Preoperative Vitamin D Deficiency and Postoperative Pain After Breast Cancer Surgery: A Prospective Cohort Study Summary

Vitamin D is widely recognized for its role in bone metabolism, but growing evidence suggests it may also influence pain perception, immune modulation, and inflammatory pathways. In recent years, researchers have explored whether low vitamin D levels contribute to higher pain sensitivity and increased opioid requirements after surgery.

A prospective observational study published in the journal Regional Anesthesia & Pain Medicine examined the relationship between preoperative vitamin D status and acute postoperative pain in women undergoing unilateral modified radical mastectomy for breast cancer. The study provides clinically relevant insights for anesthesiologists, pain specialists, and perioperative care teams.

Study Overview

This study was conducted at Fayoum University Hospital between September 2024 and April 2025. It included 184 female patients classified as ASA physical status II to III who were scheduled for elective unilateral modified radical mastectomy.

Patients were divided into two equal groups based on serum 25-hydroxyvitamin D levels:

• Vitamin D deficient group: <30 nmol/L
• Vitamin D sufficient group: ≥30 nmol/L

The primary outcome was the incidence of moderate to severe postoperative pain defined as a Numerical Rating Scale (NRS) score greater than 3 at 12 hours after surgery. Secondary outcomes included opioid consumption, pain scores over 24 hours, hemodynamic stability, adverse events, and hospital stay.

Key Findings

Higher Pain Incidence in Vitamin D Deficiency

Patients with vitamin D deficiency experienced significantly more postoperative pain. At 12 hours after surgery:

• 17.4 percent of vitamin D deficient patients reported moderate to severe pain
• 2.2 percent of vitamin D sufficient patients reported the same level of pain

This difference was statistically significant and clinically meaningful.

When pain was analyzed across the full 24-hour postoperative period, the overall pain burden remained consistently higher in the vitamin D deficient group.

Increased Opioid Requirement

One of the most important findings was the difference in analgesic consumption:

• Intraoperative fentanyl use was higher in the vitamin D deficient group
• Postoperative tramadol consumption was significantly greater in deficient patients

The difference in postoperative opioid use was particularly notable, suggesting that vitamin D status may influence postoperative analgesic needs.

Independent Risk Factor for Pain

After adjusting for confounders such as age, body mass index, ASA status, surgery duration, and intraoperative fentanyl use, vitamin D deficiency remained independently associated with postoperative pain.

• Adjusted odds ratio: 3.12
• 95 percent confidence interval: 1.58 to 6.13

This suggests that vitamin D deficiency is not just correlated with pain but may independently contribute to increased pain susceptibility in the early postoperative period.

Study Design and Methodology Highlights

The study used a prospective observational design, which strengthens the reliability of its findings compared with retrospective analyses. Key methodological features included:

• Standardized anesthesia protocol for all patients
• Blinded outcome assessment
• Controlled postoperative analgesia using patient controlled analgesia devices
• Objective measurement of serum 25-hydroxyvitamin D using ELISA testing
• Use of multivariable logistic regression to adjust for confounders

Pain was assessed using the validated 11-point Numerical Rating Scale at multiple postoperative time points including immediate recovery, 6, 12, 18, and 24 hours.

Clinical Interpretation

The findings suggest a clinically relevant association between low preoperative vitamin D levels and increased postoperative pain intensity as well as higher opioid requirements.

Several mechanisms may explain this relationship:

1. Anti-inflammatory effects of vitamin D
   Vitamin D may reduce inflammatory cytokines such as interleukin-6 and tumor necrosis factor alpha.
2. Neuromodulation
   Vitamin D may influence central and peripheral pain processing pathways.
3. Reduced pain threshold in deficiency states
   Low vitamin D levels may contribute to hypersensitivity and central sensitization.

These mechanisms remain under investigation but provide a biologically plausible explanation for the observed findings.

Postoperative Outcomes Beyond Pain

The study also evaluated secondary clinical outcomes:

• Higher incidence of postoperative nausea in vitamin D deficient patients
• Slightly longer hospital stay in the deficient group
• No significant difference in respiratory depression or serious sedation events
• Similar overall patient satisfaction between groups

The increased nausea is likely related to higher opioid consumption rather than vitamin D status directly.

Limitations of the Study

While the study provides valuable insights, several limitations must be considered:

• Single center design limits generalizability
• All participants were from one geographic population
• Short follow up period limited assessment of chronic pain outcomes
• Lack of inflammatory biomarker data
• Potential residual confounding from unmeasured variables such as psychological status, cancer stage, and preoperative anxiety
• Observational design prevents causal inference

These limitations mean the findings should be interpreted as associative rather than definitive proof of causation.

Clinical Implications

This study raises important considerations for perioperative care in breast cancer surgery patients:

• Preoperative screening for vitamin D deficiency may help identify patients at higher risk of postoperative pain
• Vitamin D supplementation could be considered as part of prehabilitation strategies, although randomized trials are needed
• Pain management protocols may need adjustment for patients with low vitamin D levels
• Further research should investigate whether correcting deficiency improves postoperative outcomes

If confirmed in interventional studies, vitamin D optimization could become a simple, low cost adjunct to multimodal analgesia strategies.

Conclusion

This prospective observational study demonstrates a significant association between preoperative vitamin D deficiency and increased postoperative pain and opioid consumption in patients undergoing unilateral modified radical mastectomy.

Patients with low vitamin D levels experienced higher pain scores, required more opioids, and showed a higher likelihood of moderate to severe pain in the early postoperative period. Vitamin D deficiency remained an independent predictor of pain after adjusting for clinical confounders.

While causality cannot be confirmed, the findings support further investigation into vitamin D as a potential modifiable factor in perioperative pain management.

Source

Abdelhady MA, Boulos ML, Hamed MA, et al. Association between preoperative vitamin D level and postoperative pain in patients undergoing breast cancer surgery: a prospective observational study. Regional Anesthesia & Pain Medicine. 2025.

Disclaimer

This article is a rephrased educational summary intended for healthcare professionals and researchers. It does not constitute medical advice, diagnosis, or treatment guidance. Clinical decisions should be based on full peer-reviewed publications, institutional protocols, and individual patient assessment.