53.9% of Egyptian women and 26% of Egyptian men are estimated to have osteopenia, the prevalence of osteoporosis in Egypt has been estimated at 28.4% in women and 21.9% in men (1). Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by dysregulated immune responses and systemic inflammation, leading to multi-organ damage (2–4). In Saudi Arabia, its prevalence is estimated at 19.28 per 100,000 individuals, with rising incidence over recent decades (5,6).

Vitamin D insufficiency is highly prevalent in SLE and may contribute to disease pathogenesis through immunomodulatory effects (7). Immune cells (B cells, T cells, antigen-presenting cells) express vitamin D receptors, enabling active vitamin D metabolites to suppress inflammatory pathways and promote tolerance (8,9). Critically, vitamin D acts as a negative acute-phase reactant: inflammation suppresses its serum levels, while immunosuppressive therapy often increases them independent of supplementation (10,11). This complicates the interpretation of low vitamin D status in active SLE.

While observational studies associate vitamin D deficiency with higher SLE disease activity, organ damage, and mortality (12-14), causal relationships remain unproven. Notably, evidence that vitamin D supplementation improves clinical outcomes (e.g., reduced flares, damage accrual, or mortality) is lacking (7,15). This represents a significant knowledge gap, as vitamin D insufficiency persists as an independent predictor of morbidity despite conventional therapy (13,14).

Therefore, this study aimed to determine the prevalence of vitamin D deficiency and insufficiency in an SLE cohort, examine relationships between circulating 25-hydroxyvitamin D, disease activity indices, and key clinical parameters, and evaluate the effects of vitamin D supplementation on immunological markers and clinical outcomes in patients with SLE.

The mean ±SD of age was 33.5±10.46. Most participants (86.8%) were females. Out of 68 participants, 50% were married, 41.18% were single, and 8.82% were divorced. Most participants (32.4%) completed a bachelor's, and 51.47% worked remotely. Only 25% exhibited a family history of connective tissue disorder, and 4.4% disclosed a history of smoking (Table 1).

Table 1. Table 1. Demographic data of the patients studied

Data is presented as frequency %.

Table 2 shows that most participants (98.53%) had illness duration over six months. Fever (2.94%) and weight loss (5.9%) were uncommon. Oral ulcers appeared in 11.76%, nasal ulcers and shortness of breath in 11.8%, and photosensitivity in 60.29%. Malar rash (19.2%) and alopecia (60.3%) were frequent, while arthritis (10.29%) and arthralgia (27.94%) were the main joint issues. Menstrual irregularities affected 36.8%, with 22.1% reporting amenorrhea. OCP use was 13.24%, and 23.53% experienced pregnancy post-diagnosis, with 22.06% reporting abortions.

Table 2. Table 2. Clinical characteristics and reproductive health of the studied patients

OCP: Oral contraceptive pills.

Pericarditis and pleuritic pain were found in 5.9% of patients, and pulmonary hypertension in 7.35%. IHD affected 7.4%, Raynaud’s phenomenon 22.06%, and DVT 8.8%. Colitis occurred in 4.41%, lymphadenopathy in 13.24%, and organomegaly in 8.82%. Dialysis was needed in 2.9%. Stroke affected 14.71%, mobility issues 19.12%, neuropathy 27.94%, and psychological symptoms 13.24% (Table 3).

Table 3. Table 3. Comorbidities of the studied patients

HTN: hypertension; IHD: ischemic heart disease; DVT: deep vein thrombosis; DM: Diabetes mellitus.

RBCs, albumin, vitamin D, and Ca were markedly more elevated post than pretreatment (p < 0.05). ESR, bilirubin, and ALP were substantially lower post than pretreatment (p < 0.05). Hemoglobin, RDW, WBCs, platelets, CRP, ALT, AST, Creatinine, urea, and random protein in urine were insignificantly different between pretreatment and post-treatment (Table 4).

Table 4. Table 4. Laboratory parameters of the patients studied ^*

Significant p-value <0.05.

RBCs: red blood cell count; RDW: red cell distribution width; WBCs: white blood cells; ESR: erythrocyte sedimentation rate; CRP: c-reactive protein; ALT: alanine aminotransferase; AST: Aspartate aminotransferase; ALP: alkaline phosphatase; Ca: calcium.

The prevalence of vitamin D insufficiency was 31 (45.6%), and deficiency was 18 (26.5%) pretreatment, and became 9 (13.2%) and 5 (7.4%), respectively, post-treatment. Vitamin D insufficiency and deficiency percentage were substantially decreased post than pretreatment (p < 0.05). SLEDAI score was considerably lower post than pretreatment (p < 0.001) (Table 5).

Table 5. Table 5. Vitamin D insufficiency and deficiency and SLEDAI score of the patients studied ^*

Significant p-value <0.05.

SLEDAI: Systemic Lupus Erythematosus Disease Activity Index.

In the pretreatment phase, vitamin D showed a substantial inverse correlation with (WBCs, ESR, ALP, and SLEDAI score) and a positive correlation with (albumin and Ca). Post-treatment, vitamin D showed a substantial inverse correlation with (bilirubin, ESR, ALP, and SLEDAI score) and a substantial positive correlation with (albumin and Ca) (Table 6).

Table 6. Table 6. Correlation between vitamin D levels and laboratory parameters of the studied patients ^*

Significant p-value <0.05.

r: Pearson coefficient; RBCs: red blood cell count; RDW: red cell distribution width; WBCs: white blood cells; ESR: erythrocyte sedimentation rate; CRP: c-reactive protein; ALT: alanine aminotransferase; AST: aspartate aminotransferase; ALP: alkaline phosphatase; Ca: calcium.

Vitamin D, a steroid hormone activated in the liver and kidneys, regulates calcium metabolism (15), suppresses Th1, enhances Tregs (19,20), affects dendritic cells and IFN genes in SLE (21,22), with deficiency common from photoprotection, renal issues, and medications (23).

The study results revealed that RBCs, albumin, vitamin D, and Ca were significantly higher post than pre. ESR, bilirubin, and ALP were substantially lower post than pre. Vitamin D insufficiency and deficiency percentage were considerably lower post-treatment than pretreatment. SLEDAI score showed a substantial decrease after post-treatment in contrast to pretreatment. In the pretreatment phase, a substantial inverse correlation was observed between vitamin D and (WBCs, ESR, ALP, and SLEDAI score), while we observed a positive correlation between vitamin D and (albumin and Ca). Additionally, a substantial negative correlation was observed between vitamin D and (bilirubin, ESR, ALP, and SLEDAI score) following treatment. Conversely, a substantial positive correlation was identified between albumin, calcium, and vitamin D.

Vitamin D is essential for the immune system, as it regulates the production of antibodies, inhibits IL-2, and the proliferation of lymphocytes (24). Vitamin D3 has been found to prevent autoimmune diseases like SLE; however, its deficiency potentially leads to SLE etiology and aggravation (25). High vitamin D3 levels have been shown to lower the disease risk by 62%. Moreover, in vitro studies have shown that vitamin D3 can prevent dendritic cell differentiation, modulate T cell phenotype and function, and prevent the production of cytokines and the proliferation of T cells (26). This suggests that vitamin D status correlates with SLE disease activity through immunomodulatory mechanisms, including dendritic cell regulation and T-cell function (27). Fibromyalgia and fibromyalgianess are increased in SLE patients, and regular exercise can help improve fatigue, cognitive dysfunction, and pain from fibromyalgia (28).

Vitamin D deficiency can exacerbate SLE symptoms and increase autoantibody generation. At the same time, its immunomodulatory effects help mitigate immunological abnormalities in SLE patients, making it a risk associated with SLE disease development (29). Vitamin D is a safe and cost-effective intervention for patients with SLE, offering immune-inflammatory-modulatory benefits. It has the potential to enhance musculoskeletal and cardiovascular symptoms, preserve immune health, and prevent the excess morbidity and mortality that are associated with vitamin D deficiency (30).

In agreement with our result, Kamen et al. (31) discovered a high percentage of patients with SLE suffer from vitamin D deficiency, with substantially reduced levels of serum 25-hydroxyvitamin D. This deficiency was particularly prevalent in African Americans and individuals with photosensitivity. Similarly, Borba et al. (32) discovered that patients with high SLE activity had lower levels of vitamin D3 in comparison to controls and low-activity patients. Moreover, Bonakdar et al. (33) and Islam et al. (34) noted that at the time of diagnosis, the majority of SLE patients exhibit vitamin D deficiency, which is correlated with an increased clinical activity. Furthermore, Mahmoud et al. (35) demonstrated that the correlation between vitamin D and (ESR and ALP) was inverse, while Ca and serum albumin exhibited a positive correlation with vitamin D. However, no correlation was observed between vitamin D and WBCs in patients with SLE. The correlation between vitamin D and (ESR and ALP) was inverse, while Ca and serum albumin exhibited a positive correlation with vitamin D. However, no relationship was observed between vitamin D and WBCs in patients with SLE. Also, Acosta Colman et al. (36) showed that there was an inverse relationship between vitamin D concentrations and SLE disease activity.

Our trial has several limitations, including a relatively limited sample size and single-center design, which limits generalizability to broader populations. The retrospective nature of the study prevented standardized follow-up intervals and comprehensive documentation of concurrent medications that could influence both vitamin D metabolism and SLE activity. Detailed information on concurrent SLE treatments, including immunosuppressive medications, corticosteroids, and other therapeutic interventions, was not systematically available, limiting our ability to isolate the independent effects of vitamin D supplementation. Additionally, data on patient adherence to supplementation protocols, baseline dietary vitamin D intake, and sun exposure patterns were not collected, which could have influenced the observed outcomes. Further prospective, controlled trials with standardized treatment protocols are needed to establish definitive guidelines for vitamin D supplementation in SLE management and to confirm the causal relationship between vitamin D status and disease activity improvement.

The prevalence of vitamin D insufficiency was 31 (45.6%), and deficiency was 18 (26.5%) pretreatment, and became 9 (13.2%) and 5 (7.4%), respectively, post-treatment. The results indicated a substantial correlation between vitamin D levels and (bilirubin, ESR, ALP, albumin, and Ca). Vitamin D deficiency showed an inverse correlation with SLE activity before treatment, while vitamin D supplementation correlated with reduced SLE activity.