Age related effects of selective and non-selective COX-2 inhibitors on bone healing

Abstract

Introduction: Fractures are increasing worldwide and with an aging population, are frequent in the elderly. The healing of fractures progresses through various phases including the inflammatory stage. Aging is associated with slower healing and the use of non steroidal anti-inflammatory drugs (NSAIDs) may interrupt bone healing processes. We designed a study to compare the effect of diclofenac and celecoxib on fracture callus histomorphometry in a rat model of different age groups.

Methods: Using 5 and 15 month old rats, fractures were induced on the left tibia and the animals allocated to receive one of the drugs. Animals were sacrificed at day 21 and 42 and the fracture callus harvested for processing and histological evaluation. Tissue proportions and histological grades were determined and compared across the groups.

Results: Across all groups, the histological grade increased with time and animals in the young diclofenac group had the highest grade at day 42 (p = 0.004). The proportion of bone increased in all groups and was highest in the young diclofenac group at day 21 and day 42 (p = 0.003). Post hoc analysis showed that the young celecoxib and old celecoxib groups had the least proportion of bone (p = 0.032 and p = 0.003). The proportion of cartilage reduced in all groups at both time points.

Conclusion: Celecoxib was associated with lower histological grade and lower proportion of bone in older animals. We urge for caution regarding the use of celecoxib in older people for the management of pain associated with fractures. Diclofenac may be a better option in this group.