Comparison of different intravenous bisphosphonate regimens for Paget's disease of bone.
This randomized study compared different intravenous bisphosphonates in PDB. Zoledronate was superior with respect to pamidronate in achieving biochemical remission, with therapeutic response maintained in most patients at 15 mo. Single neridronate and zoledronate infusion showed a similar efficacy in up to 90% of patients nonresponders to pamidronate.


BACKGROUND
Intravenous bisphosphonates represent a common therapy for Paget's disease of bone (PDB). However, there have been few head to head randomized trials comparing intravenous bisphosphonates.


METHODS
We performed a 15-mo, randomized study comparing different intravenous bisphosphonates in 90 subjects with active PDB. At baseline, patients were randomly assigned to receive pamidronate (30 mg, i.v., for 2 consecutive days every 3 mo; n = 60) or zoledronate (4 mg, i.v.; n = 30). After 6 mo, nonresponders to pamidronate were crossed over to zoledronate or neridronate (100 mg, i.v., for 2 consecutive days). The primary efficacy endpoint was therapeutic response at 6 mo, defined as normalization of alkaline phosphatase (ALP) or a reduction of at least 75% in total ALP excess.


RESULTS
At 6 mo, 97% of patients receiving zoledronate had a therapeutic response compared with 45% of patients receiving pamidronate. Normalization of ALP was achieved in 93% of patients in the zoledronate group and in 35% of patients in the pamidronate group. ALP normalization was maintained in 79% and 65% of zoledronate-treated patients after 12 and 15 mo, respectively; loss of therapeutic response was observed in 2 of 30 (6%) at 12 and 15 mo. At 6 mo, 27 patients showing therapeutic response to pamidronate continued the treatment, whereas nonresponders were crossed-over to neridronate (n = 15) or zoledronate (n = 18). Among these subjects, 14 of 15 (93%) in the neridronate group and 17 of 18 (94%) in the zoledronate group achieved a therapeutic response. Similar normalization rates were observed between neridronate- (80%) and zoledronate- (83%) treated subjects. Normalization and therapeutic response were maintained at 9 mo from treatment (corresponding to 15 mo from the baseline visit) in either neridronate or zoledronate groups.


CONCLUSIONS
Single neridronate and zoledronate infusion showed a similar efficacy in achieving biochemical remission in up to 90% of patients nonresponders to pamidronate. Therapeutic response to zoledronate seems to be maintained in most patients at 15 mo.
Merlotti
Daniela
D
Department of Internal Medicine, Endocrine, Metabolic Sciences, and Biochemistry, University of Siena, Siena, Italy. merlotti4@unisi.it
Gennari
Luigi
L
Martini
Giuseppe
G
Valleggi
Fabrizio
F
De Paola
Vincenzo
V
Avanzati
Annalisa
A
Nuti
Ranuccio
R
D000368:Aged; D004164:Diphosphonates / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D007275:Injections, Intravenous; D008297:Male; D010001:Osteitis Deformans / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D010146:Pain / Q000188:drug therapy / Q000473:pathology; D000077268:Pamidronate; D011788:Quality of Life; D013997:Time Factors; D000077211:Zoledronic Acid
D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; C053389:6-amino-1-hydroxyhexane-1,1-diphosphonate; D000077268:Pamidronate