Vitamin D, a fat-soluble secosteroid, plays a crucial role not only in calcium and phosphate metabolism but also in the regulation of neuromuscular and immune function. Beyond its traditional association with bone health, emerging literature suggests a wider spectrum of systemic effects, notably in mood regulation and musculoskeletal pain. Recent evidence indicates that vitamin D receptors are present in various brain regions involved in mood regulation, implicating vitamin D in the pathophysiology of depression. Concurrently, vitamin D deficiency has also been linked to chronic pain syndromes, especially those with musculoskeletal origins, making it a potential modifiable contributor to poor quality of life in affected individuals.[1]

Globally, hypovitaminosis D is now recognized as a pandemic, particularly in regions with limited sun exposure, urbanized indoor lifestyles, and poor dietary intake. Paradoxically, even in sun-rich countries like India, vitamin D deficiency remains alarmingly high due to factors such as clothing customs, pollution, darker skin pigmentation, and limited outdoor activity. A growing body of literature has examined vitamin D’s role in neuropsychiatric and pain disorders, yet consensus on causality remains elusive. Nevertheless, several observational studies have found associations between low serum 25(OH)D levels and increased prevalence of depressive symptoms, fatigue, and generalized body aches.[2]

Depression is one of the leading causes of disability worldwide and is often underdiagnosed in outpatient settings, especially when symptoms overlap with somatic complaints. Similarly, musculoskeletal pain is a frequent reason for outpatient consultations and is commonly attributed to non-specific etiologies. The possible unifying factor—vitamin D deficiency—warrants further clinical investigation to elucidate its role and therapeutic implications.[3]

Despite growing attention globally, few studies in Indian outpatient settings have comprehensively evaluated the triad of vitamin D deficiency, depressive symptoms, and musculoskeletal pain. Understanding this association could offer a simple, cost-effective, and potentially reversible therapeutic approach to alleviating physical and psychological distress among patients attending general medicine clinics.[4]

Aim

To assess the association between vitamin D deficiency, depression, and musculoskeletal pain among outpatients attending the general medicine department.

Objectives

1. To estimate the prevalence of vitamin D deficiency among general medicine outpatients.
2. To assess the correlation between vitamin D levels and symptoms of depression.
3. To evaluate the association between vitamin D levels and severity of musculoskeletal pain.

Source of Data: The study population comprised adult outpatients attending the General Medicine Department of a tertiary care hospital in Western India.

Study Design: This was a cross-sectional observational study.

Study Location: Department of General Medicine, at tertiary care hospital.

Study Duration: The study was conducted over a period of 12 months from January 2024 to December 2024.

Sample Size: A total of 200 patients were included in the study. The sample size was calculated based on a 95% confidence level, expected prevalence of vitamin D deficiency of 60%, and a 7% margin of error using the formula: Sample size = Z² × p × q / d²

Inclusion Criteria:

• Patients aged 18–65 years attending the general medicine outpatient department.
• Patients presenting with generalized musculoskeletal pain for ≥4 weeks without any identifiable local pathology.
• Patients willing to give informed consent.

Exclusion Criteria:

• Patients with known psychiatric illness or currently on antidepressants.
• Patients with autoimmune disorders, chronic kidney or liver disease, malignancy, or metabolic bone diseases.
• Pregnant or lactating women.
• Patients on vitamin D supplementation in the past 3 months.

Procedure and Methodology: After obtaining ethical approval and written informed consent, patients attending the general medicine OPD were screened for eligibility. Basic demographic details, medical history, and lifestyle factors were recorded. Each participant was evaluated for depressive symptoms using the validated Patient Health Questionnaire-9 (PHQ-9) scale. A score ≥10 was considered indicative of moderate to severe depression.

Musculoskeletal pain severity was assessed using the Visual Analog Scale (VAS) ranging from 0 to 10. Patients scoring ≥4 were considered to have significant pain. Venous blood samples were drawn between 9:00 and 11:00 AM after overnight fasting.

Sample Processing: 5 ml of venous blood was collected under aseptic precautions. Serum was separated by centrifugation and stored at -20°C until analysis. Serum 25-hydroxyvitamin D levels were estimated using chemiluminescence immunoassay (CLIA). Vitamin D status was categorized as:

• Deficient: <20 ng/mL
• Insufficient: 20–29 ng/mL
• Sufficient: ≥30 ng/mL

Statistical Methods: Data were entered into Microsoft Excel and analyzed using SPSS version 25.0. Continuous variables such as age and serum vitamin D levels were expressed as mean ± SD. Categorical variables were presented as proportions. The chi-square test was used for associations between categorical variables. Correlations between vitamin D levels and PHQ-9/VAS scores were assessed using Pearson’s correlation coefficient. A p-value <0.05 was considered statistically significant.

 Data Collection: A structured proforma was used to collect data, including:

• Demographic profile (age, gender, socioeconomic status)
• Lifestyle factors (sunlight exposure, diet)
• Clinical history and symptom duration
• PHQ-9 score
• VAS for musculoskeletal pain
• Laboratory reports including serum 25(OH)D levels

All data were de-identified and securely stored to maintain confidentiality.

Table 1: Baseline Characteristics of Study Participants (N=200)

The mean age of the study participants was 41.3 years with a standard deviation of 12.8 years. The majority were male (52.0%). The mean Body Mass Index (BMI) was 24.6 ± 3.9 kg/m². A substantial proportion (61.0%) of participants had low sunlight exposure (<30 minutes/day), which showed a statistically significant association with vitamin D status (χ² = 3.84, OR = 1.67, 95% CI: 1.02–2.72, p = 0.04). Approximately 44.5% followed a vegetarian diet, which was not significantly associated with vitamin D levels (χ² = 0.77, p = 0.38). The mean serum vitamin D level was 18.7 ± 7.3 ng/mL and showed a statistically significant deviation from normal (t = 2.14, 95% CI: -0.12 to 3.68, p = 0.03). The average PHQ-9 score, indicating depressive symptoms, was 10.3 ± 3.6, with a statistically significant result (t = 2.91, 95% CI: 1.02 to 4.10, p = 0.005). The mean Visual Analog Scale (VAS) score for musculoskeletal pain was 6.4 ± 2.1, also statistically significant (t = 3.02, 95% CI: 1.13 to 3.45, p = 0.003). These findings collectively suggest a notable prevalence of both depressive symptoms and pain in the vitamin D deficient population.

Table 2: Prevalence of Vitamin D Deficiency (N=200)

Among the 200 participants, 123 (61.5%) were found to have vitamin D deficiency (serum levels <20 ng/mL), with a significant chi-square value of 36.2 and a prevalence confidence interval of 54.6% to 67.9% (p < 0.001). Additionally, 24.5% had insufficient vitamin D levels (20–29 ng/mL), while only 14.0% had sufficient levels (≥30 ng/mL). The high prevalence of deficiency underscores the magnitude of this public health concern even in a general medicine outpatient setting.

Table 3: Correlation between Vitamin D Levels and Depression (PHQ-9 Score)

The mean vitamin D level of participants was 18.7 ± 7.3 ng/mL, while the mean PHQ-9 score indicating depressive symptoms was 10.3 ± 3.6. A moderate inverse correlation was observed between serum vitamin D levels and depression scores (r = -0.43), with a statistically significant correlation coefficient (95% CI: -0.52 to -0.32, p < 0.001). Both parameters showed statistically significant t-values (Vitamin D: t = 2.14, p = 0.03; PHQ-9: t = 2.91, p = 0.005). These results suggest that lower vitamin D levels may be associated with greater depressive symptoms among outpatients.

Table 4: Association between Vitamin D Levels and Musculoskeletal Pain (VAS Score)

In evaluating the association between vitamin D levels and musculoskeletal pain, the mean vitamin D level remained 18.7 ± 7.3 ng/mL, and the average VAS score was 6.4 ± 2.1. A significant inverse correlation was seen between these two variables (r = -0.39), suggesting that as vitamin D levels decreased, musculoskeletal pain severity increased. This relationship was statistically significant (95% CI for r: -0.49 to -0.27, p < 0.001), with individual t-tests also showing significance (Vitamin D: t = 2.14, p = 0.03; VAS: t = 3.02, p = 0.003). These findings support the hypothesis that vitamin D deficiency is associated with heightened perception of musculoskeletal pain.

Table 1: Baseline Characteristics: The demographic profile of the study revealed a mean age of 41.3 years and a male predominance (52.0%). This distribution aligns with findings from McCabe PS et al.(2016)[5], who reported similar adult outpatient demographics with nonspecific musculoskeletal complaints. A mean BMI of 24.6 kg/m² in our study falls within the overweight range, consistent with studies indicating higher BMI as a common comorbidity in vitamin D-deficient individuals Merlo C et al.(2015)[6].

A significant proportion of participants (61.0%) had sunlight exposure <30 minutes/day, and this was statistically associated with vitamin D deficiency (p = 0.04). This is in agreement with the work of Frigstad SO et al.(2019)[7], who observed that limited UVB exposure in urban Indian populations is a major contributor to hypovitaminosis D despite abundant sunlight. Vegetarianism was not significantly associated with vitamin D levels in our sample (p = 0.38), paralleling the findings by Abdul-Razzak K et al.(2024)[8], who found that although vegetarians often have lower dietary vitamin D intake, serum levels may not always differ significantly due to sun exposure and supplementation practices.

The mean vitamin D level (18.7 ng/mL) was below sufficiency thresholds, aligning with the national data indicating widespread vitamin D deficiency in India [3,5]. Both PHQ-9 and VAS scores were significantly elevated, suggesting notable coexisting depressive symptoms and musculoskeletal pain, respectively. This supports the hypothesis by Alkhatatbeh MJ et al.(2021)[9] that vitamin D plays a role in mood regulation and pain perception.

Table 2: Prevalence of Vitamin D Deficiency: Vitamin D deficiency was observed in 61.5% of participants, consistent with studies by Kumar Yadav R et al.(2021)[10], who found prevalence rates ranging from 50–90% in Indian urban outpatient populations. Our results fall within this expected range, with statistical significance supporting a high disease burden. Only 14% of participants had sufficient levels, reinforcing the urgent need for public health strategies to address this preventable deficiency.

 Table 3: Correlation Between Vitamin D Levels and Depression: There was a moderate negative correlation between serum vitamin D levels and PHQ-9 depression scores (r = -0.43, p < 0.001), indicating that lower vitamin D levels were significantly associated with higher depressive symptoms. This finding is strongly supported by the meta-analysis conducted by Ali OM.(2022)[11], which reported that low vitamin D levels are significantly associated with depression in both clinical and community settings. Similarly, Alshogran OY et al.(2023)[12] found improvement in depressive scores following vitamin D supplementation in vitamin D-deficient individuals.

Table 4: Association Between Vitamin D Levels and Musculoskeletal Pain: A similar inverse correlation was noted between vitamin D levels and musculoskeletal pain scores (VAS), with a correlation coefficient of -0.39 (p < 0.001). These results resonate with the findings of Thörneby A et al.(2016)[13], who reported that 93% of patients with persistent musculoskeletal pain were found to be vitamin D deficient, and that symptoms improved upon correction of the deficiency.

This cross-sectional study conducted on 200 general medicine outpatients revealed a high prevalence (61.5%) of vitamin D deficiency. A statistically significant negative correlation was found between serum vitamin D levels and both depression scores (PHQ-9) and musculoskeletal pain scores (VAS). Participants with lower vitamin D levels tended to report more severe depressive symptoms and greater intensity of musculoskeletal pain. Sunlight exposure under 30 minutes per day was also significantly associated with vitamin D deficiency. These findings highlight the potential role of vitamin D status not only in physical but also in mental health, especially in populations presenting with nonspecific symptoms. Screening for vitamin D deficiency could serve as a useful adjunct in the holistic assessment of patients with chronic pain or depressive features in outpatient settings. Early identification and correction may improve both physical and psychological outcomes.

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