title: Serum 25-hydroxyvitamin D levels modulate the acute-phase response associated with the first nitrogen-containing bisphosphonate infusion.
abstract: The acute-phase response (APR) is the most frequent side effect after the first dose of intravenous nitrogen-containing bisphosphonates (N-BPs). It has been demonstrated in vitro that N-BPs stimulate gammadelta T-cell proliferation and production of cytokines and that vitamin D is able to modulate them. Therefore, we have studied the relationship between bone metabolism parameters, particularly for 25-hydroxyvitamin D [25(OH)D], and APR in patients treated with 5 mg zoledronic acid intravenously. Ninety N-BP-naive osteoporotic women (63.7 +/- 10.6 years of age) were stratified for the occurrence of APR (APR(+)) or not (APR(-)) and quantified by body temperature and C-reactive protein (CRP). The APR(+) women had significantly lower 25(OH)D levels than the APR(-) women. Levels of 25(OH)D were normal (>30 ng/mL) in 31% of APR(+) women and in 76% of APR(-) women. The odds ratio (OR) to have APR in 25(OH)D-depleted women was 5.8 [95% confidence interval (CI) 5.30-6.29; p < .0002] unadjusted and 2.38 (95% CI 1.85-2.81; p < .028) after multiple adjustments (for age, body mass index, CRP, calcium, parathyroid hormone, and C-telopeptide of type I collagen). Levels of 25(OH)D were negatively correlated with postdose body temperature (r = -0.64, p < .0001) and CRP (r = -0.79, p < .001). An exponential increase in fever and CRP has been found with 25(OH)D levels lower than 30 ng/mL and body temperature less than 37 degrees C, whereas normal CRP was associated with 25(OH)D levels above 40 ng/mL. The association between post-N-BPs APR and 25(OH)D suggests an interesting interplay among N-BPs, 25(OH)D, and the immune system, but a causal role of 25(OH)D in APR has to be proven by a randomized, controlled trial. However, if confirmed, it should have some practical implications in preventing APR.
authors.affiliation: Department of Biochemical and Surgical Sciences, University of Verona, Verona, Italy. francesco.bertoldo@univr.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Bertoldo
authors.forename: Serena
authors.initials: S
authors.lastname: Pancheri
authors.forename: Sonia
authors.initials: S
authors.lastname: Zenari
authors.forename: Stefania
authors.initials: S
authors.lastname: Boldini
authors.forename: Benedetta
authors.initials: B
authors.lastname: Giovanazzi
authors.forename: Mirko
authors.initials: M
authors.lastname: Zanatta
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Valenti
authors.forename: Luca
authors.initials: L
authors.lastname: Dalle Carbonare
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Lo Cascio
mesh_terms: D000210:Acute-Phase Reaction / Q000150:complications / Q000503:physiopathology*; D000368:Aged; D000588:Amines / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use; D001842:Bone and Bones / Q000378:metabolism*; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008875:Middle Aged; D010024:Osteoporosis / Q000188:drug therapy*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D000588:Amines; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D014807:Vitamin D; C104450:25-hydroxyvitamin D