Disorders of bone remodeling

Feng, Xu; McDonald, Jay M.

Affiliations

¹Department of Pathology and the Center for Metabolic Bone Disease, The University of Alabama at Birmingham, Birmingham, Alabama

²Veterans Administration Medical Center, Birmingham, Alabama 35233

Abstract and keywords

The skeleton provides mechanical support for stature and locomotion, protects vital organs, and controls mineral homeostasis. A healthy skele- ton must be maintained by constant bone modeling to carry out these crucial functions throughout life. Bone remodeling involves the removal of old or damaged bone by osteoclasts (bone resorption) and the subsequent replacement of new bone formed by osteoblasts (bone formation). Normal bone remodeling requires a tight coupling of bone resorption to bone formation to guarantee no alteration in bone mass or quality after each remodeling cycle. However, this important physiological process can be derailed by a variety of factors, including menopause-associated hormonal changes, age-related factors, changes in physical activity, drugs, and secondary diseases, which lead to the development of various bone disorders in both women and men. We review the major diseases of bone remodeling, emphasizing our current understanding of the underlying pathophysiological mechanisms.

Keywords: osteoporosis; renal osteodystrophy; osteopetrosis; Paget’s disease; rickets

Links

DOI: 10.1146/annurev-pathol-011110-130203

PubMed: 20936937

WoS: 000288922800006

History

Online: 2010-10-05

Cited Works (36)

Year	Entry
1994	Parfitt AM. Osteonal and hemi‐osteonal remodeling: the spatial and temporal framework for signal traffic in adult human bone. J Cell Biochem. July 1994;55(3):273-286.
2005	Raisz LG. Pathogenesis of osteoporosis: concepts, conflicts, and prospects. J Clin Invest. December 2005;115(12):3318-3325.
1998	Lacey DL, Timms E, Tan H-L, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian Y-X, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. April 17, 1998;93(2):165-176.
1999	Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT, Martin TJ. Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev. June 1999;20(3):345-357.
1997	Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang M-S, Lüthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan H-L, Trail G, Sullivan J, Davy E, Bucay N, Renshaw-Gegg L, Hughes TM, Hill D, Pattison W, Campbell P, Sander S, Van G, Tarpley J, Derby P, Lee R, Boyle WJ; Amgen EST Program. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. April 18, 1997;89(2):309-319.
1941	Albright F, Smith PH, Richardson AM. Postmenopausal osteoporosis: its clinical features. JAMA. May 31, 1941;116(22):2465-2474.
2004	Lang T, LeBlanc A, Evans H, Lu Y, Genant H, Yu A. Cortical and trabecular bone mineral loss from the spine and hip in long‐duration spaceflight. J Bone Miner Res. June 2004;19(6):1006-1012.
2002	Riggs BL, Khosla S, Melton LJ III. Sex steroids and the construction and conservation of the adult skeleton. Endocr Rev. June 2002;23(3):279-302.
1990	Eriksen EF, Hodgson SF, Eastell R, Cedel SL, O'Fallon WM, Riggs BL. Cancellous bone remodeling in type I (postmenopausal) osteoporosis: quantitative assessment of rates of formation, resorption, and bone loss at tissue and cellular levels. J Bone Miner Res. April 1990;5(4):311-319.
1995	Manolagas SC, Jilka RL. Bone marrow, cytokines, and bone remodeling: emerging insights into the pathophysiology of osteoporosis. NEJM. February 2, 1995;332(5):305-311.
2009	Andersen TL, Sondergaard TE, Skorzynska KE, Dagnaes-Hansen F, Plesner TL, Hauge EM, Plesner T, Delaisse J-M. A physical mechanism for coupling bone resorption and formation in adult human bone. Am J Pathol. January 2009;174(1):239-247.
2006	Rubin J, Rubin C, Jacobs CR. Molecular pathways mediating mechanical signaling in bone. Gene. February 15, 2006;367:1-16.
2000	Teitelbaum SL. Bone resorption by osteoclasts. Science. September 1, 2000;289(5484):1504-1508.
1996	Garnero P, Sornay‐Rendu E, Chapuy M, Delmas PD. Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J Bone Miner Res. 1996;11(3):337-349.
1999	Kong Y-Y, Yoshida H, Sarosi I, Tan H-L, Timms E, Capparelli C, Morony S, Oliveira-dos-Santos AJ, Van G, Itie A, Khoo W, Wakeham A, Dunstan CR, Lacey DL, Mak TW, Boyle WJ, Penninger JM. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature. January 28, 1999;397(6717):315-323.
2006	Moe S, Drüeke T, Cunningham J, Goodman W, Martin K, Olgaard K, Ott S, Sprague S, Lameire N, Eknoyan G. Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. June 1, 2006;69(11):1945-1953.
1992	Jilka RL, Hangoc G, Girasole G, Passeri G, Williams DC, Abrams JS, Boyce B, Broxmeyer H, Manolagas SC. Increased osteoclast development after estrogen loss: mediation by interleukin-6. Science. July 3, 1992;257(5066):88-91.
2007	Tatsumi S, Ishii K, Amizuka N, Li M, Kobayashi T, Kohno K, Ito M, Takeshita S, Ikeda K. Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. Cell Metab. June 2007;5(6):464-475.
2010	Manolagas SC. From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis. Endocr Rev. June 2010;31(3):266-300.
2003	Eghbali-Fatourechi G, Khosla S, Sanyal A, Boyle WJ, Lacey DL, Riggs BL. Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. J Clin Invest. April 2003;111(8):1221-1230.
1982	Riggs BL, Wahner HW, Seeman E, Offord KP, Dunn WL, Mazess RB, Johnson KA, Melton LJ III. Changes in bone mineral density of the proximal femur and spine with aging: differences between the postmenopausal and senile osteoporosis syndromes. J Clin Invest. October 1982;70(4):716-723.
2000	Van Staa TP, Leufkens HGM, Abenhaim L, Zhang B, Cooper C. Use of oral corticosteroids and risk of fractures. J Bone Miner Res. June 2000;15(6):993-1000.
2007	Bonewald LF. Osteocytes as dynamic multifunctional cells. Annals NY Acad Sci. 2007;1116(1):281-290.
2001	Hauge EM, Qvesel D, Eriksen EF, Mosekilde L, Melsen F. Cancellous bone remodeling occurs in specialized compartments lined by cells expressing osteoblastic markers. J Bone Miner Res. September 2001;16(9):1575-1582.
1998	Khosla S, Melton LJ III, Atkinson EJ, O’Fallon WM, Klee GG, Riggs BL. Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women: a key role for bioavailable estrogen. J Clin Endocrinol Metab. July 1998;83(7):2266-2274.
2002	Parfitt AM. Targeted and nontargeted bone remodeling: relationship to basic multicellular unit origination and progression. Bone. January 2002;30(1):5-7.
1998	Yasuda H, Shima N, Akagawa NN, Yamaguchi K, Kinosaki M, Mochizuki S-I, Omoyasu AT, Yano K, Goto M, Murakami A, Tsuda E, Morinaga T, Igashio KH, Udagawa N, Tkahashi N, Suda T. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA. March 31, 1998;95(7):3597-3602.
1978	Heaney RP, Recker RR, Saville PD. Menopausal changes in bone remodeling. J Lab Clin Med. December 1978;92(6):964-970.
1996	Hughes DE, Dai A, Tiffee JC, Li HH, Mundy GR, Boyce BF. Estrogen promotes apoptosis of murine osteoclasts mediated by TGF–Β. Nat Med. October 1996;2(10):1132-1136.
2009	Tang Y, Wu X, Lei W, Pang L, Wan C, Shi Z, Zhao L, Nagy TR, Peng X, Hu J, Feng X, Van Hul W, Wan M, Cao X. TGF-β1-induced migration of bone mesenchymal stem cells couples bone resorption with formation. Nat Med. July 2009;15(7):757-765.
2003	Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature. May 15, 2003;423(6937):337-342.
2000	You J, Yellowley CE, Donahue HJ, Zhang Y, Chen Q, Jacobs CR. Substrate deformation levels associated with routine physical activity are less stimulatory to bone cells relative to loading-induced oscillatory fluid flow. J Biomech Eng. August 2000;122(4):387-393.
1998	Weinstein RS, Jilka RL, Parfitt AM, Manolagas SC. Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids: potential mechanisms of their deleterious effects on bone. J Clin Invest. July 15, 1998;102(2):274-282.
2001	NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA. February 14, 2001;285(6):785-795.
2000	Manolagas SC. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev. April 2000;21(2):115-137.
2010	Chen J-H, Liu C, You L, Simmons CA. Boning up on Wolff's Law: mechanical regulation of the cells that make and maintain bone. J Biomech. January 5, 2010;43(1):108-118.

Cited By (50)

Year	Entry
2015	Florencio-Silva R, Sasso GRdS, Sasso-Cerri E, Simões MJ, Cerri PS. Biology of bone tissue: structure, function, and factors that influence bone cells. BioMed Res Int. 2015;2015:421746.
2015	Jensen PR, Andersen TL, Hauge E-M, Bollerslev J, Delaissé J-M. A joined role of canopy and reversal cells in bone remodeling: lessons from glucocorticoid-induced osteoporosis. Bone. April 2015;73:16-23.
2020	Zarecki P, Hackl M, Grillari J, Debono M, Eastell R. Serum microRNAs as novel biomarkers for osteoporotic vertebral fractures. Bone. January 2020;130:115113.
2020	Moura SR, Bras JP, Freitas J, Osório H, Barbosa MA, Santos SG, Almeida MI. miR-99a in bone homeostasis: regulating osteogenic lineage commitment and osteoclast differentiation. Bone. May 2020;134:115303.
2020	Blixt N, Norton A, Zhang A, Aparicio C, Prasad H, Gopalakrishnan R, Jensen ED, Mansky KC. Loss of myocyte enhancer factor 2 expression in osteoclasts leads to opposing skeletal phenotypes. Bone. September 2020;138:115466.
2021	Cho E, Chen Z, Ding M, Seong J, Lee S, Min SH, Choi DK, Lee T-H. PMSA prevents osteoclastogenesis and estrogen-dependent bone loss in mice. Bone. January 2021;142:115707.
2021	Wang JS, Yoon S-H, Wein MN. Role of histone deacetylases in bone development and skeletal disorders. Bone. February 2021;143:115606.
2021	Goel D, Vohora D. Liver X receptors and skeleton: current state-of-knowledge. Bone. March 2021;144:115807.
2021	Lee S, Kim HS, Kim MJ, Min KY, Choi WS, You JS. Glutamine metabolite α-ketoglutarate acts as an epigenetic co-factor to interfere with osteoclast differentiation. Bone. April 2021;145:115836.
2022	Zhao Y, Hao X, Li Z, Feng X, Katz J, Michalek SM, Jiang H, Zhang P. Role of chromatin modulator Dpy30 in osteoclast differentiation and function. Bone. June 2022;159:116379.
2022	Chen J-R, Lazarenko OP, Blackburn ML. GPR109A gene deletion ameliorates gonadectomy-induced bone loss in mice. Bone. August 2022;161:116422.
2023	Shao C, Liu Y, Zhao Y, Jing Y, Li J, Lv Z, Fu T, Wang Z, Li G. DNA methyltransferases inhibitor azacitidine improves the skeletal phenotype of mild osteogenesis imperfecta by reversing the impaired osteogenesis and excessive osteoclastogenesis. Bone. May 2023;170:116706.
2023	Vis MAM, Zhao F, Bodelier ESR, Bood CM, Bulsink J, van Doeselaar M, Amirabadi HE, Ito K, Hofmann S. Osteogenesis and osteoclastogenesis on a chip: engineering a self-assembling 3D coculture. Bone. August 2023;173:116812.
2023	Lee S, Kim MJ, Ahn SI, Choi SK, Min KY, Choi WS, You JS. Epigenetic landscape analysis reveals the significance of early reduced chromatin accessibility in osteoclastogenesis. Bone. December 2023;177:116918.
2019	Li Y, Shi Z, Jules J, Chen S, Kesterson RA, Zhao D, Zhang P, Feng X. Specific RANK cytoplasmic motifs drive osteoclastogenesis. J Bone Miner Res. October 2019;34(10):1938-1951.
2020	Li Q, Wang M, Xue H, Liu W, Guo Y, Xu R, Shao B, Yuan Q. Ubiquitin‐specific protease 34 inhibits osteoclast differentiation by regulating NF‐κB signaling. J Bone Miner Res. August 2020;35(8):1597-1608.
2021	Lee J, Kim M, Lee SJ, Kim B, Choi J, Lee SM, Ham HJ, Koh J, Jeon J, Lee I. PDK2 deficiency prevents ovariectomy‐induced bone loss in mice by regulating the RANKL‐NFATc1 pathway during osteoclastogenesis. J Bone Miner Res. March 2021;36(3):553-566.
2021	Tang L, Wu M, Lu S, Zhang H, Shen Y, Shen C, Liang H, Ge H, Ding X, Wang Z. Fgf9 negatively regulates bone mass by inhibiting osteogenesis and promoting osteoclastogenesis via MAPK and PI3K/AKT signaling. J Bone Miner Res. 2021;36(4):779-791.
2022	Cherian KE, Kapoor N, Paul TV. Disrupted sleep architecture is associated with incident bone loss in Indian postmenopausal women: a prospective study. J Bone Miner Res. October 2022;37(10):1956-1962.
2023	Gong X, Sun S, Yang Y, Huang X, Gao X, Jin A, Xu H, Wang X, Liu Y, Liu J, Dai Q, Jiang L. Osteoblastic STAT3 is crucial for orthodontic force driving alveolar bone remodeling and tooth movement. J Bone Miner Res. January 2023;38(1):214-227.
2023	Dong H, Liu R, Zou K, Jin Z, Kang J, Zhang Y, Zhang X, Sun Z, Yu G, Huang N, Bretches M, Yang S-Y, Ning B. Higenamine promotes osteogenesis via IQGAP1/SMAD4 signaling pathway and prevents age- and estrogen-dependent bone loss in mice. J Bone Miner Res. May 2023;38(5):775-791.
2023	Zhang L, Zhu K, Xu J, Chen X, Sheng C, Zhang D, Yang Y, Sun L, Zhao H, Wang X, Tao B, Zhou L, Liu J. Acetyltransferases CBP/p300 control transcriptional switch of β-catenin and Stat1 promoting osteoblast differentiation. J Bone Miner Res. December 2023;38(12):1885-1899.
2020	Hart NH, Newton RU, Tan2 J, Rantalainen T, Chivers P, Siafarikas A, Nimphius S. Biological basis of bone strength: anatomy, physiology and measurement. J Musculoskel Neuron Interact. September 2020;20(3):347-371.
2019	Xie C. Analysis of the Effects of Physiological Perturbations on the Bone Remodeling Process [Master's thesis]. Boston University; 2019.
2013	Dosier CR. Bone Tissue Engineering Utilizing Adult Stem Cells in Biologically Functionalized Hydrogels [PhD thesis]. Atlanta, GA: Georgia Institute of Technology; May 2013.
2015	Priddy LB. Biomaterial Strategies for Improved Bone Healing With Bone Morphogenetic Protein-2 Delivery [PhD thesis]. Atlanta, GA: Georgia Institute of Technology; August 2015.
2012	Mulholland B. The Role of Post-Menopausal Osteoporosis in Bone Metastatic Breast Cancer and the Effect of Monocyte Chemoattractant Protein-1 [PhD thesis]. Brisbane, Australia: Griffith University; April 2012.
2023	Nilsson K. NOTUM and RSPO3 in Bone: WNT Signaling Modulators Regulating the Skeleton [PhD thesis]. University of Gothenburg; 2023.
2014	Ferro Pereira A. Cortical Bone Adaptation: A Finite-Element Study of the Mouse Tibia [PhD thesis]. Imperial College London; January 2014.
2023	Desai S. The Role of Mechanical Loading, Sex and TRAP/ACP5 on Bone Properties [PhD thesis]. Karolinska Institutet; 2023.
2020	O’Sullivan LM. Time-Sequence of Biomechanical Adaption in Trabecular Tissue During Estrogen Deficiency [PhD thesis]. National University of Ireland Galway; March 2020.
2020	Simfia I. Estrogen Deficiency Alters the Mechanobiological Responses of Osteoblasts and Osteocytes [PhD thesis]. National University of Ireland Galway; April 2020.
2022	Sattgast LH. The Relationship Between IGF-1 and Bone Turnover in a Non-Human Primate Model of Voluntary Alcohol Consumption [PhD thesis]. Oregon State University; 2022.
2017	Owen R. Tissue Engineering an in Vitro Model of Osteoporosis [PhD thesis]. Sheffield, UK: University of Sheffield; October 2017.
2019	Sadoughi S. Micromechanics of Human Bone: Role of Architecture and Tissue Material Properties [PhD thesis]. Berkeley, CA: Berkeley, University of California; 2019.
2020	Link JM. Toward Enhancing the Durability and Integration of Engineered Articular Cartilage [PhD thesis]. Irvine, CA: Irvine, University of California; 2020.
2020	Salinas EY. Using Mechanical Stimulation to Improve Tissue-Engineered Articular Cartilage for Implantation in the Knee Joint [PhD thesis]. Irvine, CA: Irvine, University of California; 2020.
2021	Arshad M. Modified Dental Composites for Bone Repair [PhD thesis]. University College London; 2021.
2016	Sebastian A. High-Throughput Analysis of WNT Signaling Pathway in Osteoblasts [PhD thesis]. Merced, CA: Merced, University of California; 2016.
2014	Gangadharan V. Delineating the Cellular Mechanism of Osteoblast Desensitization to Mechanical Stimulation [PhD thesis]. University of Delaware; 2014.
2019	Surowiec R. Novel Models to Image and Quantify Bone Drug Efficacy and Disease Progression in Vivo: Addressing the Fragility Phenotype [PhD thesis]. University of Michigan; 2019.
2023	Austermann K. Effects of Nutritive Antioxidants on Bone During Immobility [PhD thesis]. Rheinische Friedrich-Wilhelms-Universität Bonn; 2023.
2022	Nandi S. HRAS GTPase, a Novel Regulator of Bone Homeostasis: Understanding the Cellular Base of Bone Loss in Costello Syndrome [PhD thesis]. University of Ulm; 2022.
2023	Kotsanti M. Evaluation of Mandibular Cortical Bone in a Healthy Paediatric Population [Master's thesis]. National and Kapodistrian University of Athens; 2023.
2020	Kegelman CD. Combinatorial Roles of Skeletal Cell YAP and TAZ in Bone Growth, Remodeling, and Repair [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 2020.
2022	Sales EdS. The Spatio-Temporal Behavior of Basic Multicellular Units in a PTH-Induced Cortical Bone Remodeling Rabbit Model [Master's thesis]. University of Saskatchewan; August 2022.
2020	Singleton RC. A Study of Aging in Male Cortical Bone Using Nanoindentation [PhD thesis]. Knoxville, University of Tennessee; August 2020.
2019	Ma Y-HV. Regulation of Breast Cancer Cells’ Bone-Metastatic Potential by Mechanically Stimulated Osteocytes [PhD thesis]. University of Toronto; 2019.
2020	Dwyer MP. The Effect of Loss of Estrogen on Trabecular Bone Score in Women At Increased Risk of Breast Cancer [Master's thesis]. University of Toronto; 2020.
2022	Haghpanah Z. In Vitro Evaluation of Bone Cell Response to Novel 3D-Printable Nanocomposite Biomaterials for Bone Reconstruction [Master's thesis]. University of Waterloo; 2022.