The letrozole (L), exemestane (E), and anastrozole (A) pharmacodynamics (LEAP) trial: A direct comparison of bone biochemical measurements between aromatase inhibitors (AIs) in healthy postmenopausal women

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 555-555 ◽  
Author(s):  
E. McCloskey ◽  
R. Hannon ◽  
G. Lakner ◽  
G. Clack ◽  
A. Miyamoto ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Turnover ◽  
Postmenopausal Women ◽  
Bone Mineral ◽  
Smoking Status ◽  
Type I ◽  
Mineral Density ◽  
High Turnover ◽  
Normal Bone Mineral Density ◽  
Biochemical Measurements

555 Background: The LEAP trial is an open, randomized, multicenter, Phase I pharmacodynamic study comparing the effects of the AIs L, E and A on safety parameters, such as serum markers of bone formation and resorption, lipid profiles, and adrenal function in healthy postmenopausal women with normal bone mineral density at the spine and hip. Elevated bone biochemical levels indicate high turnover of bone, and correlate with a loss in bone mineral density. It has been suggested that there are differences between the effect of the steroidal AIs (E) and non-steroidal AIs (A and L) on bone turnover, with steroidal AIs having a less negative effect. Methods: Healthy volunteersfrom the UK and Hungarywere randomized to receive A (1 mg/day), L (2.5 mg/day), or E (25 mg/day) orally, once daily for 24 weeks. Changes from baseline in log-transformed bone alkaline phosphatase (ALP), serum C-telopeptide crosslinks (CTX), parathyroid hormone (PTH) and propeptide of type I procollagen (PINP) at 24 weeks on A, were compared with those on L and E by ANCOVA, adjusting for treatment, baseline measurement, BMI, smoking status and baseline estradiol. No adjustments were made for multiple comparisons. Results: A total of 102 healthy volunteers were recruited, with 90 participants evaluable at 24 weeks (29 A, 29 L, 32 E). Participant demographics were similar between the treatment groups in terms of age, years since menopause, and history of hysterectomy and oophorectomy. Bone biochemical measurement changes are presented in the table . With the exception of PTH, where there is a greater decrease in PTH with E than with A (p=0.04), there were no statistically significant differences between the AIs. Conclusions: The steroidal and non-steroidal AIs appear to have similar effects on bone biochemical measurements, and thus bone turnover. All three licensed AIs result in increases in bone turnover. [Table: see text] [Table: see text]

scholarly journals Genetic polymorphisms and their influence on therapeutic response to alendronate-a pilot study

2019 ◽  
Vol 10 (Vol.10, No.3) ◽  
pp. 243-251
Author(s):  
Alina Deniza CIUBEAN ◽  
Laszlo IRSAY ◽  
Rodica Ana UNGUR ◽  
Viorela Mihaela CIORTEA ◽  
Ileana Monica BORDA ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Lumbar Spine ◽  
Bone Turnover ◽  
Postmenopausal Women ◽  
Bone Mineral ◽  
Bone Turnover Markers ◽  
Type I Collagen ◽  
Type I ◽  
Mineral Density ◽  
Turnover Markers

Introduction: Osteoporosis has a strong genetic contribution, and several genes have been shown to influence bone mineral density. Variants in the human genome are considered important causes of differences in drug responses observed in clinical practice. In terms of bone mineral density, about 26–53% of patients do not respond to amino-bisphosphonate therapies, of which alendronate is the most widely used. Material and method: The current study is prospective, observational, analytical, longitudinal and cohort type. It included 25 postmenopausal women treated with alendronate for 1 year. Bone mineral density at lumbar spine and proximal femur was measured and bone turnover markers (C-terminal telopeptide of type I collagen and procollagen 1N-terminal propeptide) were evaluated at 0 and 12 months of treatment. Six single nucleotide polymorphisms in osteoporosis-candidate genes were genotyped (FDPS rs2297480, LRP5 rs3736228, SOST rs1234612, VKORC1 rs9934438, GGPS1 rs10925503 and RANKL rs2277439). Treatment response was evaluated by percentage changes in bone mineral density and bone turnover markers. Results: The heterozygous CT of FDPS rs2297480 showed lower increases in BMD values in the lumbar spine region and the homozygous CC of the GGPS1 rs10925503 showed lower increases in terms of BMD at the total hip region. No association was found for LRP5 rs3736228, SOST rs1234612, VKORC1 rs9934438 and RANKL rs2277439. Conclusions: Romanian postmenopausal women with osteoporosis carrying the CT genotype of FDPS rs2297480 or the CC genotype of GGPS1 rs10925503 could have an unsatisfactory response to alendronate treatment. Key words: osteoporosis; genetic polymorphism; alendronate; bone mineral density; bone turnover markers,

scholarly journals Establishing Reference Intervals for Bone Turnover Markers in the Healthy Shanghai Population and the Relationship with Bone Mineral Density in Postmenopausal Women

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Wei-Wei Hu ◽  
Zeng Zhang ◽  
Jin-Wei He ◽  
Wen-Zhen Fu ◽  
Chun Wang ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Turnover ◽  
Postmenopausal Women ◽  
Bone Mineral ◽  
Bone Turnover Markers ◽  
Reference Intervals ◽  
Type I ◽  
Reference Ranges ◽  
Mineral Density ◽  
Turnover Markers

The reference ranges of bone turnover markers (BTMs) were important during the treatment of osteoporosis, and the associations with bone mineral density (BMD) were controversial. The aim of this study was to establish the reference ranges of N-terminal procollagen of type l collagen (P1NP), osteocalcin (OC), and beta C-terminal cross-linked telopeptides of type I collagen (β-CTX) in Shanghai area and to investigate the relationships between BTMs and BMD in postmenopausal women. 2,799 subjects recruited in Shanghai City were measured BTMs to establish the reference ranges. Additional 520 healthy postmenopausal women were also measured BTMs, these women measured BMD in addition. BTMs were measured using the Roche electrochemiluminescence system. We used the age range of 35 to 45-year-olds to calculate reference intervals. The reference range of OC was 4.91 to 13.90 ng/mL for women and 5.58 to 16.57 ng/mL for men, P1NP was 13.72 to 32.90 ng/mL for women and 16.89 to 42.43 ng/mL for men, andβ-CTX was 0.112 to 0.210 ng/mL for women and 0.100 to 0.378 ng/mL for men. BTMs significantly negatively correlated with lumbar spine and femoral and total hip in postmenopausal women ( = −0.157~−0.217,P< 0.001). We established the normal reference ranges of P1NP, OC, andβ-CTX in the Shanghai area. This study also found that BTMs correlated with BMD and suggested that BTMs were the key determining factors of early BMD decreases.

scholarly journals FSHR gene polymorphisms influence bone mineral density and bone turnover in postmenopausal women

2010 ◽  
Vol 163 (1) ◽  
pp. 165-172 ◽  
Author(s):  
Domenico Rendina ◽  
Fernando Gianfrancesco ◽  
Gianpaolo De Filippo ◽  
Daniela Merlotti ◽  
Teresa Esposito ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Turnover ◽  
Postmenopausal Women ◽  
Bone Mineral ◽  
Bone Turnover Markers ◽  
Type I ◽  
Bone Homeostasis ◽  
Mineral Density ◽  
Turnover Markers ◽  
Circulating Levels

ObjectiveFSH, via its receptor (FSHR), influences bone remodeling and osteoclast proliferation and activity. The aim of this study was to evaluate the influence of two single nucleotide polymorphisms (SNPs) of theFSHRgene on bone mineral density (BMD) and bone turnover markers (bone alkaline phosphatase and type I collagen C-telopeptides) in postmenopausal women.MethodsTwo hundred and eighty-nine unrelated postmenopausal women were genotyped for the SNPs rs1394205 and rs6166. BMD was estimated using dual-energy X-ray absorptiometry and quantitative ultrasound (QUS) methodologies.ResultsAA rs6166 women showed a lower BMD (femoral neck and total body), lower stiffness index (calcaneal QUS), and higher serum levels of bone turnover markers compared to GG rs6166 women. The prevalence of osteoporosis was significantly higher in AA rs6166 women compared with GG rs6166 women. These results were not influenced by circulating levels of FSH and estrogens.ConclusionThe SNP rs6166 of theFSHRgene significantly influences BMD in postmenopausal women. In particular, AA rs6166 women are at increased risk of postmenopausal osteoporosis compared with GG rs6166 women, independently of circulating levels of FSH and estrogens. Previous studies have demonstrated that this SNP influences cell and tissue response to hyperstimulation of FSHRin vivoandin vitro. Our study results appear in agreement with these experimental data and with known biological actions of FSH/FSHR system in bone homeostasis.

scholarly journals Effect of Denosumab on Bone Mineral Density and Markers of Bone Turnover among Postmenopausal Women with Osteoporosis

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
A. Sánchez ◽  
L. R. Brun ◽  
H. Salerni ◽  
P. R. Costanzo ◽  
D. González ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Turnover ◽  
Postmenopausal Women ◽  
Bone Mineral ◽  
Bone Turnover Markers ◽  
Control Group ◽  
Bone Resorption Marker ◽  
Similar Response ◽  
Mineral Density ◽  
Turnover Markers

The aim of this study was to evaluate the effect of denosumab (Dmab) on bone mineral density (BMD) and bone turnover markers after 1 year of treatment. Additionally, the effect of Dmab in bisphosphonate-naïve patients (BP-naïve) compared to patients previously treated with bisphosphonates (BP-prior) was analyzed. This retrospective study included 425 postmenopausal women treated with Dmab for 1 year in clinical practice conditions in specialized centers from Argentina. Participants were also divided according to previous bisphosphonate treatment into BP-naïve and BP-prior. A control group of patients treated with BP not switched to Dmab matched by sex, age, and body mass index was used. Data are expressed as mean ± SEM. After 1 year of treatment with Dmab the bone formation markers total alkaline phosphatase and osteocalcin were significantly decreased (23.36% and 43.97%, resp.), as was the bone resorption marker s-CTX (69.61%). Significant increases in BMD were observed at the lumbar spine, femoral neck, and total hip without differences between BP-naïve and BP-prior. A better BMD response was found in BP-prior group compared with BP treated patients not switched to Dmab.Conclusion. Dmab treatment increased BMD and decreased bone turnover markers in the whole group, with similar response in BP-naïve and BP-prior patients. A better BMD response in BP-prior patients versus BP treated patients not switched to Dmab was observed.

scholarly journals Bone Turnover and Bone Mineral Density Are Independently Related to Selenium Status in Healthy Euthyroid Postmenopausal Women

2012 ◽  
Vol 97 (11) ◽  
pp. 4061-4070 ◽  
Author(s):  
Antonia Hoeg ◽  
Apostolos Gogakos ◽  
Elaine Murphy ◽  
Sandra Mueller ◽  
Josef Köhrle ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Turnover ◽  
Postmenopausal Women ◽  
Bone Mineral ◽  
Selenoprotein P ◽  
Selenium Status ◽  
Mineral Density ◽  
Thyroid Status ◽  
Hip Bmd

Context: Selenium status may have direct effects on bone and indirect effects through changes in thyroid hormone sensitivity. Objective: We hypothesized that variation in selenium status in healthy euthyroid postmenopausal women is associated with differences in bone turnover, bone mineral density (BMD) and fracture susceptibility. Design: The Osteoporosis and Ultrasound Study (OPUS) is a 6-yr prospective study of fracture-related factors. Setting: The study was comprised of a population-based cohort from five European cities. Participants: A total of 2374 postmenopausal women participated. Subjects with thyroid disease and nonthyroidal illness and those receiving drugs affecting thyroid status or bone metabolism were excluded, leaving a study population of 1144. Interventions: There were no interventions. Main Outcome Measures: We measured selenium (micrograms per liter); selenoprotein P (milligrams per liter); free T4 (picomoles per liter); free T3 (picomoles per liter); TSH (milliunits per liter); bone turnover markers; BMD; and vertebral, hip, and nonvertebral fractures. Results: Higher selenium levels were associated with higher hip BMD at study entry (β = 0.072, P = 0.004) and lower levels of bone formation (osteocalcin: β = −0.101, P &lt; 0.001; procollagen type 1 N-terminal propeptide: β = −0.074, P = 0.013) and resorption markers (C-telopeptide of type 1 collagen: β = −0.058, P = 0.050; N-telopeptide of type 1 collagen: β = −0.095, P = 0.002). Higher selenoprotein P was associated with higher hip (β = 0.113, P &lt; 0.001) and lumbar spine BMD (β = 0.088, P = 0.003) at study entry, higher hip BMD after the 6-yr follow-up (β = 0.106, P = 0.001) and lower osteocalcin (β = −0.077, P = 0.009), C-telopeptide of type 1 collagen (β = −0.075, P = 0.012), and N-telopeptide of type 1 collagen (β = −0.110, P &lt; 0.001). Conclusion: Selenium status is inversely related to bone turnover and positively correlated with BMD in healthy euthyroid postmenopausal women independent of thyroid status.

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