Osteogenesis imperfecta bone matrix alterations affect the resorptive function of human osteoclasts in-vitro

Osteogenesis imperfecta (OI) results most commonly from altered collagen type I that impairs both bone formation and resorption, producing a fragile bone matrix prone to fracture. While most studies emphasize deficient osteoblast function, there is a paucity of data related to the contribution of osteoclast-mediated resorption.

We investigated whether intrinsic alterations in OI bone matrix directly modulate human osteoclast activity.

Identical human osteoclast populations were seeded onto bone samples from donors with OI types 1, 3, and 4 and compared with non-OI controls. In addition, cleaned calvarial bones from the Col1a1^Aga2/+ and Col1a1^Jrt/+ mouse OI models served as substrates for human osteoclasts.

On OI type 1 bone, osteoclasts generated a greater eroded surface covered by pits, whereas trench formation remained unchanged. OI type 4 bone yielded significantly reduced eroded surface but produced deeper pits and trenches. Osteoclast behaviour on OI type 3 bone did not differ from that of healthy bone. Using Col1a1^Jrt/+ substrates, human osteoclasts displayed a general increase in resorptive activity, particularly in pit formation. Col1a1^Aga2/+ substrates similarly enhanced pit formation but reduced trench formation. Multiple linear regression confirmed that OI bone matrix preferentially stimulates pit-making osteoclasts while leaving trench-making osteoclasts largely unaffected. Independent of OI status, increasing donor age promoted trench formation.

These findings demonstrate that OI-specific matrix characteristics directly influence osteoclast resorption patterns. More broadly, they highlight the importance of extracellular matrix properties in shaping osteoclast behaviour and underscore the need to consider matrix-driven effects when interpreting bone pathologies.