ArticleBone2018
Cartilage-derived retinoic acid-sensitive protein (CD-RAP): A stage-specific biomarker of heterotopic endochondral ossification (HEO) in fibrodysplasia ossificans progressiva (FOP).
Article in Bone, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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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.
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Who cites it
7 citing papers in PubMed, 13 citations in OpenAlex.
- Palovarotene for Fibrodysplasia Ossificans Progressiva (FOP): Results of a Randomized, Placebo-Controlled, Double-Blind Phase 2 Trial.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Trial
- Heterotopic Ossification: Molecular Drivers, Subtype-Specific Mechanisms, and Translational Therapeutic Advances.Biomolecules · 2026Review
- Cellular and Molecular Mechanisms of Heterotopic Ossification in Fibrodysplasia Ossificans Progressiva.Biomedicines · 2024Review
- Study methodology and insights from the palovarotene clinical development program in fibrodysplasia ossificans progressiva.BMC medical research methodology · 2023Article
- The role of miRNA and lncRNA in heterotopic ossification pathogenesis.Stem cell research & therapy · 2022Review
- Diminished muscle integrity in patients with fibrodysplasia ossificans progressiva assessed with at-home electrical impedance myography.Scientific reports · 2022Article
- Fibrodysplasia Ossificans Progressiva: What Have We Achieved and Where Are We Now? Follow-up to the 2015 Lorentz Workshop.Frontiers in endocrinology · 2021Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundGenesis of a cartilaginous scaffold is an obligate precursor to bone formation in heterotopic endochondral ossification (HEO). We tested the hypothesis that cartilage-derived retinoic acid-sensitive protein (CD-RAP) can serve as a plasma biomarker for the pre-osseous cartilaginous stage of HEO. Palovarotene, a retinoic acid receptor-gamma (RARγ) agonist, has been proposed as a possible treatment for fibrodysplasia ossificans progressiva (FOP) and is a potent inhibitor of HEO in mouse models. Current drug development for FOP mandates the identification of stage-specific biomarkers to facilitate the evaluation of clinical trial endpoints.
resultsHere we show in an injury-induced, constitutively-active transgenic mouse model of FOP that CD-RAP levels peaked between day-7 and day-10 during the zenith of histologically-identified chondrogenesis, preceded radiographically apparent HEO, and were diminished by palovarotene. Cross-sectional analysis of CD-RAP levels in plasma samples from FOP patients demonstrated a statistically non-significant trend toward higher levels in the recent flare-up period (three weeks to three months within onset of symptoms). However, in a longitudinal subgroup analysis of patients followed for at least six months after resolution of flare-up symptoms, there was a statistically significant decrease of CD-RAP when compared to levels in the same patients at the time of active or recent exacerbations.
conclusionsThese data support the further exploration of CD-RAP as a stage-specific biomarker of HEO in FOP.
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