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Current and Developing Pharmacologic Agents for Improving Skeletal Health in Adults with Osteogenesis Imperfecta

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Abstract

Osteogenesis imperfecta (OI) is a genetic disorder characterized by increased bone fragility largely caused by defects in structure, synthesis, or post-translational processing of type I collagen. Drugs currently used to improve skeletal health in OI were initially developed to treat osteoporosis and clinical trials are ongoing to study their effectiveness in OI adults. Additionally, novel bone-protective agents are in preclinical studies and various phases of OI clinical trials. This review summarizes current knowledge on available pharmacologic agents and current drug trials involving OI participants. A PubMed online database search of all study types published in the English language using the terms “osteogenesis imperfecta,” “OI,” and “brittle bone disease” was performed in August 2022. Articles screened were restricted to adults. A ClinicalTrials.gov database search of all studies involving “osteogenesis imperfecta” was performed in August 2023. Although clinical trial data are limited, bisphosphonates and teriparatide may be useful in improving bone mineral density. As of yet, no clinical trials are available that adequately evaluate the usefulness of current therapies in reducing fracture risk. Several therapeutics, including teriparatide, setrusumab, anti-TGF-β antibodies, and allogeneic stem cells, are being studied in clinical trials. Preclinical studies involving Dickkopf-1 antagonists present promising data in non-OI bone disease, and could be useful in OI. Research is ongoing to improve therapeutic options for adults with OI and clinical trials involving gene-editing may be possible in the coming decade.

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Funding

This work was supported by the BBDC (1U54AR068069–0), a part of the NCATS’ RDCRN. BBDC is funded through a collaboration between the ORDR of NCATS, NIAMS, NIHMS, NIDCR, and NICHD. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The BBDC is also supported by the OI Foundation.

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Authors and Affiliations

  1. Department of Medicine, Division of Endocrinology, Diabetes & Clinical Nutrition, Oregon Health & Science University, Portland, OR, USA

    Winnie Liu

  2. Department of Pediatrics, Division of Endocrinology, Oregon Health & Science University, Portland, OR, USA

    Lindsey Nicol

  3. Department of Medicine, Bone and Mineral Unit, Oregon Health & Science University, Portland, OR, USA

    Eric Orwoll

Authors
  1. Winnie Liu
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  2. Lindsey Nicol
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  3. Eric Orwoll
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Correspondence to Winnie Liu.

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Conflict of Interest

Winnie Liu has nothing to disclose. Lindsey Nicol receives consulting fees from Egetis and Ultragenyx. Eric Orwoll receives consulting fees from Ultragenyx, Angitia, and Amgen.

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Liu, W., Nicol, L. & Orwoll, E. Current and Developing Pharmacologic Agents for Improving Skeletal Health in Adults with Osteogenesis Imperfecta. Calcif Tissue Int (2024). https://doi.org/10.1007/s00223-024-01188-2

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