Osteoporosis and Bone Mass Disorders: From Gene Pathways to Treatments

Genomic technologies have evolved rapidly contributing to the understanding of diseases. Genome-wide association studies (GWAS) and whole-exome sequencing have aided the identification of the genetic determinants of monogenic and complex conditions including osteoporosis and bone mass disorders. Overlap exists between the genes implicated in monogenic and complex forms of bone mass disorders, largely explained by the clustering of genes encoding factors in signaling pathways crucial for mesenchymal cell differentiation, skeletal development, and bone remodeling and metabolism. Numerous of the remaining discovered genes merit functional follow-up studies to elucidate their role in bone biology. The insight provided by genetic studies is serving the identification of biomarkers predictive of disease, redefining disease, response to treatment, and discovery of novel drug targets for skeletal disorders.

TrendsGWAS and whole-exome sequencing studies have revolutionized the identification of genetic determinants of monogenetic and complex conditions including osteoporosis and bone mass disorders.GWAS pinpoint factors in pathways crucial to bone biology (WNT, NOTCH, INDIAN HEDGEHOG signaling), which are currently targets of drug compounds for the treatment of osteoporosis and bone mass disorders.Given the hypothesis-free nature of these genomic screens, functional follow-up of the numerous remaining discovered genes will be necessary to elucidate their role in bone biology.The considerable overlap in factors and biologic pathways underlying common and monogenetic forms of osteoporosis and bone mass disorders opens new avenues for diagnosis and personalized medicine.The emerging discovery of novel skeletal biology by genetic studies is of huge potential for the identification of novel drug targets for skeletal disorders.