{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T07:11:36Z","timestamp":1793171496125,"version":"4.5.0"},"reference-count":135,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,31]],"date-time":"2022-07-31T00:00:00Z","timestamp":1659225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>As an essential component of the skeleton, bone tissue provides solid support for the body and protects vital organs. Bone tissue is a reservoir of calcium, phosphate, and other ions that can be released or stored in a controlled manner to provide constant concentration in body fluids. Normally, bone development or osteogenesis occurs through two ossification processes (intra-articular and intra-chondral), but the first produces woven bone, which is quickly replaced by stronger lamellar bone. Contrary to commonly held misconceptions, bone is a relatively dynamic organ that undergoes significant turnover compared to other organs in the body. Bone metabolism is a dynamic process that involves simultaneous bone formation and resorption, controlled by numerous factors. Bone metabolism comprises the key actions. Skeletal mass, structure, and quality are accrued and maintained throughout life, and the anabolic and catabolic actions are mostly balanced due to the tight regulation of the activity of osteoblasts and osteoclasts. This activity is also provided by circulating hormones and cytokines. Bone tissue remodeling processes are regulated by various biologically active substances secreted by bone tissue cells, namely RANK, RANKL, MMP-1, MMP-9, or type 1 collagen. Bone-derived factors (BDF) influence bone function and metabolism, and pathophysiological conditions lead to bone dysfunction. This work aims to analyze and evaluate the current literature on various local and systemic factors or immune system interactions that can affect bone metabolism and its impairments.<\/jats:p>","DOI":"10.3390\/ani12151946","type":"journal-article","created":{"date-parts":[[2022,7,31]],"date-time":"2022-07-31T21:49:02Z","timestamp":1659304142000},"page":"1946","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":138,"title":["Structural and Metabolic Changes in Bone"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8568-1770","authenticated-orcid":false,"given":"Agata","family":"Wawrzyniak","sequence":"first","affiliation":[{"name":"Institute of Medical Sciences, College of Medical Sciences, University of Rzesz\u00f3w, Rejtana Street 16c, 35-959 Rzesz\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8706-1927","authenticated-orcid":false,"given":"Krzysztof","family":"Balawender","sequence":"additional","affiliation":[{"name":"Institute of Medical Sciences, College of Medical Sciences, University of Rzesz\u00f3w, Rejtana Street 16c, 35-959 Rzesz\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"25103","DOI":"10.1074\/jbc.R109.041087","article-title":"Cellular and Molecular Mechanisms of Bone Remodeling","volume":"285","author":"Raggatt","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_2","first-page":"421746","article-title":"Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells","volume":"2015","author":"Cerri","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bcp.2017.02.001","article-title":"Osteocalcin and its endocrine functions","volume":"132","author":"Mizokami","year":"2017","journal-title":"Biochem. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1097\/HP.0000000000000881","article-title":"Modeling the Skeleton Weight of an Adult Caucasian Man","volume":"117","author":"Avtandilashvili","year":"2019","journal-title":"Health Phys."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/S0030-5898(20)31258-X","article-title":"Bone structure, composition, and mineralization","volume":"15","author":"Boskey","year":"1984","journal-title":"Orthop. Clin. N. Am."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1007\/s10856-011-4353-0","article-title":"Determination of composition and structure of spongy bone tissue in human head of femur by Raman spectral mapping","volume":"22","author":"Kozielski","year":"2011","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s00223-004-0168-z","article-title":"Bone Chemical Structure Response to Mechanical Stress Studied by High Pressure Raman Spectroscopy","volume":"76","author":"Morris","year":"2005","journal-title":"Calcif. Tissue Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1038\/nature10763","article-title":"The contribution of bone to whole-organism physiology","volume":"481","author":"Karsenty","year":"2012","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s001980200026","article-title":"The anabolic effects of parathyroid hormone","volume":"13","author":"Rubin","year":"2002","journal-title":"Osteoporos. Int."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1093\/ckj\/sfv011","article-title":"Calcitonin, the forgotten hormone: Does it deserve to be forgotten?","volume":"8","author":"Felsenfeld","year":"2015","journal-title":"Clin. Kidney J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/s41413-018-0019-6","article-title":"Paracrine and endocrine actions of bone-the functions of secretory proteins from osteoblasts, osteocytes, and osteoclasts","volume":"6","author":"Han","year":"2018","journal-title":"Bone Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.jocd.2014.08.001","article-title":"Peak Bone Mass and Patterns of Change in Total Bone Mineral Density and Bone Mineral Contents from Childhood into Young Adulthood","volume":"19","author":"Lu","year":"2016","journal-title":"J. Clin. Densitom."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.biomaterials.2018.09.028","article-title":"Bone physiology as inspiration for tissue regenerative therapies","volume":"185","author":"Lopes","year":"2018","journal-title":"Biomaterials"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1136\/jcp.2007.048868","article-title":"The cell biology of bone metabolism","volume":"61","author":"Datta","year":"2008","journal-title":"J.Clin. Pathol."},{"key":"ref_15","first-page":"9427","article-title":"Osteoporosis and fractures in liver disease: Relevance, pathogenesis and therapeutic implications","volume":"20","author":"Nakchbandi","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1006\/jtbi.2000.1073","article-title":"Theory for the Systemic Definition of Metabolic Pathways and their use in Interpreting Metabolic Function from a Pathway-Oriented Perspective","volume":"203","author":"Schilling","year":"2000","journal-title":"J. Theor. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1039\/B402005G","article-title":"Structure and mechanical quality of the collagen\u2013mineral nano-composite in bone","volume":"14","author":"Fratzl","year":"2004","journal-title":"J. Mater. Chem."},{"key":"ref_18","first-page":"347","article-title":"Biological basis of bone strength: Anatomy, physiology and measurement","volume":"20","author":"Hart","year":"2020","journal-title":"J. Musculoskelet. Neuronal Interact."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1359\/jbmr.2003.18.2.352","article-title":"Effect of long-term impact-loading on mass, size, and estimated strength of humerus and radius of female racquet-sports players: A peripheral quantitative computed tomography study between young and old starters and controls","volume":"18","author":"Kontulainen","year":"2003","journal-title":"J. Bone Miner. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.abb.2014.05.003","article-title":"Osteoblast and osteocyte: Games without frontiers","volume":"561","author":"Capulli","year":"2014","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1038\/bonekey.2015.117","article-title":"Communication of bone cells with hematopoiesis, immunity and energy metabolism","volume":"4","author":"Asada","year":"2015","journal-title":"BoneKEy Rep."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Molagoda, I.M.N., Athapaththu, A.M.G.K., ParkE, K., Choi, Y.H., Jeon, Y.J., and Young, K.G. (2022). Fermented Oyster (Crassostrea gigas) Extract Cures and Prevents Prednisolone-Induced Bone Resorption by Activating Osteoblast Differentiation. Foods, 11.","DOI":"10.3390\/foods11050678"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1002\/jbmr.443","article-title":"Smad6 is essential to limit BMP signaling during cartilage development","volume":"26","author":"Estrada","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"ref_24","first-page":"1593","article-title":"Signaling pathways governing osteoblast proliferation, differentiation and function","volume":"24","author":"Chau","year":"2009","journal-title":"Histol. Histopathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1038\/nature02040","article-title":"Osteoblastic cell sregulate the haemato-poietic stem cell niche","volume":"425","author":"Calvi","year":"2003","journal-title":"Nature"},{"key":"ref_26","first-page":"509","article-title":"Relationship between Osteopontin and Bone Mineral Density","volume":"17","author":"Vancea","year":"2021","journal-title":"Acta Endocrinol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/nature01660","article-title":"Control of osteoblast function and regulation of bone mass","volume":"423","author":"Harada","year":"2003","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"272","DOI":"10.7150\/ijbs.2929","article-title":"TGF-beta and BMP signaling in osteoblast differentiation and bone formation","volume":"8","author":"Chen","year":"2012","journal-title":"Int. J. Biol. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/ijos.2012.33","article-title":"The role of vascular endothelial growth factor in ossi-fication","volume":"4","author":"Yang","year":"2012","journal-title":"Int. J. Oral. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1677\/joe.0.1800247","article-title":"Evidence supporting dual, IGF-I-independent and IGF-I-dependent, roles for GH in promoting longitudinal bone growth","volume":"180","author":"Wang","year":"2004","journal-title":"J. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1001\/jama.291.9.1108","article-title":"Soluble RANKL and risk of nontraumatic fracture","volume":"291","author":"Schett","year":"2004","journal-title":"JAMA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e919159-1","DOI":"10.12659\/MSM.919159","article-title":"Osteopontin in Bone Metabolism and Bone Diseases","volume":"26","author":"Si","year":"2020","journal-title":"Med Sci. Monit."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1007\/s11914-021-00688-6","article-title":"Energy Metabolism of Osteocytes","volume":"19","author":"Karthik","year":"2021","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"151422","DOI":"10.1016\/j.aanat.2019.151422","article-title":"The osteocyte: A multifunctional cell within the bone","volume":"227","author":"Tresguerres","year":"2020","journal-title":"Ann. Anat. Anat. Anz."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Moriishi, T., and Komori, T. (2022). Osteocytes: Their Lacunocanalicular Structure and Mechanoresponses. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23084373"},{"key":"ref_36","first-page":"292","article-title":"Physiological and pathological osteocytic osteolysis","volume":"18","author":"Tsourdi","year":"2018","journal-title":"J. Musculoskelet. Neuronal Interact."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1152\/physrev.00043.2020","article-title":"The osteocyte as a signaling cell","volume":"102","author":"Bellido","year":"2022","journal-title":"Physiol. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1002\/dvdy.20603","article-title":"Buried alive: How osteoblasts become osteocytes","volume":"235","author":"Hall","year":"2006","journal-title":"Dev. Dyn."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s00795-015-0099-y","article-title":"The osteocyte plays multiple roles in bone remodeling and mineral homeostasis","volume":"48","author":"Chen","year":"2015","journal-title":"Med. Mol. Morphol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1093\/jmicro\/dfp032","article-title":"Amizuka N.FGF23 is mainly synthesized by osteocytes in the regularly distributed osteocytic lacunar canalicular system established after physiological bone remodeling","volume":"58","author":"Ubaidus","year":"2009","journal-title":"J. Electron Microsc."},{"key":"ref_41","first-page":"507","article-title":"1,25-Dihydroxyvitamin D insufficiency accelerates age-related bone loss by increasing oxidative stress and cell senescence","volume":"12","author":"Qiao","year":"2020","journal-title":"Am. J. Transl. Res."},{"key":"ref_42","first-page":"672","article-title":"Deletion of p16 prevents estrogen deficiency-induced osteoporosis by inhibiting oxidative stress and osteocyte senescence","volume":"12","author":"Li","year":"2020","journal-title":"Am. J. Transl. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"101608","DOI":"10.1016\/j.arr.2022.101608","article-title":"Osteocytes in bone aging: Advances, challenges, and future perspectives","volume":"77","author":"Cui","year":"2022","journal-title":"Ageing Res. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/978-3-030-36214-0_5","article-title":"The Roles of Bone Marrow-Resident Cells as a Microenvironment for Bone Metastasis","volume":"1226","author":"Shiozawa","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/nm1417","article-title":"Faculty Opinions recommendation of Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells","volume":"12","author":"Kollet","year":"2006","journal-title":"Nat. Med."},{"key":"ref_46","first-page":"189","article-title":"Osteoporosis and bone functional adaptation: Mechanobiological regulation of bone architecture in growing and adult bone, a review","volume":"37","author":"Mosley","year":"2000","journal-title":"J. Rehabil. Res. Dev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.rcl.2010.02.014","article-title":"Physiology of Bone Loss","volume":"48","author":"Clarke","year":"2010","journal-title":"Radiol. Clin. N. Am."},{"key":"ref_48","first-page":"1325","article-title":"Interaction between osteoblast and osteoclast: Impact in bone disease","volume":"19","author":"Phan","year":"2004","journal-title":"Histol. Histopathol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1359\/jbmr.080420","article-title":"Vitamin D and health: Perspectives from mice and man","volume":"23","author":"Bouillon","year":"2008","journal-title":"J. Bone Miner. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1002\/mpo.10334","article-title":"Biology of the basic multicellular unit and the pathophysiology of osteoporosis","volume":"41","author":"Jilka","year":"2003","journal-title":"Med. Pediatric Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2142","DOI":"10.1152\/japplphysiol.00564.2003","article-title":"Invited Review: Pathogenesis of osteoporosis","volume":"95","author":"Seeman","year":"2003","journal-title":"J. Appl. Physiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1111\/j.1749-6632.2002.tb04204.x","article-title":"Mechanisms of Glucocorticoid Action in Bone","volume":"966","author":"Canalis","year":"2002","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1359\/jbmr.2001.16.9.1575","article-title":"Cancellous bone remodeling occurs in specialized compartments lined by cells expressing osteoblastic markers","volume":"16","author":"Hauge","year":"2001","journal-title":"J. Bone Miner. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1359\/jbmr.2002.17.1.77","article-title":"The bone lining cell: Its role in cleaning Howship\u2019s lacunae and initiating bone formation","volume":"17","author":"Everts","year":"2002","journal-title":"J. Bone Miner. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1359\/jbmr.2001.16.9.1583","article-title":"The bone remodeling compartment: A circulatory function for bone lining cells","volume":"16","author":"Parfitt","year":"2001","journal-title":"J. Bone Miner. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"101545","DOI":"10.1016\/j.beem.2021.101545","article-title":"Bone marrow adipose tissue: Role in bone remodeling and energy metabolism","volume":"35","author":"Tencerova","year":"2021","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_57","first-page":"115","article-title":"Birth and Death of Bone Cells: Basic Regulatory Mechanisms and Implications for the Pathogenesis and Treatment of Osteoporosis","volume":"21","author":"Manolagas","year":"2000","journal-title":"Endocr. Rev."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2020\/6910312","article-title":"RANKL\/RANK\/OPG Pathway: A Mechanism Involved in Exercise-Induced Bone Remodeling","volume":"2020","author":"Tobeiha","year":"2020","journal-title":"BioMed Res. Int."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"8149","DOI":"10.1158\/0008-5472.CAN-06-4659","article-title":"Bone Morphogenetic Protein Signaling Suppresses Tumorigenesis at Gastric Epithelial Transition Zones in Mice","volume":"67","author":"Bleuming","year":"2007","journal-title":"Cancer Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3491","DOI":"10.1002\/jcb.23287","article-title":"Integration of BMP, Wnt, and notch signaling pathways in osteoblast differentiation","volume":"112","author":"Lin","year":"2011","journal-title":"J. Cell. Biochem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"32","DOI":"10.4236\/jbise.2013.68A1004","article-title":"BMP signaling in mesenchymal stem cell differentiation and bone formation","volume":"6","author":"Beederman","year":"2013","journal-title":"Biomed. Sci. Eng."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"5050","DOI":"10.1210\/endo.142.12.8536","article-title":"Minireview: The OPG\/RANKL\/RANK system","volume":"142","author":"Khosla","year":"2001","journal-title":"Endocrinology"},{"key":"ref_63","first-page":"163","article-title":"Normal bone physiology, remodelling and its hormonal regulation","volume":"40","author":"Mallorie","year":"2022","journal-title":"Surgery"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.cell.2007.05.047","article-title":"Endocrine regulation of energy metabolism by the skeleton","volume":"130","author":"Lee","year":"2007","journal-title":"Cell"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1007\/s00223-004-0288-5","article-title":"Treatment of osteoporosis in men","volume":"75","author":"Orwoll","year":"2004","journal-title":"Calcif Tissue Int."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1359\/jbmr.2002.17.5.758","article-title":"Hyperparathyroidism, humoral hypercalcemia of malignancy, and the anabolic actions of parathyroid hormone and parathyroid hormone-related protein on the skeleton","volume":"17","author":"Stewart","year":"2002","journal-title":"J. Bone Miner. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1089\/105072502760043503","article-title":"Fractures in patients with hyperthyroidism and hypothyroidism: A nationwide follow-up study in 16,249 patients","volume":"12","author":"Vestergaard","year":"2002","journal-title":"Thyroid"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0303-7207(02)00273-3","article-title":"Update on biological actions of 1 alpha,25(OH)(2)-vitamin D(3) (rapid effects) and 24R,25(OH)(2)-vitamin D(3)","volume":"197","author":"Norman","year":"2002","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0092-8674(03)00771-2","article-title":"TSH Is a Negative Regulator of Skeletal Remodeling","volume":"115","author":"Abe","year":"2003","journal-title":"Cell"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1172\/JCI10942","article-title":"Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men","volume":"106","author":"Riggs","year":"2000","journal-title":"J. Clin. Investig."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1056\/NEJMoa022464","article-title":"Bone loss and bone size after menopause","volume":"349","author":"Ahlborg","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1177\/153537020322800302","article-title":"From mouse to man: Redefining the role of insulin-like growth factor-I in the acquisition of bone mass","volume":"228","author":"Yakar","year":"2003","journal-title":"Exp. Biol. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1359\/JBMR.040134","article-title":"A meta-analysis of prior corticosteroid use and fracture risk","volume":"19","author":"Kanis","year":"2004","journal-title":"J. Bone Miner. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1210\/en.2002-220072","article-title":"Diabetes interferes with the bone formation by affecting the expression of transcription factors that regulate osteoblast differentiation","volume":"144","author":"Lu","year":"2003","journal-title":"Endocrinology"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/S8756-3282(03)00169-8","article-title":"Effects of combined treatment of insulin and human par-athyroid hormone (1\u201334) on cancellous bone mass and structure in streptozotocin-induced diabetic rats","volume":"33","author":"Suzuki","year":"2003","journal-title":"Bone"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3258","DOI":"10.1073\/pnas.0308744101","article-title":"Serum leptin level is a regulator of bone mass","volume":"101","author":"Elefteriou","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1677\/joe.0.1750405","article-title":"Leptin directly regulates bone cell function in vitro and reduces bone fragility in vivo","volume":"175","author":"Cornish","year":"2002","journal-title":"J. Endocrinol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0889-8529(02)00062-2","article-title":"Secondary osteoporosis","volume":"32","author":"Stein","year":"2003","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1210\/er.2017-00226","article-title":"Effects of Leptin on the Skeleton","volume":"39","author":"Reid","year":"2018","journal-title":"Endocr. Rev."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"75","DOI":"10.3389\/fendo.2019.00075","article-title":"Gut Hormones and Their Effect on Bone Metabolism. Potential Drug Therapies in Future Osteoporosis Treatment","volume":"10","author":"Schiellerup","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"733611","DOI":"10.3389\/fendo.2021.733611","article-title":"Endogenous Glucocorticoid Metabolism in Bone: Friend or Foe","volume":"12","author":"Martin","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1359\/JBMR.051103","article-title":"Glucocorticoid-Treated Mice Have Localized Changes in Trabecular Bone Material Properties and Osteocyte Lacunar Size That Are Not Observed in Placebo-Treated or Estrogen-Deficient Mice","volume":"21","author":"Lane","year":"2005","journal-title":"J. Bone Miner. Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1172\/JCI0214538","article-title":"Promotion of osteoclast survival and antagonism of bisphosphonate-induced osteoclast apoptosis by glucocorticoids","volume":"109","author":"Weinstein","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.bone.2016.08.024","article-title":"Activation of dimeric glucocorticoid receptors in osteoclast progenitors potentiates RANKL induced mature osteoclast bone resorbing activity","volume":"93","author":"Conaway","year":"2016","journal-title":"Bone"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1530\/eje.0.1340591","article-title":"Evidence for a role for insulin-like growth factor binding proteins in glucocorticoid inhibition of normal human osteoblast-like cell proliferation","volume":"134","author":"Chevalley","year":"1996","journal-title":"Eur. J. Endocrinol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1111\/nyas.12389","article-title":"Glucocorticoid metabolism in rheumatoid arthritis","volume":"1318","author":"Hardy","year":"2014","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_87","first-page":"525093","article-title":"Glucocorticoids and Type 2 Diabetes: From Physiology to Pathology","volume":"2012","author":"Pagotto","year":"2012","journal-title":"J. Nutr. Metab."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1002\/jcb.21414","article-title":"Dexamethasone promotes osteoclastogenesis by inhibiting osteoprotegerin through multiple levels","volume":"103","author":"Kondo","year":"2008","journal-title":"J. Cell. Biochem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1002\/art.23454","article-title":"Glucocorticoid excess in mice results in early activation of osteoclastogenesis and adipogenesis and prolonged suppression of osteogenesis: A longitudinal study of gene expression in bone tissue from glucocorticoid-treated mice","volume":"58","author":"Yao","year":"2008","journal-title":"Arthritis Rheum"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1016\/j.cell.2012.02.032","article-title":"Cellular Metabolism and Disease: What Do Metabolic Outliers Teach Us?","volume":"148","author":"DeBerardinis","year":"2012","journal-title":"Cell"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bone.2018.08.002","article-title":"Energy Metabolism and Bone","volume":"115","author":"Long","year":"2018","journal-title":"Bone"},{"key":"ref_92","first-page":"157","article-title":"Bone mineral and lean tissue loss after long duration space flight","volume":"1","author":"LeBlanc","year":"2000","journal-title":"J. Musculoskelet. Neuronal Interact."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1177\/1759720X09351779","article-title":"Paget\u2019s disease of bone: A review of epidemiology, pathophysiology and management","volume":"1","author":"Shaker","year":"2009","journal-title":"Ther. Adv. Musculoskelet. Dis."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.biocel.2007.06.009","article-title":"Endochondral ossification: How cartilage is converted into bone in the developing skeleton","volume":"40","author":"Mackie","year":"2008","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1002\/dvdy.22181","article-title":"Wnt modulators in the biotech pipeline","volume":"239","author":"Rey","year":"2010","journal-title":"Dev. Dyn."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2015\/729352","article-title":"Functional Diversity of Fibroblast Growth Factors in Bone Formation","volume":"2015","author":"Takei","year":"2015","journal-title":"Int. J. Endocrinol."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Bodine, P.V. (2010). Wnt signaling in bone development. Bone and Development, Springer.","DOI":"10.1007\/978-1-84882-822-3_9"},{"key":"ref_98","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_99","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1038\/s41580-020-00279-w","article-title":"Mechanisms of bone development and rep air","volume":"21","author":"Salhotra","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1080\/03008200290000934","article-title":"Changes in Bone Remodeling Rate Influence the Degree of Mineralization of Bone","volume":"43","author":"Boivin","year":"2002","journal-title":"Connect. Tissue Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1016\/j.immuni.2016.05.012","article-title":"Sepsis-Induced Osteoblast Ablation Causes Immunodeficiency","volume":"44","author":"Terashima","year":"2016","journal-title":"Immunity"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1359\/jbmr.2000.15.1.2","article-title":"The roles of osteoprotegerin and osteopro tegerin ligand in the paracrine regulation of bone resorption","volume":"15","author":"Hofbauer","year":"2000","journal-title":"J Bone Miner Res."},{"key":"ref_103","first-page":"14","article-title":"Interaction between bone and immune cells: Implications for postmenopausal osteoporosis","volume":"123","author":"Luntzer","year":"2021","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"511799","DOI":"10.3389\/fphys.2020.511799","article-title":"The Effect of Inflammation on Bone","volume":"11","author":"Epsley","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s11914-011-0077-9","article-title":"Bone, Inflammation, and Inflammatory Bowel Disease","volume":"9","author":"Agrawal","year":"2001","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1378\/chest.10-1427","article-title":"COPD, bone metabolism, and osteoporosis","volume":"139","author":"Lehouck","year":"2011","journal-title":"Chest."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s00198-012-2074-y","article-title":"European guidance for the diagnosis and management of osteoporosis in postmenopausal women","volume":"24","author":"Kanis","year":"2012","journal-title":"Osteoporos. Int."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"687037","DOI":"10.3389\/fimmu.2021.687037","article-title":"Immunoporosis: Role of Innate Immune Cells in Osteoporosis","volume":"12","author":"Saxena","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"23016","DOI":"10.1002\/jcla.23016","article-title":"Systemic immune-inflammationindex acts as a novel diagnostic biomarker for postmenopausal osteoporosis an could predict the risk of osteoporotic fracture","volume":"34","author":"Fang","year":"2020","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"657","DOI":"10.3389\/fimmu.2018.00657","article-title":"Immunoporosis: Immunology of Osteoporosis\u2014Role of T Cells","volume":"9","author":"Srivastava","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Suzuki, K. (2019). Chronic Inflammation as an Immunological Abnormality and Effectiveness of Exercise. Biomolecules, 9.","DOI":"10.3390\/biom9060223"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S0889-8529(02)00055-5","article-title":"Pathogenesis of osteoporosis","volume":"32","author":"Raisz","year":"2003","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Gao, Y., Patil, S., and Jia, J. (2021). The Development of Molecular Biology of Osteoporosis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22158182"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1093\/ptj\/86.1.77","article-title":"Bone Biology and the Clinical Implications for Osteoporosis","volume":"86","author":"Downey","year":"2006","journal-title":"Phys. Ther."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1007\/s00774-020-01132-y","article-title":"Role of the renin\u2013angiotensin\u2013aldosterone system in bone metabolism","volume":"38","author":"Mo","year":"2020","journal-title":"J. Bone Miner. Metab."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.abb.2008.02.028","article-title":"The response of bone to mechanical loading and disuse: Fundamental principles and influences on osteoblast\/osteocyte homeostasis","volume":"473","author":"Skerry","year":"2008","journal-title":"Arch Biochem Biophys."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1056\/NEJMp038101","article-title":"Periosteal Bone Formation\u2014A Neglected Determinant of Bone Strength","volume":"349","author":"Seeman","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1210\/edrv.23.3.0465","article-title":"Sex steroids and the construction and conservation of the adult skeleton","volume":"23","author":"Riggs","year":"2002","journal-title":"Endocr. Rev."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"35","DOI":"10.18773\/austprescr.2016.020","article-title":"Bone mineral density: Testing for osteoporosis","volume":"39","author":"Sheu","year":"2016","journal-title":"Aust. Prescr."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1136\/bmj.312.7041.1254","article-title":"Meta-analysis of how well measures of bone mineral density predict occurrence of oste-oporotic fractures","volume":"312","author":"Marshall","year":"1996","journal-title":"BMJ"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.jocd.2017.06.014","article-title":"Dual-energy X-ray Absorptiometry","volume":"20","author":"Jain","year":"2017","journal-title":"J. Clin. Densitom."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"S19","DOI":"10.1385\/JCD:5:3S:S19","article-title":"What are the criteria by which a densitometric diagnosis of osteoporosis can be made in males and non-Whites","volume":"5","author":"Binkley","year":"2002","journal-title":"J. Clin. Densitom."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1016\/S0140-6736(02)08761-5","article-title":"Osteoporosis III: Diagnosis of osteoporosis and assessment of fracture risk","volume":"359","author":"Kanis","year":"2002","journal-title":"Lancet"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1038\/sj.ijo.0802209","article-title":"Obesity: The disease of the twenty-first century","volume":"26","year":"2002","journal-title":"Int. J. Obes. Relat. Metab. Disord."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"30","DOI":"10.3389\/fendo.2016.00030","article-title":"Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders","volume":"7","author":"Choe","year":"2016","journal-title":"Front. Endocrinol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.cell.2007.10.004","article-title":"Developmental Origin of Fat: Tracking Obesity to Its Source","volume":"131","author":"Gesta","year":"2007","journal-title":"Cell"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.2741\/3786","article-title":"Brown fat biology and thermogenesis","volume":"16","author":"Richard","year":"2011","journal-title":"Front. Biosci.-Landmark"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/978-3-319-48382-5_7","article-title":"Adipose Tissue Function and Expandability as Determinants of Lipotoxicity and the Metabolic Syndrome","volume":"960","author":"Carobbio","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"203901","DOI":"10.1155\/2011\/203901","article-title":"Adipokines and osteoarthritis: Novel mol-ecules involved in the pathogenesis and progression of disease","volume":"2011","author":"Conde","year":"2011","journal-title":"Arthritis"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.cyto.2018.06.012","article-title":"Adiponectin signaling and its role in bone metabolism","volume":"112","author":"China","year":"2018","journal-title":"Cytokine"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"E827","DOI":"10.1152\/ajpendo.2001.280.6.E827","article-title":"The adipocyte: A model for integration of endocrine and metabolic signaling in energy metabolism regulation","volume":"280","author":"Muruzabal","year":"2001","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1007\/s11914-019-00552-8","article-title":"Insulin Signaling in Bone Marrow Adipocytes","volume":"17","author":"Tencerova","year":"2019","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1359\/JBMR.0301220","article-title":"Adipogenic differentiation of human adult stem cells from bone marrow stroma (MSCs)","volume":"19","author":"Sekiya","year":"2004","journal-title":"J. Bone Miner. Res."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s40519-016-0278-4","article-title":"Obesity or obesities? Controversies on the association between body mass index and premature mortality","volume":"21","author":"Bosello","year":"2016","journal-title":"Eat. Weight Disord. Stud. Anorexia, Bulim. Obes."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1007\/s00774-009-0108-0","article-title":"High weight or body mass index increase the risk of vertebral fractures in postmenopausal osteoporotic women","volume":"28","author":"Pirro","year":"2010","journal-title":"J. Bone Miner. 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