Background/Purpose: Bisphosphonates are first line therapy in the treatment of Paget’s disease (PD). Zoledronate, a third generation bisphosphonate, has showed high efficacy in the inhibition of bone resorption. The objective of this observational study was to assess short and long-term efficacy and safety of zoledronate in the treatment of active PD, in clinical practice.

Methods: Patients with active PD treated with zoledronate 5 mg were consecutively recruited between 2005 and 2011 and followed prospectively. Clinical (bone and joint pain attributed to PD) and laboratory parameters (alkaline phosphatase (ALP), bone specific alkaline phosphatase (BSALP), procollagen type 1 N-terminal propeptide (P1NP), collagen type 1 beta C-terminal telopeptide (b-CTX), seric and urinary calcium and phosphorus and parathormone levels) were determined before, at 3 and then every 6 months after treatment, up to a maximum of 60 months of follow-up. Remission was defined as normalization of ALP. Retreatement was considered when ALP levels increased more than 25% of the upper limit of normal or of the nadir achieve, in cases of non normalization of ALP. Adverse events were registered according to clinical protocol.

Results: 60 patients (60% males), with a mean age of 68±11 years and a mean disease duration of 11±9 years were included. 69% had polyostotic disease and the mean percentage of skeletal involvement (Howarth table) was of 10.8±7.6%. 68% were symptomatic: 71% of those referring bone and 54% joint pain attributed to PD. 54% were receiving analgesic or non steroidal anti-inflammatory drugs. 48.3% had been previously treated with parental pamidronate, with a cumulative dose of 234±209mg. The mean follow-up period after zoledronate infusion was of 37±13 months (minimum of 12 and maximum of 60). Only 4 patients (6.6%) required retreatment, on average 30 months after the first zoledronate infusion. A marked reduction of ALP (261,6±152,5 U/L at baseline) was observed at 3 (70%;79,6±42,6) and 6 months (74%;67,0±22,1) after zoledronate administration, being maximal at 12 months (75%;66,3±22,2)  (p<0.001). The difference of the mean values of ALP between 3 and 6 months was also significant (p<0.05). At 3 and 6 months, 95% and 96% of patients respectively, achieved remission. Maximum effect was obtained at 12 months after treatment with 98% of patients being in remission. Significant reductions of the mean levels of BSALP, P1NP, and b-CTX (p<0.001) were also verified at 3, 6 and 12 months after treatment. 47% of patients reported pain improvement: 89% at 3 months, 7% at 6 months and 4% at 12 months. Transitory side effects were registered in 15 patients, 18% referred flu-like symptoms, 10% showed asymptomatic hypocalcaemia and 30% asymptomatic hypophosphoremia. 

Conclusion: This study confirms the efficacy and safety of zoledronate in a Portuguese population of patients with active Paget’s disease. Biochemical remission was achieved in 98% of patients at 12 months and improvement of pain in 47%, the majority 3 months after treatment. Furthermore these benefits were long-term sustained with only 6.6% of patients requiring retreatment during an average follow-up of 37 months.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/zoledronate-efficacy-and-safety-in-active-pagets-disease-long-term-follow-up-and-retreatment-in-clinical-practice/