Bisphosphonates and direct fracture healing: Area to be explored.

Bisphosphonates (BPs) are widely used antiresorptive agents in the treatment of osteoporosis. They act primarily through inactivation of osteoclasts. Since the activities of osteoblasts and osteoclasts are coupled, the use of BPs is associated with delayed bone remodelling due to reduction of both osteoblastic and osteoclastic activities. Many patients sustaining osteoporotic fractures will be receiving bisphosphonates and others will be started on this treatment for secondary prevention. The question remains that if BPs delays fracture healing or remodelling, should they be delayed till the fracture union has been achieved.

Fracture healing occurs by two mechanisms, direct and indirect. Maximum osteoclastic activity occurs about 6 weeks after the indirect bone healing starts although low grade osteoclastic activity can be seen early in the fracture healing.[1] This is in contrast to direct bone healing where the osteoclasts come into play in early stages. The use of bisphosphonates in indirect bone healing is associated with increased ratio of woven to lamellar bone and increased bulk of callus. Increased volume and mineral content of callus may not confer mechanical advantage and the callus formed appears to be of inferior quality callus resulting in reduced strength to failure.[2] It has been shown in experimental models that use of BP during the first week of fracture healing did not impair indirect bone healing, but this impairment was seen if the drug was continued for a longer time.[34] Thus, cessation of BP before the peaking of osteoclastic activity in indirect fracture healing can be protective against the deleterious effects on indirect fracture healing.

Savaridas et al.[5] in an animal model studied the effect of Ibandronate (1 μg/kg) on rigid compression plate fixation of tibial osteotomy (direct bone healing model). Compared to a control group, the rodent model receiving BPs had poorer radiological, biomechanical and histological evidence of fracture healing. They concluded that in therapeutic doses BPs has an inhibitory effect on direct fracture healing. This is the only article that studied the role of BP in a direct bone healing model. Though a large number of patients are receiving BP during the fracture healing, there are no human studies at present studying in vivo effect of BP therapy on the bone healing.

Though bisphosphonates is an important drug in osteoporosis, but timing of its administration may need to be tailored in the healing phase of the fracture. In vivo studies are needed on the effect of bisphosphonates on histological rather than radiological fracture healing.