Dataset Information

New simulation model for bone formation markers in osteoporosis patients treated with once-weekly teriparatide.

ABSTRACT: Daily 20-?g and once-weekly 56.5-?g teriparatide (parathyroid hormone 1-34) treatment regimens increase bone mineral density (BMD) and prevent fractures, but changes in bone turnover markers differ between the two regimens. The aim of the present study was to explain changes in bone turnover markers using once-weekly teriparatide with a simulation model. Temporary increases in bone formation markers and subsequent decreases were observed during once-weekly teriparatide treatment for 72 weeks. These observations support the hypothesis that repeated weekly teriparatide administration stimulates bone remodeling, replacing old bone with new bone and leading to a reduction in the active remodeling surface. A simulation model was developed based on the iterative remodeling cycle that occurs on residual old bone. An increase in bone formation and a subsequent decrease were observed in the preliminary simulation. For each fitted time point, the predicted value was compared to the absolute values of the bone formation and resorption markers and lumbar BMD. The simulation model strongly matched actual changes in bone turnover markers and BMD. This simulation model indicates increased bone formation marker levels in the early stage and a subsequent decrease. It is therefore concluded that remodeling-based bone formation persisted during the entire treatment period with once-weekly teriparatide.

SUBMITTER: Tanaka S

PROVIDER: S-EPMC4472137 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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New simulation model for bone formation markers in osteoporosis patients treated with once-weekly teriparatide.

Tanaka Sakae S Adachi Taiji T Kuroda Tatsuhiko T Nakamura Toshitaka T Shiraki Masataka M Sugimoto Toshitsugu T Takeuchi Yasuhiro Y Saito Mitsuru M Bilezikian John P JP

Bone research 20141223

Daily 20-μg and once-weekly 56.5-μg teriparatide (parathyroid hormone 1-34) treatment regimens increase bone mineral density (BMD) and prevent fractures, but changes in bone turnover markers differ between the two regimens. The aim of the present study was to explain changes in bone turnover markers using once-weekly teriparatide with a simulation model. Temporary increases in bone formation markers and subsequent decreases were observed during once-weekly teriparatide treatment for 72 weeks. Th ...[more]

PMID: 26273530

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Project description:A 48-week, multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority trial (the TWICE study) conducted in Japanese primary osteoporosis patients with a high risk of fractures demonstrated that a 28.2-?g twice-weekly regimen of teriparatide can provide comparable efficacy to a 56.5-?g once-weekly regimen of teriparatide, while also improving safety.IntroductionWhile a 56.5-?g once-weekly regimen of teriparatide has high efficacy for osteoporosis, treatment continuation rates are low, with one of the major causes being adverse drug reactions such as nausea or vomiting. The TWICE study was therefore conducted to investigate whether a twice-weekly regimen with 28.2-?g teriparatide can provide comparable efficacy to the 56.5-?g once-weekly regimen while improving safety.MethodsA 48-week, multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority trial was conducted in Japan. Patients with primary osteoporosis aged ??65 years at high risk of fractures (n?=?553) were randomly allocated to the 28.2-?g twice-weekly group (n?=?277) or the 56.5-?g once-weekly group (n?=?276). The primary endpoint was the percentage change in lumbar spine (L2-L4) bone mineral density (BMD) at final follow-up.ResultsThe percentage changes in lumbar spine (L2-L4) BMD at final follow-up in the 28.2-?g twice-weekly and 56.5-?g once-weekly groups were 7.3% and 5.9%, respectively; the difference (95% confidence interval [CI]) in percentage change was 1.3% (0.400-2.283%). Since the lower limit of the 95% CI was above the pre-specified non-inferiority margin (-?1.6%), non-inferiority of the 28.2-?g twice-weekly group was demonstrated. Adverse drug reactions were significantly less frequent in the 28.2-?g twice-weekly group (39.7% vs 56.2%; p?<?0.01); the incidence of major adverse drug reactions was lower, and the number of subjects who discontinued due to adverse drug reactions was less in the 28.2-?g twice-weekly group.ConclusionsA 28.2-?g twice-weekly regimen of teriparatide can provide comparable efficacy to a 56.5-?g once-weekly regimen while improving safety.Clinical trial registrationJapicCTI-163477 .

Project description:UnlabelledChanges of the bone formation marker PINP correlated positively with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis (GIO) who received 18-month treatment with teriparatide, but not with risedronate. These results support the use of PINP as a surrogate marker of bone strength in GIO patients treated with teriparatide.IntroductionTo investigate the correlations between biochemical markers of bone turnover and vertebral strength estimated by finite element analysis (FEA) in men with GIO.MethodsA total of 92 men with GIO were included in an 18-month, randomized, open-label trial of teriparatide (20 μg/day, n = 45) and risedronate (35 mg/week, n = 47). High-resolution quantitative computed tomography images of the 12th thoracic vertebra obtained at baseline, 6 and 18 months were converted into digital nonlinear FE models and subjected to anterior bending, axial compression and torsion. Stiffness and strength were computed for each model and loading mode. Serum biochemical markers of bone formation (amino-terminal-propeptide of type I collagen [PINP]) and bone resorption (type I collagen cross-linked C-telopeptide degradation fragments [CTx]) were measured at baseline, 3 months, 6 months and 18 months. A mixed-model of repeated measures analysed changes from baseline and between-group differences. Spearman correlations assessed the relationship between changes from baseline of bone markers with FEA variables.ResultsPINP and CTx levels increased in the teriparatide group and decreased in the risedronate group. FEA-derived parameters increased in both groups, but were significantly higher at 18 months in the teriparatide group. Significant positive correlations were found between changes from baseline of PINP at 3, 6 and 18 months with changes in FE strength in the teriparatide-treated group, but not in the risedronate group.ConclusionsPositive correlations between changes in a biochemical marker of bone formation and improvement of biomechanical properties support the use of PINP as a surrogate marker of bone strength in teriparatide-treated GIO patients.

Project description:Without antiresorptive therapy, postmenopausal women lose bone mass after teriparatide (TPTD) discontinuation; estrogen treatment prevents bone loss in this setting. It is not known whether premenopausal women with regular menses lose bone mass after teriparatide discontinuation.This study aimed to test the hypothesis that normally menstruating premenopausal women with idiopathic osteoporosis (IOP) will maintain teriparatide-associated bone mineral density (BMD) gains after medication cessation.Twenty-one premenopausal IOP women previously enrolled in an open-label pilot study of teriparatide (20 mcg for 18-24 mo), had substantial BMD increases at the lumbar spine (LS; 10.8 ± 8.3%), total hip (TH; 6.2 ± 5.6%), and femoral neck (7.6 ± 3.4%). For this study, BMD was remeasured 2.0 ± 0.6 years after teriparatide cessation.Fifteen women, who had gained 11.1 ± 7.2% at LS and 6.1 ± 6.5% at TH and were premenopausal at teriparatide completion, were followed without antiresorptive treatment.Two years after completing teriparatide, BMD declined by 4.8 ± 4.3% (P = .0007) at the LS. In contrast, BMD remained stable at the femoral neck (-1.5 ± 4.2%) and TH (-1.1 ± 3.7%). Those who sustained LS bone loss >3% (-7.3 ± 2.9%; n = 10), did not differ from those with stable LS BMD (0.1 ± 1.1%; n=5) with regard to baseline body mass index, BMD at any site, or duration of followup, but were significantly older at re-evaluation (46 ± 3 vs 38 ± 7; P = .046), had larger increases in LS BMD during teriparatide treatment and higher cancellous bone remodeling on transiliac biopsy at baseline and completion of teriparatide treatment. Serum bone turnover markers did not differ at baseline or teriparatide completion, but tended to be higher at the re-evaluation timepoint in those with post-teriparatide bone loss.These findings lead us to conclude that premenopausal women with IOP, particularly those over 40, may require antiresorptive treatment to prevent bone loss after teriparatide.

Project description:In this randomized, controlled trial, treatment with once-weekly subcutaneous injection of teriparatide for 72 weeks was found to be associated with a significant reduction in the incidence of morphometric vertebral fractures compared with alendronate in women with primary osteoporosis who were at high risk of fracture.IntroductionTo determine whether the anti-fracture efficacy of teriparatide is superior to that of alendronate, a prospective, randomized, open-label, blinded-endpoint trial was performed.MethodsJapanese women aged at least 75 years were eligible for the study if they had primary osteoporosis and were at high risk of fracture. Patients were randomly assigned in a 1:1 ratio to receive sequential therapy (once-weekly subcutaneous injection of teriparatide 56.5 μg for 72 weeks followed by alendronate for 48 weeks) or monotherapy with alendronate for 120 weeks. The primary endpoint was the incidence of morphometric vertebral fractures at 72 weeks (at the end of teriparatide treatment).ResultsBetween October 2014 and December 2017, 1011 patients (505 in the teriparatide group and 506 in the alendronate group) were enrolled. Of these, 778 patients (351 and 427, respectively) were included in the primary analysis. The incidence of morphometric vertebral fractures was significantly lower in the teriparatide group (56 per 419.9 person-years, annual incidence rate 0.1334) than in the alendronate group (96 per 553.6 person-years, annual incidence rate 0.1734), with a rate ratio of 0.78 (95% confidence interval 0.61 to 0.99, P = 0.04). In both groups, adverse events were most frequently reported in the following system organ classes: infections and infestations, gastrointestinal disorders, and musculoskeletal and connective tissue disorders.ConclusionOnce-weekly subcutaneous injection of teriparatide significantly reduced the incidence of morphometric vertebral fractures compared with alendronate in women with primary osteoporosis who were at high risk of fracture.Trial registrationjRCTs031180235 and UMIN000015573, March 12, 2019.

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New simulation model for bone formation markers in osteoporosis patients treated with once-weekly teriparatide.

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New simulation model for bone formation markers in osteoporosis patients treated with once-weekly teriparatide.

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