Effects of zoledronate on the radiation-induced collagen breakdown: a prospective randomized clinical trial

Background: A negative side effect of therapeutic irradiation is the radiation-induced bone loss which can lead, in long term, to pathological fractures. Until today, the detailed mechanism is unknown. If osteoclasts would mainly contribute to the pathological bone loss, bisphosphonates could potentially counteract the osteolytic process and possibly help to prevent long-term complications. The aim of this study was to evaluate the effect of zoledronic acid on the early radiation-induced degradation of bone collagen fibrils by monitoring the urinary excretion of hydroxylysylpyridinoline and lysylpyridinoline under radiotherapy. Patients and methods: A total of 40 patients with skeletal metastases were assigned for a local radiotherapy and bisphosphonate treatment. The patients were prospectively randomized into two treatment groups: group A (n = 20) received the first zoledronate administration after and group B (n = 20) prior to the radiotherapy. Urine samples were collected from each patient on the first day, in the middle, and on the last day of the radiation therapy. Measurement of the bone metabolites hydroxylysylpyridinoline and lysylpyridinoline was performed by high-performance liquid chromatography. Statistical analysis was performed using the Mann–Whitney U test. Results: The hydroxylysylpyridinoline and lysylpyridinoline excretion decreased significantly in the combined bisphosphonate and radiotherapy group (p = 0.02, p = 0.08). No significant change of the hydroxylysylpyridinoline and lysylpyridinoline excretion was determined in the patients that received solely irradiation. Conclusion The results indicate the ability of zoledronate to prevent the early radiation-induced bone collagen degradation suggesting that the radiation-induced bone loss is mainly caused by osteoclastic bone resorption rather than by a direct radiation-induced damage (AU)

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Effects of zoledronate on the radiation-induced collagen breakdown: a prospective randomized clinical trial.

BACKGROUND: A negative side effect of therapeutic irradiation is the radiation-induced bone loss which can lead, in long term, to pathological fractures. Until today, the detailed mechanism is unknown. If osteoclasts would mainly contribute to the pathological bone loss, bisphosphonates could potentially counteract the osteolytic process and possibly help to prevent long-term complications. The aim of this study was to evaluate the effect of zoledronic acid on the early radiation-induced degradation of bone collagen fibrils by monitoring the urinary excretion of hydroxylysylpyridinoline and lysylpyridinoline under radiotherapy. PATIENTS AND METHODS: A total of 40 patients with skeletal metastases were assigned for a local radiotherapy and bisphosphonate treatment. The patients were prospectively randomized into two treatment groups: group A (n = 20) received the first zoledronate administration after and group B (n = 20) prior to the radiotherapy. Urine samples were collected from each patient on the first day, in the middle, and on the last day of the radiation therapy. Measurement of the bone metabolites hydroxylysylpyridinoline and lysylpyridinoline was performed by high-performance liquid chromatography. Statistical analysis was performed using the Mann-Whitney U test. RESULTS: The hydroxylysylpyridinoline and lysylpyridinoline excretion decreased significantly in the combined bisphosphonate and radiotherapy group (p = 0.02, p = 0.08). No significant change of the hydroxylysylpyridinoline and lysylpyridinoline excretion was determined in the patients that received solely irradiation. CONCLUSION: The results indicate the ability of zoledronate to prevent the early radiation-induced bone collagen degradation suggesting that the radiation-induced bone loss is mainly caused by osteoclastic bone resorption rather than by a direct radiation-induced damage.

Adipogenic differentiation potential of rat adipose tissue-derived subpopulations of stromal cells.

Adipose-derived stromal cells (ASCs) are mostly isolated by enzymatic digestion, centrifugation and adherent growth resulting in a very heterogeneous cell population. Therefore, other cell types in the cell culture can comprise the differentiation and proliferation potential of the ASC population. Recent studies indicated that an antibody-aided isolation of distinct ASC subpopulations provides advantages over the conventional method of ASC isolation. The aim of this study was to investigate the adipogenic differentiation potential of CD29-, CD71-, CD73- and CD90-selected ASCs in vitro. The stromal vascular fraction (SVF) was obtained from rat adipose tissue by enzymatic digestion and centrifugation. Subsequently, CD29(+)-, CD71(+)-, CD73(+)- and CD90(+) cells were isolated by magnetic activated cell sorting (MACS), seeded into culture plates and differentiated into the adipogenic lineage. ASCs isolated by adherent growth only served as controls. Adipogenic differentiation was assessed by Oil Red O staining and quantification of the adiponectin and leptin concentrations in the cell culture supernatants. Statistical analysis was carried out using one-way analysis of variance (ANOVA) followed by the Scheffe's post hoc procedure. The results showed that different subpopulations with different adipogenic differentiation potentials can be isolated by the MACS procedure. The highest adipogenic differentiation potential was determined in the CD29-selected ASC population followed by the unsorted ASC population. The CD71-, CD73- and CD90-selected cells exhibited significantly the lowest adipogenic differentiation potential. In conclusion, the CD29-selected ASCs and the unsorted ASCs exhibited a similar adipogenic differentiation potential. Therefore, we do not see a clear advantage in the application of an anti-CD29-based isolation of ASCs over the conventional technique using adherent growth. However, the research on isolation/purification methods of adipogenic ASCs should continue in order to make this stem cell source even more attractive for future adipose tissue engineering applications.

In vitro comparison of different carrier materials with rat bone marrow MSCs.

OBJECTIVES: Injectable or implantable scaffolds seeded with autologous chondrogenic cells may represent a promising option for treatment of cartilage defects in the future. Current problems with the autologous chondrocyte implantation including dedifferentiation and the development of fibrocartilage suggest the use of alternative chondrogenic cell sources such as mesenchymal stromal cells (MSCs). The aim of this study was to compare the early effects of different scaffolds on the proliferation and metabolic activity of chondrogenic MSCs in vitro. MATERIALS AND METHODS: Multipotent stromal cells were isolated from rat bone marrow, phenotyped by flow cytometry, and differentiated into distinct lineages proved by lineage-specific staining and gene expression (RT-PCR) pattern. Cell proliferation on Tutodent® Membrane, Bio-Gide®, TissuFleece E, and Belotero® Soft was quantified by the MTT and WST-1 assay and direct determination of total cell numbers. Potential cytotoxic effects of eluates obtained from the materials were quantified by lactate dehydrogenase (LDH) and 5-bromo-2-deoxyuridine (BrdU) assay. RESULTS: TissuFleece E displayed the best results regarding cell proliferation on the biomaterials and metabolic activity (MTT, WST-1) (p < 0.001). Yet, the eluates of TissuFleece E caused an increased LDH release and lower values in the BrdU test. Cell proliferations on Bio-Gide®, Tutodent® Membrane, and Belotero® Soft were similar to the control. The eluates of Belotero® Soft exhibited the highest LDH release and lowest values in the BrdU assay (p < 0.05). CONCLUSIONS: Our results support the use of Tissufleece E as scaffold for chondrogenic rat MSCs. However, it should be prewashed with culture medium before seeding of the cells. CLINICAL RELEVANCE: Tissufleece E may serve as a promising carrier material for chondrogenic MSCs for cartilage tissue engineering attempts.

The subcutaneous fat compartments in relation to aesthetically important facial folds and rhytides.

The ideal treatment of the nasolabial fold, the tear trough, the labiomandibular fold and the mentolabial sulcus is still discussed controversially. The detailed topographical anatomy of the fat compartments may clarify the anatomy of facial folds and may offer valuable information for choosing the adequate treatment modality. Nine non-fixed cadaver heads in the age range between 72 and 89 years (five female and four male) were investigated. Computed tomographic scans were performed after injection of a radiographic contrast medium directly into the fat compartments surrounding prominent facial folds. The data were analysed after multiplanar image reconstruction. The fat compartments surrounding the facial folds could be defined in each subject. Different arrangement patterns of the fat compartments around the facial rhytides were found. The nasolabial fold, the tear trough and the labiomandibular fold represent an anatomical border between adjacent fat compartments. By contrast, the glabellar fold and the labiomental sulcus have no direct relation to the boundaries of facial fat. Deep fat, underlying a facial rhytide, was identified underneath the nasolabial crease and the labiomental sulcus. In conclusion, an improvement by a compartment-specific volume augmentation of the nasolabial fold, the tear trough and the labiomandibular fold is limited by existing boundaries that extend into the skin. In the area of the nasolabial fold and the mentolabial sulcus, deep fat exists which can be used for augmentation and subsequent elevation of the folds. The treatment of the tear trough deformity appears anatomically the most challenging area since the superficial and deep fat compartments are separated by an osseo-cutaneous barrier, the orbicularis retaining ligament. In severe cases, a surgical treatment should be considered. By contrast, the glabellar fold shows the most simple anatomical architecture. The fold lies above one subcutaneous fat compartment that can be used for augmentation.

Biocompatibility of bone graft substitutes: effects on survival and proliferation of porcine multilineage stem cells in vitro.

Bone graft substitutes (BGS) are widely used in clinical practice. For stem cellbased approaches to bone tissue engineering BGS need to show sufficient biocompatibility in the in vitro setting. This study was designed to demonstrate the influence of six different BGS on the proliferation and metabolic activity of porcine mesenchymal multilineage stem cells (pMSC) in vitro. Bone-marrow derived pMSC were cultivated for 24 hours with the eluates of six different BGS. The eluates were generated by incubating the BGS three times in succession for 24 hours with a culture medium and collecting the supernatants. pMSC vitality and proliferation in the presence of eluates from the first, second, and third incubation were assessed by WST-test quantification of metabolically active cells. Culture of pMSC with eluates in all cases resulted in decreased cell numbers in an eluate concentration-dependent manner. At least a 65% loss of cells compared to controls (culture medium without eluates) could be observed in the presence of undiluted eluates. The negative influence of eluates varied significantly among BGS. In all cases, second and third eluates were less potent in their negative effects on cellular vitality/proliferation. In conclusion, the BGS examined here should be submitted to thorough preincubation before in vitro use for cell-based constructs to maximize cell viability for the tissue engineering of bone.