Reduce Bone Loss Research Articles

Eldecalcitol Add-On to Risedronate Reduces Bone Loss from Aromatase Inhibitors in Postmenopausal Breast Cancer Patients.

Aromatase inhibitors (AIs) cause bone loss and increase fracture risk in women with hormone receptor-positive early-stage breast cancer (HR+EBC). Bone antiresorptive agents are recommended for patients at risk of fragility fractures. Eldecalcitol, combined with bisphosphonate, increases bone mineral density (BMD) in primary osteoporosis. To determine the effect of eldecalcitol (0.75 ug/day) add-on therapy to risedronate (17.5 mg/week) on bone quantity and quality in women treated with AI. Open-label randomized control trial. Postmenopausal women with HR+EBC (TNM stage 0-3A) treated with risedronate for more than 12 months. 200 patients were enrolled; 196 patients were eligible for the full analysis set after excluding those without follow-up BMD data. Participants were advised to take vitamin D and calcium, yet many were vitamin D deficient or insufficient. Participants were randomly assigned in a 1:1 ratio to receive either eldecalcitol add-on therapy or risedronate monotherapy. Primary outcome was the group difference in the change of LS-BMD in 24 months. Secondary outcomes included FN-BMD, TH-BMD, trabecular bone score (TBS), and the incidence of vertebral and non-vertebral fractures. The increase at LS-, FN-, and TH-BMD at 24 months was larger in the add-on therapy group than in the monotherapy group, with a group difference (add-on therapy minus monotherapy) estimate of 0.020 g/cm2 (95% confidence interval (CI): 0.010-0.029 g/cm2, p< 0.001) for LS-BMD. The incidence rate ratio (add-on therapy/monotherapy) for morphometric vertebral fractures was 0.292 (95% CI: 0.080-1.061, p= 0.061). No group difference was detected in the change in TBS. Eldecalcitol add-on therapy increased LS-BMD in osteopenic to osteoporotic postmenopausal women treated with an AI and risedronate.

Resveratrol protects against Rankl-induced mineralized bone damage in a transgenic medaka fish model of osteoporosis

Natural substances with bone protective potential always greatly attract researchers for the development of safer and more effective drugs for osteopenia and osteoporosis. Resveratrol (RES), a plant polyphenol found in red grapes and berries has been commonly suggested as supplement for bone health. It has shown bone anabolic and anti-resorptive effects in different in vitro cell cultures and in vivo rodent models. Recently, the medaka fish (Oryzias latipes) has emerged as a valuable model organism for bone research. In this study, we present, for the first time, evidence that resveratrol, tested at five doses (25, 50, 100, 150, and 200 μM), mitigated bone loss induced by Rankl in a transgenic medaka model for osteoporosis. Notably, the dose of 150 μM exhibited the highest bone-protective and anti-resorptive effect, reducing bone loss by approximately 20%. However, at the same dose, RES did not significantly affect the signal densities of green fluorescent protein (GFP) and alizarin complexone (ALC), which represent osteoblasts and mineralized matrix, respectively, in col10a1:nlGFP transgenic medaka larvae. In these larvae, osteoblasts were marked by GFP, and bone was stained with ALC. Our findings provide significant evidence from a non-rodent model regarding the therapeutic potential of resveratrol.

Effects of Synbiotic Supplementation on Bone and Metabolic Health in Caucasian Postmenopausal Women: Rationale and Design of the OsteoPreP Trial.

Correction of decreased diversity of the gut microbiome, which is characteristic of menopause, by supplementation with a synbiotic may attenuate or prevent dysbiosis processes and preserve bone mass. We describe the rationale and design of the OsteoPreP trial aimed at evaluating the effects of 12 months of supplementation with a synbiotic on bone and metabolic health in postmenopausal Caucasian women. This is a randomized, double-blinded, placebo-controlled trial among 160 Caucasian, postmenopausal women with no current diagnosis of osteoporosis or supplementation with pro- or prebiotics, and no medical treatment affecting bone turnover. Dual-energy X-ray absorptiometry scans will be conducted at screening to confirm absence of osteoporosis. The primary outcome is the relative change (%) in total bone mineral density of the distal tibia at 12 months post-treatment between the active and placebo groups, as determined via high-resolution peripheral quantitative computed tomography. Secondary outcomes are the effects on immune system modulation and cognition, gut microbiota composition, and musculoskeletal and metabolic functions, with particular emphasis on blood glucose regulation. The trial will inform on the efficacy and safety of a synbiotic containing both aerobic and anerobic bacterial strains and a prebiotic fiber on reduction in bone loss and on indices of blood glucose regulation. This trial may pave the way for an exciting field of translational research and be the underpinnings of the prevention strategy of osteoporosis and the management of metabolic dysfunction in postmenopausal women. The trial is registered with clinicaltrials.gov (NCT05348694).

Methotrexate inhibits glucocorticoids-induced osteoclastogenesis via activating IFN-γR/STAT1 pathway in the treatment of rheumatoid arthritis

ObjectivesRheumatoid arthritis (RA) is a chronic autoimmune disease characterised by the synovitis and bone erosion. The combination therapy of glucocorticoids (GCs) and methotrexate (MTX) is recommended in early RA management,...

Impaired Development of Collagen Antibody-Induced Arthritis in Rab44-Deficient Mice.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by immune cell-mediated joint inflammation and subsequent osteoclast-dependent bone destruction. Collagen antibody-induced arthritis (CAIA) is a useful mouse model for examining the inflammatory mechanisms in human RA. Previously, we identified the novel gene Rab44, which is a member of the large Rab GTPase family and is highly expressed in immune-related cells and osteoclasts. In this study, we induced CAIA in Rab44-knockout (KO) mice to investigate the effects of Rab44 on inflammation, cell filtration, and bone destruction. Compared with wild-type (WT) mice, Rab44-KO mice showed reduced inflammation in arthritis under CAIA-inducing conditions. Rab44-KO CAIA mice exhibited reduced cell filtration in the radiocarpal joints. Consistent with these findings, Rab44-KO CAIA mice showed decreased mRNA levels of arthritis-related marker genes including genes for inflammation, cartilage turnover, bone formation, and bone absorption markers. Rab44-KO CAIA mice exhibited predominant infiltration of M2-type macrophages at inflammatory sites and reduced bone loss compared to WT CAIA mice. These results indicate that Rab44 deficiency reduces the progression of inflammation in CAIA in mice.

Preclinical Validation of MIN-T: A Novel Controlled-Released Formulation for the Adjunctive Local Application of Minocycline in Periodontitis.

Background: Adjunctive treatment of periodontitis lacks solutions which allow for enough time for wound healing in the periodontal pockets by avoiding fast re-colonization. Such a solution might be an antibiotic-containing formulation with a controlled release over a period of weeks. Here, a recently described minocycline-containing approach is qualified for further clinical development by focusing on proof-of-concept, systemic burden, resistance development, and degradation studies. Methods: Animal studies were done in two different (mouse-chamber, rat Porphyromonas gingivalis challenging) models, including effects on inflammation markers, bone loss, and bone structure. Also, serum concentrations of minocycline after local application were determined by HPLC-MS/MS. The resistance status of bacterial clinical isolates against minocycline was investigated and the degradation of the formulation was characterized by laser scanning and scanning electron microscopy. Results: Animal studies clearly demonstrated the applicability of the new formulation in the investigated models. Inflammation markers decreased in a dose-dependent manner and reduced bone loss compared to non-treated group was observed. Therefore, the systemic burden of the antibiotic was neglectable. Minocycline is still effective against oral pathogens; resistance development was not seen. The biodegradable thread was first swollen and subsequently degraded over a period of weeks. Conclusions: The results support the continued clinical development of this new formulation. A phase I clinical trial is planned to further evaluate its safety and efficacy.

Puerarin alleviates osteoporosis in rats by targeting the JAK2/STAT3 signaling pathway.

Osteoporosis (OP) is a common chronic progressive bone disease that increases fracture risk in postmenopausal women. Research suggests that puerarin (Pue) may be an effective treatment for OP. This study examined the effects and underlying mechanisms of Pue in treating postmenopausal osteoporosis (PMOP) in rats. Sprague-Dawley (SD) rats underwent bilateral ovariectomy to simulate PMOP and were then treated with subcutaneous injections of Pue. Bone mineral density (BMD) was measured using a bone densitometer. Micro-CT scans assessed femur bone structure and various parameters were calculated: bone volume fraction (BV/TV), bone surface density (BS/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), and bone surface area-to-bone volume ratio (BS/BV). Hematoxylin-eosin (HE) staining was employed to observe femoral tissue pathology. Serum levels of bone formation metabolism-related markers-osteocalcin (OC), bone alkaline phosphatase (BALP), and procollagen type I N-terminal propeptide (PINP)-were measured via enzyme-linked immunosorbent assay (ELISA). The protein expression levels of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in bone tissue were evaluated using Western blotting assay. The results showed improved bone density and reduced bone loss in rats treated with Pue. There were also significant increases in serum levels of OC and BALP, indicating enhanced osteogenesis. Furthermore, there was a decrease in activation of the JAK2/STAT3 pathway in femoral tissue, suggesting a pathway inhibition. These findings indicate that Pue may combat osteoporosis by promoting osteogenesis and inhibiting activation of the JAK2/STAT3 pathway activation.

Debridement and bone graft fusion via the lateral extracavitary approach combined with lateral and posterior screw-rod fixation in the treatment of thoracic spinal tuberculosis: A retrospective study of 38 cases

ObjectivesThoracic spinal tuberculosis (TB) is still common, and surgical treatment can rapidly relieve pain, correct deformity, reduce bone loss and prevent further damage to neurological function. We have practiced an efficient and safe surgical method. MethodsFrom January 2013 to April 2021, 38 patients with thoracic spinal TB were included in our study. Debridement and bone grafting were performed via the lateral extracavitary approach, combined with two different fixation methods. Data from these cases were analyzed retrospectively. ResultsFor all cases, the C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR) of all the patients decreased to normal levels at the last follow-up. The average visual analog scale (VAS) score was 7.5 ± 1.6 preoperatively and 0.6 ± 0.8 at the last follow-up, showing a significant reduction. The average angle of kyphosis correction was 6.3 ± 4.7°, and the loss of correction was 1.4 ± 1.6°. Neurological function was significantly improved in all cases according to the American Spinal Injury Association (ASIA) classification. Solid fusion was observed in all cases at the last follow-up. ConclusionsDebridement and bone graft fusion via the lateral extracavitary approach combined with two fixation methods can be very effective in the treatment of thoracic spinal TB.

Nutraceuticals in osteoporosis prevention.

Nutraceuticals are gaining popularity as they can contribute to bone health by delaying the onset or slowing down the progression of pathological bone loss. Osteoporosis's bone loss is a concern for older adults and a crucial aspect of aging. Maintaining healthy bones is the key to living a full and active life. Our review explores the current knowledge on the role of nutraceuticals in preventing osteoporosis by focusing on three main aspects. First, we provide an overview of osteoporosis. Second, we discuss the latest findings on natural nutraceuticals and their efficacy in reducing bone loss, emphasizing clinical trials. Third, we conduct a structured analysis to evaluate nutraceuticals' pros and cons and identify translational gaps. In conclusion, we must address several challenges to consolidate our knowledge, better support clinicians in their prescriptions, and provide people with more reliable nutritional recommendations to help them lead healthier lives.

Administration of low intensity vibration and a RANKL inhibitor, alone or in combination, reduces bone loss after spinal cord injury-induced immobilization in rats

We previously reported an ability of low-intensity vibration (LIV) to improve selected biomarkers of bone turnover and gene expression and reduce osteoclastogenesis but lacking of evident bone accrual. In this study, we demonstrate that a prolonged course of LIV that initiated at 2 weeks post-injury and continued for 8 weeks can protect against bone loss after SCI in rats. LIV stimulates bone formation and improves osteoblast differentiation potential of bone marrow stromal stem cells while inhibiting osteoclast differentiation potential of marrow hematopoietic progenitors to reduce bone resorption. We further demonstrate that the combination of LIV and RANKL antibody reduces SCI-related bone loss more than each intervention alone. Our findings that LIV is efficacious in maintaining sublesional bone mass suggests that such physical-based intervention approach would be a noninvasive, simple, inexpensive and practical intervention to treat bone loss after SCI. Because the combined administration of LIV and RANKL inhibition better preserved sublesional bone after SCI than either intervention alone, this work provides the impetus for the development of future clinical protocols based on the potential greater therapeutic efficacy of combining non-pharmacological (e.g., LIV) and pharmacological (e.g., RANKL inhibitor or other agents) approaches to treat osteoporosis after SCI or other conditions associated with severe immobilization.

Reversal of Bone Mineral Density Loss Through Lifestyle Changes: A Case Report.

Approximately 10 million individuals in the United States have osteoporosis and 44 million have low bone mineral density which puts them at risk for bone breaks. This presents a large burden on our health care system since about one-quarter of hip fracture patients never regain full function, need nursing care, and, for those over age 50, 24% die within one year. Oral bisphosphonates are often used as first-line therapy for the treatment of osteoporosis; however, patients frequently experience significant side effects. In addition, bisphosphonates inhibit bone loss by initiating apoptosis in osteoclasts that remove old bone, thus allowing old bone to accumulate and slowing the activity of osteoblasts that create new bone, thereby affecting bone quality. As an alternative, a bone-friendly lifestyle, including calcium and vitamin D consumption, exercise, smoking cessation, and a decrease in alcohol intake, may reduce bone loss. This case report describes lifestyle changes that included diet and exercise that increased bone mineral density in two years in a post-menopausal woman with no negative side effects.

Lycium barbarum glycopeptide reduces bone loss caused by exosomes derived from human gingival fibroblasts with radiation exposure

To explore the protective effect of Lycium barbanun glycopeptide (LbGP) against osteogenic inhibition induced by exosomes derived from human gingival fibroblasts (HGFs) exposed to radiation. Cultured HGFs with or without LbGP pretreatment were exposed to 8 Gy X-ray radiation, and the changes in cell apoptosis, senescence and α-SMA level were detected using RT-qPCR, Western blotting and β-galactosidase staining. The exosomes secreted by the treated cells were extracted, and after identification by electron microscopy, particle size analysis and Western blotting, the exosomes were added into primary cultured bone mesenchymal stem cells (BMSCs), and osteoclast activity and osteogenesis in the cell cultures were detected by Trap staining, Alizarin red staining, ALP staining, RT-qPCR and Western blotting. In cultured HGFs, X-ray radiation significantly increased the percentage of senescent cells, which was obviously lowered by LbGP treatment. X-ray radiation significantly reduced Bcl-2/Bax ratio and increased α -SMA expression in HGFs, and these changes were significantly suppressed by LbGP pretreatment. In rat BMSCs, incubation with the exosomes derived from HGFs with radiation exposure caused a significant increase of osteoclasts, reduced calcium nodules and lowered alkaline phosphatase expression in the cells; The opposite changes were observed in the cells treated with exosomes from LbGPpretreated HGFs, which also significantly increased the cellular expressions of the osteogenic genes (BMP2, ALP, and RUNX2) and proteins (ALP and RUNX2) as compared with the exosomes from irradiated HGFs. LbGP can effectively inhibit osteoclast activity and promote osteogenesis by acting on exosomes secreted by irradiated HGFs, suggesting its potential value for treatment of osteoradionecrosis of the jaw.

Sodium butyrate protect bone mass in lipopolysaccharide-treated rats by reducing oxidative stress and inflammatory

ABSTRACT Objective The study will be to observe the effect of Sodium butyrate (NaB) on bone loss in lipopolysaccharide (LPS)-treated rats. Methods In the rat model, we observed that changes in the expression of oxidative stress regulators, inflammatory markers and target genes were measured by immunofluorescence and RT–PCR after treatment. Changes in viability and osteogenesis of MC3T3-E1, osteoclast differentiation in RAW264.7 cells in the presence of LPS were evaluated using CCK-8, ALP staining, RES staining, and TRAP staining. Results In vitro experiments have shown that LPS-induced inhibition of JC-1, SIRT1, GPX1 and SOD2 is associated with increased levels of inflammation and oxidative stress. In addition, NaB has been found to suppress oxidative stress, inflammation and Mito SOX, promote osteogenic differentiation, and inhibit osteoclast differentiation. In addition, NaB significantly promoted SITR1 expression, repaired impaired bone metabolism, and improved bone strength and bone mineral density. Conclusion Given all this experimental evidence, the results strongly suggest that NaB can restore osteogenic activity in the presence of LPS by reducing intracellular ROS, inhibiting osteoclast differentiation and reducing bone loss in LPS-treated rat models.

Clinical and Radiographic Evaluation of Soft Tissue and Bone Status in Immediate Loaded Implants Placed Following Their Extraction in the Maxillary Anterior Region.

In the maxillary anterior region, teeth extraction leads to significant soft and hard tissue changes. Immediate implant placement following extraction aims to reduce bone loss and overall treatment time. However, it may result in adverse soft tissue changes impacting esthetics. This study evaluates the clinical and radiographic outcomes of immediately loaded implants in the maxillary anterior region, focusing on soft tissue preservation and bone status. This study, conducted from April 2022 to August 2024 at the Department of Oral and Maxillofacial Surgery, Ragas Dental College and Hospital, included 10 immediately loaded implants in seven patients. Following atraumatic extraction, implants were placed and loaded with functional provisional crowns fabricated using three-dimensional (3D) rapid prototyping models. Parameters such as crestal bone loss, buccal and palatal bone width, and interdental papilla thickness were evaluated preoperatively and postoperatively using radiographsand clinical assessments. The study found significant crestal bone loss at both mesial and distal sites over time, with the greatest loss observed at the three-month follow-up. Buccal and palatal bone width showed no significant differences preoperatively and postoperatively. Interdental papilla thickness and overall pink esthetic scores also showed no significant differences between preoperative and postoperative evaluations. Immediate implant placement in the maxillary anterior region, using 3D rapid prototyping for custom splint fabrication, demonstrated effective preservation of soft tissue profile and bone architecture. This approach provides functional and esthetic benefits, although careful monitoring of crestal bone loss is necessary.

Arctigenin Modulates Adipogenic-Osteogenic Balance in the Bone Marrow Microenvironment of Ovariectomized Rats via the MEK1/PPARγ/Wnt/β-Catenin Pathway.

Arctigenin (Ar) is a promising therapeutic candidate for postmenopausal osteoporosis (PMOP). This study explores its mechanism by examining its effects on adipogenesis and osteogenesis in ovariectomized (OVX) rats. Invitro, Ar effectively suppressed the adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) from OVX rats, reducing lipid droplet formation and downregulating proteins associated with lipid synthesis. Invivo, Ar treatment significantly reduced bone loss, inhibited adipocyte development, improved lipid metabolism, and promoted bone formation in OVX rats. Mechanistically, Ar inhibited the phosphorylation of Mitogen-Activated Protein Kinase 1 (MEK1), downregulated Peroxisome Proliferator-Activated Receptor gamma (PPARγ), promoted the accumulation of β-catenin in the nucleus, and prevented the direct binding of PPARγ to β-catenin in BMSCs. This regulation of the PPARγ/Wnt signaling axis underlies its dual role in inhibiting adipogenesis and promoting osteogenesis. Notably, co-treatment with rosiglitazone (RGZ) reversed the effects of Ar on adipogenesis and osteogenesis without affecting MEK1 inhibition. These findings offer valuable insights into arctigenin's potential as a therapeutic strategy for PMOP by modulating MEK1 signaling and regulating the PPARγ/Wnt axis.

10 Years of Convergent Neck Implants: A Systematic Review of Clinical Outcomes, Initial Original Concepts, and Changes in Surgical and Prosthetic Protocols

The study reviewed the state of the art of the clinical use of a convergent-neck-designed Prama implant. This implant was introduced approximately 10 years ago and was characterized by a specific and unique convergent neck with a microtextured surface (UTM surface) and Zirconium Titanium (ZirTi) implant body surface. The neck design was developed to adopt the biologically oriented preparation technique (BOPT). A critical analysis of the published clinical studies and an evaluation of the adopted clinical protocols were performed. A total of forty-six articles were eligible to be reviewed. Only sixteen clinical studies reported clinical outcomes on Prama implants, and nine of these were selected having the longest follow-up from different research groups. The clinical follow-up/duration of the studies ranged from 12 months to 6 years. The initially proposed protocols explored neck supracrestal–transmucosal placement and gained interest due to its minimally invasive concept and the ability to proceed without a pre-prosthesis second surgery. The following investigations dedicated attention to the subcrestal or equicrestal implant placement with the conventional flap approach. The clinical studies characterized by the transmucosal exposed neck approach reported high survival rates with a stable bone morphology and reduced bone loss during the follow-up. Further recent implementations included the introduction of different convergent neck heights that need to be evaluated. The use of intraoral scanner technologies and digital workflow resulted in a simpler methodology with control of the marginal crown morphology. The studies support the concept that the hard tissue parameters (such as marginal bone level, MBL) and soft tissue parameters (such as pink esthetic score, PES) were stable or improved during the follow-up. Definitive crowns, designed with low invasiveness for soft tissues, were possible thanks to the morphology of the neck. The clinical studies support the use of the Prama implant with the different neck positions, demonstrating hard tissue preservation and optimal esthetic results in the first years following insertion. However, the current body of evidence is not robust enough to draw definitive conclusions, especially in the long term, and further high-quality research (long-term randomized trials) is required to consolidate these early observations.

Targeted elimination of Fusobacterium nucleatum alleviates periodontitis

ABSTRACT Background Fusobacterium nucleatum, a pathobiont in periodontal disease, contributes to alveolar bone destruction. We assessed the efficacy of a new targeted antimicrobial, FP-100, in eradicating F. nucleatum from the oral microbial community in vitro and in vivo and evaluated its effectiveness in reducing bone loss in a mouse periodontitis model. Methods A multispecies bacterial community was cultured and treated with two concentrations of FP-100 over two days. Microbial profiles were examined at 24-h intervals using 16S rRNA sequencing. A ligature-induced periodontitis mouse model was employed to test FP-100 in vivo. Results FP-100 significantly reduced Fusobacterium spp. within the in vitro community (p < 0.05) without altering microbial diversity at a 2 μM concentration. In mice, cultivable F. nucleatum was undetectable in FP-100-treated ligatures but persistent in controls. Beta diversity plots showed distinct microbial structures between treated and control mice. Alveolar bone loss was significantly reduced in the FP-100 group (p = 0.018), with concurrent decreases in gingival IL-1β and TNF-α expression (p = 0.052 and 0.018, respectively). Conclusion FP-100 effectively eliminates F. nucleatum from oral microbiota and significantly reduces bone loss in a mouse periodontitis model, demonstrating its potential as a targeted therapeutic agent for periodontal disease.

The Efficacy of Body-Weight Supported Treadmill Training and Neurotrophin-Releasing Scaffold in Minimizing Bone Loss Following Spinal Cord Injury.

Spinal cord injury (SCI) can lead to significant bone loss below the level of the lesion increasing the risk of fracture and increased morbidity. Body-weight-supported treadmill training (BWSTT) and transplantation strategies using neurotrophins have been shown to improve motor function after SCI. While rehabilitation training including BWSTT has also been effective in reducing bone loss post-SCI, the effects of transplantation therapies in bone restoration are not fully understood. Furthermore, the effects of a combinational treatment strategy on bone post-SCI also remain unknown. The aim of this study was to determine the effect of a combination therapy including transplantation of scaffold-releasing neurotrophins and BWSTT on the forelimb and hindlimb bones of a T9-T10 contused SCI animals. Humerus and tibia bones were harvested for Micro-CT scanning and a three-point bending test from four animal groups, namely injury, BWSTT (injury with BWSTT), scaffold (injury with scaffold-releasing neurotrophins), and combinational (injury treated with scaffold-releasing neurotrophins and BWSTT). BWSTT and combinational groups reported higher biomechanical properties in the tibial bone (below injury level) and lower biomechanical properties in the humerus bone (above injury level) when compared to the injury and scaffold groups. Studied structural parameters, including the cortical thickness and bone volume/tissue volume (BV/TV) were also higher in the tibia and lower in the humerus bones of BWSTT and combinational groups when compared to the injury and scaffold groups. While no significant differences were observed, this study is the first to report the effects of a combinational treatment strategy on bone loss in contused SCI animals and can help guide future interventions.

Effect of photobiomodulation with different wavelengths on periodontal repair in non-hyperglycemic and hyperglycemicrats.

Hyperglycemic conditions is associated with more severe periodontitis and poorer outcomes after nonsurgical periodontal treatment (NPT). Then, these patients are candidates for adjunctive therapy associated with NPT. This study evaluates the effect of photobiomodulation (PBMT) at different wavelengths on periodontal repair in non-hyperglycemic/hyperglycemic animals. Sixty-four rats were submitted to induction of periodontitis by ligatures. Hyperglycemia was induced in half of these animals, whereas the other half remained non-hyperglycemic. The animals were subdivided into 4 groups according to the PBMT protocol applied at the time of ligature removal (n = 8): CTR: Without PBMT; IRL: PBMT with infrared laser (808 nm); RL: PBMT with red laser (660 nm); and RL-IRL: PBMT with red (660 nm) and infrared laser (808 nm). After a period of 7 days, the animals were euthanized. The parameters assessed by microtomography were the bone volume relative to total tissue volume (BV/TV%), distance from the cemento-enamel junction to the top of the bone crest (CEJ-CB), trabecular thickness, space between trabeculae, and number of trabeculae. Additionally, the percentage of inflammatory cells, blood vessels, and connective tissue matrix were assessed by histomorphometric analysis. PBMT reduced bone loss and increased trabecular density in hyperglycemic animals (p < .05), with RL being more effective in reducing linear bone loss (CEJ-CB), whereas RL-IRL was more effective in maintaining BV/TV%. PBMT reduced blood vessels and increased the connective tissue component in hyperglycemic animals (p < .05). RL-IRL reduced inflammatory cells regardless of the systemic condition of the animal (p < .05). PBMT (RL, RL-IRL) improves the repair of periodontal tissues in hyperglycemic animals.

Alendronate Functionalized Bone-Targeting Pomolic Acid Liposomes Restore Bone Homeostasis for Osteoporosis Treatment.

Osteoporosis, characterized by dysregulation of osteoclastic bone resorption and osteoblastic bone formation, severely threatens human health during aging. However, there is still no good therapy for osteoporosis, so this direction requires our continuous attention, and there is an urgent need for new drugs to solve this problem. Traditional Chinese Medicine Salvia divinorum monomer pomolic acid (PA) could effectively inhibit osteoclastogenesis and ovariectomized osteoporosis. However, its poor solubility and lack of targeting severely limits its further application. A novel bone-targeting nanomedicine (PA@TLipo) has been developed to reconstruct the osteoporotic microenvironment by encapsulating pomolic acid in alendronate-functionalized liposomes. Through a series of operations such as synthesis, purification, encapsulation, and labeling, the PA@TLipo have been prepared. Moreover, the cytotoxicity, bone targeting and anti-osteoporosis effect was verified by cell and animal experiments. In the aspect of targeting, the PA@TLipo can effectively aggregate on the bone tissue to reduce bone loss, and in terms of toxicity, PA@TLipo could increase the bone target ability in comparison to nontargeted liposome, thereby mitigating systemic cytotoxicity. Moreover, PA@TLipo inhibited osteoclast formation and bone resorption in vitro and reduced bone loss in ovariectomy-induced osteoporotic mice. In this study, a novel therapeutic agent was designed and constructed to treat osteoporosis, consisting of a liposome material as the drug pocket, PA as the anti-osteoporosis drug, and ALN as the bone-targeting molecule. And our study is the first to employ a bone-targeted delivery system to deliver PA for OVX-induced bone loss, providing an innovative solution for treating osteoporosis.