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

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.

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.

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.