What old means to bone
Open accessAbstract
The adverse effects of aging of other organs (ovaries at menopause) on the skeleton are well known, but ironically little is known of skeletal aging itself. Evidence indicates that age-related changes, such as oxidative stress, are fundamental mechanisms of the decline of bone mass and strength. Unlike the short-lived osteoclasts and osteoblasts, osteocytes--former osteoblasts entombed in the mineralized matrix--live as long as 50 years, and their death is dependent on skeletal age. Osteocyte death is a major contributor to the decline of bone strength with age, and the likely mechanisms are oxidative stress, autophagy failure and nuclear pore "leakiness". Unraveling these mechanisms should improve understanding of the age-related increase in fractures and suggest novel targets for its prevention.
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Between 60% and 80% of osteoblasts at resorption lacunae die via apoptosis.
“Between 60% and 80% of osteoblasts at resorption lacunae die via apoptosis.282”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [282]
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Onal, M., Piemontese, M., Xiong, J., Wang, Y., Han, L., Ye, S., Komatsu, M., Selig, M., Weinstein, R. S., Zhao, H., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.444190 · Cited by 206 · see citing works
“surface and are short-lived cells, osteocytes may live many months or years, depending on the location within the skeleton and the rate of bone remodeling (16).”
BackgroundSelf-citationBasic Biology of Skeletal Aging: Role of Stress Response Pathways
Almeida, M., & O’Brien, C. A. (2013) · The Journals of Gerontology Series A · doi:10.1093/gerona/glt079 · Cited by 202 · see citing works
Jilka, R. L., Noble, B., & Weinstein, R. S. (2012) · Bone · doi:10.1016/j.bone.2012.11.038 · Cited by 202 · see citing works
“As a result, the Bak/Bax-deficient osteocytes were more likely to accumulate damage by the oxidative stress and growth factor scarcity that is associated with old age [51, 52].”
BackgroundOld age causes de novo intracortical bone remodeling and porosity in mice
Piemontese, M., Almeida, M., Robling, A. G., Kim, H., Xiong, J., Thostenson, J. D., Weinstein, R. S., Manolagas, S. C., O’Brien, C. A., & Jilka, R. L. (2017) · JCI Insight · doi:10.1172/jci.insight.93771 · Cited by 198 · see citing works
“Changes in osteocyte function with age may contribute to age-related bone loss (30, 42, 43).”
BackgroundSelf-citationThe Role and Mechanism of SIRT1 in Resveratrol-regulated Osteoblast Autophagy in Osteoporosis Rats
Yang, X., Jiang, T., Wang, Y., & Guo, L. (2019) · Scientific Reports · doi:10.1038/s41598-019-44766-3 · Cited by 201 · see citing works
Biopolymeric nanocomposite scaffolds for bone tissue engineering applications – A review
Christy, P. N., Basha, S. K., Kumari, V. S., Bashir, A. K. H., Mâaza, M., Kaviyarasu, K., Arasu, M. V., Al-Dhabi, N. A., & Savarimuthu Ignacimuthu, S. J. (2019) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2019.101452 · Cited by 190 · see citing works
Cell death regulation: A new way for natural products to treat osteoporosis
Li, Z., Li, D., Chen, R., Gao, S., Xu, Z., & Li, N. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106635 · Cited by 179 · see citing works
Carson, J. A., & Manolagas, S. C. (2015) · Bone · doi:10.1016/j.bone.2015.04.015 · Cited by 171 · see citing works
“Agerelated mechanisms intrinsic to bone, including oxidative stress, declining autophagy, cell (osteocyte) senescence are protagonists in involutional osteoporosis and age-related changes in other organs and tissues, such as ovaries and adrenals, are contributory [2-4].”
BackgroundSelf-citationFrom mechanical stimulus to bone formation: A review
Rosa, N., Simões, R., Magalhães, F. D., & Marques, A. T. (2015) · Medical Engineering & Physics · doi:10.1016/j.medengphy.2015.05.015 · Cited by 165 · see citing works
“However, the mechanism by which these cells sense the mechanical loads and facilitate adaptive alterations in bone mass and architecture is not yet completely understood [10,18,29,30].”
BackgroundBone regeneration in inflammation with aging and cell-based immunomodulatory therapy
Kushioka, J., Chow, S. K., Toya, M., Tsubosaka, M., Shen, H., Gao, Q., Li, X., Zhang, N., & Goodman, S. B. (2023) · Inflammation and Regeneration · doi:10.1186/s41232-023-00279-1 · Cited by 166 · see citing works
“With aging, the balance between removing old bone and forming new bone is disrupted, resulting in osteoporosis [2].”
BackgroundAutophagy in bone: Self-eating to stay in balance
Pierrefite‐Carle, V., Santucci‐Darmanin, S., Breuil, V., Camuzard, O., & Carle, G. F. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.08.004 · Cited by 159 · see citing works
Liu, W., Zhou, L., Zhou, C., Zhang, S., Jing, J., Xie, L., Sun, N., Duan, X., Jing, W., Liang, X., et al. (2016) · Nature Communications · doi:10.1038/ncomms12794 · Cited by 156 · see citing works
Geng, Q., Gao, H., Yang, R., Guo, K., & Miao, D. (2018) · International Journal of Biological Sciences · doi:10.7150/ijbs.25783 · Cited by 152 · see citing works
“Recent studies strongly indicate that estrogen deficiency accelerates bone aging and significantly impairs the defense mechanisms of antioxidant stress [14, 44].”
BackgroundMethodMaeda, K., Yoshida, K., Nishizawa, T., Otani, K., Yamashita, Y., Okabe, H., Hadano, Y., Kayama, T., Kurosaka, D., & Saito, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052871 · Cited by 151 · see citing works
“This bone remodeling cycle is a constant process, and approximately 10% of bone mass is replaced yearly in humans [19].”
BackgroundThe Changing Sensory and Sympathetic Innervation of the Young, Adult and Aging Mouse Femur
Chartier, S. R., Mitchell, S. A. T., Majuta, L. A., & Mantyh, P. W. (2018) · Neuroscience · doi:10.1016/j.neuroscience.2018.01.047 · Cited by 146 · see citing works
Inflammation, ageing, and bone regeneration
Gibon, E., Lu, L. Y., Nathan, K., & Goodman, S. B. (2017) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2017.04.002 · Cited by 144 · see citing works
“As the body ages, the balance between removal of old bone and formation of new bone becomes reciprocally negative, leading to osteoporosis [5].”
BackgroundAutophagy: A new player in skeletal maintenance?
Hocking, L. J., Whitehouse, C., & Helfrich, M. (2012) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1668 · Cited by 143 · see citing works
“For bone cells, the ability to survive in stressful conditions such as hypoxic environments may be critical.((15)) Autophagy is also used to remove surplus organelles during terminal differentiation of erythrocytes,((16)) a process that perhaps resonates with the transition from osteoblast to osteocyte.”
BackgroundInflammaging: The driving force in osteoporosis?
Lencel, P., & Magne, D. (2010) · Medical Hypotheses · doi:10.1016/j.mehy.2010.09.023 · Cited by 141 · see citing works
“In contrary to traditional thinking that loss of estrogens at menopause is the seminal mechanism of osteoporosis, bone loss begins as soon as the third decade in both women and men, long before any decline in sex steroid production [25–28], and likely simultaneously to inflammaging.”
The Role of Osteocytes in Age-Related Bone Loss
Jilka, R. L., & O’Brien, C. A. (2016) · Current Osteoporosis Reports · doi:10.1007/s11914-016-0297-0 · Cited by 136 · see citing works
Yang, R., Chen, J., Zhang, J., Qin, R., Wang, R., Qiu, Y., Mao, Z., Goltzman, D., & Miao, D. (2019) · Aging Cell · doi:10.1111/acel.13095 · Cited by 130 · see citing works
“…of intrinsic properties in MSCs such as senescence, proliferation, and osteogenic/adipogenic differentiation potential may underlie age-related bone loss (Bergman et al., 1996; Kaneda et al., 2011; Manolagas & Parfitt, 2010; Stenderup, Justesen, Clausen, & Kassem, 2003; Zhou et al., 2008).”
BackgroundInteraction Between Bone and Muscle in Older Persons with Mobility Limitations
Ferrucci, L., Baroni, M., Ranchelli, A., Lauretani, F., Maggio, M. G., Mecocci, P., & Ruggiero, C. (2014) · Current Pharmaceutical Design · doi:10.2174/13816128113196660690 · Cited by 132 · see citing works
Xu, T., Luo, Y., Wang, J., Zhang, N., Gu, C., Li, L., Qian, D., Cai, W., Fan, J., & Yin, G. (2020) · Journal of Nanobiotechnology · doi:10.1186/s12951-020-00601-w · Cited by 129 · see citing works
The osteocyte plays multiple roles in bone remodeling and mineral homeostasis
Chen, H., Senda, T., & Kubo, K. (2015) · Medical Molecular Morphology · doi:10.1007/s00795-015-0099-y · Cited by 131 · see citing works
Insights into Oxidative Stress in Bone Tissue and Novel Challenges for Biomaterials
Cerqueni, G., Scalzone, A., Licini, C., Gentile, P., & Mattioli‐Belmonte, M. (2020) · Materials Science and Engineering C · doi:10.1016/j.msec.2021.112433 · Cited by 128 · see citing works
Penoni, D. C., Fidalgo, T. K. D. S., Torres, S. R., Varela, V. M., Masterson, D., Leão, A. T. T., & Maia, L. C. (2017) · Journal of Dental Research · doi:10.1177/0022034516682017 · Cited by 125 · see citing works
Jilka, R. L., Almeida, M., Ambrogini, E., Han, L., Roberson, P. K., Weinstein, R. S., & Manolagas, S. C. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00616.x · Cited by 124 · see citing works
“We have therefore hypothesized that PTH counteracts the pathophysiologic mechanisms that are responsible for the reduction in the number of osteoblasts and osteocytes – the seminal pathogenetic changes associated with involutional osteoporosis (Manolagas, 2010; Manolagas & Parfitt, 2010).”
BackgroundSelf-citationMeox2Cre-mediated disruption of CSF-1 leads to osteopetrosis and osteocyte defects
Harris, S. E., MacDougall, M., Horn, D., Woodruff, K., Zimmer, S. N., Rebel, V. I., Fajardo, R., Feng, J. Q., Gluhak-Heinrich, J., Harris, M. A., et al. (2012) · Bone · doi:10.1016/j.bone.2011.09.038 · Cited by 116 · see citing works
“The combination of decreased cortical thickness, mineralization, hydration and osteocyte death would be expected to reduce bone quality and strength [36].”
BackgroundEffect of Age on Regulation of Human Osteoclast Differentiation
Chung, P., Zhou, S., Eslami, B., Shen, L., LeBoff, M. S., & Glowacki, J. (2014) · Journal of Cellular Biochemistry · doi:10.1002/jcb.24792 · Cited by 116 · see citing works
Chronic hyponatremia exacerbates multiple manifestations of senescence in male rats
Bársony, J., Manigrasso, M. B., Xu, Q., Tam, H., & Verbalis, J. G. (2012) · AGE · doi:10.1007/s11357-011-9347-9 · Cited by 116 · see citing works
“Senescence-associated chronic disorders have been described extensively and include senile osteoporosis characterized by low bone mass (Manolagas and Parfitt 2010), sarcopenia (Almeida et al.”
BackgroundRapamycin reduces severity of senile osteoporosis by activating osteocyte autophagy
Luo, D., Ren, H. J., Li, T., Lian, K., & Lin, D. (2015) · Osteoporosis International · doi:10.1007/s00198-015-3325-5 · Cited by 114 · see citing works
Ucer, S., Iyer, S. V., Kim, H., Han, L., Rutlen, C., Allison, K. C., Thostenson, J. D., de Cabo, R., Jilka, R. L., O’Brien, C. A., et al. (2016) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3014 · Cited by 116 · see citing works
“Age-related changes in other organs and tissues may also contribute, but the extent of the contribution of sex steroid deficiency to the skeletal involution later in life has remained unclear.((11,56,57)) In the present work, we found that attenuation of H2O2 produced in themitochondria of mesenchymal cells attenuated…”
BackgroundResultSelf-citationSaidak, Z., Le Henaff, C., Azzi, S., Marty, C., Da Nascimento, S., Sonnet, P., & Marie, P. J. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.621219 · Cited by 113 · see citing works
“With aging, bone formation declines due to decreased osteoblast recruitment, function, and life span (2, 3).”
BackgroundWnt signaling and osteoporosis
Manolagas, S. C. (2014) · Maturitas · doi:10.1016/j.maturitas.2014.04.013 · Cited by 104 · see citing works
“ortical porosity [4,5].”
Self-citationControlled M1-to-M2 transition of aged macrophages by calcium phosphate coatings
Alhamdi, J. R., Peng, T., Al-Naggar, I. M., Hawley, K. L., Spiller, K. L., & Kuhn, L. T. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2018.07.012 · Cited by 110 · see citing works
“Discussion Older individuals are at risk for increased falls, are more likely to suffer from fractures and have delayed bone healing due to an extended in flammatory response during fracture healing (59-61).”
Corrado, A., Cici, D., Rotondo, C., Maruotti, N., & Cantatore, F. P. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21103679 · Cited by 101 · see citing works
“Conversely, transgenic mice overexpressing FoxO showed decreased osteoblast apoptosis, increased osteoblast number and bone formation rate and higher bone mass [13].”
BackgroundResultSources, health benefits, and biological properties of zeaxanthin
Bouyahya, A., Omari, N. E., Hakkur, M., Hachlafi, N. E., Charfi, S., Balahbib, A., Guaouguaou, F., Ребезов, М. Б., Maksimiuk, N., Shariati, M. A., et al. (2021) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2021.10.017 · Cited by 98 · see citing works
Postmenopausal osteoporosis in rheumatoid arthritis: The estrogen deficiency-immune mechanisms link
Sapir‐Koren, R., & Livshits, G. (2017) · Bone · doi:10.1016/j.bone.2017.06.020 · Cited by 97 · see citing works
Bone, joint and tooth development in mucopolysaccharidoses: Relevance to therapeutic options
Oussoren, E., Brands, M. M. M. G., Ruijter, G. J. G., van der Ploeg, A. T., & Reuser, A. J. J. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.07.013 · Cited by 96 · see citing works
Targeting autophagy in osteoporosis: From pathophysiology to potential therapy
Li, X., Xu, J., Dai, B., Wang, X., Guo, Q., & Qin, L. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101098 · Cited by 95 · see citing works
The Role of Autophagy in Osteoclast Differentiation and Bone Resorption Function
Montaseri, A., Giampietri, C., Rossi, M., Riccioli, A., Fattore, A. D., & Filippini, A. (2020) · Biomolecules · doi:10.3390/biom10101398 · Cited by 96 · see citing works
“Additionally, pharmacological induction/inhibition of autophagy leads to alterations of the osteocyte apoptosis rate [72,73].”
BackgroundApoptotic Osteocytes and the Control of Targeted Bone Resorption
Plotkin, L. I. (2014) · Current Osteoporosis Reports · doi:10.1007/s11914-014-0194-3 · Cited by 93 · see citing works
Dexheimer, V., Mueller, S., Braatz, F., & Richter, W. (2011) · PLoS ONE · doi:10.1371/journal.pone.0022980 · Cited by 92 · see citing works
“and delayed fracture healing [1–3] may result from an ageassociated decline in either the number or the replicative function of mesenchymal regenerative cells – adult mesenchymal stem cells”
BackgroundXia, W.-F., Jung, J.-U., Cui, S., Xiong, S., Xiong, L., Shi, X., Mei, L., & Xiong, W. (2013) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1954 · Cited by 89 · see citing works
“Accumulation of ROS results in a decrease of OB lifespan, bone formation, and bone mass in culture and in sex steroid–sufficient female or male mice.((39,40)) Deletion of FoxO transcription factors, an important defense mechanism against ROS in young adult mice, recapitulates the adverse effects of aging in bone, incl…”
BackgroundHsu, S.-H., Chen, L.-R., & Chen, K.-H. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252212139 · Cited by 90 · see citing works
“They have a long lifespan of up to 50 years, outnumbering osteoclasts by a thousandfold and osteoblasts by tenfold [54].”
Kiernan, J., Hu, S., Grynpas, M. D., Davies, J. E., & Stanford, W. L. (2016) · Stem Cells Translational Medicine · doi:10.5966/sctm.2015-0231 · Cited by 87 · see citing works
Green tea and bone health: Evidence from laboratory studies
Shen, C., Yeh, J. K., Cao, J., Chyu, M., & Wang, J.-S. (2011) · Pharmacological Research · doi:10.1016/j.phrs.2011.03.012 · Cited by 87 · see citing works
“Numerous studies have indicated that excessive oxidative stress is a pivotal pathogenic factor [33] for age-related bone loss in mice [34], rats [16], and the elderly population [35, 36] resulting in increased osteoblast and osteocyte apoptosis, and decreased osteoblast population and bone formation rate [34].”
Jilka, R. L., O’Brien, C. A., Roberson, P. K., Bonewald, L. F., Weinstein, R. S., & Manolagas, S. C. (2013) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2007 · Cited by 85 · see citing works
“As a result, Bak/Bax‐deficient osteocytes in the periosteal zone are more likely to accumulate damage during aging.((5)) Osteocyte‐enriched preparations of long bones from aged female Bak‐deficient and Bax‐deficient mice expressed higher levels of RANKL and VEGF.”
BackgroundSelf-citationMarie, P. J. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1801-2 · Cited by 85 · see citing works
Connexin 43 Channels Protect Osteocytes Against Oxidative Stress–Induced Cell Death
Kar, R., Riquelme, M. A., Werner, S. L., & Jiang, J. X. (2013) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1917 · Cited by 84 · see citing works
“Because OS is known to be a fundamentalmechanism of aging of the bone (reviewed in Manolagas and Parfitt((12))), we examined the expression of osteocytic Cx43 in bone sections from young and old mice by immunohistochemistry.”
BackgroundInfluentialBone Cell Senescence: Mechanisms and Perspectives
Marie, P. J. (2014) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2190 · Cited by 82 · see citing works
“Studies in mice and humans have shown that the relative decline in bone formation with age results from processes that are linked to reduced proliferation and differentiation of multipotent stem cells (MSCs) within the bone marrow stromal cell population (also known as bone marrow‐derivedmesenchymal stem cells and ske…”
BackgroundSikjær, T., Rejnmark, L., Thomsen, J. S., Tietze, A., Brüel, A., Andersen, G., & Mosekilde, L. (2011) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1493 · Cited by 82 · see citing works
“Changes in 3-Dimensional Bone Structure Indices in Hypoparathyroid Patients Treated With PTH(1-84): A Randomized Controlled Study”
BackgroundMethodInfluentialStrzelecka‐Kiliszek, A., Mebarek, S., Roszkowska, M., Buchet, R., Magne, D., & Pikuła, S. (2017) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2017.02.005 · Cited by 82 · see citing works
Role of Nrf2 in Fracture Healing: Clinical Aspects of Oxidative Stress
Kubo, Y., Wruck, C. J., Fragoulis, A., Drescher, W., Pape, H., Lichte, P., Fischer, H., Tohidnezhad, M., Hildebrand, F., Pufe, T., et al. (2019) · Calcified Tissue International · doi:10.1007/s00223-019-00576-3 · Cited by 81 · see citing works
Mitophagy and apoptosis mediated by ROS participate in AlCl3-induced MC3T3-E1 cell dysfunction
Liu, M., Wu, X., Cui, Y., Liu, P., Xiao, B., Zhang, X., Zhang, J., Sun, Z. R., Song, M., Shao, B., et al. (2021) · Food and Chemical Toxicology · doi:10.1016/j.fct.2021.112388 · Cited by 83 · see citing works
Johansson, J., Nordström, A., & Nordström, P. (2015) · Bone · doi:10.1016/j.bone.2015.07.001 · Cited by 80 · see citing works
“Bone loss in elderly may also be the result of the age-related reduction in the number of osteocytes through apoptosis [31].”
BackgroundFruit and Vegetable Intake and Risk of Hip Fracture: A Cohort Study of Swedish Men and Women
Byberg, L., Bellavia, A., Orsini, N., Wolk, A., & Michaëlsson, K. (2014) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2384 · Cited by 79 · see citing works
“Being rich in antioxidants, a high fruit and vegetable intake might counteract the age-related increase in oxidative stress or chronic low-grade inflammation that influences both bone health((10,59)) and muscle strength,((11)) which are important determinants of hip fracture risk.”
Chen, K., Yang, Y., Jiang, S., & Jiang, L. (2014) · Histochemistry and Cell Biology · doi:10.1007/s00418-014-1194-1 · Cited by 76 · see citing works
Zhang, B., Hou, R., Zou, Z., Luo, T., Zhang, Y., Wang, L., & Wang, B. (2017) · Redox Biology · doi:10.1016/j.redox.2017.10.021 · Cited by 76 · see citing works
“The findings of these authors suggest an underlying connection between autophagy and skeletal ageing, and the notion that a decline of autophagy with ageing may contribute to ageing-related low bone mass [11].”
BackgroundStem cells in Osteoporosis: From Biology to New Therapeutic Approaches
Paspaliaris, V., & Kolios, G. C. (2019) · Stem Cells International · doi:10.1155/2019/1730978 · Cited by 75 · see citing works
“The physiological bone remodeling process that regenerates the entire skeleton has been calculated to take place every 10 years [8].”
BackgroundConcise Review: Musculoskeletal Stem Cells to Treat Age-Related Osteoporosis
Kiernan, J., Davies, J. E., & Stanford, W. L. (2017) · Stem Cells Translational Medicine · doi:10.1002/sctm.17-0054 · Cited by 74 · see citing works
Mechanisms of palmitate-induced cell death in human osteoblasts
Gunaratnam, K., Vidal, C., Boadle, R. A., Thekkedam, C. G., & Duque, G. (2013) · Biology Open · doi:10.1242/bio.20136700 · Cited by 73 · see citing works
“the normal aging process in bone there is an increase in apoptosis and autophagy failure, and that both these processes are increased still further in osteoporotic bone (Manolagas and Parfitt, 2010).”
BackgroundGood, Bad, or Ugly: the Biological Roles of Bone Marrow Fat
Singh, L., Tyagi, S., Myers, D. E., & Duque, G. (2018) · Current Osteoporosis Reports · doi:10.1007/s11914-018-0427-y · Cited by 73 · see citing works
Spilmont, M., Léotoing, L., Davicco, M.-J., Lebecque, P., Miot-Noirault, É., Pilet, P., Rios, L. Y., Wittrant, Y., & Coxam, V. (2015) · Nutrients · doi:10.3390/nu7115465 · Cited by 72 · see citing works
“Actually, it has been reported that reactive oxygen species and low-grade inflammation, both of which contribute to the aging process [40–45], are involved in the aetiology of various degenerative diseases, such as osteoporosis [46–50].”
The role of reactive oxygen species in bone cell physiology and pathophysiology
Marques-Carvalho, A., Kim, H., & Almeida, M. (2023) · Bone Reports · doi:10.1016/j.bonr.2023.101664 · Cited by 72 · see citing works
“Extensive evidence from animals and humans indicates that a decrease in osteoblasts and bone formation is a seminal mechanism of the decreased bone mass in old age (Manolagas and Parfitt, 2010).”
BackgroundNADPH oxidases in bone homeostasis and osteoporosis
Schröder, K. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1712-2 · Cited by 71 · see citing works
“Interestingly, osteocyte death is dependent on the age of the bone, not on the age of the subject [26].”
BackgroundLin, T., Gibon, E., Loi, F., Pajarinen, J., Córdova, L. A., Nabeshima, A., Lu, L. Y., Yao, Z., & Goodman, S. B. (2016) · Journal of Orthopaedic Research® · doi:10.1002/jor.23270 · Cited by 69 · see citing works
“Aging is associated with significant bone loss and delayed fracture healing.(1,2) Fragility fractures in elderly patients have become a major issue in the aging society; the cost of medical care in United States for these fractures is projected to reach 25 billion dollars by the year 2025.”
BackgroundPhysiology of ageing of the musculoskeletal system
Boros, K., & Freemont, A. J. (2017) · Best Practice & Research Clinical Rheumatology · doi:10.1016/j.berh.2017.09.003 · Cited by 65 · see citing works
Manolagas, S. C., & PARFITT, A. M. (2012) · Bone · doi:10.1016/j.bone.2012.09.017 · Cited by 64 · see citing works
“Osteocytes are by far the more abundant cell type in bone: one thousand times more than osteoclasts and ten times more than osteoblasts [1].”
BackgroundSelf-citationFrom Stem Cells to Bone-Forming Cells
Donsante, S., Palmisano, B., Serafini, M., Robey, P. G., Corsi, A., & Riminucci, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22083989 · Cited by 63 · see citing works
“At the end of their life span of approximately 3 months [6], osteoblasts may undergo apoptosis or complete their life cycle by converting into either of two differentiated cell phenotypes: osteocytes or bone lining cells.”
BackgroundMilk extracellular vesicles accelerate osteoblastogenesis but impair bone matrix formation
Oliveira, M. C., Arntz, O. J., Davidson, E. N. B., van Lent, P. L. E. M., Koenders, M. I., van der Kraan, P. M., van den Berg, W. B., Ferreira, A. V. M., & van de Loo, F. A. J. (2015) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2015.11.017 · Cited by 62 · see citing works
“It was described that osteoblasts that escape death via apoptosis differentiate into osteocytes and are incorporated within the mineralized matrix [40].”
BackgroundBone collagen network integrity and transverse fracture toughness of human cortical bone
Willett, T. L., Dapaah, D. Y., Uppuganti, S., Granke, M., & Nyman, J. S. (2018) · Bone · doi:10.1016/j.bone.2018.10.024 · Cited by 62 · see citing works
“In fact, the decline in bone strength is disproportionately faster than the decline in bone volume.(10) Patients with bone affecting diseases such as diabetes or renal osteodystrophy do not necessarily present with low clinical aBMD but do experience higher rates of fractures.”
BackgroundRolvien, T., Schmidt, F. N., Milovanovic, P. D., Jähn, K., Riedel, C., Butscheidt, S., Püschel, K., Jeschke, A., Amling, M., & Busse, B. (2018) · Scientific Reports · doi:10.1038/s41598-018-19803-2 · Cited by 61 · see citing works
Bach-Gansmo, F. L., Brüel, A., Jensen, M. V., Ebbesen, E. N., Birkedal, H., & Thomsen, J. S. (2016) · Bone · doi:10.1016/j.bone.2016.07.003 · Cited by 60 · see citing works
“Osteocytes are by far the most abundant cells in bone, the number of osteocytes is estimated as ten times that of osteoblasts and thousand times that of osteoclasts [12].”
BackgroundNon-Nuclear–Initiated Actions of the Estrogen Receptor Protect Cortical Bone Mass
Bartell, S. M., Li, H., Kim, H., Kim, S. H., Katzenellenbogen, J. A., Katzenellenbogen, B. S., Chambliss, K. L., Shaul, P. W., Roberson, P. K., Weinstein, R. S., et al. (2013) · Molecular Endocrinology · doi:10.1210/me.2012-1368 · Cited by 58 · see citing works
“Given the relative small number of osteoclasts, compared with the numbers of other hematopoietic cells in the marrow or relative to the numbers of osteoblasts and osteocytes in bone (10 and 100 times lower, respectively) (21), the contribution of osteoclasts to the overall oxidative stress is likely to be negligible.”
BackgroundSelf-citationAge-Related Bone Mineral Density Patterns in Koreans (KNHANES IV)
Lee, E. Y., Kim, D., Kim, K. M., Kim, K. J., Choi, H. S., Rhee, Y., & Lim, S.-K. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-1488 · Cited by 59 · see citing works
Osteocytes and Skeletal Pathophysiology
Delgado‐Calle, J., & Bellido, T. (2015) · Current Molecular Biology Reports · doi:10.1007/s40610-015-0026-y · Cited by 60 · see citing works
“During aging, osteocyte density declines, with an increase in the number of empty lacunae (67;68).”
BackgroundLow-dose dexamethasone affects osteoblast viability by inducing autophagy via intracellular ROS
Zhang, S., Liu, Y., & Liang, Q. (2018) · Molecular Medicine Reports · doi:10.3892/mmr.2018.8461 · Cited by 57 · see citing works
“This function is critical for the survival of some terminally differentiated cells, such as osteoblasts and osteoclasts (40).”
Mechanisms of palmitate-induced lipotoxicity in osteocytes
Saedi, A. A., Bermeo, S., Plotkin, L. I., Myers, D. E., & Duque, G. (2019) · Bone · doi:10.1016/j.bone.2019.06.016 · Cited by 58 · see citing works
“High levels of apoptotic osteocytes and many compromised empty lacunae are observed in aging and in osteoporotic bone [10,11],”
Background
- Authors
- Manolagas, S. C., & Parfitt, A. M.
- Affiliations
- Central Arkansas Veterans Healthcare System (US)
- Corresponding author
- Manolagas, Stavros C.
- Venue
- Trends in Endocrinology & Metabolism
- Publisher
- Elsevier BV
- Published
- 2010-06
- Volume
- 21
- Issue
- 6
- Pages
- 369-374
- ISSN
- 1043-2760 (ISSN-L)
- PMC
- PMC2880220
- OpenAlex
- W2088789328
- Cited by
- 404
- References
- 74
- Citations by year
- 2026: 11 · 2025: 17 · 2024: 20 · 2023: 30 · 2022: 25 · 2021: 30 · 2020: 30 · 2019: 39 · 2018: 32 · 2017: 30 · 2016: 24 · 2015: 25 · 2014: 25 · 2013: 23 · 2012: 17
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Trends in Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs
- University of Arkansas for Medical Sciences
- National Institutes of Health (P01 AG13918)
- 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 › Endocrinology, Diabetes and Metabolism › Alkaline Phosphatase Research Studies
- Keywords
- skeletal aging, osteocyte death, oxidative stress, bone loss, bone strength, osteoblasts, osteoclasts, menopause
- MeSH terms
- Aging, Animals, Bone and Bones, Bone Diseases, Humans, Menopause, Osteocytes, Cell Death
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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