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The role of cytokines and adipocytokines in zoledronate-induced acute phase reaction in postmenopausal women with low bone mass


Correspondence: Athanasios Anastasilakis, Soulini 4, 566 25 Sykies, Greece. Tel.: +30 2310 381 697; Fax: +30 2310 381 010; E-mail:



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.

Patients and Measurements

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.


(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.


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.