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Vitamin D deficiency is prevalent throughout the world and has been long suspected
to play a role in fracture healing. The goals of this study were to evaluate
rates of union, time to union and vitamin D treatment patterns in adult
fracture patients. A retrospective review was performed by evaluating charts
and radiographs of patients who underwent fracture fixation. Vitamin D levels
were recorded postoperatively and correlated with fracture union rate and time
to union. The rate of vitamin D supplementation was also reviewed. Results
showed an 11% decrease in fracture union rate in patients with 25(OH) vitamin D
levels < 20 mg/ml compared with levels >20 mg/ml; 81% and 92%,
respectively (p=0.07). Vitamin D levels also did not significantly impact time
to union. Despite low vitamin D in 58% of included patients, only 13% were discharged
with a vitamin D prescription. These results suggest there is room for
improvement with regards to assessing and treating deficiency in fracture
patients. While an 11% decrease was noted in fracture union with Vitamin D
deficiency, our report does not provide statistically significant data to make
overarching conclusions about the role of vitamin D in fracture healing or time
to union following fixation. However, it was noted that Vitamin D
supplementation following fracture fixation may be inappropriately deficient.
Further studies are needed to define the best cutoff for treatment and to
establish the mechanisms by which vitamin D influences bony healing.
INTRODUCTION
MATERIALS AND METHODS
A retrospective chart review of our institution’s repository for
orthopedic trauma patients treated for fracture by the senior surgeon author
between June 2012 and December 2014 was performed. Institutional Review Board
approval was granted prior to initiation of this study.
RESULTS
The final cohort
consisted of 202 patients with 118 suffering multiple fractures which were
individually evaluated. The average vitamin D level was 20 mg/ml (range, 4-78
mg/ml). Vitamin D and calcium levels are reported in Table 2. A total of 84 patients had vitamin D levels >20 ng/ml
with an average of 28 ng/ml, (range, 21-78 ng/ml). Serum calcium averaged 8.7
and 8.6 in the vitamin D ≤ 20 ng/ml and >20 ng/ml groups, respectively. Rate
of union for vitamin D levels >20 ng/ml was 92%, while only 81% in the group
with vitamin D<20 ng/ml (p=0.07). Time to union was 7.3 months with vitamin
D<20 ng/ml and 8.5 months with vitamin D>20 ng/ml (p=0.07) (Table 3). Despite a postoperative
vitamin D level ≤ 20 ng/ml in 118 patients, only 15 (13%) patients were
discharged with vitamin D supplementation. Among the 202 patients,
bisphosphonates were not used in any patient and teriperatide was given in 2
(1%) patients postoperatively.
Vitamin D levels significantly influence the body’s calcium balance and
affect bony mineralization [3]. There is growing interest in the relationship
of fracture union and vitamin D levels. Despite this interest, recommendations
for therapeutic intervention following fracture fixation have not been
established. To our knowledge, no study has investigated fracture union and the
time to union based on the generally recommended cutoff of vitamin D levels. In
patients with vitamin D levels <20 ng/ml an 11% decrease was noted in union
rates without reaching statistical significance. Interestingly, faster union
was noted in vitamin D-deficient patients, however, again without statistical
significance. Several factors have been shown to influence vitamin D level. Such
reported factors include smoking, seasonal changes, and fracture [11,13,20].
Briggs et al. reported a decrease in serum 1,25(OH)2D concentrations over a 6
week period following long bone fracture. Interestingly, they noted an increase
in calcium concentration without a corresponding increase in phosphate or
parathyroid hormone [11]. Additionally, Brinker et al reported that 68% of
patients with a fracture nonunion were found to have a previously undiagnosed
vitamin D deficiency [18]; other studies have validated this conclusion [19].
Thus, many studies have now recommended vitamin D supplementation with at least
800 IU/day in fracture patients, as supplementation has little toxicity and has
an association with calcium metabolism and a link to bone healing [14,19,21].
Despite a 58% prevalence of patients with low vitamin D levels, only 13% of
patients in our study were discharged home with vitamin D prescription. The
role of bisphosphonate following fracture fixation remains unknown. However,
its use in fracture nonunion has been reported [19]. Although over half of the
patients were deemed to be vitamin D deficient, no patient was treated with
bisphosphonates postoperatively. Additionally, the effect of using
teriparatide, an rDNA injection, following fracture fixation in vitamin D
deficient patients remains unknown. While utility has been suggested, it is
impossible to draw any conclusions from this study as none of the vitamin D
deficient patients who underwent fracture fixation were being treated with bisphosphonates
or teriparatide. The primary objective of this investigation was post-surgical
fracture union as it relates to vitamin D levels. Although not statistically
significant, we demonstrate an 11% lower overall union rate amongst patients
with low vitamin D levels. These results align with prior studies, which have
identified a relationship between fracture healing and vitamin D levels
[18,19,22,23]. We hypothesize that with a more robust sample size, this
relationship may lead to statistical significance. However, studies have
disputed this relationship. Despite a small sample size, Boszczyk et al. [24] compared
diaphyseal non-unions to normally healing fractures in 35 patients and found no
difference in the prevalence of vitamin D deficiency. Despite several
publications suggesting an association between vitamin D levels and fracture
union, no established guidelines exist for a reasonable and appropriate cutoff
level for vitamin D therapeutic intervention. While several studies have used
20 ng/ml or less as a marker [16,17], the Institute of Medicine reported
cutoffs of <30 ng/ml, arguing that at >50 ng/ml, levels are more optimal
with regards to fracture patients [3]. The most sensitive and specific level
has still not been identified with regards to fracture healing and merits
further research. While the presence of fracture union, as it relates to
vitamin D levels have been researched, the influence of such levels on time to
union is unknown. In our study, vitamin D levels did not statistically influence
time to union. Unexpectedly, we noted a faster time to union in vitamin
D-deficient patients despite an overall lower union rate. This is in contrast
to other studies, which have demonstrated a higher delayed union rate amongst
vitamin D deficient patients [25]. The high incidence of polytrauma in our
cohort and its effect on time to union results is unknown. It has been
suggested that normalization of vitamin D levels following supplementation may
reduce the incidence of delayed union [25]. Thus, it stands to reason that
appropriate supplementation at the time of discharge may improve the time to
union. While this was not investigated in our report, only 13% of vitamin
D-deficient patients were discharged with a prescription for vitamin D. There
are several limitations to this study. First, poor patient follow up may have
influenced the time to union. As evident in several large trauma centers,
patient follow up compliance is often challenging. Thus, the actual time to
union may be falsely inflated secondary to this. This study cannot neither
fully support nor oppose formerly held opinions that vitamin D is important for
fracture healing and union rates given the fact that our conclusions did not
reach statistical significance. Secondly, a cutoff of 20 ng/ml or less was used
in this study to provide consistency with the current body of literature
[16,17]. However, a different cutoff value may have influenced our findings.
Further studies are needed to better establish appropriate cutoffs and
subsequently examine the success of treatment methods related to inadequate
vitamin D levels. Finally, the authors acknowledge that fracture healing is
affected by the other variables in including fracture type, diabetes, steroid
use, smoking and alcohol consumption. While these must be considered, the goal
of this study was to evaluate the independent role of vitamin D in fracture
healing. Subsequent studies should be performed to evaluate the effects of the
aforementioned variables.
CONCLUSION
While an 11% decrease was noted in fracture union with Vitamin D
deficiency, our report does not provide statistically significant data to make
overarching conclusions about the influencing role of vitamin D in fracture
healing or time to union following fixation. However, it was noted that Vitamin
D supplementation following fracture fixation may be inappropriately
deficient. Further studies establishing
the appropriate cut-off value for therapeutic intervention are needed.
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