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Low vitamin D tied to zoledronic acid reaction in postmenopausal women

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March 7, 2018

Postmenopausal women with osteoporosis and 25-hydroxyvitamin D levels less than 30 ng/mL were more likely to experience acute-phase reaction after zoledronic acid infusion compared with those with higher vitamin D levels, according to study results.

Marco Massarotti, MD, consultant rheumatologist at University Hospitals of Morecambe Bay NHS Foundation Trust in Lancaster, U.K., and colleagues evaluated data on 153 postmenopausal women with osteoporosis (mean age, 71 years; mean 25-[OH]D level, 32.2 ng/mL) undergoing their first zoledronic acid infusion to confirm the association between acute-phase reaction, or APR, and 25-(OH)D levels and to determine whether the association differs in those previously treated with oral bisphosphonates (n = 68).

The occurrence of fever or the presence of at least one influenza-like symptom, such as fatigue, malaise, bone/muscle pain or headache, that occurred within the 24 to 36 hours from zoledronic acid infusion was used to define acute-phase reaction.

Overall, acute-phase reaction occurred in 44.4% of participants; symptoms included fever plus arthromyalgia (muscle and/or joint pain; 57.4%), fever alone (33.8%), arthromyalgia alone (7.4%) and fever plus diarrhea (1.5%). Symptoms were similar among participants who were and were not previously treated with oral bisphosphonates.

Participants with acute-phase reaction had lower 25-(OH)D levels compared with those without the reaction (26.3 ng/mL vs. 37 ng/mL; P < .0001). More participants with acute-phase reaction had 25-(OH)D levels less than 30 ng/mL compared with those without reaction (65% vs. 31%; P < .0001).

Among participants previously exposed to bisphosphonates, those with acute-phase reaction had lower 25-(OH)D levels compared with those without acute-phase reaction (P = .02), and inadequate 25-(OH)D levels were more common in those with acute-phase reaction (52.5% vs. 26.7%).

“This study confirms that 25-(OH)D levels and, in particular, inadequate 25-(OH)D status, are significant factors for APR after [zoledronic acid] infusion,” the researchers wrote. “Translating our observation into clinical practice, we recommend an adequate supplementation of 25-(OH)D for patients prior to [bisphosphonates] to reduce the risk of APR. Moreover, the role of previous treatment with oral [bisphosphonates] as an independent protective factor for APR should be evaluated in a larger cohort.” – by Amber Cox

Disclosures: Massarotti reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

itj+ Perspective

Pauline Camacho

The results of the study mirror what we often see in clinical practice; specifically, that patients who happen to get IV zoledronic acid when they are vitamin D deficient have more intense bone pains and acute-phase reactions than those who are vitamin D replete. We screen all our patients for vitamin D and calcium deficiency prior to infusions of zoledronic acid to reduce the risk for hypocalcemia and acute-phase reactions. With this practice, our rate of acute-phase reaction is quite low, probably 10% to 15% or less. The study specifically focused on vitamin D deficiency, but the same may also apply to calcium deficiency, thus these both need to be addressed prior to treatment. A future study could address not only the correlation of calcium deficiency and acute-phase reaction from bisphosphonates, but also how long the patients need to be sufficient in both vitamin D and calcium before the infusions can be given..

Pauline M. Camacho, MD, FACE

Professor of Medicine
Division of Endocrinology and Metabolism
Loyola University Medical Center
Loyola University Osteoporosis and Metabolic Bone Disease Center

Disclosure: Camacho reports no relevant financial disclosures.