#apaperaday: Bisphosphonates in Glucocorticoid-Treated Patients With Duchenne Muscular Dystrophy

In today’s #apaperaday, Prof. Aartsma-Rus reads and comments on the paper titled:  Bisphosphonates in Glucocorticoid-Treated Patients With Duchenne Muscular Dystrophy: A Systematic Review and Grading of the Evidence

Paper a day on tour to present at a meeting on innovation in rare diseases from preclinical research to patients in Bari. Today’s pick is a systematic review on the impact of bisphosphonate treatment in Duchenne from Neurology by Landfeldt et al. DOI 10.1212/WNL.0000000000207948

Duchenne patients have an increased risk for osteoporosis due to less activity and weightbearing, muscle pathology, reduced sunlight and thus vitamin D deficiency and chronic use of glucocorticosteroids. Osteoporosis leads to an increased fracture risk.

Duchenne patients have a 2 fold increased risk for long bone fractures and almost all develop vertebral fractures. Treatment with bisphosphonates is used to increase the bone mineral density (BMD) is recommended in the standards of care.

Here authors performed a systematic review about the impact of this treatment. Authors found 163 publications, of which 19 were relevant and only 2 involved high quality studies (placebo controlled trials).

The studies were from 12 countries from all continents except South America (and I presume Antarctica). 10 trials used intravenous bisphosphonate treatment, 6 oral, 2 used both and 1 did not report the route of administration.

The risk of long bone and vertebral fractures appeared to reduce with intravenous bisphosphonate treatment. All studies showed improved bone mineral density, but intravenous treatment had a larger impact.

Blood analysis showed a reduction in bone turnover markers, confirming the bisphosphonate treatment did what it was supposed to be doing. Treatment was generally well tolerated, except that many patients had an ‘acute phase reaction’ after the first treatment.

This involves flu like symptoms, but can in rare cases lead to dangerous situations. Authors discuss only 2 studies provided high quality evidence. This is because bisphosphonate treatment is routinely used, so it is difficult to set up a placebo-controlled trial.

The 2 studies that did include a placebo, showed improved bone mineral density. Intravenous treatment clearly outperformed oral treatment, which is not surprising given the low bioavailability of bisphosphonate after oral ingestion.

The impact on vertebral bone density is larger than on long bones, which is not surprising: long bones are more ‘spongy’. Authors conclude their systematic review confirms the care guidelines recommendation for intravenous bisphosphonate treatment in Duchenne patients on steroids

Authors stress that treatment should be managed by clinicians with expertise, also due to the risk of post-infusion side effects. Good that authors do a data-driven confirmation for the care guideline recommendation!