Low Vitamin D Levels

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It’s well established that having a low level of vitamin D can lead to bone disease,
like rickets in children and osteoporosis in adults. But it may also increase the risks
for heart attack and premature death.
The Endocrine Society defines vitamin D deficiency as a blood level of less than 20 nanograms per milliliter (ng/mL), while vitamin D insufficiency is 21 to 29 ng/mL. Optimal levels are 30 to 100 ng/mL.

In a study published in October 2021 in The Journal of the Endocrine Society,
researchers identified 19,092 people who showed vitamin D deficiency on at least
two tests and who’d never had a heart attack. Everyone was divided into three groups. People in group A were not treated, and their blood levels remained below 20 ng/mL. Those in group B received vitamin D supplements that raised their levels into the range
of 21 to 29 ng/mL. Those in group C took enough supplements to raise their levels to
30 ng/mL or higher.
The researchers found the risk of heart attack was lower in group C than in both of the other groups. However, people in groups B and C (who all took supplements) had a lower risk of death from any cause than those in group A, who remained deficient in vitamin D. The connection? Other evidence has linked low blood levels of vitamin D to cardiovascular risk factors, such as high blood pressure, diabetes, obesity, and chronic kidney disease.
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Research study into vitamin D and calcium
Researchers based at the Yonsei University College of Medicine in Seoul, Republic of Korea, set out to evaluate the link between vitamin D and calcium and the number of patients needing revision surgery after total knee replacement surgery. Using the Korean National Health Insurance database, researchers looked at patients diagnosed with knee osteoarthritis who had primary knee replacement surgery between 2009 and 2018.
They ranked the number of patients at risk of needing revision surgery using a model
called the Cox proportional hazards model.

Of the 142,147 patients assessed, 28,403 used vitamin D and calcium while 113,744 didn’t. The study found that calcium and vitamin D significantly reduced the risk of revision knee replacement surgery. Both patients with periprosthetic joint infection and those without infections had less chance of needing revision surgery if they took calcium and vitamin D for more than a year after their knee replacement surgery. 
Similarly, implant survival rates were higher in people who took supplements for more than a year compared to those who did not. In patients who developed an infection after surgery, vitamin D and calcium taken for more than a year increased the five-year implant survival rate from 75% to 93%. In patients without infection, researchers noted a reduction in implant failure rates of 58%. The researchers concluded that a dose of 800 IU or higher of calcium and vitamin D for more than a year after knee replacement surgery lowers the chance of needing revision surgery.

How vitamin D and calcium helps
Vitamin D is essential for healthy bones and to regulate the amount of calcium in the body. As orthopaedic surgeons, we see higher complication rates after joint replacement surgery in patients whose vitamin D levels are low. Low vitamin D levels can also lead to increased joint and muscle pain. The sun’s rays are the primary source of vitamin D however it is also found in certain foods including eggs, salmon and mushrooms.

Taking a vitamin D supplement daily can boost your levels.
Calcium is vital for strong, healthy bones. Calcium deficiency can lead to bones becoming weak and breaking more easily. Osteoporosis is linked to a lack of calcium in the bones. Common sources of calcium include milk, cheese and leafy green vegetables such as kale.
These Top 5 Supplements Can Help Relieve Joint Discomfort Better than Glucosamine.

Joseph Queally provides all types of joint replacement surgery and supports the use of vitamin D and calcium to ensure the best possible outcomes. We offer detailed advice to our patients on caring for prosthetic implants and we can connect you with other specialist healthcare professions, such as nutritionists, if you require additional support.

Introduction
Vitamin D plays an important role in the musculoskeletal system of the human body. Here, we review the most current literature on vitamin D as it relates to orthopaedic surgery and the musculoskeletal system, focusing largely on non-fracture applications.

Materials and methods
A literature review was performed on the basic science of vitamin D metabolismepidemiology of vitamin D levels, role of vitamin D within the musculoskeletal system, and the correlation of vitamin D with injuries and
orthopaedic surgical outcomes.

Results
The existing literature suggests vitamin D plays multiple roles in the musculoskeletal system. Recent research has shed light on the importance of vitamin D in the setting of soft tissue healing and recovery in addition to affecting postoperative outcomes after common orthopaedic procedures.

Conclusions
Given the widespread prevalence of vitamin D deficiency, orthopaedic surgeons
should be aware of the current evidence regarding clinical implications in patients with musculoskeletal complaints.

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Keywords
Vitamin D
Athletes
Muscle function
ACL reconstruction
Rotator cuff injury
Arthroplasty
Osteoarthritis  

1. Introduction 

Vitamin D plays an important role in the musculoskeletal system of the human body. Traditionally, much of the focus on vitamin D has been placed on the regulation of bone health and fracture healing. However, recent growing evidence has shed light on the importance of vitamin D and its relation to soft tissue healing and function.
Despite recent research, there continues to remain confusion about the role of vitamin D.
Here, we review the most current literature on vitamin D as it relates to orthopaedic surgery and the musculoskeletal system, focusing largely on non-fracture applications.
We outline the basic science of vitamin D metabolismepidemiology of vitamin D levels, roles vitamin D serves within the musculoskeletal system, and the correlation of vitamin D with injuries and surgical outcomes.

2. Background

2.1. Sources of vitamin D
Vitamin D is biologically synthesized using ultraviolet B (UVB) rays from the sun.
Solar UVB rays transform 7-dehydrocholesterol to provitamin D3 at the skin level (Fig. 1). Pre-vitamin D3 is also acquired in small quantities through the consumption of liver, cod liver oil, fatty fish, and egg yolks [1][2][3]. From the skin, pre-vitamin D3 is attached to vitamin D binding protein and transported to the liver where it is converted to 25-hydroxyvitamin D3 (25 OHD), also known as calcifediol [1][3].
Through an additional hydroxylation step, predominantly in the kidneys, 25 OHD is
converted to 1,25-dihydroxyvitamin D3 or calcitriol, the active form of vitamin D.  [1][3][4].


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2.2. Basic mechanisms
Vitamin D is a secosteroid with direct hormonal interactions with over 200
genes in the human genome [5]Vitamin D receptors (VDR) on target cell nuclear membranes facilitate the endocrine and autocrine functions of vitamin D in multiple tissues [1] The endocrine function of vitamin D is largely present in the small intestine where it is instrumental in regulating serum calcium and phosphate absorption.
This modulation of serum calcium and phosphate is intertwined with the actions of parathyroid hormone (PTH) and, consequently, bone mineralization [1][3].
 
Additionally, it stimulates osteoblasts causing osteoclast activation, a crucial step in calcium mobilization and bone remodeling [6]. In addition to the endocrine effects
of vitamin D, it plays many important roles in muscular development and function.
This includes regulating phosphate accumulation in myocytes, aiding muscle function,
and metabolism after conversion to creatine phosphate.
It is also theorized to play a direct role in protein synthesis and growth.3 
Vitamin D has been found to alter myocyte responsiveness to insulin,
indirectly improving muscle recovery and construction. 

Lastly, it has been theorized that type II muscle fibers have a greater amount of VDRs
than type I, leading to type II proliferation when a hypovitaminosis D individual increases their serum vitamin D concentration [7]. Cartilage and joint capsular tissues have also been evaluated for their relationship to vitamin D.
One theory is that the vitamin D metabolite 24R,25-dihydroxyvitamin D3 plays a role
in stimulating extracellular matrix proliferation by chondrocytes. Through these effects, vitamin D plays an important role in optimizing mechanical loading [8].

2.3. Vitamin D levels
There is considerable debate as to the level of serum 25 OHD that designates a person as vitamin D deficient, insufficient, or sufficient, and there has been no minimal clinically important value established for vitamin D. The Vitamin D Council reports deficient as
0–30 ng/mL, insufficient as 31–39 ng/mL, and sufficient as 40–80 ng/mL [1].
The Endocrine Society reports deficient as 0–20 ng/mL, insufficient as 21–29 ng/mL,
and sufficient as 30–100 ng/mL [9]. The Food and Nutrition Board Institute of Medicine reports deficient as 0–11 ng/mL, insufficient as 12–20 ng/mL, and sufficient as greater than 20 ng/mL [10][11]. Thus, further studies are needed to help standardize normal ranges for vitamin D. In addition, levels categorized as deficient or insufficient should be clinically important and correlate with
injury and healing variables.

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2.4. Vitamin D supplementation
Vitamin D supplementation is available in the form of vitamin D3 (cholecalciferol),
or vitamin D2 (ergocalciferol). Although there is some debate, vitamin D3 appears to
be preferable for supplementation, with varying ranges of recommended dosages  [9][10][11][12][13][14] 
According to the Institute of Medicine, the recommended daily allowance (RDAs) for vitamin D is 600 IU for ages 1–70, and 800 IU for ages 71 and older, while the tolerable upper level (UL) is 4000 IU per day for ages 9 and older [10][11]. Treatment dosages
for low vitamin D levels are varied, with ranges between 400–1000 IU per day [13]. Recommended dosages for patients with 25OHD levels between 25–30 ng/mL are
2000–4000 IU D3 daily, and 50,000 IU once a week of D2 for 8 to 12 weeks
for those with serum 25OHD levels < 25 ng/mL [9][13]

3. Epidemiology
The National Center for Health Statistics estimates up to 32% of Americans
are deficient in vitamin D, and up to 1 billion people worldwide are estimated
to be insufficient or deficient [1] 
Prevalence of vitamin D deficiency is likely to increase due to time spent indoors and
increased use of sunscreen for skin cancer prevention. Risk factors for hypovitaminosis D
 include latitudinal location, winter season, skin melanin abundance, clothing coverage,
 kidney disease, and Crohn’s disease [1][3][15].

3.1. Athletes
Recently, there have been numerous studies evaluating the prevalence of abnormal vitamin D concentrations in the athletic population at both the collegiate and professional levels. In 2012, Villacis et al. found that 33.6% division I athletes at the University of Southern California had abnormal vitamin D levels [16].
Specifically, males, African-Americans, Hispanics, and those with a darker skin complexion were at increased risk for having low vitamin D levels. Barcal et al. showed that 74% of collegiate wrestlers had levels < 32 ng/mL in the fall, which increased to 94% in the winter and spring seasons [17]
They also found an association between low vitamin D levels and higher adiposity.
The changes in vitamin D levels on a seasonal basis are well documented. Vitale et al. performed a prospective cohort study analyzing vitamin D levels in 152 professional alpine skiers over the course of 3 full years in order to evaluate fluctuations in vitamin D [18]. Fifty one percent of these athletes at one point were vitamin D insufficient and 30% were deficient at one point over the course of three seasons.

Most athletes’ vitamin D levels peak in the summer and are lowest in the winter.
At the professional level in the United States, the prevalence of low vitamin D levels
has been studied in the National Basketball Association (NBA), National Football League (NFL) and National Hockey League (NHL). In a study by Fishman et al., 90 (32.3%) of the 279 NBA players at the NBA combine from 2009–2013 were vitamin D deficient, while 131 (47.0%) were vitamin D insufficient [19]. The mean vitamin D level in this cohort was 25.6 ± 10.2 ng/mL. Similarly, Angeline et al. found that 30% of NFL players on a single NFL team were vitamin D deficient (< 20 ng/mL), while 51% were vitamin D insufficient (20 to 31 ng/mL) [20]. In this cohort, lower vitamin D levels were associated with muscle injury. 
Maroon et al. found that African-American NFL players were more likely than white players to be vitamin D deficient [21]. In contrast, Mehran et al. found a low prevalence of vitamin D insufficiency (20–31.9 ng/mL) in the NHL, with a rate of only 13.3% in 105 hockey players across 3 NHL teams [22]. However, there were major differences in racial composition in these cohorts, with a higher percentage of white athletes in the NHL cohort compared to the NFL study. 3.8% of athletes were black and 96.2% of athletes were white in the NHL study cohort, while 84% of athletes were black in the study by Maroon et al. [21][22] Some authors espouse a 25-OH vitamin D level > 40 ng/mL as ideal in athletes.

3.2. Orthopaedic patients
Many studies have evaluated the deficiency of vitamin D in patients undergoing orthopaedic procedures. Observational cohort studies in the United States and internationally have demonstrated a high prevalence of hypovitaminosis D in these patients [23][24][25]. Additionally, recent studies have demonstrated high rates of vitamin D insufficiency and deficiency in pediatric orthopaedic patients and
adult patients undergoing foot and ankle, spine, joint replacement, and orthopaedic trauma surgeries [26][6][27][28][29]. Inkrott et al. retrospectively reviewed vitamin D levels in 218 patients undergoing shoulder arthroplasty and found that 43% of patients were vitamin D insufficient (< 30 ng/mL) and 11% were vitamin D deficient (< 20 ng/mL) [29]. In this study, low vitamin D levels were associated with increased BMI (≥ 30 kg/m2), similar to the study by Barcal et al. [21].

4. Musculoskeletal systems

4.1. Intra-articular cartilage
Recent studies have specifically investigated the effects of vitamin D on cartilage health. A systematic review by Garfinkel et al. about vitamin D and cartilage found that patients with decreased articular cartilage thickness were more likely to be vitamin D insufficient and concluded that low levels of vitamin D is a risk factor for the development of osteoarthritis (OA) [30]. Using a rodent model, Pascual-Garrido et al. found that low vitamin D levels had deleterious effects on articular cartilage as determined by histological analysis and micro-CT [31].
 Castillo et al. conducted a rat study investigating the relationship between vitamin D and the biochemical mechanisms of cartilage loss, inflammation, and OA progression and found that vitamin D supplementation had a protective effect during the initial stages of OA but not during the chronic stage [32]. In another rat study by Li et al. using ovariectomized rats, the authors found that vitamin D prevents cartilage loss through the regulation of type II collagen turnover [33]
Rai et al. evaluated the role of vitamin D in inflammation, fatty infiltration, and cartilage loss in the knee in micro swine fed a high-cholesterol diet and found increased inflammation in knee joint tissues, increased fatty infiltration in the soft tissue, and increased chondrocyte clustering in the articular cartilage, a hallmark of OA, in the vitamin D deficient and sufficient groups compared to the group supplemented with vitamin D [34].

4.2. Muscle function
Tomlinson et al. conducted a meta-analysis assessing the effects of vitamin D supplementation on upper and lower body muscle strength [35]. Results showed that there was a significant increase in muscle strength when healthy adults ages 18–40 received vitamin D3 supplementation. Rebolledo et al. performed a retrospective cohort study on the 214 athletes at the 2015 NFL combine to assess vitamin D levels and lower extremity and core muscle strains [36]. Fifty percent of athletes reported a lower extremity muscle strain or core muscle injury.
 Athletes who reported a history of injury had significantly lower levels of vitamin D compared to those who reported no injuries (p = 0.03). Additionally, athletes with inadequate levels of vitamin D had 3.61 higher odds (p < 0.001) of a hamstring strain compared to those with normal levels. However, the study was retrospective and the authors did not account for seasonal changes of vitamin D levels. Dawson-Hughes reviewed the relationship between vitamin D and muscle function and found that older adults with 25 OH D < 40 nmol/L were most likely to improve their muscle performance on strength testing with supplementation (dosing of 800–1000 IU/day) [8]. Conversely, in a randomized control trial by Saha et al. assessing the effect of calcium and vitamin D supplementation on testosterone levels and muscle strength in young males (age 20.2 ± 2.2), there was no statistically significant evidence suggesting a positive relationship with supplementation, testosterone, and muscle strength after 6 months [37].

4.3. Falls in the elderly
In the elderly, one notable area of investigation is the relationship between vitamin D and physical performance, including falls, a major cause of morbidity and mortality in this population. In reviewing the literature on the effect on vitamin D on falls and physical performance, Dhaliwal et al. found that there may be an association in older adults, although the existing literature is inconsistent [38]. However, excessive vitamin D supplementation and high serum 25 OH D levels can also increase the risk of falls in the elderly. Smith et al. conducted a double blind randomized clinical trial with elderly women given 1 of 7 possible oral vitamin D3 doses or placebo [39]
It was found that medium dosing (1600–3200 IU/per) showed the greatest reduction in falls compared to low (400–800 IU/day) or high dosing (4000–4800 IU/day). Interestingly, this study found that fall rates increased in patients with serum 25 OHD levels above 40–45 ng/mL, although the reason for this remains unclear. Duque et al. showed that vitamin D supplementation appeared to improve muscle strength and decrease falls in older patients who have low baseline levels of 25 OHD (< 30 nmol/L) [40]. Antoniak et al. conducted a meta-analysis relating vitamin D supplementation and falls in older adults found that supplementation of vitamin D decreased the risk of falls in older individuals when combined with resistance exercise [41]. In summary, vitamin D supplementation appears to be beneficial in the elderly when baseline levels of 25 OH D are low (< 30 nmol/L).

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5. Outcomes after orthopaedic surgeries

5.1. ACL reconstruction
Barker et al. studied the effects of vitamin D on strength gains after an ACL injury and subsequent reconstruction [42]. This retrospective analysis was conducted in a group of
18 Caucasian males who underwent ACL reconstruction compared to 11 control subjects without ACL injury by measuring single leg isometric strength, vitamin D, and cytokine levels 2 weeks prior to surgery and 3 months postoperative. Cytokines were elevated in the study group compared to the control group in both pre- and postoperative blood samples. Results showed that isometric leg strength increases postoperative were significantly lower in participants whose vitamin D levels were < 30 ng/mL. The authors concluded that low vitamin D levels might impair strength recovery after ACL reconstruction.
In another rat model study, Boyan et al. looked at the effects of intra-articular vitamin D injections on in vivo ACL transections [9]. Compared to placebo injections, the rats receiving vitamin D injections post in vivo ACL trans-sections showed less articular damage and lower levels of inflammatory mediators. These findings point towards some potential clinical implications on trauma induced osteoarthritis, but human clinical studies are needed to further investigate these potential correlations.

5.2. Rotator cuff injury
In a controlled laboratory study, Angeline et al. compared vitamin D deficient
rats with vitamin D sufficient control rats who underwent unilateral detachment of the supraspinatus tendon from the greater tuberosity followed by repair using bone tunnel suture fixation [43]. Results demonstrated that low vitamin D levels may negatively impact early healing of rotator cuff repair sites. It is theorized that vitamin D may have an important role in the tendon-to-bone healing process by increasing bone mineral density and strengthening skeletal muscles. However, more data is needed to determine the clinical relevance of these biochemical effects.
Oh et al. examined the relation between vitamin D levels and its effect on rotator cuff health in a retrospective study comparing vitamin D levels in patients with shoulder injuries and healthy patients with no shoulder injury [44]. The mean age of this population was 61.3 years (range, 43–80). Results showed that low vitamin D levels were associated with significant fatty degeneration of the rotator cuff muscles. Furthermore, vitamin D levels were positively correlated with isokinetic muscle torque of the shoulder.

In a clinical study evaluating the relationship of vitamin D in patients undergoing arthroscopic rotator cuff repairs for full-thickness rotator cuff tears, Ryu et al. found that low vitamin D levels were not related to outcomes after arthroscopic repair of rotator cuff muscles [45]. In this cohort, 80 patients (88%) were vitamin D insufficient, 8 (9%) were vitamin D deficient, and 3 (3%) were vitamin D sufficient.
The authors concluded that low vitamin D levels had no correlation with size of the tear, fatty infiltration in cuff muscles or the extent of the retraction, or functional outcomes as measured by the University of California, Los Angeles (UCLA) score, Constant score, and American Shoulder and Elbow Society (ASES) score at 1 year postoperatively. A major limitation of this study, however, was that only 3 patients were vitamin D sufficient. The study thus lacked power to definitely state the relationship between vitamin D and rotator cuff repair outcomes. Furthermore, the authors did not retest vitamin D levels at final follow up to adjust for variations.

5.3. Osteoarthritis
The existing literature on vitamin D levels in patients with osteoarthritis (OA) has been inconsistent. In a randomized controlled trial investigating 800 IU daily vitamin D supplementation versus placebo in 474 patients with knee OA, Arden et al. found that vitamin D supplementation did not have any effect on joint space narrowing, pain, stiffness, or functional loss [46]. This is consistent with other randomized controlled trials demonstrating no reduction in knee pain or cartilage volume loss in patients with symptomatic knee OA and low vitamin D levels [47][48].
In contrast, Zheng et al. found that vitamin D sufficiency had a beneficial effect on cartilage loss, effusion-synovitis, and physical function as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) [49].
A randomized controlled trial by Sanghi et al. demonstrated a small but statistically significant benefit of vitamin D use in patients with knee OA and vitamin D insufficiency as measured by the visual analogue scale (VAS) and WOMAC [50]. Levinger et al. found that patients with knee OA and vitamin D insufficiency (≤ 50 nmol/L) had worse knee function during balance recovery, increased pain, and locomotor dysfunction as measured by the WOMAC [51].

Similarly, Manoy et al. found that vitamin D supplementation improved quality of life, handgrip strength, physical performance, and decreased pain and oxidative protein damage in patients with OA, as measured by the WOMAC and VAS scales [52].
Several meta-analyses of vitamin D and OA have demonstrated significant associations between low vitamin D levels and knee OA, including joint space narrowing and structural changes in the knee [53][54] Regarding vitamin D supplementation in knee OA, a meta-analysis by Gao et al. found supplementation improved WOMAC pain and function, but had no effect on the prevention of tibial cartilage loss [55]. Conversely, a meta-analysis by Diao et al. found supplementation had no clinically significant effect on pain relief or joint structure improvement in patients with knee OA [56]. Despite the extensive literature on relationship between vitamin D and OA, further longitudinal studies are needed to reconcile these discrepancies in the literature.

5.4. Arthroplasty
There are several studies evaluating vitamin D status in patients undergoing arthroplasty surgeries. Shin et al. conducted a prospective cohort study with patients undergoing total knee arthroplasty (TKA) and found that early post-operative outcomes following TKA were affected by patients’ preoperative vitamin D status [57] Using a cut-off value of < 12 ng/mL to define deficiency, they found that those in the vitamin D-deficient group had significantly worse outcomes as assessed by the functional American Knee Society Score (KSS), the alternative step-test, and the six-meter walk test. 
These findings are supported by several other studies investigating vitamin D levels and pre-/post-operative functional scores in patients undergoing TKA [58][59][60]. In contrast, Lee et al. investigated vitamin D levels in patients undergoing TKA and found there was no effect of vitamin D levels on total WOMAC (p = 0.22) postoperatively, although there was an increased risk of moderate-to-severe pain in patients with low vitamin D [61]. They concluded that hypovitaminosis D was not associated with worse health-related quality of life at 3 months postoperatively following TKA.

Nawabi et al. evaluated vitamin D levels and Harris hip scores in 62 Caucasian patients undergoing THA for OA and found that vitamin D deficient patients had lower preoperative Harris hip scores (p = 0.018) and were less likely to have an excellent outcome postoperatively (p = 0.038) [62]. In contrast, Unnanuntana et al. investigated vitamin D levels and short-term functional outcomes in 219 patients following THA and found no associations between THA and functional outcomes at 6 weeks postoperatively as measured by the WOMAC, Short Form-36, 2-minute walk test, and timed get up-and-go tests [63]. Additionally, the same authors investigated vitamin D levels in a separate cohort of 200 THA patients and found no associations between vitamin D levels and in-hospital milestones, length of hospital stay, or perioperative complications [64].
In a prospective observational study by Maier et al. assessing the effect of low vitamin D levels and length of hospital stay in 1083 patients after elective hip or knee arthroplasty, patients with low vitamin D levels stayed on average 4.3 days longer post-arthroplasty than patients with adequate vitamin D levels [65]. Eighty-six percent of these patients were vitamin D insufficient, and over 60% were vitamin D deficient. Future randomized controlled clinical trials are necessary to clarify the conflicting evidence in the current literature regarding vitamin D and outcomes in total joint arthroplasty.

Recent studies have investigated postoperative complications associated with low vitamin D levels in patients undergoing arthroplasty procedures. Traven et al. retrospectively evaluated 126 revision TJA patients and found a prevalence of 55% vitamin D deficiency in this population [66]. They found that low vitamin D was associated with an increased risk of 90-day complications, including an increased risk of periprosthetic joint infection as the reason for revision surgery. These findings are supported by a study by Maier et al. [67]. A high percentage of patients requiring revision surgeries due to aseptic loosening (52%) and periprosthetic joint infection (86%) had vitamin D levels < 20 ng/mL. 
These results suggested an association between periprosthetic joint infection and vitamin D deficiency. Using an intra-articular knee implant mouse model, Hegde et al. found that vitamin D deficient mice had increased bacterial burden and neutrophil infiltration at the knee joint [68]. Furthermore, they found that replenishing the vitamin D deficient mice with supplemental vitamin D3 could reverse this effect. Further studies are needed to investigate the potential association between low vitamin D levels and increased risk of periprosthetic joint infection. Vitamin D supplementation could potentially represent a low-cost adjunct for infection prophylaxis after total joint arthroplasty
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