“Bisphosphonates: Possible Modes of Action and Implications for Dental Implant Treatment. A Review of the Literature”

Abstract

Bisphosphonates (BP) have been commonly used over the past 40 years to treat osteoporosis, Pagets’ disease, hypercalcemia of malignancy, osteolytic lesions of multiple myeloma and bone metastases associated with breast, prostate, lung and other soft tissue tumours. The main aims of this review are to: 1. Highlight the fundamental pharmacophysiological modes of action of both nitrogen and non-nitrogen bisphosphonates on bone 2. Explore their potential effects on oral hard and soft tissues 3. Discuss the implications of bisphosphonate therapy on dental implants, in particular their contribution to implant failure 4. Discuss the current recommendations and guidelines for dental implant therapy in patients receiving bisphosphonate therapy based on the available evidence. Two distinct types of bisphosphonates have been classified and differentiated according to their mode of action, chemical structure, potency, delivery, bioavailability, dosage and half-life. Bisphosphonates are classified as: 1) Nonnitrogen containing bisphosphonates (BP) and 2) Nitrogen containing bisphosphonates (N-BP). 27 studies met the study inclusion and exclusion criteria, with 8 retrospective studies and 2 case series studies evaluating the success rate of dental implants in patients with a history of bisphosphonate use, while the remaining 17 articles consisted of case series and case reports. While there are shortcomings associated with many of the reported studies, there does appear to be a certain risk associated with the both implant placement and the maintanence of osseointegrated implants in patients receiving oral bisphosphonates. A Southern Austrailian study estimated the risk of implant failure in patients receiving oral bisphosphonates to be 0.88%. Late implant failures appear to occur in patients treated with oral bisphosphonate exposure for a period >3 years especially in patients who have existing integrated implants,while early failures appear to occur in patients treated with bisphosphonates before or at the time of implant placement. Although the results from these retrospective studies and case series are conflicting to some extent, they have heightened awareness of the possible complication of BRONJ and bisphosphonate related implant failure from long term bisphosphonate use, be it oral or iv-bisphosphonates.