Table 3.

The association between vitamin D status and inflammatory responses to healthcare-associated interventions

Source	Study details	Main outcome(s)
Bertoldo et al. [76]	Design: Prospective cohort study (n = 90 elderly females with known diagnosis of osteoporosis). Intervention: Administration of 5 mg i.v. zoledronic acid. Objective: Investigated the association between 25(OH)D and APR following administration of zoledronic acid. Reference group: 25(OH)D levels > 12 ng/ml.	25(OH)D levels <12 ng/ml were associated with increased risk of APR (OR 2.38; 95% CI 1.85–2.81). Mean 25(OH)D levels dropped 17.3% (±9.6%, P <0.02) by postinfusion day 3 (compared to baseline) and was inversely correlated with CRP levels (r = − 0.79, P < 0.001)
Reid et al. [77■■]	Design: Prospective cohort study (n = 33 adult surgical patients). Intervention: Knee arthroscopy. Objective: Investigated the association between vitamin D status and postoperative inflammatory response. Reference group: Preoperative laboratory assessments.	25(OH)D levels dropped ~40% (P < 0.001) by POD2 and remained below baseline at POD5 (P < 0.001) and at 3-month follow-up (P = 0.003). DBP levels remained unchanged at POD2, POD5, and at 3-month follow-up. Albumin levels dropped ~20% (P < 0.001) by POD2, remained below baseline at POD5 (P < 0.001), but was back to baseline at 3-month follow-up. Free 25(OH)D dropped ~30% (P < 0.001) by POD2 and remained below baseline at POD5 (P < 0.001) and at 3-month follow-up (P = 0.006). CRP levels increased ~60-fold at POD2 (P < 0.001), remained elevated at POD5, but was back to baseline at 3-month follow-up. A correlation between perioperative 25(OH)D and CRP levels was not observed.
Krishnan et al. [78]	Design: Prospective cohort study (n = 19 adult surgical patients). Intervention: Cardiac surgery with intraoperative CPB. Objective: Investigated the association between vitamin D status and acute fluid loading. Reference group: Pre-CPB laboratory assessments.	25(OH)D levels dropped ~35% (P < 0.0001) following CPB and returned to baseline at POD5. 1,25(OH)2 levels dropped ~45% (P < 0.0001) following CPB and overshot by ~115% (P < 0.0001) at POD5. Albumin levels dropped ~30% following CPB (P < 0.0001) and returned to baseline by POD5. CRP levels dropped ~30% (P = 0.04) following bypass and had increased ~20-fold by POD5. Fluid balance was inversely associated with both 25(OH)D (effect size −4.9: 95% CI −6.4 to −3.4, P < 0.0001) and 1,25(OH)2D levels (effect size −14.0: 95% CI −22 to −6, P < 0.001). CRP levels were association with both 25(OH)D (effect size 0.08: 95% CI, 0.02–0.14, P < 0.01) and 1,25(OH)2D (effect size 0.62: 95% CI 0.39–0.84, P < 0.0001) levels.

25(OH)D, 25-hydroxyvitamin D; APR, acute-phase response; CI, confidence interval; CPB, cardiopulmonary bypass; CRP, C-reactive protein; DBP, vitamin D-binding protein; i.v., intravenous; POD, postoperative day.