Discover how the latest breakthrough in genetic testing and targeted intervention is revolutionizing the prevention and management of Paget’s disease of bone in our in-depth analysis of this groundbreaking randomised trial.
– by James
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Randomised trial of genetic testing and targeted intervention to prevent the development and progression of Paget’s disease of bone.
Phillips et al., Ann Rheum Dis 2023
DOI: 10.1136/ard-2023-224990
Study Summary:
A study investigated the efficacy of zoledronic acid (ZA) in preventing the progression of Paget’s disease of bone (PDB) in individuals with pathogenic SQSTM1 variants, who are at increased risk. A total of 222 participants were randomized to receive either 5 mg ZA or a placebo. The primary focus was on the development of new bone lesions, while secondary outcomes included changes in existing lesions, bone turnover markers, and PDB-related skeletal events.
Results:
- Median follow-up duration was 84 months, with 81% of participants completing the study.
- Initially, 8.1% of the ZA group and 10.8% of the placebo group had PDB lesions.
- No new lesions developed in the ZA group, while two appeared in the placebo group (odds ratio [OR] 0.41, not statistically significant).
- Poor outcomes (new, unchanged, or progressing lesions) occurred in none of the ZA group compared to eight in the placebo group (OR 0.08, p=0.003).
- At the study’s end, only one participant in the ZA group had lesions versus eleven in the placebo group.
- Biochemical markers of bone turnover were significantly reduced in the ZA group.
- One placebo participant required ZA rescue therapy due to symptomatic PDB.
- Adverse events were similar between both groups.
Significance:
The study suggests that genetic testing for SQSTM1 variants followed by ZA treatment can be a well-tolerated strategy to prevent the progression of early PDB. This approach could potentially improve clinical outcomes by allowing for earlier diagnosis and prophylactic treatment.
Contribution to Literature:
This research contributes to the literature by providing evidence that prophylactic treatment with ZA can prevent the progression of PDB in genetically susceptible individuals, highlighting the importance of early intervention.
Study Registration:
The study is registered with ISRCTN11616770.