Bone turnover markers and pharmacokinetics of a new sustained-release formulation of the cathepsin K inhibitor, ONO-5334, in healthy post-menopausal women

2014 ◽  
Vol 33 (1) ◽  
pp. 93-100 ◽  
Author(s):  
Shinichi Nagase ◽  
Michiyo Ohyama ◽  
Yoshitaka Hashimoto ◽  
Maria Small ◽  
John Sharpe ◽  
...  
2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 556-556
Author(s):  
R. Aft ◽  
M. Naughton ◽  
K. Trinkuas ◽  
M. Watson ◽  
K. Weilbaecher

556 Background: Ovarian failure secondary to adjuvant chemotherapy is known to have an adverse effect on bone mineral density and to increase bone turnover markers. The effects of chemotherapy with growth factor support in the absence of hormonal changes have not been described. The impact of zoledronic acid on these changes was also explored. Methods: We evaluated bone turnover markers in 82 women undergoing neoadjuvant chemotherapy for localized stage II/III breast cancer at initial diagnosis prior to treatment and after 4 cycles of epirubicin (75mg/m2)-docetaxel (75mg/m2) with pegylated G-CSF support with or without zoledronic acid. 47% of patients were post-menopausal and all groups were balanced for other variables. Women were randomized to receive zoledronic acid 4 mg IV every 3 weeks concurrently with chemotherapy (n=41) versus no bisphosphonate treatment (n=41). Bone turnover markers included: urinary N-telopeptide (NTx), serum bone specific alkaline phosphatase (BAP)and osteocalcin (OSTEO). Results: Women, regardless of menopausal status, who received no bisphosphonate had statistically significant increases in NTx, from baseline after 3 months of neoadjuvant chemotherapy using multivariable mixed repeated measures (p=0.0213). Women who received zoledronic acid concurrently with neoadjuvant chemotherapy had statistically significant decreases in NTx (p<0.0001), BAP (p<0.0001) and OSTEO (p=0.0295) from baseline. This is the first demonstration that anthracycline-taxane chemotherapy with growth factor support increased bone turnover markers in both post-menopausal and pre-menopausal women independent of hormone therapy, radiation therapy and surgery. Conclusions: Neoadjuvant chemotherapy with anthracycline- taxane and growth factor support increased bone resorption markers in both post-menopausal and pre-menopausal women. Zoledronic acid given concurrently with each cycle of chemotherapy reversed this increase in bone turnover markers. No significant financial relationships to disclose.


2013 ◽  
Vol 115 (4) ◽  
pp. e12-e19 ◽  
Author(s):  
Emi Yamashita-Mikami ◽  
Mikako Tanaka ◽  
Naoki Sakurai ◽  
Yoshiaki Arai ◽  
Akira Matsuo ◽  
...  

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jarika Vatrasresth ◽  
Ammarin Suwan ◽  
Krasean Panyakhamlerd

Abstract Background Compared with a natural process, surgically induced menopausal women have a higher bone loss rate. This study aims to evaluate early treatment with estradiol valerate on bone turnover markers after surgically induced menopause. Methods This prospective study included 41 pre and perimenopausal women who underwent hysterectomy with oophorectomy for benign gynecologic conditions. Two weeks after the operation, all participants were assessed for menopausal hormone therapy (MHT) indications. Estrogen therapy was prescribed for those who had indications and accepted treatment (hormone treatment group). The others who had no MHT indication were allocated to the no-treatment group. Serum CTX and P1NP levels at preoperative and 12 weeks postoperative were measured and set as the primary outcome. Within the same group, serum CTX and P1NP before and after surgical menopause were analyzed using Wilcoxon signed-rank test. ANCOVA was used to compare serum CTX and P1NP at 12 weeks after surgical menopause between the two groups. Spearman's rank correlation coefficient analysis analyzed the correlation between age and baseline bone turnover markers. A p-value of < 0.05 was considered statistically significant. Results At 12 weeks after surgery, there were no significant differences in serum CTX and P1NP levels in the hormone treatment group compared to baseline. In contrast, serum CTX and P1NP levels were significantly elevated among women who did not receive hormone treatment (p-value < 0.001 and 0.002, respectively). Serum CTX and P1NP at 12 weeks were significantly different between the two groups (p-value < 0.001 and 0.004, respectively). Conclusion Early estrogen administration with oral estradiol valerate could significantly suppress the high bone remodeling in surgically induced menopausal women. Trial registration Thai Clinical Trial Registry identification number TCTR20190808004, retrospective registered since 2019-08-08. http://www.thaiclinicaltrials.org/show/TCTR20190808004.


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