Once-Yearly Zoledronic Acid for Treatment of Postmenopausal Osteoporosis

Black, Dennis M.; Delmas, Pierre D.; Eastell, Richard; Reid, Ian R.; Boonen, Steven; Cauley, Jane A.; Cosman, Felicia; Lakatos, Péter; Leung, Ping Chung; Man, Zulema; Mautallen, Carlos; Mesenbrink, Peter; Caminis, John; Tong, Karen; Rosario-Jansen, Theresa; Krasnow, Joel; Hue, Trisha F.; Sellmeyer, Deborah E.; Eriksen, Erik Fink; Cummings, Steven R.

doi:10.1097/01.ogx.0000275406.83713.0f

Cited by 239 publications

(426 citation statements)

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“…Another limitation is that the present study did not include a control group. Antifracture trials show that treatment with calcium and vitamin D alone has a mild antiresportive effect, (2)(3)(4)6,7) and it is possible that this may have slightly blunted the anabolic effects of teriparatide reported in the present study.…”

Section: Discussionmentioning

confidence: 62%

“…(1)(2)(3)(4)(5)(6)(7)(8) Generally, these can be divided into two types: (1) antiresorptive treatments such as bisphosphonates (1,2,4,6,7) that bring about a prompt decrease in biochemical markers of bone resorption followed a few months later by a reduction in bone formation markers (9) and (2) anabolic agents (currently only parathyroid hormone) (5,10) that bring about a prompt increase in bone formation followed a few weeks later by an increase in bone resorption. (11) Many modern treatments for osteoporosis have a profound effect on bone remodeling, and studies of bone turnover have an important role in the evaluation of their effect on bone quality.…”

Section: Introductionmentioning

confidence: 99%

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Differential effects of teriparatide on regional bone formation using 18F-fluoride positron emission tomography

Frost

Siddique

Blake

et al. 2010

Journal of Bone and Mineral Research

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Teriparatide increases skeletal mass, bone turnover markers, and bone strength, but local effects on bone tissue may vary between skeletal sites. We used positron emission tomography (PET) to study 18 F-fluoride plasma clearance (K i ) at the spine and standardized uptake values (SUVs) at the spine, pelvis, total hip, and femoral shaft in 18 postmenopausal women with osteoporosis. Subjects underwent a 1-hour dynamic scan of the lumbar spine and a 10-minute static scan of the pelvis and femurs at baseline and after 6 months of treatment with 20 mg/day teriparatide. Blood samples were taken to derive the arterial input function and lumbar spine K i values evaluated using a three-compartment model. SUVs were calculated for the spine, pelvis, total hip, and femoral shaft. After 6 months treatment with teriparatide, spine K i values increased by 24% (p ¼ .0003), while other model parameters were unchanged except for the fraction of tracer going to bone mineral (k 3 /[k 2 þ k 3 ]), which increased by 23% (p ¼ .0006). In contrast to K i , spine SUVs increased by only 3% (p ¼ .84). The discrepancy between changes in K i and SUVs was explained by a 20% decrease in 18 F À plasma concentration. SUVs increased by 37% at the femoral shaft (p ¼ .0019), 20% at the total hip (p ¼ .032), and 11% at the pelvis (p ¼ .070). Changes in bone turnover markers and BMD were consistent with previous trials. We conclude that the changes in bone formation rate during teriparatide treatment as measured by 18 F À PET differ at different skeletal sites, with larger increases in cortical bone than at trabecular sites. ß

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Section: Discussionmentioning

confidence: 62%

Section: Introductionmentioning

confidence: 99%

Differential effects of teriparatide on regional bone formation using 18F-fluoride positron emission tomography

Frost

Siddique

Blake

et al. 2010

Journal of Bone and Mineral Research

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“…This is not unexpected as the percentage change in BTM in response to raloxifene is less than that for other osteoporosis treatments such as bisphosphonates [4,20,27,28] . For example we have reported previously in a study of postmenopausal women treated with bisphosphonates (TRIO study) that 12 weeks of alendronate therapy resulted in 98% responders by CTX and 82% by PINP for LSC; that contrasts with the response to raloxifene therapy at 12 weeks which was 38% for CTX and 52% for PINP (Table 3) [20] .…”

Section: Discussionmentioning

confidence: 85%

Response of bone turnover markers to raloxifene treatment in postmenopausal women with osteopenia

et al. 2016

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Introduction: The change in bone turnover markers (BTM) in response to osteoporosis therapy can be assessed by a decrease beyond the least significant change (LSC) or below the mean of the reference interval (RI). We compared the performance of these two approaches in women treated with raloxifene.Methods: Fifty postmenopausal osteopenic women, (age 51-72y) were randomised to raloxifene or no treatment for 2 years. Blood samples were collected for the measurement of BTM. The LSC for each marker was calculated from the untreated women and the RI obtained from healthy premenopausal women (age 35-40y). Bone mineral density (BMD) was measured at the spine and hip.Results: There was a decrease in BTM in response to raloxifene treatment; percentage change at 12 weeks, CTX -39% (95% CI -48 to -28) and PINP -32% (95% CI -40 to -23) P<0.001. The proportion of women classified as responding to treatment using LSC at 12 weeks was: CTX 38%, PINP 52%, at 48 weeks CTX 60%, PINP 65%. For the RI approach; at 12 weeks CTX and PINP 38%, at 48 weeks CTX 40%, PINP 45%. There was a significant difference in the change in spine BMD in the raloxifene treated group compared to the no-treatment group at week 48; difference 0.031 g/cm2, (95% CI 0.016 to 0.046, P<0.001).Conclusions: The two approaches identified women that reached the target for treatment using BTM.Both LSC and RI criteria appear useful in identifying treatment response but the two approaches do not fully overlap and may be complementary.

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“…This equates to an incidence of ∼4/10,000 patient-years. By comparison, there was one case of ONJ in both the zoledronate and placebo groups in Black et al [13], 1 during 1914 patients-years of observation in the study extensions [10,14], and no cases in the other phase 3 zoledronate study [15]. These data do not suggest a difference in incidences of this problem with these two medications.…”

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confidence: 79%

Denosumab after 8 years

Reid

2015

Osteoporos Int

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It is now more than 20 years since the alendronate phase 3 program produced the first trials demonstrating global antifracture efficacy for an osteoporosis medication [1,2]. This brought the osteoporosis field into the era of evidence-based medicine. The euphoria that followed from knowing that the interventions we were prescribing really were preventing fractures soon passed as durations of therapy reached 3 years, the endpoint of most fracture prevention clinical trials. A series of unanswered questions then arose. How long should treatment be continued? Are there long-term side-effects? Do these drugs continue to prevent fractures and, if so, is their continued use necessary for sustained fracture prevention? For alendronate, some of these questions were answered by the FLEX trial, which suggested that dose reduction with long-term use did not reduce efficacy, and that for patients whose femoral neck bone density was no longer in the osteoporotic range, drug discontinuation did not negatively impact on fracture rate [3,4]. Similar data have now been published from the zoledronate extension studies [5].In the last decade, osteonecrosis of the jaw (ONJ) and transverse stress fractures of the femoral shaft, referred to as an atypical femoral fractures (AFFs), have emerged as significant new safety concerns associated with the long-term use of anti-resorptive drugs. Most information on these problems is from case series or from analyses of medical claims databases.Some such studies have even suggested that the incidence of atypical femoral fractures attributable to bisphosphonate use might exceed the number of hip fractures prevented by these drugs [6], though other analyses do not support this conclusion [7]. In this context, longer-term data from clinical trials become critically important in assessing the ongoing safety and efficacy of medications for osteoporosis. Longer clinical trials are desirable, though maintaining patients at high risk of fracture on placebo raises ethical and practical issues. The next-best option is to continue long-term follow-up of the cohorts of patients involved in the pivotal clinical trials. While not as robust as a longterm randomized controlled trial because a control group is not continued on placebo, this strategy does provide longitudinal data on a well-characterized cohort, allowing fracture rates and adverse events to be related to duration of therapy. It also allows documentation of chronic effects on bone turnover markers and bone density. The loss of a control group for these measures is not such a problem, since current technology usually generates stable measurements, and the evolution of these parameters in placebo-treated women with osteoporosis is already well documented.The recent report by Papapoulos et al. in Osteoporosis International provides important new information regarding the efficacy and safety of the anti-RANKL monoclonal antibody, denosumab [8]. This drug is a potent antiresorptive which reduces median bone formation rate to zero after 2-3 years use ...

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Once-Yearly Zoledronic Acid for Treatment of Postmenopausal Osteoporosis

Cited by 239 publications

References 0 publications

Differential effects of teriparatide on regional bone formation using 18F-fluoride positron emission tomography

Differential effects of teriparatide on regional bone formation using 18F-fluoride positron emission tomography

Response of bone turnover markers to raloxifene treatment in postmenopausal women with osteopenia

Denosumab after 8 years

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