ORIGINAL ARTICLE
Effectiveness of Vitamin D Therapy in
Orthopaedic Trauma Patients
Daniel S. Robertson, MD,* Tyler Jenkins, MD, Yvonne M. Murtha, MD,
Gregory J. Della Rocca, MD, PhD, David A. Volgas, MD,
James P. Stannard, MD, and Brett D. Crist, MD
Objective: The purpose of this study was to determine the
effectiveness of our vitamin D treatment protocol in managing low
serum vitamin D levels in orthopaedic trauma patients.
Methods: A retrospective review was conducted of all orthopaedic
trauma patients at a university level I trauma center over 20 months.
Patients were included if they had an initial and repeat 25-hydroxy
(OH) vitamin D serum level available. Vitamin D deciency was
dened as serum 25-hydroxy vitamin D level with less than 20 ng/mL.
Vitamin D insufciency was dened as serum 25-hydroxy vitamin D
level between 20 and 32 ng/mL. The standard regimen for all patients
was over-the-counter vitamin D3 1000 IU and 1500 mg of calcium
daily. Patients with vitamin D deciency or insufciency also received
50,000 IU of ergocalciferol (D2) weekly until their 25-hydroxyvitamin
D level normalized or their fracture healed. No compliance monitoring
was performed except for questioning at each clinic visit.
Results: A total of 201 patients met the inclusion criteria. Thirty-
two patients had a normal initial 25-hydroxyvitamin D level, and
84% maintained their normal level, whereas 16% became insuf-
cient or decient. There were 88 patients insufcient initially and
54.5% improved to normal and 8% became decient. In the vitamin
D deciency group (81), 26% remained decient and 74% improved
to insufcient. The average increase in serum 25-OH vitamin D with
treatment (in nanograms per milliliter) was statistically signicant for
both the insufcient and decient groups.
Conclusions: Vitamin D therapy improved the majority of the
patients vitamin D-25-OH level but did not normalize most. Patients
with initial deciency had the largest improvement. This study in-
dicates that vigilance is required to adequately treat a low serum
vitamin D-25-OH level.
Key Words: vitamin D deciency, musculoskeletal trauma, fracture
healing
Accepted for publication June 1, 2015.
From the *Department of Orthopaedics, University of Texas Health Science
Center at San Antonio, San Antonio, TX; Department of Orthopaedic
Surgery, Northwestern University Feinberg School of Medicine, Chicago,
IL; and Department of Orthopaedic Surgery, University of Missouri
School of Medicine, Columbia, MO.
Presented at the Orthopaedic Trauma Association, Annual Meeting, October
12, 2013, Phoenix, AZ.
The authors report no conict of interest.
Reprints: Brett D. Crist, MD, Department of Orthopaedic Surgery, University
of Missouri, One Hospital Drive, N119, Columbia, MO 65212 (e-mail:
cristb@health.missouri.edu).
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J Orthop Trauma  Volume 29, Number 11, November 2015
Copyright 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Level of Evidence: Therapeutic Level IV. See Instructions for
Authors for a complete description of levels of evidence.
(J Orthop Trauma 2015;29:e451e453)
INTRODUCTION
Vitamin D is an important prohormone in the regulation
and maintenance of numerous physiologic systems in the
human. It plays a role in cardiac, immune, digestive systems,
and the musculoskeletal system.1,2 Low vitamin D levels are
associated with a higher incidence of fracture in the elderly3
and recalcitrant tibial nonunions.4
At our institution, we reviewed our orthopaedic trauma
patients with fractures who had serum 25-hydroxy (25-OH)
vitamin levels available over a 20-month period. Records for
889 patients were reviewed, and 77% of them had either 25-
OH vitamin D deciency or insufciency, as dened by
Hollis.5,6 During this review period, it was noted that a signif-
icant number of patients had a low serum 25-OH vitamin D
level. Based on these ndings and its potential implications in
patient outcomes, our center implemented a protocol-driven
effort to supplement patients during the fracture healing
period. The purpose of this study was to evaluate the effec-
tiveness of our vitamin D treatment protocol in orthopaedic
trauma patients. Our hypothesis was that vitamin D therapy
normalized serum 25-OH vitamin D levels.
PATIENTS AND METHODS
After institutional review board approval, a retrospective
review was performed for all orthopaedic trauma patients
with a fracture at our American College of Surgeons veried
level I university trauma center from January 1, 2009 to
September 30, 2010. Patient inclusion criteria were they had
to be at least 18 years old, they had a fracture managed by one
of 4 attending orthopaedic trauma surgeons, and they had an
available serum 25-OH vitamin D level available within 2
weeks from their injury and a repeat 25-OH vitamin D level
available.
The 25-OH form of vitamin D is the inactive serum form
but is found to be the most accurate measure of systemic
vitamin D levels.7 During the review period when serum vita-
min D levels were obtained, the standard regimen for all pa-
tients was over-the-counter vitamin D3 1000 IU and 1500 mg
of calcium daily. Patients with serum 25-OH vitamin D de-
ciency or insufciency8 also received an 8-week prescription
www.jorthotrauma.com | e451
 Robertson et al
for weekly 50,000 IU ergocalciferol (D2) until their 25-OH
vitamin D level normalized or their fracture healed, which
correlated with the risk assessment performed by Hathcock
et al.9 No complications were noted. Patients with either a his-
tory of hypercalcemia or at risk for hypercalcemianoted as
calcium levels higher than 10.5 mg/dLwere excluded from
this regimen. Standard clinic follow-up was performed at 2-,
6-, and 12-week visits and then every 23 months until fracture
healing occurred. Follow-up serum 25-OH vitamin D levels
were encouraged after the 8-week course of ergocalciferol,
per our protocol. No compliance monitoring was performed
except for questioning at each clinic visit. We gave calcium
and vitamin D supplementation prescriptions when patients left
the hospital and on follow-up veried that these were on their
medication lists. We then provided patients information on
over-the-counter calcium and vitamin D supplements and the
required amounts they needed to take.
Statistical Methods
Descriptive statistics including the mean, median, and
mode were calculated. A x2 test was performed if all cell fre-
quencies were greater than 5. The Fisher exact probability test
was used if any of the cell frequencies were 5 or less. We
performed 1-sample T tests to calculate signicant change in
values. P values ,0.05 were considered statistically signicant.
Definitions
Vitamin D deciency was dened as serum 25-hydroxy
vitamin D level with less than 20 ng/mL. Vitamin D
insufciency was dened as serum 25-hydroxy vitamin D
level between 20 and 32 ng/mL.8 By comparison, the Institute
of Medicine and the Endocrine Society dene deciency as
less than 20 ng/mL and between 2129 ng/mL, respectively.10
RESULTS
Two hundred one patients had initial and repeat serum
25-OH vitamin D levels. Of the 32 patients with a normal
initial 25-OH vitamin D level, 84% (27) remained normal and
16% (5) became insufcient or decient during clinical
follow-up (Table 1). The average change in 25-OH vitamin
D levels for this subgroup was an increase of 1.9 ng/mL and
was not statistically signicant (P = 0.17). The insufcient
group consisted of 88 patients. Forty-eight patients (54.5%) in
TABLE 1. Initial Serum 25-OH Vitamin D Levels for Each
Patient Group, Follow-up Vitamin D Levels, and Average
Change
Average Average Average
Initial Repeat Increase in
Vitamin Vitamin Vitamin
D-25 Level, D-25 Level, D-25 Level,
Vitamin D-25-OH Level ng/mL ng/mL ng/mL
Normal ($32 ng/mL) 39.13 41.03 1.90
Insufciency (,32 ng/mL) 25.19 33.98 8.79*
Deciency (,20 ng/mL) 13.74 28.67 14.93*
*P , 0.05.
e452 | www.jorthotrauma.com
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J Orthop Trauma  Volume 29, Number 11, November 2015
the insufcient group improved to normal, and 7 patients
(8%) became decient. The remaining 33 patients (37.5%)
remained insufcient. The average change for the insufcient
group was an increase of 8.79 ng/mL with treatment and was
statistically signicant (P , 0.05). Of the 81 patients with 25-
OH vitamin D deciency, 26% (21) remained decient and
74% (60) improved to the insufcient level. The decient
group had the largest average increase of 14.93 ng/mL and
was also statistically signicant (P , 0.05). Follow-up values
were determined after 8 weeks of therapy.
DISCUSSION
Although vitamin D therapy improved the majority of
the patients serum 25-OH vitamin D with initial insufciency
or deciency, it was not as successful as we hoped. Patients
with initial deciency and insufciency had the largest im-
provements but neither normalized. However, there were sig-
nicant changes in the levels for those with the lowest levels
of 25-OH vitamin D.
Vitamin D deciency is estimated to affect about 1
billion people worldwide and is linked to multiple medical
maladies including cancer, diabetes, cardiovascular disease,
and musculoskeletal health.11 Vitamin D deciency has been
associated with fragility fractures3 and tibial nonunions.4
Approximately 40% of elective sports-related orthopaedic
surgery patients have low vitamin D levels.12 However, the
direct consequence of having a low serum 25-OH vitamin D
level and an orthopaedic injurysuch as fracture nonunion or
infectionis unknown.
The limitations of this study go beyond its retrospective
nature. Medication adherence, even with a prescription from
a physician, ranges from 19% to 100%.13 Patients with low
serum 25-OH vitamin D were given a prescription for weekly
ergocalciferol, and all patients were given the recommendation
for over-the-counter daily supplementation of calcium and vita-
min D. Patients were asked at each clinic visit if they were
taking the medications as recommended and were entered in
their medical record. However, even in the best of circumstan-
ces, adherence to treatment was not validated with pill counts.
Therefore, the efcacy of the treatment regimen would have
been more accurate with more strict protocols.
Furthermore, there is the natural uctuation in vitamin
D levels in normal healthy adults. Melin et al14 monitored
vitamin D levels and the bone mineral density (BMD) of
patients femoral necks over a 12-month period. There was
a regular uctuation of vitamin D levels with higher levels in
the months after summer and lower levels in months after
winter. There was a statistically signicant positive correla-
tion of vitamin D levels and femoral neck BMD across the
study group, but there was no signicant change in BMD with
change in vitamin D levels. What can be acknowledged from
this and other articles is that low vitamin D levels are com-
mon among many different patients and that these levels are
not static. Establishing the best way to restore normal levels
quickly and safely may be an adjunct to our orthopaedic care
not only in trauma patients but also in patients who require
bone growth (eg, bone tendon bone allograft healing or bony
ongrowth for arthroplasty).
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 J Orthop Trauma  Volume 29, Number 11, November 2015
Our study indicates that continued vigilance is required
to adequately treat a low serum 25-OH vitamin D level.
Treating vitamin D insufciency or deciency with a standard
regimen does raise serum levels, but more effective regimens
and closer monitoring is required. Understanding the actual
complications associated with low vitamin D in fracture
patients is also important because most fractures do heal
despite a signicant number of patients with low serum 25-OH
vitamin D. Future studies will prospectively evaluate treatment
regimens and the effect of low vitamin D on complications of
orthopaedic trauma. We will also study ways on why these
patients fracture healing patterns did or did not respond to
regimental vitamin D treatments.
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Copyright 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
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