Waldron · Journal of clinical pathology 2013 · prospective before-and-after observational study · n=30

Vitamin D: a negative acute phase reactant.

Cited 276 times in the scientific literature.

Level 4 - case-series / case-control

Uncontrolled prospective before-and-after observational study (case series)

PubMed 23454726 · doi:10.1136/jclinpath-2012-201301 · record verified 2026-08-27

What was done

Serum 25-hydroxyvitamin D [25-(OH)D], serum vitamin D binding protein (VDBP), urinary VDBP, and C-reactive protein (CRP) were measured in 30 patients immediately before and 48 hours after elective knee or hip arthroplasty to assess how acute systemic inflammation affects circulating vitamin D markers.

What was found

Following surgery, mean (SD) CRP increased from 5.0 (5.5) to 116.0 (81.2) mg/L (p < 0.0001) and urinary VDBP/creatinine ratio rose from 8 (9) to 20 (25) pg/mmol (p = 0.0004). Concurrently, serum 25-(OH)D dropped from 56.2 (30.3) to 46.0 (27.6) nmol/L (p = 0.0006) and serum VDBP dropped from 334 (43) to 298 (37) mg/L (p < 0.0001).

Why it matters

Serum 25-(OH)D acts as a negative acute phase reactant, meaning acute or chronic inflammatory states transiently depress measured circulating levels. This makes 25-(OH)D an unreliable biomarker of baseline vitamin D status during active inflammation and suggests low vitamin D may often be a consequence rather than a cause of inflammatory disease.

Limits

The study included a small sample size (n = 30) from a single clinical setting (elective joint replacement) and measured outcomes at only one post-operative time point (48 hours). It lacked an unoperated control group to rule out perioperative confounders such as hemodilution from intravenous fluid administration, and did not follow patients until inflammatory resolution to track recovery of vitamin D levels.

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