Background Zoledronic acid (AZ), characterized by its high antiresorptive activity, has restored the excessive pagetic bone remodeling, reduce or suppress the biological activity, influence on clinical features, and prevent the onset and progression of complications. Therefore, it is considered first-line treatment for Paget disease of bone (PDB).The most common adverse event occurring after the administration of this drug is flu-like syndrome, described between 10% and 50% of patients receiving treatment for the first time, significantly reducing their incidence following administration of doses. This syndrome is characterized by fever, arthralgia and transient increase in plasma levels of IL-6, TNF and IFN.Nowadays, there is not known exactly the molecular basis of this syndrome yet.Statins play an important role in the mevalonate pathway, blocking the production of proinflammatory cytokines secreted by T cells gamma/delta, by reducing the bioavailability of the intermediate substrates.
Objectives Characterization and incidence of adverse events (AEs) secondary to treatment with AZ in patients with PDB. Evaluate the impact of statins on AZ-induced flu-like syndrome.
Methods A prospective open-label study was conducted in fifty patients with active PDB after 2 years period. Each patient received a single 5 mg intravenous infusion of ZA over a 15-minute period.
Results Baseline characteristics of patients with active PD: Gender (Female/Male): 50 patients (23F/27M).Mean age at diagnosis (years): 59±12.5. Mean duration of the disease (years): 14.5±8.5. Scintigraphic distribution: Polyostotic(62%)/Monostotic(38%). Regarding to AE, there was not hematological, renal, gastrointestinal or liver toxicity detected after infusion of 5 mg ZA nor during the following period. The most frequent side effect was flu-like symptoms, observed in 54% of patients, showing a higher incidence than in the literature. The incidence of fever was detected in 100% of the patients affected, with the average body temperature of 38.3 ° C, lasting 36h. The incidence of arthralgia was 68% lasting 72 hours.There was no statistically significant correlation between the presence of flu-like syndrome and a gender, scintigraphic distribution, duration of the disease, number of locations, serum alkaline phosphatase (ALP) at diagnosis.Instead, it was observed a statistically significant correlation between age at diagnosis, baseline plasma calcium, 1,25-dihydroxyvitamin D3 at baseline and prolonged therapy (>3 months) with statins, with the presence of flu-like syndrome. Patients presenting flu-like symptoms had a lower age at diagnosis, baseline plasma calcium levels below average, plasma levels of 1,25-dihydroxyvitamin D3 above average, and did not maintain statin therapy.
Conclusions The most important AE was the flu-like symptoms, occurred in 54%, with mild to moderate and transient intensity. It has been observed that the absence of AE has been correlated with prolonged intake of statins. Currently, we do not know the dose and duration of statin therapy prior to the infusion of AZ, to reduce or prevent the onset of the flu-like syndrome, and the influence of statins on long-term efficacy of AZ. Therefore, it would be necessary to carry on studies that could confirm and, at the same time, clarify the biological plausibility of this phenomenon.
Disclosure of Interest None Declared.