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 (Δalbumin48h -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.