Bone Resorption Research Articles (Page 1)

Abstract Denosumab is a fully human monoclonal antibody that increases bone mineral density, inhibits bone resorption and reduces fracture risk. This double-blind, randomised, parallel group study aimed to demonstrate the pharmacokinetic (PK) equivalence and compare the pharmacodynamic (PD), safety and immunogenicity profiles of the proposed denosumab biosimilar FKS518 versus the originator (reference) denosumab. Healthy males (28–55 years) were randomised to a single 60 mg subcutaneous injection of FKS518 or the reference denosumab (Prolia®) and were followed for 40 weeks after drug injection. The primary endpoints were area under the concentration-time curve (AUC) from time zero to infinity, AUC from time zero to the last quantifiable concentration, and maximum observed serum concentration. A total of 213 subjects were injected. PK equivalence was demonstrated as the 90% confidence intervals for the geometric least squares means ratio FKS518/reference denosumab for the three primary PK parameters were fully contained within the predefined bioequivalence limits. Secondary PK, PD, safety and local tolerability endpoints also supported the similarity of FKS518 and reference denosumab. No anti-drug antibodies were detected in either treatment group. These results demonstrate that FKS518 is equivalent to originator denosumab with respect to PK profile.

If a prosthetically guided implant rehabilitation is to be carried out, the patient must have adequate bone volume, which is not always present due to bone resorption in the alveolar process. An ef-fective technique in regenerative surgery involves the use of titanium mesh to recreate the missing bone volume. A new generation of meshes have been created, presenting a new texture with mi-croholes and possessing space-making and barrier effects. The primary objective of this study was to measure the height and width of the regenerated bone following the use of a new-generation customized titanium mesh. This retrospective case series involved 18 patients (23 bone atrophies) who underwent bone-regeneration surgery with a titanium mesh and received subsequent implant placement. An average vertical bone gain of 5.2 ± 2.9 mm and an average horizontal bone gain of 12.3 ± 2.6 mm were achieved, as well as an average regenerated bone volume of 3.2 ± 1.3 cm3. One failure occurred (4.3%), and in three cases (13%) it was necessary to perform a minor second surgery. The average follow-up time for implants after loading was 22.3 ± 15.6 months. This study shows the innovation of new-generation titanium mesh and its microperforated texture that offers both a space-making effect and a partial barrier effect. This has led to excellent regeneration results, with a significant improvement in treated vertical and horizontal defects and reduced operating times. Future studies with longer follow-ups are necessary to confirm these findings.

Introduction This study aims to investigate the effects of aerobic exercise on the bones of obese male mice induced by a high-fat diet and determine the related mechanisms. Results will provide a reference for exercise-related recommendations in the early adulthood of rodents. Methods Sixty male C57BL/6 mice were raised to 5 weeks of age and then stratified randomly by body weight into a normal diet group and a high-fat diet group for a 12-week dietary intervention. After 12 weeks, successfully modeled obese male mice were stratified randomly by body weight into an obese control group and an obese exercise group. Twenty mice from the normal diet group were stratified randomly by body weight into a control group and an exercise group. A 10-week aerobic treadmill exercise intervention was conducted, and the feed administered to each group was not changed. Results High-fat diet-induced obesity causes abnormalities in body weight, blood glucose, and lipid metabolism in mice, inhibits bone formation, promotes bone resorption, and leads to decreased bone mass in obese male mice. Conclusion These findings are mainly related to the inhibition of the WNT signaling pathway and the dysregulation of adipokines. Aerobic exercise can effectively reduce the body weight of obese male mice and alleviate abnormalities in glucose and lipid metabolism. To some extent, it also alleviates the inhibition effect of obesity on WNT pathway signaling, promotes bone formation, and inhibits bone resorption.

Periodontitis is a common periodontal disease encountered worldwide; it is a chronic inflammatory condition that eventually leads to the destruction of supporting periodontal structures. Periodontal biomarkers are authentically important for assessing the activity of the disease and its treatment outcomes. Cross-linked carboxyl-terminal telopeptide of type I collagen (ICTP) represents one member of a significant group of molecules that are largely associated with bone resorptive diseases. Gingival inflammation can be distinguished from progressive periodontitis when ICTP can be applied clinically, as it is an existing biomarker specific to bone degradation. The present review article elaborates the role of ICTP as an implicit bio marker in estimating periodontal health and disease.

Background: Osteoporosis is a systemic skeletal disease characterized by reduced bone mineral density (BMD) and microarchitectural deterioration, leading to increased fragility and fracture risk. It represents a major global public health challenge, disproportionately affecting postmenopausal females due to the abrupt decline in estrogen, which accelerates bone resorption. The condition is often asymptomatic until a fragility fracture occurs, resulting in significant pain, disability, mortality, and societal cost. Aim: This article synthesizes the etiology, epidemiology, and pathophysiology of osteoporosis in females and advocates for an interdisciplinary management approach. It aims to outline comprehensive evaluation strategies and evidence-based treatments, integrating the roles of nursing, family medicine, laboratory services, and social care to close pervasive screening and treatment gaps. Methods: A comprehensive review is presented, covering the disease's historical context, pathophysiological mechanisms (including the RANKL/RANK/OPG axis), and diagnostic criteria using dual-energy X-ray absorptiometry (DXA). Risk assessment tools like FRAX and laboratory evaluations for secondary causes are detailed. Management strategies, including pharmacological and non-pharmacological interventions, are systematically reviewed. Results: Osteoporosis management requires a multifaceted strategy. First-line pharmacotherapy includes bisphosphonates and denosumab, while anabolic agents (e.g., teriparatide, romosozumab) are reserved for very high-risk patients. Non-pharmacological foundations encompass calcium, vitamin D, weight-bearing exercise, and fall prevention. Successful outcomes depend on coordinated, interprofessional care to improve diagnosis, treatment adherence, and persistence. Conclusion: A proactive, interdisciplinary model is essential to transform osteoporosis from a "silent epidemic" into a managed chronic condition, thereby reducing the immense personal and economic burden of fragility fractures.

Brown tumors (BTs) are rare osteolytic lesions that typically occur in association with primary or secondary hyperparathyroidism (PHP and SHP). Excessive secretion of parathyroid hormone induces increased bone resorption, resulting in lesions characterized by fibrosis, vascularization, and hemosiderin deposition. The most common sites include the jaws, ribs, pelvis, and long bones. Clinical manifestations may involve pain, swelling, or pathological fractures. We present the case of a mandibular BT in a 48-year-old female with chronic renal failure and secondary hyperparathyroidism. The patient exhibited progressive mandibular swelling with radiological features resembling an aggressive odontogenic or malignant lesion. Laboratory analysis confirmed markedly elevated parathyroid hormone levels, while scintigraphy demonstrated increased focal uptake in the mandible and ribs. Histopathological evaluation revealed multinucleated giant cells within a fibrous stroma, consistent with BT. Despite initiation of systemic endocrine therapy, the lesion continued to enlarge, necessitating complete surgical excision of the mandibular mass. This case underscores the diagnostic dilemmas of mandibular BT, which may closely mimic aggressive jaw pathologies. Importantly, while many BTs regress after systemic management of hyperparathyroidism, this case illustrates that surgical excision may be unavoidable in patients with unstable systemic status or progressive local disease. Comprehensive clinical, radiological, laboratory, and histopathological evaluation remains essential to ensure timely diagnosis and appropriate treatment.

Carpal tunnel syndrome (CTS) is the most common nerve entrapment disorder, affecting 1% to 5% of adults, primarily women aged 40-60. It results from median nerve compression, causing pain, numbness, and reduced grip strength. Risk factors include rheumatoid arthritis, pregnancy, and hypertension. Advanced cases may present with painless skin ulcers, suggesting an ulceromutilating variant. An 83-year-old retired seamstress with hypertension, rheumatoid arthritis, and bilateral CTS, diagnosed nine years ago, developed progressive sensory-motor deficits and painless ulcers on her left hand despite successful right-hand surgery. Electromyography confirmed severe left CTS and the clinical presentation suggested an ulceromutilating variant. She was referred for corrective surgery. Painless ulcers in CTS are rare but have been reported since 1979, resulting from prolonged nerve compression and skin necrosis. Early diagnosis and surgery are crucial to prevent irreversible damage, like bone resorption. This case emphasizes the need to consider this variant in advanced CTS.

ABSTRACT Bone homeostasis is maintained by the balance between bone resorption and bone formation. Disruption of bone homeostasis is closely linked to various bone‐related diseases, such as rheumatoid arthritis (RA), osteoporosis, peri‐implantitis (PI), and periodontal disease (PD). The quest to reduce the incidence of complications and alleviate the side effects of current therapeutic strategies remain an ongoing challenge. Owing to its minimal side effects, good controllability, and high selectivity, low‐temperature plasma (LTP) has found a wide range of medical applications, such as promoting wound healing, killing tumor cells, and functioning as an antimicrobial agent. In recent years, LTP has also been increasingly utilized in orthopedics and dentistry, owing to its potential to promote osseointegration, facilitate the repair of bone defects, and exhibit anti‐inflammatory properties. In this paper, this paper discusses the biological effects and mechanisms of LTP on osteoblasts, osteoclasts, and macrophages, as well as explore the potential differential impacts of various LTP sources and parameters. Additionally, this paper discusses the clinical applications of LTP in orthopedics and dentistry.

Wheat germ-derived bioactive peptides have attracted substantial attention for their antioxidant and immunomodulatory properties. However, their potential roles and mechanisms in mitigating osteoporosis remain unclear. This study investigated the antiosteoporotic effects of RPPSFF (RPP), a bioactive peptide isolated from wheat germ, and elucidated its molecular mechanism in maintaining bone homeostasis. Using a mouse model of D-galactose-induced aging and an MC3T3-E1 osteoblast model of senescence, we found that RPP significantly enhanced osteogenesis, inhibited bone resorption, and improved systemic antioxidant capacity and bone microarchitecture. Mechanistic analysis through siRNA-mediated gene silencing, pull-down assay, and molecular docking revealed that RPP directly binds to the transcription factor YY1, thereby activating the AMPK/SIRT1 signaling pathway. These findings indicate that RPP modulates oxidative stress and bone metabolism through the YY1/AMPK/SIRT1 pathway, providing a basis for the development of peptide-based nutritional interventions for age-related osteoporosis.

Anatomical variations in canine dentition, including supernumerary roots, are uncommon but clinically significant, since, among other issues, these structures can accelerate the process of alveolar bone resorption or require a more complex extraction procedure to prevent root fracture. This report describes a rare bilateral occurrence of supernumerary roots in the maxillary third premolars (107 and 207) of a 15-year-old female dog. Radiographic evaluation confirmed three distinct roots per tooth. The teeth were extracted due to severe periodontal disease affecting the supporting structures. This case emphasizes the importance of routine intraoral radiographs in veterinary dentistry for detecting anatomical anomalies and contributes to the understanding of dental variations in dogs.

One of the severe complications of diabetes mellitus is diabetic foot syndrome, which develops in 20-80% of patients, and which is the cause of disability in 66-70%, and mortality in this category of patients ranges from 30 to 68%. Indications for surgical treatment in patients with diabetic foot syndrome are purulent-destructive processes that occur on the foot due to impaired blood supply and innervation of soft tissues. Surgical interventions in patients with purulent-necrotic lesions of diabetic foot syndrome often end in amputations. The consensus among surgeons is that patients with complicated forms of diabetic foot syndrome should undergo economical operations while preserving the supporting function of the foot. In this case, the affected area is removed within the visible changes in the soft tissues, and the maximum amount of bone is removed, which should preserve the supporting function of the foot. The article analyzes the histostructure of bone tissue in 128 patients with mixed (75%) and ischemic (25%) forms of diabetic foot syndrome without radiological signs of bone tissue destruction. The depth of soft tissue damage corresponded to Wagner grade 0-2. In 97% of patients, the humeral bone index was 0.8 and below, and the oxygen tension index was below 60 millimeters of mercury. In 97 (76%) patients, blood flow was restored: 87 (68%) patients by balloon angioplasty, and 10 (8%) by bypass surgery. The changes in the structure of bone tissue after angiocorrection can only be associated with improved blood flow. Intraoperative bone tissue biopsies were taken from a macroscopically unchanged bone area, in which there were also no signs of destruction on prematurely made radiographs. The results of the histological study showed that impaired blood circulation in the limb tissues over a long period of time leads to the development of destructive processes in the bones, which are not manifested clinically and radiographically. In the bone structure, there is a disruption of the matrix calcification process, a decrease in the thickness of the cortex, expansion of osteon canals, and thinning of the trabecular meshwork, which is a sign of the bone resorption process. The processes of bone tissue destruction caused by impaired blood supply are reversible. Performing angiocorrection with complete restoration of blood flow will prevent the appearance of signs of bone tissue regeneration in the form of the formation of vessels in the bone and periosteum, which contribute to the formation of new bone substance. Thus, preserving blood flow in the foot is the main condition for performing economical resections in patients with various complications of diabetic foot syndrome.

Diabetes mellitus (DM) exacerbates periodontitis as the high-glucose (HG) environment aggravates local inflammation and periodontal bone resorption. Restoring periodontal homeostasis and promoting periodontal bone repair/regeneration are major challenges for the treatment of diabetic periodontitis. This study introduces antler stem cell-derived exosomes (AnSC-exos) as a potent therapeutic for treating diabetic periodontitis via leveraging the shared cranial neural crest cell (CNCC) origin of antlers and periodontal tissues. Using a rat model of diabetic periodontitis, we demonstrate that AnSC-exos effectively alleviate tissue abnormalities and alveolar bone destruction and resorption in periodontitis under DM conditions; the outcome was significantly more potent than human bone marrow mesenchymal stem cell exosomes (hBMSC-exos). Mechanistically, AnSC-exos exhibited dual regenerative actions: (1) restoring the osteogenic ability of resident MSCs by not only reversing high glucose (HG)-induced suppression of proliferation and migration, but more importantly, enhancing cell survival, reducing cell death, and strengthening differentiation toward osteogenic lineages under HG conditions; and (2) attenuating inflammation through potently scavenging excessive ROS production induced by HG, and inhibiting HG-mediated p65 nuclear translocation, thereby leading to a reduced M1/M2 macrophage ratio. In conclusion, the superior efficacy of AnSC-exos highlights their tissue-specific regenerative advantage and establishes AnSC-exos as a promising cell-free therapy that simultaneously targets osteogenic impairment and ROS-driven inflammation in diabetic periodontitis. Further characterization of active components within the exosomes holds significant promise for developing effective clinical treatments for diabetic periodontitis.

The present study aimed to determine the acute effects of high-intensity dynamic resistance training (HI-DRT) and whole-body electromyostimulation (WB-EMS) on markers of bone formation and resorption in young healthy women. Using a crossover design, 17 students of dentistry (26.5 ± 4.0 years, 21.5 ± 2.5 kg/m2) were randomly assigned to begin either with HI-DRT (five exercises, three sets to repetition maximum) or 20 min of non-superimposed, low-frequency (85 Hz), intermitted (6 s impulse/4 s impulse break) WB-EMS. The study outcome parameters were total Procollagen Type-1 N-Terminal Propeptide (P1NP) and Type-I Collagen Cross-Linked C-Telopeptide (CTX), which were sampled immediately prior to and 15 min post intervention. ANCOVA was applied to determine the main effects, i.e., differences in pre–post changes in CTX and P1NP between the interventions. No participant was lost to follow-up or reported adverse effects related to the exercises. Briefly, we observed significant differences (p = 0.019, d′ = 1.19) for changes in P1NP that were maintained in the HI-DRT (p = 0.446) and decreased in the WB-EMS group (p = 0.002). In contrast, we did not observe differences for HI-DRT- vs. WB-EMS-induced CTX changes (p = 0.509; d′ = 0.134). In summary, while HI-DRT provides significantly more favorable effects on bone formation markers compared to WB-EMS, the clinical significance of this finding in predicting the general effectiveness of an exercise protocol on bone strength remains to be determined. (Clinical trials.gov; registration date: 2025-02-06; ID: NCT06813092.)

Cleidocranial dysplasia (CCD), a rare genetic disorder primarily caused by Runt-related transcription factor 2 (RUNX2) heterozygous mutation, serves as a representative model for investigating regulatory mechanisms of RUNX2 in bone remodeling and tooth eruption. As a master transcription factor governing mineralized tissue development, RUNX2 orchestrates bone remodeling and tooth eruption through diverse regulatory networks. It drives alveolar bone formation via transcriptional activation, integration of multiple signaling cascades, and epigenetic modifications, thereby generating the biomechanical force for tooth eruption. Concurrently, RUNX2 promotes osteoblastic secretion of osteoclastogenic factors and directly regulates osteoclast precursor differentiation, facilitating bone resorption at the coronal aspect of dental follicles to estavlish the eruption pathway. Furthermore, RUNX2 modulates eruption progression by participating in stress-induced biological signal transduction within dental follicle cells (DFCs), remodeling the DFCs microenvironment, and regulating DFCs senescence. RUNX2 also influences root development via the NOTUM-Wnt axis, providing auxiliary biomechanical conditions conducive to eruption. This review systematically delineates the pivotal role of RUNX2 in coordinating bone remodeling and tooth eruption. Future studies should leverage organoid models and multi-omics technologies to further elucidate the spatiotemporal regulatory networks of RUNX2, potentially advancing precision diagnostics and therapeutics for rare skeletal-dental developmental disorders.

BackgroundRheumatoid arthritis (RA) is characterized by synovial inflammation and bone erosion driven by osteoblast-osteoclast imbalance. Qingre Huoxue decoction (QRHXD), a traditional Chinese medicine, alleviates RA symptoms, yet its mechanism in mitigating bone erosion remains unclear.MethodsNetwork pharmacology identified active compounds and targets of QRHXD. Collagen-induced arthritis (CIA) rats were treated with QRHXD or Methotrexate. Arthritis severity (HE staining), bone microstructure (X-ray micro-CT), osteoblast/osteoclast markers (RT-qPCR, TRAP staining), and ATF4 expression (Western blot, immunofluorescence staining) were assessed. Primary osteoblasts from CIA rats were treated with QRHXD or its active compound to validate ATF4 modulation.ResultsQRHXD reduced joint swelling, arthritis scores, and bone loss in CIA rats, restoring trabecular parameters (Tb.N, Tb.Th, BV/TV) and suppressing bone resorption markers (TRAP, CTX-1, RANKL). Moreover, the number of osteoclast was significantly reduced. Protein interaction analysis highlighted ATF4 as a core regulator of bone remodeling and potentially regulated by the active compound Quercetin in QRHXD. Both QRHXD and Quercetin inhibited ATF4 hyperactivation in CIA osteoblasts, rebalancing RUNX2 and RANKL expression, with Quercetin showing greater efficacy. Molecular docking further exhibited strong binding affinity between Quercetin and the ATF4-regulating transcription factors RAD21, CBFB and HDAC2.ConclusionQRHXD attenuates bone erosion in RA by inhibiting ATF4 hyperactivation via Quercetin, restoring osteoblast-osteoclast crosstalk.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13018-025-06333-7.

Mandibular prognathism (MP) is the most common type of dentomaxillofacial deformity in East Asian populations. Genetic studies have revealed several MP-associated loci, suggesting that MP could be inherited as familial MP (fMP). However, functional verifications and in-depth mechanistic investigations of these loci are limited. For this study, we recruited 5 fMP families with 17 fMP members and 7 normal members. We first compared the clinical features of the 17 fMP members with 31 nonfamilial MP patients, finding a stronger mandibular overgrowth phenotype in the fMP subjects. Next, we performed whole-exome sequencing analysis with members of the 5 fMP families and singled out a potential fMP-associated pathogenic variant in the CASR gene (namely, rs117375173); the mutation introduces an amino acid substitution (A601G) in exon 7 and confers gain of function in Calcium-Sensing Receptor (CaSR). The rs11735173 variant changes the CaSR protein structure toward a semiactive state, similar to CaSR activated by L-tryptophan (L-Trp). To verify the regulating roles of CASR in mandibular bone growth, we further generated different mouse models with abnormal CaSR function. L-Trp administration effectively activated CaSR/GNAQ expression in vivo and in vitro. The MC3T3-E1 cell line transfected with CaSR with rs117375173 (CaSRA601G) showed increased osteogenic differentiation and collagen synthesis at the transcriptional level. Local injection of L-Trp in the mandible of growing mice significantly increased the mandibular length and BMD, due to activated osteogenic activity and suppressed bone resorption. At the same time, loss of function of CaSR in osteogenic progenitors caused mandibular growth retardation in Gli1-CreER; Casrfl/fl; tdTomatofl/+ mice. In conclusion, our study reveals that abnormal functioning of CaSR affects mandibular bone development and may contribute to the pathogenesis of fMP, providing a theoretical and experimental basis for the early diagnosis of and therapeutic strategies for fMP in clinical practice.

To investigate the role of serine in modulating macrophage polarisation and periodontal inflammation. Saliva samples were obtained from periodontitis patients, healthy individuals and periodontitis remission patients for salivary metabolomics analysis. C57BL/6J mice were used to establish a ligature-induced periodontitis model. THP-1 cells were used invitro to explore the mechanism underlying serine-mediated periodontitis. Micro-computed tomography, immunohistochemistry, quantitative real-time polymerase chain reaction, flow cytometry, western blotting, RNA sequencing and NAD+/NADH detection were performed to explore the role of serine in periodontitis and the underlying mechanism. Salivary serine concentrations were significantly elevated in patients with periodontitis and correlated with disease severity. Invivo experiments showed that locally elevated serine concentrations exacerbated alveolar bone resorption in a mouse model of periodontitis. Transcriptomic analysis revealed that serine stimulation activated inflammation-related pathways, particularly the nicotinamide salvage pathway, which modulates NAD+ levels. Inhibition of intracellular serine transport using L-phenylglycine (L-phg) and mitochondrial complex I (MCI) activity using rotenone reduced inflammatory macrophage polarisation, decreased inflammatory markers and alleviated periodontal tissue damage. Serine-induced inflammatory macrophage polarisation, mediated through NAD+ signalling, plays a key role in periodontitis pathogenesis. Targeting serine transport and NAD+ metabolism may offer new therapeutic strategies for managing periodontitis.

Leptin Receptor-Expressing (LepR+) Fibroblasts Activated by BMP Signaling Promote Bone Resorption in Developmental Odontogenic Cysts.

Fe₃O₄-MXene as a dual-function root canal agent for disinfection and osteoclast inhibition in persistent apical periodontitis.

Mesothelin as a biomarker and potential therapeutic target in rheumatoid arthritis bone destruction.