{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T01:26:45Z","timestamp":1789694805283,"version":"4.0.1"},"reference-count":171,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T00:00:00Z","timestamp":1615939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["1I01BX002349-01, 2I01 BX001262-05, 1I01 BX004269-01"],"award-info":[{"award-number":["1I01BX002349-01, 2I01 BX001262-05, 1I01 BX004269-01"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"name":"South Carolina Spinal Cord Injury Research Fund","award":["2015 P-01, SCIRF 2015 P-04, SCIRF 2015 I-01, SCIRF 2016 I-03, and SCIRF 2018 I-01"],"award-info":[{"award-number":["2015 P-01, SCIRF 2015 P-04, SCIRF 2015 I-01, SCIRF 2016 I-03, and SCIRF 2018 I-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Spinal cord injury (SCI) affects approximately 300,000 people in the United States. Most individuals who sustain severe SCI also develop subsequent osteoporosis. However, beyond immobilization-related lack of long bone loading, multiple mechanisms of SCI-related bone density loss are incompletely understood. Recent findings suggest neuronal impairment and disability may lead to an upregulation of receptor activator of nuclear factor-\u03baB ligand (RANKL), which promotes bone resorption. Disruption of Wnt signaling and dysregulation of RANKL may also contribute to the pathogenesis of SCI-related osteoporosis. Estrogenic effects may protect bones from resorption by decreasing the upregulation of RANKL. This review will discuss the current proposed physiological and cellular mechanisms explaining osteoporosis associated with SCI. In addition, we will discuss emerging pharmacological and physiological treatment strategies, including the promising effects of estrogen on cellular protection.<\/jats:p>","DOI":"10.3390\/ijms22063057","type":"journal-article","created":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T11:48:22Z","timestamp":1615981702000},"page":"3057","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["The Pathophysiology of Osteoporosis after Spinal Cord Injury"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9650-3216","authenticated-orcid":false,"given":"Ramsha","family":"Shams","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Medical University of South Carolina, 96 Jonathan Lucas St., Charleston, SC 29425, USA"},{"name":"Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA"},{"name":"Department of Health and Human Performance, The Citadel, 171 Moultrie St., Charleston, SC 29409, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5906-408X","authenticated-orcid":false,"given":"Kelsey P.","family":"Drasites","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical University of South Carolina, 96 Jonathan Lucas St., Charleston, SC 29425, USA"},{"name":"Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA"},{"name":"Department of Health and Human Performance, The Citadel, 171 Moultrie St., Charleston, SC 29409, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vandana","family":"Zaman","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical University of South Carolina, 96 Jonathan Lucas St., Charleston, SC 29425, USA"},{"name":"Ralph H. Johnson Veterans Administration Medical Center, 109 Bee St., Charleston, SC 29401, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Matzelle","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical University of South Carolina, 96 Jonathan Lucas St., Charleston, SC 29425, USA"},{"name":"Ralph H. Johnson Veterans Administration Medical Center, 109 Bee St., Charleston, SC 29401, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald C.","family":"Shields","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical University of South Carolina, 96 Jonathan Lucas St., Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8936-1763","authenticated-orcid":false,"given":"Dena P.","family":"Garner","sequence":"additional","affiliation":[{"name":"Department of Health and Human Performance, The Citadel, 171 Moultrie St., Charleston, SC 29409, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Sole","sequence":"additional","affiliation":[{"name":"Department of Health and Human Performance, The Citadel, 171 Moultrie St., Charleston, SC 29409, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6386-9390","authenticated-orcid":false,"given":"Azizul","family":"Haque","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narendra L.","family":"Banik","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical University of South Carolina, 96 Jonathan Lucas St., Charleston, SC 29425, USA"},{"name":"Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA"},{"name":"Ralph H. 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Spinal Cord.","DOI":"10.1038\/s41393-020-00567-4"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1007\/s11011-014-9547-y","article-title":"Recent advances in the pharmacologic treatment of spinal cord injury","volume":"30","author":"Cox","year":"2015","journal-title":"Metab. Brain Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"282","DOI":"10.3389\/fneur.2019.00282","article-title":"Traumatic Spinal Cord Injury: An Overview of Pathophysiology, Models and Acute Injury Mechanisms","volume":"10","author":"Alizadeh","year":"2019","journal-title":"Front. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1080\/10790268.2017.1329076","article-title":"Assessment and management of acute spinal cord injury: From point of injury to rehabilitation","volume":"40","author":"Hachem","year":"2017","journal-title":"J. Spinal Cord Med."},{"key":"ref_7","first-page":"541","article-title":"Spinal Cord Injury Scarring and Inflammation: Therapies Targeting Glial and Inflammatory Responses","volume":"15","author":"Orr","year":"2018","journal-title":"Neurother. J. Am. Soc. Exp. Neurother."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2703","DOI":"10.1007\/s00198-018-4733-0","article-title":"Bone fragility after spinal cord injury: Reductions in stiffness and bone mineral at the distal femur and proximal tibia as a function of time","volume":"29","author":"Haider","year":"2018","journal-title":"Osteoporos Int."},{"key":"ref_9","first-page":"127","article-title":"Spinal Cord Injury and Osteoporosis: Causes, Mechanisms, and Rehabilitation Strategies","volume":"1","author":"Tan","year":"2013","journal-title":"Int. J. Phys. Med. Rehabil"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.afos.2016.06.003","article-title":"The effects of spinal cord injury on bone loss and dysregulation of the calcium\/parathyroid hormone loop in mice","volume":"2","author":"Bethea","year":"2016","journal-title":"Osteoporos Sarcopenia"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.ecl.2012.04.006","article-title":"Pathophysiology of osteoporosis: New mechanistic insights","volume":"41","author":"Armas","year":"2012","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"El-Kotob, R., Craven, B.C., Thabane, L., Papaioannou, A., Adachi, J.D., and Giangregorio, L.M. (2020). Exploring changes in bone mass in individuals with a chronic spinal cord injury. Osteoporos Int.","DOI":"10.1007\/s00198-020-05705-5"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1007\/s11914-012-0117-0","article-title":"Spinal cord injury-induced osteoporosis: Pathogenesis and emerging therapies","volume":"10","author":"Battaglino","year":"2012","journal-title":"Curr. Osteoporos Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"239","DOI":"10.4103\/1735-5362.228954","article-title":"A study on OPG\/RANK\/RANKL axis in osteoporotic bile duct-ligated rats and the involvement of nitrergic and opioidergic systems","volume":"13","author":"Doustimotlagh","year":"2018","journal-title":"Res. Pharm. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7433","DOI":"10.1073\/pnas.1109036109","article-title":"Anabolic action of parathyroid hormone regulated by the beta2-adrenergic receptor","volume":"109","author":"Hanyu","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1111\/j.1600-0765.2008.01177.x","article-title":"Cervical sympathectomy causes alveolar bone loss in an experimental rat model","volume":"44","author":"Kim","year":"2009","journal-title":"J. Periodontal. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1161\/CIRCRESAHA.119.314758","article-title":"Sympathetic Enhancement of Memory T-Cell Homing and Hypertension Sensitization","volume":"126","author":"Xiao","year":"2020","journal-title":"Circ. Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Rodriguez, G., Berri, M., Lin, P., Kamdar, N., Mahmoudi, E., and Peterson, M.D. (2020). Musculoskeletal morbidity following spinal cord injury: A longitudinal cohort study of privately-insured beneficiaries. Bone, 115700.","DOI":"10.1016\/j.bone.2020.115700"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/sj.sc.3101487","article-title":"Maintenance of exercise participation in individuals with spinal cord injury: Effects on quality of life, stress and pain","volume":"41","author":"Ditor","year":"2003","journal-title":"Spinal Cord"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1002\/jbmr.2059","article-title":"Reversing LRP5-dependent osteoporosis and SOST deficiency-induced sclerosing bone disorders by altering WNT signaling activity","volume":"29","author":"Chang","year":"2014","journal-title":"J. Bone Min. Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Cheng, L., Khalaf, A.T., Lin, T., Ran, L., Shi, Z., Wan, J., Zhou, X., and Zou, L. (2020). Exercise Promotes the Osteoinduction of HA\/beta-TCP Biomaterials via the Wnt Signaling Pathway. Metabolites, 10.","DOI":"10.3390\/metabo10030090"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.4103\/1673-5374.274326","article-title":"Electrical stimulation and denervated muscles after spinal cord injury","volume":"15","author":"Chandrasekaran","year":"2020","journal-title":"Neural Regen. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/sj.sc.3100679","article-title":"Muscle atrophy is prevented in patients with acute spinal cord injury using functional electrical stimulation","volume":"36","author":"Baldi","year":"1998","journal-title":"Spinal Cord"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s11914-011-0085-9","article-title":"Inhibition of cathepsin K for treatment of osteoporosis","volume":"10","author":"Boonen","year":"2012","journal-title":"Curr. Osteoporos Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4705","DOI":"10.2147\/IJN.S241163","article-title":"Ultra-Small Lysozyme-Protected Gold Nanoclusters as Nanomedicines Inducing Osteogenic Differentiation","volume":"15","author":"Li","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Anesi, A., Generali, L., Sandoni, L., Pozzi, S., and Grande, A. (2019). From Osteoclast Differentiation to Osteonecrosis of the Jaw: Molecular and Clinical Insights. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20194925"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.cmet.2006.05.012","article-title":"Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis","volume":"4","author":"Zhao","year":"2006","journal-title":"Cell Metab."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"17600","DOI":"10.1002\/jcp.28384","article-title":"Rhoifolin ameliorates titanium particle-stimulated osteolysis and attenuates osteoclastogenesis via RANKL-induced NF-kappaB and MAPK pathways","volume":"234","author":"Liao","year":"2019","journal-title":"J. Cell Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Jeong, S., Seong, J.H., Kang, J.H., Lee, D.S., and Yim, M. (2020). Dynamin-related protein 1 positively regulates osteoclast differentiation and bone loss. Febs Lett.","DOI":"10.1002\/1873-3468.13963"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"109235","DOI":"10.1016\/j.cbi.2020.109235","article-title":"Ellagic acid blocks RANKL-RANK interaction and suppresses RANKL-induced osteoclastogenesis by inhibiting RANK signaling pathways","volume":"331","author":"Xu","year":"2020","journal-title":"Chem. Biol. Interact."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1016\/j.ajpath.2013.11.022","article-title":"Osteoblast recruitment routes in human cancellous bone remodeling","volume":"184","author":"Kristensen","year":"2014","journal-title":"Am. J. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/bonekey.2013.215","article-title":"Coupling the activities of bone formation and resorption: A multitude of signals within the basic multicellular unit","volume":"3","author":"Sims","year":"2014","journal-title":"Bonekey Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"115628","DOI":"10.1016\/j.bone.2020.115628","article-title":"Re-thinking the bone remodeling cycle mechanism and the origin of bone loss","volume":"141","author":"Delaisse","year":"2020","journal-title":"Bone"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1007\/s00198-005-2028-8","article-title":"Osteoporosis after spinal cord injury","volume":"17","author":"Jiang","year":"2006","journal-title":"Osteoporos Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1007\/s002239900547","article-title":"Increased osteoclast-like cells formation in long-term bone marrow cultures from patients with a spinal cord injury","volume":"63","author":"Demulder","year":"1998","journal-title":"Calcif. Tissue Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1136\/ard.2005.037465","article-title":"Immunohistological examination of open sacroiliac biopsies of patients with ankylosing spondylitis: Detection of tumour necrosis factor alpha in two patients with early disease and transforming growth factor beta in three more advanced cases","volume":"65","author":"Francois","year":"2006","journal-title":"Ann. Rheum. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4226","DOI":"10.4049\/jimmunol.144.11.4226","article-title":"IL-6 stimulates osteoclast-like multinucleated cell formation in long term human marrow cultures by inducing IL-1 release","volume":"144","author":"Kurihara","year":"1990","journal-title":"J. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/j.bone.2007.12.224","article-title":"Osteocytes, mechanosensing and Wnt signaling","volume":"42","author":"Bonewald","year":"2008","journal-title":"Bone"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s11914-020-00564-9","article-title":"Osteocyte-Mediated Translation of Mechanical Stimuli to Cellular Signaling and Its Role in Bone and Non-bone-Related Clinical Complications","volume":"18","author":"Yan","year":"2020","journal-title":"Curr. Osteoporos Rep."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Kovacs, B., Vajda, E., and Nagy, E.E. (2019). Regulatory Effects and Interactions of the Wnt and OPG-RANKL-RANK Signaling at the Bone-Cartilage Interface in Osteoarthritis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184653"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1186\/s12967-014-0334-7","article-title":"Achyranthes bidentata extract exerts osteoprotective effects on steroid-induced osteonecrosis of the femoral head in rats by regulating RANKL\/RANK\/OPG signaling","volume":"12","author":"Jiang","year":"2014","journal-title":"J. Transl. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.pmrj.2014.08.948","article-title":"Osteoporosis in individuals with spinal cord injury","volume":"7","author":"Bauman","year":"2015","journal-title":"Pm R"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1016\/j.jcot.2019.07.004","article-title":"Vitamin D for skeletal and non-skeletal health: What we should know","volume":"10","author":"Charoenngam","year":"2019","journal-title":"J. Clin. Orthop. Trauma"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2968","DOI":"10.1111\/j.1582-4934.2012.01624.x","article-title":"Spinal cord injury causes bone loss through peroxisome proliferator-activated receptor-gamma and Wnt signalling","volume":"16","author":"Yan","year":"2012","journal-title":"J. Cell Mol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1089\/scd.2006.0044","article-title":"Osteogenic differentiation of murine embryonic stem cells is mediated by fibroblast growth factor receptors","volume":"16","author":"Speicher","year":"2007","journal-title":"Stem Cells Dev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.gene.2006.04.028","article-title":"Coordinated fibroblast growth factor and heparan sulfate regulation of osteogenesis","volume":"379","author":"Jackson","year":"2006","journal-title":"Gene"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1083\/jcb.110.6.2195","article-title":"Transforming growth factor-beta and the initiation of chondrogenesis and osteogenesis in the rat femur","volume":"110","author":"Joyce","year":"1990","journal-title":"J. Cell Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1097\/00003086-199801000-00006","article-title":"Bone morphogenetic protein and bone morphogenetic protein gene family in bone formation and repair","volume":"346","author":"Wozney","year":"1998","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2941","DOI":"10.1101\/gad.1709008","article-title":"PPARgamma and C\/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale","volume":"22","author":"Lefterova","year":"2008","journal-title":"Genes Dev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/S0092-8674(00)80258-5","article-title":"Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts","volume":"89","author":"Komori","year":"1997","journal-title":"Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0092-8674(01)00622-5","article-title":"The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation","volume":"108","author":"Nakashima","year":"2002","journal-title":"Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1002\/jcb.20958","article-title":"Regulation of osteoblast differentiation by transcription factors","volume":"99","author":"Komori","year":"2006","journal-title":"J. Cell Biochem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1016\/j.cell.2015.05.029","article-title":"Glucose Uptake and Runx2 Synergize to Orchestrate Osteoblast Differentiation and Bone Formation","volume":"161","author":"Wei","year":"2015","journal-title":"Cell"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Rahman, S., Czernik, P.J., Lu, Y., and Lecka-Czernik, B. (2012). beta-catenin directly sequesters adipocytic and insulin sensitizing activities but not osteoblastic activity of PPARgamma2 in marrow mesenchymal stem cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0051746"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Chen, X., Chen, J., Xu, D., Zhao, S., Song, H., and Peng, Y. (2017). Effects of Osteoglycin (OGN) on treating senile osteoporosis by regulating MSCs. BMC Musculoskelet. Disord., 18.","DOI":"10.1186\/s12891-017-1779-7"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1002\/(SICI)1097-4644(19990901)74:3<357::AID-JCB5>3.0.CO;2-7","article-title":"Inhibition of Osf2\/Cbfa1 expression and terminal osteoblast differentiation by PPARgamma2","volume":"74","author":"Gubrij","year":"1999","journal-title":"J. Cell Biochem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/382225a0","article-title":"A new member of the frizzled family from Drosophila functions as a Wingless receptor","volume":"382","author":"Bhanot","year":"1996","journal-title":"Nature"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.cell.2006.04.009","article-title":"Secretion of Wnt ligands requires Evi, a conserved transmembrane protein","volume":"125","author":"Bartscherer","year":"2006","journal-title":"Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"12816","DOI":"10.1074\/jbc.M200187200","article-title":"Drosophila segment polarity gene product porcupine stimulates the posttranslational N-glycosylation of wingless in the endoplasmic reticulum","volume":"277","author":"Tanaka","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.cell.2006.02.049","article-title":"Wntless, a conserved membrane protein dedicated to the secretion of Wnt proteins from signaling cells","volume":"125","author":"Banziger","year":"2006","journal-title":"Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1038\/cdd.2015.168","article-title":"Fate decision of mesenchymal stem cells: Adipocytes or osteoblasts?","volume":"23","author":"Chen","year":"2016","journal-title":"Cell Death Differ."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Maeda, K., Kobayashi, Y., Koide, M., Uehara, S., Okamoto, M., Ishihara, A., Kayama, T., Saito, M., and Marumo, K. (2019). The Regulation of Bone Metabolism and Disorders by Wnt Signaling. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225525"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1038\/cdd.2014.8","article-title":"Canonical Wnt signalling activates TAZ through PP1A during osteogenic differentiation","volume":"21","author":"Byun","year":"2014","journal-title":"Cell Death Differ."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1359\/jbmr.070810","article-title":"Wnt10b increases postnatal bone formation by enhancing osteoblast differentiation","volume":"22","author":"Bennett","year":"2007","journal-title":"J. Bone Min. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.1002\/jbmr.118","article-title":"Wnt10b deficiency results in age-dependent loss of bone mass and progressive reduction of mesenchymal progenitor cells","volume":"25","author":"Stevens","year":"2010","journal-title":"J. Bone Min. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.ydbio.2005.09.045","article-title":"Conditional deletion of beta-catenin in the mesenchyme of the developing mouse uterus results in a switch to adipogenesis in the myometrium","volume":"288","author":"Arango","year":"2005","journal-title":"Dev. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Luther, J., Yorgan, T.A., Rolvien, T., Ulsamer, L., Koehne, T., Liao, N., Keller, D., Vollersen, N., Teufel, S., and Neven, M. (2018). Wnt1 is an Lrp5-independent bone-anabolic Wnt ligand. Sci. Transl. Med., 10.","DOI":"10.1126\/scitranslmed.aau7137"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2678","DOI":"10.1172\/JCI92617","article-title":"Osteocyte-specific WNT1 regulates osteoblast function during bone homeostasis","volume":"127","author":"Joeng","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1038\/nm.3586","article-title":"Wnt4 signaling prevents skeletal aging and inflammation by inhibiting nuclear factor-kappaB","volume":"20","author":"Yu","year":"2014","journal-title":"Nat. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/nm.2653","article-title":"Wnt5a-Ror2 signaling between osteoblast-lineage cells and osteoclast precursors enhances osteoclastogenesis","volume":"18","author":"Maeda","year":"2012","journal-title":"Nat. Med."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Chen, J., Tu, X., Esen, E., Joeng, K.S., Lin, C., Arbeit, J.M., Ruegg, M.A., Hall, M.N., Ma, L., and Long, F. (2014). WNT7B promotes bone formation in part through mTORC1. PLoS Genet., 10.","DOI":"10.1371\/journal.pgen.1004145"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3324","DOI":"10.1073\/pnas.0408742102","article-title":"Regulation of osteoblastogenesis and bone mass by Wnt10b","volume":"102","author":"Bennett","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1038\/nm.3654","article-title":"Osteoblast-derived WNT16 represses osteoclastogenesis and prevents cortical bone fragility fractures","volume":"20","author":"Henning","year":"2014","journal-title":"Nat. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1359\/jbmr.090411","article-title":"Sclerostin mediates bone response to mechanical unloading through antagonizing Wnt\/beta-catenin signaling","volume":"24","author":"Lin","year":"2009","journal-title":"J. Bone Min. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"a015081","DOI":"10.1101\/cshperspect.a015081","article-title":"Secreted and transmembrane wnt inhibitors and activators","volume":"5","author":"Cruciat","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.ctrv.2017.11.002","article-title":"Targeting the Wnt\/beta-catenin pathway in cancer: Update on effectors and inhibitors","volume":"62","author":"Krishnamurthy","year":"2018","journal-title":"Cancer Treat Rev."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1038\/35083081","article-title":"Novel mechanism of Wnt signalling inhibition mediated by Dickkopf-1 interaction with LRP6\/Arrow","volume":"3","author":"Bafico","year":"2001","journal-title":"Nat. Cell Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/35077108","article-title":"LDL-receptor-related protein 6 is a receptor for Dickkopf proteins","volume":"411","author":"Mao","year":"2001","journal-title":"Nature"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1359\/jbmr.060311","article-title":"Deletion of a single allele of the Dkk1 gene leads to an increase in bone formation and bone mass","volume":"21","author":"Morvan","year":"2006","journal-title":"J. Bone Min. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1007\/s00774-017-0847-2","article-title":"Assessment of the effect of systemic delivery of sclerostin antibodies on Wnt signaling in distraction osteogenesis","volume":"36","author":"Alzahrani","year":"2018","journal-title":"J. Bone Min. Metab."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1038\/bonekey.2015.82","article-title":"The regulation of osteoclast differentiation by Wnt signals","volume":"4","author":"Kobayashi","year":"2015","journal-title":"Bonekey Rep."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1359\/jbmr.080216","article-title":"Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength","volume":"23","author":"Li","year":"2008","journal-title":"J. Bone Min. Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3212","DOI":"10.3892\/mmr.2015.3152","article-title":"Receptor activator of nuclear factor-kappaB ligand (RANKL)\/RANK\/osteoprotegerin system in bone and other tissues (review)","volume":"11","author":"Liu","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S0092-8674(00)80209-3","article-title":"Osteoprotegerin: A novel secreted protein involved in the regulation of bone density","volume":"89","author":"Simonet","year":"1997","journal-title":"Cell"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.pharmthera.2016.06.017","article-title":"From bones to blood pressure, developing novel biologic approaches targeting the osteoprotegein pathway for pulmonary vascular disease","volume":"169","author":"Dawson","year":"2017","journal-title":"Pharm. Ther."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1007\/s00223-016-0185-8","article-title":"The Role of Tumor Necrosis Factor Alpha and TNF Superfamily Members in Bone Damage in Patients with End-Stage Chronic Obstructive Lung Disease Prior to Lung Transplantation","volume":"99","author":"Kochetkova","year":"2016","journal-title":"Calcif. Tissue Int."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1006\/bbrc.1998.9788","article-title":"RANK is the essential signaling receptor for osteoclast differentiation factor in osteoclastogenesis","volume":"253","author":"Nakagawa","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1101\/gad.12.9.1260","article-title":"osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification","volume":"12","author":"Bucay","year":"1998","journal-title":"Genes Dev."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"3540","DOI":"10.1073\/pnas.96.7.3540","article-title":"Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand","volume":"96","author":"Hsu","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/36593","article-title":"A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function","volume":"390","author":"Anderson","year":"1997","journal-title":"Nature"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.4049\/jimmunol.1102063","article-title":"Development and Function of Murine B Cells Lacking RANK","volume":"188","author":"Perlot","year":"2012","journal-title":"J. Immunol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/s41526-020-00118-4","article-title":"Hindlimb unloading causes regional loading-dependent changes in osteocyte inflammatory cytokines that are modulated by exogenous irisin treatment","volume":"6","author":"Metzger","year":"2020","journal-title":"NPJ Microgravity"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Qiu, H., Qin, A., Cheng, T., Chim, S.M., Smithers, L., Chen, K., Song, D., Liu, Q., Zhao, J., and Wang, C. (2020). A missense mutation sheds light on a novel structure-function relationship of RANKL. J. Cell Physiol.","DOI":"10.1002\/jcp.30045"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0092-8674(00)81569-X","article-title":"Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation","volume":"93","author":"Lacey","year":"1998","journal-title":"Cell"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"3597","DOI":"10.1073\/pnas.95.7.3597","article-title":"Osteoclast differentiation factor is a ligand for osteoprotegerin\/osteoclastogenesis-inhibitory factor and is identical to TRANCE\/RANKL","volume":"95","author":"Yasuda","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/S8756-3282(99)00210-0","article-title":"Osteoblasts\/stromal cells stimulate osteoclast activation through expression of osteoclast differentiation factor\/RANKL but not macrophage colony-stimulating factor","volume":"25","author":"Udagawa","year":"1999","journal-title":"Bone"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1002\/jbmr.5650040106","article-title":"Prostaglandins promote osteoclastlike cell formation by a mechanism involving cyclic adenosine 3\u2019,5\u2019-monophosphate in mouse bone marrow cell cultures","volume":"4","author":"Akatsu","year":"1989","journal-title":"J. Bone Min. Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1002\/jbmr.5650060212","article-title":"Role of prostaglandins in interleukin-1-induced bone resorption in mice in vitro","volume":"6","author":"Akatsu","year":"1991","journal-title":"J. Bone Min. Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1210\/endo-123-3-1504","article-title":"Induction of calcitonin receptors by 1 alpha, 25-dihydroxyvitamin D3 in osteoclast-like multinucleated cells formed from mouse bone marrow cells","volume":"123","author":"Takahashi","year":"1988","journal-title":"Endocrinology"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/jbmr.5650060114","article-title":"Structural requirements for the action of parathyroid hormone-related protein (PTHrP) on bone resorption by isolated osteoclasts","volume":"6","author":"Evely","year":"1991","journal-title":"J. Bone Min. Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"7724","DOI":"10.1074\/jbc.274.12.7724","article-title":"Activation of NF-kappaB by RANK requires tumor necrosis factor receptor-associated factor (TRAF) 6 and NF-kappaB-inducing kinase. Identification of a novel TRAF6 interaction motif","volume":"274","author":"Darnay","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Cheon, Y.H., Lee, C.H., Jeong, D.H., Kwak, S.C., Kim, S., Lee, M.S., and Kim, J.Y. (2020). Dual Oxidase Maturation Factor 1 Positively Regulates RANKL-Induced Osteoclastogenesis via Activating Reactive Oxygen Species and TRAF6-Mediated Signaling. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176416"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.3389\/fphar.2020.01048","article-title":"Inhibitory Effect of Cudratrixanthone U on RANKL-Induced Osteoclast Differentiation and Function in Macrophages and BMM Cells","volume":"11","author":"Kim","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.phymed.2018.06.020","article-title":"Icariin abrogates osteoclast formation through the regulation of the RANKL-mediated TRAF6\/NF-kappaB\/ERK signaling pathway in Raw264.7 cells","volume":"51","author":"Kim","year":"2018","journal-title":"Phytomedicine"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1182\/blood-2004-09-3662","article-title":"A crucial role for reactive oxygen species in RANKL-induced osteoclast differentiation","volume":"106","author":"Lee","year":"2005","journal-title":"Blood"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Chen, H., Fang, C., Zhi, X., Song, S., Gu, Y., Chen, X., Cui, J., Hu, Y., Weng, W., and Zhou, Q. (2020). Neobavaisoflavone inhibits osteoclastogenesis through blocking RANKL signalling-mediated TRAF6 and c-Src recruitment and NF-kappaB, MAPK and Akt pathways. J. Cell Mol. Med.","DOI":"10.1111\/jcmm.15543"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Qian, Z., Zhong, Z., Ni, S., Li, D., Zhang, F., Zhou, Y., Kang, Z., Qian, J., and Yu, B. (2020). Cytisine attenuates bone loss of ovariectomy mouse by preventing RANKL-induced osteoclastogenesis. J. Cell Mol. Med.","DOI":"10.1111\/jcmm.15622"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Liu, Y., Zeng, W., Ma, C., Wang, Z., Wang, C., Li, S., He, W., Zhang, Q., Xu, J., and Zhou, C. (2020). Maackiain dampens osteoclastogenesis via attenuating RANKL-stimulated NF-kappaB signalling pathway and NFATc1 activity. J. Cell Mol. Med.","DOI":"10.1111\/jcmm.15647"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"44347","DOI":"10.1074\/jbc.M202009200","article-title":"A RANK\/TRAF6-dependent Signal Transduction Pathway Is Essential for Osteoclast Cytoskeletal Organization and Resorptive Function","volume":"277","author":"Armstrong","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.bone.2015.05.021","article-title":"Osteoclast fusion is initiated by a small subset of RANKL-stimulated monocyte progenitors, which can fuse to RANKL-unstimulated progenitors","volume":"79","author":"Levaot","year":"2015","journal-title":"Bone"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/s41393-019-0377-y","article-title":"Gene expression changes are associated with severe bone loss and deficient fracture callus formation in rats with complete spinal cord injury","volume":"58","author":"Butezloff","year":"2020","journal-title":"Spinal Cord"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Udagawa, N., Koide, M., Nakamura, M., Nakamichi, Y., Yamashita, T., Uehara, S., Kobayashi, Y., Furuya, Y., Yasuda, H., and Fukuda, C. (2020). Osteoclast differentiation by RANKL and OPG signaling pathways. J. Bone Min. Metab.","DOI":"10.1007\/s00774-020-01162-6"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.expneurol.2014.01.008","article-title":"Sex steroids and neuroprotection in spinal cord injury: A review of preclinical investigations","volume":"259","author":"Elkabes","year":"2014","journal-title":"Exp. Neurol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1089\/neu.2014.3730","article-title":"Nanoparticle Estrogen in Rat Spinal Cord Injury Elicits Rapid Anti-Inflammatory Effects in Plasma, Cerebrospinal Fluid, and Tissue","volume":"32","author":"Cox","year":"2015","journal-title":"J. Neurotrauma"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1001\/jama.2013.278040","article-title":"Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women\u2019s Health Initiative randomized trials","volume":"310","author":"Manson","year":"2013","journal-title":"JAMA"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1111\/jnc.13464","article-title":"Administration of low dose estrogen attenuates gliosis and protects neurons in acute spinal cord injury in rats","volume":"136","author":"Samantaray","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1089\/neu.2009.1069","article-title":"Effect of endogenous androgens on 17beta-estradiol-mediated protection after spinal cord injury in male rats","volume":"27","author":"Kachadroka","year":"2010","journal-title":"J. Neurotrauma"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1002\/jnr.22337","article-title":"Postinjury estrogen treatment of chronic spinal cord injury improves locomotor function in rats","volume":"88","author":"Sribnick","year":"2010","journal-title":"J. Neurosci. Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"3230","DOI":"10.1097\/CCM.0b013e3182657560","article-title":"G-protein coupled estrogen receptor 1 mediated estrogenic neuroprotection against spinal cord injury","volume":"40","author":"Hu","year":"2012","journal-title":"Crit. Care Med."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1089\/neu.2006.0167","article-title":"Gender differences in spinal cord injury are not estrogen-dependent","volume":"24","author":"Swartz","year":"2007","journal-title":"J. Neurotrauma"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1016\/j.yexcr.2009.01.014","article-title":"Estrogen inhibits RANKL-stimulated osteoclastic differentiation of human monocytes through estrogen and RANKL-regulated interaction of estrogen receptor-\u03b1 with BCAR1 and Traf6","volume":"315","author":"Robinson","year":"2009","journal-title":"Exp. Cell Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1002\/jcb.24700","article-title":"Estrogen Inhibits RANKL-Induced Osteoclastic Differentiation by Increasing the Expression of TRPV5 Channel","volume":"115","author":"Chen","year":"2014","journal-title":"J. Cell. Biochem."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1111\/jcpt.12429","article-title":"Randomized trial comparing efficacies of zoledronate and alendronate for improving bone mineral density and inhibiting bone remodelling in women with post-menopausal osteoporosis","volume":"41","author":"Tan","year":"2016","journal-title":"J. Clin. Pharm. Ther."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1111\/j.1471-0528.1989.tb03260.x","article-title":"The pathophysiology of peri- and postmenopausal bone loss","volume":"96","author":"Nilas","year":"1989","journal-title":"Br. J. Obstet. Gynaecol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1056\/NEJMoa0809493","article-title":"Denosumab for prevention of fractures in postmenopausal women with osteoporosis","volume":"361","author":"Cummings","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1196\/annals.1346.047","article-title":"Interactive Effect of Interleukin-6 and Prostaglandin E2 on Osteoclastogenesis via the OPG\/RANKL\/RANK System","volume":"1068","author":"Liu","year":"2006","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.lfs.2004.10.079","article-title":"IL-1\u03b1 stimulates the formation of osteoclast-like cells by increasing M-CSF and PGE2 production and decreasing OPG production by osteoblasts","volume":"77","author":"Tanabe","year":"2005","journal-title":"Life Sci."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"3396","DOI":"10.1002\/jcp.25784","article-title":"TNF-\u03b1 promotes osteoclastogenesis through JNK signaling-dependent induction of Semaphorin3D expression in estrogen-deficiency induced osteoporosis","volume":"232","author":"Sang","year":"2017","journal-title":"J. Cell. Physiol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1097\/gme.0b013e3181920c77","article-title":"Relationship between circulating tumor necrosis factor system and bone mass before and after estrogen plus progestogen therapy","volume":"16","author":"Kim","year":"2009","journal-title":"Menopause"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/S8756-3282(02)00953-5","article-title":"The effects of estrogen on osteoprotegerin, RANKL, and estrogen receptor expression in human osteoblasts","volume":"32","author":"Bord","year":"2003","journal-title":"Bone"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1902\/jop.2007.070073","article-title":"RANKL Inhibition Through Osteoprotegerin Blocks Bone Loss in Experimental Periodontitis","volume":"78","author":"Jin","year":"2007","journal-title":"J. Periodontol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1038\/nm1096-1132","article-title":"Estrogen promotes apoptosis of murine osteoclasts mediated by TGF-beta","volume":"2","author":"Hughes","year":"1996","journal-title":"Nat. Med."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.bbrc.2020.07.083","article-title":"Tussilagone promotes osteoclast apoptosis and prevents estrogen deficiency-induced osteoporosis in mice","volume":"531","author":"Ryoo","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1111\/jnc.13610","article-title":"Administration of low dose estrogen attenuates persistent inflammation, promotes angiogenesis, and improves locomotor function following chronic spinal cord injury in rats","volume":"137","author":"Samantaray","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1007\/s12035-017-0400-2","article-title":"Estrogen Attenuates Local Inflammasome Expression and Activation after Spinal Cord Injury","volume":"55","author":"Zendedel","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1007\/s00198-011-1879-4","article-title":"High dose compressive loads attenuate bone mineral loss in humans with spinal cord injury","volume":"23","author":"Saha","year":"2012","journal-title":"Osteoporos Int."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1111\/j.1600-079X.2010.00751.x","article-title":"Synergistic effect of melatonin on exercise-induced neuronal reconstruction and functional recovery in a spinal cord injury animal model","volume":"48","author":"Park","year":"2010","journal-title":"J. Pineal Res."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1002\/jbmr.1833","article-title":"Bone blood flow and metabolism in humans: Effect of muscular exercise and other physiological perturbations","volume":"28","author":"Heinonen","year":"2013","journal-title":"J. Bone Min. Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"53","DOI":"10.3109\/17453678308992869","article-title":"Bone blood flow in conscious dogs at rest and during exercise","volume":"54","year":"1983","journal-title":"Acta Orthop. Scand."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Zhou, L., Huang, Y., Zhao, J., Yang, H., and Kuai, F. (2020). Oridonin promotes osteogenesis through Wnt\/beta-catenin pathway and inhibits RANKL-induced osteoclastogenesis in vitro. Life Sci., 118563.","DOI":"10.1016\/j.lfs.2020.118563"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"394","DOI":"10.26444\/aaem\/110527","article-title":"Bone losses in obese, ovariectomized rats appear to be independent from sclerostin-induced inhibition of the Wnt\/beta-catenin pathway","volume":"27","author":"Radzki","year":"2020","journal-title":"Ann. Agric. Environ. Med."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1007\/s00198-012-2155-y","article-title":"Effects of anti-resorptive agents on trabecular bone score (TBS) in older women","volume":"24","author":"Krieg","year":"2013","journal-title":"Osteoporos Int."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1089\/neu.2004.21.1371","article-title":"Targeting recovery: Priorities of the spinal cord-injured population","volume":"21","author":"Anderson","year":"2004","journal-title":"J. Neurotrauma"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1152\/jappl.1995.79.6.1889","article-title":"Electrical stimulation of leg muscles increases tibial trabecular bone formation in unloaded rats","volume":"79","author":"Zerath","year":"1995","journal-title":"J. Appl. Physiol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s00421-012-2416-7","article-title":"Time-course response in serum markers of bone turnover to a single-bout of electrical stimulation in patients with recent spinal cord injury","volume":"113","year":"2013","journal-title":"Eur. J. Appl. Physiol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s00198-011-1758-z","article-title":"Effects of strontium ranelate and alendronate on bone microstructure in women with osteoporosis. Results of a 2-year study","volume":"23","author":"Rizzoli","year":"2012","journal-title":"Osteoporos Int."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1093\/rheumatology\/37.1.51","article-title":"The use of cyclical etidronate in osteoporosis: Changes after completion of 3 years treatment","volume":"37","author":"Fairney","year":"1998","journal-title":"Rheumatology"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1007\/s00198-007-0540-8","article-title":"Mechanisms of action of bisphosphonates: Similarities and differences and their potential influence on clinical efficacy","volume":"19","author":"Russell","year":"2008","journal-title":"Osteoporos Int."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/s00198-010-1221-6","article-title":"Early treatment with zoledronic acid prevents bone loss at the hip following acute spinal cord injury","volume":"22","author":"Bubbear","year":"2011","journal-title":"Osteoporos Int."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.pmrj.2016.01.012","article-title":"Zoledronic Acid Treatment After Acute Spinal Cord Injury: Results of a Randomized, Placebo-Controlled Pilot Trial","volume":"8","author":"Schnitzer","year":"2016","journal-title":"Pm R"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1007\/s00223-007-9012-6","article-title":"Treatment with zoledronic acid ameliorates negative geometric changes in the proximal femur following acute spinal cord injury","volume":"80","author":"Shapiro","year":"2007","journal-title":"Calcif. Tissue Int."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1615\/CritRevPhysRehabilMed.2016018768","article-title":"Effect of Zoledronic Acid on Osteoporosis after Chronic Spinal Cord Injury: A Randomized Controlled Trial","volume":"28","author":"Varghese","year":"2016","journal-title":"Crit. Rev. Phys. Rehabil. Med."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1359\/jbmr.091035","article-title":"Odanacatib, a cathepsin-K inhibitor for osteoporosis: A two-year study in postmenopausal women with low bone density","volume":"25","author":"Bone","year":"2010","journal-title":"J. Bone Miner. Res."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1111\/j.1365-2125.2012.04471.x","article-title":"Odanacatib, a selective cathepsin K inhibitor to treat osteoporosis: Safety, tolerability, pharmacokinetics and pharmacodynamics-results from single oral dose studies in healthy volunteers","volume":"75","author":"Stoch","year":"2013","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1161\/CIRCULATIONAHA.105.561449","article-title":"Disruption of the cathepsin K gene reduces atherosclerosis progression and induces plaque fibrosis but accelerates macrophage foam cell formation","volume":"113","author":"Lutgens","year":"2006","journal-title":"Circulation"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/S2213-8587(19)30346-8","article-title":"Odanacatib for the treatment of postmenopausal osteoporosis: Results of the LOFT multicentre, randomised, double-blind, placebo-controlled trial and LOFT Extension study","volume":"7","author":"McClung","year":"2019","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1096\/fj.05-4221fje","article-title":"Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation","volume":"19","author":"Poole","year":"2005","journal-title":"Faseb J."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1056\/NEJMoa1305224","article-title":"Romosozumab in Postmenopausal Women with Low Bone Mineral Density","volume":"370","author":"McClung","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1056\/NEJMoa1607948","article-title":"Romosozumab Treatment in Postmenopausal Women with Osteoporosis","volume":"375","author":"Cosman","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"110817","DOI":"10.1016\/j.mce.2020.110817","article-title":"WISP-2 expression induced by Teriparatide treatment affects in vitro osteoblast differentiation and improves in vivo osteogenesis","volume":"513","author":"Smargiassi","year":"2020","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1007\/s00198-011-1666-2","article-title":"Teriparatide increases the maturation of circulating osteoblast precursors","volume":"23","author":"Tamone","year":"2012","journal-title":"Osteoporos Int."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s00223-016-0143-5","article-title":"Fracture Rate, Quality of Life and Back Pain in Patients with Osteoporosis Treated with Teriparatide: 24-Month Results from the Extended Forsteo Observational Study (ExFOS)","volume":"99","author":"Langdahl","year":"2016","journal-title":"Calcif. Tissue Int."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1056\/NEJM200105103441904","article-title":"Effect of Parathyroid Hormone (1-34) on Fractures and Bone Mineral Density in Postmenopausal Women with Osteoporosis","volume":"344","author":"Neer","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1007\/s00198-016-3534-6","article-title":"Teriparatide for osteoporosis: Importance of the full course","volume":"27","author":"Lindsay","year":"2016","journal-title":"Osteoporos Int."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1080\/01926230252929882","article-title":"Skeletal changes in rats given daily subcutaneous injections of recombinant human parathyroid hormone (1-34) for 2 years and relevance to human safety","volume":"30","author":"Vahle","year":"2002","journal-title":"Toxicol. Pathol."},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"Brodetska, L., Natrus, L., Lisakovska, O., Kaniura, O., Iakovenko, L., Skrypnyk, I., and Flis, P. (2020). The regulatory role of the RANKL\/RANK\/OPG signaling pathway in the mechanisms of tooth eruption in patients with impacted teeth. BMC Oral. Health, 20.","DOI":"10.1186\/s12903-020-01251-y"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1016\/j.immuni.2015.10.017","article-title":"Inhibition of the TNF Family Cytokine RANKL Prevents Autoimmune Inflammation in the Central Nervous System","volume":"43","author":"Guerrini","year":"2015","journal-title":"Immunity"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1136\/bjsports-2018-099723","article-title":"Oestrogen replacement improves bone mineral density in oligo-amenorrhoeic athletes: A randomised clinical trial","volume":"53","author":"Ackerman","year":"2019","journal-title":"Br. J. Sports Med."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1001\/jama.290.13.1729","article-title":"Effects of Estrogen Plus Progestin on Risk of Fracture and Bone Mineral Density: The Women\u2019s Health Initiative Randomized Trial","volume":"290","author":"Cauley","year":"2003","journal-title":"JAMA J. Am. Med Assoc."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"897","DOI":"10.7326\/0003-4819-130-11-199906010-00005","article-title":"The effect of low-dose continuous estrogen and progesterone therapy with calcium and vitamin D on bone in elderly women. A randomized, controlled trial","volume":"130","author":"Recker","year":"1999","journal-title":"Ann. Intern. Med."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1001\/jama.288.3.321","article-title":"Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results From the Women\u2019s Health Initiative randomized controlled trial","volume":"288","author":"Rossouw","year":"2002","journal-title":"JAMA"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/6\/3057\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:36:54Z","timestamp":1760161014000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/6\/3057"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,17]]},"references-count":171,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["ijms22063057"],"URL":"https:\/\/doi.org\/10.3390\/ijms22063057","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,17]]}}}