scholarly journals Effect Of Local Modulation In Enzymatic Homeostasis On Bone Turnover Marker Dynamics In Blood At Substituting Femur Defects With Vaterite Scaffolds

2020 ◽  
Vol 9 (4) ◽  
Author(s):  
Aleksey N. Ivanov ◽  
Yuliya A. Chibrikova ◽  
Mariia S. Saveleva ◽  
Vladimir V. Ostrovskij ◽  
Igor A. Norkin

The goal of this research was the investigation of concentration changes in the blood bone turnover markers during local modulation of enzymatic homeostasis by means of targeted delivery of alkaline phosphatase (ALP) with polycaprolactone (PCL) and vaterite (VT) scaffolds implanted into the femur defects in white rats. Material and Methods ― The tests of PCL/VT/ALP scaffold implantations into the bone defects were performed on 30 white rats, and the serum of intact animals was used as the control. ELISA and multiplex assay were used to find inflammatory and bone turnover markers including monocyte chemoattractant-1, sclerostin, fibroblast growth factor-23, connective tissue growth factor (CTGF), osteoprotegerin, osteocalcin, β-сross laps and the activity of tartrate-resistant acid phosphatase-5b in the blood of experimental animals. The activity of serum ALP was tested with the conventional kinetic method. The morphology of the reparative processes was verified by microscopy of specimens taken from the implantation areas and stained with hematoxylin or eosin. Results ― The PCL/VT/ALP scaffold implantations into the bone defects of white rats caused active osteogenesis along with the steady rise in osteocalcin concentration in blood. ALP activity in the blood did not depend on the exogenous enzyme in the scaffold and rose by the 28th day after the implantations. The targeted ALP delivery into the defect area caused the rise in CTGF concentration as well as the decrease in blood sclerostin within a short time after the implantations. Conclusion ― The modulation of the local enzyme homeostasis by means of the targeted ALP delivery with PCL/VT scaffolds stimulated reparative osteogenesis within a short time after the implantations with no changes to the bloodstream or local inflammatory changes suggesting their biocompatibility and the safety in use.

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.


Hepatology ◽  
1998 ◽  
Vol 28 (3) ◽  
pp. 695-699 ◽  
Author(s):  
Francisco J. Gallego-Rojo ◽  
Jorge L. Gonzalez-Calvin ◽  
Manuel Muñoz-Torres ◽  
Jose L. Mundi ◽  
Ramon Fernandez-Perez ◽  
...  

2019 ◽  
Vol 13 (1) ◽  
pp. 75-84 ◽  
Author(s):  
Myles Wolf ◽  
Geoffrey A Block ◽  
Glenn M Chertow ◽  
Kerry Cooper ◽  
Bruno Fouqueray ◽  
...  

Abstract Background Etelcalcetide is an intravenous calcimimetic approved for treatment of secondary hyperparathyroidism (sHPT) in patients receiving hemodialysis. Besides lowering parathyroid hormone (PTH), etelcalcetide also significantly reduces fibroblast growth factor 23 (FGF23), but the mechanisms are unknown. Methods To investigate potential mediators of etelcalcetide-induced FGF23 reduction, we performed secondary analyses of the 26-week randomized trials that compared the effects on PTH of etelcalcetide (n = 509) versus placebo (n = 514) and etelcalcetide (n = 340) versus cinacalcet (n = 343) in adults with sHPT receiving hemodialysis. We analyzed changes in FGF23 in relation to changes in PTH, calcium, phosphate and bone turnover markers. We also investigated how concomitant treatments aimed at mitigating hypocalcemia altered the FGF23-lowering effects of etelcalcetide. Results Etelcalcetide reduced FGF23 [median % change (quartile 1–quartile 3)] from baseline to the end of the trial significantly more than placebo [–56% (–85 to –7) versus +2% (–40 to +65); P &lt; 0.001] and cinacalcet [–68% (–87 to –26) versus –41% (–76 to +25); P &lt; 0.001]. Reductions in FGF23 correlated strongly with reductions in calcium and phosphate, but not with PTH; correlations with bone turnover markers were inconsistent and of borderline significance. Increases in concomitant vitamin D administration partially attenuated the FGF23-lowering effect of etelcalcetide, but increased dialysate calcium concentration versus no increase and increased dose of calcium supplementation versus no increase did not attenuate the FGF23-lowering effects of etelcalcetide. Conclusion These data suggest that etelcalcetide potently lowers FGF23 in patients with sHPT receiving hemodialysis and that the effect remains detectable among patients who receive concomitant treatments aimed at mitigating treatment-associated decreases in serum calcium.


Bone ◽  
2013 ◽  
Vol 56 (1) ◽  
pp. 184-190 ◽  
Author(s):  
Inga Niemann ◽  
Anke Hannemann ◽  
Matthias Nauck ◽  
Christin Spielhagen ◽  
Henry Völzke ◽  
...  

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