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  • Author: Tazio Maleitzke x
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Mara Meyer Günderoth Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal Surgery, Berlin, Germany
Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff Institute, Berlin, Germany

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Alexandra Bannach-Brown Berlin Institute of Health at Charité – Universitätsmedizin Berlin, QUEST Center for Responsible Research, Berlin, Germany

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Tobias Winkler Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal Surgery, Berlin, Germany
Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff Institute, Berlin, Germany
Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin Institute of Health Center for Regenerative Therapies, Berlin, Germany

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Johannes Keller Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

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Robert Karl Zahn Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal Surgery, Berlin, Germany

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Tazio Maleitzke Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal Surgery, Berlin, Germany
Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff Institute, Berlin, Germany
Trauma Orthopaedic Research Copenhagen Hvidovre (TORCH), Department of Orthopaedic Surgery, Copenhagen University Hospital – Amager and Hvidovre, Hvidovre, Denmark
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

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Purpose

  • The aim of this study was to investigate the efficacy of calcitonin (CT) in animal models of experimental osteoarthritis (OA) and rheumatoid arthritis (RA), as new stabilized CT formulations are currently being introduced.

Methods

  • A comprehensive and systemic literature search was conducted in PubMed/MEDLINE and Embase databases to identify articles with original data on CT treatment of preclinical OA and RA. Methodological quality was assessed using the Systematic Review Centre for Laboratory Animal Experimentation’s risk of bias tool for animal intervention studies. To provide summary estimates of efficacy, a meta-analysis was conducted for outcomes reported in four or more studies, using a random-effects model. Subgroup analyses were employed to correct for study specifics.

Results

  • Twenty-six studies were ultimately evaluated and data from 16 studies could be analyzed in the meta-analysis, which included the following outcomes: bone mineral density, bone volume, levels of cross-linked C-telopeptide of type I collagen, histopathological arthritis score, and mechanical allodynia. For all considered outcome parameters, CT-treated groups were significantly superior to control groups (P = 0.002; P = 0.01; P < 0.00001; P < 0.00001; P = 0.04). For most outcomes, effect sizes were significantly greater in OA than in RA (P ≤ 0.025). High in-between study heterogeneity was detected.

Conclusion

  • There is preclinical evidence for an antioxidant, anti-inflammatory, antinociceptive, cartilage- and bone-protective effect of CT in RA and OA. Given these effects, CT presents a promising agent for the treatment of both diseases, although the potential seems to be greater in OA.

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Tobias Winkler Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal Surgery, Berlin, Germany
Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff Institute, Berlin, Germany
Berlin Institute of Health Center for Regenerative Therapies, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany

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Sven Geissler Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff Institute, Berlin, Germany
Berlin Institute of Health Center for Regenerative Therapies, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany

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Tazio Maleitzke Berlin Institute of Health Center for Regenerative Therapies, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany
Trauma Orthopaedic Research Copenhagen Hvidovre (TORCH), Department of Orthopaedic Surgery, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

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Carsten Perka Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal Surgery, Berlin, Germany

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Georg N Duda Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal Surgery, Berlin, Germany
Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff Institute, Berlin, Germany
Berlin Institute of Health Center for Regenerative Therapies, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany

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Alexander Hildebrandt Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal Surgery, Berlin, Germany
Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff Institute, Berlin, Germany

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  • Advanced therapies are expected to play a crucial role in supporting repair after injury, halting the degeneration of musculoskeletal tissue to enable and promote physical activity.

  • Despite advancements, the progress in developing advanced therapies in orthopaedics lags behind specialties like oncology, since innovative regenerative treatment strategies fall short of their expectations in musculoskeletal clinical trials.

  • Researchers should focus on understanding the mechanism of action behind the investigated target before conducting clinical trials.

  • Strategic research networks are needed that not only enhance scientific exchange among like-minded researchers but need to include early on commercial views, companies and venture perspectives, regulatory insights and reimbursement perspectives. Only in such collaborations essential roadblocks towards clinical trials and go-to-patients be overcome.

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