Comparison of intravenous and intramuscular neridronate regimens for the treatment of paget disease of bone

Abstract

Aminobisphosphonates actually represent the most common treatment for Paget disease of bone (PDB). In a previous study we demonstrated that either zoledronic acid (4 mg) or neridronate (200 mg) given as a single intravenous infusion showed a similar shortterm efficacy in achieving biochemical remission in up to 90% of patient nonresponders to pamidronate. In this study we compared the long-term (36 months) effects of a same neridronate dose (200 mg) given as an intravenous (100-mg infusion for 2 consecutive days) or intramuscular (25-mg injection weekly for 2 months) regimen in 56 patients with active PDB. All patients were advised to receive calcium plus vitamin D supplementation throughout the study period. At 6 months, 92.6% and 96.5% of patients receiving intravenous and intramuscular neridronate, respectively, achieved a therapeutic response [defined as normalization of alkaline phosphatase (ALP) levels or a reduction of at least 75% in total ALP excess]. The response to treatment was significantly correlated with baseline ALP and 25-hydroxyvitamin D [25(OH)D] levels at 6 months. The decrease in ALP levels was highest in patients with higher baseline total or bonespecific ALP levels and with higher 25(OH)D levels at 6 months. Response rates were maintained at 12 months but decreased progressively at 24 and 36 months without significant differences between the two neridronate regimens. Both regimens were well tolerated. The only relevant side effect was an acute-phase response occurring in 14% of the patients. In conclusion, these results indicate that a 200-mg intramuscular neridronate course has a similar efficacy as an intravenous infusion of the same dose for the treatment of PDB and might be of particular value for patients intolerant to oral bisphosphonates and unwilling or unable to undergo intravenous infusions. ß

Neridronate: From Experimental Data to Clinical Use

“…The symptoms usually appear 24 to 36 hours after the first administration, mainly in previously untreated patients, and persist for less than 36 hours. 24,27,29,31,43 Other reported adverse events include headache, diarrhoea, and dermatitis. 30 No cases of jaw osteonecrosis have been reported in patients treated with neridronate, even after longer periods of treatment.…”

Clinical development of neridronate: potential for new applications

“…On the basis of the results obtained in this study, the authors consequently performed a randomized open-label study evaluating the long-term efficacy of the same neridronate dose (200 mg), either administered as an intravenous or intramuscular regimen, in 56 patients with PDB, with a 3-year follow-up 28. After 6 months, 92.6% of patients receiving intravenous neridronate and 96.5% of patients with intramuscular regimen achieved a therapeutic response in terms of normalization of alkaline phosphatase levels or reduction of at least 75% in total alkaline phosphatase excess (Figure 2).…”

Paget’s disease of bone: epidemiology, pathogenesis and pharmacotherapy

“…Even though its potency is lower than zoledronic acid, in a recent comparative study, this compound, given as intravenous 100 mg infusion for 2 consecutive days, was as effective as zoledronic acid in achieving a therapeutic response at 6 months in > 90% of patients non-responders to pamidronate treatment [96]. A subsequent study confirmed the efficacy of a single neridronate course (100 mg for 2 consecutive days), with remission rates in 93 and 90% of patients at 6 and 12 months, respectively [97]. In contrast to what observed with zoledronic acid, a progressive decrease in response rates was observed after 1 year from infusion of neridronate, and therapeutic response at 36 months was maintained in 48% of PDB cases.…”

“…In contrast to what observed with zoledronic acid, a progressive decrease in response rates was observed after 1 year from infusion of neridronate, and therapeutic response at 36 months was maintained in 48% of PDB cases. Of interest, the same study demonstrated a comparable efficacy at all time points of a same cumulative neridronate dose (200 mg) given as intramuscular regimen (25 mg injection weekly for 2 months) [97]. This might be of particular value for patients intolerant to oral bisphosphonates and unwilling or unable to undergo intravenous infusions.…”