Treatment With Once-Weekly Alendronate 70 mg Compared With Once-Weekly Risedronate 35 mg in Women With Postmenopausal Osteoporosis: A Randomized Double-Blind Study

Rosen, Clifford J.; Hochberg, Marc C.; Bonnick, Sydney Lou; McClung, Michael R.; Miller, Paul D.; Broy, Susan B.; Kagan, Risa; Chen, Erluo; Petruschke, Richard A.; Thompson, Desmond; Papp, Anne E. de; Investigators, for the Fosamax Actonel Comparison

doi:10.1359/jbmr.2005.20.1.141

Cited by 68 publications

(89 citation statements)

References 38 publications

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“…Selection of the noninferiority margin was based on clinical relevancy of antifracture benefit. Previous studies of antiresorptive therapies (28)(29)(30)(31) demonstrated that lumbar spine BMD increases of 3% or more are associated with an antifracture benefit. In addition, the À2.0% noninferiority margin ensured that the combination therapy would be statistically superior to a putative placebo based on the data from the pivotal placebo-controlled teriparatide study by Neer and colleagues (3) using the method described by Hasselblad and Kong.…”

Section: Discussionmentioning

confidence: 99%

Effects of intravenous zoledronic acid plus subcutaneous teriparatide [rhPTH(1–34)] in postmenopausal osteoporosis

Cosman

Eriksen

Recknor

et al. 2010

Journal of Bone and Mineral Research

312

173

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Clinical data suggest concomitant therapy with bisphosphonates and parathyroid hormone (PTH) may blunt the anabolic effect of PTH; rodent models suggest that infrequently administered bisphosphonates may interact differently. To evaluate the effects of combination therapy with an intravenous infusion of zoledronic acid 5 mg and daily subcutaneous recombinant human (rh)PTH(1-34) (teriparatide) 20 mg versus either agent alone on bone mineral density (BMD) and bone turnover markers, we conducted a 1-year multicenter, multinational, randomized, partial double-blinded, controlled trial. 412 postmenopausal women with osteoporosis (mean age 65 AE 9 years) were randomized to a single infusion of zoledronic acid 5 mg plus daily subcutaneous teriparatide 20 mg (n ¼ 137), zoledronic acid alone (n ¼ 137), or teriparatide alone (n ¼ 138). The primary endpoint was percentage increase in lumbar spine BMD (assessed by dual-energy X-ray absorptiometry [DXA]) at 52 weeks versus baseline. Secondary endpoints included change in BMD at the spine at earlier time points and at the total hip, trochanter, and femoral neck at all time points. At week 52, lumbar spine BMD had increased 7.5%, 7.0%, and 4.4% in the combination, teriparatide, and zoledronic acid groups, respectively ( p < .001 for combination and teriparatide versus zoledronic acid). In the combination group, spine BMD increased more rapidly than with either agent alone ( p < .001 versus both teriparatide and zoledronic acid at 13 and 26 weeks). Combination therapy increased total-hip BMD more than teriparatide alone at all times (all p < .01) and more than zoledronic acid at 13 weeks ( p < .05), with final 52-week increments of 2.3%, 1.1%, and 2.2% in the combination, teriparatide, and zoledronic acid groups, respectively. With combination therapy, bone formation (assessed by serum N-terminal propeptide of type I collagen [PINP]) increased from 0 to 4 weeks, declined minimally from 4 to 8 weeks, and then rose throughout the trial, with levels above baseline from 6 to 12 months. Bone resorption (assessed by serum b-C-telopeptide of type I collagen [b-CTX]) was markedly reduced with combination therapy from 0 to 8 weeks (a reduction of similar magnitude to that seen with zoledronic acid alone), followed by a gradual increase after week 8, with levels remaining above baseline for the latter half of the year. Levels for both markers were significantly lower with combination therapy versus teriparatide alone ( p < .002). Limitations of the study included its short duration, lack of endpoints beyond DXA-based BMD (e.g., quantitative computed tomography and finite-element modeling for bone strength), lack of teriparatide placebo, and insufficient power for fracture outcomes. We conclude that while teriparatide increases spine BMD more than zoledronic acid and zoledronic acid increases hip BMD more than teriparatide, combination therapy provides the largest, most rapid increments when both spine and hip sites are considered. ß

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Section: Discussionmentioning

confidence: 99%

Effects of intravenous zoledronic acid plus subcutaneous teriparatide [rhPTH(1–34)] in postmenopausal osteoporosis

Cosman

Eriksen

Recknor

et al. 2010

Journal of Bone and Mineral Research

312

173

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“…There is comparative evidence that alendronate results in a greater reduction in bone turnover markers (BTMs) than risedronate [12] and that ibandronate results in an earlier response, but a reduction of similar magnitude to alendronate [13] .…”

Section: Introductionmentioning

confidence: 99%

Response of bone turnover markers to three oral bisphosphonate therapies in postmenopausal osteoporosis: the TRIO study

et al. 2015

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Introduction: Biochemical response to bisphosphonate therapy can be assessed using either a decrease in bone turnover marker beyond the least significant change (LSC) or a reduction to within a reference interval (RI). We compared the performance of these target responses and determined whether response was related to the type of bisphosphonate, compliance and baseline bone turnover markers.Methods: Biochemical responses to three oral bisphosphonates were assessed in an open, controlled trial comprising 172 postmenopausal osteoporotic women (age 53-84 years), randomized to alendronate, ibandronate or risedronate, plus calcium and vitamin D supplementation for two years. The LSC for each marker was derived within the study population whereas RIs were obtained from a control group of healthy premenopausal women (age 35-40 years).Results: Over 70% of women achieved a target response for serum CTX and PINP, irrespective of the approach used. The percentage decrease at 12 weeks was greater for women with baseline PINP above the RI -63% (difference 13%, 95%CI 0 to 27.1, P=0.049) and good compliance -67% (difference 15.9%, 95%CI 6.3 to 25.5, P=0.001). Responders had a greater increase in spine bone density compared to non-responders; for example 6.2% vs. 2.3%, (difference 3.9%, 95%CI 1.6 to 6.3, p=0.0011) for PINP LSC. The magnitude of change in bone markers was greater with ibandronate and alendronate than risedronate.Conclusions: Both approaches to response identified similar proportions of women as responders. Nonresponders had smaller increases in BMD and we suggest that biochemical assessment of response is a useful tool for the management of women with postmenopausal osteoporosis.Key words: postmenopausal osteoporosis, bone turnover markers, variability, bisphosphonate Mini Abstract (50 words)We used bone turnover markers to identify women who responded to bisphosphonate treatment for osteoporosis.Response was more likely with alendronate and ibandronate, than risedronate. There was a greater decrease in bone markers if baseline bone turnover markers were higher and if the patient took more than 80% of her medication.

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“…(5)(6)(7) This was confirmed in a head-to-head study in which ALN produced significantly greater decreases in all biochemical markers of bone turnover compared to RIS in women with postmenopausal osteoporosis. (8,9) We have previously reported that RIS arrested the tissue aging encountered in untreated osteoporosis, (13) although it should be kept in mind that the study in that report was a clinical trial, thus potentially not representative of the ''real'' world due to likely compliance differences. (30)(31)(32)(33) In addition, differences have been seen in effects on intrinsic bone material properties in animal studies.…”

Section: Discussionmentioning

confidence: 98%

“…Unfortunately, the study was not powered to include fracture incidence as an outcome. (8,9) Bone quality (encompassing the structural and material properties of bone) is an important contributor to bone strength, (10) and depends on bone turnover as well as factors independent of bone turnover. (11) Spectroscopic analysis of biopsies from postmenopausal women who received either placebo or ALN (10 mg/d) for 3 years revealed no significant changes between the two groups in spectroscopic markers of bone quality (mineral/matrix ratio, crystallinity, carbonate/amide I ratio, and collagen maturity), except for a significant increase in cortical bone mineral content in the patients who were receiving ALN.…”

Section: Introductionmentioning

confidence: 99%

Effects of alendronate and risedronate on bone material properties in actively forming trabecular bone surfaces

Hofstetter

Gamsjaeger

Phipps³

et al. 2012

Journal of Bone and Mineral Research

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We used Raman and Fourier transform infrared microspectroscopy (FTIRM) analysis to examine the intrinsic bone material properties at actively bone-forming trabecular surfaces in iliac crest biopsies from women with postmenopausal osteoporosis (PMO) who were treated with either alendronate (ALN) or risedronate (RIS). At eight study sites, women were identified who had postmenopausal osteoporosis (PMO), were at least 5 years postmenopause, and had been on long-term therapy (either 3-5 years or >5 years) with daily or weekly ALN or RIS. Following standard tetracycline labeling, biopsies were collected from 102 women (33 treated with ALN for 3-5 years , 35 with ALN for >5 years , 26 with RIS for 3-5 years , and 8 with RIS for >5 years ) and were analyzed at anatomical areas of similar tissue age in bone-forming areas (within the fluorescent double labels). The following outcomes were monitored and reported: mineral to matrix ratio (corresponding to ash weight), relative proteoglycan content (regulating mineralization commencement), mineral maturity (indicative of the mineral crystallite chemistry and stoichiometry, and having a direct bearing on crystallite shape and size), and the ratio of two of the major enzymatic collagen cross-links (pyridinoline/divalent). In RIS-5 there was a significant decrease in the relative proteoglycan content (À5.83% compared to ALN-5), while in both RIS-3 and RIS-5 there was significantly lower mineral maturity/ crystallinity (À6.78% and À13.68% versus ALN-3 and ALN-5, respectively), and pyridinoline/divalent collagen cross-link ratio (À23.09% and À41.85% versus ALN-3 and ALN-5, respectively). The results of the present study indicate that ALN and RIS exert differential effects on the intrinsic bone material properties at actively bone-forming trabecular surfaces. ß

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Treatment With Once-Weekly Alendronate 70 mg Compared With Once-Weekly Risedronate 35 mg in Women With Postmenopausal Osteoporosis: A Randomized Double-Blind Study

Cited by 68 publications

References 38 publications

Effects of intravenous zoledronic acid plus subcutaneous teriparatide [rhPTH(1–34)] in postmenopausal osteoporosis

Effects of intravenous zoledronic acid plus subcutaneous teriparatide [rhPTH(1–34)] in postmenopausal osteoporosis

Response of bone turnover markers to three oral bisphosphonate therapies in postmenopausal osteoporosis: the TRIO study

Effects of alendronate and risedronate on bone material properties in actively forming trabecular bone surfaces

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