Effect of Topical PTH 1-34 Functionalized to Biogran® in the Process of Alveolar Repair in Rats Submitted to Orchiectomy

(1) Background: There are many therapies for osteoporosis control and bone maintenance; anabolic drugs such as teriparatide and bone grafts help in the repair process and stimulate bone formation. Thus, the aim of the present study was to evaluate the behavior of repaired bone in the presence of PTH (teriparatide) associated with Biogran® (biomaterial) through a sonochemical procedure after extraction in rats. (2) Methods: The insertion of Biogran® with PTH in the alveolus was performed 30 days after incisor extraction. Euthanasia occurred after 60 days. (3) Results: The use of local treatment of PTH loaded with Biogran® in healthy rats promoted good results for micro-CT, with an increase in percentage and bone volume, number and trabecular separation and less total porosity. Greater immunostaining for Wnt, β-Catenin and osteocalcin proteins and lower expression for Thrombospondin-Related Adhesive Protein (TRAP), which shows an increase in the number of osteoblasts and inhibition of osteoclast action. However, the treated orchiectomized groups did not obtain such expressive results. (4) Conclusion: The use of Biogran® with PTH improved alveolar repair in rats. However, new researches with more efficient doses must be studied to collaborate effectively with the formation of a quality bone after the orchiectomy.

Role of the Microbiome in Regulating Bone Metabolism and Susceptibility to Osteoporosis

The human microbiota functions at the interface between diet, medication-use, lifestyle, host immune development and health. It is therefore closely aligned with many of the recognised modifiable factors that influence bone mass accrual in the young, and bone maintenance and skeletal decline in older populations. While understanding of the relationship between micro-organisms and bone health is still in its infancy, two decades of broader microbiome research and discovery supports a role of the human gut microbiome in the regulation of bone metabolism and pathogenesis of osteoporosis as well as its prevention and treatment. Pre-clinical research has demonstrated biological interactions between the microbiome and bone metabolism. Furthermore, observational studies and randomized clinical trials have indicated that therapeutic manipulation of the microbiota by oral administration of probiotics may influence bone turnover and prevent bone loss in humans. In this paper, we summarize the content, discussion and conclusions of a workshop held by the Osteoporosis and Bone Research Academy of the Royal Osteoporosis Society in October, 2020. We provide a detailed review of the literature examining the relationship between the microbiota and bone health in animal models and in humans, as well as formulating the agenda for key research priorities required to advance this field. We also underscore the potential pitfalls in this research field that should be avoided and provide methodological recommendations to facilitate bridging the gap from promising concept to a potential cause and intervention target for osteoporosis.

A Review of Current Concepts in Full Arch Rehabilitation with Dental Implants

Various causes can be responsible for tooth loss. In general, caries, periodontal disease, facial trauma, pathology of the jaws, among other causes, could lead to the loss of a tooth or a group of teeth. As a consequence, the stimuli that participate in bone maintenance are compromised and bone reduction occurs gradually, making it difficult to use conventional prostheses. Fortunately, technological advances applied to dental implantology have allowed us to perform full-arch prosthetic treatments, managing to rehabilitate the form, function, esthetics and lost self-esteem in patients with severe atrophy of the jaws. The objective of this chapter is to describe the key and current aspects in full-arch rehabilitation with dental implants.

Peri-Implant Tissue Behaviour Next to Different Titanium Surfaces: 16-Year Post-Trial Follow-Up

The present post-trial follow-up investigated the influence of titanium implants with different surface treatments on clinical behavior of soft and hard peri-implant tissues. Each of the 18 included patients received at least two adjacent implants: one control implant with a dual acid-etched (DAE) surface in their apical portion and a machined coronal part, and one test implant with a DAE surface up to its coronal portion. Peri-implant bone level change (BLC), probing depth (PD), bleeding on probing (BOP) and plaque index (PI) were recorded. A total of 42 implants was inserted. The mean follow-up period was 9.3 years (range: 5–16 years) and there were six dropouts. No implant failed. Moderate crestal bone remodeling occurred during the first year after implant insertion, with lower bone loss next to test implants compared to control ones (0.80 vs. 1.39 mm; p = 0.002). This difference was also detected at the 5- (p = 0.011), 6- (p = 0.008) and 7-year follow-up appointment (p = 0.027). No statistically significant differences were found in bone resorption between implants rehabilitated with ceramic vs. composite resin veneering material. No statistically significant differences were detected between test and control implants for BOP, PI, and PD at any time point. The results of the present study suggest that DAE surfaces reduce peri-implant bone loss in the initial phase of healing compared to machined surfaces, while they do not significantly affect soft peri-implant tissue and bone maintenance in the long-term. In conclusion, the minimally rough surfaces favour peri-implant bone maintenance and their effect is greater in the first year post implant insertion.

Caspase-1 Inhibition Impacts the Formation of Chondrogenic Nodules, and the Expression of Markers Related to Osteogenic Differentiation and Lipid Metabolism

Caspase-1, as the main pro-inflammatory cysteine protease, was investigated mostly with respect to inflammation-related processes. Interestingly, caspase-1 was identified as being involved in lipid metabolism, which is extremely important for the proper differentiation of chondrocytes. Based on a screening investigation, general caspase inhibition impacts the expression of Cd36 in chondrocytes, the fatty acid translocase with a significant impact on lipid metabolism. However, the engagement of individual caspases in the effect has not yet been identified. Therefore, the hypothesis that caspase-1 might be a candidate here appears challenging. The primary aim of this study thus was to find out whether the inhibition of caspase-1 activity would affect Cd36 expression in a chondrogenic micromass model. The expression of Pparg, a regulator Cd36, was examined as well. In the caspase-1 inhibited samples, both molecules were significantly downregulated. Notably, in the treated group, the formation of the chondrogenic nodules was apparently disrupted, and the subcellular deposition of lipids and polysaccharides showed an abnormal pattern. To further investigate this observation, the samples were subjected to an osteogenic PCR array containing selected markers related to cartilage/bone cell differentiation. Among affected molecules, Bmp7 and Gdf10 showed a significantly increased expression, while Itgam, Mmp9, Vdr, and Rankl decreased. Notably, Rankl is a key marker in bone remodeling/homeostasis and thus is a target in several treatment strategies, including a variety of fatty acids, and is balanced by its decoy receptor Opg (osteoprotegerin). To evaluate the effect of Cd36 downregulation on Rankl and Opg, Cd36 silencing was performed using micromass cultures. After Cd36 silencing, the expression of Rankl was downregulated and Opg upregulated, which was an inverse effect to caspase-1 inhibition (and Cd36 upregulation). These results demonstrate new functions of caspase-1 in chondrocyte differentiation and lipid metabolism-related pathways. The effect on the Rankl/Opg ratio, critical for bone maintenance and pathology, including osteoarthritis, is particularly important here as well.

Bothrops moojeni Venom and Its Components Strongly Affect Osteoclasts’ Maturation and Protein Patterns

Osteoclasts (OCs) are important for bone maintenance, calcium balance, and tissue regeneration regulation and are involved in different inflammatory diseases. Our study aimed to evaluate the effect of Bothrops moojeni’s venom and its low and high molecular mass (HMM and LMM) fractions on human peripheral blood mononuclear cell (PBMC)-derived OCs’ in vitro differentiation. Bothrops moojeni, a Brazilian lanced-head viper, presents a rich but not well-explored, venom composition. This venom is a potent inducer of inflammation, which can be used as a tool to investigate the inflammatory process. Human PBMCs were isolated and induced to OC differentiation following routine protocol. On the fourth day of differentiation, the venom was added at different concentrations (5, 0.5, and 0.05 µg/mL). We observed a significant reduction of TRAP+ (tartrate-resistant acid phosphatase) OCs at the concentration of 5 µg/mL. We evaluated the F-actin-rich OCs structure’s integrity; disruption of its integrity reflects bone adsorption capacity. F-actin rings phalloidin staining demonstrated that venom provoked their disruption in treated OCs. HMM, fraction reduces TRAP+ OCs at a concentration of 5 µg/mL and LMM fraction at 1 µg/mL, respectively. Our results indicate morphological changes that the venom induced cause in OCs. We analyzed the pattern of soluble proteins found in the conditioned cell culture medium OCs treated with venom and its fractions using mass spectrometry (LC-MS/IT-Tof). The proteomic analyses indicate the possible pathways and molecular mechanisms involved in OC reduction after the treatment.

Monitoring the reduction and maintenance of periprosthetic bone tissue in cementless primary hip endoprosthesis with alendronate therapy

Loss of periprosthetic bone tissue in primary hip endoprostheses is common in clinical practice. This loss can be progressive and in extreme conditions can jeopardize the longevity of the prosthesis. In order to monitor the function of Alendronate therapy for bone maintenance, the study included 50 patients with implanted total cement-free hip endoprosthesis (TPH). The first group of 25 patients received Alendronate, calcium and vitamin D3 orally postoperatively. The second group of 25 patients were examined postoperatively without therapy. Patients were followed by radiographic and dual-energy X-ray absorptiometry (DXA) at 6 and 12 months. The study showed that in patients with TPH there was a difference in the X-ray findings as well as occurrence of osteolysis in certain Gruen zones, which was confirmed by changes in the state of bone mineral density (BMD) and bone mineral content (BMC) in the interval between 6 and 12 months using the DXA method. Alendronate therapy after TPH implantation allows reduction of periprosthetic bone mass loss, maintenance of bone mineralization and implant hardening.

Prospective radiographic evaluation of peri-implant bone maintenance on osseointegrated implants with frictional morse taper connection and platform switching: Cases report

Objective: The aim of the present study was to evaluate radiographically the remodeling of the peri-implant bone crest in prosthetic friction morse cone implants, with platform switching, after 12 months of application of prosthetic load. Materials and Methods: 16 implants were installed, in 10 patients, rehabilitated with partial, single and multiple metal-ceramic prostheses, submitted to prosthetic function in the period of 12 months. Periapical radiographs to measure the distance between the mesial and distal marginal bone crest and the platform of each implant, were performed at the time of installing the prostheses and 12 months later. The images obtained at different intervals were digitized and analyzed using Image J software TD. Results: At the time of installing the prostheses, the averages of measurements on the distal and mesial surfaces were 0.57 mm (standard deviation 0.45) and 0.55 mm (standard deviation 0.41) respectively. After 12 months in function, the averages obtained were 0.59 mm (standard deviation 0.48) on the distal surface and 0.57 mm on the mesial surface, (standard deviation 0.34). Conclusion: In this radiographic evaluation, it was possible to observe that the implants with prosthetic connection of the frictional Cone Morse type with platform switching presented an average of 0.2mm of cervical bone remodeling, after 12 months in function, seeming to be a good alternative for periodic bone maintenance deploy.

The receptor activator of nuclear factor κΒ ligand receptor leucine-rich repeat-containing G-protein-coupled receptor 4 contributes to parathyroid hormone–induced vascular calcification

Graphical Abstract Background In chronic kidney disease, serum phosphorus (P) elevations stimulate parathyroid hormone (PTH) production, causing severe alterations in the bone–vasculature axis. PTH is the main regulator of the receptor activator of nuclear factor κB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system, which is essential for bone maintenance and also plays an important role in vascular smooth muscle cell (VSMC) calcification. The discovery of a new RANKL receptor, leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4), which is important for osteoblast differentiation but with an unknown role in vascular calcification (VC), led us to examine the contribution of LGR4 in high P/high PTH–driven VC. Methods In vivo studies were conducted in subtotally nephrectomized rats fed a normal or high P diet, with and without parathyroidectomy (PTX). PTX rats were supplemented with PTH(1–34) to achieve physiological serum PTH levels. In vitro studies were performed in rat aortic VSMCs cultured in control medium, calcifying medium (CM) or CM plus 10−7 versus 10−9 M PTH. Results Rats fed a high P diet had a significantly increased aortic calcium (Ca) content. Similarly, Ca deposition was higher in VSMCs exposed to CM. Both conditions were associated with increased RANKL and LGR4 and decreased OPG aorta expression and were exacerbated by high PTH. Silencing of LGR4 or parathyroid hormone receptor 1 (PTH1R) attenuated the high PTH–driven increases in Ca deposition. Furthermore, PTH1R silencing and pharmacological inhibition of protein kinase A (PKA), but not protein kinase C, prevented the increases in RANKL and LGR4 and decreased OPG. Treatment with PKA agonist corroborated that LGR4 regulation is a PTH/PKA-driven process. Conclusions High PTH increases LGR4 and RANKL and decreases OPG expression in the aorta, thereby favouring VC. The hormone’s direct pro-calcifying actions involve PTH1R binding and PKA activation.