Comparison of a Single Infusion of Zoledronic Acid with Risedronate for Paget's Disease

Reid, Ian R.; Miller, Paul D.; Lyles, Kenneth W.; Fraser, William D.; Brown, Jacques P.; Saïdi, Y.; Mesenbrink, Peter; Su, Guoqin; Pak, Judy; Zelenakas, K.; Luchi, Monica; Richardson, Peter; Hosking, David J.

doi:10.1056/nejmoa044241

Cited by 381 publications

(254 citation statements)

References 22 publications

(6 reference statements)

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Section: Accepted M Manuscriptmentioning

confidence: 99%

“…The magnitude of remodeling suppression has been shown to differ in several separate head-to-head studies using serum and urine biomarkers [8][9][10]. These studies consistently show alendronate suppresses remodeling more than risedronate [8,9] while zoledronate suppresses more than risedronate [10]. No head-tohead assessments of bone remodeling among the BPs has been conducted using histology as an outcome, yet based on iliac crest biopsy studies from the major clinical trials the percent suppression of remodeling relative to placebo-treated controls tends to be quite similar over 3 years with daily risedronate (-40%) [11], daily alendronate (-92%) [12], intermittent oral ibandronate (-50%) [13], and zoledronate (-63%) [14].…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

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Bisphosphonate effects on bone turnover, microdamage, and mechanical properties: What we think we know and what we know that we don't know

Allen

Burr

2011

Bone

191

159

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This is the author's manuscript of the article published in final edited form as: Allen M. R., Burr D.B. (2011 A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT AbstractThe bisphosphonates (BPs) have been useful tools in our understanding of the role that bone remodeling plays in skeletal health. The purpose of this paper is to outline what we know, and what is still unknown, about the role that BPs play in modulating bone turnover, how this affects microdamage accumulation, and ultimately what the effects of these changes elicited by BPs are to the structural and the material biomechanical properties of the skeleton. We know thatBPs suppress remodeling site-specifically, probably do not have a direct effect on formation, and that the individual BPs vary with respect to speed of onset, duration of effect and magnitude of suppression. However, we do not know if these differences are meaningful in a clinical sense, how much remodeling is sufficient, the optimal duration of treatment, or how long it takes to restore remodeling to pre-treatment levels. We also know that suppression is intimately tied to microdamage accumulation, which is also site-specific, that BPs impair targeted repair of damage, and that they can reduce the energy absorption capacity of bone at the tissue level.However, the BPs are clearly effective at preventing fracture, and generally increase bone mineral density and whole bone strength, so we do not know whether these changes in damage accumulation and repair, or the mechanical effects at the tissue level, are clinically meaningful.The mechanical effects of BPs to the fatigue life of bone, or BP effects on bone subject to an impact, are entirely unknown. This paper reviews the literature on these topics, and identifies gaps in knowledge that can be addressed with further research.

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Section: Accepted M Manuscriptmentioning

confidence: 99%

Section: Accepted M Manuscriptmentioning

confidence: 99%

Bisphosphonate effects on bone turnover, microdamage, and mechanical properties: What we think we know and what we know that we don't know

Allen

Burr

2011

Bone

191

159

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show abstract

“…91 For many years pamidronate given by intravenous infusion was used extensively, 92 but the newer and more potent bisphosphonates can produce even more profound suppression of disease activity than was possible with the bisphosphonates available in previous years. 93,94 The latest advance is with zoledronate, 95 which, when given as a single 5-mg infusion, produced a greater and longerlasting suppression of excess bone turnover than even oral risedronate given at 30 mg/day over 2 months, hitherto one of the most effective treatments.…”

Section: Clinical Applications Of Bisphosphonatesmentioning

confidence: 99%

Bisphosphonates: Mode of Action and Pharmacology

2007

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The profound effects of the bisphosphonates on calcium metabolism were discovered over 30 years ago, and they are now well established as the major drugs used for the treatment of bone diseases associated with excessive resorption. Their principal uses are for Paget disease of bone, myeloma, bone metastases, and osteoporosis in adults, but there has been increasing and successful application in pediatric bone diseases, notably osteogenesis imperfecta. Bisphosphonates are structural analogues of inorganic pyrophosphate but are resistant to enzymatic and chemical breakdown. Bisphosphonates inhibit bone resorption by selective adsorption to mineral surfaces and subsequent internalization by bone-resorbing osteoclasts where they interfere with various biochemical processes. The simpler, non-nitrogen-containing bisphosphonates (eg, clodronate and etidronate) can be metabolically incorporated into nonhydrolysable analogues of adenosine triphosphate (ATP) that may inhibit ATP-dependent intracellular enzymes. In contrast, the more potent, nitrogen-containing bisphosphonates (eg, pamidronate, alendronate, risedronate, ibandronate, and zoledronate) inhibit a key enzyme, farnesyl pyrophosphate synthase, in the mevalonate pathway, thereby preventing the biosynthesis of isoprenoid compounds that are essential for the posttranslational modification of small guanosine triphosphate (GTP)-binding proteins (which are also GTPases) such as Rab, Rho, and Rac. The inhibition of protein prenylation and the disruption of the function of these key regulatory proteins explains the loss of osteoclast activity. The recently elucidated crystal structure of farnesyl diphosphate reveals how bisphosphonates bind to and inhibit at the active site via their critical nitrogen atoms. Although bisphosphonates are now established as an important class of drugs for the treatment of many bone diseases, there is new knowledge about how they work and the subtle but potentially important differences that exist between individual bisphosphonates. Understanding these may help to explain differences in potency, onset and duration of action, and clinical effectiveness.www.pediatrics.org/cgi

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“…Extending this further, the effects of once-yearly zoledronic acid on BMD and bone turnover were found to be equivalent to an every-3-month regimen [75]. A recent study demonstrated that a single Guise 1129 www.TheOncologist.com injection of zoledronic acid was superior to daily treatment with risedronate for Paget's disease, characterized by high bone turnover [76]. Ongoing trials are evaluating whether this yearly dosing regimen can also reduce fracture risk in patients with osteoporosis.…”

Section: Alternate Bisphosphonate Dosing Regimensmentioning

confidence: 99%

Bone Loss and Fracture Risk Associated with Cancer Therapy

2006

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Background. Cancer patients experience osteoporosis resulting from accelerated loss of bone mineral density (BMD) caused by their treatment. Such bone loss greatly increases the risk for fracture and can have other serious effects on quality of life.Methods. In the current report, the author focuses on studies of cancer therapy-associated bone loss, its prevalence and pathogenesis, and resulting clinical impact. Options for management and prevention are also reviewed, including treatment guidelines where available.Results. A variety of cancer therapies, including hormonal therapy, chemotherapy, and glucocorticoids, affect gonadal hormone production, which increases bone resorption and decreases BMD. Such bone loss occurs more rapidly and to a greater degree than normal age-related osteoporosis, increases the risk for fracture

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Comparison of a Single Infusion of Zoledronic Acid with Risedronate for Paget's Disease

Abstract: 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.

Cited by 381 publications

References 22 publications

Bisphosphonate effects on bone turnover, microdamage, and mechanical properties: What we think we know and what we know that we don't know

Bisphosphonate effects on bone turnover, microdamage, and mechanical properties: What we think we know and what we know that we don't know

Bisphosphonates: Mode of Action and Pharmacology

Bone Loss and Fracture Risk Associated with Cancer Therapy

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