This study assessed the efficacy of 200 mg of
aminohexane bisphosphonate (
neridronate) administered by
intravenous infusion in a single dose or in two separate doses on consecutive days in 32 patients (16 males and 16 females, average age 66 years) affected by active
Paget's disease of bone. Fifteen patients had never been treated with any
antiresorptive agent and 17 had had unsatisfactory results from a prior
clodronate treatment. All of the latter patients had failed to enter a remission stage (i.e., normalization of bone turnover was not reported at any time during treatment) and had had a full relapse within 6 months after
clodronate infusion. In the present study bone-specific
alkaline phosphatase (bAp),
deoxypyridinoline (dPyr), and N- and C-terminal
polypeptide of
collagen type 1 (Ntx, Ctx) were determined before
neridronate administration and at 1, 3, 6, and 12 months thereafter. Basal values of bAp were 51.7 +/- 2.3 microg/L, range 31.7-92.5 (normal range 6.2-23.6). No statistical differences in markers of bone turnover were evident in the basal state between new pagetic patients (bAp = 55.1 +/- 4.1) and those suffering a relapse after
clodronate (bAp = 48.8 +/- 2.6).
Neridronate induced an average percent change from baseline in excess bAp of 68.0 +/- 4.3 and in excess dPyr, Ntx, and Ctx of 68.1 +/- 11, 60.6 +/- 8.5, and 86.7 +/- 7.8, respectively. Markers of
bone resorption declined more slowly in patients treated previously with
clodronate, although the average change in percent decrement from baseline in excess bAp as well as in excess of
bone resorption markers was not different from that registered in untreated pagetic patients. Response to treatment, defined as a percent decrement from baseline in excess bAp of 50% or more at any time during the 12-month follow-up, was observed in 27 patients (84.4%). Remission (a drop in bAp to within normal range) was achieved in 21 patients (65.6%) and was maintained in 12 at 12-month follow-up, with no significant differences between either 1- or 2-day infusions, or between new pagetic patients and those relapsing after
clodronate. In 15 of 21 patients requiring
analgesics to alleviate bone
pain,
pain was reduced or completely alleviated in 8. A slight, short-lived
acute phase reaction (
fever and/or arthromyalgia) occurred in 6 patients. To summarize, 200 mg of intravenous
neridronate, in one or two doses, significantly reduced the biochemical indices of disease activity in the majority of patients, showing a normalization of bAp in more than 60%. We conclude that
neridronate can be used safely in the treatment of patients with
Paget's disease of bone either as a first
bisphosphonate treatment or as
retreatment for patients relapsing after
clodronate.