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Abstract：
Paget\'s disease of bone (PDB) is characterised by increased and disorganised bone remodelling affecting one or more skeletal sites. Complications include bone pain, deformity, deafness and pathological fractures. Mutations in sequestosome-1 (SQSTM1) are strongly associated with the development of PDB. Bisphosphonate therapy can improve bone pain in PDB, but there is no evidence that treatment alters the natural history of PDB or prevents complications. The Zoledronate in the Prevention of Paget\'s disease trial (ZiPP) will determine if prophylactic therapy with the bisphosphonate zoledronic acid (ZA) can delay or prevent the development of PDB in people who carry SQSTM1 mutations.
People with a family history of PDB aged >30 years who test positive for SQSTM1 mutations are eligible to take part. At the baseline visit, participants will be screened for the presence of bone lesions by radionuclide bone scan. Biochemical markers of bone turnover will be measured and questionnaires completed to assess pain, health-related quality of life (HRQoL), anxiety and depression. Participants will be randomised to receive a single intravenous infusion of 5 mg ZA or placebo and followed up annually for between 4 and 8 years at which point baseline assessments will be repeated. The primary endpoint will be new bone lesions assessed by radionuclide bone scan. Secondary endpoints will include changes in biochemical markers of bone turnover, pain, HRQoL, anxiety, depression and PDB-related skeletal events.
The study was approved by the Fife and Forth Valley Research Ethics Committee on 22 December 2008 (08/S0501/84). Following completion of the trial, a manuscript will be submitted to a peer-reviewed journal. The results of this trial will inform clinical practice by determining if early intervention with ZA in presymptomatic individuals with SQSTM1 mutations can prevent or slow the development of bone lesions with an adverse event profile that is acceptable.
ISRCTN11616770.
People with a family history of PDB aged >30 years who test positive for SQSTM1 mutations are eligible to take part. At the baseline visit, participants will be screened for the presence of bone lesions by radionuclide bone scan. Biochemical markers of bone turnover will be measured and questionnaires completed to assess pain, health-related quality of life (HRQoL), anxiety and depression. Participants will be randomised to receive a single intravenous infusion of 5 mg ZA or placebo and followed up annually for between 4 and 8 years at which point baseline assessments will be repeated. The primary endpoint will be new bone lesions assessed by radionuclide bone scan. Secondary endpoints will include changes in biochemical markers of bone turnover, pain, HRQoL, anxiety, depression and PDB-related skeletal events.
The study was approved by the Fife and Forth Valley Research Ethics Committee on 22 December 2008 (08/S0501/84). Following completion of the trial, a manuscript will be submitted to a peer-reviewed journal. The results of this trial will inform clinical practice by determining if early intervention with ZA in presymptomatic individuals with SQSTM1 mutations can prevent or slow the development of bone lesions with an adverse event profile that is acceptable.
ISRCTN11616770.
摘要：
Paget骨病（PDB）的特征是骨重塑增加和混乱，影响一个或多个骨骼部位。并发症包括骨痛，畸形,耳聋和病理性骨折。螯合体-1（SQSTM1）的突变与PDB的发展密切相关。双膦酸盐治疗可以改善PDB的骨痛，但没有证据表明治疗改变了PDB的自然史或预防了并发症.唑来膦酸盐预防Paget疾病试验（ZiPP）将确定双膦酸盐唑来膦酸（ZA）的预防性治疗是否可以延迟或预防携带SQSTM1突变的人PDB的发展。
有30岁以上PDB家族史且SQSTM1突变检测呈阳性的人有资格参加。在基线访问时，通过放射性核素骨扫描对参与者进行骨病变筛查.将测量骨转换的生化标志物，并完成问卷以评估疼痛，健康相关生活质量（HRQoL），焦虑和抑郁。参与者将被随机分配接受5mgZA或安慰剂的单次静脉输注，并每年随访4至8年，此时将重复进行基线评估。主要终点将是通过放射性核素骨扫描评估的新骨病变。次要终点将包括骨转换的生化标志物的变化，疼痛,HRQoL,焦虑,抑郁症和PDB相关骨骼事件。
这项研究于2008年12月22日获得Fife和ForthValley研究伦理委员会的批准（08/S0501/84）。审判结束后,手稿将提交给同行评审的期刊.该试验的结果将通过确定在有SQSTM1突变的症状前个体中对ZA的早期干预是否可以预防或减缓具有可接受的不良事件特征的骨病变的发展来为临床实践提供信息。
ISRCTN11616770。
有30岁以上PDB家族史且SQSTM1突变检测呈阳性的人有资格参加。在基线访问时，通过放射性核素骨扫描对参与者进行骨病变筛查.将测量骨转换的生化标志物，并完成问卷以评估疼痛，健康相关生活质量（HRQoL），焦虑和抑郁。参与者将被随机分配接受5mgZA或安慰剂的单次静脉输注，并每年随访4至8年，此时将重复进行基线评估。主要终点将是通过放射性核素骨扫描评估的新骨病变。次要终点将包括骨转换的生化标志物的变化，疼痛,HRQoL,焦虑,抑郁症和PDB相关骨骼事件。
这项研究于2008年12月22日获得Fife和ForthValley研究伦理委员会的批准（08/S0501/84）。审判结束后,手稿将提交给同行评审的期刊.该试验的结果将通过确定在有SQSTM1突变的症状前个体中对ZA的早期干预是否可以预防或减缓具有可接受的不良事件特征的骨病变的发展来为临床实践提供信息。
ISRCTN11616770。
