Osteologie 2016; 25(02): 77-82
DOI: 10.1055/s-0037-1619005
Osteocyte: Morphology & Function
Schattauer GmbH

Osteocytic vs. anosteocytic bone

A review with special emphasis on teleost fish boneZellulärer vs. azellulärer KnochenEine Übersicht mit Hauptaugenmerk auf Echten Knochenfischen (Teleostei)
T. Rolvien
1   Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
B. Busse
1   Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
› Author Affiliations
Further Information

Publication History

received: 29 February 2016

accepted: 10 March 2016

Publication Date:
22 December 2017 (online)


When comparing mammalian osteocyte-containing bone with anosteocytic (“acellular”) fish bone, it is noteworthy that anosteocytic bone is capable of bone remodeling processes and participation in the organism’s mineral homeostasis - two features that are attributed to osteocytic cells. As there is an evolutionary drift towards anosteocytic skeletons throughout teleost fish, osteocytic routes may either not been necessary anymore or it simply indicates that there are other non-osteocytic pathways. The lack of osteocytes in spite of osteoid produced by osteoblasts and bone matrix deposition in anosteocytic fish presumes that some mechanisms prevent the transformation of osteoblasts to osteocytes. The anosteocytic bone may form osteon-like structures, adapt to changing loading regimes and is subject to osteoclastic bone resorption. Considering the multiple types of osteocytic and anosteocytic bone matrices among teleost fish, the availability of mononucleated osteoclasts capable of bone resorption, high bone mineral density and an stabilizing mineralized notochord sheath, are only some observations that need to be studied further. Of note, there is evidence that intermediate stages between osteocytic and anosteocytic bone are present in some species. In fact, the European eel is one example that presents with effective multinucleated osteoclasts, small and few osteocyte lacunae with unknown network characteristics. Further investigation and imaging of osteocytic and non-osteocytic osseous structures will help to provide novel understanding of these essential characteristics in bone biology.


Vergleicht man den zellulären Knochen von Säugetieren mit azellulärem Knochen in Fischen, so ist es bemerkenswert, dass azellulärer Knochen an Knochenumbaumechanismen sowie auch an der Mineralhomöostase des Organismus beteiligt ist– zwei Charakteristiken, die generell mit Osteozyten in Verbindung gebracht werden. Echte Knochenfische (Teleostei) zeichnen sich durch eine evolutionäre Entwicklung von azellulärem Knochen aus. Das bedeutet, dass Osteozyten in ihrer Funktion entweder nicht mehr notwendig waren oder es tatsächlich noch andere Kommunikationswege im azellulären Knochen gibt. Das Fehlen von Osteozyten trotz einer funktionierenden Osteoid- und Knochenmatrixdeposition durch Osteoblasten lässt annehmen, dass Mechanismen vorhanden sind, die den Übergang von Osteoblasten zu Osteozyten verhindern. Azellulärer Knochen ist in der Lage, osteonartige Strukturen zu formen, sich veränderten Belastungen anzupassen sowie osteoklastäre Knochenresorption zuzulassen. Berücksichtigt man die große Vielfalt von zellulären und azellulären Knochenformen unter den Teleostei, sind das Vorhandensein von resorptionsfähigen mono nukleären Osteoklasten, eine hohe Knochenmineralisation sowie die stabilisierende mineralisierte Chorda dorsalis nur einige Besonderheiten, die weiter erforscht werden sollten. Es gibt Anzeichen, die für evolutionäre Stadien zwischen zellulärem und azellulärem Knochen sprechen. So zeigt der Europäische Aal Anguilla anguilla effektive Knochen resorption durch Osteoklasten und wenige kleine Osteozytenlakunen mit unbekanntem Netzwerkcharakter. Die Untersuchung und Bildgebung von osteozytären und nicht osteozytären Strukturen auf den verschiedenen hierarchischen Knochenebenen werden weiter helfen, diese für die Knochenbiologie zu Grunde liegenden Mechanismen besser zu verstehen.

  • References

  • 1 Bonewald LF, Johnson ML. Osteocytes, Mechanosensing and Wnt Signaling. Bone 2008; 42 (04) 606-615.
  • 2 Milovanovic P, Zimmermann EA, Hahn M. et al. Osteocytic canalicular networks: morphological implications for altered mechanosensitivity. ACS Nano 2013; 07 (09) 7542-7551.
  • 3 Franz-Odendaal TA, Hall BK, Witten PE. Buried alive: how osteoblasts become osteocytes. Dev Dynam 2006; 235 (01) 176-190.
  • 4 Ekanayake S, Hall BK. Ultrastructure of the osteogenesis of acellular vertebral bone in the Japanese medaka, Oryzias latipes (teleostei, cyprinidontidae). Am J Anat 1988; 182 (03) 241-249.
  • 5 Witten PE, Huysseune A. A comparative view on mechanisms and functions of skeletal remodelling in teleost fish, with special emphasis on osteoclasts and their function. Biol Rev 2009; 84 (02) 315-346.
  • 6 Bonewald LF. Osteocytes as dynamic multifunctional cells. Ann N Y Acad Sci 2007; 1116: 281-290.
  • 7 Busse B, Djonic D, Milovanovic P. et al. Decrease in the osteocyte lacunar density accompanied by hypermineralized lacunar occlusion reveals failure and delay of remodeling in aged human bone. Aging Cell 2010; 09 (06) 1065-1075.
  • 8 Feng JQ, Ward LM, Liu S. et al. Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism. Nat Genet 2006; 38 (11) 1310-1315.
  • 9 Teti A, Zallone A. Do osteocytes contribute to bone mineral homeostasis? Osteocytic osteolysis revisited. Bone 2009; 44 (01) 11-16.
  • 10 Qing H, Ardeshirpour L, Pajevic PD. et al. Demonstration of osteocytic perilacunar/canalicular remodeling in mice during lactation. J Bone Miner Res 2012; 27 (05) 1018-1029.
  • 11 Busse B, Bale HA, Zimmermann EA. et al. Vitamin D deficiency induces early signs of aging in human bone, increasing the risk of fracture. Sci Transl Med 2013; 05 (193) 193ra88.
  • 12 Tatsumi S, Ishii K, Amizuka N. et al. Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. Cell Metab 2007; 05 (06) 464-475.
  • 13 Moss ML. Studies of the acellular bone of teleost fish. I. Morphological and systematic variations. Acta Anat 1962; 46: 343-462.
  • 14 Nelson JS. Fishes of the World. Hoboken, New Jersey: Wiley; 2006
  • 15 Smith MM, Hall BK. Development and evolutionary origins of vertebrate skeletogenic and odontogenic tissues. Biol Rev 1990; 65 (03) 277-373.
  • 16 Smith-Vaniz WF, Kaufman LS, Glowacki J. Species-specific patterns of hyperostosis in marine teleost fishes. Mar Biol 1995; 121 (04) 573-580.
  • 17 Parenti LR. The phylogenetic significance of bone types in euteleost fishes. Zool J Linn Soc-Lond 1986; 87 (01) 37-51.
  • 18 Kölliker A. On the different types in the microstructure of the skeletons of osseus fish. P Roy Soc Lond 1859; 09: 656-668.
  • 19 Ekanayake S, Hall BK. The development of acellularity of the vertebral bone of the Japanese medaka, Oryzias latipes (Teleostei; Cyprinidontidae). J Morphol 1987; 193 (03) 253-261.
  • 20 Hughes D, Bassett J, Moffat L. Histological identification of osteocytes in the allegedly acellular bone of the sea breams Acanthopagrus australis, Pagrus auratus and Rhabdosargus sarba (Sparidae, Perciformes, Teleostei). Anat Embryol 1994; 190 (02) 163-179.
  • 21 Persson P, Björnsson BT, Takagi Y. Characterization of morphology and physiological actions of scale osteoclasts in the rainbow trout. J Fish Biol 1999; 54 (03) 669-684.
  • 22 Persson P, Sundell K, Björnsson BT, Lundqvist H. Calcium metabolism and osmoregulation during sexual maturation of river running Atlantic salmon. J Fish Biol 1998; 52 (02) 334-349.
  • 23 Witten PE, Villwock W, Peters N, Hall BK. Bone resorption and bone remodelling in juvenile carp, Cyprinus carpio L. J Appl Ichthyol 2000; 16 (06) 254-261.
  • 24 Helfrich MH. Osteoclast diseases. Microsc Res Techniq 2003; 61 (06) 514-532.
  • 25 Zimmermann EA, Kohne T, Bale HA. et al. Modifications to nano- and microstructural quality and the effects on mechanical integrity in Paget’ s disease of bone. J Bone Miner Res 2015; 30 (02) 264-273.
  • 26 Jobke B, Milovanovic P, Amling M, Busse B. Bisphosphonate-osteoclasts: changes in osteoclast morphology and function induced by antiresorptive nitrogen-containing bisphosphonate treatment in osteoporosis patients. Bone 2014; 59: 37-43.
  • 27 Witten PE. Enzyme histochemical characteristics of osteoblasts and mononucleated osteoclasts in a teleost fish with acellular bone (Oreochromis niloticus, Cichlidae). Cell Tissue Res 1997; 287 (03) 591-599.
  • 28 Weiss RE, Watabe N. Studies on the biology of fish bone. III. Ultrastructure of osteogenesis and resorption in osteocytic (cellular) and anosteocytic (acellular) bones. Calcified Tissue Int 1979; 28 (01) 43-56.
  • 29 Parfitt AM. Osteonal and hemiosteonal remodeling: The spatial and temporal framework for signal traffic in adult human bone. J Cell Biochem 1994; 55 (03) 273-286.
  • 30 Qiu S, Rao DS, Fyhrie DP. et al. The morphological association between microcracks and osteocyte lacunae in human cortical bone. Bone 2005; 37 (01) 10-15.
  • 31 Manolagas SC. Choreography from the tomb: An emerging role of dying osteocytes in the purposeful, and perhaps not so purposeful, targeting of bone remodeling. BoneKEy-Osteovision 2006; 03 (01) 5-14.
  • 32 Baron R, Rawadi G, Roman-Roman S. Wnt Signaling: A Key Regulator of Bone Mass. Curr Top Dev Biol 2006; 76: 103-127.
  • 33 Xiong J, O’Brien CA. Osteocyte RANKL: new insights into the control of bone remodeling. J Bone Miner Res 2012; 27 (03) 499-505.
  • 34 Atkins A, Dean MN, Habegger ML. et al. Remodeling in bone without osteocytes: billfish challenge bone structure-function paradigms. Proc Natl Acad Sci USA 2014; 111 (45) 16047-16052.
  • 35 Meunier FJ, Deschamps M, Lecomte F, Kacem A. Le squelette des poissons téléostéens: structure, développement, physiologie, pathologie. Bull Soc Zool Fr 2008; 133: 9-32.
  • 36 Kranenbarg S, van Cleynenbreugel T, Schipper H, van Leeuwen J. Adaptive bone formation in acellular vertebrae of sea bass (Dicentrarchus labrax L.). J Exp Biol 2005; 208 (Pt 18) 3493-3502.
  • 37 Li X, Ominsky MS, Niu QT. et al. Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res 2008; 23 (06) 860-869.
  • 38 Wijenayaka AR, Kogawa M, Lim HP. et al. Sclerostin stimulates osteocyte support of osteoclast activity by a RANKL-dependent pathway. PLoS One 2011; 06 (10) e25900.
  • 39 To TT, Witten PE, Renn J. et al. Rankl-induced osteoclastogenesis leads to loss of mineralization in a medaka osteoporosis model. Development 2012; 139 (01) 141-150.
  • 40 Shahar R, Dean MN. The enigmas of bone without osteocytes. BoneKEy reports 2013; 02: 343.
  • 41 Horton JM, Summers AP. The material properties of acellular bone in a teleost fish. J Exp Biol 2009; 212 (Pt 9): 1413-1420.
  • 42 Cohen L, Dean M, Shipov A. et al. Comparison of structural, architectural and mechanical aspects of cellular and acellular bone in two teleost fish. J Exp Biol 2012; 215 (Pt 11): 1983-1993.
  • 43 Bernhard A, Milovanovic P, Zimmermann EA. et al. Micro-morphological properties of osteons reveal changes in cortical bone stability during aging, osteoporosis, and bisphosphonate treatment in women. Osteoporosis Int 2013; 24 (10) 2671-2680.
  • 44 Milovanovic P, Zimmermann EA, Riedel C. et al. Multi-level characterization of human femoral cortices and their underlying osteocyte network reveal trends in quality of young, aged, osteoporotic and antiresorptive-treated bone. Biomaterials 2015; 45: 46-55.
  • 45 Zimmermann EA, Schaible E, Gludovatz B. et al. Intrinsic mechanical behavior of femoral cortical bone in young, osteoporotic and bisphosphonate-treated individuals in low- and high energy fracture conditions. Sci Rep 2016; 06: 21072.
  • 46 Mullender MG, Tan SD, Vico L. et al. Differences in osteocyte density and bone histomorphometry between men and women and between healthy and osteoporotic subjects. Calcif Tissue Internat 2005; 77 (05) 291-296.
  • 47 Yajima A, Inaba M, Tominaga Y. et al. Increased osteocyte death and mineralization inside bone after parathyroidectomy in patients with secondary hyperparathyroidism. J Bone Miner Res 2010; 25 (11) 2374-2381.
  • 48 Frost H. Micropetrosis. J Bone Joint Surg Am 1960; 42-A: 144-150.
  • 49 Bakker A, Klein-Nulend J, Burger E. Shear stress inhibits while disuse promotes osteocyte apoptosis. Biochem Bioph Res Co 2004; 320 (04) 1163-1168.
  • 50 Marotti G, Farneti D, Remaggi F, Tartari F. Morphometric investigation on osteocytes in human auditory ossicles. Ann Anat 1998; 180 (05) 449-453.
  • 51 Palumbo C, Cavani F, Sena P. et al. Osteocyte apoptosis and absence of bone remodeling in human auditory ossicles and scleral ossicles of lower vertebrates: a mere coincidence or linked processes?. Calcif Tissue Internat 2012; 90 (03) 211-218.
  • 52 van Ginneken V, Antonissen E, Muller UK. et al. Eel migration to the Sargasso: remarkably high swimming efficiency and low energy costs. J Exp Biol 2005; 208 (Pt 7): 1329-1335.
  • 53 Skedros JG. Osteocyte lacuna population densities in sheep, elk and horse calcanei. Cells Tissues Organs 2005; 181 (01) 23-37.
  • 54 Cao L, Moriishi T, Miyazaki T. et al. Comparative morphology of the osteocyte lacunocanalicular system in various vertebrates. J Bone Miner Metab 2011; 29 (06) 662-670.
  • 55 Bensimon-Brito A, Cardeira J, Cancela ML. et al. Distinct patterns of notochord mineralization in zebrafish coincide with the localization of Osteocalcin isoform 1 during early vertebral centra formation. BMC Dev Biol 2012; 12: 28.
  • 56 Arratia G, Schultze HP, Casciotta J. Vertebral column and associated elements in dipnoans and comparison with other fishes: development and homology. J Morphol 2001; 250 (02) 101-172.
  • 57 Lopez E, Mac IIntyre, Martelly E. et al. Paradoxical effect of 1,25 dihydroxycholecalciferol on osteoblastic and osteoclastic activity in the skeleton of the eel Anguilla anguilla L. Calcif Tissue Internat 1980; 32 (01) 83-87.
  • 58 Kacem A, Meunier FJ. Halastatic demineralization in the vertebrae of Atlantic salmon, during their spawning migration. J Fish Biol 2003; 63 (05) 1122-1130.
  • 59 Moss ML. Studies of the acellular bone of teleost fish. II. Response to fracture under normal and ac alcemic conditions. Acta Anat 1962; 48 (1–2): 46-60.