Peri-implant marginal bone stability remains a major determinant of long-term implant success, yet clinical studies report early marginal bone changes ranging from near-stable conditions in some protocols to approximately 1–2 mm during the first year in more traditional series, underscoring considerable biological variability. In the present review, a remodeling-dominant state refers to turnover-led peri-implant adaptation with limited net cortical gain, whereas modeling-driven apposition refers to uncoupled surface bone addition and cortical reinforcement. We conducted a structured narrative review of PubMed/MEDLINE, Scopus, and Web of Science for literature published between 2000 and February 2026 and qualitatively synthesized direct peri-implant evidence, craniofacial/oral non-implant evidence, and extrapolative mechanobiology from long-bone and systemic models. The available literature supports osteocyte-centered SOST/Wnt regulation as biologically plausible for peri-implant cortical adaptation; however, direct human peri-implant molecular validation remains limited. Based on this synthesis, we propose a hypothesis-generating framework in which mechanical signal profile, microenvironmental stability, and host-related factors influence the probability of transition from a remodeling-dominant to a modeling-dominant peri-implant state. This framework should therefore be interpreted as a testable conceptual model rather than a validated peri-implant mechanism. Its main value lies in organizing current evidence and defining priorities for translational studies that integrate molecular, imaging, and biomechanical endpoints.

Background: Orthodontic tooth movement is traditionally explained through mechanical deformation of the periodontal ligament (PDL); however, increasing evidence indicates that immune mechanisms critically shape bone remodeling outcomes. Mechanical stimuli influence immune cell recruitment, cytokine release, and phenotypic polarization, but these components are rarely integrated into a unified framework. Conceptual framework: We propose the Osteoimmune Axis Model, a conceptual framework describing how mechanical loading may bias immune polarity and thereby gate periodontal remodeling. Compressive loading appears to favor an M1 macrophage/Th17-dominant program associated with pro-inflammatory cytokines and enhanced RANKL-mediated osteoclastogenesis. In contrast, tensile or physiological strains may favor M2 macrophages and regulatory T cells (Treg), supporting IL-10, TGF-β, angiogenesis, extracellular-matrix repair, and osteoblastic activity. Stromal cells are proposed to act as mechanosensors and immune amplifiers that shape cytokine gradients and feedback loops. Predictions: The model predicts that identical forces may produce divergent outcomes depending on immune baseline; load duration may be more destructive than peak magnitude; tensile strain may stabilize M2/Treg pathways; thin periodontal phenotypes may shift toward the catabolic pole at lower mechanical loads; ROS may amplify immune-mediated bone loss; and immunomodulation may raise the threshold for pathological remodeling. Conclusion: The Osteoimmune Axis integrates mechanobiology and immunology into a testable framework for explaining variability in orthodontic periodontal remodeling and for generating hypothesis-driven, immune-aware risk assessment.

Tooth agenesis is a common developmental anomaly of the human dentition, ranging from hypodontia to oligodontia, yet its marked phenotypic variability remains insufficiently explained. This review synthesizes developmental and molecular evidence on epithelial–mesenchymal interactions during early odontogenesis and proposes a signaling-threshold framework for human tooth agenesis. We focus on the coordinated roles of Wnt/β-catenin, bone morphogenetic protein (BMP), fibroblast growth factor (FGF), and Sonic hedgehog (SHH) pathways and on recurrent disease-associated genes, including MSX1, PAX9, WNT10A, and AXIN2, as quantitative modulators of pathway activity rather than binary determinants of tooth identity. Within this framework, successful tooth initiation may depend on whether integrated signaling output exceeds a field-specific activation threshold within spatially graded developmental regions of the dental arch. Differences in signaling amplitude, duration, and transcriptional responsiveness may therefore account for distal tooth susceptibility, variable penetrance, arch asymmetry, and the broad clinical spectrum from mild hypodontia to severe oligodontia. By integrating molecular genetics with developmental field theory, this model provides a testable systems-level explanation for selective tooth absence and highlights priority directions for future functional and genotype–phenotype studies.

Background: Cephalometric reference values describe incisor orientation but do not establish whether the root movement required to achieve them is appropriate for an individual alveolar housing. Objectives: This study aimed to propose a structural compatibility framework in which cephalometric normalization is a conditional treatment objective for permanent maxillary and mandibular incisors. Materials and Methods: A narrative conceptual analysis integrated published anatomical, cephalometric, and biomechanical evidence. The framework combines intended movement with root orientation, root position, alveolar dimensions, cortical clearance, and maxillary root–incisive canal relationships. No patient-level measurements or clinical validation were performed. Results: The conceptual synthesis distinguishes selecting an angular target from assessing the root trajectory needed to reach it. Axis discordance (Δθ) is retained as a candidate orientation descriptor, not an independent measure of biological risk. Existing anatomical measurements are organized to identify potential conflicts between angular correction and local structural constraints. Conclusions: Achieving a cephalometric reference value should not, by itself, be interpreted as biological improvement. The proposed framework makes the reconciliation of angular objectives, root trajectory, and tissue preservation explicit. Measurement reliability, added value over existing assessment, and clinical benefit require separate evaluation.

Maxillary expansion combines sutural skeletal displacement with variable alveolar, dental, and periodontal responses. Because these effects are often reported as a single transverse outcome, their biological contributions are difficult to separate. We reviewed clinical, histological, and experimental evidence on midpalatal and circummaxillary sutural remodeling, alveolar deformation, anchorage-related periodontal loading, and used this evidence to formulate a three-compartment model. The sutural skeletal domain is the intended orthopedic target; the alveolar and dentoalveolar domain describes adaptive load transfer; and the anchorage-related periodontal domain captures non-target tissue responses. These labels describe treatment roles and do not imply a fixed sequence or biological independence. Experimental studies report overlapping mechanosensing, cellular recruitment, osteoclast-related margin turnover, immune and vascular activity, and osteogenesis within expanded sutures. Direct longitudinal molecular data in humans remain scarce, and the order of these events is unresolved. Clinical imaging also shows that comparable transverse corrections can contain different proportions of sutural opening, alveolar bending, dental tipping, and buccal cortical change. The model distinguishes skeletal correction from accompanying dentoalveolar and periodontal effects and yields testable predictions for multimodal imaging, tissue-specific biological measurements, histology, and patient-specific computational modeling. We present it as a provisional analytic model, not as a validated biological classification or clinical prediction rule.

Background: Hypoxic and oxidative stress states tightly regulate bone and periodontal remodeling, yet the field lacks an integrated conceptual framework explaining how fluctuating oxygen availability and redox signaling determine anabolic versus catabolic outcomes. Although hypoxia-inducible factor-1α (HIF-1α), reactive oxygen species (ROS), and reperfusion injury are individually well-studied, their coordinated role in defining tissue remodeling thresholds remains unclear. Methods: This Perspective synthesizes mechanistic evidence from cellular, molecular, and tissue-level studies on hypoxia, redox biology, perfusion dynamics, osteoimmunology, and bone remodeling. Published data were evaluated to characterize how oxygen tension, ROS generation, and inflammatory signaling interact under mechanical or metabolic stress. A conceptual model (“Hypoxostat Model”) was constructed to describe the regulatory balance between hypoxia-driven catabolism and oxygenation-driven anabolism. Hypothesis: The Hypoxostat Model proposes that tissues operate within a dynamic oxygen-dependent regulatory window. Moderate hypoxia transiently activates HIF-1α, angiogenesis, and osteogenic compensation, whereas deeper or sustained hypoxia collapses perfusion, increases ROS, amplifies IL-1β/TNF-α/IL-17A signaling, and promotes RANKL-mediated osteoclastogenesis. Reoxygenation phases trigger additional oxidative bursts, further biasing tissues toward destructive remodeling. Thin periodontal phenotypes exhibit reduced perfusion reserve and increased sensitivity to hypoxia–ROS transitions, lowering their threshold for entry into catabolic remodeling domains. Conclusions: Hypoxia and redox signaling function as a bistable regulatory system controlling bone and periodontal remodeling. The Hypoxostat Model provides a unifying framework linking oxygen tension, ROS dynamics, inflammatory cytokines, and remodeling outcomes. Recognizing hypoxia–reoxygenation behavior as a mechanistic switch may improve prediction of tissue vulnerability and guide therapeutic strategies aimed at modulating redox balance or enhancing local perfusion.