Pro-inflammatory cytokines mediate the decrease in serum 25(OH)D concentrations after total knee arthroplasty?

Med Hypotheses. 2014 Feb;82(2):134-7. doi: 10.1016/j.mehy.2013.11.020. Epub 2013 Dec 1.


Vitamin D is a fat-soluble micronutrient that regulates inflammation and skeletal muscle size and function. Inflammation and skeletal muscle dysfunction (i.e., atrophy and weakness) are predominant impairments that continue to challenge the rehabilitation from total knee arthroplasty (TKA). Data suggest a decrease in serum 25-hydroxyvitamin D (25(OH)D) concentrations after TKA. Despite the decrease being attributed to a systemic inflammatory response, it is unclear what inflammatory mediator(s) is contributing to the decrease in serum 25(OH)D concentrations after TKA. In immune cells, pro-inflammatory cytokines mediate the enzymatic conversion of 25(OH)D to 1,25-dihydroxyvitamin D, implying that pro-inflammatory cytokines contribute to the decrease in substrate availability (i.e., 25(OH)D). We propose the hypothesis that pro-inflammatory cytokines mediate the decrease in serum 25(OH)D concentrations after TKA. To complement the supporting literature for the proposed hypothesis, we analyzed serum 25(OH)D and pro-inflammatory cytokine concentrations prior to and serially after TKA in a case subject (female; age, 62 year; height, 160 cm; body mass, 63 kg; body mass index, 26.5 kg/m(2)). The subtle decrease (12%) from pre-surgery to 2-d post-surgery and the more pronounced decrease (74%) from 3-week to 8-week post-surgery in serum 25(OH)D concentrations corresponded with the increase in serum pro-inflammatory cytokine (i.e., TNF-α, IFN-γ, IL-1β, GM-CSF, and IL-6) concentrations. This observation lends credence to the proposed hypothesis that pro-inflammatory cytokines could contribute to the decrease in serum 25(OH)D concentrations after TKA. Clearly, future research is needed to confirm the proposed hypothesis and to identify if attenuating the decrease in serum 25(OH)D concentrations improves patient outcomes after TKA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthroplasty, Replacement, Knee / adverse effects*
  • C-Reactive Protein / metabolism
  • Cytokines / metabolism
  • Female
  • Humans
  • Inflammation
  • Luminescence
  • Middle Aged
  • Models, Theoretical
  • Postoperative Period
  • Treatment Outcome
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D Deficiency / complications


  • Cytokines
  • Vitamin D
  • C-Reactive Protein
  • 25-hydroxyvitamin D