Defining the role of bisphosphonates for osteonecrosis of the knee: a systematic review

Abstract

Osteonecrosis of the knee encompasses three conditions: spontaneous, secondary, and postarthroscopic. Treatment options include nonoperative treatment, joint preserving surgery, and arthroplasty. Bisphosphonates have been shown to successfully prevent bone resorption in animal studies and hip osteonecrosis. This article aims to systematically review the available evidence that bisphosphonates reduce pain and improve function in patients with knee osteonecrosis. A systematic review using the online databases Medline and EMBASE was conducted. All studies that assessed the use of bisphosphonates in the treatment of knee osteonecrosis were included. Critical appraisal using a validated quality assessment scale and the CONSORT statement was performed. Eight studies were eligible for inclusion, the total number of patients was 89, and the overall rate of side effects was 12%. Seven studies reported cases of spontaneous osteonecrosis; the mean time until MRI resolution ranged from 4-6 mo but a randomized controlled trial reported no improvement in clinical or radiographic outcome when compared to placebo. Two studies reviewed postarthroscopic cases with the largest study reporting an 80% improvement in pain and 67% radiographic resolution. One study reported three cases of secondary knee osteonecrosis in children suffering from acute lymphoblastic leukemia and only one demonstrated improvement in pain or MRI findings. Evidence from case series suggests bisphosphonates may have a role in knee osteonecrosis, but this was not validated in the single published randomized controlled trial, which had several important limitations. The lack of high-quality evidence necessitates further robust research to evaluate if bisphosphonates are an efficacious treatment modality.