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Disorders of Bone Remodeling
Open accessAbstract
The skeleton provides mechanical support for stature and locomotion, protects vital organs, and controls mineral homeostasis. A healthy skeleton 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.
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“OPG, a soluble receptor also produced by osteoblasts that acts as a decoy receptor and neutralizes RANKL, prevents RANKL from interacting with RANK and consequently inhibits osteoclast proliferation, activity, and survival [73, 74].”
From The Effect of Tobacco Smoking on Bone Mass: An Overview of Pathophysiologic Mechanisms (2018) · cites this paper as [73]
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“Once RANKL binds to its natural receptor, expressed by osteoclast precursor cells, it stimulates osteoclast precursor differentiation to active mature osteoclasts and accelerates bone resorption [73].”
From The Effect of Tobacco Smoking on Bone Mass: An Overview of Pathophysiologic Mechanisms (2018) · cites this paper as [73]
In the citing paper
“Abnormal increase in osteoclast formation and activity leads to some bone diseases such as osteoporosis, where resorption exceeds formation causing decreased bone density and increased bone fractures [105].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [105]
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“In patients with chronic liver disease, the balance between osteoclasts and osteoblasts is affected by liver disease, resulting in BRU imbalance [46,50].”
From Bone diseases in patients with chronic liver disease (2019) · cites this paper as [46]
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“Greater bone resorption, caused by dysregulation of osteoclasts or greater osteoclastogenesis, is one of the principal mechanisms of osteoporosis.((30,31)) Therefore, most of the current osteoporosis treatments target osteoclasts (eg, estrogen replacement, bisphosphonates, and anti-RANKL antibodies), but these approac…”
BackgroundBiofabrication of vasculature in microphysiological models of bone
Whelan, I. T., Moeendarbary, E., Hoey, D. A., & Kelly, D. J. (2021) · Biofabrication · doi:10.1088/1758-5090/ac04f7 · Cited by 31
“The coordinated actions of osteoclasts, osteoblasts and osteocytes underpin bone physiology andmany of its most common pathologies, such as osteoporosis [17], Paget’s disease, and renal osteodystrophy [18].”
BackgroundFeito, M. J., Casarrubios, L., Oñaderra, M., Gómez-Duro, M., Arribas, P., Polo-Montalvo, A., Vallet‐Regí, M., Arcos, D., & Portolés, M. T. (2021) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2021.112110 · Cited by 31
Phromnoi, K., Yodkeeree, S., Pintha, K., Mapoung, S., Suttajit, M., Saenjum, C., & Dejkriengkraikul, P. (2022) · Molecules · doi:10.3390/molecules27030824 · Cited by 30
“The disturbance of this balance results in several bone diseases, including arthritis, periodontitis, and osteoporosis [1,2].”
BackgroundInhibition of Cdk5 increases osteoblast differentiation and bone mass and improves fracture healing
Ahmad, M., Krüger, B. T., Kroll, T. C., Vettorazzi, S., Dorn, A.-K., Mengele, F., Lee, S., Nandi, S., Yilmaz, D., Stolz, M., et al. (2022) · Bone Research · doi:10.1038/s41413-022-00195-z · Cited by 31
The Role of SIRT3 in the Osteoporosis
Hu, S., & Wang, S. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.893678 · Cited by 31
Yao, X., Liu, Z., Ma, N., Jiang, W., Zhou, Z. Y., Chen, B., Guan, W., Yan, J.-J., & Yang, M. (2023) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2023/3602962 · Cited by 31
“Under certain pathological conditions, an imbalance between bone formation and bone resorption may occur, which leads to the development of osteoporosis [51].”
BackgroundNormal bone physiology, remodelling and its hormonal regulation
Bayliss, L. E., Mahoney, D. J., & Monk, A. P. (2012) · Surgery (Oxford) · doi:10.1016/j.mpsur.2011.12.009 · Cited by 30
Non-Viral Delivery System and Targeted Bone Disease Therapy
Qadir, A., Gao, Y., Patil, S., Tian, Y. E., Lin, X., Dang, K., Jiang, S., Li, Y., Miao, Z., & Qian, A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20030565 · Cited by 31
“They are required in proper balance with osteoblasts to maintain adequate bone mass, otherwise it may lead to serious disorders like osteoporosis, bone tumors, and Paget’s disease [96].”
BackgroundExercise maintains bone homeostasis by promoting osteogenesis through STAT3
Huang, X., Zhu, Y., Sun, S., Gao, X., Yang, Y., Xu, H., Jin, A., Liu, Y., Jia, H., Dai, Q., et al. (2023) · International Journal of Biological Sciences · doi:10.7150/ijbs.82744 · Cited by 29
“Bone homeostasis is the balance between bone formation and bone resorption [5, 6].”
BackgroundLiu, H., Xiao, H., Lin, S., Zhou, H., Cheng, Y., Xie, B., & Xu, D. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1372399 · Cited by 35
“However, under some pathological conditions, such as osteoporosis, both bone mass and strength are decreased. surface, which in turn promotes osteoclast attachment to the RGD-binding site, where the mineralized matrix is dissolved to form the Howship lacuna (Feng and McDonald, 2011).”
BackgroundHu, H., Zhang, Z.-Y., Luo, Z. X., Ti, H., Wu, J., Nie, H., Yuan, Z., Wu, X. L., Zhang, K.-Y., Shi, S., et al. (2025) · Cell Death Discovery · doi:10.1038/s41420-025-02633-3 · Cited by 40
Lü, D., Li, J., Liu, H., Foxa, G. E., Weaver, K., Li, J., Williams, B. O., & Yang, T. (2018) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3469 · Cited by 28
“This is consistent with the notion that trabecular bone is themajor site for bone remodeling andmore susceptible to changes of bone resorption activity than is cortical bone.((53))”
BackgroundMechanoregulation of Bone Remodeling and Healing as Inspiration for Self-Repair in Materials
Weinkamer, R., Eberl, C., & Fratzl, P. (2019) · Biomimetics · doi:10.3390/biomimetics4030046 · Cited by 29
“This so-called remodeling imbalance results in age-related loss of bone mass [18].”
BackgroundGPR39 agonist TC-G 1008 promotes osteoblast differentiation and mineralization in MC3T3-E1 cells
Chai, X., Zhang, W., Chang, B., Feng, X., Song, J., Li, L., Yu, C., Zhao, J., & Si, H. (2019) · Artificial Cells Nanomedicine and Biotechnology · doi:10.1080/21691401.2019.1649270 · Cited by 29
“In healthy conditions, bone undergoes constant modeling and remodeling to absorb mature tissue and synthesize new tissue [2].”
BackgroundSelf-citationGone Caving: Roles of the Transcriptional Regulators YAP and TAZ in Skeletal Development
Kegelman, C. D., Collins, J. M., Nijsure, M. P., Eastburn, E. A., & Boerckel, J. D. (2020) · Current Osteoporosis Reports · doi:10.1007/s11914-020-00605-3 · Cited by 29
Abuna, R. P. F., Almeida, L. O., Souza, A. T. P., Fernandes, R. R., Sverzut, T. F. V., Rosa, A. L., & Beloti, M. M. (2020) · Journal of Cellular Physiology · doi:10.1002/jcp.30131 · Cited by 29
“Steroid hormone deficiency produces osteoporosis type I, whereas age‐related bone loss causes osteoporosis type II, and both are related in terms of fat gain at the expense of bone mass, irrespective of gender (Feng & McDonald, 2011; Horstman et al., 2012).”
BackgroundZhu, Y., Dai, B., Li, X., Liu, W., Wang, J., Xu, J., Xu, S., He, X. M., Zhang, S., Li, Q., et al. (2022) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.2c10615 · Cited by 30
Zong, J., Wang, X., Zhou, X., Wang, C., Chen, L., Yin, L., He, B., & Deng, Z. (2015) · Oncology Reports · doi:10.3892/or.2015.4430 · Cited by 30
“Bone remodeling consists of both resorption by osteoclasts (1-5) and new bone formation by osteoblasts (3,5).”
BackgroundTeong, B., Kuo, S. M., Tsai, W.-H., Ho, M., Chen, C., & Huang, H. H. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18040822 · Cited by 29
“This is also termed metabolic bone diseases [1].”
BackgroundLewis, J. W., Frost, K., Neag, G., Wahid, M., Finlay, M., Northall, E., Abudu, O., Kemble, S., Davis, E. T., Powell, E., et al. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101574 · Cited by 27
Endocortical bone loss in osteoporosis: The role of bone surface availability
Buenzli, P. R., David, C., Thomasb, L., Clementb, J. G., & Pivonka, P. (2013) · QUT ePrints (Queensland University of Technology) · Cited by 28
He, S., Zhang, H., Yang, L., Zhang, Z., Zhang, X., Zhou, N., & Hu, Z. (2021) · Aging · doi:10.18632/aging.202434 · Cited by 28
“The development and maintenance of the skeletal system is a dynamic process that is regulated by bone remodeling and modeling [1].”
BackgroundGao, W., Chen, L., Zhao, K., Hou, M., & Wen, Y. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04594-6 · Cited by 29
“Moreover, the disruption of this balance leads to various bone metabolic diseases [95].”
BackgroundThe Role of Traditional Chinese Medicines in the Treatment of Osteoporosis
Wang, L., Huang, X., Qin, J., Qi, B., Sun, C., Guo, X., Liu, Q., Liu, Y., Ma, Y., Wei, X., et al. (2024) · The American Journal of Chinese Medicine · doi:10.1142/s0192415x24500393 · Cited by 28
Dong, Q. Z., Fu, H., Li, W., Ji, X., Yin, Y., Zhang, Y., Zhu, Y., Li, G., Jia, H., Zhang, H., et al. (2025) · Bone Research · doi:10.1038/s41413-024-00394-w · Cited by 29
Maintenance of Bone Homeostasis by DLL1‐Mediated Notch Signaling
Muguruma, Y., Hozumi, K., Warita, H., Yahata, T., Uno, T., Ito, M., & Ando, K. (2016) · Journal of Cellular Physiology · doi:10.1002/jcp.25647 · Cited by 26
“An imbalance in this coupled activity of osteoclasts and osteoblasts leads to pathologic conditions, such as osteosclerosis, osteopetrosis, and osteoporosis (Feng and McDonald, 2011).”
BackgroundSymmank, J., Chorus, M., Appel, S., Marciniak, J., Knaup, I., Bastian, A., Hennig, C., Döding, A., Schulze‐Späte, U., Jacobs, C., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-72736-7 · Cited by 27
Armbrecht, G., Minh, H. N., Massmann, J., & Raum, K. (2021) · JBMR Plus · doi:10.1002/jbm4.10536 · Cited by 26
“Osteoporosis (OP) is an age-associated disorder of bone remodeling leading to reduced bone mass, structural deterioration, and increased bone fragility.((1)) Although OP is generally thought of as a “woman’s disease,”((2)) men account for a third of OP-related hip fractures in Europe.”
BackgroundIezaki, T., Onishi, Y., Ozaki, K., Fukasawa, K., Takahata, Y., Nakamura, Y., Fujikawa, K., Takarada, T., Yoneda, Y., Yamashita, Y., et al. (2015) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2720 · Cited by 29
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“Introduction Bone quantity is controlled via the balance between bo e resorption by osteoclasts and bone formation by osteoblasts [1].”
BackgroundThe Association Between the Concentration of Serum Magnesium and Postmenopausal Osteoporosis
Chang, J., Yu, D., Ji, J., Wang, N., Yu, S., & Yu, B. N. (2020) · Frontiers in Medicine · doi:10.3389/fmed.2020.00381 · Cited by 27
“The inclusion criteria for eligible studies were as follows: (1) studies involving human subjects, (2) observational studies, (3) studies focusing on the association between the concentration of serum Mg and osteoporosis or osteopenia, (4) studies included data on the concentration of serum Mg for patients with osteop…”
BackgroundInfluentialThe role of cells and signal pathways in subchondral bone in osteoarthritis
Luo, P., Yuan, Q., Yang, M., Wan, X., & Xu, P. (2023) · Bone and Joint Research · doi:10.1302/2046-3758.129.bjr-2023-0081.r1 · Cited by 28
Do Dairy Minerals Have a Positive Effect on Bone Health?
Burrow, K., Young, W., McConnell, M. A., Carne, A., & Bekhit, A. E. A. (2018) · Comprehensive Reviews in Food Science and Food Safety · doi:10.1111/1541-4337.12364 · Cited by 27
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“Bone is continuously regenerated by bone cells including osteoblast lineages, which maintain a healthy skeleton throughout life [13,14].”
BackgroundMyeong, J.-Y., Jung, H.-Y., Chae, H.-S., Cho, H. H., Kim, D., Jang, Y.-J., & Park, J.-I. (2023) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-023-10065-7 · Cited by 26
“Bone is a dynamic organ in which osteoblast-mediated formation and osteoclast-mediated resorption are strictly regulated both temporally and spatially [1, 2].”
Background
Metadata
- Authors
- Feng, X., & McDonald, J. M.
- Affiliations
- University of Alabama at Birmingham (US)
- ORCID
- Feng, Xu
- Venue
- Annual Review of Pathology: Mechanisms of Disease
- Publisher
- Annual Reviews
- Published
- 2011-02-28
- Volume
- 6
- Issue
- 1
- Pages
- 121-145
- ISSN
- 1553-4006 (ISSN-L)
- 1553-4014
- PMC
- PMC3571087
- OpenAlex
- W2166266977
- Cited by
- 1,272
- References
- 171
- Citations by year
- 2026: 59 · 2025: 109 · 2024: 102 · 2023: 124 · 2022: 135 · 2021: 142 · 2020: 107 · 2019: 117 · 2018: 86 · 2017: 68 · 2016: 59 · 2015: 47 · 2014: 36 · 2013: 37 · 2012: 29
- FWCI
- 3.28
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Annual Review of Pathology Mechanisms of Disease (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA109119)
- National Institute of Neurological Disorders and Stroke (R21NS061677, NS061677)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (5P30 AR0406031, R01AR047830, AR 47830, R01AR050235)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Oncology › Bone health and treatments
- Keywords
- bone remodeling, bone resorption, bone formation, osteoclasts, osteoblasts, bone disease, menopause, hormonal changes, age-related bone loss, physical activity, drug-induced bone loss, mineral homeostasis, pathophysiology
- MeSH terms
- Animals, Bone Diseases, Humans, Bone Remodeling
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