Bone Abstracts

Paget’s disease of bone (PDB) is a common metabolic bone disease characterised by increased and disorganised bone remodelling affecting one or more skeletal sites. Bisphosphonates are highly effective at suppressing bone turnover in PDB but it remains unclear whether greater suppression of bone turnover improves clinical outcome. In the PRISM study, we previously reported that PDB patients randomised to ‘intensive’ treatment aimed at normalising alkaline phosphatase (ALP) levels had a similar long-term outcome as those randomised to ‘symptomatic’ treatment aimed at controlling symptoms. Here, we report initial results from an extension of the PRISM study (PRISM-EZ) in which zoledronic acid was used as the bisphosphonate of first choice in the ‘intensive’ arm. We studied 502 patients who consented to take part in the extension; 270 continued to receive intensive treatment and 232 continued to receive symptomatic treatment. The treatment groups were well matched at entry to the extension for age, previous fracture, previous orthopaedic surgery, bone deformity and quality of life scores. As expected mean±SEM ALP values at entry to the extension were lower in the intensive group; (0.85±0.04 vs 1.04±0.06, P=0.012, where 1.0 is the upper limit of normal). The ALP values decreased further in the intensive group and were consistently lower throughout follow-up (0.71±0.04 vs 1.01±0.06, P<0.0001). There were no differences between the groups in quality of life scores or bone pain. Fractures were more common during follow up in the intensive group (8.2 vs 4.7%; hazard ratio=1.80 (0.87–3.71) although most (82%) affected non-Pagetic bone. The difference in fractures between the groups was not significant (P=0.11). We conclude that more profound suppression of ALP levels with bisphosphonates including zoledronic acid was not associated with clinical benefit in this group of patients with PDB.