Dataset Information

Effects of teriparatide retreatment in osteoporotic men and women.

ABSTRACT: The stimulatory effect of teriparatide on bone mineral density (BMD) and bone turnover is initially exuberant, but then diminishes.Our objective was to determine whether retreating with teriparatide after a drug-free period can restore the initial exuberant response to teriparatide.This was a planned extension of a randomized controlled trial conducted in a single university hospital.Subjects previously participated in a 30-month randomized trial comparing the effects of alendronate (group 1), teriparatide (group 2), or both (group 3) on BMD and bone turnover in men and women with low BMD (phase 1). Subjects who completed phase 1 on their assigned therapy entered phase 2 (months 30-42), during which teriparatide was stopped in groups 2 and 3. Teriparatide was administered to all subjects during months 42 to 54 (phase 3).We compared changes in BMD and markers of bone turnover (serum osteocalcin, N-terminal propeptide of type 1 collagen, and N-telopeptide) between phase 1 and 3 in subjects receiving teriparatide alone.Posterior-anterior and lateral spine BMD increased 12.5 +/- 1.5 and 16.9 +/- 1.7%, respectively, during the first 12 months of teriparatide administration and 5.2 +/- 0.8 and 6.2 +/- 1.8%, respectively, during teriparatide retreatment (P < 0.001 and P = 0.001). Increases in osteocalcin (P < 0.001), N-terminal propeptide of type 1 collagen (P < 0.001), and N-telopeptide (P < 0.001) were greater during the first period of teriparatide administration.The response to teriparatide is attenuated when readministered after a 12-month hiatus.

SUBMITTER: Finkelstein JS

PROVIDER: S-EPMC2708954 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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Effects of teriparatide retreatment in osteoporotic men and women.

Finkelstein Joel S JS Wyland Jason J JJ Leder Benjamin Z BZ Burnett-Bowie Sherri-Ann M SM Lee Hang H Jüppner Harald H Neer Robert M RM

The Journal of clinical endocrinology and metabolism 20090428 7

<h4>Context</h4>The stimulatory effect of teriparatide on bone mineral density (BMD) and bone turnover is initially exuberant, but then diminishes.<h4>Objective</h4>Our objective was to determine whether retreating with teriparatide after a drug-free period can restore the initial exuberant response to teriparatide.<h4>Design and setting</h4>This was a planned extension of a randomized controlled trial conducted in a single university hospital.<h4>Patients and intervention</h4>Subjects previousl ...[more]

PMID: 19401368

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Project description:ContextIn postmenopausal women, bone mineral density (BMD) declines after teriparatide therapy is stopped. The pattern of BMD loss after teriparatide therapy is stopped in men is less clear.ObjectiveThe aim of the study was to determine whether the pattern of teriparatide-induced bone accrual and post-teriparatide bone loss differs between postmenopausal women and eugonadal men.DesignWe conducted a prospective cohort substudy.PatientsThe study included 14 postmenopausal women and 17 eugonadal men, ages 46-85 yr, with lumbar spine or femoral neck BMD T-scores below -2.InterventionTeriparatide (37 microg sc daily) was administered for 24 months, followed by 12 months off therapy.Main outcome measuresWe measured BMD at various anatomic sites by dual-energy x-ray absorptiometry, trabecular spine BMD by quantitative computed tomography, and bone turnover markers during the treatment and observation periods. The response to teriparatide administration and discontinuation was compared between females and males.ResultsBMD of the spine, femoral neck, total hip, and trabecular spine increased similarly during the treatment period in men and women, whereas BMD at the radius was stable in men but decreased by 8.1 +/- 3.3% in women (P < 0.0001). After teriparatide was stopped, BMD at the posterior-anterior spine decreased by 7.1 +/- 3.8% in women and by 4.1 +/- 3.5% in men (P = 0.036). BMD at the total hip and femoral neck decreased by 3.8 +/- 3.9 and 3.1 +/- 4.3%, respectively, in women but remained stable in men (P < 0.05 for both sites). BMD at the distal radius remained stable in men but increased in women by 1.6 +/- 3.1% (P = 0.069).ConclusionsTeriparatide appears to increase BMD similarly in postmenopausal women and eugonadal men with osteoporosis. After teriparatide is stopped, the decline in BMD is greater in women than in men. If confirmed in larger cohorts, these findings would suggest that the indication for immediate antiresorptive therapy after teriparatide may not be as urgent in men as in women.

Project description:Teriparatide, currently only available in brand form in the United States, is a costly drug approved for the treatment of postmenopausal osteoporotic women who are at high risk of fracture. Because market exclusivity for brand teriparatide expired in August 2019 in the US, we sought to understand the potential health economic impact of the availability of generic or biosimilar (generic/biosimilar) teriparatide. We examined the cost-effectiveness of daily teriparatide for 2?years followed by weekly alendronate for 10?years (ie, sequential teriparatide/alendronate) compared with alendronate alone for 10?years in community-dwelling white osteoporotic women with prior vertebral fracture at ages 65, 70, 75, and 80. Using an updated version of previously validated Markov microsimulation models, we obtained incremental cost-effectiveness ratios (ICERs) (dollars [$] per quality-adjusted life year [QALY]) with a willingness-to-pay (WTP) of $150,000 per QALY from a societal perspective with a lifelong time horizon. In the base case, we estimated the annual cost of teriparatide to be $20,161, based on the assumption of 10% brand usage (at a cost of $27,618) and 90% generic/biosimilar usage (priced 30% lower than brand). The ICERs of sequential teriparatide/alendronate compared with alendronate alone were greater than $280,000 per QALY at all ages examined. In deterministic sensitivity analyses, results were sensitive to teriparatide's cost, with the cost of a generic/biosimilar product needing to be 65% to 85% lower than brand for sequential teriparatide/alendronate to be cost-effective. In probabilistic sensitivity analyses, under the assumption that the annual cost of teriparatide was $20,161, the probabilities of sequential teriparatide/alendronate being cost-effective were less than 4% at a WTP of $150,000 per QALY. In conclusion, among community-dwelling older osteoporotic women with prior vertebral fracture in the US, even with the potential availability of generic/biosimilar teriparatide, sequential teriparatide/alendronate would not be cost-effective unless the cost of generic/biosimilar teriparatide were heavily discounted with respect to the current brand cost. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Project description:Using a Markov microsimulation model among hypothetical cohorts of community-dwelling older osteoporotic Japanese women with prior vertebral fracture over a lifetime horizon, we found that daily subcutaneous teriparatide for 2 years followed by weekly oral alendronate for 8 years was not cost-effective compared with alendronate monotherapy for 10 years.PurposeTeriparatide has proven efficacy in reducing osteoporotic fractures, but with substantial cost. We examined the cost-effectiveness of sequential teriparatide/alendronate (i.e., daily subcutaneous teriparatide for 2 years followed by weekly oral alendronate for 8 years) compared with alendronate monotherapy for 10 years among community-dwelling older osteoporotic women with prior clinical or morphometric vertebral fracture in Japan.MethodsUsing a previously validated and updated Markov microsimulation model, we obtained incremental cost-effectiveness ratios (Japanese yen [¥] (or US dollars [$]) per quality-adjusted life year [QALY]) from the perspective of a single payer responsible for both public healthcare and long-term care. We assumed a lifetime horizon with a willingness-to-pay of ¥5million (or $47,500) per QALY in the base case. We modeled the cost of biosimilar teriparatide, which has been available since November 2019 in Japan, assuming the efficacy was the same as that of the brand version.ResultsIn the base case, sequential teriparatide/alendronate was not cost-effective compared with alendronate monotherapy. In deterministic sensitivity analyses, sequential teriparatide/alendronate would become cost-effective with 85%, 50%, and 15% price discounts to teriparatide at ages 70, 75, and 80, respectively, compared to the current biosimilar cost. Otherwise, results were especially sensitive to changes that affected efficacy of teriparatide or alendronate. In probabilistic sensitivity analyses, the probabilities of sequential teriparatide/alendronate being cost-effective were 0%, 1%, and 37% at ages 70, 75, and 80, respectively.ConclusionsAmong high-risk osteoporotic women in Japan, sequential teriparatide/alendronate was not cost-effective compared with alendronate monotherapy, even with the availability of biosimilar teriparatide.

Project description:To examine the degree of trauma in major osteoporotic fractures (MOF) in men versus women, we used data from 15,698 adults aged ?65 years enrolled in the Osteoporotic Fractures in Men (MrOS) study (5994 men) and the Study of Osteoporotic Fractures (SOF) (9704 women). Participants were contacted tri-annually to ascertain incident fractures, which were confirmed by radiographic reports and coded according to degree of self-reported trauma. Trauma was classified as low (fall from ? standing height; fall on stairs, steps, or curb; minimal trauma other than fall [coughing, turning over]); moderate (collisions with objects during normal activity without associated fall); or high (fall from > standing height; severe trauma [motor vehicle accident, assault]). MOF included hip, clinical vertebral, wrist, and humerus fractures. Mean fracture follow-up was 9.1 years in SOF and 8.7 years in MrOS. A total of 14.6% of the MOF in men versus 6.3% of the MOF in women were classified as high trauma (p < 0.001); men versus women more often experienced fractures resulting from severe trauma as well as from fall > standing height. High-trauma fractures were more significantly common in men versus women at the hip (p = 0.002) and wrist (p < 0.001) but not at the spine or humerus. Among participants with MOF, the odds ratio of a fracture related to high-trauma fracture among men versus women was 3.12 (95% confidence interval [CI] 1.70-5.71) after adjustment for traditional risk factors. Findings were similar in analyses limited to participants with hip fractures (odds ratio [OR] = 3.34, 95% CI 1.04-10.67) and those with wrist fracture (OR = 5.68, 95% CI 2.03-15.85). Among community-dwelling older adults, MOF are more likely to be related to high trauma in men than in women. These findings are not explained by sex differences in conventional risk factors and may reflect a greater propensity among men to engage in risky behavior. © 2015 American Society for Bone and Mineral Research.

Project description:ObjectiveTo bridge the efficacy and compare the safety of the 24-week teriparatide treatment in a Chinese osteoporosis study (NCT00414973) to a large international trial (FPT, NCT00670501) to determine whether long-term results from the international study were applicable to Chinese patients.MethodsIn this post-hoc analysis, a propensity score matching method was used to select patients with similar baseline characteristics. Patients were female with osteoporosis at high risk of fracture, aged ≥55 years, and had no history of rheumatoid arthritis or corticosteroid use. Outcomes included percentage changes in lumbar-spine bone mineral density (LS-BMD) from baseline to 24 weeks, safety in matched-pair patients, and long-term percentage changes in LS-BMD and fragility fracture incidence in the matched fracture prevention trial (FPT) population. The determination of the acceptability of bridging results was based on the International Conference on Harmonization E5 guidelines.ResultsA total number of 228 patients from each study were matched and paired. Patients were similar at baseline (P-values >0.33) except for ethnicity (98% Caucasian for FPT). For changes in LS-BMD from baseline to week 24, treatment with teriparatide showed significantly greater increases (P-values <0.001; least-squares mean difference: 5.0% in the Chinese study and 5.4% in FPT) than comparator (calcitonin/placebo). The safety profiles over 24 weeks were similar between two studies. For matched-pair FPT patients, long-term changes in LS-BMD were significantly greater (least-squares mean difference: 11.5%, P<0.001) and the fragility fracture rate was marginally lower in the teriparatide group compared with the placebo group (13.1% vs 22.3%, P=0.070).ConclusionAssuming similar pharmacokinetic profiles for teriparatide between populations, comparable increases in LS-BMD and consistent safety profiles within 24 weeks of the treatment suggest long-term LS-BMD results from the FPT may be applicable to Chinese population.

Project description:Data on treatment of glucocorticoid-induced osteoporosis (GIO) in men are scarce. We performed a randomized, open-label trial in men who have taken glucocorticoids (GC) for ≥3 months, and had an areal bone mineral density (aBMD) T-score ≤ -1.5 standard deviations. Subjects received 20 μg/d teriparatide (n = 45) or 35 mg/week risedronate (n = 47) for 18 months. Primary objective was to compare lumbar spine (L1 -L3 ) BMD measured by quantitative computed tomography (QCT). Secondary outcomes included BMD and microstructure measured by high-resolution QCT (HRQCT) at the 12th thoracic vertebra, biomechanical effects for axial compression, anterior bending, and axial torsion evaluated by finite element (FE) analysis from HRQCT data, aBMD by dual X-ray absorptiometry, biochemical markers, and safety. Computed tomography scans were performed at 0, 6, and 18 months. A mixed model repeated measures analysis was performed to compare changes from baseline between groups. Mean age was 56.3 years. Median GC dose and duration were 8.8 mg/d and 6.4 years, respectively; 39.1% of subjects had a prevalent fracture, and 32.6% received prior bisphosphonate treatment. At 18 months, trabecular BMD had significantly increased for both treatments, with significantly greater increases with teriparatide (16.3% versus 3.8%; p = 0.004). HRQCT trabecular and cortical variables significantly increased for both treatments with significantly larger improvements for teriparatide for integral and trabecular BMD and bone surface to volume ratio (BS/BV) as a microstructural measure. Vertebral strength increases at 18 months were significant in both groups (teriparatide: 26.0% to 34.0%; risedronate: 4.2% to 6.7%), with significantly higher increases in the teriparatide group for all loading modes (0.005 < p < 0.015). Adverse events were similar between groups. None of the patients on teriparatide but five (10.6%) on risedronate developed new clinical fractures (p = 0.056). In conclusion, in this 18-month trial in men with GIO, teriparatide showed larger improvements in spinal BMD, microstructure, and FE-derived strength than risedronate.

Dataset Information

Effects of teriparatide retreatment in osteoporotic men and women.

Publications

Effects of teriparatide retreatment in osteoporotic men and women.

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