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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.282”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [282]
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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
“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
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 86
Mitophagy and apoptosis mediated by ROS participate in AlCl3-induced MC3T3-E1 cell dysfunction
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Johansson, J., Nordström, A., & Nordström, P. (2015) · Bone · doi:10.1016/j.bone.2015.07.001 · Cited by 80
“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
“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.”
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“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
“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
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Mechanisms of palmitate-induced cell death in human osteoblasts
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“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
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“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].”
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“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
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“Interestingly, osteocyte death is dependent on the age of the bone, not on the age of the subject [26].”
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“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
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Manolagas, S. C., & PARFITT, A. M. (2012) · Bone · doi:10.1016/j.bone.2012.09.017 · Cited by 65
“Osteocytes are by far the more abundant cell type in bone: one thousand times more than osteoclasts and ten times more than osteoblasts [1].”
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“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
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“It was described that osteoblasts that escape death via apoptosis differentiate into osteocytes and are incorporated within the mineralized matrix [40].”
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“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.”
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“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
“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)
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Osteocytes and Skeletal Pathophysiology
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“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
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“This function is critical for the survival of some terminally differentiated cells, such as osteoblasts and osteoclasts (40).”
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“High levels of apoptotic osteocytes and many compromised empty lacunae are observed in aging and in osteoporotic bone [10,11],”
Background
Metadata
- 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
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