Dataset Information

Effect of Teriparatide Treatment on Circulating Periostin and Its Relationship to Regulators of Bone Formation and BMD in Postmenopausal Women With Osteoporosis.

ABSTRACT: Context:Treatment of postmenopausal osteoporosis with teriparatide parathyroid hormone amino terminal 1-34 increases bone formation and improves bone microarchitecture. A possible modulator of action is periostin. In vitro experiments have shown that periostin might regulate osteoblast differentiation and bone formation through Wnt signaling. The effect of teriparatide on periostin is not currently known. Objectives:To determine the effect of teriparatide treatment on circulating levels of periostin and other regulators of bone formation and investigate how changes in periostin relate to changes in bone turnover markers, regulators of bone formation, and bone mineral density (BMD). Participants and Design:Twenty women with osteoporosis; a 2-year open-label single-arm study. Intervention:Teriparatide 20 µg was administered by subcutaneous injection daily for 104 weeks. Periostin, sclerostin, and Dickkopf-related protein 1, procollagen type I N-terminal propeptide (PINP), and C-telopeptide of type I collagen were measured in fasting serum collected at baseline (two visits) and then at weeks 1, 2, 4, 12, 26, 52, 78, and 104. BMD was measured at the lumbar spine, total hip, and femoral neck using dual energy x-ray absorptiometry. Results:Periostin levels increased by 6.6% [95% confidence interval (CI), -0.4 to 13.5] after 26 weeks of teriparatide treatment and significantly by 12.5% (95% CI, 3.3 to 21.0; P < 0.01) after 52 weeks. The change in periostin correlated positively with the change in the lumbar spine BMD at week 52 (r = 0.567; 95% CI, 0.137 to 0.817; P < 0.05) and femoral neck BMD at week 104 (r = 0.682; 95% CI, 0.261 to 0.885; P < 0.01). Conclusions:Teriparatide therapy increases periostin secretion; it is unclear whether this increase mediates the effect of the drug on bone.

SUBMITTER: Gossiel F

PROVIDER: S-EPMC6457025 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effect of Teriparatide Treatment on Circulating Periostin and Its Relationship to Regulators of Bone Formation and BMD in Postmenopausal Women With Osteoporosis.

Gossiel Fatma F Scott Jessica R JR Paggiosi Margaret A MA Naylor Kim E KE McCloskey Eugene V EV Peel Nicola F A NFA Walsh Jennifer S JS Eastell Richard R

The Journal of clinical endocrinology and metabolism 20180401 4

<h4>Context</h4>Treatment of postmenopausal osteoporosis with teriparatide parathyroid hormone amino terminal 1-34 increases bone formation and improves bone microarchitecture. A possible modulator of action is periostin. In vitro experiments have shown that periostin might regulate osteoblast differentiation and bone formation through Wnt signaling. The effect of teriparatide on periostin is not currently known.<h4>Objectives</h4>To determine the effect of teriparatide treatment on circulating ...[more]

PMID: 29365099

Similar Datasets

Project description:MicroRNAs regulate bone homeostasis, and circulating microRNAs have been proposed as novel bone biomarkers. The effect of anti-osteoporotic treatment on circulating microRNAs has not been described in detail. Therefore, we performed a comprehensive analysis of microRNA serum levels in ovariectomized (OVX) and sham-operated (SHAM) rats over 12 weeks of antiresorptive or osteoanabolic treatment. Forty-two Sprague Dawley rats underwent SHAM surgery (n = 10) or ovariectomy (n = 32). After 8 weeks, OVX rats were randomized to antiresorptive treatment with zoledronate (n = 11), osteoanabolic treatment with teriparatide (n = 11), or vehicle treatment (n = 10). Serum samples were collected at weeks 8, 12, 16, and 20 after surgery. A total of 91 microRNAs were analyzed by RT-qPCR in serum samples collected at week 20. Based on the results, 29 microRNAs were selected for longitudinal analysis at all four study time points. Changes in bone mineral density and microstructure were followed up by in vivo micro-CT and ex vivo nano-CT. Ovariectomy resulted in the loss of trabecular bone, which was reversed by osteoanabolic and antiresorptive treatment. Differential expression analysis identified 11 circulating miRNAs that were significantly regulated after treatment. For example, miR-107 and miR-31-5p increased in vehicle-treated OVX animals, whereas they decreased during teriparatide treatment. Additional miRNAs were identified that showed significant correlations to bone microstructure or bone miRNA expression, including miR-203a-3p, which exhibited a significant negative correlation to vertebral and tibial trabecular bone volume fraction (%). Longitudinal analysis confirmed eight microRNAs with significant changes in serum over time that were prevented by teriparatide and zoledronate treatment (miR-34a-5p, miR-31-5p, miR-30d-3p, miR-378a-5p) or teriparatide treatment only (miR-375-3p, miR-183-5p, miR-203a-3p, miR-203b-3p). Gene target network analysis identified WNT and Notch signaling as the main signaling pathways controlled by these miRNAs. Thus, ovariectomy results in time-dependent deregulation of circulating miRNAs compared with SHAM animals. Anti-osteoporotic treatments can rescue this effect, showing that bone-related miRNAs might act as novel biomarkers for treatment monitoring. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

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:We have previously reported that premenopausal women with idiopathic osteoporosis (IOP) have profound microarchitectural deficiencies and heterogeneous bone remodeling. Those with the lowest bone formation rate have higher baseline serum insulin-like growth factor-1 (IGF-1) levels and less robust response to teriparatide. Because IGF-1 stimulates bone formation and is critical for teriparatide action on osteoblasts, these findings suggest a state of IGF-1 resistance in some IOP women. To further investigate the hypothesis that osteoblast and IGF-1-related mechanisms mediate differential responsiveness to teriparatide in IOP, we studied circulating osteoblast progenitor (COP) cells and their IGF-1 receptor (IGF-1R) expression. In premenopausal women with IOP, peripheral blood mononuclear cells (PBMCs) were obtained at baseline (n = 25) and over 24 months of teriparatide treatment (n = 11). Flow cytometry was used to identify and quantify COPs (non-hematopoetic lineage cells expressing osteocalcin and RUNX2) and to quantify IGF-1R expression levels. At baseline, both the percent of PBMCs that were COPs (%COP) and COP cell-surface IGF-1R expression correlated directly with several histomorphometric indices of bone formation in tetracycline-labeled transiliac biopsies. In treated subjects, both %COP and IGF-1R expression increased promptly after teriparatide, returning toward baseline by 18 months. Although neither baseline %COP nor increase in %COP after 3 months predicted the bone mineral density (BMD) response to teriparatide, the percent increase in IGF-1R expression on COPs at 3 months correlated directly with the BMD response to teriparatide. Additionally, lower IGF-1R expression after teriparatide was associated with higher body fat, suggesting links between teriparatide resistance, body composition, and the GH/IGF-1 axis. In conclusion, these assays may be useful to characterize bone remodeling noninvasively and may serve to predict early response to teriparatide and possibly other bone formation-stimulating medications. These new tools may also have utility in the mechanistic investigation of teriparatide resistance in premenopausal IOP and perhaps in other populations. © 2017 American Society for Bone and Mineral Research.

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.

Dataset Information

Effect of Teriparatide Treatment on Circulating Periostin and Its Relationship to Regulators of Bone Formation and BMD in Postmenopausal Women With Osteoporosis.

Publications

Effect of Teriparatide Treatment on Circulating Periostin and Its Relationship to Regulators of Bone Formation and BMD in Postmenopausal Women With Osteoporosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets