Papers by S. Verberckmoes
Kidney International, 2005
Time-evolution and reversibility of strontium-induced osteomalacia in chronic renal failure rats.... more Time-evolution and reversibility of strontium-induced osteomalacia in chronic renal failure rats. Background. Patients with impaired renal function can accumulate strontium in the bone, which has been associated with the development of osteomalacia. A causal role for strontium in the development of the disease was presented in chronic renal failure (CRF) rats. Strontium-ranelate has been put forward as a therapeutic agent in the treatment of osteoporosis. Since the target population for strontium treatment consists mainly in postmenopausal osteoporotic women, who may have a reduced renal function, the risk for osteomalacia should be considered. Methods. To determine the time evolution and reversibility of the strontium-induced mineralization defect, CRF rats were loaded with strontium (2 g/L) (± 200 mg/kg/day) during 2, 6, and 12 weeks, followed by a washout period of 0, 2, 4, or 8 weeks. Results. Histologic examination of the bone of the animals treated with strontium revealed signs of osteomalacia already after 2 weeks. Animals that received strontium during 6 and 12 weeks had a significantly higher osteoid perimeter, area and thickness as compared to CRF controls. After 12 weeks, the mineralization was significantly affected, as evidenced by a lower double-labeled surface, mineral apposition and bone formation rate in combination with an increased osteoid maturation time and mineralization lag time. The osteoblast perimeter was significantly lower in the strontium-treated animals. After the washout periods, these effects were reversed and the bone lesions evolved to the values of CRF controls. This went along with an 18% reduction of the bone strontium content. A significant rise in serum alkaline phosphatase (ALP) activity was apparent in the strontium-treated animals as compared to CRF controls. This was not only due to higher levels of the bone ALP but also to those of the liver and the intestinal isoenzymes. Serum parathyroid hormone (PTH) levels decreased during strontium treatment. After cessation of the treatment, the serum ALP activity and PTH concentration reversed to control levels.
Journal of the American Society of Nephrology, 2010
Journal of Hypertension, 2011
Background and objective Whether treatment with vitamin D receptor activators contributes to card... more Background and objective Whether treatment with vitamin D receptor activators contributes to cardiovascular disease in patients with chronic kidney disease is a matter of debate. We studied mechanisms involved in vitamin Drelated vascular calcifications in vivo and in vitro. Methods Aortic calcifications were induced in subtotally nephrectomized (SNX) rats by treatment with a high dose (0.25 mg/kg per day) of 1,25-dihydroxyvitamin D 3 (calcitriol) given for 6 weeks. Likewise, primary rat vascular smooth muscle cells (VSMCs) were incubated with calcitriol at concentrations ranging from 10 S11 to 10 S7 mol/l. Immunohistochemistry revealed that the aortic expression of osteopontin, osteocalcin and bone sialoprotein was significantly increased in calcitriol-treated SNX rats compared to untreated SNX controls. In addition, aortic expression of the transient receptor potential vanilloid calcium channel 6 (TRPV6) and calbindin D9k was significantly up-regulated by treatment with calcitriol. Furthermore, calcitriol significantly increased expression of the osteogenic transcription factor osterix. In-vitro studies showed similar results, confirming that these effects could be attributed to treatment with calcitriol. Conclusions High-dose calcitriol treatment induces an osteoblastic phenotype in VSMC both in SNX rats and in vitro, associated with up-regulation of proteins regulating mineralization and calcium transport, and of the osteogenic transcription factor osterix.
Calcified Tissue International, 2004
In a previous experimental study using a chronic renal failure rat model, a dose-related multipha... more In a previous experimental study using a chronic renal failure rat model, a dose-related multiphasic effect of strontium (Sr) on bone formation was found that could be reproduced in an in vitro setup using primary rat osteoblasts. The results from the latter study allowed us to distinguish between a reduced nodule formation in the presence of an intact mineralization at low Sr-doses (1 lg/ml) and an interference of the element with the hydroxyapatite (HA) formation at high doses (20-100 lg/ml). To further investigate the latter effect of Sr on physicochemical bone mineral properties, an in vitro study was set up in which the UMR-106 rat osteosarcoma cell line was exposed to Sr, added to the cell culture medium in a concentration range varying between 0-100 lg/ml. Temporal growth and functionality of the culture was investigated by measurement of the alkaline phosphatase activity and calcium (Ca) concentration in the culture medium (used as an index of Ca-incorporation, i.e., HA formation) at various time points. At the end of the culture period (14 days post-confluence), samples of the mineralized cultures were taken for further analysis using X-ray diffraction (XRD) and Fourier Transform Infra-Red Spectroscopy (FTIR). Synthetic HA doped with various Sr concentrations (based on the cell culture and previous experimental studies and yielding Sr/(Sr+Ca) ratios ranging from 0-60%), was prepared and examined for crystal growth and solubility. Crystal size was assessed using scanning electron microscopy (SEM). Ca incorporation indicated a reduced mineralization in the 20 and 100 lg/ml Sr groups vs. controls. Sr-doped synthetic HA showed a significant dose-dependent reduction in crystal growth, as assessed by SEM, and an increase in solubility, apparent from 12.7% Sr/(Sr+Ca) on. Moreover, in both mineralized cultures and synthetic HA, XRD and FTIR analysis showed a reduced crystallinity and altered crystal lattice at similar concentrations. These new data support our previous in vivo and in vitro findings and point to a potential physicochemical interference of Sr with HA formation and crystal properties in vivo.
Bone, 2009
Background: The anti-fracture effects of ibandronate and other bisphosphonates were proven in sev... more Background: The anti-fracture effects of ibandronate and other bisphosphonates were proven in several large fracture outcome studies in postmenopausal osteoporosis. However, in clinical practice, the treatment effectiveness is dependent on long-term therapeutic adherence with oral bisphosphonates, which is often suboptimal. This is mainly caused by the complex and inconvenient dosing instructions, but could possibly be improved by larger dosing intervals. Patients and methods: This is a non-interventional study (NIS) of more than 12,000 patients with postmenopausal osteoporosis throughout Germany. Compliance, tolerability, therapeutic adherence and patient satisfaction with 150 mg once-monthly oral ibandronate were measured within the first 12 months of treatment. The compliance-effect relationship in reference to the incidence of osteoporotic fractures was examined. After 3 and 6 months of observation, additional data on patient satisfaction, user-friendliness and tolerability were obtained. Results: Complete data sets of more than 8000 patients were available. More than 90% of these patients were fully compliant after 12 months of treatment. From the physician's perspective, the patient satisfaction and tolerability after 6 months with once-monthly ibandronate were "very good" or "good" in more than 90% of their patients. User-friendliness was rated with "very good" or "good" for more than 95% of patients. Conclusion: Due to good tolerability, user-friendliness and patient satisfaction, treatment with once-monthly oral ibandronate demonstrates an optimal compliance in more than 90% of patients. As compared to analyses from U.S. databases in weekly administered oral bisphosphonates, 150 mg once-monthly oral ibandronate shows clearly a better persistence. How the improved compliance and persistence might influence anti-fracture effectiveness in clinical practice will be addressed in further analyses of this German noninterventional study.
X-Ray Spectrometry, 2007
X-RAY SPECTROMETRY X-Ray Spectrom. 2007; 36: 42–49 Published online 18 December 2006 in Wiley Int... more X-RAY SPECTROMETRY X-Ray Spectrom. 2007; 36: 42–49 Published online 18 December 2006 in Wiley InterScience (www.interscience.wiley.com) DOI: 10.1002/xrs.929 ... Strontium incorporates at sites critical for bone ... Line Oste,1† Steven C. Verberckmoes,1† Geert J. ...
Reproduction, Fertility and Development, 2004
The use of AI in the buffalo species is still marginal due to traditional lower conception rates ... more The use of AI in the buffalo species is still marginal due to traditional lower conception rates when compared to cattle. However recently a number of studies in this field have revealed a promising increase in the efficiency of synchronization protocols for AI linked to more acceptable pregnancy rates. The possibility of using lower spermatozoa concentration of high quality buffalo bulls for AI without reduction in pregnancy outcome can be an additional offset, especially if such spermatozoa can be sexed and used for better reproductive management in buffalo farms. Within this conceptual framework, a new artificial insemination device for semen deposition near the utero-tubal junction (UTJ) in cattle (Ghent device), developed at the University of Ghent (Belgium), has been used in this study. The Ghent device is made of disposable materials and consists of 2 hollow plastic tubes, wherein a catheter filled with semen is introduced. The outer tube is completely rigid, while the inner ...
Reproduction in Domestic Animals, 2005
At the time of AI following Ovsynch protocol, a total of 51 buffaloes were randomly divided in a ... more At the time of AI following Ovsynch protocol, a total of 51 buffaloes were randomly divided in a first group (n = 30) subjected to conventional AI into the uterine body with 20 million non-sex sorted frozen-thawed spermatozoa, while a second group (n = 21) was inseminated near the utero-tubal junction (UTJ) ipsilateral to the ovary carrying the preovulatory follicle with 2.5 million live (4 million total) sex-sorted frozen-thawed spermatozoa. The semen used for flowcytometric sorting was collected and processed on a farm in Italy, and then shipped to a laboratory in Germany. Eleven buffaloes were inseminated with X-chromosome bearing spermatozoa and 10 with Y-chromosome bearing spermatozoa. Conception rates after conventional and UTJ inseminations were 43.3% (n = 13) and 42.8% (n = 9) respectively (p = 0.97). Eight of the nine foetuses obtained after insemination with sexed spermatozoa corresponded to the sex as predicted by the cell sorting procedure (five male and four female foetuses by ultrasound vs six male and three female foetuses by cell sorting). In conclusion, for the first time buffalo semen has been successfully subjected to procedures for flowcytometric sperm sorting and freezing. Low doses of sexed spermatozoa have been deposited near the UTJ giving conception rates similar to those of conventional AI with full dose.
Kidney International, 2007
Journal of the American Society of Nephrology, 2010
Accelerated intimal and medial calcification and sclerosis accompany the increased cardiovascular... more Accelerated intimal and medial calcification and sclerosis accompany the increased cardiovascular mortality of dialysis patients, but the pathomechanisms initiating microcalcifications of the media are largely unknown. In this study, we systematically investigated the ultrastructural properties of medial calcifications from patients with uremia. We collected iliac artery segments from 30 dialysis patients before kidney transplantation and studied them by radiography, microcomputed tomography, light microscopy, and transmission electron microscopy including electron energy loss spectrometry, energy dispersive spectroscopy, and electron diffraction. In addition, we performed synchrotron x-ray analyses and immunogold labeling to detect inhibitors of calcification. Von Kossa staining revealed calcification of 53% of the arteries. The diameter of these microcalcifications ranged from 20 to 500 nm, with a core-shell structure consisting of up to three layers (subshells). Many of the calcifications consisted of 2-to 10-nm nanocrystals and showed a hydroxyapatite and whitlockite crystalline structure and mineral phase. Immunogold labeling of calcification foci revealed the calcification inhibitors fetuin-A, osteopontin, and matrix gla protein. These observations suggest that uremic microcalcifications originate from nanocrystals, are chemically diverse, and intimately associate with proteinaceous inhibitors of calcification. Furthermore, considering the core-shell structure of the calcifications, apoptotic bodies or matrix vesicles may serve as a calcification nidus.
In a previous experimental study using a chronic renal failure rat model, a dose-related multipha... more In a previous experimental study using a chronic renal failure rat model, a dose-related multiphasic effect of strontium (Sr) on bone formation was found that could be reproduced in an in vitro set-up using primary rat osteoblasts. The results from the latter study allowed us to distinguish between a reduced nodule formation in the presence of an intact mineralization at low Sr-doses (1 lg/ml) and an interference of the element with the hydroxyapatite (HA) formation at high doses (20-100 lg/ml). To further investigate the latter effect of Sr on physicochemical bone mineral properties, an in vitro study was set up in which the UMR-106 rat osteosarcoma cell line was exposed to Sr, added to the cell culture medium in a concentration range varying between 0-100 lg/ml. Temporal growth and functionality of the culture was investigated by measurement of the alkaline phosphatase activity and calcium (Ca) concentration in the culture medium (used as an index of Ca-incorporation, i.e., HA formation) at various time points. At the end of the culture period (14 days post-confluence), samples of the mineralized cultures were taken for further analysis using X-ray diffraction (XRD) and Fourier Transform Infra-Red Spectroscopy (FTIR). Synthetic HA doped with various Sr concentrations (based on the cell culture and previous experimental studies and yielding Sr/(Sr+Ca) ratios ranging from 0-60%), was prepared and examined for crystal growth and solubility. Crystal size was assessed using scanning electron microscopy (SEM). Ca incorporation indicated a reduced mineralization in the 20 and 100 lg/ml Sr groups vs. controls. Sr-doped synthetic HA showed a significant dose-dependent reduction in crystal growth, as assessed by SEM, and an increase in solubility, apparent from 12.7% Sr/(Sr+Ca) on. Moreover, in both mineralized cultures and synthetic HA, XRD and FTIR analysis showed a reduced crystallinity and altered crystal lattice at similar concentrations. These new data support our previous in vivo and in vitro findings and point to a potential physicochemical interference of Sr with HA formation and crystal properties in vivo.
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Papers by S. Verberckmoes