Intensive bisphosphonate therapy not effective for adults with Paget’s disease

Adults with Paget’s disease of the bone treated with bisphosphonate therapy even if they were not experiencing bone pain were more likely to experience fractures and orthopedic procedures than adults who were treated with bisphosphonates only when symptomatic, according to recent study findings presented at The American Society for Bone and Mineral Research Annual Meeting.

Adrian Tan, MD, ChB, an MD student at The University of Edinburgh, and colleagues analyzed data from 502 adults with Paget’s disease of the bone who had participated in the PRISM study, a study comparing the benefits of symptom-directed use of bisphosphonates with bisphosphonate therapy assigned even in the absence of any symptoms for a mean of 4.3 years. In the extension study (PRISM-EZ), adults were assigned zoledronic acid for an additional 3 years using the same treatment allocation; symptomatic adults (n = 232) were treated with bisphosphonates only if reporting bone pain; adults in the intensive group (n = 270) were assigned bisphosphonate therapy even if they did not report symptoms, with the aim of maintaining alkaline phosphatase levels (ALP) in the normal range. Zoledronic acid was the bisphosphonate of first choice in the intensive arm; treatment groups were matched at entry to the extension for age, previous fracture, previous orthopedic surgery, bone deformity and quality of life scores.

Mean levels of ALP were significantly lower in the intensive group (P = .02); the difference between groups increased as the study progressed. There were more fractures and orthopedic procedures in the intensive group compared with the symptomatic group (26 vs. 13; 15 vs. 8). A time to event analysis, after adjusting for baseline characteristics, found that the risk for both fractures and orthopedic procedures as a combined endpoint was significantly increased in the intensive group (HR = 1.85; 95% CI, 1.04-3.27). Within the cohort, about 25% of fractures and 50% of orthopedic events occurred in the Pagetic bone. Overall adverse events did not differ between groups; one patient in the intensive group developed osteonecrosis of the jaw.

“Intensive bisphosphonate therapy confers no clinical benefit in patients with [Paget’s disease of bone] and may be harmful,” the researchers wrote. “Treatment should be directed at treating symptoms rather than normalizing ALP values.” – by Regina Schaffer

Reference:

Tan A, et al. Abstract 1069. Presented at: The American Society for Bone and Mineral Research Annual Meeting; Oct. 9-12, 2015; Seattle.

Disclosure: This study received funding from Arthritis Research U.K. Tan reports no relevant financial disclosures.