Randomized Teriparatide [Human Parathyroid Hormone (PTH) 1–34] Once-Weekly Efficacy Research (TOWER) Trial for Examining the Reduction in New Vertebral Fractures in Subjects with Primary Osteoporosis and High Fracture Risk

Nakamura, Toshio; Sugimoto, Toshitsugu; Nakano, Tetsuo; Kishimoto, Hiroyuki; Ito, Masako; Fukunaga, Masao; Hagino, Hiroshi; Sone, Toshio; Yoshikawa, Hideki; Nishizawà, Yoshiki; Fujita, Takeshi; Shiraki, Masataka

doi:10.1210/jc.2011-3479

Cited by 219 publications

(228 citation statements)

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“…The Teriparatide Once-Weekly Efficacy Research (TOWER) trial enrolled 578 subjects including postmenopausal women and older men with primary osteoporosis and prevalent vertebral fracture who were randomly assigned to weekly subcutaneous injections of teriparatide (56.5 mg) or placebo for 72 weeks as previously reported 13 . Efficacy and safety were evaluated in 572 subjects ( Figure 1).…”

Section: Original Trial Subjects and Treatmentmentioning

confidence: 99%

“…Thus, the incidences of vertebral fracture were obtained at the end of the 1 year follow-up study from the end of the original trial and from the start of the original trial 13 . The incidences were also evaluated based on the follow-up therapeutic regimens (two groups), either bisphosphonates or other therapeutic regimens such as raloxifene, alfacalcidol, or other clinical therapeutics.…”

Section: Vertebral Fracturesmentioning

confidence: 99%

“…Once-daily injections of 20 mg rhPTH 1-34 have been shown to potently increase BMD and reduce the risk of fracture in postmenopausal women and men with osteoporosis by increasing bone formation and resorption [9][10][11][12] . Recently, another regimen of teriparatide treatment, a weekly subcutaneous injection of hPTH 1-34 (56.5 mg), has been proven effective at increasing BMD and reducing the risk of vertebral fracture by increasing bone formation and reducing bone resorption in postmenopausal women and older men with osteoporosis and prevalent vertebral fracture 13 . Because use of teriparatide injections is approved for only 18 to 24 months, it is important to consider whether anti-osteoporotic therapy is necessary to sustain the reduced risk of fracture and maintain the gains of bone mass achieved with teriparatide.…”

Section: Introductionmentioning

confidence: 99%

“…The purpose of this study was to evaluate patients with primary osteoporosis who had been treated with weekly injections of teriparatide for 72 weeks 13 then sequentially given bisphosphonates or other therapeutic regimens such as raloxifene or alfacalcidol for 1 year.…”

Section: Introductionmentioning

confidence: 99%

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Vertebral fracture risk after once-weekly teriparatide injections: follow-up study of Teriparatide Once-Weekly Efficacy Research (TOWER) trial

Sugimoto

Shiraki

Nakano

et al. 2013

Current Medical Research and Opinion

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c i a l D i s t r i b u t i o n U n a u t h o r i z e d u s e p r o h i b i t e d . A u t h o r i s e d u s e r s c a n d o w n l o a d , d i s p l a y , v i e w a n d p r i n t a s i n g l e c o p y f o r p e r s o n a l u s eCurrent Medical Research & Opinion Vol. 29, No. 3, 2013, 195-203 AbstractObjective:To evaluate fracture risk and bone mineral density (BMD) in patients with primary osteoporosis, 1 year after completing 72 weeks of weekly teriparatide injections. Research design and methods:After 72 weeks of teriparatide injections or placebo (original trial), treatment was unblinded and subjects were subsequently treated with bisphosphonates or other therapeutic regimens at the discretion of their physicians and followed for 1 year. Spine radiographs and BMD measurements at the lumbar spine, femoral neck, and total hip by dual energy X-ray absorptiometry were performed. Main outcome measure:Incident vertebral fracture rate. Results:A total of 465 patients were enrolled and 447 (96.1%) completed the study. In the 1 year follow-up period, new morphometric vertebral fractures occurred in 7/203 (3.4%) in the post-teriparatide group and 33/241 (13.7%) in the post-placebo group (relative risk [RR]: 0.23, 95% confidence interval [CI]: 0.10 to 0.52, P50.05). The cumulative incidences from the start of the original trial were 4.9% and 22.8%, respectively (RR: 0.18, 95% CI: 0.09 to 0.36, P50.05). There were no significant differences in incidences of vertebral fractures between subsequent therapeutic regimens in the post-teriparatide group. In subjects treated with bisphosphonates, mean BMD values further significantly increased by 9.6%, 2.9%, and 4.1% at the lumbar spine, femoral neck, and total hip, respectively (P50.05). Conclusions:The reduced risk of vertebral fracture was sustained for 1 year after completion of 72 weeks of weekly teriparatide injections. The effects did not differ between subsequent therapeutic regimens. BMD gains continued with sequential bisphosphonate treatment, but not with the other sequential therapeutic regimens. Bisphosphonates seem to be a useful choice as a subsequent treatment to weekly teriparatide. Limitation:This study was an observational follow-up study and the regimens of subsequent medication after discontinuation of the original TOWER trial were not randomly allocated.

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Section: Original Trial Subjects and Treatmentmentioning

confidence: 99%

Section: Vertebral Fracturesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Vertebral fracture risk after once-weekly teriparatide injections: follow-up study of Teriparatide Once-Weekly Efficacy Research (TOWER) trial

Sugimoto

Shiraki

Nakano

et al. 2013

Current Medical Research and Opinion

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“…While changes in bone formation markers with weekly teriparatide are similar to the daily regimen (32,33), the u-NTX, reflecting bone resorption falls, after an initial tendency to rise. Black and cols.…”

Section: Pthmentioning

confidence: 84%

Bone markers and osteoporosis therapy

Bandeira

Costa

Filho

et al. 2014

Arq Bras Endocrinol Metab

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Several factors are involved in determining bone quality including bone density, bone turnover, the extent of trabecular bone connectivity, cortical porosity and geometry. Metabolically active and in a continuous process of remodeling, approximately 20% of bone tissue is renewed annually. Bone turn over markers (BTM) are frequently used in clinical trials and to provide valid information about the effectiveness of osteoporosis treatment, reflecting the state of bone metabolism and its response to treatment, although they are not useful alone to estimate bone loss. In this review the behavior of BTM from different clinical trials or different osteoporotic drugs will be addressed. Arq Bras Endocrinol Metab. 2014;58(5):504-13 Keywords Bone markers; osteoporosis; bone density ReSumoDiversos fatores estão envolvidos na determinação da qualidade óssea, incluindo a densidade óssea, a remodelação óssea, a extensão da conectividade do osso trabecular, porosidade cortical e geometria. Metabolicamente ativo e, em um processo contínuo de remodelação, cerca de 20% do tecido ósseo é renovado anualmente. Por sua vez, marcadores de turnover ósseo (BTM) são frequentemente utilizados em estudos clínicos e fornecem informações válidas sobre a eficácia do tratamento da osteoporose, o que reflete o metabolismo ósseo e sua resposta ao tratamento, embora eles não sejam úteis somente para estimar a perda óssea. Nesta revisão, o comportamento dos BTM em ensaios clínicos diferentes e com diferentes drogas osteoporóticas será abordado. one is a specific type of tissue composed primarily of type I collagen impregnated with minerals in the form of hydroxyapatite crystals. Several factors are involved in determining bone quality including bone density, bone turnover, the extent of trabecular bone connectivity, cortical porosity and geometry (Figure 1) (1). Metabolically active and in a continuous process of remodeling, approximately 20% of bone tissue is renewed annually (2). This complex process begins at birth and is maintained throughout life. The active cellular participants in this process, often configured as multiple multicellular units, are osteoclasts, osteoblasts and osteocytes.The system is highly regulated by many factors. For example, osteoprotegerin (OPG) (osteoprotegerin), receptor activator of NF-kappaB (RANK) and its cognate ligand, (RANKL), form a metabolic regulatory system focused upon bone resorption (3). Additionally there are other factors that influence bone turnover, such as parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (calcitriol), prostaglandin E2 and interleukins (4). The process of bone turnover leads to the release of factors that give highly relevant information on rates of bone formation and resorption (Figure 2).

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Association Between Drug Treatments for Patients With Osteoporosis and Overall Mortality Rates

et al. 2019

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IMPORTANCE Previous studies have reported that drug treatments, particularly treatment with bisphosphonates, is associated with reduced overall mortality rates in addition to decreased fracture risk. If so, drug treatments should be recommended for this reason alone, regardless of a patient's risk of fracture.OBJECTIVE To assess whether randomized clinical trials demonstrate that treatment with bisphosphonates, particularly zoledronate, is associated with reduced mortality rates.DATA SOURCES Science Direct, MEDLINE, Embase, and the Cochrane Library were searched for randomized placebo-controlled clinical trials of drug treatments for osteoporosis published after 2009 and published or in press before April 19, 2019. Conference abstracts from annual osteoporosis society meetings were also included in the search.STUDY SELECTION Included studies were clinical trials that (1) were randomized and placebo-controlled; (2) studied drug treatments with proven antifracture efficacy; (3) used agents at the approved dose for treatment of osteoporosis; and (4) had a duration of 1 year or more. Abstracts from the literature searches were reviewed for inclusion and exclusion criteria, and mortality rate data were abstracted from the article by 1 researcher and validated by a second. A total of 2045 records were screened; 38 (1.8%) were included in the meta-analyses. DATA EXTRACTION AND SYNTHESISThe Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist was followed for abstracting data and assessing data quality and validity. Data were pooled using random-effects models, and between-study variability was assessed using the I 2 index. The risk of bias for each study was assessed, and funnel plots and Egger and Begg statistics were used to evaluate publication bias. MAIN OUTCOMES AND MEASURESAssociations of all drug treatments, particularly bisphosphonate and zoledronate treatments, with overall mortality. RESULTSOf 38 clinical trials that included 101 642 unique participants, 38 were included in the meta-analyses of all drug treatments (45 594 participants randomized to placebo; 56 048 to treatment); 21 clinical trials, of bisphosphonate treatments (20 244 participants randomized to placebo; 22 623 to treatment); and 6 clinical trials, of zoledronate treatments (6944 participants randomized to placebo; 6926 to treatment). No significant association was found between all drug treatments for osteoporosis and overall mortality rate (risk ratio [RR], 0.98; 95% CI, 0.91-1.05; I 2 = 0%). Clinical trials of bisphosphonate treatment (RR, 0.95; 95% CI, 0.86-1.04) showed no significant association with overall mortality. Also, clinical trials of zoledronate treatment (RR, 0.88; 95% CI, 0.68-1.13) showed no association with overall mortality rate; however, evidence existed for heterogeneity of the results (I 2 = 48.2%). CONCLUSIONS AND RELEVANCEResults of this meta-analysis suggest that bisphosphonate treatment may not be associated with reduced overall mortality rates in addition to decreased fracture risk an...

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Randomized Teriparatide [Human Parathyroid Hormone (PTH) 1–34] Once-Weekly Efficacy Research (TOWER) Trial for Examining the Reduction in New Vertebral Fractures in Subjects with Primary Osteoporosis and High Fracture Risk

Abstract: Weekly s.c. administration of teriparatide at a dose of 56.5 μg may provide another option of anabolic treatments in patients with osteoporosis at higher fracture risk.

Cited by 219 publications

References 33 publications

Vertebral fracture risk after once-weekly teriparatide injections: follow-up study of Teriparatide Once-Weekly Efficacy Research (TOWER) trial

Vertebral fracture risk after once-weekly teriparatide injections: follow-up study of Teriparatide Once-Weekly Efficacy Research (TOWER) trial

Bone markers and osteoporosis therapy

Association Between Drug Treatments for Patients With Osteoporosis and Overall Mortality Rates

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