"Acute-phase reactions to zoledronate in clinical practice: a prospective single center study of 1,150 patients.".

PURPOSE: To determine the frequency, type, and severity of acute-phase reaction (APR) following zoledronate (ZOL) infusion, identify associated clinical risk factors, and compare treatment-naïve patients with those receiving ZOL as sequential therapy. A secondary objective was to assess recall bias through a 90-day retest. METHODS: A prospective study was conducted at a single bone clinic. Patients who received 5 mg ZOL were invited to complete questionnaires at 3 and 7 days post-infusion. Symptom frequency and severity were analyzed, and clinical factors were assessed using multivariate logistic regression. Symptoms with intensity ≥ 8 on a 0-10 Numerical Rating Scale (NRS) were considered severe. RESULTS: The mean age of the 1,150 patients was 66.9 ± 8.5 years, 97% were women. At least one symptom was reported by 867 (75%) patients. The most common were general and musculoskeletal symptoms (61 and 58%), followed by gastrointestinal (23%), ocular (13%), and fever (8%). Severe symptoms were reported by 22%. While 94% expressed willingness to repeat treatment, severe symptoms were significantly associated with treatment decline: 68% of those who declined versus 19% among those willing to continue (p < 0.001). A 90-day retest revealed systematic under-recall of mild general, musculoskeletal, and gastrointestinal symptoms (McNemar p < 0.05), whereas fever, ocular, and severe symptoms remained stable over time. First-time infusion was significantly associated with all symptoms and severity, whereas older age predicted a lower risk of general, gastrointestinal, fever, and severe symptoms. Among first-infusion patients (n = 704), prior bisphosphonate was associated with a reduced frequency and severity of symptoms. Preventive analgesics were associated with lower risk of general and musculoskeletal symptoms. CONCLUSION: This real-life study shows a high frequency of APR when symptoms are assessed shortly after ZOL infusion with mild symptoms systematically underestimated over time. First infusion, younger age, and lack of prior bisphosphonate exposure were the main risk factors identified. These findings support improving pre-infusion counseling in higher-risk patients to reduce anxiety and support long-term adherence to osteoporosis treatment.