title: Total 25(OH) vitamin D, free 25(OH) vitamin D and markers of bone turnover in cirrhotics with and without synthetic dysfunction.
abstract: OBJECTIVE
  Current clinical assays for total 25-hydroxy (OH) vitamin D measure vitamin D bound to vitamin D-binding protein (DBP) and albumin plus unbound ('free') D. We investigated the relationship between total and free 25(OH)D with bone metabolism markers in normal (>3.5 g/dl) vs. low (≤3.5 g/dl) albumin cirrhotics.
  
  
  METHODS
  Eighty-two cirrhotics underwent measurement of free and total 25(OH)D by immunoassay, DBP and markers of bone metabolism [intact parathyroid hormone (iPTH), C-telopeptide (CTX), bone-specific alkaline phosphatase (BSAP), osteocalcin, amino-terminal pro-peptide of type 1-collagen (P1NP)]. Pearson's coefficients assessed relevant associations.
  
  
  RESULTS
  Cirrhotics with low (n = 54) vs. normal (n = 28) albumin had lower total 25(OH)D (12.1 vs. 21.7 ng/ml), free 25(OH)D (6.2vs.8.6 pg/ml) and DBP(91.4 vs. 140.3 μg/ml) [P < 0.01 for each]. iPTH was similar in low and normal albumin groups (33 vs. 28 pg/ml; P = 0.38), although serum CTX(0.46vs.0.28 ng/ml) and BSAP(31.7 vs. 24.8 μg/L) were increased (P < 0.01). An inverse relationship was observed between total 25(OH)D and iPTH in normal (r = -0.47, P = 0.01) but not low albumin cirrhotics (r = 0.07, P = 0.62). Similar associations were seen between free 25(OH)D and iPTH(Normal: r = -0.46, P = 0.01; Low: r = -0.03, P = 0.84). BSAP, osteocalcin and P1NP were elevated above the normal range in all cirrhotics but not consistently associated with total or free 25(OH)D.
  
  
  CONCLUSIONS
  Cirrhotics with low vs. normal albumin have lower levels of DBP, total and free 25(OH)D. The expected relationship between total or free 25(OH)D with iPTH was observed in normal but not in low albumin cirrhotics, demonstrating that total 25(OH)D is not an accurate marker of bioactive vitamin D status in cirrhotics with synthetic dysfunction. Additional investigation into the role of vitamin D supplementation and its impact on bone mineral homoeostasis in this population is needed.
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Lai
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, CA, USA.|Department of Dermatology, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Bikle
authors.affiliation: Department of Medicine, St. Elizabeth's Medical Center, Boston, MA, USA.
authors.forename: Blanca
authors.initials: B
authors.lastname: Lizaola
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Hilary
authors.initials: H
authors.lastname: Hayssen
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Norah A
authors.initials: NA
authors.lastname: Terrault
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, CA, USA.|Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Janice B
authors.initials: JB
authors.lastname: Schwartz
mesh_terms: D000418:Albumins / Q000032:analysis*; D000469:Alkaline Phosphatase / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016723:Bone Remodeling; D002118:Calcium / Q000097:blood; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood*; D011446:Prospective Studies; D014807:Vitamin D / Q000097:blood*; D014809:Vitamin D-Binding Protein / Q000097:blood*
chemical_list: D000418:Albumins; D015415:Biomarkers; D010281:Parathyroid Hormone; D014809:Vitamin D-Binding Protein; D014807:Vitamin D; D000469:Alkaline Phosphatase; D002118:Calcium
keywords: albumin; free hormone hypothesis; metabolic bone disease; parathyroid hormone; vitamin D-binding protein