Randomised trial of genetic testing and targeted intervention to prevent the development and progression of Paget's disease of bone.
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Phillips Jonathan, Subedi Deepak, Lewis Steff C, Keerie Catriona, Cronin Owen, Porteous Mary, Moore David, Cetnarskyj Roseanne, Ranganath Lakshminarayan, Selby Peter L, Turgut Tolga, Hampson Geeta, Chandra Rama, Ho Shu, Tobias Jon, Young-Min Steven, McKenna Malachi J, Crowley Rachel K, Fraser William D, Tang Jonathan C Y, Gennari Luigi, Nuti Rannuccio, Brandi Maria Luisa, Del Pino-Montes Javier, Devogelaer Jean-Pierre, Durnez Anne, Isaia Giovanni Carlo, Di Stefano Marco, Guanabens Nuria, Blanch Rubio Josep, Seibel Markus J, Walsh John P, Rea Sarah L, Kotowicz Mark A, Nicholson Geoffrey C, Duncan Emma L, Major Gabor, Horne Anne, Gilchrist Nigel, Ralston Stuart H
Аннотация
METHODS: We randomised 222 individuals at increased risk of PDB because of pathogenic SQSTM1 variants to receive 5 mg zoledronic acid (ZA) or placebo. The primary outcome was new bone lesions assessed by radionuclide bone scan. Secondary outcomes included change in existing lesions, biochemical markers of bone turnover and skeletal events related to PDB.
RESULTS: The median duration of follow-up was 84 months (range 0-127) and 180 participants (81%) completed the study. At baseline, 9 (8.1%) of the ZA group had PDB lesions vs 12 (10.8%) of the placebo group. Two of 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). Eight of the placebo group had a poor outcome (lesions which were new, unchanged or progressing) compared with none of the ZA group (OR 0.08, 95% CI 0.00 to 0.42, p=0.003). At the study end, 1 participant in the ZA group had lesions compared with 11 in the placebo group. Biochemical markers of bone turnover were significantly reduced in the ZA group. One participant allocated to placebo required rescue therapy with ZA because of symptomatic disease. The number and severity of adverse events did not differ between groups.
CONCLUSIONS: Genetic testing for pathogenic SQSTM1 variants coupled with intervention with ZA is well tolerated and has favourable effects on the progression of early PDB.
TRIAL REGISTRATION NUMBER: ISRCTN11616770.