Preventive Role of Vitamin D Supplementation for Acute Phase Reaction after Bisphosphonate Infusion in Paget's Disease

Daniela Merlotti, Domenico Rendina, Riccardo Muscariello, Tommaso Picchioni, Mario Alessandri, Gianpaolo De Filippo, Maria Materozzi, Simone Bianciardi, Maria Beatrice Franci, Barbara Lucani, Simone Cenci, Pasquale Strazzullo, Ranuccio Nuti, Luigi Gennari

Research output: Contribution to journalArticlepeer-review


Context: Intravenous aminobisphosphonates (N-BPs) can induce an acute phase reaction (APR) in up to 40% to 70% of first infusions, causing discomfort and often requiring intervention with analgesics or antipyretics. Objective: Our aim was to explore the risk factors of APR in a large sample of patients with Paget's disease of bone (PDB) and to assess the possible preventive effects of Vitamin D administration. Methods: An observational analysis was performed in 330 patients with PDB at the time of N-BP infusion. Then, an interventional study was performed in 66 patients with active, untreated PDB to evaluate if Vitamin D administration (oral cholecalciferol 50 000 IU/weekly for 8 weeks before infusion) may prevent APR. Results: In a retrospective study, APR occurred in 47.6% and 18.3% of naive or previously treated patients, respectively. Its prevalence progressively increased in relation to the severity of Vitamin D deficiency, reaching 80.0% in patients with 25-hydroxyVitamin D (25OHD) levels below 10 ng/mL (relative risk (RR) = 3.7; 95% confidence interval (CI) 2.8-4.7, P <. 0001), even in cases previously treated with N-BPs. Moreover, APR occurred more frequently in patients who experienced a previous APR (RR = 2.8; 95% CI 1.5-5.2; P <. 001) or in carriers of SQSTM1 mutation (RR = 2.3; 95% CI 1.3-4.2; P =. 005). In the interventional study, Vitamin D supplementation prevented APR in most cases, equivalent to a RR of 0.31 (95% CI 0.14-0.67; P <. 005) with respect to prevalence rates of the observational cohort. A similar trend was observed concerning the occurrence of hypocalcemia. Conclusions: The achievement of adequate 25OHD levels is recommended before N-BP infusion in order to minimize the risk of APR or hypocalcemia in PDB.

Original languageEnglish
Article numberdgz138
JournalJournal of Clinical Endocrinology and Metabolism
Issue number3
Publication statusPublished - Jan 8 2020


  • acute phase reaction
  • bisphosphonates
  • bone turnover
  • Paget's disease of bone
  • parathyroid hormone
  • Vitamin D

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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