Intermittent versus continuous clodronate administration in postmenopausal women with low bone mass.

The aim of the study was to compare the effects on bone mass and turnover of continuous vs. intermittent clodronate administration on 120 postmenopausal women (average age 61 years) with low bone mass (femoral neck bone mineral density [BMD] of at least -1 SD or more, T-score), with another 30 women as a control group. Participants were given 1800 mg of clodronate every 6 months over 2 years using different treatment patterns: a) two continuous regimens, consisting of a daily oral dose of 400 mg or 100 mg every 10 days by intramuscular injection, the latter being considered continuous because the interval between injections is shorter than the time employed by each bone remodelling unit to complete the resorption phase of a remodelling cycle; and b) two intermittent regimens, consisting of 1800 mg every 6 months administered either as a single 18-h intravenous infusion or by separate infusions of 300 mg over 6 consecutive days. All women, including those in the control group, received calcium and vitamin D supplementation. After 2 years, continuous clodronate regimens caused an increase in BMD both at lumbar spine and proximal femur (L(1-4) BMD = 3.07% and 2.69%; femoral neck = 2.12% and 2.09%, respectively, with intramuscular and oral regimens). Intermittent clodronate administration was associated with a small increase or a stabilization in bone mass (L(1-4) BMD = 0.53% and 1.22%; femoral neck = 0.30% and 0.77%, respectively, with 1- and 6-day intravenous infusion regimens). From the 12th month, changes in spine and femoral neck BMD after continuous regimens were statistically different compared with that obtained with intermittent ones. Twenty-five of the 150 women (16.7%) discontinued the study before the end of the 2-year follow-up, but of these, only 7 dropped out because of adverse events related to the treatment itself. To summarize, intermittent clodronate administration could be a suitable option for the prevention of osteoporosis.

Paget's disease of bone: benefits of neridonate as a first treatment and in cases of relapse after clodronate.

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.

Cyclical intravenous clodronate in postmenopausal osteoporosis: results of a long-term clinical trial.

We report the results of long-term cyclical clodronate therapy (200 mg IV infusion every 3 weeks) on 235 women with postmenopausal osteoporosis recruited over 6 years. A retrospective analysis of clinical and instrumental findings in 183 postmenopausal osteoporotic patients was used as control data. Clodronate was well-tolerated and compliance was good. Bone mineral density (BMD) increased significantly and the upward trend persisted for all 6 years of therapy (5.69 +/- 0.184%) vs. controls: -1.47% +/- 0.813%, p <0.0001). The increase in BMD was greater in the 145 patients without vertebral fractures before starting clodronate. From year 3 onward clodronate reduced the incidence of new vertebral fractures. In closed subsets of patients and controls monitored for 3 and 4 years, respectively, the number of patients developing new vertebral fractures fell significantly in the clodronate group (two-sided p value = 0.0671 and p <0.0026, respectively). This trend was more marked in patients who were fracture-free at the beginning of each year. Cyclical clodronate is a safe and effective therapy for established osteoporosis, but clinical trials are necessary to compare its efficacy versus continuous therapy and, as in the case of the other bisphosphonates, to investigate its mechanisms of action in depth.