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Ian R Reid,
Kenneth Lyles,
Guoqin Su, Jacques P Brown,
John P Walsh,
Javier del Pino-Montes,
Paul D Miller,
William D Fraser,
Susan Cafoncelli,
Christina Bucci-Rechtweg,
David J Hosking
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ABSTRACT: Two trials have shown that a single 5-mg infusion of zoledronic acid achieves much higher response rates in Paget disease of bone than risedronate. The duration of this effect is unknown. We have conducted an open follow-up of responders from the two trials (152 originally treated with zoledronic acid, 115 with risedronate) out to 6.5 years without further intervention. Endpoints were times to relapse (ie, return of serum total alkaline phosphatase activity to within 20% of the pretreatment value) or loss of response (response = normalization of alkaline phosphatase or 75% or greater reduction in its excess). Bone turnover markers were lower in the zoledronic acid group throughout follow-up, with mean alkaline phosphatase (ALP) remaining within the reference range in these patients, whereas the mean in the risedronate group was above normal from 1 year. Relapse rates were substantially greater in the risedronate group (23 of 115, 20%) than in those treated with zoledronic acid (1 of 152, 0.7%, p < .001), and loss of response occurred in 19 (12.5%) zoledronic acid patients compared with 71 (62%) risedronate patients (p < .0001). Risk ratios for relapse and loss of response in zoledronic acid patients were 0.02 [95% confidence interval (CI) 0.00-0.18] and 0.12 (95% CI 0.07-0.19), respectively. Changes from baseline in quality of life, assessed using SF-36 scores, were more positive in the zoledronic acid group across the follow-up period (p = .01). Bone markers at 6 months were predictive of response duration. These data demonstrate an unprecedented duration of remission of Paget disease following treatment with zoledronic acid, accompanied by an improved quality of life.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 06/2011; 26(9):2261-70. · 6.04 Impact Factor
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David Hosking,
Kenneth Lyles, Jacques P Brown,
William D Fraser,
Paul Miller,
Manuel Diaz Curiel,
Jean-Pierre Devogelaer,
Michael Hooper,
Guoqin Su,
Ken Zelenakas,
Judy Pak,
Taiwo Fashola,
Youssef Saidi,
Erik Fink Eriksen,
Ian R Reid
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ABSTRACT: A single 5-mg infusion of zoledronic acid restores biochemical markers of bone turnover into the reference range in the majority of patients with Paget's disease and maintains biochemical remission for at least 2 years. This effect is largely independent of pretreatment disease activity and prior bisphosphonate therapy.
Zoledronic acid (ZOL) is a potent bisphosphonate that produces a rapid and complete control of the increased bone turnover of Paget's disease. Long-term control of disease activity is an important aim of treatment in the hope that this will reduce the risk of complications such as deformity, fracture, and degenerative joint disease.
This study compares the ability of ZOL 5 mg given as a 15-minute intravenous infusion with risedronate (RIS) 30 mg daily by mouth for 60 days to maintain long-term control of bone turnover. No bisphosphonate was given during the extension study. All patients (n = 296) who achieved a therapeutic response, defined as normalization or a >75% reduction in the total alkaline phosphatase (total ALP) excess above the midpoint of the reference range, were eligible for inclusion.
ZOL maintained the mean level of total ALP at the middle of the reference range, whereas those treated with risedronate showed a linear increase in total ALP from the 6-month post-treatment time-point. Both treatments resulted in a linear relationship between the 6-month nadir and 24-month total ALP. The relationship for RIS was shifted upward, showing that for a given level of post-treatment biochemical activity, bone turnover increased with time. This was in contrast to the ZOL-treated patients where total ALP generally remained unchanged over this 18-month extension period. A similar pattern of response was seen with the other bone turnover markers.
ZOL maintains bone turnover within the reference range over 24 months from the initiation of treatment. A reduction in the incidence and severity of long-term complications may require persistent normalization of bone turnover over many years, and this now seems a realistic possibility with ZOL.
Journal of Bone and Mineral Research 02/2007; 22(1):142-8. · 6.37 Impact Factor
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Ian R Reid,
Paul Miller,
Kenneth Lyles,
William Fraser, Jacques P Brown,
Youssef Saidi,
Peter Mesenbrink,
Guoqin Su,
Judy Pak,
Ken Zelenakas,
Monica Luchi,
Peter Richardson,
David Hosking
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ABSTRACT: The advent of bisphosphonates advanced therapy for Paget's disease, but more effective and convenient agents are needed to increase adherence. Zoledronic acid, a bisphosphonate administered as a single intravenous infusion, might meet these needs.
In two identical, randomized, double-blind, actively controlled trials of 6 months' duration, we compared one 15-minute infusion of 5 mg of zoledronic acid with 60 days of oral risedronate (30 mg per day). The primary efficacy end point was the rate of therapeutic response at six months, defined as a normalization of alkaline phosphatase levels or a reduction of at least 75 percent in the total alkaline phosphatase excess. The results of the studies were pooled.
At six months, 96.0 percent of patients receiving zoledronic acid had a therapeutic response (169 of 176), as compared with 74.3 percent of patients receiving risedronate (127 of 171, P<0.001). Alkaline phosphatase levels normalized in 88.6 percent of patients in the zoledronic acid group and 57.9 percent of patients in the risedronate group (P<0.001). Zoledronic acid was associated with a shorter median time to a first therapeutic response (64 vs. 89 days, P<0.001). Higher response rates in the zoledronic acid group were consistent across all demographic, disease-severity, and treatment-history subgroups and with changes in other bone-turnover markers. The physical-component summary score of the Medical Outcomes Study 36-item Short-Form General Health Survey, a measure of the quality of life, increased significantly from baseline at both three and six months in the zoledronic acid group and differed significantly from those in the risedronate group at three months. Pain scores improved in both groups. During post-trial follow-up (median, 190 days), 21 of 82 patients in the risedronate group had a loss of therapeutic response, as compared with 1 of 113 patients in the zoledronic acid group (P<0.001).
A single infusion of zoledronic acid produces more rapid, more complete, and more sustained responses in Paget's disease than does daily treatment with risedronate.
New England Journal of Medicine 10/2005; 353(9):898-908. · 53.30 Impact Factor
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Ian R. Reid, Jacques P. Brown,
Peter Burckhardt,
Zebulun Horowitz,
Peter Richardson,
Ulrich Trechsel,
Albert Widmer,
Jean-Pierre Devogelaer,
Jean-Marc Kaufman,
Philippe Jaeger,
Jean-Jacques Body,
Pierre J. Meunier
Obstetrical and Gynecological Survey 12/2002; 58(1):33-35. · 2.51 Impact Factor
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Ian R Reid, Jacques P Brown,
Peter Burckhardt,
Zebulun Horowitz,
Peter Richardson,
Ulrich Trechsel,
Albert Widmer,
Jean-Pierre Devogelaer,
Jean-Marc Kaufman,
Philippe Jaeger, [......],
Jochen Ittner,
Georg Leb,
Hans Mallmin,
Timothy Murray,
Sergio Ortolani,
Alessandro Rubinacci,
Maria Saaf,
Goran Samsioe,
Leon Verbruggen,
Pierre J Meunier
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ABSTRACT: Bisphosphonates are effective agents for the management of osteoporosis. Their low bioavailability and low potency necessitate frequent administration on an empty stomach, which may reduce compliance. Gastrointestinal intolerance limits maximal dosing. Although intermittent intravenous treatments have been used, the optimal doses and dosing interval have not been systematically explored.
We studied the effects of five regimens of zoledronic acid, the most potent bisphosphonate, on bone turnover and density in 351 postmenopausal women with low bone mineral density in a one-year, randomized, double-blind, placebo-controlled trial. Women received placebo or intravenous zoledronic acid in doses of 0.25 mg, 0.5 mg, or 1 mg at three-month intervals. In addition, one group received a total annual dose of 4 mg as a single dose, and another received two doses of 2 mg each, six months apart. Lumbar-spine bone mineral density was the primary end point.
There were similar increases in bone mineral density in all the zoledronic acid groups to values for the spine that were 4.3 to 5.1 percent higher than those in the placebo group (P<0.001) and values for the femoral neck that were 3.1 to 3.5 percent higher than those in the placebo group (P<0.001). Biochemical markers of bone resorption were significantly suppressed throughout the study in all zoledronic acid groups. Myalgia and pyrexia occurred more commonly in the zoledronic acid groups, but treatment-related dropout rates were similar to that in the placebo group.
Zoledronic acid infusions given at intervals of up to one year produce effects on bone turnover and bone density as great as those achieved with daily oral dosing with bisphosphonates with proven efficacy against fractures, suggesting that an annual infusion of zoledronic acid might be an effective treatment for postmenopausal osteoporosis.
New England Journal of Medicine 03/2002; 346(9):653-61. · 53.30 Impact Factor
