What is osteoporosis?

Osteoporosis is a bone disease that develops when bone mineral density and bone mass decreases, or when the structure and strength of bone changes. This can lead to a decrease in bone strength that can increase the risk of fractures (broken bones)1.

Osteoporosis is often regarded as a “silent” disease as there are typically no symptoms until a bone is broken. Osteoporosis affects women and men of all races and ethnic groups, although more women get osteoporosis. Osteoporosis can occur at any age, although the risk for developing the disease increases as one gets older. For many women, the disease begins to develop a year or two before menopause.

One in three Singaporean women over 50 years old has osteoporosis. Among females more than 60 years, 50% and 25% of the populations were at intermediate and high risk of developing osteoporosis respectively2. It has been estimated that the costs of managing hip fractures in Singapore will reach USD$145 million in 20502.

Our approach to osteoporosis

Discovered relationship between bone formation and loss

Osteoporosis increases the risk of bone fractures. In addition, the fractures heal poorly because porous bones grow back slowly. The aim of osteoporosis treatment is to restore the natural balance between bone formation and loss as bone is a tissue that is in a constant process of remodeling and it is continuously reabsorbed and re-formed by specialized cells.

When our scientists discovered the RANK ligand signaling pathway, we were able to understand how the body regulates this relationship between bone formation and loss. Two proteins RANK ligand (RANKL) and osteoprotegerin (OPG) – are involved. RANKL is essential for the development of cells that degrade bone to initiate normal bone remodeling and mediate bone loss by increasing their resorptive activity (osteoclasts). OPG binds and neutralizes RANKL and thus inhibits osteoclast activity. In a healthy body, bone formation and loss are in balance. When hormone levels fall - for example after menopause - and in the case of malignant or other diseases, the relationship between the production of RANKL and OPG becomes unbalanced. RANKL expression dominates and bone loss increases.

Our scientists managed to develop a monoclonal antibody that binds to RANKL. This prevents RANKL from activating its receptor RANK on the surface of osteoclasts and their precursor cells. Disrupting the RANKL/RANK interaction inhibits osteoclast formation, function, and survival and counteracts osteoclast-mediated bone loss.

  • References

    1. National Institute of Arthritis and Musculoskeletal and Skin Diseases. 2022. Osteoporosis. Available at: https://www.niams.nih.gov/health-topics/osteoporosis
    2. Tan H. C. Seng J. J. B. & Low L. L. 2021. Osteoporosis awareness among patients in Singapore (oasis)-a community hospital perspective. Archives of Osteoporosis 151–151. Available at: https://doi.org/10.1007/s11657-021-01012-6