Percentage Of Bone Research Articles

Significance of medication discontinuation on bisphosphonate-related jaw osteonecrosis in a rat model

Bisphosphonate (BP) discontinuation has been advised as a measure to prevent the incidence of bisphosphonate-related osteonecrosis of the jaw (BRONJ), however, its efficacy remains controversial. This study aimed to analyze the efficacy of BP discontinuation in reducing BRONJ severity following tooth extraction in a rat model. Thirty-four male Sprague–Dawley rats were divided into two BRONJ model categories: oral administration (PO) of alendronate (1 mg/kg) for 3 and 8 weeks and intraperitoneal (IP) injection of pamidronate (3 mg/kg) and dexamethasone (1 mg/kg) for 20 days. The PO model was divided into five groups (a control group without BPs and four experimental groups with 1-week discontinuation). The IP model was divided into two groups consisting of group I (without discontinuation) and group II (1-week discontinuation). One molar from both sides of the mandible was extracted. After extraction, the PO models were sacrificed at 3 and 5 weeks, and the IP models were sacrificed either immediately or at 2, 4, 6, and 8 weeks. Micro-CT showed non-significant differences among PO groups but significant differences were observed between IP groups. Most bone remodeling parameters within group I of the IP model differed significantly (p-value < 0.05). Histologically, group I showed a significantly higher percentage of necrotic bone than group II (51.93 ± 12.75%, p < 0.05) and a higher number of detached osteoclasts in TRAP staining. With discontinuation of medication for at least 1 week in rats, the effects of BPs on alveolar bone are suppressed and bone turnover and osteoclast functions are restored.

Bone Modeling after Orthodontic Extrusion: A Histomorphometric Pilot Study.

During osteogenesis and bone modeling, high vascularity and osteoblastic/osteoclastic cell activity have been detected. A decrease in this activity is a sign of complete bone formation and maturation. Alveolar bone maturation seems to occur within weeks and months; however, the precise timing of the alveolar bone modeling is still unknown. The aim of this clinical pilot study was to investigate the bone modeling of neo-apposed tissue during orthodontic extrusive movements, through a histomorphometric analysis of human biopsies. This study was conducted on third mandibular molars sockets, and all teeth were extracted after orthodontic extrusion between 2010 and 2014. After different stabilization timings, extractions were performed, and a specimen of neo-deposed bone was harvested from each socket for the histomorphometric analysis. Histological parameters were evaluated to identify bone quantity and quality. This study included 12 teeth extracted from 9 patients. All specimens were composed of bone tissue. Bone samples taken after 1 and 1.5 months of stabilization presented remarkable percentages of woven bone, while after 2 months, a relevant decrease was observed. Histomorphometric analysis suggested that after orthodontic extrusion, a period of stabilization of 2 months allows the neo-deposed bone to mature.

Healing Patterns of Non-Collagenated Bovine and Collagenated Porcine Xenografts Used for Sinus Floor Elevation: A Histological Study in Rabbits.

Objective: To compare healing of collagenated and non-collagenated xenografts used for maxillary sinus floor elevation. Materials and Methods: Two different xenografts were used: deproteinized bovine bone (DBBM group) and collagenated corticocancellous porcine bone (collagenated group). Healing was studied after 2, 4, and 8 weeks. The loss of dimensions of the elevated area and the percentages of new bone, xenograft remnants, osteoclastic zones, vessels, inflammatory infiltrates, and soft tissues were analyzed. Three regions were evaluated: close to the bone walls (bone wall region), subjacent the sinus mucosa (submucosa region), and the center of the elevated area (middle region). The primary variables were the percentage of new bone and xenograft remnants. Results: Between 2 and 8 weeks, the elevated areas showed a reduction of 16.3% and 52.2% in the DBBM and collagenated groups, respectively (p < 0.01 between the two areas after 8 weeks). After 8 weeks, the highest content of new bone was observed in the bone wall region, which was higher in the collagenated group than in the DBBM group (41.6% and 28.6%, respectively; p < 0.01). A similar quantity of new bone was found between the two groups in other regions. A higher percentage of vessels in all regions evaluated (p < 0.01) and soft tissue in the sub-mucosa region (p < 0.05) was found in the collagenated group than in the DBBM group. Conclusions: The present study showed that both xenografts allowed new bone formation. In comparison with the non-collagenated xenograft, the collagenated xenograft underwent higher resorption, resulting in greater shrinkage of the elevated space after sinus lifting and a higher content of new bone in the regions close to the bone walls. Clinical relevance: In this study, the region adjacent to the bone wall showed the highest new bone content. This region resembles the base of the sinus, closest to the sinus floor and walls, and is the most important region from a clinical point of view because it is where the implant will be installed. Residues of the biomaterial remained after 8 weeks of healing. Other reports have shown that these biomaterial residues may interfere with the integration of implants.

Contribution to Bone Formation of the Schneiderian Membrane after Sinus Augmentation: A Histological Study in Rabbits.

to evaluate bone formation in close contact with the sinus mucosa after different periods from sinus augmentation and the influence on healing of the presence of an inward dis-placed bone window. Eighteen rabbits were included in the experiment. A trap-door technique was applied at the test sites, and the bony window was elevated inward (inward window; IW) together with the sinus mucosa. At the control sites, the bony window was removed before the elevation of the sinus mucosa. The elevated space was filled with deproteinized bovine bone mineral (DBBM) and both access windows were covered with a collagen membrane. Histometric measurements were performed subjacent the sinus mucosa after 2, 4, and 8 weeks of healing. Very few sinuses presented small percentages of new bone in close contact with the sinus mucosa in the various period examined. The presence of bone in the neighbor areas might have influenced bone formation close to the sinus mucosa. The inward displaced bone window supported bone formation close to the sinus mucosa only in the earliest period of healing, while the bone walls increased their influence over time. The lack of increased new bone percentage over time in the most central regions of the elevated sinus mucosa do not support the hypothesis that the sinus mucosa may express its potential in bone formation. It can be speculated that the new bone found in the intermediate and middle regions of the control sites in the earliest period of healing might be due to residual of bone from the osteotomy. Very small amounts of new bone were found subjacent to the sinus mucosa, mostly formed from the bone walls, the inward displaced bone window or from possible bone residues from the osteotomy procedures. The lack of increased new bone percentage over time in the most central regions of the elevated sinus mucosa indicates that the contribution to bone formation provided by the sinus mucosa is limited.

Comparison of Cytomorphology and Histopathology in Myelodysplastic Syndromes (MDS)

Introduction: Bone marrow cytomorphology, cytogenetics and molecular analyses are essential tools for diagnosing a myelodysplastic syndrome. MDS are characterized by dysplastic features of hematopoietic cells and may also show an increased blast cell count. Histopathology can provide additional information on bone marrow fibrosis and cellularity. We analysed correlations and differences between cytomorphological and histopathological findings at diagnosis. Patients and methods: In the Duesseldorf MDS registry, we identified 127 patients with detailed information available on bone marrow cytomorphology, blast count, blood cell counts and clinical features, who also had a bone marrow core biopsy taken at the time of diagnosis. From their formalin-fixed, paraffin-embedded histopathology specimens new sections and stains were made and evaluated by one reviewing pathologist (SB) who assessed a predefined set of features. The pathologist had no knowledge of the cytomorphological findings, except for the information that the specimen was from a "patient with myelodysplastic syndrome". Statistical analyses were performed by SPSS. Procedures were in accordance with the current version of the Helsinki Declaration. Informed consent was obtained from all patients included in the study. Results: The estimation of the percentage of CD34-positive cells by histopathology differed significantly from the cytomorphologically assessed medullary blast count, with a trend towards histopathological underestimation of blast cells (figure 1). Assessment of dysmegakaryopoiesis by histopathology identified 44 cases with dysplastic features, which were deemed inconspicious by cytomorphology. Histopathology yielded a significant positive correlation (p=0.002) between cellularity and degree of dysmegakaryopoiesis, and these two features were also correlated with higher-risk WHO subtypes. Fibrosis and dysmegakaryopoiesis were negatively correlated. Bone marrow cellularity seemed to be overestimated by cytomorphology compared with histopathology. The percentage of erythropoietic cells did not correlate well between cytomorphological and histopathological review. Neither WHO subtype nor medullary blast count showed an association with the proportion of erythropoiesis, regardless of the mode of evaluation. All patients with expanded erythropoiesis also showed signs of dysmegakaryopoiesis. There was no case of cytomorphologically diagnosed MDS that was not confirmed by histopathology, and 48% of MDS diagnoses were identical as to their WHO subtype. However, in 66 cases (52%), the WHO type diagnosed by histopathology differed from the WHO type diagnosed by cytomorphology. The discrepancy was mainly due to differing estimates of medullary blast counts. In our cohort, the degree of fibrosis positively correlated with bone marrow cellularity, a finding that appeared counterintuitive to clinical experience. Increased cellularity also correlated with higher-risk MDS subgroups. Prognosis in terms of overall survival was influenced by the following parameters: Cytomorphologically assessed medullary blast count, bone marrow cellularity, fibrosis, and percentage of erythropoiesis, the latter assessed by histopathology. Patients with of grade 2 or 3 fibrosis had an inferior outcome (figure 2). Conclusions: In our study, histopathology was fully congruent with bone marrow cytology as far as making a diagnosis of MDS is concerned. Histopathology, though, often underestimated the blast count and showed difficulty in identifying the correct MDS type according to the WHO classification. Histopathology is also at a disadvantage regarding evaluation of single cell morphology, with the exception of assessing certain aspects of dysmegakaryopoiesis. A clear advantage of histopathology is its exclusive capability of gauging bone marrow fibrosis and cellularity, both of which are relevant for the diagnosis and prognosis of MDS. We conclude that cytomorphology and histopathology should both be harnessed to optimize the characterization of a patient's myelodysplastic syndrome. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Retrospective Analysis of Residual Hairy Cell Leukemia Measured By IHC or Flow Cytometry and Frontline Treatment with Pentostatin on Time to Next Treatment

Introduction: Pentostatin (pent) and cladribine (2CdA) are purine analogs used as frontline therapy for Hairy Cell Leukemia (HCL). Both agents can induce long-term remissions, but neither is considered curative. A better understanding of the factors that predict time to next therapy (TTNT) is needed to improve prognostication and monitoring after frontline therapy. The presence of minimal residual disease (MRD), as measured by advanced molecular techniques such as PCR, IHC, and flow cytometry, has been associated with reduced relapse-free survival in HCL. However, there is no uniform method for detecting MRD in HCL. Furthermore, most data regarding MRD has been collected from patients treated with 2CdA and less is known about MRD status after pent. Our institution has a large cohort of HCL patients treated with pent in the frontline setting. Thus, we performed a retrospective analysis to investigate (1) the impact of persistent HCL as measured by IHC or flow cytometry on TTNT after any frontline therapy, (2) the effect of pent on TTNT, and (3) the effect of MRD status after pent on TTNT. Methods: We conducted a retrospective analysis of HCL patients treated at Ohio State University on an IRB approved protocol. Patients with less than 1 year of follow up were excluded from the analysis. Bone marrow biopsy reports were collected at diagnosis and within 1 year of starting frontline therapy. MRD was defined as the lack of detectable HCL by morphological analysis, but the presence of HCL by IHC or flow cytometry. TTNT was calculated from the first HCL treatment to the initiation of next treatment treating death as a competing risk. The associations between TTNT and patient characteristics as well as percent bone marrow HCL measured by IHC and flow cytometry following completion of first line therapy were evaluated using Fine and Gray subdistribution hazard models accounting for competing risks. Results: 149 patients met criteria for this analysis. Median age a diagnosis was 51, 78% were male, and 7.4% had variant HCL. There were no significant differences in baseline characteristics for patients treated with pent or 2CdA. Univariable analysis of baseline characteristics found that a palpable spleen at diagnosis (HR 2.65, 95% CI 1.51-4.63, p=0.001) and variant HCL (HR 2.62, 95% CI 1.36-5.05, p=0.004) had significantly shorter TTNT. Patients who received pent (n=39, median number of infusions 14) as frontline treatment had significantly longer (HR 0.40, 95% CI 0.20-0.79, p=0.008) TTNT compared to 2CdA (n=72, Figure 1). By our definition of MRD, there were 47 total patients whose MRD status could be accurately determined. Univariable analysis showed MRD positivity after frontline treatment, regardless of agent, trended towards a shorter TTNT but was not statistically significant (HR 2.5, 95% CI 0.75-8.28, p=0.13). This was also true following treatment with pent (n=25, HR 5.83, 95% CI 0.53-64.43, p=0.15) whereas no trend was seen after 2CdA (n=15, HR 1.05, 95% CI 0.09-11.7, p=0.97). Univariable analysis of all patients, regardless of frontline treatment, showed that IHC ranges of 1-5% (HR 3.16, 95% CI 1.12-8.90, p=0.029), and >5% (HR 9.75, 95% CI 4.12-23.09 p<0.001) had significantly shorter TTNT compared to IHC<1% (Figure 2). Similarly, residual HCL burden measured by flow cytometry of 1-5% (HR 4.63, 95% CI 1.95-10.99, p=0.001) and >5% (HR 12.26, 95% CI 4.27-35.24 p<0.001) had significantly shorter TTNT. Following pent, residual HCL ranges measured by IHC of 1-5% (HR 8.82, 95% CI 1.22-63.84, p=0.031) and >5% (HR 29.17, 95% CI 3.99-213.42, p=0.001) had significantly shorter TTNT compared to <1%. Residual HCL ranges of 1-5% (HR 5.79, 95% CI 1.28-26.12, p=0.022) and >5% (HR 21.2, 95% CI 3.09-145.64, p=0.002) by flow cytometry after pent also had significantly shorter TTNT. Similar results were observed following 2CdA. Conclusions: Pent and 2CdA are considered efficacious in terms of achieving complete remission in HCL. Our finding that pent was associated with a significantly longer TTNT compared to 2CdA suggests there could be additional clinical differences between these agents, but drawing definitive conclusions is difficult due to the retrospective nature of this work. Finally, our data suggest that assessment of the degree of residual HCL burden measured by either IHC or flow cytometry yields important prognostic information. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Renal Toxicity with Carfilzomib in Multiple Myeloma: Secondary Analysis of SWOG S1304 Comparing Low-Dose Versus High-Dose Carfilzomib

Introduction: Randomized controlled trials (RCTs) testing carfilzomib-based combination regimens in myeloma have demonstrated a signal of increased renal toxicity, with a relative risk of 2.3 for grade≥3 toxicities with carfilzomib-based versus non-carfilzomib-based regimens (Ball et al. Annals of Hematology. 2020). Nonetheless, there are insufficient data on detailed characterization of carfilzomib-induced renal toxicity, especially in patients treated with carfilzomib alone or with dexamethasone, without the confounding effect of additional classes of anti-myeloma therapy. The objective of our study was to estimate the incidence, timing, nature, and potential risk-factors of carfilzomib-induced renal toxicity using data from S1304 which compared two doses of carfilzomib (56 mg/m2 (K56) vs 27 mg/m2 (K27) twice-weekly), both with dexamethasone, in relapsed/refractory myeloma (Ailawadhi et al. Clinical Cancer Research. 2020). Methods: Individual patient-level data from S1304 trial (NCT01903811) were utilized to estimate the incidence, nature, and timing of renal toxicities. The toxicity of interest was acute kidney injury (AKI), in which, we included the adverse event description of "increased creatinine". Baseline characteristics in patients who developed AKI versus those who didn't were compared using Fisher's exact test. Results: Our analysis on renal toxicity included 123 patients, with 57 patients randomized to K56 and 66 to K27 arms. All-grade AKI/increased creatinine (hereafter, referred to as AKI) was seen in 21 patients overall (17.1%), with grade≥3 toxicity seen in 6 patients (4.9%). By treatment arms, the incidence of all-grade and grade≥3 AKI for K56 was 21.1% and 5.3% respectively, whereas for K27 arm it was 13.6% and 4.5%, respectively. The median time to onset of AKI was 2.5 (range, 2-3) and 2 (range, 1-7) cycles for all-grade and grade≥3 respectively. Kidney toxicities of interest other than AKI were CKD and proteinuria. The overall incidence of all-grade CKD and proteinuria were low at 1.6% and 2.4% respectively, with no grade ≥3 events. The incidence of CKD in K56 and K27 arms was 1.8% and 1.5% respectively, whereas that for proteinuria was 1.8% and 3% respectively. The median time to onset of CKD was 3.5 cycles (range, 3-4) and that of proteinuria was 2 cycles (range, 1-9). Subsequently, we investigated any potential differences in baseline patient-specific, disease-specific, or treatment-specific characteristics between patients who developed AKI versus those who did not (Table 1). The only variable that showed a near-significant difference between the two was percent bone marrow plasma cells (BMPC), with %BMPC in the two groups being 41% vs 18% respectively (p=0.052). There was no significant difference in the proportion of patients receiving K56 between the two groups (56% vs 45% respectively; p=0.45). Next, we performed a 3-month landmark analysis to estimate progression-free survival (PFS) stratified by development of any-grade AKI that was at least possibly attributable to study treatment prior to 3 months following randomization. There was no significant difference in median PFS between patients who developed kidney toxicity versus those who did not. Conclusion: In summary, we showed that ≥grade 3 AKI is observed in ~5% of patients receiving carfilzomib plus dexamethasone, with most events occurring early at a median of about 2 cycles from treatment initiation. Furthermore, high tumor burden at baseline is a potential predictor of AKI with carfilzomib, whereas dose-intensity of carfilzomib was not different between patients who developed AKI versus those who didn't. Our findings are comparable to that of the ARROW trial which tested once weekly (70 mg/m2) versus twice-weekly (27 mg/m2) carfilzomib, and demonstrated grade≥3 AKI in 4% and 6% of patients, respectively. Future studies should investigate additional risk-factors and reversibility of carfilzomib-induced renal toxicity as well as impact on survival in larger patient cohorts. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Genetic Iron Overload Aggravates and Pharmacological Iron Restriction Improves MDS Pathophysiology in a Preclinical Mouse Model

Background: Patients with myelodysplastic syndromes (MDS) are prone to develop iron overload as a consequence of ineffective erythropoiesis and chronic transfusion therapy. Although iron overload is a common feature in MDS, it remains unclear whether and how iron excess is detrimental for MDS pathophysiology. Aims: This study aimed at characterizing altered iron homeostasis in a preclinical MDS mouse model, understanding the molecular mechanisms underlying iron toxicity and unraveling the potential therapeutic value of pharmacologic iron restriction in this disease condition. Methods: To this end, we took advantage of complementary approaches and analyzed the effect of iron overload obtained through genetic activation of the iron exporter ferroportin (FPNC326S), and iron restriction achieved through the administration of the FPN inhibitor vamifeport in NUP98-HOXD13 MDS mice, starting at 3 or 5 months of age. Results: At steady-state MDS mice develop an iron overload phenotype, hallmarked by low hepcidin levels, elevated serum iron and transferrin saturation, non-transferrin-bound iron (NTBI) formation and tissue iron deposition. This is associated with anemia and low WBCs in the peripheral blood. FPNC326S MDS mice show an aggravated iron phenotype, with further elevated NTBI and tissue iron accumulation and still inappropriately low hepcidin levels. Vamifeport administration in MDS mice reduced serum iron (194.8 vs 141.8 mg/dl; P<0.05) and NTBI formation (0.62 vs 0 μM; P<0.05) and prevented tissue iron loading. While iron excess in FPNC326S MDS mice did not improve erythropoiesis and hematologic parameters in the peripheral blood, iron restriction by vamifeport significantly ameliorated anemia (Hb 9.5 vs 11.4 g/dl; RBC 5.4 vs 6.9x106 cells/ml; P<0.05) and maturation of bone marrow as well as splenic RBCs in MDS mice. The improved ineffective erythropoiesis was associated with reduced oxidative stress and apoptosis in erythroid progenitors. Importantly, we observed a major role of the iron status in myeloid expansion in MDS. The number of immature myeloid blasts and myeloid progenitors in the bone marrow of MDS mice were aggravated by iron overload in FPNC326S MDS mice and attenuated by iron restriction in vamifeport-treated MDS mice compared to control MDS animals. Myeloid bias, monitored as percentage bone marrow myeloid cells, was exacerbated by iron overload (54.3 vs 43.1% bone marrow mononuclear cells - BMNCs) and alleviated by iron restriction (67.5 vs 74.8% BMNCs; P<0.05). This was associated with increased and reduced inflammatory activation of bone marrow macrophages in FPNC326S MDS and vamifeport-treated MDS mice, respectively. This observation demonstrates a role for NTBI in driving the reported pro-inflammatory activation of MDS monocytes/macrophages (Fuster JJ et al, Science 2017; Jaiswal S et al, NEJM 2017; Cull AH et al, Exp Hematol 2017) and suggests that this iron-driven mechanism contributes to myeloid expansion. Overall, these alterations translated into a faster and delayed transition to AML in iron-overloaded and iron-restricted MDS mice, respectively. Finally, iron overload aggravated and iron restriction alleviated ROS formation, DNA damage and pyroptotic cell death in HSPCs. By reducing the intracellular labile iron pool, vamifeport improved HSPC quality and survival, partially rescuing the stem cell pool size (0.16 vs 0.38% Lin-BMNCs; P<0.05) in MDS mice. The ameliorated HSPC pool, reduced myeloid bias and inflammation, and attenuated ineffective erythropoiesis resulted in improved hematologic parameters for more than 3 months, and a significant survival increment in iron-restricted compared to control MDS mice (>45 days; P=0.037). We further demonstrate that a subgroup of mice can benefit from late iron restriction by vamifeport administration at 5 months of age, resulting in improved anemia and prolonged survival. Conclusion: Our results show for the first time in a preclinical mouse model of MDS that iron excess driven by ineffective erythropoiesis has pathological implication in transfusion-independent MDS. These effects are likely aggravated by transfusions causing additional iron overload. Finally, iron restriction achieved through pharmacologic FPN inhibition by the oral FPN inhibitor vamifeport significantly improves MDS pathophysiology, uncovering the therapeutic potential of early prevention of NTBI formation in MDS.

Histological evaluation of the incorporation and remodeling of structural allografts in critical size metaphyseal femur defects in rats of different ages.

Insufficient bone regeneration is a common issue for patients with extensive bone damage, therefore the use of allografts is required. With increasing life expectancy, there is a higher risk of bone repair issues after fractures or orthopedic surgical intervention. We studied incorporation and remodeling of structural allografts in critical size metaphyseal femur defects in 52 rats aged 3-month-old and 12-month-old who underwent surgeries creating a bone defect, which was either filled with a structural allograft (3-month-old - 3moAllo; 12-month-old - 12moAllo) or left empty (3-month-old - 3moE; 12-month-old - 12moE). Histological analyses were performed 14, 28 and 90 days after the surgery. The percentage of bone and fibrous tissues, and allograft relative to the defect area was evaluated. The transmission electron microscopy was carried out 14 days after allograft implantation. When the defect was empty, slower bone regeneration was observed in 12moE rats versus 3moE, leading to sufficient irregularities in the anatomic structure of the femur 90 days after the surgery. When a structural allograft was used, the area of the fibrous tissue was larger in the defects of 12moAllo compared with 3moAllo rats 90 days after surgery. No age-related differences were found in the allograft remodeling and structures of the osteocytes, osteoblasts, and osteoclasts over the observation period. Evident issues with bone regeneration were found in critical size defects both of 12moE and 12moAllo rats. However, the allograft use allowed the bone maintaining anatomic structure 90 days after the surgery.

Acceleration of Bone Fracture Healing through the Use of Bovine Hydroxyapatite or Calcium Lactate Oral and Implant Bovine Hydroxyapatite-Gelatin on Bone Defect Animal Model.

Bone grafts a commonly used therapeutic technique for the reconstruction and facilitation of bone regeneration due to fractures. BHA-GEL (bovine hydroxyapatite-gelatin) pellet implants have been shown to be able accelerate the process of bone repair by looking at the percentage of new bone, and the contact between the composite and bone. Based on these results, a study was conducted by placing BHA-GEL (9:1) pellet implants in rabbit femoral bone defects, accompanied by 500 mg oral supplement of BHA or calcium lactate to determine the effectiveness of addition supplements. The research model used was a burr hole defect model with a diameter of 4.2 mm in the cortical part of the rabbit femur. On the 7th, 14th and 28th days after treatment, a total of 48 New Zealand rabbits were divided into four groups, namely defect (control), implant, implant + oral BHA, and implant + oral calcium lactate. Animal tests were terminated and evaluated based on X-ray radiology results, Hematoxylin-Eosin staining, vascular endothelial growth Factor (VEGF), osteocalcin, and enzyme-linked immunosorbent assay (ELISA) for bone alkaline phosphatase (BALP) and calcium levels. From this research can be concluded that Oral BHA supplementation with BHA-GEL pellet implants showed faster healing of bone defects compared to oral calcium lactate with BHA-GEL pellet implants.

BOBOT BADAN AKHIR DAN PERSENTASE BONELESS BROILER YANG DIBERIKAN BUNGKIL INTI SAWIT SEBAGAI PAKAN SUBTITUSI DEDAK PADI

This study aims to examine the response of final body weight and growth of broiler chest muscle given fermented and unfermented palm kernel cake as raw material for substitution of rice bran in broiler rations. This study used a completely randomized design consisting of 5 treatments and 4 replications filled with 2 chickens each. The treatments consisted of P0 (control), P1 (10% palm kernel cake), P2 (10% fermented palm kernel cake), P3 (15% fermented palm kernel cake), and P4 (20% palm kernel cake). The results showed that the treatment had a significant effect (P&lt;0.05) on the final weight or slaughter weight and the percentage of boneless breast meat, but had no significant effect (P&gt;0.05) on the percentage of breast bone and the ratio of bone meat. The addition of palm kernel cake up to 15% can increase the boneless broiler breast meat, although it tends to reduce the final weight of the broiler. So that the substitution of rice bran with fermented palm kernel cake can be replaced by up to 15%. Keywords: Palm kernel cake, Boneless, Boneless broiler meat, Meat and bone ratio

Low-Molecular-Weight Heparins (LMWH) and Synthetic Factor X Inhibitors Can Impair the Osseointegration Process of a Titanium Implant in an Interventional Animal Study.

Background and objectives: Cementless total hip arthroplasty is a common surgical procedure and perioperative thromboprophylaxis is used to prevent deep vein thrombosis or pulmonary embolism. Osseointegration is important for long-term implant survival, and there is no research on the effect of different thromboprophylaxis agents on the process of osseointegration. Materials and Methods: Seventy rats were allocated as follows: Group I (control group), Group II (enoxaparin), Group III (nadroparin), and Group IV (fondaparinux). Ovariectomy was performed on all subjects, followed by the introduction of an intramedullary titanium implant into the femur. Thromboprophylaxis was administered accordingly to each treatment group for 35 days postoperatively. Results: Group I had statistically significantly lower anti-Xa levels compared to treatment groups. Micro-CT analysis showed that nadroparin had lower values compared to control in bone volume (0.12 vs. 0.21, p = 0.01) and percent bone volume (1.46 vs. 1.93, p = 0.047). The pull-out test showed statistically significant differences between the control group (8.81 N) compared to enoxaparin, nadroparin, and fondaparinux groups (4.53 N, 4 N and 4.07 N, respectively). Nadroparin had a lower histological cortical bone tissue and a higher width of fibrous tissue (27.49 μm and 86.9 μm) at the peri-implant area, compared to control (43.2 μm and 39.2 μm), enoxaparin (39.6 μm and 24 μm), and fondaparinux (36.2 μm and 32.7 μm). Conclusions: Short-term administration of enoxaparin, nadroparin, and fondaparinux can reduce the osseointegration of titanium implants, with nadroparin having the most negative effect. These results show that enoxaparin and fondaparinux are preferred to be administered due to a lesser negative impact on the initial implant fixation.

ODP077 Adipopenia is associated with low bone mass in community-dwelling non-underweight adults, independent of sarcopenia

Abstract The interaction between fat, muscle, and bone mass is complex. Although sarcopenia and underweight are well-established risk factors for osteoporosis, the association between low body fat percent (adipopenia) and low bone mass in non-underweight adults remains unclear. In Korean National Health and Nutrition Examination Survey dataset 2008-2011, we analyzed individuals aged 50 or older with body mass index (BMI)≥18.5 kg/m 2 . Appendicular skeletal muscle mass (ASMM) and body fat percent were measured using dual-energy x-ray absorptiometry. Sarcopenia was defined as ASMM/height 2 &amp;lt;7. 0 kg/m 2 and &amp;lt;5.4 kg/m 2 in men and women, respectively. Subjects were grouped into adipopenia (&amp;lt;17% in men and &amp;lt;30% in women; 1 standard deviation below the mean of the study population with round down to integer value), normal, or obesity (&amp;gt;30% in men and &amp;gt;40% in women) according to body fat percent. Osteoporosis was defined as T-score≤ -2.5 at the lumbar spine, femoral neck, or total hip. Among 5830 subjects (women 50.2%, mean age 63.9±8.5 years), 793 subjects had adipopenia (13.6%). The adipopenia group had a higher prevalence of osteoporosis (31%) compared to normal (21%) or obesity groups (27%; p&amp;lt;0. 001). Body fat percent showed a positive association with bone mineral density at all sites after adjustment for age, sex, height, and lean mass. In the multivariable logistic model, the presence of adipopenia was associated with 61% elevated odds of osteoporosis (adjusted odds ratio [aOR] 1.61, p&amp;lt;0. 001), independent of sarcopenia (aOR 1.71, p&amp;lt;0. 001), age, sex, height, and covariates, which remained robust in sensitivity analysis with sex-specific lowest 20% quantile thresholds (roughly &amp;lt;18.4% in men; &amp;lt;31.5% in women). In conclusion, adipopenia was associated with osteoporosis independent of sarcopenia in non-underweight adults, which merits further investigation. Presentation: No date and time listed

Effectiveness of antimicrobial photodynamic therapy mediated by butyl toluidine blue in preventing medication-related osteonecrosis of the jaws in rats

BackgroundMedication-related osteonecrosis of the jaws (MRONJ) is difficult to treat, therefore, prevention would be the ideal clinical approach. This study evaluated the effectiveness of antimicrobial photodynamic therapy (aPDT), mediated by butyl toluidine blue (BuTB) in the prevention of MRONJ-like lesions after tooth extraction in rats. MethodsTwenty-eight senescent female rats were distributed in groups: VEH and VEH-aPDT, treated with vehicle, ZOL and ZOL-aPDT, treated with 100 µg/Kg of zoledronate, both treatments every three days over seven weeks. After three weeks from the commencement of treatment, the mandibular first molar was extracted. For the VEH and ZOL groups, no local treatment was performed, while with the VEH-aPDT and ZOL-aPDT groups, photodynamic treatment was carried out at 0, 2, and 4 days after extraction. For aPDT, 500μl of BuTB solution was deposited on the dental extraction site (0.5 mg/ml; 60 s), followed by irradiation with low-level laser (InGaAIP; 660 nm; 35 mW; 74.2 J/cm²; 60 s). After 28 postoperative days, euthanasia was performed. The hemimandibles were processed to: (1) histological analysis of tissue repair; (2) histometric analysis of the percentage of newly formed bone tissue (PNFBT) and percentage of non-vital bone tissue (PNVBT); (3) immunohistochemical analysis for tartrate-resistant acid phosphatase (TRAP). ResultsThe ZOL and ZOL-aPDT groups showed less TRAP-positive cells when compared with VEH and VEH-aPDT. The ZOL group demonstrated great compromise in the tissue repair process, consistent with MRONJ-like lesions. VEH, VEH-aPDT and ZOL-aPDT presented a favorable tissue repair process. PNFBT in the ZOL group was lower than in the VEH, VEH-aPDT and ZOL-aPDT groups, whereas PNVBT in the ZOL group was higher than in the VEH, VEH-aPDT and ZOL-aPDT groups. Conclusion: aPDT mediated by BuTB prevented the occurrence of MRONJ-like lesions after tooth extraction in rats.

Study on the morphology of nutrient foramens in humerus and its surgical implications

Long bones have large or small foramina for the entry of the blood-vessels. Such foramens are known as the nutrient foramina which are large in the shafts of the largest long bones. Such foramina lead to nutrient canals through which the blood vessels enters the bone supplying the medullary cavity. The site of entry and the direction of the nutrient foramina are almost constant and are directed away from the growing ends. The nutrient artery that passes through these foramina are the main source of blood supply to humerus and is particularly important during growth period in the embryo and foetus and also during the early stage of ossification. a. To determine the direction of nutrient foramen in humerus. b. To determine the number of nutrient foramen of humerus. c. To determine the location of nutrient foramen of humerus. The study was conducted on 120 adult humeri that were obtained from the Department of Anatomy, Sri Devaraj Urs medical college, Kolar, karnataka. Bones were segregated into right and left and observed for the direction, number and location of nutrient foramens in humerus In the present study, the percentage of humerus bones with one nutrient foramen was 87% and two foramina was 9% and absent in 4%. Single nutrient foramen on right humerus bones was 92% and left side was 4% and absent in 4%. Single nutrient foramen on left humerus bones was 83% and left side was 13% and absent in 4%. 59% of the bones had nutrient foramen that were located on the medial border. Following which, the order was Anteromedial surface in (25%), Lateral border in (5%), Posterior surface in (3%) and anterior border in (3%). 81% had the nutrient foramen that was located in the middle 1/3rd, 11% at the junction between middle 1/3rd and lower 1/3rd and 3% in the lower 1/3rd of humerus. All the nutrient foramina were directed towards the elbow joint and was away from the growing end as per the law of ossification. Nutrient artery is the main source of blood supply to long bones that enters through the nutrient foramen. The surgical and anatomical knowledge of nutrient foramen in humerus or any long bone is important for orthopaedic surgeons and general surgeons during surgical procedures on the humerus such as vascular surgeries, bone grafting and transplantation.

SPECT/CT imaging features of cystic degeneration of the talus and their relation to pathological findings

BackgroundOsteochondral lesions of the talus (OLTs) are a common orthopedic condition. The image presentation is very similar to that of ischemic necrosis of the talus complicated by a talar neck fracture, but the two are very different lesions. When abnormalities in bone density (or signal) of the talar body (apex of the fornix) with concomitant bone defects and cystic changes are found on X-ray, computed tomography (CT), or magnetic resonance imaging, it is important to accurately determine the nature of the lesion and make a correct diagnosis for the treatment and prognosis of the patient. The purpose of this study was to explore the imaging features of three-phase single-photon emission computed tomography (SPECT)/CT images of cystic lesions of the talus.MethodsA total of 189 patients with chronic pain in the ankle joint suspected to be caused by cystic degeneration of the talus were enrolled. All patients underwent 99mTc-methyl diphosphonate (99mTc-MDP) three-phase SPECT/CT bone imaging and delayed scans in our hospital. The location, range of involvement, classification, CT value, and radioactivity uptake of the sclerotic areas of cystic lesions on the talus, and the continuity of the articular surface, were recorded. All recorded parameters were analyzed in comparison with pathological results.ResultsEighty-three percent (157/189) of the talar cysts were located on the medial fornix, largely involving the anterior middle part (43.27%), with larger cysts involving the posterior part (9.6%). Sixty-three percent (119/189) of the patients had type I lesions and 37% (70/189) had type II lesions. The articular surface of the medial dome of the talus was intact in all patients, but the subchondral bony articular surface was rough in 88% (166/189) of patients. The coincidence rate for the location, type, and range of involvement of cystic lesions with the pathological results was 87.83% (166/189). The mean CT value of the cystic lesions was 45 ± 15 HU (30–60 HU). The percentages of pathological chondrogenesis in high CT value ≥ 50 HU (19/70) and low CT value < 50 HU (51/70) groups were 89.47% (17/19) and 29.14% (15/51) (χ2 = 20.12, p < 0.001), respectively. The target/background ratio (T/B ratio) of the radioactivity-uptake area of the talus vault was 2.0 ± 0.5 (1.5–2.5). The percentages of pathological new trabecular bone in those with a T/B ratio ≥ 2.0 (157/189) and T/B ratio < 2.0 (32/189) were 82.80% (130/157) and 25.00% (8/32; χ2 = 45.08, p < 0.001), respectively.ConclusionsThree-phase bone imaging could identify damage of the talus caused by cystic degeneration, while delayed SPECT/CT images showed advantages for displaying bone microstructure, blood supplement, and bone metabolism when examining the location, range of involvement, classification, and repair of cystic lesions of the talus.

Morphometric Study of Sacral Hiatus in Dry Adult Human Sacra: Its Clinical Relevance in Caudal Epidural Block.

Correct localization of the sacral hiatus is essential for administering a successful caudal epidural block. The present study was undertaken to find out the anatomical variations of sacral hiatus by a metrical method so that it could help anaesthesiologists in the clinical field. The study was performed on 140 (83 male and 57 female) adult human sacra. Various parameters of the sacrum studied were as follows: the shape of the hiatus, length of the sacral hiatus, transverse width at the base and anteroposterior diameter at the level of the apex. For each parameter, the mean value (calculated in mm), standard deviation, range and percentage of bones identified correctly were calculated. Various shapes of sacral hiatuswere observed, including inverted "U" in 73 (52.14%), inverted "V" in 33 (23.57%), irregular in 10 (7.14%), elongated in 10 (7.14%) and dumbbell-shaped in 12 (8.57%). Absent sacral hiatus was observed in two (1.43%) specimens. The mean value for the length of sacral hiatus from the apex to the midpoint of the base was found to be 23.26 mm in males and 22.38 mm in females. However, the parameter was found to be statistically not significant. The mean value for transverse width at the base of hiatus was found to be 14.19 mm in males and 13.54 mm in females. The mean value for the anteroposterior diameter of the sacral canal at the apex was found to be 4.57 mm in males and 4.32 mm in females. Both the above parameters were found to be statistically not significant. The anatomical knowledge of sacral hiatus and its variations are important in caudal epidural anaesthesia, and it may improve the success rate of caudal epidural anaesthesia.

Milk kefir therapy improves the skeletal response to resistance exercise in rats submitted to glucocorticoid-induced osteoporosis.

Glucocorticoid-induced osteoporosis (GIO) has emerged as a challenge after long-term glucocorticoids (GCs) administration. Exercise has been an important non-pharmacological option, while medications modulate bone remodeling despite adverse effects. In this way, milk Kefir (MK) therapy stands out as a safe alternative to improve bone metabolism. Our study aimed to investigate the effect of MK associated to resistance exercise on bone loss in rats with GIO. For this, sixty male Wistar rats were divided into 2 groups: normal (N) and subjected to GIO, which was subdivided into 4 groups: control (C), milk kefir therapy (K), Exercise (Ex), and Exercise+K (ExK). GIO was induced by dexamethasone (7mg/kg - i.m.; 1×/wk, 5wk). MK was administered daily (1×/day; 0.7ml/animal) and the climb exercise with load was performed 3×/wk; both for 16wk. Femur was collected for assessment of bone microarchitecture, quality and metabolism. GIO markedly reduced trabecular bone volume density (BV/TV) (-35%), trabecular thickness (Tb.Th) (-33%), mineral content of femur (-26%) as well as bone collagen content (-56%). Bone strength and its biomechanical properties given by flexural strength (-81%), fracture load (-80%), and the number of osteocytes (-84%) were lowered after GIO. GCs reduced osteoblast number and function while increased osteoclast number, altering bone remodeling (p<0.05). On the other hand, ExK significantly improved bone microarchitecture and quality, marked by fractal dimension increase (+38%), cortical volume (+34%), BV/TV (+34%), Tb.Th (+33%), mineral content and collagen maturity, while reduced the space between trabecula (-34%). The Ex and ExK increased the number of osteocytes (p<0.05) and they were able to reverse the lower osteoblast number. Both treatments used alone significantly enhanced bone biomechanical properties, but the ExK showed a more significant improvement. ExK ameliorated bone strength and biomechanics (p<0.05) and stimulated bone formation and modulated bone remodeling (p<0.05). MK and exercise administered isolated or in association increased the percentage of collagen bone filling after GIO (p<0.05), but only ExK improved collagen maturity. Our results showed that MK associated to resistance exercise enhanced bone microarchitecture, quality and metabolism, being therefore an interesting tool to improve skeletal response during GIO.

Histomorphometric Analysis of Residual Alveolar Ridge Preserved using Collagen Cell Occlusive Membrane Alone and Along with Demineralized Bone Matrix Following Tooth Extraction: A Randomized Control Trial.

The changes in the volume and dimensions of the alveolar bone after tooth extraction often lead to challenges in prosthetic rehabilitation of the same necessitating ridge preservation procedures (RPP). The aim of this randomized clinical trial was to evaluate and compare the dimensional and histomorphometric changes of the sites preserved using the collagen membrane with and without demineralized bone matrix (DMBM). Interventional, parallel-design, double blinded, randomized controlled trail. A randomized controlled trial was designed with 45 participants having at least 2 teeth indicated for were enrolled in this study. The sites were randomly assigned to the control group (RPP using collagen membrane) and the test group (RPP using collagen membrane with DMBM). The clinical parameters assessed were alveolar bone width and alveolar bone height. Histomorphometric analysis was carried out on tissue trephined from the preserved sites to evaluate the percentage of bone and connective tissue (CT %) formed 8 months postRPP. Shapiro - Wilk test and paired and unpaired t-test. Horizontal resorption was significantly less in the test group (7.375 ± 1.64). Histomorphometry of these sites revealed a complete absence of residual graft particles, presence of trabecular bone, and a more mineralized matrix (63.256%) as compared to the control sites (46.833%). The use of DMBM along with the collagen membrane for RPP yielded better results both clinically and histomorphometically.

Evaluation of Articular Morphology and Congruency using a Combination of 3 Dimensional CT Based Bone Segmentation and Joint Surface Mapping

Category: Hindfoot; Ankle; Other Introduction/Purpose: Recently joint congruence has been given a lot of focus in studies evaluating foot and ankle deformities. XR and WBCT scans are the commonly used techniques, however, neither can accurately reflect articular surfaces particularly in joints where only partial bone surfaces are covered by articular cartilage. This study introduced a novel technique using 3D surface mapping and CT bone segmentation to assess articular morphology and congruence of the calcaneocuboid (CC) joint. Methods: A CT scan of a fresh frozen cadaveric foot without trauma history nor deformity was taken and then the calcaneus and cuboid bones were dissected free with all soft tissue removed. Segmentation and reconstruction of the calcaneus and cuboid from the CT scan was performed using Materialise Mimics. Surface mapping and digital reconstructions of the calcaneus and cuboid bones as well as the calcaneocuboid articular surfaces were then obtained using an Artec Space Spider 3D scanner. Both the CT and surface mapping reconstructions were imported into Geomagic Studio 10 where the reconstructed calcaneus via CT was merged with the reconstructed calcaneus via surface mapping. The same procedures were performed with the reconstructions of the cuboid. Then cartilage surfaces from the calcaneocuboid joint of the surface mapping reconstruction were outlined on and compared to the bone surfaces underneath. Results: The articular surfaces of the calcaneocuboid joint were shaped according to the bone contour noting however that on both sides, the articular surface did not fully match the bone surface. On the calcaneal side, the dimension of the bone surface was 357.72 mm2, while the articular surface was 300.92 mm2 (percentage of bone covered by cartilage: 84.12%). On the Cuboid side, the dimension of the bone surface was 372.41 mm2 while the articular surface was 302.60 mm2 (percentage of bone covered by cartilage: 81.25%). When restoring the articulation of the reconstructed calcaneus and cuboid, there was incongruence of the two bone surfaces with the dorsolateral corner of the calcaneus and the plantarmedial corner of the cuboid uncovered by its contralateral bone. The same applied to the articular surfaces but at a smaller uncovering level (Figure 1). Conclusion: Even with 3D CT segmentation and reconstruction of articulating bones, one has no knowledge of the precise articular surface of a joint. 3D surface scanning is a reliable method to study morphology of the cartilage surface of a joint. 3D CT reconstruction combined with 3D surface mapping is a useful tool for studying both the bony surface and the cartilage surface of a joint. This study has implications for treatment of any joint in the foot which appears subluxated on XR or CT scans and where this may represent the normal bone morphology but not true subluxation. Articular congruence study under weightbearing condition is currently under investigation by our research group.