TY - JOUR
T1 - Randomised trial of genetic testing and targeted intervention to prevent the development and progression of Paget's disease of bone
AU - Phillips, Jonathan
AU - Subedi, Deepak
AU - Lewis, Steff C
AU - Keerie, Catriona
AU - Cronin, Owen
AU - Porteous, Mary
AU - Moore, David
AU - Cetnarskyj, Roseanne
AU - Ranganath, Lakshminarayan
AU - Selby, Peter L.
AU - Turgut, Tolga
AU - Hampson, Geeta
AU - Chandra, Rama
AU - Ho, Shu
AU - Tobias, Jon
AU - Young-Min, Steven
AU - McKenna, Malachi J
AU - Crowley, Rachel K
AU - Fraser, William D
AU - Tang, Jonathan C Y
AU - Gennari, Luigi
AU - Nuti, Rannuccio
AU - Brandi, Maria Luisa
AU - Del Pino-Montes, Javier
AU - Devogelaer, Jean-Pierre
AU - Durnez, Anne
AU - Isaia, Giovanni Carlo
AU - Di Stefano, Marco
AU - Guanabens, Nuria
AU - Blanch Rubio, Josep
AU - Seibel, Markus J
AU - Walsh, John P
AU - Rea, Sarah L
AU - Kotowicz, Mark A
AU - Nicholson, Geoffrey C
AU - Duncan, Emma L
AU - Major, Gabor
AU - Horne, Anne
AU - Gilchrist, Nigel
AU - Ralston, Stuart H
N1 - Publisher Copyright:
© Author(s)(or their employer(s)) 2024.
PY - 2024/4
Y1 - 2024/4
N2 - Introduction Paget’s disease of bone (PDB) frequently presents at an advanced stage with irreversible skeletal damage. Clinical outcomes might be improved by earlier diagnosis and prophylactic treatment. 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.
AB - Introduction Paget’s disease of bone (PDB) frequently presents at an advanced stage with irreversible skeletal damage. Clinical outcomes might be improved by earlier diagnosis and prophylactic treatment. 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.
UR - http://www.scopus.com/inward/record.url?scp=85187778309&partnerID=8YFLogxK
U2 - 10.1136/ard-2023-224990
DO - 10.1136/ard-2023-224990
M3 - Article
C2 - 38123339
SN - 0003-4967
VL - 83
SP - 529
EP - 536
JO - Annals of the Rheumatic Diseases
JF - Annals of the Rheumatic Diseases
IS - 4
M1 - 224990
ER -