Zoledronate In the Prevention of Paget's Disease: Long Term Extension
Zoledronate In the Prevention of Paget's Disease: Long Term Extension
Paget's disease of the bone (PDB) is a metabolic bone disorder which in some individuals can
 cause pain, bone deformity, arthritis and deafness, although in many patients it does not
 cause symptoms. Paget's disease has a strong genetic component and SQSTM1 is the most
 important susceptibility gene. People who inherit mutations in SQSTM1 have a high risk of
 developing PDB later in life. This study is an extension of the ZiPP (Zoledronate in the
 Prevention of Paget's) study which was is randomised trial currently in progress to determine
 if the bisphosphonate zoledronic acid (ZA) can prevent or delay the development of PDB-like
 bone lesions compared with a dummy treatment (placebo) in people who inherit SQSMT1 gene
 mutations. Although the ZiPP study will provide information on whether early ZA treatment can
 favourably influence bone lesion development the significance of this to the patient in terms
 of symptoms is unclear as yet. The aim of the extension study is to keep these individuals
 under surveillance for any symptoms or signs of PDB over a further 5 year period and to
 evaluate if there has been any progression of PDB-like lesions by bone scan at the end of
 this period.
It is at present unclear whether intervention with bisphosphonates is of clinical benefit in
 early PDB. Although the ZiPP study is expected to provide information on whether ZA can
 favourably influence the development of bone lesions characteristic of early PDB as
 determined by radionuclide bone scan imaging, longer term follow up is required to determine
 if this will translate into clinical benefit. The extension study described here will provide
 new information on the natural history of PDB by follow up of people that took part in the
 ZIPP trial. Although the ZIPP-LTE study is an observational study, treatment for PDB may be
 given to participants according to normal clinical practice if they develop signs or symptoms
 of PDB during the extension. Treatment will therefore be offered to all participants that
 develop symptoms of PDB during follow up. Additionally, subjects that were previously been
 exposed to ZA in the core study will also be offered further ZA or another bisphosphonate
 licensed for PDB if they develop evidence of increased metabolic activity thought to be due
 to PDB, even if asymptomatic. The reason for this is that adverse effects are rare in
 patients who have previously been treated with ZA but are common on first exposure to ZA.
 Both therapeutic approaches are commonly used in patients with early PDB with no evidence
 that one is superior to another. In addition to providing information on the natural history
 of PDB, part of the aim of the extension will be to evaluate the risks and benefits of these
 two approaches to standard care of in terms of new lesion development, pain, quality of life
 and adverse events in the context of people who inherit SQSTM1 mutations.
Inclusion Criteria:

 -  Subject that participated in ZiPP

 -  Participant willing and able to consent and comply with the study protocol.

 Exclusion Criteria:

 -  Unable or unwilling to provide informed consent