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Abstract：
BACKGROUND: 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.
BACKGROUND: ISRCTN11616770.
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.
BACKGROUND: ISRCTN11616770.
摘要：
背景：佩吉特骨病（PDB）经常在晚期出现不可逆的骨骼损伤。早期诊断和预防性治疗可能会改善临床结果。
方法：我们将222名因致病性SQSTM1变异而导致PDB风险增加的个体随机分组接受5mg唑来膦酸(ZA)或安慰剂。主要结果是通过放射性核素骨扫描评估的新骨病变。次要结果包括现有病变的改变，与PDB相关的骨转换和骨骼事件的生化标志物。
结果：中位随访时间为84个月（范围0-127），180名参与者（81％）完成了研究。在基线,ZA组9例（8.1%）有PDB损伤，安慰剂组12例（10.8%）。安慰剂组中有两个出现了新的病变，而ZA组中没有出现新的病变（OR0.41，95％CI0.00至3.43，p=0.25）。安慰剂组中有8个结果不佳（新出现的病变，未改变或进展)与无ZA组相比(OR0.08，95%CI0.00至0.42，p=0.003)。在研究结束时，ZA组有1名参与者有病变，而安慰剂组有11名。ZA组骨转换的生化标志物显著降低。由于有症状的疾病，一名分配给安慰剂的参与者需要使用ZA进行抢救治疗。两组之间不良事件的数量和严重程度没有差异。
结论：致病性SQSTM1变异体的基因检测加上ZA的干预具有良好的耐受性，对早期PDB的进展具有有利的影响。
背景：ISRCTN11616770。
方法：我们将222名因致病性SQSTM1变异而导致PDB风险增加的个体随机分组接受5mg唑来膦酸(ZA)或安慰剂。主要结果是通过放射性核素骨扫描评估的新骨病变。次要结果包括现有病变的改变，与PDB相关的骨转换和骨骼事件的生化标志物。
结果：中位随访时间为84个月（范围0-127），180名参与者（81％）完成了研究。在基线,ZA组9例（8.1%）有PDB损伤，安慰剂组12例（10.8%）。安慰剂组中有两个出现了新的病变，而ZA组中没有出现新的病变（OR0.41，95％CI0.00至3.43，p=0.25）。安慰剂组中有8个结果不佳（新出现的病变，未改变或进展)与无ZA组相比(OR0.08，95%CI0.00至0.42，p=0.003)。在研究结束时，ZA组有1名参与者有病变，而安慰剂组有11名。ZA组骨转换的生化标志物显著降低。由于有症状的疾病，一名分配给安慰剂的参与者需要使用ZA进行抢救治疗。两组之间不良事件的数量和严重程度没有差异。
结论：致病性SQSTM1变异体的基因检测加上ZA的干预具有良好的耐受性，对早期PDB的进展具有有利的影响。
背景：ISRCTN11616770。
