Zoledronate in the Prevention of Paget’s disease (ZiPP)

The ZiPP study is a clinical research study run by the Edinburgh Clinical Trials Unit. The team at the Paget's Association were part of the Steering Committee. [2020]

First Results of the ZiPP Study Revealed

Genetic factors are known to be important in the development of Paget’s disease. Apart from age, having a family history of the disease is one of the most important risk factors for the development of Paget’s. The Zoledronate in the Prevention of Paget’s disease (ZiPP) study was designed to investigate the feasibility of conducting a large-scale program of genetic testing, coupled with targeted intervention with zoledronic acid or a dummy treatment (placebo), in people with a family history of Paget’s disease. Although we now know that there are more than 13 gene variants that predispose to Paget’s disease, the ZiPP study focused only on people who tested positive for variants in the SQSTM1 gene, which are the single most common cause of Paget’s disease.

The ZiPP investigators published the results of the baseline characteristics of people who took part in the study earlier this year in the Journal of Bone and Mineral Research. Of the 222 people who took part in the study 20 (9%) had early signs of Paget’s disease, which was seen on bone scans carried out at the baseline study visits. While biochemical markers of bone turnover, such as alkaline phosphatase and other markers, were, on average, higher in people who had evidence of Paget’s on their bone scan, in most cases, they were still in the normal range. The authors also commented that none of the participants, with evidence of early Paget’s disease on their scan, had any symptoms or signs of the condition.

The researchers concluded that, in its early stages, Paget’s is a clinically silent condition and may remain so for many years until complications develop. This is in keeping with the findings of a previous study by researchers at the Paget’s Association’s Centre of Excellence in Edinburgh, which revealed that in about 40% of individuals, Paget’s first presents with a complication of the disease, such as deformity, fracture, or deafness. Lead author Dr Owen Cronin said “The ZiPP study has shown that a programme of genetic testing, coupled with therapeutic intervention, is acceptable to people with a family history of Paget’s disease. We are now waiting eagerly for the remaining participants to complete their end of study visits so that we can determine if the bisphosphonate, zoledronic acid, can halt the disease”.

Reference: Cronin et al. (2020). Characteristics of Early Paget’s Disease in SQSTM1 Mutation Carriers: Baseline Analysis of the ZiPP Study Cohort. J Bone Miner Res, 35: 1246-1252. doi:10.1002/jbmr.4007

This summary was published in Paget's News, the magazine of the Paget's Association, in 2020.