Trial reportBMC musculoskeletal disorders2018
A protocol for a multicentre, randomised, double-blind, placebo-controlled trial to compare the effect of annual infusions of zoledronic acid to placebo on knee structural change and knee pain over 24 months in knee osteoarthritis patients - ZAP2.
Trial report in BMC musculoskeletal disorders, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05204836 (Altering Bone Microarchitecture and Mechanics by Off-label Pharmaceutical Intervention), which is not on this map. Cited by 15 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Altering Bone Microarchitecture and Mechanics by Off-label Pharmaceutical Intervention
Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Clinical Efficacy and Safety of Zoledronic Acid Combined with PVP/PKP in the Treatment of Osteoporotic Vertebral Compression Fracture: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.BioMed research international · 2021Pooled it
- A pilot randomized controlled trial evaluating outdoor community walking for knee osteoarthritis: walk.Clinical rheumatology · 2023Trial
- Trial
- Effect of Preoperative Zoledronic Acid Administration on Pain Intensity after Percutaneous Vertebroplasty for Osteoporotic Vertebral Compression Fractures.Pain research & management · 2020Trial
- Pain Phenotype in Knee Osteoarthritis: Implications for Mechanism-Based Therapy.Orthopaedic surgery · 2025Review
- Bone Marrow Aspirate Concentrate (BMAC) for Knee Osteoarthritis: A Narrative Review of Clinical Efficacy and Future Directions.Medicina (Kaunas, Lithuania) · 2025Review
- Bone marrow lesions in osteoarthritis: biomarker or treatment target? A narrative review.Skeletal radiology · 2025Review
- Bone marrow lesions in osteoarthritis: From basic science to clinical implications.Bone reports · 2023Article
- Indication and adverse event profiles of denosumab and zoledronic acid: based on U.S. FDA adverse event reporting system (FAERS).Frontiers in pharmacology · 2023Article
- Effect of alendronate sodium plus vitamin DBMC musculoskeletal disorders · 2022Article
- Can metformin relieve tibiofemoral cartilage volume loss and knee symptoms in overweight knee osteoarthritis patients? Study protocol for a randomized, double-blind, and placebo-controlled trial.BMC musculoskeletal disorders · 2022Article
- Microenvironment in subchondral bone: predominant regulator for the treatment of osteoarthritis.Annals of the rheumatic diseases · 2021Review
- From Pathogenesis to Therapy in Knee Osteoarthritis: Bench-to-Bedside.International journal of molecular sciences · 2021Review
- Molecular Classification of Knee Osteoarthritis.Frontiers in cell and developmental biology · 2021Review
- Zoledronic acid plus methylprednisoloneTherapeutic advances in musculoskeletal disease · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundBisphosphonates are a class of drugs that slow bone loss and are a promising candidate to treat knee osteoarthritis (OA) patients. In a pilot study, we demonstrated that zoledronic acid reduced knee pain and size of subchondral bone marrow lesions (BMLs) over 6 months in knee OA patients with significant knee pain and BMLs. A longer, larger study is required to assess whether decreases in BML size will translate to reductions in cartilage loss over time. We are currently conducting a multicentre, randomised, double-blind, placebo-controlled trial over 24 months that aims to compare the effect of annual infusions of zoledronic acid to placebo on knee structural change (assessed using magnetic resonance imaging (MRI)) and knee pain in knee OA patients.
methodsTwo hundred sixty-four patients with clinical knee OA, significant knee pain and subchondral BMLs present on MRI will be recruited in Hobart, Melbourne, Sydney and Adelaide. They will be randomly allocated to the two arms of the study, receiving an annual identical intravenous infusion of either 100 mL of fluid containing zoledronic acid (5 mg/100 mL) or placebo (0.9% NaCl 100 mL), at baseline and 1 year later. MRI of the study knee will be performed at screening, month 6 and 24. Knee structure, symptoms and function will be assessed using validated methods. The primary outcome is absolute change in tibiofemoral cartilage volume (mm DISCUSSION: This study will provide high-quality evidence to assess whether zoledronic acid has a novel disease modifying effect in OA by slowing cartilage loss and reducing pain. If zoledronic acid proves effective, it suggests great potential for cost savings through a delay or reduced need for joint replacement surgery, and potential for great improvements in quality of life for OA suffers.
trial registrationAustralian New Zealand Clinical Trials Registry: ACTRN12613000039785 , registered on 14 January 2013.
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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.