Disease Pathophysiology Research Report
Target Disease - Disease Name: Osteoporosis - MONDO ID: MONDO:0005292 - Category: Complex
Pathophysiology description Osteoporosis is driven by chronic imbalance in bone remodeling: increased osteoclast-mediated resorption relative to osteoblast-mediated formation, with osteocytes as mechanosensory regulators orchestrating both arms. Osteoclastogenesis is initiated when RANKL (TNFSF11) on osteoblast-lineage cells and osteocytes engages RANK (TNFRSF11A) on myeloid precursors; OPG (TNFRSF11B) acts as a soluble decoy receptor to limit this interaction. Estrogen deficiency, inflammaging, oxidative stress, cellular senescence, disrupted mechanotransduction, a bias of bone marrow mesenchymal stem cells (BMSCs) toward adipogenesis, and gut–immune dysregulation converge to enhance RANKL/M‑CSF signaling and suppress osteoanabolic Wnt/β‑catenin pathways (notably via osteocyte‑derived sclerostin/DKK1), producing trabecular and cortical bone loss and microarchitectural deterioration (elahmer2024mechanisticinsightsand pages 2-3, zhao2025beyondboneloss pages 4-6, zhao2025beyondboneloss pages 2-4).
| Mechanism / Pathway | Key genes / proteins (HGNC) | Cell types (CL terms where applicable) | Cellular components (GO-CC) | Anatomical locations (UBERON) | Mechanistic notes | Evidence (context IDs) and Year |
|---|---|---|---|---|---|---|
| RANKL / RANK / OPG axis | TNFSF11 (RANKL), TNFRSF11A (RANK), TNFRSF11B (OPG) | Osteoblasts (CL:0000064), osteocytes (CL:0000182), osteoprogenitors | Extracellular region (GO:0005615); plasma membrane (GO:0005886) | Trabecular bone surface (UBERON:0002371); cortical bone (UBERON:0002807) | Osteoblast/osteocyte-derived RANKL binds RANK on osteoclast precursors to drive osteoclastogenesis; OPG is a soluble decoy limiting RANKL activity; dysregulation → increased resorption. | (elahmer2024mechanisticinsightsand pages 2-3, zhao2025beyondboneloss pages 4-6) 2024 / 2025 |
| Wnt / β-catenin — sclerostin / DKK1 regulation | SOST (sclerostin), DKK1, CTNNB1 (β-catenin), LRP5/6 | Osteocytes (major SOST source), osteoblasts | Extracellular region (GO:0005615); nucleus (GO:0005634) | Bone (UBERON:0000104) | Osteocyte-secreted sclerostin and DKK1 antagonize Wnt → ↓β-catenin signaling and osteoblast differentiation; anti-sclerostin therapy (romosozumab) is anabolic. | (elahmer2024mechanisticinsightsand pages 2-3, zhao2025beyondboneloss pages 4-6) 2024 / 2025 |
| Estrogen deficiency & pro‑inflammatory cytokines | ESR1, TNF (TNF), IL1B, IL6, IL17A, TNFSF11 (RANKL) | Th17 cells (CL:0000739), Tregs (CL:0000810), B cells, osteoblasts, osteocytes | Extracellular region (GO:0005615); receptor complex (GO:0043235) | Postmenopausal bone, bone marrow (UBERON:0002371) | Loss of estrogen increases TNF‑α, IL‑1, IL‑6 and IL‑17 → upregulates RANKL/M‑CSF, suppresses OPG and promotes osteoclastogenesis and bone resorption. | (zhao2025beyondboneloss pages 4-6, elahmer2024mechanisticinsightsand pages 25-26) 2025 / 2024 |
| Oxidative stress — Nrf2 / FOXO / SIRT axis | NFE2L2 (Nrf2), KEAP1, FOXO1/3, SIRT1, SIRT3 | Osteoblasts, osteocytes, BMSCs (mesenchymal stem cells) | Mitochondrion (GO:0005739); nucleus (GO:0005634) | Bone marrow (UBERON:0002371); bone tissue | Excess ROS impairs osteoblastogenesis, induces apoptosis and activates NF‑κB-driven osteoclastogenesis; Nrf2/Keap1 is protective; SIRT/FOXO and SIRT3 support mitochondrial function and antioxidant responses. | (zhao2025beyondboneloss pages 4-6, elahmer2024mechanisticinsightsand pages 25-26) 2025 / 2024 |
| Cellular senescence and SASP | CDKN2A (p16INK4a), TP53, IL6, IL8, MMPs | Senescent osteocytes, senescent osteoblasts, senescent BMSCs | Secretory vesicle (GO:0099503); extracellular region (GO:0005615) | Bone tissue, lacuno‑canalicular network (UBERON:0002106) | Accumulation of senescent bone cells secretes SASP (IL‑6, IL‑8, proteases) that drive local inflammation, increase osteoclast activity and impair bone formation; senolytic clearance preserves bone in models. | (zhao2025beyondboneloss pages 4-6, elahmer2024mechanisticinsightsand pages 25-26) 2025 / 2024 |
| BMSC lineage shift → marrow adiposity | RUNX2, PPARG (PPARγ), CEBPA | Bone marrow mesenchymal stem cells (BMSCs) | Nucleus / chromatin (GO:0005634 / GO:0000785) | Bone marrow (UBERON:0002371) | Aging, oxidative stress or glucocorticoids downregulate RUNX2 and upregulate PPARγ → BMSC adipogenic differentiation at expense of osteoblastogenesis, increasing marrow fat and reducing bone formation. | (zhao2025beyondboneloss pages 4-6, zhao2025beyondboneloss pages 6-8) 2025 / 2025 |
| Osteocyte mechanotransduction (sclerostin; Piezo1) | SOST (sclerostin), PIEZO1 | Osteocytes (CL:0000182) | Plasma membrane (GO:0005886); lacuno‑canalicular network (GO:0120027) | Cortical and trabecular bone (UBERON:0002807 / UBERON:0002371) | Mechanical loading suppresses sclerostin and promotes Wnt signaling; Piezo1 acts as a mechanosensor in osteocytes—mechanical unloading increases sclerostin and RANKL, promoting resorption. | (elahmer2024mechanisticinsightsand pages 2-3, zhao2025beyondboneloss pages 4-6) 2024 / 2025 |
| Gut microbiome → bone axis (Th17 / Treg; SCFAs) | IL17A, FOXP3, WNT10B (induced), microbial metabolites (butyrate) | Intestinal epithelial cells, Th17 (CL:0000739), Treg (CL:0000810) | Extracellular region; microbial metabolite compartment | Gut (UBERON:0002107) → bone marrow (UBERON:0002371) | SCFAs (e.g., butyrate) promote Treg differentiation, suppress osteoclastogenesis and can stimulate Wnt10b via Treg→CD8+ axis; dysbiosis shifts Th17/Treg balance increasing RANKL and bone loss; human RCTs show mixed effects on BMD. | (zhao2025beyondboneloss pages 6-8, zhao2025beyondboneloss pages 4-6) 2025 / 2025 |
| Denosumab discontinuation (rebound) — RANKL / OPG source mapping | TNFSF11 (RANKL), TNFRSF11B (OPG) | Bone‑surface osteoprogenitors, osteocytes, osteoblasts | Extracellular region (GO:0005615); plasma membrane (GO:0005886) | Trabecular bone surface; endocortical surface (UBERON:0002371 / UBERON:0002807) | Anti‑RANKL therapy (denosumab) suppresses resorption, but discontinuation is followed by rapid rebound resorption due to accumulated RANKL‑expressing bone surface cells and reduced local OPG expression (readily recruits osteoclasts). | (elahmer2024mechanisticinsightsand pages 25-26, elahmer2024mechanisticinsightsand pages 1-2) 2024 / 2024 |
Table: Concise reference table mapping major molecular/cellular mechanisms in osteoporosis with key genes, cells, subcellular locations, anatomical sites, short mechanistic notes, and the context evidence IDs (pqac‑...) plus publication years used to build the summary.
1) Core Pathophysiology - Primary mechanisms - Excess osteoclastogenesis via RANKL/RANK with insufficient OPG: “OPG…competes with RANK to bind RANKL, thereby limiting osteoclastogenesis.” Osteocytes can regulate osteoclasts via RANKL (URL: https://doi.org/10.3390/biomedicines13061443; Jun 2025) (zhao2025beyondboneloss pages 2-4). - Suppressed osteoblastogenesis via Wnt antagonism: osteocytes secrete sclerostin (SOST) and DKK1 to inhibit Wnt/β‑catenin, curtailing formation; PTH suppresses sclerostin to enable Wnt-driven bone formation (URL: https://doi.org/10.3390/biomedicines12081635; Jul 2024) (elahmer2024mechanisticinsightsand pages 2-3). - Estrogen deficiency drives pro‑inflammatory cytokines (TNF‑α, IL‑1, IL‑6; IL‑17 from Th17 cells), which increase RANKL/M‑CSF and reduce OPG, accelerating osteoclast maturation and resorption (URL: https://doi.org/10.3390/biomedicines13061443; Jun 2025) (zhao2025beyondboneloss pages 4-6, zhao2025beyondboneloss pages 2-4). - Oxidative stress/Nrf2–FOXO–SIRT axis: Excess ROS impairs osteoblastogenesis and promotes osteoblast/osteocyte apoptosis while activating NF‑κB–c‑Fos–NFATc1 osteoclast programs; the Nrf2/Keap1/ARE pathway is protective. Aging shifts BMSCs toward adipogenesis via ↑PPARγ2 and ↓RUNX2/Dlx5 (URL: https://doi.org/10.3390/biomedicines13061443; Jun 2025) (zhao2025beyondboneloss pages 4-6). - Cellular senescence/SASP: Senescent bone cells secrete IL‑6/IL‑8 and proteases that enhance resorption and impair formation; “eliminating senescent cells or inhibiting SASP preserves trabecular and cortical mass” (URL: https://doi.org/10.3390/biomedicines13061443; Jun 2025) (zhao2025beyondboneloss pages 4-6). - Mechanotransduction failure: Unloading increases osteocyte sclerostin and RANKL, tipping remodeling toward resorption; loading suppresses sclerostin and promotes Wnt signaling (URL: https://doi.org/10.3390/biomedicines12081635; Jul 2024) (elahmer2024mechanisticinsightsand pages 2-3). - Gut–bone axis: SCFAs such as butyrate promote Treg differentiation and can restrain osteoclastogenesis; microbiome shifts alter Th17/Treg balance and bone turnover (URL: https://doi.org/10.3390/biomedicines13061443; Jun 2025) (zhao2025beyondboneloss pages 6-8). - Molecular pathways dysregulated - RANKL/RANK/OPG; Wnt/β‑catenin (LRP5/6, β‑catenin) inhibited by sclerostin/DKK1; NF‑κB/MAPK downstream of inflammatory cytokines; Nrf2/Keap1 antioxidant signaling; PI3K/AKT/mTOR and JNK in oxidative stress responses; PPARγ-mediated adipogenesis (elahmer2024mechanisticinsightsand pages 2-3, zhao2025beyondboneloss pages 4-6, zhao2025beyondboneloss pages 2-4). - Cellular processes affected - Osteoclast differentiation/activation; osteoblast differentiation (RUNX2/OSX) and matrix mineralization; osteocyte viability and lacuno‑canalicular network signaling; BMSC fate choice between osteogenesis and adipogenesis; immune cell–bone crosstalk (Th17/Treg) (elahmer2024mechanisticinsightsand pages 2-3, zhao2025beyondboneloss pages 4-6, zhao2025beyondboneloss pages 2-4).
2) Key Molecular Players - Genes/Proteins (HGNC) - TNFSF11 (RANKL), TNFRSF11A (RANK), TNFRSF11B (OPG) (elahmer2024mechanisticinsightsand pages 2-3, zhao2025beyondboneloss pages 2-4) - SOST (sclerostin), DKK1, CTNNB1 (β‑catenin), LRP5/6 (elahmer2024mechanisticinsightsand pages 2-3) - Cytokines: TNF, IL1B, IL6, IL17A (zhao2025beyondboneloss pages 4-6, zhao2025beyondboneloss pages 2-4) - NFE2L2 (Nrf2), KEAP1, FOXO1/3, SIRT1/3 (zhao2025beyondboneloss pages 4-6) - RUNX2, SP7/OSX, PPARG (zhao2025beyondboneloss pages 4-6) - Cathepsin K, TRAP (osteoclast effector molecules) (elahmer2024mechanisticinsightsand pages 2-3) - Chemical entities (CHEBI) and drugs - Denosumab (anti‑RANKL mAb), bisphosphonates, PTH analogs, anti‑sclerostin therapy (romosozumab) (elahmer2024mechanisticinsightsand pages 1-2, elahmer2024mechanisticinsightsand pages 2-3) - Reactive oxygen species (ROS) (CHEBI:26523) and antioxidants via Nrf2 pathway (zhao2025beyondboneloss pages 4-6) - Cell types (CL) - Osteoclasts (CL:0000092), osteoblasts (CL:0000064), osteocytes (CL:0000182), BMSCs, Th17 (CL:0000739), Treg (CL:0000810) (elahmer2024mechanisticinsightsand pages 2-3, zhao2025beyondboneloss pages 4-6, zhao2025beyondboneloss pages 6-8) - Anatomical locations (UBERON) - Trabecular bone surface (UBERON:0002371), cortical bone (UBERON:0002807), bone marrow (UBERON:0002371), lacuno‑canalicular network (UBERON:0002106) (elahmer2024mechanisticinsightsand pages 2-3)
3) Biological Processes (GO terms) disrupted - Osteoclast differentiation (GO:0030316); bone resorption (GO:0045453) via RANKL/RANK (elahmer2024mechanisticinsightsand pages 2-3) - Osteoblast differentiation (GO:0001649), ossification (GO:0001503), Wnt signaling (GO:0016055) inhibited by sclerostin/DKK1 (elahmer2024mechanisticinsightsand pages 2-3) - Response to oxidative stress (GO:0006979); Nrf2 signaling; activation of NF‑κB (GO:0007259) in osteoclastogenesis (zhao2025beyondboneloss pages 4-6) - Regulation of inflammatory response (GO:0050727) including TNF/IL‑1/IL‑6/IL‑17 (zhao2025beyondboneloss pages 4-6) - Cellular senescence and SASP (GO:0090398; secretory program) (zhao2025beyondboneloss pages 4-6) - Regulation of cell differentiation toward adipocyte lineage (GO:0045598) via PPARγ (zhao2025beyondboneloss pages 4-6) - Mechanosensory signaling (GO:0007165) in osteocytes; regulation of sclerostin (elahmer2024mechanisticinsightsand pages 2-3)
4) Cellular Components (GO-CC) - Extracellular region (GO:0005615): RANKL, OPG, cytokines (elahmer2024mechanisticinsightsand pages 2-3) - Plasma membrane (GO:0005886): RANK receptor; mechanosensors (general) (elahmer2024mechanisticinsightsand pages 2-3) - Nucleus (GO:0005634): β‑catenin/TCF complexes; FOXO; Nrf2 (zhao2025beyondboneloss pages 4-6) - Mitochondrion (GO:0005739): source of ROS; SIRT3 function (zhao2025beyondboneloss pages 4-6) - Lacuno‑canalicular network (GO contextual to osteocytes): mechanotransduction (elahmer2024mechanisticinsightsand pages 2-3)
5) Disease Progression - Initiating factors: estrogen decline, aging, glucocorticoids, unloading, dysbiosis → increased inflammatory cytokines and oxidative stress, impaired mechanotransduction (zhao2025beyondboneloss pages 4-6, zhao2025beyondboneloss pages 2-4, elahmer2024mechanisticinsightsand pages 2-3). - Early molecular changes: ↑RANKL/M‑CSF, ↓OPG; ↑sclerostin/DKK1; ROS accumulation; senescent cell accrual with SASP; BMSC fate shift to adipocytes (zhao2025beyondboneloss pages 4-6, elahmer2024mechanisticinsightsand pages 2-3). - Cellular/structural outcomes: ↑osteoclast number/activity; ↓osteoblast differentiation and matrix mineralization; osteocyte apoptosis and LCN disruption; trabecular thinning and cortical porosity (elahmer2024mechanisticinsightsand pages 2-3, zhao2025beyondboneloss pages 4-6). - Clinical manifestation: decreased BMD, microarchitectural deterioration, fragility fractures; rebound bone loss upon abrupt denosumab discontinuation due to accumulated osteoclastogenic “activation sites” on bone surfaces with high RANKL and low OPG (URL: https://doi.org/10.1038/s41413-024-00362-4; Oct 2024) (elahmer2024mechanisticinsightsand pages 25-26).
6) Phenotypic Manifestations (HP terms) - HP:0000939 (Osteoporosis), HP:0002818 (Pathologic fracture), HP:0002757 (Decreased bone mineral density) (linked to remodeling imbalance and Wnt suppression) (elahmer2024mechanisticinsightsand pages 2-3, elahmer2024mechanisticinsightsand pages 1-2).
Evidence items and selected direct quotes - “OPG…competes with RANK to bind RANKL, thereby limiting osteoclastogenesis.” URL: https://doi.org/10.3390/biomedicines13061443; Published: Jun 2025 (zhao2025beyondboneloss pages 2-4). - “Osteocytes secrete sclerostin to inhibit Wnt signaling… PTH downregulates sclerostin to permit Wnt-driven formation.” URL: https://doi.org/10.3390/biomedicines12081635; Published: Jul 2024 (elahmer2024mechanisticinsightsand pages 2-3). - “Oxidative stress… impairs bone formation by reducing osteoblastogenesis, increasing osteoblast and osteocyte apoptosis, and enhancing osteoclastogenesis… the Nrf2/Keap1/ARE axis is protective.” URL: https://doi.org/10.3390/biomedicines13061443; Published: Jun 2025 (zhao2025beyondboneloss pages 4-6). - “Cellular senescence and SASP… eliminating senescent cells or inhibiting SASP preserves trabecular and cortical mass.” URL: https://doi.org/10.3390/biomedicines13061443; Published: Jun 2025 (zhao2025beyondboneloss pages 4-6). - Denosumab rebound mechanism: “bone surface cells and osteocytes conjointly regulate the activation of osteoclastogenesis… OPG:Fc treatment induces a local accumulation of osteoclastogenic activation sites, ready to recruit and activate osteoclasts upon treatment discontinuation.” URL: https://doi.org/10.1038/s41413-024-00362-4; Published: Oct 2024 (elahmer2024mechanisticinsightsand pages 25-26).
Current applications and real‑world implementations (therapy–mechanism mapping) - Anti‑resorptives: bisphosphonates (inhibit osteoclast function); denosumab (anti‑RANKL, suppresses osteoclastogenesis). Clinical caveat: denosumab discontinuation is associated with “extensive wave of rebound resorption” due to accumulated RANKL+ bone-surface activation sites and reduced local OPG—necessitating transition strategies (URL: https://doi.org/10.1038/s41413-024-00362-4; Oct 2024) (elahmer2024mechanisticinsightsand pages 25-26, elahmer2024mechanisticinsightsand pages 1-2). - Anabolics: PTH analogs (intermittent PTH enhances formation, partly via downregulating sclerostin and activating Wnt); anti‑sclerostin (romosozumab) lifts Wnt inhibition to stimulate bone formation (URL: https://doi.org/10.3390/biomedicines12081635; Jul 2024) (elahmer2024mechanisticinsightsand pages 2-3, elahmer2024mechanisticinsightsand pages 1-2). - Emerging mechanism‑targeted adjuncts: antioxidant/Nrf2‑targeting strategies; senolytics/SASP modulators; microbiome interventions to rebalance Th17/Treg and SCFAs—human RCT/meta‑analysis signals are mixed and require standardization of protocols (URLs: https://doi.org/10.3390/biomedicines13061443 Jun 2025; https://doi.org/10.3389/fendo.2024.1487998 Nov 2024) (zhao2025beyondboneloss pages 6-8, zhao2025beyondboneloss pages 4-6).
Expert opinions and analysis - Integrated osteoimmunology: Reviews emphasize immune–bone crosstalk regulating RANKL/OPG and the Th17/Treg axis as pivotal to postmenopausal bone loss, highlighting cytokine networks (TNF‑α, IL‑1, IL‑6, IL‑17) and the gut–bone axis as therapeutic frontiers (URL: https://doi.org/10.3390/biomedicines13061443; Jun 2025) (zhao2025beyondboneloss pages 6-8, zhao2025beyondboneloss pages 4-6). - Mechanotransduction: Osteocytes are “master regulators”; loading suppresses sclerostin enabling Wnt‑mediated formation; unloading increases sclerostin/RANKL, coupling disuse with resorption (URL: https://doi.org/10.3390/biomedicines12081635; Jul 2024) (elahmer2024mechanisticinsightsand pages 2-3). - Denosumab rebound biology: in situ mapping supports that bone-surface osteoprogenitors (Tnfsf11+; Mmp13+) and osteocytes coordinate osteoclastogenic “hotspots,” explaining the clinical rebound if anti‑resorptive blockade is withdrawn without bridging therapy (URL: https://doi.org/10.1038/s41413-024-00362-4; Oct 2024) (elahmer2024mechanisticinsightsand pages 25-26).
Relevant statistics and data - Diagnostic threshold and burden: WHO T‑score ≤ −2.5 SD defines osteoporosis; global burden is substantial with major regional cost estimates in the US, EU, and Asia Pacific highlighted (URL: https://doi.org/10.3390/biomedicines12081635; Jul 2024) (elahmer2024mechanisticinsightsand pages 1-2). - Serum markers: Meta‑analysis indicates the OPG/RANKL ratio is significantly lower in osteoporosis versus controls, supporting its role in bone turnover assessment (URL: https://doi.org/10.1186/s13018-023-04179-5; Nov 2023) ( is not available; note: within provided context, meta‑analysis summary is beyond the available citation IDs—so detailed numeric reporting is limited).
Gene/protein annotations with ontology terms - TNFSF11 (RANKL): GO:0042535 positive regulation of tumor necrosis factor superfamily cytokine production; GO:0030316 osteoclast differentiation; located in extracellular region; expressed by osteoblasts/osteocytes (CL:0000064/CL:0000182) (elahmer2024mechanisticinsightsand pages 2-3, zhao2025beyondboneloss pages 2-4). - TNFRSF11B (OPG): GO:0035631 OPG ligand activity; extracellular region; decoy receptor reducing osteoclastogenesis (elahmer2024mechanisticinsightsand pages 2-3, zhao2025beyondboneloss pages 2-4). - SOST (sclerostin): negative regulation of canonical Wnt signaling (GO:0090090); extracellular region; osteocyte source (CL:0000182) (elahmer2024mechanisticinsightsand pages 2-3). - CTNNB1 (β‑catenin): canonical Wnt signaling (GO:0060070), nucleus/cytosol (GO:0005634/GO:0005829) in osteoblasts (CL:0000064) (elahmer2024mechanisticinsightsand pages 2-3). - NFE2L2 (Nrf2)/KEAP1: response to oxidative stress (GO:0006979); nucleus/cytosol; osteoblasts/osteocytes/BMSCs (zhao2025beyondboneloss pages 4-6). - RUNX2/SP7 (OSX): osteoblast differentiation (GO:0001649); nucleus (elahmer2024mechanisticinsightsand pages 2-3, zhao2025beyondboneloss pages 4-6). - PPARG: adipocyte differentiation (GO:0045444); drives BMSC adipogenesis (zhao2025beyondboneloss pages 4-6).
Phenotype associations (HP terms) - HP:0000939 Osteoporosis; HP:0002757 Decreased bone mineral density; HP:0002818 Pathologic fracture; HP:0002937 Osteopenia (early stage) (elahmer2024mechanisticinsightsand pages 1-2, elahmer2024mechanisticinsightsand pages 2-3).
Cell type involvement (CL terms) - CL:0000092 Osteoclast; CL:0000064 Osteoblast; CL:0000182 Osteocyte; CL:0000739 Th17; CL:0000810 Treg (elahmer2024mechanisticinsightsand pages 2-3, zhao2025beyondboneloss pages 4-6, zhao2025beyondboneloss pages 6-8).
Anatomical locations (UBERON terms) - UBERON:0002371 Trabecular bone; UBERON:0002807 Cortical bone; UBERON:0002371 Bone marrow; UBERON:0002106 Lacuno‑canalicular network (elahmer2024mechanisticinsightsand pages 2-3, elahmer2024mechanisticinsightsand pages 25-26).
Chemical entities (CHEBI) - ROS (CHEBI:26523); calcium ions (CHEBI:29108) in mechanosignaling; anti‑resorptive/anabolic drugs as therapeutic chemical entities (zhao2025beyondboneloss pages 4-6, elahmer2024mechanisticinsightsand pages 2-3, elahmer2024mechanisticinsightsand pages 1-2).
Recent developments and latest research (priority 2023–2024) - 2024 mechanistic review consolidates RANKL/RANK/OPG and Wnt/sclerostin roles and therapy classes, with global burden and WHO diagnostic thresholds (URL: https://doi.org/10.3390/biomedicines12081635; Jul 2024) (elahmer2024mechanisticinsightsand pages 1-2). - 2024 denosumab rebound mechanism mapped by in situ hybridization, identifying bone-surface Tnfsf11+ osteoprogenitors and reduced OPG priming rebound osteoclastogenesis on discontinuation (URL: https://doi.org/10.1038/s41413-024-00362-4; Oct 2024) (elahmer2024mechanisticinsightsand pages 25-26). - 2025 review highlights oxidative stress, senescence, mitochondrial dysfunction, and gut–immune axes (SCFAs, Th17/Treg) as integrated contributors and targets (URL: https://doi.org/10.3390/biomedicines13061443; Jun 2025) (zhao2025beyondboneloss pages 4-6, zhao2025beyondboneloss pages 6-8).
Limitations - Some requested quantitative statistics (e.g., precise fracture incidence and prevalence by region) and several human RCT effect sizes on probiotics exceed the available citation IDs in the current context; therefore, only general burden statements and mechanisms from accessible sources are reported (elahmer2024mechanisticinsightsand pages 1-2).
References (URLs and publication dates) - Elahmer et al., Biomedicines. “Mechanistic Insights and Therapeutic Strategies in Osteoporosis” (Published Jul 23, 2024). URL: https://doi.org/10.3390/biomedicines12081635 (elahmer2024mechanisticinsightsand pages 2-3, elahmer2024mechanisticinsightsand pages 1-2). - Zhao et al., Biomedicines. “Beyond Bone Loss: A Biology Perspective…” (Published Jun 2025). URL: https://doi.org/10.3390/biomedicines13061443 (zhao2025beyondboneloss pages 4-6, zhao2025beyondboneloss pages 2-4, zhao2025beyondboneloss pages 6-8, zhao2025beyondboneloss pages 18-20). - El‑Masri et al., Bone Research. “Mapping RANKL- and OPG-expressing cells…” (Published Oct 2024). URL: https://doi.org/10.1038/s41413-024-00362-4 (elahmer2024mechanisticinsightsand pages 25-26).
References
(elahmer2024mechanisticinsightsand pages 2-3): Nyruz Ramadan Elahmer, Sok Kuan Wong, Norazlina Mohamed, Ekram Alias, Kok-Yong Chin, and Norliza Muhammad. Mechanistic insights and therapeutic strategies in osteoporosis: a comprehensive review. Biomedicines, 12:1635, Jul 2024. URL: https://doi.org/10.3390/biomedicines12081635, doi:10.3390/biomedicines12081635. This article has 36 citations and is from a poor quality or predatory journal.
(zhao2025beyondboneloss pages 4-6): Yixin Zhao, Jihan Wang, Lijuan Xu, Haofeng Xu, Yuzhu Yan, Heping Zhao, and Yuzhu Yan. Beyond bone loss: a biology perspective on osteoporosis pathogenesis, multi-omics approaches, and interconnected mechanisms. Biomedicines, 13:1443, Jun 2025. URL: https://doi.org/10.3390/biomedicines13061443, doi:10.3390/biomedicines13061443. This article has 6 citations and is from a poor quality or predatory journal.
(zhao2025beyondboneloss pages 2-4): Yixin Zhao, Jihan Wang, Lijuan Xu, Haofeng Xu, Yuzhu Yan, Heping Zhao, and Yuzhu Yan. Beyond bone loss: a biology perspective on osteoporosis pathogenesis, multi-omics approaches, and interconnected mechanisms. Biomedicines, 13:1443, Jun 2025. URL: https://doi.org/10.3390/biomedicines13061443, doi:10.3390/biomedicines13061443. This article has 6 citations and is from a poor quality or predatory journal.
(elahmer2024mechanisticinsightsand pages 25-26): Nyruz Ramadan Elahmer, Sok Kuan Wong, Norazlina Mohamed, Ekram Alias, Kok-Yong Chin, and Norliza Muhammad. Mechanistic insights and therapeutic strategies in osteoporosis: a comprehensive review. Biomedicines, 12:1635, Jul 2024. URL: https://doi.org/10.3390/biomedicines12081635, doi:10.3390/biomedicines12081635. This article has 36 citations and is from a poor quality or predatory journal.
(zhao2025beyondboneloss pages 6-8): Yixin Zhao, Jihan Wang, Lijuan Xu, Haofeng Xu, Yuzhu Yan, Heping Zhao, and Yuzhu Yan. Beyond bone loss: a biology perspective on osteoporosis pathogenesis, multi-omics approaches, and interconnected mechanisms. Biomedicines, 13:1443, Jun 2025. URL: https://doi.org/10.3390/biomedicines13061443, doi:10.3390/biomedicines13061443. This article has 6 citations and is from a poor quality or predatory journal.
(elahmer2024mechanisticinsightsand pages 1-2): Nyruz Ramadan Elahmer, Sok Kuan Wong, Norazlina Mohamed, Ekram Alias, Kok-Yong Chin, and Norliza Muhammad. Mechanistic insights and therapeutic strategies in osteoporosis: a comprehensive review. Biomedicines, 12:1635, Jul 2024. URL: https://doi.org/10.3390/biomedicines12081635, doi:10.3390/biomedicines12081635. This article has 36 citations and is from a poor quality or predatory journal.
(zhao2025beyondboneloss pages 18-20): Yixin Zhao, Jihan Wang, Lijuan Xu, Haofeng Xu, Yuzhu Yan, Heping Zhao, and Yuzhu Yan. Beyond bone loss: a biology perspective on osteoporosis pathogenesis, multi-omics approaches, and interconnected mechanisms. Biomedicines, 13:1443, Jun 2025. URL: https://doi.org/10.3390/biomedicines13061443, doi:10.3390/biomedicines13061443. This article has 6 citations and is from a poor quality or predatory journal.
name: Osteoporosis
creation_date: '2025-12-18T17:01:35Z'
updated_date: '2026-03-17T00:00:00Z'
category: Complex
parents:
- Musculoskeletal Disease
- Metabolic Disease
disease_term:
preferred_term: osteoporosis
term:
id: MONDO:0005298
label: osteoporosis
pathophysiology:
- name: Bone Remodeling Imbalance
description: >
Increased osteoclast-mediated bone resorption relative to osteoblast- mediated
bone formation leads to net bone loss. This imbalance accelerates with aging and
estrogen deficiency.
cell_types:
- preferred_term: Osteoclast
term:
id: CL:0000092
label: osteoclast
- preferred_term: Osteoblast
term:
id: CL:0000062
label: osteoblast
biological_processes:
- preferred_term: Bone Remodeling
term:
id: GO:0046849
label: bone remodeling
evidence:
- reference: PMID:21874760
reference_title: "Aromatase activity and bone loss."
supports: SUPPORT
snippet: aromatase activity and estrogen production are necessary for longitudinal
bone growth, attainment of peak bone mass, the pubertal growth spurt, epiphyseal
closure, and normal bone remodeling in young individuals.
explanation: Demonstrates that estrogen, produced by aromatase, is essential for
normal bone remodeling and that deficiency leads to bone loss
- reference: PMID:23748068
reference_title: "Aromatase deficiency, a rare syndrome: case report."
supports: SUPPORT
snippet: Estrogen deficiency can induce delayed epiphyseal closure, eunuchoid
body habitus, osteopenia, and osteoporosis in both genders.
explanation: Clinical evidence showing that estrogen deficiency directly causes
osteoporosis through impaired bone remodeling
- name: RANKL/OPG Dysregulation
description: >
Increased RANKL and decreased osteoprotegerin (OPG) ratio promotes osteoclast
differentiation and activation. Estrogen normally suppresses RANKL and increases
OPG. Microgravity further exacerbates this imbalance by directly increasing the
osteoblast RANKL/OPG ratio.
biological_processes:
- preferred_term: Osteoclast Differentiation
term:
id: GO:0030316
label: osteoclast differentiation
evidence:
- reference: PMID:33692806
reference_title: "Role of the IL-23/IL-17 Pathway in Rheumatic Diseases: An Overview."
supports: SUPPORT
snippet: The differentiation of osteoclasts is induced significantly in the presence
of IL-17 either directly (207), or indirectly, through upregulation of RANKL.
explanation: Demonstrates that RANKL upregulation is a key mechanism for osteoclast
differentiation and bone resorption
- reference: PMID:21874760
reference_title: "Aromatase activity and bone loss."
supports: SUPPORT
snippet: with aging, individual differences in aromatase activity and thus in
estrogen levels may significantly affect bone loss and fracture risk in both
genders.
explanation: Shows that age-related decline in estrogen production affects bone
metabolism, linking to RANKL/OPG dysregulation
- reference: PMID:16927271
reference_title: "Modeled microgravity stimulates osteoclastogenesis and bone resorption by increasing osteoblast RANKL/OPG ratio."
supports: SUPPORT
evidence_source: IN_VITRO
snippet: microgravity is capable to indirectly stimulate osteoclast formation
and activity by regulating osteoblast secretion of crucial regulatory factors
such as RANKL and OPG
explanation: Simulated microgravity using NASA Rotating Wall Vessel increases
osteoblast RANKL/OPG ratio, stimulating osteoclastogenesis and bone resorption
- reference: PMID:26318907
reference_title: "Osteoprotegerin is an effective countermeasure for spaceflight-induced bone loss in mice."
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: SF/VEH mice had lower BV/TV vs. GC/VEH mice, while SF/OPG-Fc mice had
greater BV/TV than SF/VEH or GC/VEH
explanation: OPG-Fc (RANKL inhibitor) prevented spaceflight-induced bone loss
in mice during 12-day shuttle mission, confirming RANKL pathway centrality
- name: Microarchitectural Deterioration
description: >
Loss of trabecular connectivity and cortical thinning compromises bone strength
beyond what BMD alone indicates. Leads to fragility fractures with minimal trauma.
Spaceflight accelerates this process, with incomplete microarchitectural recovery
even one year post-flight.
evidence:
- reference: PMID:23748068
reference_title: "Aromatase deficiency, a rare syndrome: case report."
supports: SUPPORT
snippet: recurrent bone fractures associated with minimal trauma starting in puberty
explanation: Clinical case demonstrating that estrogen deficiency leads to fragility
fractures due to compromised bone microarchitecture
- reference: PMID:35773442
reference_title: "Incomplete recovery of bone strength and trabecular microarchitecture at the distal tibia 1 year after return from long duration spaceflight."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: nine of 17 astronauts did not fully recover tibia total BMD after 12-months
explanation: HR-pQCT imaging of astronauts shows incomplete recovery of trabecular
microarchitecture at weight-bearing tibia one year after long-duration spaceflight,
equivalent to a decade of terrestrial bone aging
- reference: PMID:31897866
reference_title: "Spaceflight-Induced Bone Tissue Changes that Affect Bone Quality and Increase Fracture Risk."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: bone structural quality (e.g., trabecular microarchitecture) is diminished
and the quality of bone material is reduced via impaired tissue mineralization,
maturation, and maintenance (e.g., mediated by osteocytes)
explanation: Review of spaceflight-induced bone quality changes beyond BMD, showing
both structural and material quality are compromised in microgravity
- reference: PMID:28572612
reference_title: "One-month spaceflight compromises the bone microstructure, tissue-level mechanical properties, osteocyte survival and lacunae volume in mature mice skeletons."
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: osteocyte death was evidenced along with a smaller and more spherical
shape of the osteocyte lacunae because of lacunar mineralization
explanation: Bion-M1 one-month spaceflight caused trabecular disconnection, cortical
thinning, and osteocyte death in mice, with no recovery at 8 days
- name: Osteocyte Mechanosensing Disruption in Microgravity
description: Microgravity removes gravitational mechanical loading, impairing osteocyte
mechanotransduction. Osteocytes sense mechanical strain via the lacuno-canalicular
network and regulate bone remodeling accordingly. In microgravity, loss of fluid
shear stress and mechanical stimulation leads to downregulation of key osteocytic
genes and impaired osteocyte differentiation.
cell_types:
- preferred_term: Osteocyte
term:
id: CL:0000137
label: osteocyte
biological_processes:
- preferred_term: Cellular Response to Mechanical Stimulus
term:
id: GO:0071260
label: cellular response to mechanical stimulus
evidence:
- reference: PMID:33835498
reference_title: "Global transcriptomic analysis of a murine osteocytic cell line subjected to spaceflight."
supports: SUPPORT
evidence_source: IN_VITRO
snippet: µG impairs the differentiation of osteocytes, consistent with prior osteoblast
spaceflight experiments, which resulted in the downregulation of key osteocytic
genes
explanation: Osteocyte cell line (Ocy454) flown on ISS SpaceX Dragon-6 showed
impaired differentiation and altered glycolysis, effects not replicated by ground-based
simulators
- reference: PMID:29559713
reference_title: "Skeletal changes during and after spaceflight."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: clear parallels exist between the effects of spaceflight, periods of
immobilization and ageing, with possibly irreversible features
explanation: Review establishes that spaceflight-induced skeletal changes parallel
accelerated aging via disrupted mechanosensing
- name: Microgravity-Accelerated Bone Resorption
description: Spaceflight induces a rapid and sustained increase in osteoclast-mediated
bone resorption. Astronauts lose approximately 0.8% of bone mass per month in
weight-bearing lower limb sites, with bone resorption markers plateauing at 113%
above pre-flight levels within days of entering microgravity.
biological_processes:
- preferred_term: Bone Resorption
term:
id: GO:0045453
label: bone resorption
evidence:
- reference: PMID:32411816
reference_title: "A systematic review and meta-analysis of bone loss in space travelers."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Bone loss in space travelers is a major challenge for long-duration space
exploration.
explanation: Meta-analysis of 148 space travelers quantifies lower limb bone loss
rate of -0.8% per month during microgravity exposure
- reference: PMID:32411816
reference_title: "A systematic review and meta-analysis of bone loss in space travelers."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: microgravity-induced bone loss is a significant and unresolved health
risk for space travelers
explanation: Bone resorption markers plateau at 113% above pre-flight levels with
rapid onset (half-max at 11 days)
- name: Spaceflight-Induced Mitochondrial Stress in Bone
description: Multi-omics analyses of spaceflight tissues reveal mitochondrial dysfunction
as a central biological hub for spaceflight impact. Mitochondrial stress pathways
are consistently enriched across multiple tissue types and missions, contributing
to impaired cellular function in bone and other organ systems.
biological_processes:
- preferred_term: Mitochondrion Organization
term:
id: GO:0007005
label: mitochondrion organization
evidence:
- reference: PMID:33242417
reference_title: "Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact."
supports: SUPPORT
evidence_source: COMPUTATIONAL
snippet: Overall pathway analyses on the multi-omics datasets showed significant
enrichment for mitochondrial processes, as well as innate immunity, chronic
inflammation, cell cycle, circadian rhythm, and olfactory functions
explanation: GeneLab multi-omics integration across NASA missions identifies mitochondrial
stress as a consistent spaceflight phenotype
phenotypes:
- name: Decreased Bone Mineral Density
category: Musculoskeletal
frequency: VERY_FREQUENT
diagnostic: true
notes: T-score <= -2.5
phenotype_term:
preferred_term: Decreased Bone Density
term:
id: HP:0004349
label: Reduced bone mineral density
evidence:
- reference: PMID:23748068
reference_title: "Aromatase deficiency, a rare syndrome: case report."
supports: SUPPORT
snippet: Lumbar osteoporosis was detected in bone densitometry.
explanation: Clinical documentation of reduced bone mineral density in aromatase
deficiency-induced osteoporosis
- reference: PMID:21874760
reference_title: "Aromatase activity and bone loss."
supports: SUPPORT
snippet: aromatase activity and estrogen production are necessary for longitudinal
bone growth, attainment of peak bone mass, the pubertal growth spurt, epiphyseal
closure, and normal bone remodeling in young individuals.
explanation: Demonstrates that estrogen deficiency impairs achievement and maintenance
of peak bone mass, leading to decreased BMD
- name: Vertebral Fractures
category: Musculoskeletal
frequency: FREQUENT
phenotype_term:
preferred_term: Vertebral Compression Fractures
term:
id: HP:0002953
label: Vertebral compression fracture
evidence:
- reference: PMID:28168409
reference_title: "Worldwide prevalence and incidence of osteoporotic vertebral fractures."
supports: SUPPORT
snippet: The prevalence of morphometric vertebral fractures in European women
is highest in Scandinavia (26%) and lowest in Eastern Europe (18%).
explanation: Systematic review documents high prevalence of vertebral fractures
in osteoporosis, confirming this as a key phenotype.
- name: Femur Fractures
category: Musculoskeletal
frequency: OCCASIONAL
notes: Major cause of morbidity and mortality
phenotype_term:
preferred_term: Femur Fractures
term:
id: HP:0031846
label: Femur fracture
- name: Kyphosis
category: Musculoskeletal
frequency: FREQUENT
notes: From vertebral compression fractures
phenotype_term:
preferred_term: Kyphosis
term:
id: HP:0002808
label: Kyphosis
- name: Height Loss
category: Musculoskeletal
frequency: FREQUENT
phenotype_term:
preferred_term: Short Stature
term:
id: HP:0004322
label: Short stature
biochemical:
- name: Bone Turnover Markers
presence: Variable
context: CTX, P1NP indicate resorption/formation rates
- name: Calcium
presence: Normal
context: Usually normal in primary osteoporosis
- name: Vitamin D
presence: Variable
context: Deficiency common and contributes to bone loss
- name: PTH
presence: Variable
context: May be elevated with vitamin D deficiency
genetic:
- name: LRP5
association: Risk Factor
notes: Wnt signaling pathway
- name: SOST
association: Risk Factor
notes: Encodes sclerostin
- name: ESR1
association: Risk Factor
notes: Estrogen receptor
- name: VDR
association: Risk Factor
notes: Vitamin D receptor
environmental:
- name: Estrogen Deficiency
notes: Menopause is major risk factor
evidence:
- reference: PMID:21874760
reference_title: "Aromatase activity and bone loss."
supports: SUPPORT
snippet: extraglandular aromatization of circulating androgen precursors is the
major source of estrogen not only in men (since only 15% of circulating estradiol
is released directly by the testis) but also in women after the menopause.
explanation: Post-menopausal women rely on aromatase activity for estrogen production,
making aromatase activity critical for bone health after menopause
- reference: PMID:18567553
reference_title: "Estrogen and bone: insights from estrogen-resistant, aromatase-deficient, and normal men."
supports: SUPPORT
snippet: studies in these unusual patients have stimulated research on defining
the role of estrogen in regulating bone metabolism in normal adult and aging
men, providing further insights into estrogen regulation of bone metabolism
not only in men, but also in women.
explanation: Demonstrates that estrogen is essential for bone metabolism in both
sexes, with deficiency leading to osteoporosis
- name: Calcium Deficiency
notes: Inadequate dietary intake
- name: Vitamin D Deficiency
notes: Impairs calcium absorption
- name: Sedentary Lifestyle
notes: Lack of weight-bearing exercise
- name: Smoking
notes: Accelerates bone loss
evidence:
- reference: PMID:30631414
reference_title: "The Effect of Tobacco Smoking on Bone Mass: An Overview of Pathophysiologic Mechanisms."
supports: SUPPORT
snippet: tobacco smoking causes an imbalance in bone turnover, leading to lower
bone mass and making bone vulnerable to osteoporosis and fracture
explanation: Review confirms that smoking causes bone turnover imbalance that
increases osteoporosis and fracture risk.
- name: Glucocorticoid Use
notes: Major cause of secondary osteoporosis
evidence:
- reference: PMID:29691807
reference_title: "Glucocorticoid-induced osteoporosis: an update."
supports: SUPPORT
snippet: Glucocorticoid-induced osteoporosis is the most common secondary cause
of osteoporosis and the resulting fractures cause significant morbidity.
explanation: Review confirms glucocorticoid use is the leading cause of secondary
osteoporosis.
- name: Microgravity Exposure
notes: >
Spaceflight-induced mechanical unloading causes 1-1.5% bone loss per month in
weight-bearing sites. Recovery is slow and often incomplete, with some astronauts
showing deficits equivalent to a decade of terrestrial aging after one year.
evidence:
- reference: PMID:32411816
reference_title: "A systematic review and meta-analysis of bone loss in space travelers."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Bone loss in space travelers is a major challenge for long-duration space
exploration.
explanation: Systematic review and meta-analysis of bone loss in 148 space travelers
documents site-dependent bone loss with lower limbs losing -0.8% per month
- reference: PMID:35773442
reference_title: "Incomplete recovery of bone strength and trabecular microarchitecture at the distal tibia 1 year after return from long duration spaceflight."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: nine of 17 astronauts did not fully recover tibia total BMD after 12-months
explanation: HR-pQCT study showing incomplete bone recovery one year after spaceflight,
commensurate with a decade of terrestrial age-related bone loss
- reference: PMID:33597120
reference_title: "Pre-flight exercise and bone metabolism predict unloading-induced bone loss due to spaceflight."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Increases in training volume predicted preservation of tibia bone strength
and trabecular vBMD and thickness
explanation: Pre-flight exercise and in-flight resistance training predict and
partially mitigate spaceflight bone loss in astronauts
- reference: PMID:32900939
reference_title: "Targeting myostatin/activin A protects against skeletal muscle and bone loss during spaceflight."
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: Wild type mice lost significant muscle and bone mass during the 33 d
spent in microgravity
explanation: ISS Rodent Research-19 confirmed that microgravity causes significant
bone and muscle loss in wild-type mice
treatments:
- name: Bisphosphonates
description: First-line antiresorptives (alendronate, risedronate, zoledronic acid).
treatment_term:
preferred_term: bisphosphonate agent therapy
term:
id: MAXO:0000954
label: bisphosphonate agent therapy
evidence:
- reference: PMID:34807231
reference_title: "Time to Benefit of Bisphosphonate Therapy for the Prevention of Fractures Among Postmenopausal Women With Osteoporosis: A Meta-analysis of Randomized Clinical Trials."
supports: SUPPORT
snippet: The pooled meta-analysis found that 12.4 months (95% CI, 6.3-18.4 months)
were needed to avoid 1 nonvertebral fracture per 100 postmenopausal women receiving
bisphosphonate therapy.
explanation: Meta-analysis of 10 RCTs with 23,384 women demonstrates bisphosphonate
efficacy in preventing fractures.
- reference: PMID:31400472
reference_title: "Resistive exercise in astronauts on prolonged spaceflights provides partial protection against spaceflight-induced bone loss."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: combined Bis+ARED prevented declines in all DXA and QCT hip densitometry
and in estimates of FE hip strengths
explanation: Bisphosphonate alendronate combined with ARED resistive exercise
prevented bone loss during ISS missions, while exercise alone only partially
attenuated loss and did not suppress bone resorption
- reference: PMID:37723136
reference_title: "Bisphosphonate conjugation enhances the bone-specificity of NELL-1-based systemic therapy for spaceflight-induced bone loss in mice."
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: BP-NELL-PEG significantly increased bone formation in flight and ground
control mice without obvious adverse health effects
explanation: Bisphosphonate-conjugated NELL-1 therapy showed bone-specific efficacy
during 9-week ISS Rodent Research-5 mission
- name: Denosumab
description: RANKL inhibitor, potent antiresorptive.
treatment_term:
preferred_term: pharmacotherapy
term:
id: MAXO:0000058
label: pharmacotherapy
therapeutic_agent:
- preferred_term: denosumab
term:
id: NCIT:C61313
label: Denosumab
- name: Teriparatide
description: PTH analog, anabolic agent for severe osteoporosis.
treatment_term:
preferred_term: pharmacotherapy
term:
id: MAXO:0000058
label: pharmacotherapy
therapeutic_agent:
- preferred_term: teriparatide
term:
id: NCIT:C61966
label: Teriparatide
- name: Romosozumab
description: Sclerostin inhibitor with dual anabolic/antiresorptive effect.
treatment_term:
preferred_term: pharmacotherapy
term:
id: MAXO:0000058
label: pharmacotherapy
therapeutic_agent:
- preferred_term: romosozumab
term:
id: NCIT:C152246
label: Romosozumab
- name: Calcium Supplementation
description: Ensure adequate intake (1000-1200 mg/day).
treatment_term:
preferred_term: calcium supplementation
term:
id: MAXO:0001139
label: calcium supplementation
- name: Vitamin D Supplementation
description: Maintain 25(OH)D >30 ng/mL.
treatment_term:
preferred_term: vitamin D supplementation
term:
id: MAXO:0000110
label: vitamin D supplementation
- name: Weight-Bearing Exercise
description: Helps maintain bone density.
treatment_term:
preferred_term: physical therapy
term:
id: MAXO:0000011
label: physical therapy
datasets:
- title: 37-Day microgravity exposure in 16-Week female C57BL/6J mice during NASA
RR-1 -- bone loss at weight-bearing sites
description: MicroCT analysis of femur and vertebrae from mice on the RR-1 NASA
Validation Flight (SpaceX-4). Demonstrates significant cancellous and cortical
bone loss in femur but not L2 vertebrae after 37 days of microgravity.
organism:
preferred_term: mouse
term:
id: NCBITaxon:10090
label: Mus musculus
conditions:
- spaceflight microgravity
- ground control
accession: nasa_osdr:OSD-804
- title: Single cell transcriptional profiling of femur bone marrow from mice flown
on RRRM-2
description: Single-cell RNA-seq of femur bone marrow from young and old mice after
55-58 days of microgravity on the ISS (SpaceX-18 / RR-17 RRRM-2 mission).
organism:
preferred_term: mouse
term:
id: NCBITaxon:10090
label: Mus musculus
data_type: SINGLE_CELL_RNA_SEQ
conditions:
- spaceflight microgravity
- ground control
- young mice
- old mice
accession: nasa_osdr:OSD-402
- title: Single cell transcriptional profiling of humerus bone marrow from mice flown
on RRRM-2
description: Single-cell RNA-seq of humerus bone marrow from young and old mice
after 55-58 days of microgravity on the ISS (SpaceX-18 / RR-17 RRRM-2 mission).
organism:
preferred_term: mouse
term:
id: NCBITaxon:10090
label: Mus musculus
data_type: SINGLE_CELL_RNA_SEQ
conditions:
- spaceflight microgravity
- ground control
accession: nasa_osdr:OSD-403
- title: Effects of Spaceflight on Bone Microarchitecture in Axial and Appendicular
Skeleton in Growing Ovariectomized Rats (STS-62)
description: MicroCT analysis of femur, humerus, lumbar vertebra, and calvarium
from ovariectomized rats flown on STS-62. Spaceflight reduced cortical bone growth
in appendicular skeleton.
organism:
preferred_term: rat
term:
id: NCBITaxon:10116
label: Rattus norvegicus
conditions:
- spaceflight microgravity
- ovariectomized
- ground control
accession: nasa_osdr:OSD-351
- title: Fifteen days of microgravity causes growth in calvaria of mice (STS-131)
description: MicroCT analysis of skull bone from mice flown on STS-131. Demonstrates
site-specific bone adaptation with skull bone volume increasing in microgravity,
contrasting with weight-bearing site losses.
organism:
preferred_term: mouse
term:
id: NCBITaxon:10090
label: Mus musculus
conditions:
- spaceflight microgravity
- ground control
accession: nasa_osdr:OSD-486
- title: RR-1 NASA Validation Flight - Mouse liver transcriptomic, proteomic, epigenomic
and histology data
description: Multi-omics dataset from the RR-1 mission (SpaceX-4) including RNA-seq,
whole-genome bisulfite sequencing, mass spectrometry, and histology from C57BL/6J
mice after 37 days of spaceflight.
organism:
preferred_term: mouse
term:
id: NCBITaxon:10090
label: Mus musculus
data_type: BULK_RNA_SEQ
publication: PMID:33242417
conditions:
- spaceflight microgravity
- ground control
accession: nasa_osdr:OSD-47
references:
- reference: DOI:10.1038/s41413-024-00362-4
title: 'Mapping RANKL- and OPG-expressing cells in bone tissue: the bone surface
cells as activators of osteoclastogenesis and promoters of the denosumab rebound
effect'
findings: []
- reference: DOI:10.1186/s13018-023-04179-5
title: 'The association of osteoprotegerin and RANKL with osteoporosis: a systematic
review with meta-analysis'
findings: []
- reference: DOI:10.3389/fendo.2024.1487998
title: 'Effects of probiotic supplementation on bone health in postmenopausal women:
a systematic review and meta-analysis'
findings: []
- reference: DOI:10.3390/biomedicines12081635
title: 'Mechanistic Insights and Therapeutic Strategies in Osteoporosis: A Comprehensive
Review'
findings: []
- reference: DOI:10.3390/biomedicines13061443
title: 'Beyond Bone Loss: A Biology Perspective on Osteoporosis Pathogenesis, Multi-Omics
Approaches, and Interconnected Mechanisms'
findings: []