Vitamin D regulates osteocyte survival and perilacunar remodeling in human and murine bone
Abstract
Osteocytes are the most abundant bone cells and are highly regulated by external stimuli. Vitamin D and osteocytes cooperatively regulate bone remodeling as well as phosphate and calcium homeostasis. However, it is unclear if vitamin D regulates osteocyte number, connectivity or size in the setting of altered bone formation or impaired mineralization. Sixty iliac crest biopsies of patients with varying vitamin D levels were examined to analyze osteocyte number, osteocyte connectivity and osteocyte viability using high-resolution imaging. Osteocyte parameters were also quantified in mice lacking the vitamin D receptor (Vdr-/-) and in wildtype littermates. The cortical and cancellous bone of patients with vitamin D deficiency exhibited a significant decrease in the number of viable osteocytes, as well as increased osteocyte apoptosis and impaired osteocyte connectivity, based on evaluation of the canalicular network. The number of osteocytes was also decreased in Vdr-deficient mice, in comparison to wildtype controls, and this was accompanied by enlargement of osteocyte lacunae. A high calcium diet normalized the osteocyte lacunar area in Vdr-deficient mice, but failed to normalize osteocyte number. Thus, a diet-independent decrease in osteocyte number in Vdr-deficient mice suggests a mechanism that is directly dependent on the VDR, since vitamin D may promote the transition from osteoblasts to osteocytes. The increase in lacunar area the in Vdr-deficient mice, which is normalized by the high calcium diet suggests this phenotype is due to osteocytic osteolysis. These investigations demonstrate that vitamin D plays a role in the regulation of osteocyte number and perilacunar remodeling.
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1,25(OH)2D3 regulates osteocyte perilacunar remodeling and canalicular organization through the activation of matrix resorption genes.
“c) regulates osteocyte perilacunar remodeling and canalicular organization through the activation of matrix resorption genes.102”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [102]
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Bone remodeling: an operational process ensuring survival and bone mechanical competence
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No Signature of Osteocytic Osteolysis in Cortical Bone from Lactating NMRI Mice
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“V have been observed in rodents on parathyroid hormone (PTH) treatment, (31) in patients with vitamin D de fi ciency, (32) and during lactation, (33) suggesting that different mechanisms may in fl uence Lc.V.”
BackgroundVitamin D and Metabolic Supplementation in Orthopedic Trauma
Nino, S., Soin, S. P., & Avilucea, F. R. (2019) · Orthopedic Clinics of North America · doi:10.1016/j.ocl.2018.12.001 · Cited by 12 · see citing works
Stürznickel, J., Hinz, N., Delsmann, M. M., Hoenig, T., & Rolvien, T. (2022) · The American Journal of Sports Medicine · doi:10.1177/03635465221120385 · Cited by 10 · see citing works
“The role of vitamin D in bone remodeling and the relevance of balanced calcium homeostasis have been the subject of previous research and have already been highlighted for various skeletal diseases.(31,32) Vitamin D deficiency has been shown to be highly prevalent in athletes in general(3) and to represent a distinct…”
BackgroundSelf-citationBone health and hyperglycemia in pediatric populations
Bilinski, W. J., Paradowski, P. T., & Sypniewska, G. (2020) · Critical Reviews in Clinical Laboratory Sciences · doi:10.1080/10408363.2020.1739619 · Cited by 10 · see citing works
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Butscheidt, S., Kroge, S. V., Stürznickel, J., Beil, F. T., Gehrke, T. A., Püschel, K., Amling, M., Hahn, M. P., & Rolvien, T. (2021) · PubMed · doi:10.2106/jbjs.20.01943 · Cited by 8 · see citing works
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“11 Moreover, it is initiated in conditions such as osteomalacia 12 and rickets.”
BackgroundFu, R., & Yang, H. (2024) · Physics of Fluids · doi:10.1063/5.0242900 · Cited by 8 · see citing works
Jadzic, J. S., Plumeyer, C., Djukić, D., Živković, V., Nikolić, S., Veldhuis‐Vlug, A. G., Tomanović, N., Djuric, M. P., Milovanovic, P. D., Busse, B., et al. (2025) · Journal of Bone and Mineral Research · doi:10.1093/jbmr/zjaf065 · Cited by 10 · see citing works
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Micropetrosis in hemodialysis patients
Yajima, A., Tsuchiya, K., Burr, D. B., Murata, T., Nakamura, M., Inaba, M., Tominaga, Y., Tanizawa, T., Nakayama, T., Ito, A., et al. (2021) · Bone Reports · doi:10.1016/j.bonr.2021.101150 · Cited by 6 · see citing works
Schmidt, B., Sonne, C., Nachtsheim, D. A., Dietz, R., Oheim, R., Rolvien, T., Persson, S., Amling, M., & Siebert, U. (2020) · Environment International · doi:10.1016/j.envint.2020.105968 · Cited by 6 · see citing works
“It not only serves for the renewal of bone in response to skeletal loading, but also for the maintenance of mineral homeostasis (i.e., calcium, phosphate) (Rolvien et al., 2017).”
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“Gray-value images were converted to analyze the calcium content of the bone matrix, reflecting the bone mineral density distribution (BMDD), as previously described [20, 21].”
MethodSelf-citationPrevention of Hypomineralization In Auditory Ossicles of Vitamin D Receptor (Vdr) Deficient Mice
Delsmann, M. M., Peichl, J., Yorgan, T. A., Beil, F. T., Amling, M., Demay, M. B., & Rolvien, T. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.901265 · Cited by 5 · see citing works
“org 2 type (WT) littermates were included from a previous study for high-resolution skeletal analysis of auditory ossicles (7).”
BackgroundMethodSelf-citationHistological Assessment of Endochondral Ossification and Bone Mineralization
Hasegawa, T., Hongo, H., Yamamoto, T., Muneyama, T., Miyamoto, Y., & Amizuka, N. (2023) · Endocrines · doi:10.3390/endocrines4010006 · Cited by 5 · see citing works
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Insights into the Molecular and Hormonal Regulation of Complications of X-Linked Hypophosphatemia
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“An enlargement of osteocyte lacunae has already been demonstrated as a reversible phenomenon in lactation 36 and vitamin D deficiency 37 to release calcium from skeletal stores, also referred to as osteocytic osteolysis or perilacunar/canalicular remodeling.”
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Evaluation of the effect of vitamin D level on greater tuberosity primary bone marrow edema
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“9,10 There are studies in the literature reporting a relationship between BMO in the foot/ankle and vitamin D deficiency.”
BackgroundTHE ROLE OF VITAMIN D IN THE FUNCTIONING OF BONE CELLS
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Isolated Lacunar Skull Defect in a Newborn
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Beyond bones, vitamin D as a sunshine hormone in type 2 diabetes mellitus and its complications
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“20 On the other hand, bone resorption leads to elevated levels of calcium and phosphorus in the blood, which accelerates calcium deposition and bone mineralization.”
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Articular and skeletal affection in regularly dialyzed patients with end-stage renal disease
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“This leads to osteocyte apoptosis [26] and dysregulation of genes controlling osteoblast function and local remodeling signals, including the RANKL/ OPG axis, contributing to an anabolic bone state.”
- Authors
- Rolvien, T., Krause, M., Jeschke, A., Yorgan, T., Püschel, K., Schinke, T., Busse, B., Demay, M. B., & Amling, M.
- Affiliations
- University Medical Center Hamburg-Eppendorf (DE)
- Harvard University (US)
- Corresponding author
- Amling, Michael
- ORCID
- Venue
- Bone
- Publisher
- Elsevier BV
- Published
- 2017-10
- Volume
- 103
- Pages
- 78-87
- ISSN
- 1873-2763 (ISSN-L)
- 8756-3282
- OpenAlex
- W2732802085
- Cited by
- 74
- References
- 49
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 7 · 2023: 8 · 2022: 9 · 2021: 10 · 2020: 13 · 2019: 12 · 2018: 9 · 2017: 1
- FWCI
- 7.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Bone (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
- 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
- Keywords
- vitamin D, osteocytes, osteocyte survival, vitamin D receptor, osteocyte apoptosis, vitamin D deficiency, high-calcium diet, bone remodeling, calcium homeostasis, phosphate homeostasis, iliac crest bone
- MeSH terms
- Animals, Cell Survival, Humans, Osteocytes, Vitamin D, Vitamin D Deficiency, Bone Remodeling, Receptors, Calcitriol, Mice, Knockout, Mice
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