Cited by 405Bone Metabolism and DiseasesBone health and osteoporosis researchAlkaline Phosphatase Research Studies

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What old means to bone

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Manolagas, Stavros C., Parfitt, A. Michael·2010·Trends in Endocrinology & Metabolism

DOI 10.1016/j.tem.2010.01.010PMC PMC2880220

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Abstract

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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Nrf2 Activation as a Therapeutic Target for Flavonoids in Aging-Related Osteoporosis
Messeha, S. S., Fidudusola, F. F., Gendy, S., Latinwo, L. M., Odewumi, C. O., & Soliman, K. F. A. (2025) · Nutrients · doi:10.3390/nu17020267 · Cited by 9
Machine Learning-Based CT Radiomics Model to Predict the Risk of Hip Fragility Fracture
Yuan, J., Li, B., Zhang, C., Wang, J., Huang, B., & Ma, L. (2025) · Academic Radiology · doi:10.1016/j.acra.2025.01.023 · Cited by 9
“…level and antioxidant capacity in the endocrine system with age, as well as increased level of endogenous glucocorticoid, may lead to loss of bone volume, degradation of trabecular micro-architecture and eventual replacement by adipose tissue, resulting in increased risk of fracture (27,28).”
Development of empirical anti-inflammatory diet index: a cross-sectional study
Kałuża, J., Hellerström, L., Kaluza, D., Chabok, A., Åkesson, A., Michaëlsson, K., & Wolk, A. (2025) · Nutrition Journal · doi:10.1186/s12937-025-01165-x · Cited by 9
“It has been established that low-grade inflammation promotes cardiovascular disease (CVD) [3, 4], type 2 diabetes [5], osteoporosis [6, 7], and cancers [4, 8].”
Degradation‐Resistant Hypoxia Inducible Factor‐2α in Murine Osteocytes Promotes a High Bone Mass Phenotype
Mendoza, S. V., Murugesh, D. K., Christiansen, B., Genetos, Z. O., Loots, G. G., Genetos, D. C., & Yellowley, C. E. (2023) · JBMR Plus · doi:10.1002/jbm4.10724 · Cited by 9
Bone Cells Metabolic Changes Induced by Ageing
Cardoneanu, A., Rezuș, C., Tamba, B.-I., & Rezuş, E. (2023) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-3-031-26576-1_2 · Cited by 9
Is a Healthy Diet Also Suitable for the Prevention of Fragility Fractures?
Lemming, E. W., & Byberg, L. (2020) · Nutrients · doi:10.3390/nu12092642 · Cited by 9
“Other pathogenic mechanisms that contribute to age-related bone loss are inflammation and sequential or concomitant oxidative stress [1].”
Background
A Combined Process Algebraic and Stochastic Approach to Bone Remodeling
Lió, P., Merelli, E., Paoletti, N., & Viceconti, M. (2011) · Electronic Notes in Theoretical Computer Science · doi:10.1016/j.entcs.2011.09.034 · Cited by 9
“In the process of bone remodeling (BR), old bone is continuously replaced by new tissue [9]; this ensures that the mechanical integrity of the bone is maintained and, in healthy conditions, there are no global changes in the morphology.”
Background
Osteocyte Dendrites: How Do They Grow, Mature, and Degenerate in Mineralized Bone?
Guerra, R. M., Fowler, V. M., & Wang, L. (2024) · Cytoskeleton · doi:10.1002/cm.21964 · Cited by 10
“Both systems allow propagation of biochemical signaling (and electric potentials in the brain) with long-term stability, given the decades-long life span for functioning osteocytes and neurons (Manolagas and Parfitt 2010).”
Application of extracellular vesicles in diabetic osteoporosis
Jia, X., Zhang, G., & Yu, D. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1466775 · Cited by 11
“60% to 80% of osteoblasts differentiated by BMSCs undergo apoptosis, and the remaining osteoblasts become mature osteoblasts (36).”
Multiple verification in computational modeling of bone pathologies
Lió, P., Merelli, E., & Paoletti, N. (2011) · Electronic Proceedings in Theoretical Computer Science · doi:10.4204/eptcs.67.8 · Cited by 9
“In order to maintain the mechanical properties of the bones, old bone is continuously replaced by new tissue [14].”
Background
Association between dietary vitamin E and osteoporosis in older adults in the United States
Zhuang, R., Hou, W., Zhang, T., & Wang, T. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1410581 · Cited by 8
Phosvitin and its hydrolysate promote differentiation and inhibit TNF-ɑ induced inflammation in MC3T3-E1 cells via ERK and AKT pathways
Ren, J., Chakrabarti, S., & Wu, J. (2019) · Journal of Functional Foods · doi:10.1016/j.jff.2018.12.025 · Cited by 8
Use of backscattered scanning electron microscopy to quantify the bone tissues of mid‐thoracic human ribs
Beresheim, A. C., Pfeiffer, S., Grynpas, M. D., & Alblas, A. (2019) · American Journal of Physical Anthropology · doi:10.1002/ajpa.23716 · Cited by 9
A Computational Multiscale Framework for Bone Remodeling: Coupling Apparent Density Evolution and Microscale Shape Optimization
Vemparala, B., Ji, M., Mageswaran, P., Knapik, G. G., Dibs, K. N., Blakaj, D. M., Bourekas, E. C., Mendel, E., Marras, W. S., & Soghrati, S. (2025) · International Journal for Numerical Methods in Biomedical Engineering · doi:10.1002/cnm.70097 · Cited by 7
“Similarly, it is known that osteocytes have an average lifespan of 25 years and some can live up to 50 years [42].”
Influential
Structure, composition, mechanics and growth of spines of the dorsal fin of blue tilapia Oreochromis aureus and common carp Cyprinus carpio
Kalish-Achrai, N., Ornan, E. M., & Shahar, R. (2017) · Journal of Fish Biology · doi:10.1111/jfb.13287 · Cited by 6
A novel non-invasive method for predicting bone mineral density and fracture risk using demographic and anthropometric measures
Aflatooni, J. O., Martin, S. E., Edilbi, A., Gadangi, P., Singer, W., Loving, R., Domakonda, S., Solanki, N., McCulloch, P. C., & Lambert, B. S. (2023) · Sports Medicine and Health Science · doi:10.1016/j.smhs.2023.09.003 · Cited by 7
Genetic Evidence Supporting a Causal Association Between mTOR-Dependent EIF-4E Circulating Protein Level and Osteoporosis
Cheng, T., Zhang, Y., Fan, K., Hu, J.-X., Wang, Q., Wang, Q., Liu, L., Zhang, H., Hou, Y.-P., Li, X., et al. (2023) · Advances in Therapy · doi:10.1007/s12325-023-02676-x · Cited by 7
The stability of water‐ and fat‐soluble vitamin in dentifrices according to pH level and storage type
Park, J., Kim, K., Choi, Y., Park, Y., & Kwon, H. (2015) · Biomedical Chromatography · doi:10.1002/bmc.3535 · Cited by 7
Voluntary wheel running mitigates the stress-induced bone loss in ovariectomized rats
Lertsinthai, P., Charoenphandhu, J., Suntornsaratoon, P., Krishnamra, N., & Charoenphandhu, N. (2014) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-014-0597-3 · Cited by 7
“Estrogen deficiency has been known to increase bone loss and susceptibility to stress and mood disorder in postmenopausal women [1, 2].”
Background
SPA0355 prevents ovariectomy-induced bone loss in mice
Ha, S. H., Zhang, Z., Moon, Y. J., Park, I. W., Cho, Y. G., Jeon, R., & Park, B. (2019) · Korean Journal of Physiology and Pharmacology · doi:10.4196/kjpp.2019.23.1.47 · Cited by 7
Skeletal stem cells and their contribution to skeletal fragility: senescence and rejuvenation
Aldahmash, A. M. (2015) · Biogerontology · doi:10.1007/s10522-015-9623-7 · Cited by 8
“Bone remodeling leads to full regeneration of the whole skeleton every 10 years during the adult human life (Manolagas and Parfitt 2010).”
Background
Emerging Roles of Eosinophils in Bone
Andreev, D., & Porschitz, P. (2025) · Current Osteoporosis Reports · doi:10.1007/s11914-025-00913-6 · Cited by 5
“Notably, approximately 10% of cal - cified bone is remodeled annually in the human body [17].”
Heart Failure and Osteoporosis: Shared Challenges in the Aging Population
Spoladore, R., Ciampi, C. M., Ossola, P., Sultana, A., Spreafico, L. P., Farina, A., & Fragasso, G. (2025) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd12020069 · Cited by 5
“The bone remodeling process is choreographed by osteocytes, which are derived from osteoblasts entrapped in the mineralized matrix [19].”
Osteoporosis
Paoletti, N., Lió, P., Merelli, E., & Viceconti, M. (2011) · Computational Methods in Systems Biology · doi:10.1145/2037509.2037536 · Cited by 5
“In the process of bone remodeling (BR), old bone is continuously replaced by new tissue [24]; this ensures that the mechanical integrity of the bone is maintained and, in healthy conditions, there are no global changes in the morphology.”
Background
The Potential of Materials Analysis by Electron Rutherford Backscattering as Illustrated by a Case Study of Mouse Bones and Related Compounds
Vos, M., Tőkési, K., & Benkő, I. (2013) · Microscopy and Microanalysis · doi:10.1017/s143192761300041x · Cited by 5
Osteocytic oxygen sensing: Distinct impacts of VHL and HIF-2alpha on bone integrity
Mendoza, S. V., Wells, K. V., Murugesh, D. K., Hum, N. R., Sebastian, A., Gorman, B. M., Wong, A., Osipov, B., Christiansen, B., Loots, G. G., et al. (2024) · Bone · doi:10.1016/j.bone.2024.117339 · Cited by 5
“Embedded within mineralized matrix of cortical and trabecular bone, osteocytes can persist for decades [8] and serve essential roles in mechanosensing, mineral homeostasis, and hematopoiesis [9].”
Curcumin and Its Potential Effects on the Development of Postmenopausal Osteoporosis
Folwarczna, J. (2013) · Humana Press eBooks · doi:10.1007/978-1-62703-373-2_13 · Cited by 5
Major and trace elements in mouse bone measured by surface and bulk sensitive methods
Benkő, I., Rajta, I., Csík, A., Tóth, J., Benkö, K., Géresi, K., Ungvári, É., Szabó, B., Sarkadi, G., Paripás, B., et al. (2011) · Nuclear Instruments and Methods in Physics Research Section B Beam Interactions with Materials and Atoms · doi:10.1016/j.nimb.2011.10.059 · Cited by 5
Primary cementless hip arthroplasty as a potential risk factor for non-union after long-stem revision arthroplasty in periprosthetic femoral fractures
Boesmueller, S., Michel, M., Hofbauer, M., & Platzer, P. (2014) · International Orthopaedics · doi:10.1007/s00264-014-2489-5 · Cited by 5
“Osteoporosis as a dominating factor is strongly correlatedwith female gender and advanced age and is known to result from an imbalance of bone resorption and apposition as well as reduced bone turnover rate, which might have a negative influence on bone healing [34, 35].”
Background
The interaction between vitamin C and bone health: a narrative review
Falchetti, A., & Cosso, R. (2018) · Expert Review of Precision Medicine and Drug Development · doi:10.1080/23808993.2018.1482211 · Cited by 5
“OBLs have a shorter lifespan, and their death depends on the skeletal age [33].”
Background
Comparative profiles of DNA methylation and differential gene expression in osteocytic areas from aged and young mice
Yu, W., Fu, J., Wu, W., & Wu, J. (2020) · Cell Biochemistry and Function · doi:10.1002/cbf.3539 · Cited by 6
Skeletal Aging: From Bench to Bed Side
Manolagas, S. C., & Cummings, S. R. (2013) · The Journals of Gerontology Series A · doi:10.1093/gerona/glt125 · Cited by 5
Self-citation
Meat consumption and the risk of hip fracture in women and men: two prospective Swedish cohort studies
Lemming, E. W., Byberg, L., Höijer, J., Baron, J. A., Wolk, A., & Michaëlsson, K. (2024) · European Journal of Nutrition · doi:10.1007/s00394-024-03385-z · Cited by 4
“However, in addition to age-related bone loss [1], sarcopenia [6, 7] contributes to the fracture risk by affecting balance and causing falls.”
Background
Local and Systemic Regulation of Mineralization: Role of Coupling Factors, Pyrophosphate, Polyphosphates, Vitamin D, Fetuin, Matrix Gla Protein, and Osteopontin
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Panoramic Radiomorphometric Indices of Mandible: Biomarker for Osteoporosis
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Effects of Donepezil on the Musculoskeletal System in Female Rats
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“Estrogen deficiency occurring in postmenopausal women causes changes in bone remodeling leading to decreased bone mass, disordered microstructure and decreased strength [9,10,12]; moreover, some data indicate the possible effects of estrogen deficiency on cognition in humans [73–75].”
Background
Dietary fatty acids and incident hip fractures in cohorts of women and men. A relative validation and follow-up study
Lemming, E. W., Byberg, L., Höijer, J., Larsson, S. C., Wolk, A., & Michaëlsson, K. (2024) · The journal of nutrition health & aging · doi:10.1016/j.jnha.2024.100247 · Cited by 4
“The risk of fracture is not only related to age-related bone loss [11] but also to sarcopenia [12,13], which influences balance and falls.”
Background
Bioenergetic programs of cancellous and cortical bone are distinct and differ with age and mechanical loading
Chlebek, C., McNeill, T. J., Huang, M., Raynor, M. S., & van der Meulen, M. C. H. (2025) · Scientific Reports · doi:10.1038/s41598-025-02141-5 · Cited by 4
Osteosarcopenia as a Lipotoxic Disease
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Authors: Manolagas, S. C., & Parfitt, A. M.
Affiliations: Central Arkansas Veterans Healthcare System (US)
Corresponding author: Manolagas, Stavros C.
ORCID: 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)
DOI: 10.1016/j.tem.2010.01.010
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
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

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