Bone-Targeting Antibodies for Skeletal Precision Therapy

Abstract

Therapeutic antibodies have transformed the treatment of cancer, inflammation, infection, and disorders of bone biology by recognizing disease-associated molecular targets with high specificity. However, achieving therapeutically effective antibody concentrations at the site of disease remains a major challenge, as systemic administration does not inherently result in efficient tissue-specific delivery. Bone is a particularly demanding destination because mineralized matrix, limited vascular access, marrow complexity, and active remodeling can restrict local antibody exposure. Recent advances in bone-targeting antibody design point to a powerful reframing in which antibodies can be engineered not only for antigen specificity but also for tissue specificity. By attaching hydroxyapatite-binding motifs such as bisphosphonates or acidic peptides, antibodies can be endowed with bone-homing capabilities. The efficacy of this strategy has now been validated across multiple preclinical disease models, including breast cancer bone metastasis and osteoporosis-related bone loss. The next challenge is to define how affinity, valency, conjugation site, circulation time, and release should be tuned for each skeletal disease.