Prevalence of Vitamin D Insufficiency and Deficiency in Young, Female Patients With Lower Extremity Musculoskeletal Complaints

Abstract

Background:

Low levels of vitamin D have well-known impacts on bone health, but vitamin D also has a more global role throughout many tissues, including skeletal muscle. The high prevalence of hypovitaminosis D and the vast physiological features of vitamin D have led researchers to examine the influence of vitamin D on physical performance and injury. Because of the critical role of vitamin D in maintaining musculoskeletal health and function, a high rate of hypovitaminosis D among female patients with a variety of musculoskeletal issues could be of high clinical relevance.

Hypothesis:

There is a high prevalence of low vitamin D in female patients with both acute and overuse sports-related issues of both soft tissue and bone.

Study Design:

Prospective cohort study.

Level of Evidence:

Level 3.

Methods:

Female patients, aged 16 to 40 years, presenting with lower extremity injury diagnosed within the past 4 weeks, no use of multivitamin or vitamin D supplement, and no history of malabsorption syndrome met the inclusion criteria. Vitamin D levels were assessed and categorized as normal (≥32 ng/mL) and low, which includes insufficient (20.01-31.9 ng/mL) and deficient (≤20 ng/mL).

Results:

Of the 105 patients enrolled, 65.7% had low vitamin D. Within the low vitamin D cohort, 40.6% were deficient and 59.4% were insufficient. Injuries were grouped into overuse or acute with 74 overuse injuries and 31 acute injuries, exhibiting low vitamin D prevalence of 60.8% and 77.4%, respectively. Patients with ligamentous/cartilaginous injuries exhibited the highest percentage of low vitamin D (76.5%), followed by those with patellofemoral-related complaints (71.0%), muscle/tendon injuries (54.6%), and bone stress injuries (45.5%). In univariable analysis, older age, non-White race, less physical activity, less high-intensity interval training days, less endurance training days, and more rest days showed an association with low vitamin D, but none showed an independent association in multivariable analysis.

Conclusion:

The prevalence of low vitamin D in female patients with various musculoskeletal complaints was high. Clinicians should evaluate for low vitamin D in both acute and overuse injuries.

Clinical Relevance:

In addition to screening, this study suggests that clinicians should evaluate for low vitamin D levels beyond bone stress injuries in the setting of acute and overuse injuries.

Vitamin D deficiency is a growing and underrecognized problem in many populations, estimated to affect 1 billion people worldwide.²⁷ Low vitamin D levels have been found in athletes from a variety of sports and of different levels,^{11,16,34,35,38,60,62,63} particularly those who train indoors or have a dark skin tone.^34,60 Active individuals commonly have low vitamin D,^11,60 but there are few studies correlating injury risk in relation to vitamin D levels. The association between low vitamin D, predisposition to sports injury, and delayed recovery requires further research.²

The roles of vitamin D in bone health, calcium homeostasis, and stress fracture risk have been supported by biomolecular and clinical research.^41,42 Clinically low vitamin D levels have been correlated with a significantly higher incidence of stress fractures in athletes and active individuals when compared with individuals with adequate vitamin D.^{12,13,35,39,50,51} Both high- and low-energy traumatic fractures are also correlated with vitamin D insufficiency in females.^10,49,56 Given the significance of vitamin D in skeletal health, identifying and treating low levels is critical for patient outcomes.

Vitamin D deficiency can cause deficits in muscle function^{2,8,21,42,45,58} and performance,^9,35,62 which affects rehabilitation.^4,5 In addition, research has demonstrated the role of vitamin D in pain pathways.^18,29,36 In a retrospective study of orthopaedic surgical cases, orthopaedic trauma and sports patients had 66% and 52% incidence of low vitamin D levels, respectively.⁷ In a study of 577 consecutive elective foot and ankle surgery patients, only 1 in 6 patients had a normal vitamin D level and 1 in 5 was grossly deficient.³

This study further investigated the prevalence of vitamin D insufficiency and deficiency (low vitamin D) in a female athlete cohort aged 16 to 40 years presented with lower extremity overuse and acute musculoskeletal injuries. We hypothesized a high prevalence of low vitamin D in female patients with both acute and overuse sports-related issues of both soft tissue and bone. This study aimed to establish an association between low vitamin D and an increased risk of certain types of lower extremity injuries.

Methods

The institutional review board at the Hospital for Special Surgery (HSS) provided approval for this study. This population-based study included female patients presented with lower extremity musculoskeletal injuries or musculoskeletal pain from a sports medicine practice. Inclusion criteria to participate in the study included: female sex, aged 16 to 40 years, presenting with a lower extremity injury diagnosed within the past 4 weeks, no use of a multivitamin or vitamin D supplement, and no history of malabsorption syndrome. Participation in the study was voluntary and required completion of a questionnaire and a blood draw. Patient information was de-identified, and collected data were securely stored in the secure REDCap data collection system developed by Vanderbilt University.

Patients were informed of the results of the vitamin D testing and were counseled on appropriate vitamin D supplementation if results demonstrated insufficiency or deficiency.

Vitamin D levels were defined as normal (≥32 ng/mL), insufficient (20.01-31.9 ng/mL), and deficient (≤20 ng/mL). “Low vitamin D” was defined to include both insufficient and deficient levels. For consistency, the patient’s blood was drawn only at HSS and samples were analyzed at the HSS laboratory. An assay of the serum 25-hydroxyvitamin D levels was performed and the results were provided to the research study team and the patient. The HSS laboratory uses the Architect i2000 System (Abbott), a chemiluminescent microparticle immunoassay, for 25-hydroxyvitamin D testing.

Statistical Analysis

Chi-squared tests were used to compare differences in proportions, and 1-way analysis of variance tests were used to compare means. A logistic regression model was also developed with the binary outcome low vitamin D versus normal. Several factors were evaluated in a univariable model to determine its effect on vitamin D status. Factors that were statistically significant (P < 0.05) were evaluated in a multivariable model to determine its independent effect on vitamin D status.

Results

A total of 105 consecutive patients, aged 16 to 40 years, were enrolled in the study, with a mean age of 28 years (SD, 6). The participants included 38 (36%) with patellofemoral-related complaints, 34 (32%) with ligament/cartilage injuries, 22 (21%) with bone stress injuries, and 11 (11%) with tendon/muscle injuries. Further patient characteristics are provided in Table 1. Of the 105 patients enrolled, 69 (65.7%) had low vitamin D levels and 36 (34.3%) were deemed sufficient. Within the low vitamin D cohort, 59.4% (41/69) were insufficient and 40.6% (28 of 69) deficient. Injuries were further grouped into overuse or acute (Table 2), with 74 overuse injuries and 31 acute injuries, representing 70.5% and 29.5% of the study population, respectively. The overuse injury cohort exhibited a low vitamin D prevalence of 60.8% (45 of 74), while the acute injury cohort exhibited a low vitamin D prevalence of 77.4% (24 of 31). Of the 45 patients in the overuse injury cohort with low vitamin D, 55.6% (25 of 45) were insufficient and 44.4% (20 of 45) deficient. Of the 24 patients in the acute injury cohort with low vitamin D, 66.7% (16/24) were insufficient and 33.3% (8/24) deficient.

Table 1.

Patient characteristics

	No. of Patients	%
Ethnicity
Other race	25	23.8
White	80	76.2
Skin type
Fair/very fair	66	62.9
Other	39	37.1
Total	105	100
Injury type
Bone	22	20.9
Ligament/cartilage	34	32.4
Patellofemoral-related	38	36.2
Tendon/muscle	11	10.5
Total	105	100
Acute or overuse injury
Acute	31	29.5
Overuse	74	70.5
Total	105	100
Season enrolled
Fall	25	23.8
Winter	35	33.3
Spring	33	31.4
Summer	12	11.4
Total	105	100
Activity level
Competitive	15	14.3
Regular vigorous	39	37.1
Regular moderate	31	29.5
Light/inactive	20	19.1
Total	105	100
Activity location
Indoors	49	46.7
Outdoors	23	21.9
Both	33	31.4
Total	105	100
HIIT days per week
None	35	33.3
1-3	48	45.7
4+	22	21.0
Total	105	100.0
Endurance training days per week
None	16	15.2
1-3	55	52.4
4+	34	32.4
Total	105	100
Rest days per week
<1 (rarely)	12	11.4
1-2	62	59.1
3+	31	29.5
Total	105	100

HIIT, high-intensity interval training.

Table 2.

Categorization of acute versus overuse injuries

Acute	Overuse
Ligamentous tears	Bone
ACL	Stress fractures
MCL	Stress reactions
MPFL	Shin splints
Meniscal tears	Patellofemoral
Ankle sprains	Patellofemoral pain syndrome
Patellar dislocations	Patellofemoral chondromalacia
	Tendinopathy

ACL, anterior cruciate ligament; MCL, medial collateral ligament; MPFL, medial patellofemoral ligament.

Those with ligament/cartilage injuries exhibited the highest percentage of low vitamin D at 76.5% (26 of 34), followed by those with patellofemoral-related complaints (71.0%; 27 of 38), muscle/tendon injuries (54.6%; 6 of 11), and bone stress injuries (45.5%; 10 of 22) (Table 3; Figure 1). The difference between these cohorts approached statistical significance (χ² = 12.2; P = 0.06). Vitamin D levels for the bone stress injuries cohort exhibited the highest mean, 37 ng/mL, compared with the muscle/tendon injuries cohort (29 ng/mL), ligament/cartilage injuries cohort (28 ng/mL), and patellofemoral-related injuries cohort (26 ng/mL). A comparison of the means among these groups indicated a statistically significant difference (analysis of variance F = 4.74; P = 0.004).

Table 3.

Vitamin D levels by injury type

	Vitamin D Sufficient, n	Vitamin D Insufficient, n	Vitamin D Deficient, n	Low Vitamin D, n (%)	Total, n
Injury type
Bone	12	8	2	10 (45.5)	22
Ligament/cartilage	8	18	8	26 (76.5)	34
Patellofemoral-related	11	13	14	27 (71.0)	38
Tendon/muscle	5	2	4	6 (54.6)	11
Total	36	41	28	69 (65.7)	105
Overuse	29	25	20	45 (60.8)	74
Acute	7	16	8	24 (77.4)	31

Figure 1.

Percentage of low vitamin D levels by injury cohort.

Vitamin D levels based on season were analyzed. There was no evidence of a seasonality effect, though the lowest proportion of patients were enrolled during the summer months (11%).

In univariable analysis, the following factors showed an association with low vitamin D: older age, non-White race, less activity, fewer high-intensity interval training days, fewer endurance training days, and more rest days (Table 4). However, no factors showed a significant association in multivariable analysis (Table 5).

Table 4.

Univariable analysis of potential risk factors for low vitamin D

Variable	Odds Ratio (95% CI)	P
Age	1.08 (1.01, 1.16)	0.03*
White	0.19 (0.05, 0.70)	0.01*
Fair skin	1.34 (0.59, 3.06)	0.49
Overuse injury	0.45 (0.17, 1.19)	0.11
Increasing activity level	0.35 (0.21, 0.60)	<0.001*
Previous stress fracture	0.43 (0.18, 1.05)	0.07
Previous traumatic fracture	0.55 (0.21, 1.43)	0.22
Previous surgery	0.98 (0.39, 2.49)	0.97
Menstrual cycle within 35 days	1.69 (0.60, 4.73)	0.32
Use of birth control	0.41 (0.13, 1.35)	0.14
Most time spent indoors	1.36 (0.60, 3.07)	0.46
Increasing HIIT days	0.42 (0.23, 0.76)	0.004*
Increasing endurance days	0.41 (0.21, 0.79)	0.008*
Increasing rest days	2.77 (1.34, 5.76)	0.006*
Eating disorder	0.63 (0.18, 2.23)	0.47
Total sun exposure	0.80 (0.56, 1.16)	0.24
Increasing sunscreen use	0.88 (0.66, 1.17)	0.37

HIIT, high-intensity interval training.

^*P < 0.05.

Table 5.

Multivariable analysis of potential risk factors for low vitamin D

Variable	Odds Ratio (95% CI)	P
Age	1.03 (0.95, 1.12)	0.41
White	0.35 (0.08, 1.53)	0.16
Increasing activity level	0.63 (0.32, 1.26)	0.19
Increasing HIIT days	0.69 (0.34, 1.40)	0.30
Increasing endurance days	0.68 (0.29, 1.58)	0.37
Increasing rest days	1.83 (0.79, 4.28)	0.16

HIIT, high-intensity interval training.

Discussion

The global and national prevalence of vitamin D insufficiency and deficiency is well-documented^27,28; however, the literature is scarce regarding data in athletes, specifically female athletes and premenopausal women.

Vitamin D levels were evaluated in 105 female patients presenting with a lower extremity musculoskeletal injury. A vitamin D level of <32 ng/mL was used as an indicator of abnormally low vitamin D. The prevalence of low vitamin D in this cohort was 65.7%. This is greater than expected and significant given that only 23.5% of females in the United States have low vitamin D as reported by the National Center for Health Statistics, Centers for Disease Control and Prevention.²⁸ Consistent with prior data, older age,²² non-White race,⁶⁰ and less activity⁵⁹ were associated with low vitamin D in univariable analysis, though no specific factors were significant in multivariable analysis.

The prevalence of low vitamin D in athletes has been described, though there is a paucity of studies conducted in female athletes. In a study of male professional basketball players, 79% were low in vitamin D.¹⁶ Prevalence studies in National Football League (NFL) players showed low levels of vitamin D ranging from 59% to 81%.^35,48,52 Among professional ice hockey players, none were found to be vitamin D deficient and only 13% to be insufficient, despite the indoor nature of the sport. However, the authors note that race and skin tone were most likely differentiating factors.³⁸ A cohort study of college athletes demonstrated that Black race and dark skin tone were the greatest predictors of abnormal vitamin D levels.⁶⁰ Studies in male athletes show high prevalence of low vitamin D but many include predominantly African American athletes who are known to have lower vitamin D levels than Caucasian athletes. African Americans made up 78% of the NFL athletes in a study that demonstrated a 59% prevalence of low vitamin D.⁴⁸ The clinical impact of low total 25-hydroxyvitamin D in this population has been questioned, as lower vitamin D–binding protein in African American athletes may result in similar levels of bioavailable 25-hydroxyvitamin D when compared with White athletes.⁴⁶ In this study, 76.2% of the study cohort identified as Caucasian and only 3.8% identified as Black or African American, thus the prevalence of low vitamin D cannot be attributed to vitamin D–binding protein. While differences in vitamin D levels do exist between racial groups, further research is needed to identify the clinical relevance of these differences in injury risk and supplementation recommendations.

Because of vitamin D’s important role in bone health, much of the current literature has focused on the association between vitamin D levels and risk of bone stress injuries in the athletically active population.^{12,13,39,51,54} Low vitamin D levels can contribute to mild increases in parathyroid hormone concentration due to 1,25-hydroxyvitamin D’s role in regulation of calcium absorption from the gut, resulting in increased bone turnover.²³ Studies have shown that low levels of vitamin D^13,39,50 and high serum parathyroid hormone⁵⁹ are associated with stress fractures, and supplementation of calcium and vitamin D reduces the incidence of stress fractures by as much as 20%.³⁰ Vitamin D levels for the bone stress injuries cohort in the current study exhibited the highest mean (37 ng/mL) and the highest percentage of participants with sufficient vitamin D levels (54.5%) when compared with the other injury cohorts. However, when examined outside the confines of this study, 45.5% prevalence of low vitamin D in the bone stress injuries cohort was still higher than average.

In studies of the general population, vitamin D deficiency has been linked to decreased strength^14,18,19,20 and increased falls.^{6,15,17,18,43,55,57} Decreasing levels of vitamin D has been associated with connective tissue and muscle injuries in collegiate swimmers³¹; additionally, NFL players with a history of lower extremity muscle strain or core muscle injury were more likely to have low vitamin D.⁴⁸ In addition to increased risk of injury, low vitamin D can impair strength recovery,^4,5 which can affect rehabilitation. In the NFL Combine study, where 59% of athletes had low vitamin D, 86% of those who missed game time had low vitamin D, suggesting the severity of the injury and/or recovery may have been affected by low vitamin D.⁴⁸ These effects on muscle function and power could explain the increased risk of muscle, tendon, ligament, and cartilage injury seen in this study.

Based on the available literature about the importance of vitamin D in optimal muscle function, pain, inflammation, and sports performance, athletes should supplement for levels less than 30 ng/mL, however, there are no clear benefits to achieving levels greater than 50 ng/mL.⁵³ A meta-analysis of randomized controlled trials investigated the effect of vitamin D supplementation on muscle strength in a young and active cohort.⁵⁸ The study concluded that vitamin D supplementation demonstrated a statistically significant positive effect on upper and lower limb strength indices. Vitamin D levels correlated positively with muscle power, force velocity, and jump height in female adolescents⁶²; and supplementing with vitamin D improved performance metrics in soccer players,⁹ ballet dancers,⁶³ and judo athletes.⁶⁴

Several studies have shown a correlation between low vitamin D and nonspecific musculoskeletal pain.^{1,24,25,29,33,44} Female patients with widespread pain had higher reports of pain if their vitamin D was low, which also corresponded to more abnormalities on nerve conduction studies.²⁹ Vitamin D has anti-inflammatory effects^26,61 and vitamin D supplementation leads to decreased prostaglandin synthesis and decreased musculoskeletal pain,^32,47 which may affect the presentation of the nontraumatic injury patients. This study showed that 71% of patients with patellofemoral-related complaints had low vitamin D, perhaps further supporting the possible association that exists between vitamin D levels and their effects on inflammation and pain. Additionally, the effect of low vitamin D on muscle function may affect one’s risk for developing patellofemoral pain and affect rehabilitation, given the critical role strengthening plays in patellofemoral pain.^37,40

Limitations

There are several limitations to this study. A larger sample size would increase power, possibly identifying more independent risk factors for low vitamin D, and ensure a representative distribution of the population. Though we tried to account for confounding variables such as sun exposure, there may have been other factors not addressed and those variables related to training habits, sun exposure, and dietary habits were subjectively reported.

Conclusion

In addition to screening, this study suggests that clinicians should be evaluating for low vitamin D beyond bone stress injuries in the setting of acute and overuse injuries. The prevalence of low vitamin D in female patients presenting with a variety of musculoskeletal complaints is high, particularly in those with ligament and cartilage injuries.