The Effects of Signaling-Selective Parathyroid Hormone Analogs on Osteoporotic Osteocyte Apoptosis

Objectives: To compare the effects of signaling-selective parathyroid hormone analogs [G1, R19]hPTH(1–28) [GR(1–28)] and [G1, R19]hPTH(1–34) [GR(1–34)] on osteoporotic osteocyte apoptosis, and to explore the mechanism of the anti-osteoporotic difference. Methods: The osteoporosis model was established in eighty adult female C57BL/6 mice aged 12 weeks. The mice were subcutaneously administered with GR(1–28) and GR(1–34) 5 days per week for 8 weeks. Bilateral femur samples were collected at 4 and 8 weeks, and micro-computed tomography (CT), H&E staining and immunohistochemical staining analyses were performed. Results: From micro-CT analysis, GR(1–34) increased proximal femoral bone mineral density (BMD) and relative bone volume (BV/TV), which was higher than GR(1–28) did. In addition, more trabecular number (Tb.N), thinner trabecular thickness (Tb.Th) and wider trabecular separation (Tb.Sp) were measured at week 8 using GR(1–34). From H&E and immunohistochemical staining, a stronger apoptosis inhibition was induced by GR(1–34) with more Bcl-2 secretion but less Bax expression, as opposed to GR(1–28). Conclusions: GR(1–34) shows better anti-osteoporotic effects than GR(1–28), which appears to be attributed to the activation of the PLC-independent PKC signaling pathway triggered by the former, inhibiting osteocyte apoptosis through up-regulation of Bcl-2 and down-regulation of Bax to increase bone mass and improving trabecular bone microstructure to enhance bone quality by reducing trabecular number, increasing trabecular thickness and trabecular space.

Extracorporeal Shockwave Therapy Modulates the Expressions of Proinflammatory Cytokines IL33 and IL17A, and Their Receptors ST2 and IL17RA, within the Articular Cartilage in Early Avascular Necrosis of the Femoral Head in a Rat Model

Avascular necrosis (AVN) of the femoral head (AVNFH) is a disease caused by injury to the blood supply of the femoral head, resulting in a collapse with osteonecrosis and damage to the articular cartilage. Extracorporeal shockwave therapy (ESWT) has been demonstrated to improve AVNFH owing to its anti-inflammation activity, angiogenesis effect, and tissue regeneration in clinical treatment. However, there are still so many pieces of the jigsaw that need to be fit into place in order to ascertain the mechanism of ESWT for the treatment of AVNFH. The study demonstrated that ESWT significantly protected the trabecular bone volume fraction BV/TV ( P < 0.01 ) and the trabecular thickness ( P < 0.001 ), while in contrast, the trabecular number and trabecular separation were not significantly different after treatment as compared with AVNFH. ESWT protected the articular cartilage in animal model of AVNFH. The levels of IL1-β and IL33 were significantly induced in the AVNFH group ( P < 0.001 ) as compared with Sham and ESWT groups and reduced in ESWT group ( P < 0.001 ) as compared with AVNFH group. In addition, the expression of the receptor of IL33, ST2, was reduced in AVNFH and induced after ESWT ( P < 0.001 ). The expression of IL17A was induced in the AVNFH group ( P < 0.001 ) and reduced in the ESWT group ( P < 0.001 ). Further, the expression of the receptor of IL17A, IL17RA, was reduced in the AVNFH group ( P < 0.001 ) and improved to a normal level in the ESWT group as compared with Sham group ( P < 0.001 ). Taken together, the results of the study indicated that ESWT modulated the expression of IL1-β, pro-inflammatory cytokines IL33 and IL17A, and their receptors ST2 and IL17RA, to protect against loss of the extracellular matrix in the articular cartilage of early AVNFH.

Comparison of anterior and posterior trabecular bone microstructure of human mandible using cone-beam CT and micro CT

Background The aim of this study was to compare the trabecular bone microstructures of anterior and posterior edentulous regions of human mandible using cone-beam computed tomography (CBCT) and micro computed tomography (µCT). Methods Twenty volumes of interests consisting of six anterior and fourteen posterior edentulous regions were obtained from human mandibular cadavers. A CBCT system with a resolution of 80 µm (3D Accuitomo 170, J. Morita, Kyoto, Japan) and a µCT system with a resolution of 35 µm (SkyScan 1173, Kontich, Belgium) were used to scan the mandibles. Three structural parameters namely, trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp) were analysed using CTAn software (v 1.11, SkyScan, Kontich, Belgium). For each system, the measurements obtained from anterior and posterior regions were tested using independent sample t-test. Subsequently, all measurements between systems were tested using paired t-test. Results In CBCT, all parameters of the anterior and posterior mandible showed no significant differences (p > 0.05). However, µCT showed a significant different of Tb.Th (p = 0.023) between anterior and posterior region. Regardless of regions, the measurements obtained using both imaging systems were significantly different (p ≤ 0.021) for Tb.Th and Tb.N. Conclusions The current study demonstrated that only the variation of Tb.Th between anterior and posterior edentulous region of mandible can be detected using µCT. In addition, CBCT is less feasible than µCT in assessing trabecular bone microstructures at both regions.

Assessment of Bone Regeneration Using Tooth Ash and Injectable Platelet Rich Fibrin: A Microcomputed Tomographic (CT) Analysis

Introduction: One of the main challenge of bone graft or socket preservation in particular is to get good quality and quantity of bone in short time prior to implant bed preparation. The buccal bone at the crest of the ridge is a very thin bone and usually resorb faster than the rest of alveolar bone which may hinder an optimum dento-osseous implant insertion. The purpose of this study will be to assess the bone regeneration capabilities of Tooth Ash Particles (TAP) with injectable Plasma Rich Fibrin (i-PRF) and Tooth Ash Particles (TAP) alone at defects created in the goat mandible bone using micro-computed tomographic (micro-CT). Materials and Methods: A total, 54 bone defect (5 mm × 8 mm) were performed in the 18 goats. The created defect received different treatment (Tx): Tx.A: Unfilled defect (allow natural bone regeneration; Tx.B: Tooth Ash particle (TAP) alone; Tx.C: Tooth Ash + injectable PRF (TAP/i-PRF). Six goats, were sacrificed at different time points:Group 1: at 2nd week, Group2: at 5th week and Group3 at 8th week. The newly formed bone (NFB) was analyzed using micro-CT at different time points. Quantitative and qualitative assessment were carried out namely; the volume of new bone formation (NF-BV) within the defect and its mineral density (NF-BMD), Trabecular Thickness (Tb Th), Trabecular Number (Tb N) and Trabecular Separation (Tb Sp). Result: By 8th week, the mean NF-BV was 69.482 ± 6.554 mm3 (cubic millimeter), 65.872±6.804 mm3, 26.820±14.643 mm3, while the mean NF-BMD was 0.417±0.119g/mm3, 0.786±0.036 g/mm3, 0.805±0.033 g/mm3 for the defects which received Tx.C, Tx.B and Tx.A respectively. At 8th weekTb Th of NFB was 0.612±0.168, 0.913±0.112, and 0.701 ±0.126, Trabecular Number of NFB was 2.062±0.946, 1.002±0.155, and 1.816±2.042 and, Trabecular Separation of NFB was 0.330 ±0.131, 0.559 ±0.110, and 0.495 ±0.258 for the defects which received Tx.A, Tx.B and Tx.C respectively. Conclusion: Micro-CT study demonstrated that tooth ash particles mixed with injectable Platelet Rich Fibrin (i-PRF) on mandibular bone defect in goat’s model, resulting in new bone with significantly higher volume, mineral density and less remodeling rate when compared with normal bone regeneration of unfilled defects.

Experimental study exploring the factors that promote rib fragility in the elderly

Rib fractures represent a common injury type due to blunt chest trauma, affecting hospital stay and mortality especially in elderly patients. Factors promoting rib fragility, however, are little investigated. The purpose of this in vitro study was to explore potential determinants of human rib fragility in the elderly. 89 ribs from 13 human donors (55–99 years) were loaded in antero-posterior compression until fracture using a material testing machine, while surface strains were captured using a digital image correlation system. The effects of age, sex, bone mineral density, rib level and side, four global morphological factors (e.g. rib length), and seven rib cross-sectional morphological factors (e.g. cortical thickness, determined by μCT), on fracture load were statistically examined using Pearson correlation coefficients, Mann–Whitney U test as well as Kruskal–Wallis test with Dunn-Bonferroni post hoc correction. Fracture load showed significant dependencies (p < 0.05) from bone mineral density, age, antero-posterior rib length, cortical thickness, bone volume/tissue volume ratio, trabecular number, trabecular separation, and both cross-sectional area moments of inertia and was significantly higher at rib levels 7 and 8 compared to level 4 (p = 0.001/0.013), whereas side had no significant effect (p = 0.989). Cortical thickness exhibited the highest correlation with fracture load (r = 0.722), followed by the high correlation of fracture load with the area moment of inertia around the longitudinal rib cross-sectional axis (r = 0.687). High correlations with maximum external rib surface strain were detected for bone volume/tissue volume ratio (r = 0.631) and trabecular number (r = 0.648), which both also showed high correlations with the minimum internal rib surface strain (r = − 0.644/ − 0.559). Together with rib level, the determinants cortical thickness, area moment of inertia around the longitudinal rib cross-sectional axis, as well as bone mineral density exhibited the largest effects on human rib fragility with regard to the fracture load. Sex, rib cage side, and global morphology, in contrast, did not affect rib fragility in this study. When checking elderly patients for rib fractures due to blunt chest trauma, patients with low bone mineral density and the mid-thoracic area should be carefully examined.

β-Hydroxy-β-Methylbutyrate (HMB) Supplementation Prevents Bone Loss during Pregnancy—Novel Evidence from a Spiny Mouse (Acomys cahirinus) Model

The aim of this study was to determine the effects of ß-hydroxy-ß-methylbutyrate (HMB) supplementation during pregnancy on postpartum bone tissue quality by assessing changes in trabecular and compact bone as well as in hyaline and epiphyseal cartilage. The experiment was carried out on adult 6-month-old female spiny mice (Acomys cahirinus) divided into three groups: pregnant control (PregCont), pregnant HMB-treated (supplemented with 0.02 g/kg b.w of HMB during the second trimester of pregnancy, PregHMB), and non-pregnant females (NonPreg). Cross-sectional area and cortical index of the femoral mid-shaft, stiffness, and Young modulus were significantly greater in the PregHMB group. Whole-bone mineral density was similar in all groups, and HMB supplementation increased trabecular number. Growth plate cartilage was the thinnest, while the articular cartilage was the thickest in the PregHMB group. HMB supplementation increased the content of proteoglycans in the articular cartilage and the percentage of immature collagen content in metaphyseal trabeculae and compact bone. In summary, dietary HMB supplementation during the second trimester of pregnancy intensifies bone metabolic processes and prevents bone loss during pregnancy.

Electroacupuncture stimulation at BL20, BL23 and SP6 prevents hind limb unloading–induced osteoporosis in rats

Background: Bone loss induced by microgravity is a serious problem in space flight. However, the effects of acupuncture stimulation on osteoporosis induced by microgravity have not been studied. With the goal of developing an effective countermeasure, our aim was to evaluate the effects of electroacupuncture (EA) stimulation at BL20, BL23, and SP6 on osteoporosis induced by simulated microgravity in rats. Methods: Thirty male Wistar rats (aged 10 weeks) were randomly divided into three groups: healthy control group (CON, n = 10), hind limb unloading by tail-suspension group (T-S, n = 10), and EA treatment group (TRE, n = 10). Rats in the T-S and TRE groups were subjected to tail-suspension at −30° for 30 days, while the CON group experienced freedom of activity. In this period, the TRE group received EA treatment at BL20, BL23, and SP6 for 30 min every other day, which continued for 30 days. The microarchitecture of the proximal tibia and the biomechanical features of the femur in the rats were analyzed. In addition, the levels of serum biomarkers bone alkaline phosphatase (BALP) and osteocalcin (BGP) were measured. Results: Compared with the CON group, the value of bone volume/total volume (BV/TV) and trabecular number (Tb.N) of the tibias in the TRE group remarkably decreased ( p < 0.01). However, these changes were markedly less than those of the T-S group after 4 weeks of EA treatment ( p < 0.05). Moreover, the serum concentration of BGP in the TRE group was also significantly higher than that of the T-S group ( p < 0.05). Conclusions: These findings indicate that EA stimulation at BL20, BL23, and SP6 retards osteoporosis induced by hind limb unloading in rats.

Osseointegration of a novel dental implant in canine

This study aimed to compare and verify the osseointegration performance of a novel implant (NI) in vivo, which could provide a useful scientific basis for the further development of NIs. Thirty-two NIs treated with hydrofluoric acid and anodization and sixteen control implants (CIs) were placed in the mandibles of 8 beagles. Micro-CT showed that the trabecular number (Tb.N) significantly increased and trabecular separation (Tb.Sp) significantly decreased in the NIs at 2 weeks. Significant differences were found in the trabecular thickness, Tb.N, Tb.Sp, bone surface/bone volume ratio, and bone volume/total volume ratio between the two groups from the 2nd–4th weeks. However, there were no significant differences between the two groups in the bone volume density at 2, 4, 8, or 12 weeks or bone-implant contact at 2 or 4 weeks, but the BIC in the CIs was higher than that in the NIs at the 8th and 12th weeks. Meanwhile, the histological staining showed a similar osseointegration process between the two groups over time. Overall, the NIs could be used as new potential implants after further improvement.

Electrospun Poly(butylene-adipate-co-terephthalate)/Nano-hyDroxyapatite/Graphene Nanoribbon Scaffolds Improved the In Vivo Osteogenesis of the Neoformed Bone

Electrospun ultrathin fibrous scaffold filed with synthetic nanohydroxyapatite (nHAp) and graphene nanoribbons (GNR) has bioactive and osteoconductive properties and is a plausible strategy to improve bone regeneration. Poly(butylene-adipate-co-terephthalate) (PBAT) has been studied as fibrous scaffolds due to its low crystallinity, faster biodegradability, and good mechanical properties; however, its potential for in vivo applications remains underexplored. We proposed the application of electrospun PBAT with high contents of incorporated nHAp and nHAp/GNR nanoparticles as bone grafts. Ultrathin PBAT, PBAT/nHAp, and PBAT/nHAp/GNR fibers were produced using an electrospinning apparatus. The produced fibers were characterized morphologically and structurally using scanning electron (SEM) and high-resolution transmission electron (TEM) microscopies, respectively. Mechanical properties were analyzed using a texturometer. All scaffolds were implanted into critical tibia defects in rats and analyzed after two weeks using radiography, microcomputed tomography, histological, histomorphometric, and biomechanical analyses. The results showed through SEM and high-resolution TEM characterized the average diameters of the fibers (ranged from 0.208 µm ± 0.035 to 0.388 µm ± 0.087) and nHAp (crystallite around 0.28, 0.34, and 0.69 nm) and nHAp/GNR (200–300 nm) nanoparticles distribution into PBAT matrices. Ultrathin fibers were obtained, and the incorporated nHAp and nHAp/GNR nanoparticles were well distributed into PBAT matrices. The addition of nHAp and nHAp/GNR nanoparticles improved the elastic modulus of the ultrathin fibers compared to neat PBAT. High loads of nHAp/GNR (PBATnH5G group) improved the in vivo lamellar bone formation promoting greater radiographic density, trabecular number and stiffness in the defect area 2 weeks after implantation than control and PBAT groups.

Subchondral Trabecular Microstructure and Articular Cartilage Damage Variations Between Osteoarthritis and Osteoporotic Osteoarthritis: A Cross-sectional Cohort Study

Osteoporotic osteoarthritis (OP-OA) is a specific type of OA. In this study, we aimed to assess the subchondral plate and rod microstructural differences between OA and OP-OA patients by using an individual trabeculae segmentation (ITS) system and to analyze the relationships between subchondral microstructures and cartilage damage in OA and OP-OA patients. Overall, 31 femoral heads were included in this study, which included 11 samples with OA and 13 samples with OP-OA; the normal control (NC) group contained 7 healthy femoral heads. ITS was performed to segment the subchondral trabecular bone into plate and rod trabeculae based on microcomputed tomography (micro-CT) images. We compared the plate and rod trabeculae of the subchondral trabecular bone between OA and OP-OA patients. The Osteoarthritis Research Society International (OARSI) score was employed to evaluate cartilage damage based on histological observations. Pearson's correlation coefficient and linear regression analysis were applied to analyze the relationships between subchondral microstructures and articular cartilage damage. Results showed that several microstructural parameters, including bone volume fraction (BV/TV), plate bone volume fraction (pBV/TV), rod bone volume fraction (rBV/TV), plate trabecular number (pTb.N), rod trabecular number (rTb.N), junction density between rod and plate (R-P Junc.D), and junction density between plate and plate (P-P Junc.D), were significantly decreased in patients with OP-OA compared with those in patients with OA (p &lt; 0.05). Histological observations indicated that cartilage damage was more serious in patients with OP-OA than that in patients with OA (p &lt; 0.05). Moreover, BV/TV, pBV/TV, pTb.N, and pTb.Th were significantly related to the OARSI score in both OA and OP-OA patients. These results indicated that there were differences in the subchondral rod and plate trabeculae between OA and OP-OA patients. Subchondral decreased plate trabeculae (pBV/TV, pTb.N, and pTb.Th) might account for cartilage damage in the progression of OP-OA. This study provided new insights to research OA when it is combined with OP.