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Genetic Evaluation for Monogenic Disorders of Low Bone Mass and Increased Bone Fragility: What Clinicians Need to Know

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Abstract

Purpose of Review

The purpose of this review is to outline the principles of clinical genetic testing and to provide practical guidance to clinicians in navigating genetic testing for patients with suspected monogenic forms of osteoporosis.

Recent Findings

Heritability assessments and genome-wide association studies have clearly shown the significant contributions of genetic variations to the pathogenesis of osteoporosis. Currently, over 50 monogenic disorders that present primarily with low bone mass and increased risk of fractures have been described. The widespread availability of clinical genetic testing offers a valuable opportunity to correctly diagnose individuals with monogenic forms of osteoporosis, thus instituting appropriate surveillance and treatment.

Summary

Clinical genetic testing may identify the appropriate diagnosis in a subset of patients with low bone mass, multiple or unusual fractures, and severe or early-onset osteoporosis, and thus clinicians should be aware of how to incorporate such testing into their clinical practices.

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Funding

This work was supported in part by the NIH Brittle Bone Disorders Consortium (BBDC) (U54 AR068069). BBDC is a part of the National Center for Advancing Translational Sciences’ (NCATS) Rare Diseases Clinical Research Network (RDCRN), and is funded through a collaboration between NCATS, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute of Dental and Craniofacial Research (NIDCR), National Institute of Mental Health (NIMH), and the Eunice Kennedy Shriver National Institutes of Child Health and Development (NICHD). This work was also supported in part by funding of The Baylor College of Medicine Intellectual and Developmental Disabilities Research Center (P50HD103555) from the Eunice Kennedy Shriver NICHD. This work was funded by the NIH NIDCR (DE031162 and DE031288 to BL), the NHLBI (T32 HL092332 to EB), and the Lawrence Family Bone Disease Program of Texas.

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  1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA

    Emily Busse, Brendan Lee & Sandesh C. S. Nagamani

  2. Medical Scientist Training Program, Baylor College of Medicine, Houston, TX, USA

    Emily Busse

  3. Texas Children’s Hospital, Houston, TX, USA

    Brendan Lee & Sandesh C. S. Nagamani

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Correspondence to Brendan Lee.

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EB and SCSN declare no competing interests. BL reports non-financial support and other from Baylor Genetics Laboratory, personal fees from Biomarin, other from Acer Therapeutics, other from Sanofi, and other from GQ Bio Therapeutics during the conduct of the study; grants from Sanofi, grants from Kirin Kyowa outside the submitted work.

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Busse, E., Lee, B. & Nagamani, S.C.S. Genetic Evaluation for Monogenic Disorders of Low Bone Mass and Increased Bone Fragility: What Clinicians Need to Know. Curr Osteoporos Rep (2024). https://doi.org/10.1007/s11914-024-00870-6

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