Trial reportBreast cancer research and treatment2018
A phase II study evaluating the efficacy of zoledronic acid in prevention of aromatase inhibitor-associated musculoskeletal symptoms: the ZAP trial.
Trial report in Breast cancer research and treatment, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Effectiveness and safety of bone protective interventions to mitigate bone loss and skeletal fractures experienced by patients with non-metastatic breast cancer: a systematic review and meta-analysis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026Pooled it
- Comparing g-computation, propensity score-based weighting, and targeted maximum likelihood estimation for analyzing externally controlled trials with both measured and unmeasured confounders: a simulation study.BMC medical research methodology · 2023Trial
- Genome-wide association study of aromatase inhibitor discontinuation due to musculoskeletal symptoms.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2022Trial
- A randomized, double-blind, placebo-controlled trial of testosterone for treatment of postmenopausal women with aromatase inhibitor-induced arthralgias: Alliance study A221102.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2021Trial
- Design, Conduct, and Analysis of Externally Controlled Trials.JAMA network open · 2025Article
- Aromatase Inhibitor Musculoskeletal Syndrome and Bone Loss: a Review of the Current Literature.Current oncology reports · 2023Review
- The bone-muscle connection in breast cancer: implications and therapeutic strategies to preserve musculoskeletal health.Breast cancer research : BCR · 2022Review
- Review
- Aromatase inhibitor-associated musculoskeletal pain: An overview of pathophysiology and treatment modalities.SAGE open medicine · 2022Review
- Updated guidance on the management of cancer treatment-induced bone loss (CTIBL) in pre- and postmenopausal women with early-stage breast cancer.Journal of bone oncology · 2021Review
- Aromatase Inhibitor-Associated Musculoskeletal Syndrome: Understanding Mechanisms and Management.Frontiers in endocrinology · 2021Review
- Aromatase Inhibitors-Induced Musculoskeletal Disorders: Current Knowledge on Clinical and Molecular Aspects.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 1 country.
Funding
Abstract
purposeAromatase inhibitor-associated musculoskeletal symptoms (AIMSS) are common adverse events of AIs often leading to drug discontinuation. We initiated a prospective clinical trial to evaluate whether bisphosphonates are associated with reduced incidence of AIMSS.
methodsIn the single-arm trial, the Zoledronic Acid Prophylaxis (ZAP) trial, we compared the incidence of AIMSS against historical controls from the Exemestane and Letrozole Pharmacogenomics (ELPh) trial. Eligible women were postmenopausal with stage 0-III breast cancer planning to receive adjuvant AIs. AIMSS was assessed using the Health Assessment Questionnaire and Visual Analog Scale over 12 months in both trials. Participants in the ZAP trial received zoledronic acid prior to initiating letrozole and after 6 months; ELPh participants included in the analysis were taking letrozole but not bisphosphonates. We analyzed patient-reported outcomes (PROs) and bone density in the ZAP trial using mixed-effects linear regression models and paired t tests, respectively.
resultsFrom 2011 to 2013, 59 postmenopausal women enrolled in ZAP trial. All 59 (100%) women received baseline and 52 (88%) received 6-month zoledronic acid, and had similar characteristics to historical controls from the ELPh trial (n = 206). Cumulatively during the first year of AI, 37 and 67% of ZAP and ELPh participants reported AIMSS (p < 0.001), respectively. Within the ZAP trial, we did not observe significant changes in other PROs; however, we report improvements in bone mineral density.
conclusionsCompared to historical controls, zoledronic acid administered concomitantly with adjuvant AIs was associated with a reduced incidence of AIMSS. A randomized controlled trial is required to confirm these findings.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.