The following is a summary of “Randomized trial of genetic testing and targeted intervention to prevent the development and progression of Paget’s disease of bone,” published in the December 2023 issue of Rheumatology by Phillips et al.

Researchers launched a retrospective analysis to evaluate whether earlier Paget’s disease of bone (PDB) diagnosis and preventative treatment using zoledronic acid could optimize clinical outcomes in this often late-diagnosed skeletal disorder.

They randomized 222 individuals with heightened PDB risk due to pathogenic SQSTM1 variants, assigning them to receive 5 mg zoledronic acid (ZA) or a placebo. The primary outcome assessed new bone lesions through a radionuclide bone scan. Secondary outcomes encompassed changes in existing lesions, bone turnover biochemical markers, and PDB-related skeletal events.

The results showed a median follow-up duration of 84 months (range 0–127), with 180 participants (81%) completing the study. At baseline, 8.1% of the ZA group had PDB lesions compared to 10.8% in the placebo group. Two in the placebo group developed new lesions versus none in the ZA group (OR 0.41, 95% CI 0.00 to 3.43, P=0.25). Poor outcomes (new, unchanged, or progressing lesions) occurred in 8 of the placebo group versus none in the ZA group (OR 0.08, 95% CI 0.00 to 0.42, P=0.003). At the end of the study, 1 participant in the ZA group had lesions compared to 11 in the placebo group. Early Paget patients with harmful SQSTM1 variants saw significant bone turnover reduction and safety with targeted ZA while highlighting its potential in asymptomatic cases.

They concluded that early Paget patients with harmful SQSTM1 variants benefited from safe and effective ZA treatment after genetic testing.

Source: ard.bmj.com/content/early/2023/12/20/ard-2023-224990