Increased Bone Deposition Research Articles

Applications of Bioactive Strontium Compounds in Dentistry.

Divalent cations have captured the interest of researchers in biomedical and dental fields due to their beneficial effects on bone formation. These metallic elements are similar to trace elements found in human bone. Strontium is a divalent cation commonly found in various biomaterials. Since strontium has a radius similar to calcium, it has been used to replace calcium in many calcium-containing biomaterials. Strontium has the ability to inhibit bone resorption and increase bone deposition, making it useful in the treatment of osteoporosis. Strontium has also been used as a radiopacifier in dentistry and has been incorporated into a variety of dental materials to improve their radiopacity. Furthermore, strontium has been shown to improve the antimicrobial and mechanical properties of dental materials, promote enamel remineralization, alleviate dentin hypersensitivity, and enhance dentin regeneration. The objective of this review is to provide a comprehensive review of the applications of strontium in dentistry.

Piezoelectric effects on bone modeling for enhanced sustainability

Bone tissue possesses piezoelectric properties, allowing mechanical forces to be converted into electrical potentials. Piezoelectricity has been demonstrated to play a crucial role in bone remodelling and adaptability. Bone remodelling models that consider strain adaptation, both with and without piezoelectric effects, were simulated and validated in this study. This simulation help to better comprehend the interplay between mechanical and electrical stimulations during these processes. This study aimed to optimise the modelling of piezoelectric effects in bone modelling analysis. The connection between mechanical loads applied to bones and the resulting electrical charges generated by the piezoelectric effect was examined. Furthermore, mathematical modelling and simulation techniques were employed to enhance the piezoelectric effect and promote bone tissue growth and repair. The findings from this research have substantial implications for developing novel therapies for bone-related diseases and injuries. It was observed that electrically stimulated bone surfaces increased bone deposition. In some instances of physical disability or osteoporosis, therapeutic electrical stimulation can supplement the mechanical stresses of regular exercise to prevent bone loss. Consequently, the bone remodelling method on the software platform enables easy application and repetition of finite element analysis. This study significantly benefits bone tissue/biomedical engineering, particularly in bone remodelling, healing, and repair.

High bone mass and cam morphology are independently related to hip osteoarthritis: findings from the High Bone Mass cohort

BackgroundHigh bone mass (HBM, BMD Z-score ≥ + 3.2) and cam morphology (bulging of lateral femoral head) are associated with greater odds of prevalent radiographic hip osteoarthritis (rHOA). As cam morphology is itself a manifestation of increased bone deposition around the femoral head, it is conceivable that cam morphology may mediate the relationship between HBM and rHOA. We therefore aimed to determine if individuals with HBM have increased odds of prevalent cam morphology. In addition, we investigated whether the relationship between cam and prevalent and incident osteoarthritis was preserved in a HBM population.MethodsIn the HBM study, a UK based cohort of adults with unexplained HBM and their relatives and spouses (controls), we determined the presence of cam morphology using semi-automatic methods of alpha angle derivation from pelvic radiographs. Associations between HBM status and presence of cam morphology, and between cam morphology and presence of rHOA (or its subphenotypes: osteophytes, joint space narrowing, cysts, and subchondral sclerosis) were determined using multivariable logistic regression, adjusting for age, sex, height, weight, and adolescent physical activity levels. The association between cam at baseline and incidence of rHOA after an average of 8 years was determined. Generalised estimating equations accounted for individual-level clustering.ResultsThe study included 352 individuals, of whom 235 (66.7%) were female and 234 (66.5%) had HBM. Included individuals contributed 694 hips, of which 143 had a cam deformity (20.6%). There was no evidence of an association between HBM and cam morphology (OR = 0.97 [95% CI: 0.63–1.51], p = 0.90) but a strong relationship was observed between cam morphology and rHOA (OR = 3.96 [2.63–5.98], p = 5.46 × 10–11) and rHOA subphenotypes joint space narrowing (OR = 3.70 [2.48–5.54], p = 1.76 × 10–10), subchondral sclerosis (OR = 3.28 [1.60–6.60], p = 9.57 × 10–4) and osteophytes (OR = 3.01 [1.87–4.87], p = 6.37 × 10–6). Cam morphology was not associated with incident osteoarthritis (OR = 0.76 [0.16–3.49], p = 0.72).ConclusionsThe relationship between cam morphology and rHOA seen in other studies is preserved in a HBM population. This study suggests that the risk of OA conferred by high BMD and by cam morphology are mediated via distinct pathways.

Vascularised periosteal free flap reconstruction for medication-related osteonecrosis of the jaw: a case series

Introduction: The standard of care for medication-related osteonecrosis of the jaw (MRONJ) involves anti-biotics and local debridement to promote tissue healing over exposed bone. We compare outcomes for patients with advanced MRONJ managed with vascularised periosteal radial forearm free flap (RFFF) ver-sus local nasolabial flap and conservative dental measures. Methods: A retrospective case series of patients presenting to the Alfred Hospital for evaluation and man-agement of stage II or above MRONJ between 1 January 2014 and 30 June 2018. The hospital database was searched And a medical record review performed. Results of pre- and post-treatment imaging were ana-lysed bya single senior radiologist blinded to treatment modality . Asymptomatic wound closure, radio-logical evidence of disease cessation and patient satisfaction at six months post-treatment according to treatment type were assessed. Results: Of the ten patients included in the study, four received dental measures, three received local na-solabial flap and three received RFFF flap. All flap reconstruction (6/6) showed asymptomatic wound clo-sure and patient satisfaction at six months follow-up compared to patients managed with dental measures (1/4). All RFFF patients (3/3) showed increased bone deposition radiologically at six months compared to the dental group who showed a mixed (3/4) picture or worsened (1/4) picture. Nasolabial flap patients showed a mixed (2/3) or improved radiological picture (1/3). Conclusion: MRONJ is a relapsing disease. Preliminary evidence suggests that radical debridement with local nasolabial flap or RFFF reconstruction for advanced MRONJ is more effective at halting the disease and alleviating morbidity than conservative dental measures alone.

Prevalence and Distribution of Lesions in the Nasal Bones and Mandibles of a Sample of 144 Riding Horses

Simple SummaryThe use of restrictive nosebands in equestrian sports is of increasing concern to veterinarians and equitation scientists. Tightly fitting (restrictive) nosebands are primarily used to keep the horse’s mouth closed in a bid to increase the rider’s control of the horse and avoid penalties that may arise from mouth opening during competitions. The chief concern is that restricting behaviour by tightening the noseband may cause distress and apply pressure to the tissues of the horse’s head. It has been suggested that this pressure may cause injury to the soft tissues of the face and possibly the underlying bones. This opportunistic study of mature cavalry horses (n = 144) was designed to explore relationships between visual and palpable damage to structures that underlie the nosebands of horses and any related bony changes in affected horses, as evidenced by radiography. For nasal bones, the radiologists reported bone deposition in at least 6.9% of the horses and bone thinning in at least 33.3% of the horses, respectively. By palpation, at least 82% of the horses had palpable bone deposition of the nasal bones and at least 32% had palpable bone thinning. For the lower jaw, the radiologists reported increased bone deposition in 18.8–32.6% of the horses but no bone thinning. By palpation, at least 30.67% of the horses had palpable bone deposition in the lower jaw and at least 10.4% had palpable bone thinning. These radiographic results suggest that bone thinning is more apparent in the nasal bones than in the lower jaw and that both palpable and radiographic bone deposition are more likely in the mandible than in the nasal bones. This is the first confirmation of bony lesions at the site typically subjected to pressure from restrictive nosebands. That said, we note that the current study provides no evidence of a causal link between any piece of gear or its putative tightness and the lesions in these anatomical locations. The causes of these palpable and radiographic changes at the site of nosebands merit further investigation because inadvertently damaging the bones of horses as part of equitation is difficult to justify on ethical grounds.Restrictive nosebands are used in equestrian sports to hold the bit in place and reduce mouth-opening, a response that can attract penalties in some sports and is thought to reduce the rider’s control of the horse. Sustained pressure from such tightly fitted (restrictive) nosebands denies normal behaviour and thus, causes frustration and distress that can jeopardise horse welfare. It also may push the cheek against the molar teeth, compress soft tissues including blood vessels and nerves, and possibly induce chronic changes to underlying bone. This study of mature cavalry horses (n = 144) was designed to explore relationships between visual and palpable damage to structures that underlie the nosebands of horses and any related bony changes in those horses as evidenced by radiography. Working independently of each other, two researchers inspected the horses for visual changes and palpable changes before the horses were radiographed. The radiographs were assessed by a separate pair of veterinary radiologists, again working independently of each other. Among the current population of horses, 37.5% had one or more radiographic changes to the nasal bones according to both radiologists, and 13.8% had one or more radiographic changes to the mandible. For nasal bones, the two radiologists reported bone deposition in 6.9% and 8.3% of the horses and bone thinning in 33.3% and 56.9% of the horses, respectively. By palpation, they found that 82% and 84% of the horses had palpable bone deposition of the nasal bones and 32% and 33.4% had palpable bone thinning. For the mandibles, the radiologists reported increased bone deposition in 18.8% and 32.6% of the horses but no bone thinning. By palpation, the two examiners reported 30.6% and 32.7% of the horses had palpable bone deposition and 10.4% and 11.1% had palpable bone thinning. This is the first report of lesions to the mandible at this site and this article presents the first confirmation of bony lesions at the site typically subjected to pressure from restrictive nosebands. These results suggest that radiographic bone thinning is more apparent in the nasal bones of riding horses than in the mandible and that both palpable and radiographic bone deposition are more likely in the mandible than in the nasal bones. That said, we note that the current study provides no evidence of a causal link between any piece of gear or its putative tightness and the lesions in these anatomical locations. Further studies are needed to identify risk factors for these clusters of lesions. The inadvertent deformation of bones in the horse’s head for competitive advantage is difficult to justify on ethical grounds.

Maresin 1 resolves aged-associated macrophage inflammation to improve bone regeneration.

Inflammaging is associated with poor tissue regeneration observed in advanced age. Specifically, protracted inflammation after acute injury has been associated with decreased bone fracture healing and increased rates of nonunion in elderly patients. Here, we investigated the efficacy of using Maresin 1 (MaR1), an omega-3 fatty acid-derived pro-resolving agent, to resolve inflammation after tibial fracture injury and subsequently improving aged bone healing. Aged (24-month-old mice) underwent tibial fracture surgery and were either treated with vehicle or MaR1 3 days after injury. Fracture calluses were harvested 7 days, 14 days, 21 days, and 28 days after injury to investigate inflammatory response, cartilage development, bone deposition, and mechanical integrity, respectively. Healing bones from MaR1-treated mice displayed decreased cartilage formation and increased bone deposition which resulted in increased structural stiffness and increased force to fracture in the later stages of repair. In the early stages, MaR1 treatment decreased the number of pro-inflammatory macrophages within the fracture callus and decreased the level of inflammatory biomarkers in circulation. In tissue culture models, MaR1 treatment of bone marrow-derived macrophages from aged mice protected cells form a pro-inflammatory phenotype and induced an anti-inflammatory fate. Furthermore, the secretome of MaR1-treated bone marrow-derived macrophages was identified as osteoinductive, enhancing osteoblast differentiation of bone marrow stromal cells. Our findings here identify resolution of inflammation, and MaR1 itself, to be a point of intervention to improve aged bone healing.

SAT-402 Investigating Analogues of Parathyroid Hormone (PTH) and PTH-Related Peptide (PTHrP) to Improve Anabolic: Catabolic Response Ratios Using UMR106-01 Osteocytic Cells

Osteoporosis, the most common bone disease in humans, is characterised by decreased bone mass and increased fracture risk1. Osteoporosis development is associated with an imbalance of bone resorption and deposition mediated by all three bone cell types; osteoblasts, osteocytes and osteoclasts2. Current treatments for osteoporosis either prevent further bone resorption (Bisphosphonates and anti-RANKL) or increase bone deposition through anabolism (Teriparatide and Abaloparatide)3. The two anabolic treatments are truncated analogues of endogenous peptides; parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP), respectively. Both are administered intermittently, act on PTH1R receptors on osteoblasts and osteocytes leading to an increase in bone mineral density and bone strength. However, both treatments also have side-effects of hypercalcemia and cortical bone porosity caused by osteoclast stimulation. We therefore compared an array of PTH and PTHrP analogues for potential stimulation of catabolic side effects and desired anabolic effects. Screening assays used are UMR106-01 osteocytic cells that have high levels of PTH1R to measure mRNAs involved in anabolic responses (suppression of WNT inhibitors SOST and Dkk1) and catabolic responses (stimulation of RANKL/OPG, IL6). Peptides were also analysed by real-time cellular impedance assays (xCELLigence) to measure unbiased receptor stimulation. xCELLigence assays showed PTH1-34, PTHrP1-34 and Abaloparatide had the highest potencies (3.7 nM,1.4 nM,1.7nM respectively) while Tyr1PTH1-34 and PTH2-34 had significantly decreased potencies (64nM and 130nM), the β-arrestin biased agonist, D-Trp12Tyr34PTH7–34, had no effect. PTH1-34 potently inhibited SOST (IC50 0.29nM), and catabolic genes (RANK/OPG EC50 0.5nM, IL6 EC50 2.5nM). PTHrP1-34 provided higher potencies for anabolic (inhibited SOST IC50 0.08nM) and catabolic (RANKL/OPG EC50 0.3nM, IL6 EC50 1nM) genes. Altering the first amino acid to Tyrosine; Tyr1PTH1-34 caused potent anabolic responses (SOST IC50 0.97nM) yet showed decreased potency for catabolic responses (RANKL/OPG EC50 20nM, IL6 EC50 > 100nM). Removing the first amino acid of PTH to PTH2-34 drastically decreases the effectiveness of the peptide (OPG, SOST and RANKL IC50 – no effect, IL6 EC50 > 100nM). These results indicate the importance of the N-terminal amino acid for PTH affinity and efficacy and suggest that Tyr1PTH1-34 may offer the best combination of bone stimulation without causing hypercalcemia.References 1 A.Gupta, L. March. (2016) Treating osteoporosis, Aust Prescr 2 Chen X, et al. (2018) Osteoblast–osteoclast interactions. Connect. Tissue Res 3 Tu KN, et al. (2018) Osteoporosis: A review of treatment options. P T

Local orthodontic force initiates widespread remodelling of the maxillary alveolar bone

Abstract Objectives To clarify the effects of a local orthodontic force on alveolar bone by analysing bone remodelling in different regions of the maxilla during orthodontic tooth movement (OTM). Methods An OTM model was established in rats. Histological changes in the maxilla were analysed using TRAP staining, IHC staining for CTSK and haematoxylin and eosin (H and E) staining. The root bifurcation region of the alveolar bone of the first (M1), second (M2) and third (M3) molars were selected as the regions of interest (ROIs), which were further divided into a cervical and an apical level. Sequential fluorochrome labelling was performed to analyse bone deposition rates. Results The maxillary left first molars were moved mesially. TRAP staining and IHC staining for CTSK showed orthodontic force increased osteoclast numbers in all six ROIs at both the cervical and apical levels. H and E staining indicated elevated osteoblast numbers in the OTM group in all induced regions. Sequential fluorochrome labelling exhibited increased bone deposition rates around M1, M2 and M3 in the OTM group. Conclusions An orthodontic force applied to the first molar could initiate widespread remodelling of the maxillary alveolar bone, which was not restricted to the tension and pressure sites. This may revise the orthodontic biomechanical theory and provide new insights for clinical work.

Consumption of Rabbiteye Blueberry Results in Accumulation of Hippuric Acid in the Bone Marrow and Increased Bone Deposition in Ovariectomized Rats but Few Other Bone Benefits (P06-064-19)

ObjectivesDetermine the effects of an 8-wk chronic consumption of two different blueberry varieties at varying doses on calcium balance, calcium kinetics, bone microarchitecture and polyphenol metabolism and distribution in ovariectomized rats. MethodsEighty 5-mo old ovariectomized rats were sorted by weight and block-randomized to an 8-wk chronic feeding treatment of a polyphenol-free (control), 2.5% or 5% `Montgomery ́ (Mont) rabbiteye blueberry (V. ashei) or 5% wild lowbush blueberry (Wild BB) (V. angustifolium) (% w/w). During week 0 and week 8, rats went through a calcium balance study to determine calcium absorption and retention. At the end of week 8, rats were dosed with 45Ca and serial blood draws were done from baseline up to 48 h post-dose to map Ca kinetics. At sacrifice, the right femur was collected to determine differences in bone strength and microarchitecture of trabecular and cortical bone through MicroCT and a three-point bending test. A 24 h urine collection was done at baseline and during week 8 of treatment to determine urinary phenolic acid excretion and the left femur bone marrow phenolic acid accumulation through UPLC-MS/MS. ResultsA blueberry enriched diet had no effect on cortical bone microarchitecture, with a trend towards increased trabecular bone protection (p = 0.08). No differences were observed in bone strength. During baseline, a 2.5% Mont diet significantly increased Ca retention, but the effect was lost after the 8 weeks of treatment when rats had stabilized to treatment. Calcium kinetics showed that Mont 5% significantly increased Ca absorption and bone turnover (p < 0.05), while Mont 2.5% and Wild BB 5% did not. An accumulation of hippuric acid in the bone marrow was detected with the Mont blueberry treatments and it was significantly and positively correlated with bone deposition. The metabolism of phenolic acids was significantly affected by a chronic consumption of the treatment diets, resulting in significant phenolic acid profiles and excretion shifts. ConclusionsA blueberry-enriched diet had minimal effects on bone after stabilized to ovariectomy and the effects differ depending on blueberry variety and dose. Funding SourcesNational Institute of Health (NIH) and National Center for Complementary and Integrative Health (NCCIH).

Growth-dependent phenotype in FasL-deficient mandibular/alveolar bone.

FASL (CD178) is known for its role in triggering apoptosis, mostly in relation with immune cells but additional functions have been reported more recently, including those in bone development. Examination of postnatal FasL-deficient mice (gld) showed an increased bone deposition in adult mice when compared with wild types. However, a different phenotype was observed prenatally, when the gld bone was underdeveloped. The aim of the following investigation was to evaluate this indication for an growth-dependent bone phenotype of gld mice and to search for the 'switch point'. This study focused on the mandibular/alveolar bone as an important structure for tooth anchorage. In vivo micro-computed tomography (CT) analysis was performed at different stages during the first month (6, 12 and 24days) of postnatal bone development. In 6-day-old gld mice, a decrease in bone volume/tissue volume (BV/TV), trabecular thickness and trabecular number was revealed. In contrast, the 12-day-old gld mice showed an increased BV/TV and trabecular thickness in the alveolar bone. The same observation applied for bone status in 24-day-old gld mice. Therefore, changes in the bone phenotype occurred between day 6 and 12 of the postnatal development. The switch point is likely related to the changing proportion of bone cells at these stages of development, when the number of osteocytes increases. Indeed, the immunohistochemical analysis of FASL localized this protein in osteoblasts, whereas osteocytes were mostly negative at examined stages. The impact of FASL particularly on osteoblasts would agree with an earlier in vivo observed effect of FASL deficiency on expression of Mmp2, typical for osteoblasts, in the gld mandibular/alveolar bone. Notably, an age-dependent bone phenotype was reported in Mmp2-deficient mice.

Microscopic markers of an infradian biorhythm in human juvenile ribs

Recent studies have indicated that there may be an infradian systemic biorhythm that coordinates aspects of human hard tissue growth and influences adult body size. Here we investigate if evidence of this biorhythm retained in human teeth as the periodicity of Retzius lines (RP) corresponds with the microstructural growth of a non-weight bearing bone, the rib, in a sample of 50 human juvenile skeletons. Using static histomorphometric methods, the RP of one permanent tooth from each skeleton was calculated and combined with measures of bone remodeling in a rib from the same individual. Results provide the first evidence that the infradian biorhythm is linked to bone remodeling in children. Retzius periodicity was negatively correlated with relative osteon area (r = -0.563, p = 0.008) and positively related to Haversian canal area (r = 0.635, p = 0.002) and diameter (r = 0.671, p = 0.001) in children between the age of 8 to 12 years. There was also a negative correlation between RP and the relative cortical area of ribs (r = -0.500, p = 0.048). Relationships between bone remodeling and the biorhythm were much more variable in younger children. Results imply that as the biorhythm speeds up there is increased bone deposition during remodeling of the rib, leading to the larger osteonal lamellar bone areas and smaller Haversian canals in children between 8 and 12 years of age. Our results support the idea that there is an infradian biorhythm that coordinates aspects of human hard tissue growth.

Selection and Characterization of a DNA Aptamer Specifically Targeting Human HECT Ubiquitin Ligase WWP1.

Nucleic acid aptamers hold promise as therapeutic tools for specific, tailored inhibition of protein targets with several advantages when compared to small molecules or antibodies. Nuclear WW domain containing E3 ubiquitin ligase 1 (WWP1) ubiquitin ligase poly-ubiquitinates Runt-related transcription factor 2 (Runx2), a key transcription factor associated with osteoblast differentiation. Since WWP1 and an adapter known as Schnurri-3 are negative regulators of osteoblast function, the disruption of this complex has the potential to increase bone deposition for osteoporosis therapy. Here, we develop new DNA aptamers that bind and inhibit WWP1 then investigate efficacy in an osteoblastic cell culture. DNA aptamers were selected against three different truncations of the HECT domain of WWP1. Aptamers which bind specifically to a C-lobe HECT domain truncation were observed to enrich during the selection procedure. One particular DNA aptamer termed C3A was further evaluated for its ability to bind WWP1 and inhibit its ubiquitination activity. C3A showed a low µM binding affinity to WWP1 and was observed to be a non-competitive inhibitor of WWP1 HECT ubiquitin ligase activity. When SaOS-2 osteoblastic cells were treated with C3A, partial localization to the nucleus was observed. The C3A aptamer was also demonstrated to specifically promote extracellular mineralization in cell culture experiments. The C3A aptamer has potential for further development as a novel osteoporosis therapeutic strategy. Our results demonstrate that aptamer-mediated inhibition of protein ubiquitination can be a novel therapeutic strategy.

A genomic characterization of the influence of silver nanoparticles on bone differentiation in MC3T3-E1 cells.

Silver nanoparticles (AgNPs) have been widely used in a variety of biomedical applications. Previous studies demonstrated that AgNPs significantly enhanced bone cell mineralization and differentiation in MC3T3-1 cells, a model in vitro system, when compared to several other NPs. This increased bone deposition was evaluated by phenotypic measurements and assessment of the expression of miRNAs associated with regulation of bone morphogenic proteins. In the present study, we used RNA-seq technology, a more direct measurement of gene expression, to investigate further the mechanisms of bone differentiation induced by AgNP treatment. Key factors associated with the osteoclast pathway were significantly increased in response to AgNP exposure including Bmp4, Bmp6 and Fosl1. In addition, genes of metabolism and toxicity pathways were significantly regulated as well. Although this study suggests the potential for AgNPs to influence bone morphogenesis in injury or disease applications, further investigation into the efficacy and safety of AgNPs in bone regeneration is warranted.

Endoscopic Management of Inverted Papilloma Using CT Scan as the Predictor of Tumour Origin

Introduction&#x0D; Inverted papillomas are notorious for recurrence. The surgical cause attributed to recurrence is failure to achieve good surgical exposure and inadequate clearance of disease. Pre-operative prediction about the site of origin by CT Scan may contribute to a better surgical outcome. This study was undertaken to assess if focal hyperostosis on pre-operative CT scan can be considered to be a predictor of the site of tumour origin and correlate with endoscopic finding of the site of origin.&#x0D; Materials and Method&#x0D; A prospective descriptive study was carried out between Jan 2014 and May 2016. Fifteen patients of histopathologically proven inverted papilloma that reported during this time period were evaluated using contrast enhanced CT Scan and subsequently underwent endoscopic excision of tumour identifying the tumour origin. Assessment of age, gender, symptoms, pre-operative staging, location of the tumour origin on CT Scan and surgical correlation of origin was done. Post-operative follow-up was done at 1 month, 3 months and 6 monthly thereafter.&#x0D; Results&#x0D; Six (40%) were classified as Krouse II and nine (60%) were classified as Krouse III. 12 (80%) arising from maxillary sinus, 02 (13.3%) arising from maxillary sinus and anterior ethmoids and 01 (6.7%) from sphenoid. Thirteen (86.7%) cases CT scan could predict the tumour origin which was confirmed during surgery. All cases managed by endoscopic technique with no recurrence or co-existence of malignancy.&#x0D; Discussion&#x0D; Focal hyperostosis in the walls of paranasal sinus is seen to be associated with IP tumour origin, the cause of which is not fully understood. It is hypothesized that tumour induced inflammation at the site of origin leads to bone remodeling and increased bone deposition with vascularity at the site of attachment.&#x0D; Conclusion&#x0D; CT scan is a good predictor of tumour origin and a conservative endoscopic approach can be planned accordingly for complete clearance of disease.

MP41-13 VITAMIN D REPLACEMENT IN RECURRENT RENAL STONE FORMERS WITH HYPERCALCIURIA DOES NOT INCREASE URINE CALCIUM EXCRETION OR RENAL STONE GROWTH

You have accessJournal of UrologyStone Disease: Medical Therapy1 Apr 2015MP41-13 VITAMIN D REPLACEMENT IN RECURRENT RENAL STONE FORMERS WITH HYPERCALCIURIA DOES NOT INCREASE URINE CALCIUM EXCRETION OR RENAL STONE GROWTH Luke McGuinness, Robert Calvert, and Vinita Mishra Luke McGuinnessLuke McGuinness More articles by this author , Robert CalvertRobert Calvert More articles by this author , and Vinita MishraVinita Mishra More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1641AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Reduced vitamin D levels are found in up to 50% of recurrent renal stone patients. Reluctance to replace vitamin D in these patients exists due to a theoretical risk of increased intestinal calcium absorption and subsequent renal excretion. Recent evidence suggests that increased absorption might be offset by increased bone deposition with no effect on urine excretion. We aim to assess the effect of pharmacological correction of low vitamin D in hypercalciuric renal stone formers compared to those with adequate vitamin D in a metabolic stone clinic. METHODS Retrospective review of 30 recurrent renal stone formers with hypercalciuria was undertaken. Serum 25 hydroxyvitamin D (25OHD) and 24hr urine biochemistry were measured in all patients at baseline and during follow-up. Renal stone growth was assessed with abdominal x-rays. Hypercalciuria was treated with diet and diuresis advice and pharmacotherapy (thiazide/ potassium citrate/allopurinol). Those with low 25OHD levels (¡Ü50nmol/L) were prescribed vitamin D replacement (VDR). Outcomes of 24hr urine biochemistry and new stone growth were compared between those on VDR (n= 17) and those with adequate 25OHD levels (n= 13). RESULTS Nine patients (30%) had vitamin D deficiency (¡Ü30nmol/L), 8 (27%) had insufficiency (>30 and ¡Ü50nmol/L) and 13 (43%) had adequate levels (>50nmol/L). 17 patients were prescribed vitamin D replacement (mean duration 14 months). 13 patients with adequate levels had mean follow-up of 22 months. No significant difference in baseline 24hr urine biochemistry was seen. Patients on VDR had an increase in 25OHD (33.6 to 74.7nmol/L, p<0.001) whilst 24hr urine calcium levels reduced non-significantly (9.33 to 8.78mmol/24hr, p>0.1). Patients with adequate 25OHD level (64.7nmol/L) had a significant decrease in urinary calcium (10.6 to 8.28mmol/24hr, p=0.003). No other significant changes were seen on urine biochemistry. The mean decrease in urine calcium in those on VDR (0.43mmol/24hr) compared to those with adequate 25OHD (2.28mmol/24hr) was not significant (p=0.15). 10 patients had new stone growth; 6 patients (35%) on VDR and 4 patients (31%) with adequate 25OHD (p>0.5). CONCLUSIONS Low vitamin D levels are present in more than half of hypercalciuric stone formers. Vitamin D replacement does not adversely affect urine calcium levels in patients with low vitamin D status or increase renal stone risk compared to those with adequate levels. Furthermore a beneficial effect may exist due to increased bone mineralisation but further evaluation is required. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e505 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Luke McGuinness More articles by this author Robert Calvert More articles by this author Vinita Mishra More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Differential osteogenicity of multiple donor-derived human mesenchymal stem cells and osteoblasts in monolayer, scaffold-based 3D culture and in vivo.

We set out to compare the osteogenicity of human mesenchymal stem (hMSCs) and osteoblasts (hOBs). Upon osteogenic induction in monolayer, hMSCs showed superior matrix mineralization expressing characteristic bone-related genes. For scaffold cultures, both cell types presented spindle-shaped, osteoblast-like morphologies forming a dense, interconnected network of high viability. On the scaffolds, hOBs proliferated faster. A general upregulation of parathyroid hormone-related protein (PTHrP), osteoprotegrin (OPG), receptor activator of NF-κB ligand (RANKL), sclerostin (SOST), and dentin matrix protein 1 (DMP1) was observed for both cell types. Simultaneously, PTHrP, RANKL and DMP-1 expression decreased under osteogenic stimulation, while OPG and SOST increased significantly. Following transplantation into NOD/SCID mice, μCT and histology showed increased bone deposition with hOBs. The bone was vascularized, and amounts further increased for both cell types after recombinant human bone morphogenic protein 7 (rhBMP-7) addition also stimulating osteoclastogenesis. Complete bone organogenesis was evidenced by the presence of osteocytes and hematopoietic precursors. Our study results support the asking to develop 3D cellular models closely mimicking the functions of living tissues suitable for in vivo translation.

Enhanced bioactivity of polyvinylidene chloride films using argon ion bombardment for guided bone regeneration.

Polyvinylidene chloride (PVDC) is a long chain carbon synthetic polymer. The objective of this study was to improve the bioactivity of PVDC films through surface modification using argon (Ar) ion bombardment to create Ar-modified PVDC films (Ar-PVDC) to address the clinical problems of guided bone regeneration (GBR), which is technique-sensitive, and low bone regenerative ability. First, the effects of Ar ion bombardment, a low temperature plasma etching technique widely used in industry, on PVDC film wettability, surface chemistry, and morphology were confirmed. Next, fibroblast-like and osteoblast-like cell attachment and proliferation on Ar-PVDC were assessed. As a preclinical in vivo study, Ar-PVDC was used to cover a critical-sized bone defect on rat calvaria and osteoconductivity was evaluated by micro-computed tomography analysis and histological examinations. We found that the contact angle of PVDC film decreased by 50° because of the production of -OH groups on the PVDC film surface, though surface morphological was unchanged at 30 min after Ar ion bombardment. We demonstrated that cell attachment increased by about 40% and proliferation by more than 140% because of increased wettability, and 2.4 times greater bone regeneration was observed at week 3 with Ar-PVDC compared with untreated PVDC films. These results suggest that Ar ion bombardment modification of PVDC surfaces improves osteoconductivity, indicating its potential to increase bone deposition during GBR.

F-Spondin Deficient Mice Have a High Bone Mass Phenotype

F-spondin is a pericellular matrix protein upregulated in developing growth plate cartilage and articular cartilage during osteoarthritis. To address its function in bone and cartilage in vivo, we generated mice that were deficient for the F-spondin gene, Spon1. Spon1 − /− mice were viable and developed normally to adulthood with no major skeletal abnormalities. At 6 months, femurs and tibiae of Spon1 − /− mice exhibited increased bone mass, evidenced by histological staining and micro CT analyses, which persisted up to 12 months. In contrast, no major abnormalities were observed in articular cartilage at any age group. Immunohistochemical staining of femurs and tibiae revealed increased levels of periostin, alkaline phosphate and tartrate resistant acid phosphatase (TRAP) activity in the growth plate region of Spon1 − /− mice, suggesting elevated bone synthesis and turnover. However, there were no differences in serum levels of TRAP, the bone resorption marker, CTX-1, or osteoclast differentiation potential between genotypes. Knockout mice also exhibited reduced levels of TGF-β1 in serum and cultured costal chondrocytes relative to wild type. This was accompanied by increased levels of the BMP-regulatory SMADs, P-SMAD1/5 in tibiae and chondrocytes. Our findings indicate a previously unrecognized role for Spon1 as a negative regulator of bone mass. We speculate that Spon1 deletion leads to a local and systemic reduction of TGF-β levels resulting in increased BMP signaling and increased bone deposition in adult mice.

Calcium kinetics during bed rest with artificial gravity and exercise countermeasures.

We assessed the potential for countermeasures to lessen the loss of bone calcium during bed rest. Subjects ingested less calcium during bed rest, and with artificial gravity, they also absorbed less calcium. With exercise, they excreted less calcium. To retain bone during bed rest, calcium intake needs to be maintained. This study aims to assess the potential for artificial gravity (AG) and exercise (EX) to mitigate loss of bone calcium during space flight. We performed two studies: (1) a 21-day bed rest (BR) study with subjects receiving 1h/day AG (n = 8) or no AG (n = 7) and (2) a 28-day BR study with 1h/day resistance EX (n = 10) or no EX (n = 3). In both studies, stable isotopes of Ca were administered orally and intravenously, at baseline and after 10days of BR, and blood, urine, and feces were sampled for up to 14days post dosing. Tracers were measured using thermal ionization mass spectrometry. Data were analyzed by compartmental modeling. Less Ca was absorbed during BR, resulting in lower Ca balance in BR+AG (-6.04 ± 3.38mmol/day, P = 0.023). However, Ca balance did not change with BR+EX, even though absorbed Ca decreased and urinary Ca excretion increased, because endogenous excretion decreased, and there was a trend for increased bone deposition (P = 0.06). Urinary N-telopeptide excretion increased in controls during BR, but not in the EX group. Markers of bone formation were not different between treatment groups for either study. Ca intake decreased during BR (by 5.4mmol/day in the AG study and 2.8mmol/day in the EX study), resulting in lower absorbed Ca. During BR (or space flight), Ca intake needs to be maintained or even increased with countermeasures such as exercise, to enable maintenance of bone Ca.

Biodegradability engineering of biodegradable Mg alloys: Tailoring the electrochemical properties and microstructure of constituent phases

Crystalline Mg-based alloys with a distinct reduction in hydrogen evolution were prepared through both electrochemical and microstructural engineering of the constituent phases. The addition of Zn to Mg-Ca alloy modified the corrosion potentials of two constituent phases (Mg + Mg2Ca), which prevented the formation of a galvanic circuit and achieved a comparable corrosion rate to high purity Mg. Furthermore, effective grain refinement induced by the extrusion allowed the achievement of much lower corrosion rate than high purity Mg. Animal studies confirmed the large reduction in hydrogen evolution and revealed good tissue compatibility with increased bone deposition around the newly developed Mg alloy implants. Thus, high strength Mg-Ca-Zn alloys with medically acceptable corrosion rate were developed and showed great potential for use in a new generation of biodegradable implants.