Teriparatide or Alendronate in Glucocorticoid-Induced Osteoporosis

Shane, Elizabeth; Boonen, Steven; Marín, Fernando; Donley, David W.; Taylor, Kathleen A.; Dalsky, G. P.; Marcus, Robert

doi:10.1097/01.ogx.0000310357.43258.f1

Cited by 90 publications

(119 citation statements)

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“…There were significantly fewer new vertebral fractures in the teriparatide group than in the alendronate group (0.6% versus 6.1%, respectively, p ¼ 0.004). (28) In the follow-up 18-month extension trial, significant differences in BMD and fracture risk between the two groups were maintained. (29) PTH(1-84) ] has also shown efficacy in postmenopausal osteoporosis and is approved for use in Europe.…”

Section: Journal Of Bone and Mineral Researchmentioning

confidence: 97%

“…Teriparatide's osteoanabolic activity is ideally suited to counter the deleterious effects of glucocorticoids such as reduced bone formation and increased osteoblastic apoptosis. In 2007, Saag and colleagues (28) conducted a headto-head study comparing daily parenteral teriparatide (20 mg) with daily oral alendronate (10 mg) in 428 osteoporotic patients who had received glucocorticoids for at least 3 months ( 5 mg prednisone daily or equivalent). Significant densitometric differences between the groups were evident by 6 months, and by 18 months the teriparatide group showed lumbar spine BMD increases of 7.2% versus the alendronate group, which showed increases of only 3.4% (p < 0.001).…”

Section: Journal Of Bone and Mineral Researchmentioning

confidence: 99%

“…(20) Similar results were reported in other clinical trials, which also showed little or no incidence of hypercalcemia within 24 hours after teriparatide injection. (26,28,29,79,80) In a post hoc analysis, Miller and colleagues (81) showed a significantly higher incidence of hypercalcemia in patients with moderate renal impairment (glomerular filtration rate [GFR] 30-49 mL/min).…”

Section: Hypercalcemia and Hypercalciuriamentioning

confidence: 99%

“…The landmark trial conducted by Neer and colleagues (20) found that only 6% of patients taking teriparatide withdrew before the end of the study; high rates of persistence have also been found in subsequent studies in the United States and Canada. (28,(86)(87)(88) Trials that have reported compliance rates of PTH(1-84) demonstrate a range of 75% to 97.6% compliance (30,32,84,89) ; in the TOP study, 64% of the PTH-treated cohort and 70% of the placebo arm completed the study. (31) A British observational study showed a persistence rate of 87% at 12 months of treatment; this was likely influenced by the comprehensive education and follow-up program provided to each patient on PTH.…”

Section: Safety In Hypoparathyroidism Trialsmentioning

confidence: 99%

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Safety of osteoanabolic therapy: A decade of experience

Capriani

Irani

Bilezikian

2012

Journal of Bone and Mineral Research

132

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IntroductionO steoporosis is a prevalent disease that affects more than 10 million Americans. The lifetime risk of an osteoporosisrelated fracture is 50% for Caucasian women and 25% for men. Hip fractures carry a 10% to 20% increase in mortality rate within the first year after fracture. (1) The burden of the hip and other fractures can result in chronic pain, disability and other indices of reduced quality of life.Amidst these sobering statistics is the welcome advent over the past two decades of effective pharmacological therapies that reduce fracture risk. The therapies approved for the management of osteoporosis include bisphosphonates, raloxifene (a selective estrogen-receptor modulator), calcitonin, denosumab, strontium ranelate, and parathyroid hormone and PTH(1-84)]. The fulllength PTH molecule and its foreshortened amino-terminal fragment (teriparatide) are currently the only osteoanabolic agents approved for use. PTH(1-84) is not available in the United States. In November, 2002, teriparatide was approved by the U.S. Food and Drug Administration (FDA) for the treatment of postmenopausal osteoporosis and, later, in men. The approval came with restrictions in duration of therapy (18-24 months) and was limited to individuals with advanced osteoporosis at high risk for fracture. Reasons for these limitations relate, at least in part, to the unexpected occurrence of osteosarcoma and other bone neoplasms in Fischer 344 rat toxicity studies. In fact, the pivotal phase 3 trial of teriparatide was suspended when these rat toxicity data became available. The effects on rats was doseand duration-dependent, with rats being treated for approximately 80% of their lifetime and at doses three to 58 times the currently approved human dose. (2) Similar toxicity was seen for PTH(1-84) (3) Given the clear-cut efficacy data when the results of the abbreviated clinical trial results for teriparatide were analyzed, the FDA and equivalent other agencies in Europe and elsewhere granted approval of teriparatide with the stipulations that it should be used for no longer than 2 years. In the United States, the drug carries a ''black box warning'' and contraindicates its use in patients with existing risk factors for osteosarcoma, including Paget's disease of bone, prior skeletal radiation, and children with open epiphyses.Teriparatide has now been used in the United States for 10 years. With a decade of experience, it is timely to review the efficacy and safety profile of this medication. PTH(1-84) will also be reviewed. This perspective will be limited to PTH formulations that are available for the treatment of osteoporosis; we will not be discussing other anabolic agents that are currently being studied but are not yet approved, such as the sclerostin antibody (http://clinicaltrials.gov/ct2/results?term ¼ sclerostin þ anti-þ antibody). PTH mechanisms of actionTeriparatide is an amino-terminal fragment of PTH that is biologically identical to the amino-terminal fragment of human PTH. This fragment contains all the classical bio...

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Section: Journal Of Bone and Mineral Researchmentioning

confidence: 97%

Section: Journal Of Bone and Mineral Researchmentioning

confidence: 99%

Section: Hypercalcemia and Hypercalciuriamentioning

confidence: 99%

Section: Safety In Hypoparathyroidism Trialsmentioning

confidence: 99%

See 2 more Smart Citations

Safety of osteoanabolic therapy: A decade of experience

Capriani

Irani

Bilezikian

2012

Journal of Bone and Mineral Research

132

View full text Add to dashboard Cite

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“…(4,8,9) In one head-to-head comparison of alendronate and teriparatide in patients with glucocorticoid-induced osteoporosis, vertebral fracture (but not nonvertebral fracture) incidence was lower with teriparatide than with alendronate. (10) At the hip, teriparatide increases areal BMD as assessed by dual-energy X-ray absorptiometry (DXA), (3) volumetric BMD as assessed by quantitative computed tomography (QCT), (11) cortical cross-sectional area (but not diameter) of the femoral neck (11,12) and hip strength as assessed by finiteelement modeling (9) and by hip structural analysis. (12) However, the pivotal teriparatide trial (3) was not powered adequately for hip fracture outcome (there were only 9 hip fractures), and the areal BMD effects of teriparatide at the hip as assessed by DXA are smaller than those seen in the spine (3) and not consistently greater than those of alendronate.…”

Section: Introductionmentioning

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

Self Cite

318

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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