A single infusion of Zoledronic acid suppressed bone turnover markers for up to seven years: Results from the Zoledronate in the Prevention of Paget's disease (ZiPP) study

Jonathan Tang, William Fraser, Jonathan Phillips, Isabelle Piec, Rachel Dunn, Catriona Keerie, Steff Lewis, Stuart Ralston

Research output: Contribution to conferencePaperpeer-review


Zoledronate in the Prevention of Paget’s disease (ZiPP) trial (ClinicalTrials.gov ID:NCT03859895) is a multi-centre, double-blind, placebo-controlled, randomised trial of Zoledronic acid (ZA) in sequestosome1 (SQSTM1) mutation carriers. SQSTM1 mutation has high penetrance and is associated with the early onset of Paget’s disease of bone.
Participants with the SQSTM1 genotype received either a single dose of IV 5mg ZA (Aclasta, Novartis); intervention group n=111, age mean (range) 49.8 (32-74)yrs, or placebo n=111, 50.5 (32-75)yrs. Serum samples collected were rapidly centrifuged/stored frozen for bone markers CTX (resorption), PINP (formation) and BSALP (osteoblasts activity) every 12 months from baseline for five years and at end-of-study(EoS) 2-yr follow-up. Urine bone resorption marker uNTX and radionuclide bone scans were performed at baseline/EoS.
In the Intervention group, CTX and PINP showed respective decreases in serum concentrations of average -44.8% and -29.2% across all time points; greatest reductions were observed at 12mths (CTX -57.6%,PINP -46.7%), and remained below baseline concentrations to EoS (CTX -15.2%,PINP -20%). Serum BSALP showed a -20.9% decrease at 12mths then returned to baseline concentration at 36mths. uNTX showed a -36% decrease at EoS. Treatment effect (zoledronate vs placebo) was highly significant for CTX and PINP (ANCOVA p<0.0001) and significant for BSALP (p=0.0005). Bone scans revealed ZA treatment effect was associated with lower risks of developing new bone lesions (odds ratio, 95%CI: 0.406, 0.0-3.425,p=0.246), and further activities of existing lesions in patients (0.083, 0.0-0.424,p=0.003).
We showed in SQSTM1 mutation carriers, a single treatment of 5mg ZA can achieve long-term suppression of bone resorption and formation markers for up to 7 years. ZA treatment is beneficial against the formation of bone lesions and improves outcome in patients with existing lesions. The different rates of decrease in bone markers offer insights into the bone remodelling process post ZA administration.
Original languageEnglish
Publication statusPublished - 2023

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