The role of cytokines and adipocytokines in zoledronate-induced acute phase reaction in postmenopausal women with low bone mass.
OBJECTIVE
Patients treated with intravenous zoledronate frequently experience an acute phase reaction (APR) characterized by flu-like symptoms and increased levels of inflammatory cytokines. We aimed to define the role of various cytokines/adipocytokines in zoledronate-induced APR and develop a prognostic model for its prediction.


METHODS
Fifty-one postmenopausal women with low bone mass were subjected to zoledronate intravenous infusion. Patients were divided into those who experienced APR (APR+) and those who did not (APR-). APR was clinically defined by body temperature and the visual analogue pain scale for musculoskeletal symptoms. White blood cell count, leucocytic subpopulations, C-reactive protein, interleukin-6, tumour necrosis factor-alpha, visfatin, resistin and leptin were measured before and 48 h following the infusion. The quantitative insulin sensitivity check index (QUICKI) and homoeostasis model of assessment - insulin resistance (HOMA-IR) were calculated to assess insulin sensitivity and resistance, respectively.


RESULTS
(APR+) patients were younger and had lower baseline visfatin and higher baseline lymphocytes and phosphate compared with APR- patients. QUICKI decreased and HOMA-IR increased in APR+ patients while remained unchanged in APR- patients. In binary logistic regression analysis, a model containing previous bisphosphonate treatment, age, body mass index, lymphocytes and visfatin, which predicted zoledronate-induced APR with 82·1% sensitivity and 73·9% specificity, was selected. In this model, lymphocytes (P = 0·010) and visfatin (P = 0·029) at baseline could independently predict APR.


CONCLUSIONS
Zoledronate-induced APR is associated with serum increases of pro-inflammatory cytokines and an increase of insulin resistance. Patients with higher lymphocytes and lower visfatin levels at baseline are at higher risk for APR.
Department of Endocrinology, 424 General Military Hospital, Thessaloniki, Greece.
Athanasios D
AD
Anastasilakis
Stergios A
SA
Polyzos
Sideris
S
Delaroudis
Ilias
I
Bisbinas
Grigorios T
GT
Sakellariou
Athina
A
Gkiomisi
Evridiki
E
Papadopoulou
Spyridon
S
Gerou
Polyzois
P
Makras
D000210:Acute-Phase Reaction / Q000139:chemically induced*; D054392:Adipokines / Q000502:physiology*; D000367:Age Factors; D000368:Aged; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000009:adverse effects*; D016207:Cytokines / Q000502:physiology*; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects*; D007333:Insulin Resistance; D018655:Lymphocyte Count; D008875:Middle Aged; D054409:Nicotinamide Phosphoribosyltransferase; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D017698:Postmenopause; D012307:Risk Factors; D000077211:Zoledronic Acid
D054392:Adipokines; D050071:Bone Density Conservation Agents; D016207:Cytokines; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D054409:Nicotinamide Phosphoribosyltransferase