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Endocrine Abstracts (2022) 81 OC8.4 | DOI: 10.1530/endoabs.81.OC8.4

ECE2022 Oral Communications Oral Communications 8: Calcium and Bone (6 abstracts)

Is the “rebound phenomenon” following Denosumab discontinuation a risk factor for Zoledronic acid acute phase adverse reactions?

Marta Zampogna 1 , Giorgia Grassi 1 , Alberto Ghielmetti 1 , Serena Palmieri 2 , Maura Arosio 1 & Cristina Eller Vainicher 2


1University of Milan, Department of Clinical Sciences and Community Health, Italy; 2Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Unit of Endocrinology, Italy


Background: Zoledronic acid (ZOL) administration may cause acute phase adverse reactions (APR), which manifest with fever, malaise, bone and muscular pain, headache and/or gastrointestinal disturbances. Previous data suggest that high N-terminal propeptide of type 1 collagen (P1NP) and low 25, OH-vitaminD (VitD) levels are associated with higher incidence of APR, while the previous use of bisphosphonates is a protective factor. Lately, ZOL has been frequently used to mitigate the “rebound phenomenon” following Denosumab (Dmab) discontinuation. The aim of our study is to evaluate whether the use of ZOL in patients discontinuing Dmab (postDmab) may be associated with an increase in incidence and severity of APR, as compared with patients without prior antiosteoporotic therapy (naïve) and the presence of possible factors associated with APR.

Methods: we retrospectively evaluated 112 patients (56 postDmab and 56 naïve) treated with ZOL 5 mg intravenously for osteoporosis in our center during the last 24 months. Bisphosphonates treatment preceding ZOL administration, including previous ZOL infusions, was considered an exclusion criterion. All patients were taking vitamin D and calcium. In all patients we evaluated femoral neck (FN) and lumbar spine (LS) bone mineral density (BMD), C-terminal telopeptide (CTX) and VitD levels.

Results: PostDmab patients were older (71.4±8.7 vs 65.1±11.4 years, P=0.001), had higher BMD (LS T-score -2.3±0.8 vs -3.1±1.2, P=0.0001, FN T-score -2.0±0.8 vs -2.4±0.8, P=0.011) and lower CTX levels (452±350 vs 630±307 pg/ml P=0.008) as compared to naïve patients, while the prevalence of fractures (56.3 vs 43.8% P=0.333; respectively postDmab and naïve) and the VitD levels (40.4±13.9 vs 42.8±23.1 ng/ml, P=0.509; respectively postDmab and naïve) were comparable in the two groups. No difference was found in the overall APR rate (65.3 vs 58%, P=0.156; respectively postDmab and naïve) or in the moderate-severe APR rate (34.7 vs 42%, P=0.156 respectively postDmab and naïve) between the two groups. The logistic regression analysis showed a significant association between CTX levels and the occurrence of moderate-severe APR, regardless of age, group (naïve or postDmab) and VitD levels (OR 1.002, 95% CI 1.000-1.003, P=0.027).

Conclusions: In our cohort of ZOL treated patients we found a higher incidence of APR than reported in literature without significant differences between postDmab and naïve patients. In our cohort of VitD sufficient patients, CTX seems to be the only factor significantly associated with an increased risk of moderate-severe APR post ZOL infusion.

Volume 81

European Congress of Endocrinology 2022

Milan, Italy
21 May 2022 - 24 May 2022

European Society of Endocrinology 

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