When it comes to Paget’s disease of bone, it looks like an accepted treatment isn’t panning out. The research, published in the January 2017 edition of the Journal of Bone and Mineral Research, found that long-term intensive bisphosphonate therapy showed no clinical benefit over giving bisphosphonates only when patients felt bone pain.
Paget’s: Fracture Risk INCREASED With Intensive Treatment
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The study is entitled, “Long-Term Randomized Trial of Intensive Versus Symptomatic Management in Paget’s Disease of Bone: The PRISM-EZ Study.”
Stuart Ralston, M.D. was a senior author of study. Dr. Ralston is the Arthritis Research UK Professor of Rheumatology at the Centre for Genomic and Experimental Medicine Institute of Genetics and Molecular Medicine at the University of Edinburgh. He told OTW, “Many experts have considered that it is a good thing to try and suppress high bone turnover (usually assessed clinically by measurement of total alkaline phosphatase or ALP) with bisphosphonates in Paget’s disease of bone (so that bone turnover is normal or low normal) in the hope that this will prevent complications like bone fractures and reduce the risk of patients needing orthopedic surgery. The PRISM-EZ study (and its predecessor PRISM) were designed to evaluate whether this is beneficial.”
“The study showed that suppressing bone turnover with ‘intensive’ bisphosphonate therapy aimed at maximally suppressing ALP was of no clear clinical benefit. Also patients allocated to that treatment had a trend for an increased risk of fracture, an increased risk of orthopedic procedures and more serious adverse events. Individually these events were not significantly different between the groups, but overall there is a concern that ‘intensive’ treatment may be harmful. It is certainly not beneficial.”
“It was surprising to find that fracture risk was increased almost two-fold with intensive treatment and orthopedic procedures were about 50% more common. For patients with Paget’s disease, bisphosphonates should be given to treat bone pain if present, but should not be given with the aim of suppressing ALP levels.”
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This is a fascinating development. In my practice we've seen similar outcomes with the revised protocol. The key differentiator seems to be patient selection criteria. Has anyone else noticed the correlation with BMI thresholds?
Great point. I'd push back slightly on the conclusion, the sample size in the cited study is too small to draw population-level inferences. That said, the directional signal is compelling and worth a larger RCT.
We implemented a similar approach last year. Early results are promising but we're still gathering 12-month follow-up data. Happy to share our protocol if anyone is interested.
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