clearance, clinical examination findings, and changes on MRI. However, these measures have not been applied consistently, and their relative time courses and relationships with subsequent injury are not well understood.
This multisite, prospective observational cohort study follows athletes for one year after an MRI-confirmed lower-extremity BSI. The study does not assign an investigational treatment. Participants continue to receive clinical care for their injury and are provided with a standardized, progressive return-to-run framework developed with clinicians and physical therapists experienced in treating runners with BSIs. The primary purpose of the study is to characterize the time course and variability of candidate clinical, functional, and imaging indicators of BSI recovery. Using the date of the diagnostic MRI as a common reference point will allow recovery milestones to be evaluated consistently across participants and injury locations.
Participants complete an initial study visit shortly after diagnosis and return for follow-up assessments during the early recovery period. The timing of follow-up visits differs for femoral-neck injuries because these injuries generally require a longer period of recovery. Study assessments include serial symptom and functional surveys, standardized clinical severity assessments, and repeat MRI of the injured site. Participants report their progression through the return-to-run program in a training diary and complete brief electronic surveys during recovery. After completion of the return-to-run program, participants are contacted monthly through the one-year follow-up to identify any clinically diagnosed subsequent BSI.
Additional assessments are used to explore biological, behavioral, and mechanical factors that may be associated with recovery or subsequent injury. A fasting blood sample collected at baseline is used to measure clinical markers related to bone health and bone metabolism and to conduct exploratory serum protein analyses. Validated questionnaires assess eating attitudes, risk factors for low energy availability, sleep, symptoms of depression and anxiety, and body appreciation. After recovery, a single-leg hopping assessment is used to estimate lower-extremity movement characteristics and loading of the injured and uninjured limbs. Participants who already use a compatible Garmin smartwatch may optionally authorize collection of activity, running, heart-rate, and sleep data.
Analyses will first describe the distribution, timing, and variability of the candidate recovery indicators for the overall cohort and by injury location and sex. Exploratory analyses will evaluate whether recovery indicators, baseline biomarkers, questionnaire measures, training patterns, or movement characteristics are associated with a clinically diagnosed subsequent BSI during the one-year follow-up. Return-to-run adherence will also be described, and sensitivity analyses will examine whether results differ after accounting for adherence. Because the study is intended to characterize recovery and generate estimates for future research rather than test the efficacy of an intervention, enrollment is based on recruitment feasibility rather than a formal hypothesis-testing power calculation.
Eligibility
Inclusion Criteria:
- Diagnosed BSI of the tibia, metatarsal two, three, or four, femoral neck or femoral shaft by MRI, grade two or higher on the Fredericson grading scale7
- Age 16-35 years
- Body Mass Index 17.5-30 kg/m2
- Self-reported minimum of three hours per week of endurance exercise that includes running at least fifteen miles per week during three months prior to injury
- Study enrollment within three weeks of MRI
Exclusion Criteria:
- Self-reported history of endocrine disorder that impacts bone health (e.g., diabetes, hyperthyroidism, or primary hyperparathyroidism)
- Self-reported history of bone disease or other bone disorder (e.g., osteopetrosis, osteogenesis imperfecta, osteomalacia, rickets, Paget's disease, or multiple myeloma)
- Use of thyroid hormone replacement at suppressive doses for a history of thyroid cancer
- History of chemotherapy or radiation treatment for cancer in the past 5 years
- Currently taking or have taken oral glucocorticoids for greater than three months (e.g., prednisone or hydrocortisone)
- Current or prior use of osteoporosis medications (e.g., bisphosphonates, teriparatide)
- Current use of anti-seizure medications (e.g. Phenytoin (Dilantin), Carbamazepine (Tegretol), Phenobarbitol)
- Currently pregnant
- Currently lactating
- Contraindications to MRI
- BSI is planned to be managed operatively
- Tibial BSI on the anterior aspect of the bone
- Participants that are non-English speaking


