Compromised Activation of Vitamin D After Elective Surgery: A Prospective Pilot Study

Surgical stress reduces concentrations of most proteins in serum and necessitates a rapid adjustment of hormones dependent on protein binding. Activation of vitamin D by renal 1α-hydroxylation is dependent on protein binding because 1,25-dihydroxyvitamin D (1,25(OH)₂D₃) is formed after megalin-mediated reabsorption of 25-hydroxyvitamin D (25OHD) bound to vitamin D binding protein (DBP). Postoperative alterations in serum concentrations of DBP and albumin may therefore impair 1,25(OH)₂D₃ production. Our objective was to determine sex-specific changes in serum concentrations of vitamin D metabolites and sex steroids 2, 6, 24, and 48 hours and 3 weeks postoperatively. Fourteen women and eleven men aged 45 to 77 years without severe comorbidities undergoing unilateral total knee arthroplasty participated in this prospective study in a tertiary center for arthroplasty (trial ID: NCT02336932). The main outcome measures were total and free serum concentrations of 25OHD, 1,25(OH)₂D₃, 24,25-dihydroxyvitamin-D, DBP, albumin, sex hormone binding globulin (SHBG), calcium, and parathyroid hormone (PTH). Serum albumin and SHBG decreased postoperatively (Δalbumin_48h -18% [-22%; -14%]). Unexpectedly, concentrations of DBP and 25OHD remained unaltered, but 1,25(OH)₂D₃ declined postoperatively. 1,25(OH)₂D₃ was 3 weeks after surgery -24% (-40%; -8%) lower than preoperative levels, whereas 24,25-dihydroxyvitamin-D remained unchanged in postmenopausal women. The calculated conversion rate of 25OHD to 1,25(OH)₂D₃ was strongly associated with serum 25-OHD and PTH preoperatively, whereas serum calcium was most predictive postoperatively. In conclusion, surgery had no effect on serum concentrations of DBP, 25OHD, and PTH, whereas production of 1,25(OH)₂D₃ was markedly reduced. Further studies are needed to determine duration and putative outcome effects of this postoperative 1,25(OH)₂D₃ deficit in women, which in part may be due to discordance in CYP27B1 and CYP24A1 activity.