The Experts below are selected from a list of 1164 Experts worldwide ranked by ideXlab platform
Adi Cohen - One of the best experts on this subject based on the ideXlab platform.
-
effect of teriparatide on bone remodeling and density in premenopausal Idiopathic Osteoporosis a phase ii trial
The Journal of Clinical Endocrinology and Metabolism, 2020Co-Authors: Adi Cohen, Robert R. Recker, Joan M. Lappe, David W. Dempster, Hua Zhou, Stephanie Shiau, Nandini Nair, Thomas L Nickolas, Sanchita Agarwal, Mafo KamandakossehAbstract:Context Premenopausal women with Idiopathic Osteoporosis (IOP) have abnormal skeletal microarchitecture and variable tissue-level bone formation rate (BFR). Objectives Compare 6 months (M) of teriparatide versus placebo on areal bone mineral density (aBMD) by dual-energy x-ray absorptiometry (DXA), bone turnover markers (BTMs) and BFR at 3M by quadruple-labeled transiliac biopsy. Characterize 12M and 24M effects of teriparatide on aBMD and whether BTMs and BFR predict response. Design 6M phase 2 randomized controlled trial (RCT) followed by open extension. Setting Tertiary referral centers. Patients Premenopausal women with IOP. Interventions A total of 41 women were randomized to either teriparatide 20 mcg (n = 28) or placebo (n = 13). After 6M, those on placebo switched to teriparatide for 24M; those on teriparatide continued for 18M. Main outcome measures 6M RCT: Between-group differences in lumbar spine (LS) aBMD (percent change from baseline), 3M BFR, and hypercalcemia. Open-label extension: Within-group change in LS aBMD over 12M and 24M. Secondary outcomes included aBMD change at other sites and relationship between BTMs, BFR, and changes in aBMD. Findings Over 6M, LS aBMD increased by 5.5% (95% CI: 3.83, 7.19) in teriparatide and 1.5% (95% CI: -0.73, 3.83) in placebo (P = 0.007). There were increases in 3M BTMs, and BFR (cancellous and endocortical BFR: between-groups P = 0.004). Over 24M, teriparatide increased LS aBMD by 13.2% (95% CI: 10.3, 16.2), total hip by 5.2% (95% CI: 3.7, 6.7) and femoral neck by 5.0% (95% CI: 3.2, 6.7; all P ≤ 0.001). Serum N-terminal propeptides of procollagen type 1 (P1NP) and 3M endocortical BFR were moderately associated with LS aBMD response. Teriparatide was well-tolerated. Conclusions Teriparatide increased BFR and formation markers and was associated with marked aBMD improvements in most premenopausal women (82%) with IOP.
-
women with pregnancy and lactation associated Osteoporosis plo have low bone remodeling rates at the tissue level
Journal of Bone and Mineral Research, 2019Co-Authors: Adi Cohen, David W. Dempster, Hua Zhou, Mariana Bucovsky, Julie Stubby, Mafo Kamandakosseh, Ralph Muller, Elliott Goff, Ivelisse Colon, Thomas L NickolasAbstract:Pregnancy and lactation-associated Osteoporosis (PLO) is a rare, severe, early form of Osteoporosis in which young women present with fractures, usually multiple vertebral fractures, during late pregnancy or lactation. In studies of Idiopathic Osteoporosis (IOP) in premenopausal women, we enrolled 78 women with low-trauma fractures and 40 healthy controls, all with normal menses and no secondary cause of bone loss. In 15 of the affected women, the PLO subgroup, fractures had occurred during late pregnancy or lactation. We hypothesized that clinical, bone structural, and metabolic characteristics would differ between women with PLO and those with (non-PLO) IOP and controls. All were evaluated > 12 months postpartum, when structural and remodeling characteristics would be expected to reflect baseline premenopausal status rather than transient postpartum changes. As previously reported, affected subjects (PLO and IOP) had BMD and microarchitectural deficiencies compared to controls. Women with PLO did not differ from those with IOP in terms of age, BMI, body fat, menarcheal age, parity, or age at first pregnancy. However, women with PLO had a more severe clinical presentation than those with IOP: more fractures (5.5 ± 3.3 versus 2.6 ± 2.1; p = 0.005); more vertebral fractures (80% versus 17%; p < 0.001); and higher prevalence of multiple fractures. BMD deficits were more profound and cortical width tended to be lower in PLO. PLO subjects also had significantly lower tissue-level mineral apposition rate and bone formation rates (0.005 ± 0.005 versus 0.011 ± 0.010 mm2 /mm/year; p = 0.006), as well as lower serum P1NP (33 ± 12 versus 44 ± 18 µg/L; p = 0.02) and CTX (257 ± 102 versus 355 ± 193 pg/mL; p = 0.01) than IOP. The finding that women with PLO have a low bone remodeling state assessed more than a year postpartum increases our understanding of the pathogenic mechanism of PLO. We conclude that women with PLO may have underlying osteoblast functional deficits which could affect their therapeutic response to osteoanabolic medications. © 2019 American Society for Bone and Mineral Research.
-
igf 1 receptor expression on circulating osteoblast progenitor cells predicts tissue based bone formation rate and response to teriparatide in premenopausal women with Idiopathic Osteoporosis
Journal of Bone and Mineral Research, 2017Co-Authors: Adi Cohen, Robert R. Recker, Joan M. Lappe, David W. Dempster, Hua Zhou, Stavroula Kousteni, Brygida Bisikirska, Jayesh Shah, Sanil J Manavalan, Donald J McmahonAbstract: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 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. While neither baseline %COP nor increase in %COP after three months predicted the 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. This article is protected by copyright. All rights reserved
-
igf 1 receptor expression on circulating osteoblast progenitor cells predicts tissue based bone formation rate and response to teriparatide in premenopausal women with Idiopathic Osteoporosis
Journal of Bone and Mineral Research, 2017Co-Authors: Adi Cohen, Robert R. Recker, Joan M. Lappe, David W. Dempster, Hua Zhou, Stavroula Kousteni, Brygida Bisikirska, Jayesh Shah, Sanil J Manavalan, Donald J McmahonAbstract: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.
-
Bone Density After Teriparatide Discontinuation in Premenopausal Idiopathic Osteoporosis
The Journal of clinical endocrinology and metabolism, 2015Co-Authors: Adi Cohen, Mafo Kamanda-kosseh, Robert R. Recker, Joan M. Lappe, David W. Dempster, Hua Zhou, Serge Cremers, Mariana Bucovsky, Julie Stubby, Elizabeth ShaneAbstract:Context: 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. Objective: 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. Design: 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. Participants: 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 an...
Donald J Mcmahon - One of the best experts on this subject based on the ideXlab platform.
-
igf 1 receptor expression on circulating osteoblast progenitor cells predicts tissue based bone formation rate and response to teriparatide in premenopausal women with Idiopathic Osteoporosis
Journal of Bone and Mineral Research, 2017Co-Authors: Adi Cohen, Robert R. Recker, Joan M. Lappe, David W. Dempster, Hua Zhou, Stavroula Kousteni, Brygida Bisikirska, Jayesh Shah, Sanil J Manavalan, Donald J McmahonAbstract: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.
-
igf 1 receptor expression on circulating osteoblast progenitor cells predicts tissue based bone formation rate and response to teriparatide in premenopausal women with Idiopathic Osteoporosis
Journal of Bone and Mineral Research, 2017Co-Authors: Adi Cohen, Robert R. Recker, Joan M. Lappe, David W. Dempster, Hua Zhou, Stavroula Kousteni, Brygida Bisikirska, Jayesh Shah, Sanil J Manavalan, Donald J McmahonAbstract: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 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. While neither baseline %COP nor increase in %COP after three months predicted the 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. This article is protected by copyright. All rights reserved
-
teriparatide for Idiopathic Osteoporosis in premenopausal women a pilot study
The Journal of Clinical Endocrinology and Metabolism, 2013Co-Authors: Adi Cohen, Robert R. Recker, Joan M. Lappe, David W. Dempster, Hua Zhou, Serge Cremers, Thomas L Nickolas, Donald J Mcmahon, Emily M Stein, Ralph MullerAbstract:Context: Premenopausal women with Idiopathic Osteoporosis (IOP) have abnormal cortical and trabecular bone microarchitecture. Objective: The purpose of this study was to test the hypotheses that teriparatide increases bone mineral density (BMD) and bone formation and improves trabecular microarchitecture and stiffness in women with IOP. Design: This was an open-label pilot study. Setting: The setting was a tertiary care referral center. Patients: Participants were 21 premenopausal women with unexplained fragility fractures or low BMD. Intervention: Teriparatide was administered at 20 μg daily for 18 to 24 months. Main Outcome Measures: The primary endpoint was within-subject percent change in lumbar spine BMD. Secondary endpoints included percent change in hip and forearm BMD, transiliac biopsy parameters (trabecular bone volume, microarchitecture, stiffness, and adipocytes), serum N-terminal propeptide of procollagen type 1 (P1NP), and C-telopeptide. Results: BMD increased at the spine (10.8 ± 8.3% [SD])...
-
central qct reveals lower volumetric bmd and stiffness in premenopausal women with Idiopathic Osteoporosis regardless of fracture history
The Journal of Clinical Endocrinology and Metabolism, 2012Co-Authors: Adi Cohen, David W. Dempster, Donald J Mcmahon, Emily M Stein, Polly Young, Edward X Guo, Sherry X Liu, Thomas Lang, Chiyuan Zhang, Isra SaeedAbstract:Context: Idiopathic Osteoporosis (IOP) affects otherwise healthy young individuals with intact gonadal function and no secondary cause of bone fragility. In premenopausal women with IOP, a low trauma fracture is evidence of impaired bone quality and strength. The extent to which low bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) reflects low volumetric BMD, bone microstructure, and strength is uncertain in the absence of low trauma fracture. Objective:Theobjectiveofthestudywastocomparethree-dimensionalvolumetricBMDandbone stiffness in premenopausal women with IOP based on fracture history, those with Idiopathic low BMD (Z score 2.0) and no low trauma fracture, and normal age-matched controls. Design: We measured volumetric BMD and bone geometry by central quantitative computed tomography (cQCT) scans of the spine and hip and estimated bone stiffness by finite element analysis of cQCT data sets in 32 premenopausal women with IOP, 12 with Idiopathic low BMD, and 34 controls. Results:Subjects had comparable decreases in total and trabecular volumetric BMD, cortical thickness, and whole-bone stiffness compared with controls, regardless of fracture history. These differences remained significant after controlling for age, body mass index, and bone size. The positive predictive values of a DXA Z score of 2.0 or less for a cQCT volumetric BMD Z score of 2.0 or less were 95% at the lumbar spine, 90% at the total hip, and 86% at the femoral neck. Conclusion: Women with Idiopathic low BMD alone and those with low trauma fractures had comparable deficits in bone mass, structure, and stiffness. Low areal BMD by DXA is fairly accurate for predicting low volumetric BMD by cQCT. These results are consistent with three-dimensional bone imaging at the iliac crest, radius, and tibia in premenopausal IOP and suggest that the term Osteoporosis may be appropriate in women with Z scores below 2.0, whether or not there is a history of fracture. (J Clin Endocrinol Metab 97: 4244–4252, 2012)
-
increased marrow adiposity in premenopausal women with Idiopathic Osteoporosis
The Journal of Clinical Endocrinology and Metabolism, 2012Co-Authors: Adi Cohen, David W. Dempster, Hua Zhou, Thomas L Nickolas, Ralph Muller, Donald J Mcmahon, Emily M Stein, Thomas Kohler, Alexander Zwahlen, Joan M. LappeAbstract:Context: We have previously reported that premenopausal women with Idiopathic Osteoporosis based on fractures (IOP) or Idiopathic low bone mineral density (ILBMD) exhibit markedly reduced bone mass, profoundly abnormal trabecular microstructure, and significant deficits in trabecular bone stiffness. Bone remodeling was heterogeneous. Those with low bone turnover had evidence of osteoblast dysfunction and the most marked deficits in microstructure and stiffness. Objective: Because osteoblasts and marrow adipocytes derive from a common mesenchymal precursor and excess marrow fat has been implicated in the pathogenesis of bone fragility in anorexia nervosa, glucocorticoid excess, and thiazolidinedione exposure, we hypothesized that marrow adiposity would be higher in affected women and inversely related to bone mass, microarchitecture, bone formation rate, and osteoblast number. Design: We analyzed tetracycline-labeled transiliac biopsy specimens in 64 premenopausal women with IOP or ILBMD and 40 controls by...
David W. Dempster - One of the best experts on this subject based on the ideXlab platform.
-
effect of teriparatide on bone remodeling and density in premenopausal Idiopathic Osteoporosis a phase ii trial
The Journal of Clinical Endocrinology and Metabolism, 2020Co-Authors: Adi Cohen, Robert R. Recker, Joan M. Lappe, David W. Dempster, Hua Zhou, Stephanie Shiau, Nandini Nair, Thomas L Nickolas, Sanchita Agarwal, Mafo KamandakossehAbstract:Context Premenopausal women with Idiopathic Osteoporosis (IOP) have abnormal skeletal microarchitecture and variable tissue-level bone formation rate (BFR). Objectives Compare 6 months (M) of teriparatide versus placebo on areal bone mineral density (aBMD) by dual-energy x-ray absorptiometry (DXA), bone turnover markers (BTMs) and BFR at 3M by quadruple-labeled transiliac biopsy. Characterize 12M and 24M effects of teriparatide on aBMD and whether BTMs and BFR predict response. Design 6M phase 2 randomized controlled trial (RCT) followed by open extension. Setting Tertiary referral centers. Patients Premenopausal women with IOP. Interventions A total of 41 women were randomized to either teriparatide 20 mcg (n = 28) or placebo (n = 13). After 6M, those on placebo switched to teriparatide for 24M; those on teriparatide continued for 18M. Main outcome measures 6M RCT: Between-group differences in lumbar spine (LS) aBMD (percent change from baseline), 3M BFR, and hypercalcemia. Open-label extension: Within-group change in LS aBMD over 12M and 24M. Secondary outcomes included aBMD change at other sites and relationship between BTMs, BFR, and changes in aBMD. Findings Over 6M, LS aBMD increased by 5.5% (95% CI: 3.83, 7.19) in teriparatide and 1.5% (95% CI: -0.73, 3.83) in placebo (P = 0.007). There were increases in 3M BTMs, and BFR (cancellous and endocortical BFR: between-groups P = 0.004). Over 24M, teriparatide increased LS aBMD by 13.2% (95% CI: 10.3, 16.2), total hip by 5.2% (95% CI: 3.7, 6.7) and femoral neck by 5.0% (95% CI: 3.2, 6.7; all P ≤ 0.001). Serum N-terminal propeptides of procollagen type 1 (P1NP) and 3M endocortical BFR were moderately associated with LS aBMD response. Teriparatide was well-tolerated. Conclusions Teriparatide increased BFR and formation markers and was associated with marked aBMD improvements in most premenopausal women (82%) with IOP.
-
women with pregnancy and lactation associated Osteoporosis plo have low bone remodeling rates at the tissue level
Journal of Bone and Mineral Research, 2019Co-Authors: Adi Cohen, David W. Dempster, Hua Zhou, Mariana Bucovsky, Julie Stubby, Mafo Kamandakosseh, Ralph Muller, Elliott Goff, Ivelisse Colon, Thomas L NickolasAbstract:Pregnancy and lactation-associated Osteoporosis (PLO) is a rare, severe, early form of Osteoporosis in which young women present with fractures, usually multiple vertebral fractures, during late pregnancy or lactation. In studies of Idiopathic Osteoporosis (IOP) in premenopausal women, we enrolled 78 women with low-trauma fractures and 40 healthy controls, all with normal menses and no secondary cause of bone loss. In 15 of the affected women, the PLO subgroup, fractures had occurred during late pregnancy or lactation. We hypothesized that clinical, bone structural, and metabolic characteristics would differ between women with PLO and those with (non-PLO) IOP and controls. All were evaluated > 12 months postpartum, when structural and remodeling characteristics would be expected to reflect baseline premenopausal status rather than transient postpartum changes. As previously reported, affected subjects (PLO and IOP) had BMD and microarchitectural deficiencies compared to controls. Women with PLO did not differ from those with IOP in terms of age, BMI, body fat, menarcheal age, parity, or age at first pregnancy. However, women with PLO had a more severe clinical presentation than those with IOP: more fractures (5.5 ± 3.3 versus 2.6 ± 2.1; p = 0.005); more vertebral fractures (80% versus 17%; p < 0.001); and higher prevalence of multiple fractures. BMD deficits were more profound and cortical width tended to be lower in PLO. PLO subjects also had significantly lower tissue-level mineral apposition rate and bone formation rates (0.005 ± 0.005 versus 0.011 ± 0.010 mm2 /mm/year; p = 0.006), as well as lower serum P1NP (33 ± 12 versus 44 ± 18 µg/L; p = 0.02) and CTX (257 ± 102 versus 355 ± 193 pg/mL; p = 0.01) than IOP. The finding that women with PLO have a low bone remodeling state assessed more than a year postpartum increases our understanding of the pathogenic mechanism of PLO. We conclude that women with PLO may have underlying osteoblast functional deficits which could affect their therapeutic response to osteoanabolic medications. © 2019 American Society for Bone and Mineral Research.
-
igf 1 receptor expression on circulating osteoblast progenitor cells predicts tissue based bone formation rate and response to teriparatide in premenopausal women with Idiopathic Osteoporosis
Journal of Bone and Mineral Research, 2017Co-Authors: Adi Cohen, Robert R. Recker, Joan M. Lappe, David W. Dempster, Hua Zhou, Stavroula Kousteni, Brygida Bisikirska, Jayesh Shah, Sanil J Manavalan, Donald J McmahonAbstract: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 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. While neither baseline %COP nor increase in %COP after three months predicted the 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. This article is protected by copyright. All rights reserved
-
igf 1 receptor expression on circulating osteoblast progenitor cells predicts tissue based bone formation rate and response to teriparatide in premenopausal women with Idiopathic Osteoporosis
Journal of Bone and Mineral Research, 2017Co-Authors: Adi Cohen, Robert R. Recker, Joan M. Lappe, David W. Dempster, Hua Zhou, Stavroula Kousteni, Brygida Bisikirska, Jayesh Shah, Sanil J Manavalan, Donald J McmahonAbstract: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.
-
Bone Density After Teriparatide Discontinuation in Premenopausal Idiopathic Osteoporosis
The Journal of clinical endocrinology and metabolism, 2015Co-Authors: Adi Cohen, Mafo Kamanda-kosseh, Robert R. Recker, Joan M. Lappe, David W. Dempster, Hua Zhou, Serge Cremers, Mariana Bucovsky, Julie Stubby, Elizabeth ShaneAbstract:Context: 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. Objective: 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. Design: 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. Participants: 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 an...
Hua Zhou - One of the best experts on this subject based on the ideXlab platform.
-
effect of teriparatide on bone remodeling and density in premenopausal Idiopathic Osteoporosis a phase ii trial
The Journal of Clinical Endocrinology and Metabolism, 2020Co-Authors: Adi Cohen, Robert R. Recker, Joan M. Lappe, David W. Dempster, Hua Zhou, Stephanie Shiau, Nandini Nair, Thomas L Nickolas, Sanchita Agarwal, Mafo KamandakossehAbstract:Context Premenopausal women with Idiopathic Osteoporosis (IOP) have abnormal skeletal microarchitecture and variable tissue-level bone formation rate (BFR). Objectives Compare 6 months (M) of teriparatide versus placebo on areal bone mineral density (aBMD) by dual-energy x-ray absorptiometry (DXA), bone turnover markers (BTMs) and BFR at 3M by quadruple-labeled transiliac biopsy. Characterize 12M and 24M effects of teriparatide on aBMD and whether BTMs and BFR predict response. Design 6M phase 2 randomized controlled trial (RCT) followed by open extension. Setting Tertiary referral centers. Patients Premenopausal women with IOP. Interventions A total of 41 women were randomized to either teriparatide 20 mcg (n = 28) or placebo (n = 13). After 6M, those on placebo switched to teriparatide for 24M; those on teriparatide continued for 18M. Main outcome measures 6M RCT: Between-group differences in lumbar spine (LS) aBMD (percent change from baseline), 3M BFR, and hypercalcemia. Open-label extension: Within-group change in LS aBMD over 12M and 24M. Secondary outcomes included aBMD change at other sites and relationship between BTMs, BFR, and changes in aBMD. Findings Over 6M, LS aBMD increased by 5.5% (95% CI: 3.83, 7.19) in teriparatide and 1.5% (95% CI: -0.73, 3.83) in placebo (P = 0.007). There were increases in 3M BTMs, and BFR (cancellous and endocortical BFR: between-groups P = 0.004). Over 24M, teriparatide increased LS aBMD by 13.2% (95% CI: 10.3, 16.2), total hip by 5.2% (95% CI: 3.7, 6.7) and femoral neck by 5.0% (95% CI: 3.2, 6.7; all P ≤ 0.001). Serum N-terminal propeptides of procollagen type 1 (P1NP) and 3M endocortical BFR were moderately associated with LS aBMD response. Teriparatide was well-tolerated. Conclusions Teriparatide increased BFR and formation markers and was associated with marked aBMD improvements in most premenopausal women (82%) with IOP.
-
women with pregnancy and lactation associated Osteoporosis plo have low bone remodeling rates at the tissue level
Journal of Bone and Mineral Research, 2019Co-Authors: Adi Cohen, David W. Dempster, Hua Zhou, Mariana Bucovsky, Julie Stubby, Mafo Kamandakosseh, Ralph Muller, Elliott Goff, Ivelisse Colon, Thomas L NickolasAbstract:Pregnancy and lactation-associated Osteoporosis (PLO) is a rare, severe, early form of Osteoporosis in which young women present with fractures, usually multiple vertebral fractures, during late pregnancy or lactation. In studies of Idiopathic Osteoporosis (IOP) in premenopausal women, we enrolled 78 women with low-trauma fractures and 40 healthy controls, all with normal menses and no secondary cause of bone loss. In 15 of the affected women, the PLO subgroup, fractures had occurred during late pregnancy or lactation. We hypothesized that clinical, bone structural, and metabolic characteristics would differ between women with PLO and those with (non-PLO) IOP and controls. All were evaluated > 12 months postpartum, when structural and remodeling characteristics would be expected to reflect baseline premenopausal status rather than transient postpartum changes. As previously reported, affected subjects (PLO and IOP) had BMD and microarchitectural deficiencies compared to controls. Women with PLO did not differ from those with IOP in terms of age, BMI, body fat, menarcheal age, parity, or age at first pregnancy. However, women with PLO had a more severe clinical presentation than those with IOP: more fractures (5.5 ± 3.3 versus 2.6 ± 2.1; p = 0.005); more vertebral fractures (80% versus 17%; p < 0.001); and higher prevalence of multiple fractures. BMD deficits were more profound and cortical width tended to be lower in PLO. PLO subjects also had significantly lower tissue-level mineral apposition rate and bone formation rates (0.005 ± 0.005 versus 0.011 ± 0.010 mm2 /mm/year; p = 0.006), as well as lower serum P1NP (33 ± 12 versus 44 ± 18 µg/L; p = 0.02) and CTX (257 ± 102 versus 355 ± 193 pg/mL; p = 0.01) than IOP. The finding that women with PLO have a low bone remodeling state assessed more than a year postpartum increases our understanding of the pathogenic mechanism of PLO. We conclude that women with PLO may have underlying osteoblast functional deficits which could affect their therapeutic response to osteoanabolic medications. © 2019 American Society for Bone and Mineral Research.
-
igf 1 receptor expression on circulating osteoblast progenitor cells predicts tissue based bone formation rate and response to teriparatide in premenopausal women with Idiopathic Osteoporosis
Journal of Bone and Mineral Research, 2017Co-Authors: Adi Cohen, Robert R. Recker, Joan M. Lappe, David W. Dempster, Hua Zhou, Stavroula Kousteni, Brygida Bisikirska, Jayesh Shah, Sanil J Manavalan, Donald J McmahonAbstract: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 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. While neither baseline %COP nor increase in %COP after three months predicted the 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. This article is protected by copyright. All rights reserved
-
igf 1 receptor expression on circulating osteoblast progenitor cells predicts tissue based bone formation rate and response to teriparatide in premenopausal women with Idiopathic Osteoporosis
Journal of Bone and Mineral Research, 2017Co-Authors: Adi Cohen, Robert R. Recker, Joan M. Lappe, David W. Dempster, Hua Zhou, Stavroula Kousteni, Brygida Bisikirska, Jayesh Shah, Sanil J Manavalan, Donald J McmahonAbstract: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.
-
Bone Density After Teriparatide Discontinuation in Premenopausal Idiopathic Osteoporosis
The Journal of clinical endocrinology and metabolism, 2015Co-Authors: Adi Cohen, Mafo Kamanda-kosseh, Robert R. Recker, Joan M. Lappe, David W. Dempster, Hua Zhou, Serge Cremers, Mariana Bucovsky, Julie Stubby, Elizabeth ShaneAbstract:Context: 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. Objective: 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. Design: 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. Participants: 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 an...
Joan M. Lappe - One of the best experts on this subject based on the ideXlab platform.
-
effect of teriparatide on bone remodeling and density in premenopausal Idiopathic Osteoporosis a phase ii trial
The Journal of Clinical Endocrinology and Metabolism, 2020Co-Authors: Adi Cohen, Robert R. Recker, Joan M. Lappe, David W. Dempster, Hua Zhou, Stephanie Shiau, Nandini Nair, Thomas L Nickolas, Sanchita Agarwal, Mafo KamandakossehAbstract:Context Premenopausal women with Idiopathic Osteoporosis (IOP) have abnormal skeletal microarchitecture and variable tissue-level bone formation rate (BFR). Objectives Compare 6 months (M) of teriparatide versus placebo on areal bone mineral density (aBMD) by dual-energy x-ray absorptiometry (DXA), bone turnover markers (BTMs) and BFR at 3M by quadruple-labeled transiliac biopsy. Characterize 12M and 24M effects of teriparatide on aBMD and whether BTMs and BFR predict response. Design 6M phase 2 randomized controlled trial (RCT) followed by open extension. Setting Tertiary referral centers. Patients Premenopausal women with IOP. Interventions A total of 41 women were randomized to either teriparatide 20 mcg (n = 28) or placebo (n = 13). After 6M, those on placebo switched to teriparatide for 24M; those on teriparatide continued for 18M. Main outcome measures 6M RCT: Between-group differences in lumbar spine (LS) aBMD (percent change from baseline), 3M BFR, and hypercalcemia. Open-label extension: Within-group change in LS aBMD over 12M and 24M. Secondary outcomes included aBMD change at other sites and relationship between BTMs, BFR, and changes in aBMD. Findings Over 6M, LS aBMD increased by 5.5% (95% CI: 3.83, 7.19) in teriparatide and 1.5% (95% CI: -0.73, 3.83) in placebo (P = 0.007). There were increases in 3M BTMs, and BFR (cancellous and endocortical BFR: between-groups P = 0.004). Over 24M, teriparatide increased LS aBMD by 13.2% (95% CI: 10.3, 16.2), total hip by 5.2% (95% CI: 3.7, 6.7) and femoral neck by 5.0% (95% CI: 3.2, 6.7; all P ≤ 0.001). Serum N-terminal propeptides of procollagen type 1 (P1NP) and 3M endocortical BFR were moderately associated with LS aBMD response. Teriparatide was well-tolerated. Conclusions Teriparatide increased BFR and formation markers and was associated with marked aBMD improvements in most premenopausal women (82%) with IOP.
-
igf 1 receptor expression on circulating osteoblast progenitor cells predicts tissue based bone formation rate and response to teriparatide in premenopausal women with Idiopathic Osteoporosis
Journal of Bone and Mineral Research, 2017Co-Authors: Adi Cohen, Robert R. Recker, Joan M. Lappe, David W. Dempster, Hua Zhou, Stavroula Kousteni, Brygida Bisikirska, Jayesh Shah, Sanil J Manavalan, Donald J McmahonAbstract: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 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. While neither baseline %COP nor increase in %COP after three months predicted the 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. This article is protected by copyright. All rights reserved
-
igf 1 receptor expression on circulating osteoblast progenitor cells predicts tissue based bone formation rate and response to teriparatide in premenopausal women with Idiopathic Osteoporosis
Journal of Bone and Mineral Research, 2017Co-Authors: Adi Cohen, Robert R. Recker, Joan M. Lappe, David W. Dempster, Hua Zhou, Stavroula Kousteni, Brygida Bisikirska, Jayesh Shah, Sanil J Manavalan, Donald J McmahonAbstract: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.
-
Bone Density After Teriparatide Discontinuation in Premenopausal Idiopathic Osteoporosis
The Journal of clinical endocrinology and metabolism, 2015Co-Authors: Adi Cohen, Mafo Kamanda-kosseh, Robert R. Recker, Joan M. Lappe, David W. Dempster, Hua Zhou, Serge Cremers, Mariana Bucovsky, Julie Stubby, Elizabeth ShaneAbstract:Context: 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. Objective: 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. Design: 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. Participants: 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 an...
-
teriparatide increases strength of the peripheral skeleton in premenopausal women with Idiopathic Osteoporosis a pilot hr pqct study
The Journal of Clinical Endocrinology and Metabolism, 2014Co-Authors: Kyle K Nishiyama, Adi Cohen, Robert R. Recker, Joan M. Lappe, David W. Dempster, Polly Young, Ji Wang, Edward X Guo, Elizabeth ShaneAbstract:Context: In premenopausal women with Idiopathic Osteoporosis (IOP), treatment with teriparatide leads to substantial improvement in bone density and quality at central skeletal sites. The effects of teriparatide may differ on cortical and trabecular bone and also at the central and the peripheral skeleton. Objective: The objective of the study was to determine whether teriparatide was associated with improvements in compartmental volumetric bone mineral density (BMD), bone microarchitecture, and estimated bone strength of the distal radius and tibia as assessed by high-resolution peripheral quantitative computed tomography. Design, Setting, and Participants: Premenopausal women (n = 20, age 41 ± 5 y) with IOP (low trauma fractures and/or Z-scores ≤ −2.0) were scanned with high-resolution peripheral quantitative computed tomography at baseline and after 18 months of teriparatide treatment. Cortical and trabecular volumetric BMD and microarchitecture were measured by both standard and advanced techniques, i...
