Comparison of Ultrasound and X-ray as Screening Tests for Diagnosis of Lower Extremity Stress Fracture.
Comparison of Ultrasound and X-ray as Screening Tests for Diagnosis of Lower Extremity Stress Fracture.
Hypothesis: Diagnostic ultrasound is an appropriate screening test for acute stress fracture
 in the lower extremity and is superior to x-ray.

 Primary Aims: To determine if diagnostic ultrasound is an appropriate screening test with
 high sensitivity and at least moderate specificity for the identification of acute stress
 fractures of the lower extremity.

 Methods: In this double-blind, prospective clinical study, subjects (age 14 years and up)
 suspected to have an acute stress fracture of the lower extremity will be recruited from the
 Sports Medicine clinic at the University of Virginia Health System in the Department of
 Physical Medicine & Rehabilitation. Subjects will undergo the traditional diagnostic
 algorithm including screening x-ray as part of standard care. Subjects will then undergo a
 confirmatory MRI of the region of concern if the initial x-ray was negative as part of
 standard care. Any subject who does not require an MRI for clinical purposes (initial X-ray
 was positive) will have one completed for research purposes. All subjects will also undergo
 diagnostic ultrasound performed by a separate, blinded physician competent in diagnostic
 ultrasound for research purposes. A statistician in the Department of Public Health at the
 University of Virginia will be performing statistical analysis during data analysis. Findings
 will be analyzed using a McNemar chi-square test to evaluate for significant differences
 between the sensitivities of ultrasound and x-ray.
Primary aims: To determine if diagnostic ultrasound is an appropriate screening test (high
 sensitivity and at least moderate specificity) and non-inferior to x-ray for diagnosis of
 acute stress fracture of the lower extremity.

 Secondary Aims: To determine what grade(s) of acute stress fracture that x-ray and ultrasound
 are capable of detecting reliably and accurately.

 Population: Subjects will be recruited from the Sports Medicine clinic at the University of
 Virginia Health System in the Department of Physical Medicine and Rehabilitation. Subjects
 will have suspected acute stress fracture of the lower extremity and will be age 14 years and
 older. Anatomic locations included in this study are as follows: all bones of the foot and
 ankle, tibia, fibula, and femoral shaft. Patients with suspected stress fracture of the
 femoral neck will be excluded due to the difficulty of appropriate ultrasound evaluation
 secondary to depth as well as the potential for significant morbidity if not diagnosed
 properly. We estimate that the Sports Medicine clinic diagnoses approximately 12 acute stress
 fractures per month per physician amongst the three physician's clinics involved in this
 study. Therefore, our anticipated number of subjects over a 6 month period will be at least
 216 patients.

 Design: In this double-blind , prospective clinical study, subjects suspected to have an
 acute stress fracture of the lower extremity will be recruited from Sports Medicine Clinic
 (conducted by two physicians boarded in Physical Medicine and Rehabilitation and one
 physician board in Family Medicine and all boarded in Sports Medicine). When patients present
 to one of three physicians in Sports Medicine Clinic with a suspected acute stress fracture
 of the lower extremity, they will be offered the opportunity to enroll. Subjects will be
 required to have already undergone the initial step of the traditional diagnostic algorithm
 with x-ray of the suspicious region on the day of enrollment. All subjects will then be
 scheduled to undergo diagnostic ultrasound at a separate appointment with ultrasound
 procedure performed by a blinded clinical physician boarded in Physical Medicine and
 Rehabilitation, competent in performing and reading diagnostic ultrasound. All patients will
 then undergo a confirmatory MRI of the region of concern. Subject recruitment and data
 collection are expected to be completed over a six-month period. A statistician in the
 Department of Public Health at the University of Virginia will be performing statistical
 analysis. We plan to analyze findings using a McNemar chi-square test to evaluate for
 significant differences between the sensitivities of ultrasound and x-ray in diagnosing acute
 stress fracture of the lower extremity. All x-ray and MRI obtained for this study will be
 read by a Radiologist board certified in Musculoskeletal Radiology.

 Diagnostic ultrasound performance: The physician performing the ultrasound will be blinded to
 the results of the x-ray and MRI. The physician performing the ultrasound will be informed of
 the bone in question (ex. Tibia) and will be able to perform a focused history and exam. The
 bone in which acute stress fracture is suspected will then be scanned throughout its length
 in two orthogonal views. The criteria for diagnosing acute stress fracture on ultrasound
 include displaying 2 out of 3 of the following: hypoechoic periosteal elevation of cortical
 bone, visible cortical disruption, hyperemia surrounding the periosteal lesion on power
 Doppler. The ultrasound physician will then be asked to make a determination whether the
 ultrasound study is positive for acute stress fracture or negative/indeterminate.

 Statistical Analysis/Power Analysis: Sensitivity and specificity of diagnostic ultrasound and
 x-ray were calculated. MRI was used as the gold standard confirmatory test. Positive
 predictive value and Negative predictive value were also calculated for comparison. A priori
 power analysis determined a sample size of 186 was needed to obtain a power of 80%. The
 primary aim will be analyzed using a bootstrap test to compare the x-ray sensitivity to the
 ultrasound sensitivity. In order to account for the paired nature of the data, the bootstrap
 sampling will be at the subject level and will draw pairs with the x-ray and ultrasound
 outcomes associated with individual subjects. A statistician from the University of Virginia
 was hired for all statistical calculations.

 Subject Recruitment: Subjects presenting to the Sports Medicine clinic with suspected acute
 stress fracture of the lower extremity on initial presentation will be offered participation.
 Participation includes an additional clinic visit with a separate physician to perform a
 diagnostic ultrasound of the area of concern in addition to the standard work up they would
 receive for their presenting complaint. Informed consent was obtained at the time of study
 enrollment. Subjective will be offered ultrasound evaluation as well as follow up
 confirmatory MRI. The cost of follow up MRI is included in the study to prevent selection
 bias based on insurance coverage for MRI. The costs associated with the additional clinic
 visit for diagnostic ultrasound is also included in the study budget.
Inclusion Criteria:

 -  age 14 years and up

 -  suspected acute stress fracture of the lower extremity

 -  symptoms < 4 weeks

 -  x-ray ordered by clinician to which subjects originally present with suspected stress
 fracture

 Exclusion Criteria:

 -  age < 14

 -  unable to provide consent

 -  unable to undergo MRI (implantable pacemaker or other device not compatible for MRI)

 -  previous diagnosis of acute stress fracture in the location of interest

 -  previous XR or MRI obtained at an outside clinic/facility prior to presentation

 -  previously implanted hardware (ex. orthopedic screws or plates) at location of
 interest

 -  symptoms > 8 weeks

 -  depth from skin surface to bone surface that exceeds the capability of ultrasound for
 visualization

 -  Pregnant (self-reported)

 -  Subject is known to all clinicians who would be completing the diagnostic ultrasound
 component of the study

 -  Open wound at site of suspected stress fracture