Vitamin D3 Supplementation and Stress Fracture Occurrence in High-Risk Collegiate Athletes
Phase: NA
Conditions: Vitamin D Deficiency, Stress Fracture, Athletic Injuries, Orthopedic Disorder
Sponsor: Prisma Health-Midlands

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Vitamin D and Stress Fractures 
 
 
Most Recent IRB approval: 8-2-2017 
 
Study Title:  Vitamin D3 Supplementation and Stress Fracture Occurrence in High-Risk 
Collegiate Athletes 
 
Principal Investigator: J Benjamin Jackson, MD; University of South Carolina Department of            
Orthopaedic Surgery 
 
Co-Investigators: Christian Askew; USC School of Medicine, Graduate Student 
       Toni-Torres-McGehee PhD, ATC University of South Carolina Department 
of Athletics 
       Kevin Williams, MD Palmetto Health/University of South Carolina 
Department of Orthopaedic Surgery 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Vitamin D and Stress Fractures 
 
 
Most Recent IRB approval: 8-2-2017 
 
 
Background/Justification 
 
 
Although active vitamin D3 (1,25-dihydroxyvitamin D) has numerous functions in the 
body, one of its more important roles is maintaining serum calcium levels.  By regulating 
osteoclast activity, it modifies bone resorption to keep serum calcium levels within homeostatic 
ranges.  Thus, it is a crucial vitamin for overall bone health.  Inactive forms of vitamin D are 
synthesized in the skin as well as absorbed from the diet, and then converted into the active form 
when necessary.  Studies have shown that populations living in higher latitudes, receiving less 
sun exposure, and those with poor diets have an increased susceptibility to vitamin D 
insufficiency or deficiency .1,2,3  These low levels may affect bone health, which in turn may lead 
to skeletal injuries. 
 
One area of particular interest is the effects of  vitamin D deficiency on stress fracture 
occurrences.  As bones and muscles undergo stress from training or increased activity, 
remodeling occurs to adjust for this change and improves the structural integrity of the bone.  
Normally, a conditioned athlete or an individual with a rapid change in activity with adequate 
calcium and vitamin D levels will be able to compensate for this added stress.  However, a 
deficiency in vitamin D has been shown to decrease bone repair.  When tissue demand from 
stress outweighs tissue repair, overuse injuries occur.  This is the basis behind studying vitamin 
D supplementation and occurrence of stress fractures.   
 
 
According to a review by Neal et al., the study of vitamin D levels and stress fracture 
occurrences is a relatively new topic.1  The best understood data comes from studies on military 
recruits, due to their rapid increase in activity and musculoskeletal stress.  However, there is 
much less data regarding the effects of vitamin D levels on stress fracture occurrences in 
conditioned athletes .1  Furthermore, since levels of vitamin D have been shown to vary with 
season and sunlight exposure, this leads to the idea that indoor sports and winter seasons may at 
a higher risk for stress fractures.  One study by Valimaki et al.(need reference number here) 
showed a significant increase in vitamin D levels in Finnish men over a period of 6 months.  
First measurements in July listed only 0.9% of their subjects having levels below 20 nM/L, while 
in the winter the number of subjects in the deficient range increased to 38.9% .4 These findings 
support the idea that vitamin D levels are different at various seasons of the year.   
 
 
As mentioned, there are several studies on vitamin D levels and/or calcium levels and 
their relationship with bone health.  One study by Lappe et al.  examined this relationship in 
female navy recruits by running a double-blind study, giving vitamin D and calcium 
supplementation to half of the subjects and a placebo to the other half.4  There were 3700 recruits 
that finished the study, and 309 recruits were diagnosed with at least one stress fracture.  From 
the data, their results concluded that group with supplementation showed a decrease in stress 
fracture occurrence by roughly 21% compared to the control group .5  This significant decrease 
shows that supplementation of both vitamin D and calcium benefited in maintaining adequate 
bone health.  The study also showed a reversal in bone mineral content.  They found that vitamin 
D and calcium supplementation not only stopped bone mineral loss, but also began increasing 
total content by 2-3%.   
 

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Vitamin D and Stress Fractures 
 
 
Most Recent IRB approval: 8-2-2017 
 
 
 In a 2014 literature review by Dao et al., a total of 9 studies from 238 original listings 
were found to focus strictly on vitamin D levels and stress fracture occurrences in the military .6  
Through their analysis, the general consensus was that stress fractures were more prominent in 
individuals with low vitamin D levels, both at the time of recruitment and at the time of 
diagnosis.  This review also noted a lack of studies and data taken from athletes.  One 
unpublished study of note by Shindle showed that 51% of National Football League athletes 
were vitamin D insufficient, and 30% were technically deficient .2  Tenforde et al. also reviewed 
literature on calcium and vitamin D supplementation and found that retrospective studies contain 
mixed results and there are very few prospective studies .7  They also noted the lack of data on 
male athletes, with most research focusing on females roughly between the ages of 18 and 26.   
 
 
In testing for bone mineral density, the standard for measurement comes from dual-
energy X-ray absorptiometry.  DXA is a method used to distinguish between soft tissue and 
bone, and also provides information about bone structure and mineralization.  Many studies have 
examined the use of quantitative ultrasound as a replacement for DXA in determining the risk of 
fracture in the elder population .8,9,10  Ultrasound imaging is much less invasive, less expensive, 
and unlike DXA it does not involve the use of ionizing radiation.  Among others, one study by 
Pluijm et al. found that ultrasound results were strong predictors of bone mineral density and risk 
of bone fracture .8  Although ultrasound has not been studied as thoroughly as DXA, results have 
suggested it is comparable in determination of fracture risk between different study groups .8,9,10 
 
 
After examining current literature, it is clear that vitamin D plays a crucial role in bone 
health and can affect the rate of skeletal-related injuries.  Studies on military recruits provide 
promising data, but an important difference to note is musculoskeletal strength in recruits 
compared to conditioned athletes.  Therefore, it is necessary to study the effects of vitamin D 
supplementation on bone health in athletes in order to help prevent stress fractures and related 
injuries.  Our study would add to the current deficit in this area of research and would allow 
athletes and teams to adjust diets and training plans accordingly.  The principal investigator has 
observed an increase rate in stress fractures in those athletes who participate in the following 
sports: basketball, soccer, track/field, and cross country for both male and females athletes.  The 
overall aim is to demonstrate the evidence of stress fracture prevention in order to keep athletes 
performing at their highest abilities.   
 
Objectives/Research Aims 
 
Objectives 
 
 
The main objective of this study is to find a correlation between vitamin D deficiency and 
stress fracture occurrences in athletes who participate in high-risk activities.  These high-risk 
athletes undergo elevated bone turnover, which requires adequate levels of vitamin D in order to 
support bone health.  It is hypothesized  that  providing supplemental treatment to athletes 
showing lower than normal serum vitamin D levels will decrease the occurrence of stress 
fractures.  By recording the dates and specific occurrences of fractures, it may be possible to 
correlate injury rates with seasons, providing more supportive data to pre-existing literature.   
 

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Vitamin D and Stress Fractures 
 
 
Most Recent IRB approval: 8-2-2017 
 
This area of research is lacking in the quantity of prospective studies.  Previous studies 
primarily focus on adolescent, elder, or military recruit populations.  While literature has shown 
that vitamin D plays an important role in bone health, there are no previous studies that directly 
examine vitamin D deficiency and supplemental treatment in conditioned collegiate athlete 
populations.  This study will add to the existing knowledge and will provide a more specific 
analysis for athletes. 
 
Specific Aims 
 
1. To compare the proportions of student athletes experiencing stress fractures during the 
2015-16 academic year with the five previous years. 
 
2. To compare the proportions of 2015-16 academic year student athletes experiencing 
stress fractures in the vitamin D insufficient or deficient group and the group with 
vitamin D levels ≥30 ng/mL. 
 
3. In 2015-16 athletes, to explore associations between the TRIAD questionnaire risk 
factors and low baseline vitamin D levels.   
 
4. In 2015-16 athletes, to explore associations between the TRIAD questionnaire risk 
factors and subsequent stress fractures.   
 
 
Setting 
 
 
This study will focus on athletes who are at a higher risk of lower extremity stress 
fractures.  Specifically, this study will be looking at male and female athletes on the track, cross-
country, soccer, and basketball teams at the University of South Carolina.  During the pre-season 
physical of each student athlete, serum vitamin D levels will be taken and recorded.  There will 
be a certified nurse to draw the blood samples.  This will take place at the University of South 
Carolina Athletic Department and/or the Palmetto Health Lab at 2 Medical Park.  Potentially, 
every athlete of the given teams will be enrolled in the study unless they choose not to.  Only 
subjects showing concentrations below 30 ng/mL, which is indicative of insufficient or deficient 
levels, will be provided supplemental treatment of 25-(OH) vitamin D.  Every enrolled subject 
will be monitored for injury throughout the season.  Any and all injuries will be positively 
identified, and any confirmed stress fractures will be recorded.  Data from prospective seasons 
will be compared to an incidence percentage of athletes from previous seasons.  Previous athletes 
did not receive any vitamin D treatment.  These will be used as a control to determine if 
treatment affected the occurrence of stress fractures.  All physicals and tests will be performed at 
the USC Sports Medicine clinic by the sports medicine staff.  
 
 
Resources Available 
 
 
Track, cross-country, soccer, and basketball are all considered high-risk sports due to the 
constantly high loads being placed on the lower extremities.  Basketball is also included because 

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Most Recent IRB approval: 8-2-2017 
 
of the extreme stresses involved when jumping.  Combining all four sports as a single cohort 
would provide an adequate number of athletes to form a test group.  Each sport’s season occurs 
at different times of the year, and indoor sports like basketball and track may have athletes with 
less sun exposure.  This will allow a comparison of occurrences across different sports, not just 
between treatment and control groups.  Depending on the number of individuals meeting criteria 
for the study, it may be necessary to extend the timeframe to multiple seasons.  The initial phase 
of the study will include a retrospective analysis of data from deficient athletes in these sports 
from past seasons that have not received any supplemental treatment.  This will be used to find 
the percentage of stress fracture incidences occurring during those seasons. 
 
 
The staff directly working on the study will consist of a licensed orthopedic surgeon, a 
doctor of athletic training and nutrition, a physician in occupational medicine, a research 
assistant, and a master’s student.  During each individual sport’s season, other athletic trainers, 
physicians, and coaching staff may offer assistance as well.  Every individual engaged with the 
study will be familiar with the basics of the topic and protocol as a minimum.  The physicians 
will provide most of the expertise and insight when providing care for the athletes.  Should any 
unexpected consequences arise, the staff and athletes will have direct access to both orthopedic 
and athletic training facilities as well as the linked hospital and clinics.  The staff is in constant 
communication and will have regular meetings in order to stay current on the progress of the 
study.    
 
 
Prior Approvals 
 
 
Each individual sports team member, along with the coaching staff, team physicians, and 
athletic trainers, will be informed of the study.  Approval will be required from the teams listed, 
as well as from the University of South Carolina Orthopedic Clinic.  
 
 
Study Design 
 
a) Recruitment Methods 
 
 
Potential subjects will be screened from men’s and women’s track and field, soccer, and 
basketball teams, and women’s cross-country.  Individual players of each described team will be 
informed of the study during their pre-season physical.  It is hoped that every player on the 
specified teams will be able to enroll in the study, whether they are vitamin D deficient or not. 
 
Any subject that has consented and meets inclusion/exclusion criteria will be tested for 
serum vitamin D levels, and those individuals showing deficiency will be provided supplemental 
treatment in order to raise vitamin D levels to normal ranges.  Individuals who do not show 
deficiency levels will included in the study, but will not receive any treatment.  These subjects 
will be added to an additional control group.  There will be no payment for enrollment in the 
study. 
 
b) Inclusion/Exclusion Criteria 

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Most Recent IRB approval: 8-2-2017 
 
 
 
Each individual who has given consent will have blood work tested.  Should serum 
vitamin D levels be lower than 30 ng/mL, they will be included in the treatment group.  Subjects 
with normal ranges will be included in the prospective control group.  Both male and female 
athletes will be eligible to enroll.  Any individual who currently has a stress fracture or is in the 
stage of recovering from a lower extremity musculoskeletal injury will be excluded from the 
study.  Questionnaires will be provided in order to gather an understanding of diet, exercise 
regimen, and related lifestyle questions.  Specifically, there will be a question regarding current 
vitamin D or other multivitamin supplement currently being taken, what the dosage is, and how 
often it is taken.  Female athletes will be provided a separate questionnaire in regards to 
individual dietary habits and menstrual cycle. 
 
 
 
c) Local Number of Subjects 
 
 
The number of subjects in the study will be based on the number of individuals meeting 
the inclusion/exclusion criteria and provide written consent.  They will be drawn from men’s 
basketball, soccer, and track/field, and women’s basketball, soccer, track/field, and cross-
country.  There will be no cutoff to the number of individuals accepted.  Tentatively, there will 
be roughly 200 athletes enrolled in the study.    
 
 
d) Study-Wide Number of Subjects 
 
 
The number of subjects in the prospective portion of the study will be the number of 
qualified enrollees.  This number may change, depending on the length of the study.  Should it be 
necessary to extend the timeline, the study will enroll new subjects for the second season, but 
will still include them in the test group.  
 
e) Study Timelines 
 
Each enrolled subject will be monitored from the time of their pre-season physical to the 
conclusion of activities for their particular sport.  The pre-season physicals will occur in August 
2015, prior to the start of the school year.  Subjects will be enrolled in the study even if the sports 
season has not begun.  In the event of a study extension, any athlete partaking in a subsequent 
season will be asked to remain in the study as long as inclusion/exclusion criteria is met.  The 
estimated date of completion is July of 2016, but may be extended if the data is inadequate for 
completion of the study.   
 
 
Following the initial examination, all subjects will have serum 25(OH) vitamin D levels 
tested again in January.  Subjects with deficient levels receiving treatment will undergo a follow-
up examination 8 weeks from the initial treatment.  This will help determine if subjects are 
responding to the treatment.   
 
f) Study Endpoints 
 

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Vitamin D and Stress Fractures 
 
 
Most Recent IRB approval: 8-2-2017 
 
 
The primary endpoint of this study will be marked as when enough data has been 
collected to show a correlation between supplemental treatment and stress fracture occurrence, 
whether it is positive or negative.  Tentatively, data collection for the study will stop at the 
conclusion of the last sports season.  It may be necessary to extend the study for an additional 
school year if there are not enough data points to show a true correlation.     
 
 
Supplemental treatment of 25(OH) vitamin D3 may have several adverse effects, 
including hypervitaminosis D and hypercalcemia.  Should any subject show symptoms of these 
issues, they may be removed from the study. 
 
g) Procedures Involved 
 
Prospective:  Subjects will be enrolled starting in August 2015, following the pre-season 
physical.  It is possible many subjects, including returning athletes, may have taken summer 
physicals, and those subjects will be recruited and tested at a date upon return to school.  
Subjects should be tested prior to the start of individual seasons, although some overlap may 
occur.  A flowchart is attached. 
Potential enrollees will be provided a simple questionnaire regarding dietary habits.  This 
will help the researchers understand individuals’ nutritional intake, more specifically vitamin D 
sources.  They will also be provided an informative page on vitamin D function and treatment for 
deficiencies.  During the physical, each subject will have blood drawn and baseline serum 
25(OH) vitamin D3 will be recorded.  Supplemental vitamin D3 treatment will be given in 
50,000 IU dosages once a week for 8 weeks following the initial examination.  The prescription 
will be: Vitamin D3 50,000 IU oral capsule take 1 pill per week for 8 weeks. Subjects receiving 
supplemental treatment will then have vitamin D3 levels checked again at 8 weeks to ensure 
serum levels have risen.  These values will be recorded.  Should serum levels of vitamin D3 
remain below the target value of 30 ng/mL, these subjects will be treated again following the 
same protocol as the primary treatment to ensure the levels rise.  The subjects will then be 
followed throughout the course of the season, including all training activities, practices, and 
games. 
 
Both deficient and normal subjects will be re-tested in January upon return from winter 
break.  Subjects showing serum 25(OH) vitamin D3 levels below normal will be given 
supplemental treatment of 50,000 IU dosages once a week for 8 weeks.  These subjects may have 
new or recurring deficiencies.  Serum levels will be checked again following the end of treatment 
to ensure levels have risen.  Any subject that was within normal ranges in the fall sports season 
that drops to deficient ranges will be treated with the same dosage as the primary treatment.  
Should their serum vitamin D3 levels fail to rise after 8 weeks, a secondary treatment will be 
administered following the same protocol as the primary treatment.   
 
Throughout the seasons, any subject complaining of pain or injury to the lower extremity 
will undergo examination by the physician in order to positively diagnosis the injury.  Each 
positively identified stress fracture will be recorded for that subject, and the appropriate 
treatment and rehabilitation will ensue.  The lower extremity will be defined as any portion of 
the femur, tibia, fibula, and bones of the foot and ankle.  Should an injury occur that does not 

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Vitamin D and Stress Fractures 
 
 
Most Recent IRB approval: 8-2-2017 
 
directly relate to a stress fracture or the lower extremity, the subject will remain in the study.  
However, these subjects will be included in a separate analysis.   
 
 
 
Other than normal activities required for each sport, the main risk to each subject 
primarily involves taking blood samples.  Although sampling is routine, there will still be risks 
of bleeding, bruising, dizziness, and possible infections.  Allowing only trained individuals to 
take blood samples will minimize these risks.  Any injury that occurs during a sports event or 
training activity will be handled accordingly by one of the physicians or athletic trainers on site.  
All injuries, regardless of nature, will be recorded per subject. 
 
 
 
Blood samples will be tested for 25(OH) vitamin D levels using the order (Vitamin D 25-
OH, Calcifediol Request).  The data will be kept for each subject, day of recording, and level on 
an Excel spreadsheet.  Any stress fracture reported will be listed on the same spreadsheet, along 
with the date of occurrence and severity, per subject. 
 
Each team’s athletic training staff will administer one vitamin D capsule to each team 
member once a week before a scheduled meeting or practice.  This will help ensure every athlete 
takes the proper dosage, no dosages are skipped, and every week is accounted for.  Athletes may 
still have decreased levels after the first course, and a second round of 8-week treatment will be 
administered.  Should the second round of treatment fail to elevate vitamin D levels, the January 
test will confirm and treatment will continue.  As many students leave to visit family during 
break, it will be rather difficult to monitor every athlete’s levels during this timeframe. 
 
 
  
 
 
Retrospective:  The retrospective portion of the study will involve review of athletes of 
the same sports teams and inclusion/exclusion criteria from seasons up to four years ago.  
Review of previous athlete information will be drawn from electronic records kept by the athletic 
training staff, both electronic and hand-written records kept by the orthopedic staff, and any lab 
records retained at Palmetto Health.  The information that will be obtained will include athlete 
demographics, their respective sports, stress fracture occurrences, and vitamin D levels if this 
was noted.  The time period for the retrospective chart review will be from January 2010 through 
August 2015. The rate of stress fracture occurrence will be compared to the prospective 
treatment phase.  It is important to note that individuals in the retrospective analysis will not 
have personal information reported, as the main purpose is to determine a baseline stress fracture  
rate. 
 
Analysis of the historic group will follow similar protocol as the recruitment of new subjects.  
Information from previous subjects will include including gender, age and sports team 
information.  Additional information obtained will include stress fracture occurrence(s) and 
location, and vitamin D levels (if recorded).   
 
h) Data and Specimen Banking 
 

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Data for each enrolled subject will consist of name, age, gender, ethnicity, and sports 
team.  Any personal or private information collected will only be used during data analysis.  This 
may contain information regarding menstruation, dietary habits, and previous pregnancies.  
Names and private information of subjects will not be released outside of personnel directly 
attached to the study, and they will not be included in the final study publication.  Serum 25(OH) 
vitamin D levels for each subject will be recorded at the initial examination and 8 weeks 
following the beginning of treatment.  Every injury diagnosis will be recorded per individual.  
There will be no blood sample banking after vitamin D levels are determined.      
 
i) Statistical Analysis    
 
Sample Size Justification 
A power analysis was performed using PASS 2008 software on the research aim to compare the 
proportion of athletes that experience a stress fracture in those with normal vitamin D levels 
(either normal at baseline or treated by supplementation) compared to four previous years when 
this approach was not used.  You can see that if the proportion of athletes experiencing stress 
fracture in the control group is 10%, then if the true reduction in the treated group was to 4% or 
less, we would have greater than 80% chance (power) in this study to achieve statistical 
significance in a test of the two proportions. 
 
Two Independent Proportions (Null Case) Power Analysis 
 
Numeric Results of Tests Based on the Difference: P1 - P2 
H0: P1-P2=0. H1: P1-P2=D1<>0. Test Statistic: Z test with pooled variance 
 
 
Sample Sample 
Prop|H1 
Prop 
 
 
 
 
 
 
Size 
Size 
Grp 1 or 
Grp 2 or 
Diff 
Diff 
 
 
 
 
Grp 1 
Grp 2 
Trtmnt 
Control 
if H0 
if H1 
Target 
 
Power 
N1 
N2 
P1 
P2 
D0 
D1 
Alpha 
0.9946 
200 
800 
0.0200 
0.1000 
0.0000 
-0.0800 
0.0500 
0.9509 
200 
800 
0.0300 
0.1000 
0.0000 
-0.0700 
0.0500 
0.8220 
200 
800 
0.0400 
0.1000 
0.0000 
-0.0600 
0.0500 
0.6188 
200 
800 
0.0500 
0.1000 
0.0000 
-0.0500 
0.0500 
0.4048 
200 
800 
0.0600 
0.1000 
0.0000 
-0.0400 
0.0500 
0.2337 
200 
800 
0.0700 
0.1000 
0.0000 
-0.0300 
0.0500 
0.1224 
200 
800 
0.0800 
0.1000 
0.0000 
-0.0200 
0.0500 
 
 
Statistical Analyses 
 
1. To compare the proportions of student athletes experiencing stress fractures during the 
2015-15 academic year with the four previous years. 
 
A large sample test of the difference in two independent proportions will be carried out, 
along with computation of 95% confidence interval on the difference between the two 
proportions.  An exploratory logistic regression model will be built with stress fracture as 
the outcome, group (2015-16 versus the previous four years) as the major predictor 
variable and type of sport and gender as covariates. 
 

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2. To compare the proportions of 2015-16 academic year student athletes experiencing 
stress fractures in the vitamin D insufficient or deficient group and the group with 
vitamin D levels ≥30 ng/mL. 
 
A large sample test of the difference in two independent proportions will be carried out, 
along with computation of 95% confidence interval on the difference between the two 
proportions.  An exploratory logistic regression model will be built with stress fracture as 
the outcome, group (baseline vitamin D deficient versus normal baseline vitamin D level) 
as the major predictor variable and type of sport and gender as covariates. 
 
3. In 2015-16 athletes, to explore associations between the TRIAD questionnaire risk 
factors and low baseline vitamin D levels. 
 
Exploratory descriptive and inferential statistics will be carried out, including the 
building of linear and logistic regression models, looking for an association between the 
questionnaire items and baseline vitamin D levels (continuous and dichotomized). 
 
4. In 2015-16 athletes, to explore associations between the TRIAD questionnaire risk 
factors and subsequent stress fractures. 
 
Exploratory descriptive and inferential statistics will be carried out, including the 
building of logistic regression models, looking for an association between the 
questionnaire items and the subsequent occurrence of a stress fracture. 
 
 
j) Data Management 
 
 
Data collected will include preliminary vitamin D3 serum levels, vitamin D3 serum 
levels in January, and vitamin D3 levels eight weeks post-supplementation.  Additionally, should 
a stress fracture or other injury occur, the following information will be recorded: name of 
subject, team, date of injury, activity to cause injury, and location of injury.  Each data point will 
be recorded on a spreadsheet and saved for final analysis.  Each individual working on this study 
will be to date with all required CITI and HIPAA training.  Only individuals directly involved 
with the study will have access to records for the subjects.  
 
k) Confidentiality  
 
 
Blood samples used for testing vitamin D3 levels will only be kept temporarily.  Once 
each subject has been tested, serum levels will be recorded and samples will be disposed of 
following laboratory safe handling procedures.  The data collected for each subject will be 
recorded.  Any follow-up vitamin D3 tests will follow the same order.  Only individuals directly 
working on the study will have access to the data collected.  Personnel collecting blood samples 
for the vitamin D3 test will temporarily have access to the results for the specific subject being 
tested.   
 
l) Provisions to Monitor the Data to Ensure the Safety of Subjects 

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Subjects in this study are only at minimal risk with regards to treatment and testing.  
Difficulties may arise during administration of vitamin D supplements and during blood 
sampling.   
 
m) Withdrawal of Subjects 
 
 
There are several circumstances that may require the subject to be withdrawn from the 
study without consent.  Any subject that ceases activities and involvement with a given sports 
team will be withdrawn from the study.  Likewise, if a subject develops an injury that is not 
within the parameters of the study will be withdrawn from the study.  These injuries may 
include, but are not limited to, fractures to bones not defined as lower extremity, severe muscles 
strains that inhibit their ability to perform, ligament sprains or tears that are not directly related to 
bone strength in the lower extremity, and any other injury that requires the subject to stop sports 
related activities.  Any subject that becomes pregnant during the study will be removed from the 
study.   
 
 
Should it be deemed necessary for a subject to be withdrawn without consent, the subject 
will be notified and will sign a form acknowledging their release.  Any data collected from the 
subject prior to removal will be kept for partial analysis but will not be included in the final 
analysis with subjects completing the entire study.  Subjects being removed from the study will 
stop receiving supplemental treatment as part of the study, but may continue if it is beneficial for 
any injury or health related condition that occurs.  Subjects will still be under the supervision of 
physicians and athletic training staff.   
 
 
 
8) Risks to the Subjects 
 
 
Subjects in the study are being examined for occurrence of stress fractures in the lower 
extremities.  The main purpose of the study is prevention of these injuries, however they are still 
likely to occur.  Stress fractures are the primary injury of note related to this study.  Stress 
fractures show a range of symptoms, from mild discomfort and tenderness to the region, to 
severe pain and the inability for the subject to function normally.  Each injury will be treated 
individually in order to promote the quickest and safest recovery.  Being a sports related study, 
other injuries and difficulties that may occur outside of the parameters of the study may include 
torn muscles, tendons, or ligaments, ligament sprains and muscle strains, meniscus tears, bone 
fractures above the lower extremities, concussions, bruising, dehydration, fainting during 
training or events, and heat stress.  These injuries will be treated by appropriate personnel, but 
will not be applied towards analysis in the study. 
 
 
Blood sampling in order to obtain serum 25(OH) vitamin D levels can impact subjects 
differently.  The risks are minimal, but may include slight pain or discomfort, bruising, bleeding, 
dizziness, becoming light-headed, or fainting.  However, blood tests are a normal part of medical 
treatment and these risks do not put the subject in danger.  Supplementation of vitamin D is 
considered a safe treatment as long as dosages are monitored and adequate.  Doses higher than 
necessary may lead the subject to experience weakness, headaches, dry-mouth, nausea, or other 

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discomforts.  Several possible difficulties may arise from the increased serum calcium levels due 
to vitamin D. These include heart arrhythmias, kidney problems, and over-active parathyroid 
function. These problems are very minimal and are unlikely to occur.  
 
 
9) Potential Benefits to the Subjects 
 
 
Subjects enrolled in the study will be receiving supplemental treatment for insufficient 
serum vitamin D levels.  Benefits to the subjects may include increased structural integrity of 
bones, decreased likelihood of musculoskeletal injury, higher athletic performance, and 
increased overall bone health.  It is hoped that supplementation reduces the risk of stress fracture 
injury, thus allowing the athlete to perform at peak levels.  Many stress fractures can lead to 
surgical intervention, and a reduction in stress fracture rate and/or severity will reduce the need 
for surgery.  
 
 
10) Provisions to Protect the Privacy Interests of Subjects 
 
 
Information obtained from subjects will be secure and only visible to personnel directly 
involved with the study.  Each subject will be informed of who has access to the information and 
data collected.  The release of any data, or publication of final results, will not be linked to any 
personally identifiable information of a subject.  Private information will not be shared with 
anyone outside of the researchers and will only be used to distinguish between inclusion and 
exclusion from the study.  Subject information will not be shared between subjects in the study. 
 
 
11) Compensation for Research-Related Injury 
 
 
The research-related risks to the subjects are minimal.  Stress fractures, or other injuries 
that occur during sports activities, are a risk each subject is aware of when joining the team.  
These are not included as a research-related risk. 
 
12) Economic Burden to Subjects 
 
 
Subjects are not responsible for any costs of treatment during the study.  Vitamin D tests 
and treatment will be covered by funds allocated for the purpose of the study.  Physicians and 
athletic training staff will treat injuries that develop during sports-related activities.  These 
injuries may or may not be related to the study.   
 
 
13) Bibliographic References 
 
1. Neal S, Sykes J, Rigby M, Hess B 2015. A review and clinical summary of vitamin D in 
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