Osteologie 2016; 25(02): 92-100
DOI: 10.1055/s-0037-1619004
Osteocyte: Morphology & Function
Schattauer GmbH

Osteocyte size, shape, orientation, and population density

Scaling relationships, interpretation of load history, and mechanical consequencesGröße, Form, Orientierung und Zelldichte von OsteozytenSkalierungsbeziehung, Interpretation der Belastungsart und mechanische Konsequenzen
J. G. Skedros
1   University of Utah Department of Orthopaedic Surgery and Department of Veterans Affairs Medical Center, Salt Lake City, Utah, U.S.A.
,
D. J. Weaver
1   University of Utah Department of Orthopaedic Surgery and Department of Veterans Affairs Medical Center, Salt Lake City, Utah, U.S.A.
,
M. S. Doutré
1   University of Utah Department of Orthopaedic Surgery and Department of Veterans Affairs Medical Center, Salt Lake City, Utah, U.S.A.
› Author Affiliations
Further Information

Publication History

received: 23 February 2016

accepted after revision: 31 March 2016

Publication Date:
22 December 2017 (online)

Summary

Despite being encased in lacunae, osteocytes are extensively interconnected and have several mechanisms that enable them to physically and chemically appraise their environment and adjust to it. In the perspective that cell-cell and cell-matrix interactions mediate these functions and are critically important during the formation of a mechanically competent bone organ, we focus on several considerations: (1) osteocyte lacunae are not always occupied by living cells and the percent lacuna vacancy can increase with aging, some diseases, and experimental perturbations, (2) the potential for the population density and/or sizes and shapes of osteocytes (or of their lacunae) and of their cell processes (typically seen as the canaliculi in which they reside) in helping investigators interpret the load history of a bone or bone region, and (3) scaling relationships between osteocyte density and various parameters, including animal mass and metabolism. We also point out that all of these considerations are being impacted by high-resolution three-dimensional imaging technologies that allow increased accuracy when quantifying details of lacunar-canalicular geometries.

Zusammenfassung

Auch wenn sie in Lakunen eingebettet sind, sind Osteozyten umfangreich verschaltet und verfügen über eine Vielzahl von Mechanismen, die es ihnen ermöglicht, ihre Umgebung in physikalischer und chemischer Hinsicht zu erkunden und sich den Gegebenheiten anzupassen. Unter dem Blickwinkel betrachtet, dass diese Funktionen über Zell-Zell- und Zell-Matrix-Interaktionen vermittelt werden und von besonderer Bedeutung für die Bildung eines mechanisch kompetenten Knochens sind, konzentrieren wir uns auf verschiedene Betrachtungen: (1) Nicht alle Osteozytenlakunen sind von Osteozyten besiedelt und der Anteil leerer Lakunen kann im Alter sowie durch Krankheit und experimentelle Pertubationen zunehmen, (2) das Potenzial für die Zelldichte und/oder Größe und Form der Osteozyten (oder ihrer Lakunen) und ihrer Zellprozesse (typischerweise als Kanalikuli betrachtet), die den Forschern dabei helfen, die Belastungsart eines Knochens und einer Knochenregion zu interpretieren, und (3) die Skalierungsbeziehung zwischen der Osteozytendichte und verschiedenen Parametern, einschließlich Tiergewicht und Stoffwechsel. Wir zeigen außerdem auf, dass alle diese Betrachtungen durch hochauflösende 3D-Bildgebungsverfahren beeinflusst werden, da diese eine höhere Genauigkeit bei der Quantifizierung von Einzelheiten der lakuno-kanalikunären Geometrie erlauben.

 
  • References

  • 1 Kerschnitzki M, Wagermaier W, Roschger P. et al. The organization of the osteocyte network mirrors the extracellular matrix orientation in bone. J Struct Biol 2011; 173 (02) 303-311.
  • 2 Schneider P, Meier M, Wepf R, Muller R. Towards quantitative 3D imaging of the osteocyte lacuno-canalicular network. Bone 2010; 47 (05) 848-858.
  • 3 Turner CH, Robling AG, Duncan RL, Burr DB. Do bone cells behave like a neuronal network?. Calcif Tissue Int 2002; 70 (06) 435-442.
  • 4 Colopy SA, Benz-Dean J, Barrett JG. et al. Response of the osteocyte syncytium adjacent to and distant from linear microcracks during adaptation to cyclic fatigue loading. Bone 2004; 35: 881-891.
  • 5 Power J, Noble BS, Loveridge N. et al. Osteocyte lacunar occupancy in the femoral neck cortex: an association with cortical remodeling in hip fracture cases and controls. Calcif Tissue Int 2001; 69: 13-19.
  • 6 Qiu S, Rao DS, Palnitkar S, Parfitt AM. Reduced iliac cancellous osteocyte density in patients with osteoporotic vertebral fracture. J Bone Miner Res 2003; 18 (09) 1657-1663.
  • 7 Qiu S, Rao DS, Palnitkar S, Parfitt AM. Age and distance from the surface but not menopause reduce osteocyte density in human cancellous bone. Bone 2002; 31 (02) 313-318.
  • 8 Sambrook PN, Hughes DR, Nelson AE. et al. Osteocyte viability with glucocorticoid treatment: relation to histomorphometry. Ann Rheum Dis 2003; 62 (12) 1215-1217.
  • 9 Iwamoto J, Matsumoto H, Takeda T. et al. Effects of vitamin K2 on cortical and cancellous bone mass, cortical osteocyte and lacunar system, and porosity in sciatic neurectomized rats. Calcif Tissue Int 2010; 87 (03) 254-262.
  • 10 Skedros JG, Grunander TR, Hamrick MW. Spatial distribution of osteocyte lacunae in equine radii and third metacarpals: considerations for cellular communication, microdamage detection and metabolism. Cells, Tissues, Organs 2005; 180 (04) 215-236.
  • 11 Skedros JG. Osteocyte lacuna population densities in sheep, elk and horse calcanei. Cells Tissues Organs 2005; 181 (01) 23-37.
  • 12 Da Costa Gómez TM, Barrett JG, Sample SJ. et al. Up-regulation of site-specific remodeling without accumulation of microcracking and loss of osteocytes. Bone 2005; 37 (01) 16-24.
  • 13 Bloch SL, Kristensen SL, Sorensen MS. The viability of perilabyrinthine osteocytes: a quantitative study using bulk-stained undecalcified human temporal bones. Anat Rec (Hoboken) 2012; 295 (07) 1101-1108.
  • 14 Mullender MG, van der Meer DD, Huiskes R, Lips P. Osteocyte density changes in aging and osteoporosis. Bone 1996; 18: 109-113.
  • 15 Frost HM. In vivo osteocyte death. Am J Orthop 1960; 42-A: 138-143.
  • 16 Baud CA, Auil E. Osteocyte differential count in normal human alveolar bone. Acta Anat 1971; 78: 287-299.
  • 17 Wong SYP, Evans RA, Needs C. et al. The effect of age on bone composition and viability in the femoral head. J Bone and Joint Surg 1985; 67 (A) 274-283.
  • 18 Wong SYP, Evans RA, Needs C. et al. The pathogenesis of osteoarthritis of the hip. Clin Orthop Rel Res 1987; 214: 305-312.
  • 19 Mullender MG, Huiskes R, Versleyen H, Buma P. Osteocyte density and histomorphometric parameters in cancellous bone of the proximal femur in five mammalian species. J Orthop Res 1996; 14: 972-979.
  • 20 Vashishth D, Verborgt O, Divine G. et al. Decline in osteocyte lacunar density in human cortical bone is associated with accumulation of microcracks with age. Bone 2000; 26 (04) 375-380.
  • 21 Carter Y, Thomas CD, Clement JG, Cooper DM. Femoral osteocyte lacunar density, volume and morphology in women across the lifespan. J Struct Biol 2013; 183 (03) 519-526.
  • 22 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.
  • 23 Jast J, Jasiuk I. Age-related changes in the 3D hierarchical structure of rat tibia cortical bone characterized by high-resolution micro-CT. J Appl Physiol 2013; 114 (07) 923-933.
  • 24 Vashishth D, Koontz J, Fyhrie D. Age-dependence of osteocyte lacunar density is sexually dimorphic in human vertebral cancellous bone. 46th Annual Meeting of the Orthopaedic Research Society 2000; 702.
  • 25 McCreadie BR, Hollister SJ. Strain concentrations surrounding an ellipsoid model of lacunae and osteocytes. Comput Methods Biomech Biomed Engin 1997; 01 (01) 61-68.
  • 26 Bozal CB, Sanchez LM, Mandalunis PM, Ubios AM. Histomorphometric study and three-dimensional reconstruction of the osteocyte lacuno-canalicular network one hour after applying tensile and compressive forces. Cells Tissues Organs 2013; 197 (06) 474-483.
  • 27 Britz HM, Carter Y, Jokihaara J. et al. Prolonged unloading in growing rats reduces cortical osteocyte lacunar density and volume in the distal tibia. Bone 2012; 51 (05) 913-919.
  • 28 Sugawara Y, Kamioka H, Ishihara Y. et al. The early mouse 3D osteocyte network in the presence and absence of mechanical loading. Bone 2013; 52 (01) 189-196.
  • 29 Vatsa A, Breuls RG, Semeins CM. et al. Osteocyte morphology in fibula and calvaria – is there a role for mechanosensing?. Bone 2008; 43 (03) 452-458.
  • 30 van Oers RF, Wang H, Bacabac RG. Osteocyte shape and mechanical loading. Curr Osteoporos Rep 2015; 13 (02) 61-66.
  • 31 Martin RB. Fatigue microdamage as an essential element of bone mechanics and biology. Calcif Tissue Int 2003; 73 (02) 101-107.
  • 32 Skedros JG. Interpreting load history in limb-bone diaphyses: important considerations and their biomechanical foundations. In Crowder C, Stout S. editors Bone Histology: An Anthropological Perspective. Boca Raton, Florida, USA: CRC Press; 2012: 153-220.
  • 33 Britz HM, Thomas CD, Clement JG, Cooper DM. The relation of femoral osteon geometry to age, sex, height and weight. Bone 2009; 45 (01) 77-83.
  • 34 Skedros JG, Mason MW, Bloebaum RD. Modeling and remodeling in a developing artiodactyl calcaneus: a model for evaluating Frost’ s mechanostat hypothesis and its corollaries. Anat Rec 2001; 263: 167-185.
  • 35 Skedros JG, Su SC, Bloebaum RD. Biomechanical implications of mineral content and microstructural variations in cortical bone of horse, elk, and sheep calcanei. Anat Rec 1997; 249 (03) 297-316.
  • 36 Skedros JG, Keenan KE, Williams TJ, Kiser CJ. Secondary osteon size and collagen/lamellar organization (“osteon morphotypes”) are not coupled, but potentially adapt independently for local strain mode or magnitude. J Struct Biol 2013; 181 (02) 95-107.
  • 37 Judex S, Gross TS, Zernicke RF. Strain gradients correlate with sites of exercise-induced bone-forming surfaces in adult skeleton. J Bone Miner Res 1997; 12: 1737-1745.
  • 38 Marotti G, Canè V, Palazzini S, Palumbo C. Structure-function relationships in the osteocyte. Ital J Miner Electrolyte Metab 1990; 04: 93-106.
  • 39 Hobdell MH, Howe CE. Variation in bone matrix volume associated with osteocyte lucunae in mammalian and reptilian bone. Isr J Med Sci 1971; 07 (03) 492-493.
  • 40 Remaggi F, Canè V, Palumbo C, Ferretti M. Histomorphometric study on the osteocyte lacuno-canalicular network in animals of different species. I. Woven-fibered and parallel-fibered bones. Ital J Anat Embryol 1998; 103: 145-155.
  • 41 Ferretti M, Muglia MA, Remaggi F. et al. Histomorphometric study on the osteocyte lacuno-canalicular network in animals of different species. II. Parallel-fibered and lamellar bones. Ital J Anat Embryol 1999; 104: 121-131.
  • 42 Fyhrie DP, Kimura JH. NACOB presentation Keynote lecture. Cancellous bone biomechanics. North American Congress on Biomechanics. J Biomech 1999; 32: 1139-1148.
  • 43 Stein KW, Werner J. Preliminary analysis of osteocyte lacunar density in long bones of tetrapods: all measures are bigger in sauropod dinosaurs. PLoS One 2013; 08 (10) e77109.
  • 44 Cubo J, Roy NL, Martinez-Maza C, Montes L. Paleohistological estimation of bone growth rate in extinct archosaurs. Paleobiology 2012; 38: 335-349.
  • 45 Hernandez CJ, Majeska RJ, Schaffler MB. Osteocyte density in woven bone. Bone 2004; 35 (05) 1095-1099.
  • 46 Bromage TG, Lacruz RS, Hogg R. et al. Lamellar bone is an incremental tissue reconciling enamel rhythms, body size, and organismal life history. Calcif Tissue Int 2009; 84 (05) 388-404.
  • 47 Canè V, Marotti G, Volpi G. et al. Size and density of osteocyte lacunae in different regions of long bones. Calcif Tissue Int 1982; 34 (06) 558-563.
  • 48 D’Emic MD, Benson RB. Measurement, variation, and scaling of osteocyte lacunae: a case study in birds. Bone 2013; 57 (01) 300-310.
  • 49 Skedros JG, Hunt KJ, Hughes PE, Winet H. Ontogenetic and regional morphologic variations in the turkey ulna diaphysis: implications for functional adaptation of cortical bone. Anat Rec A Discov Mol Cell Evol Biol 2003; 273 (01) 609-629.
  • 50 Christen P, Ito K, van Rietbergen B. A potential mechanism for allometric trabecular bone scaling in terrestrial mammals. J Anat 2015; 226 (03) 236-243.
  • 51 Vashishth D, Gibson G, Kimura J. et al. Determination of bone volume by osteocyte population. Anat Rec 2002; 267 (04) 292-295.
  • 52 Bromage TG, Juwayeyi YM, Katris JA. et al. The scaling of human osteocyte lacuna density with body size and metabolism. Comptes Rendus Palevol 2016; 15: 33-40.
  • 53 Bigley RF, Gibeling JC, Stover SM. et al. Volume effects on yield strength of equine cortical bone. J Mech Behav Biomed Mater 2008; 01 (04) 295-302.
  • 54 Bigley RF, Gibeling JC, Stover SM. et al. Volume effects on fatigue life of equine cortical bone. J Biomech 2007; 40 (16) 3548-3554.
  • 55 Taylor D, O’Brien F, Prina-Mello A. et al. Compression data on bovine bone confirms that a “stressed volume” principle explains the variability of fatigue strength results. J Biomech 1999; 32 (11) 1199-1203.
  • 56 Martin RB. Fatigue damage, remodeling, and the minimization of skeletal weight. J Theor Biol 2003; 220 (02) 271-276.
  • 57 Taylor D. Scaling effects in the fatigue strength of bones from different animals. J Theor Biol 2000; 206: 299-306.
  • 58 Biewener AA. Biomechanics of mammalian terrestrial locomotion. Science 1990; 250 4984 1097-1103.
  • 59 Biewener AA. Biomechanical consequences of scaling. J Exp Biol 2005; 208 (Pt 9) 1665-1676.
  • 60 Cardoso L, Fritton SP, Gailani G. et al. Advances in assessment of bone porosity, permeability and interstitial fluid flow. J Biomech 2013; 46 (02) 253-265.
  • 61 Hannah KM, Thomas CD, Clement JG. et al. Bimodal distribution of osteocyte lacunar size in the human femoral cortex as revealed by micro-CT. Bone 2010; 47 (05) 866-871.
  • 62 Skedros JG, Grunander TR, Hamrick MW. Spatial distribution of osteocyte lacunae in equine radii and third metacarpals: considerations for cellular communication, microdamage detection and metabolism. Cells Tissues Organs 2005; 180 (04) 215-236.
  • 63 Dong P, Haupert S, Hesse B. et al. 3D osteocyte lacunar morphometric properties and distributions in human femoral cortical bone using synchrotron radiation micro-CT images. Bone 2014; 60: 172-185.
  • 64 Maggiano IS, Maggiano CM, Clement JG. et al. Three-dimensional reconstruction of Haversian systems in human cortical bone using synchrotron radiation-based micro-CT: morphology and quantification of branching and transverse connections across age. J Anat 2016; 228 (05) 719-732.
  • 65 Torres-Lagares D, Tulasne JF, Pouget C. et al. Structure and remodelling of the human parietal bone: an age and gender histomorphometric study. J Craniomaxillofac Surg 2010; 38 (05) 325-330.
  • 66 Qiu S, Rao DS, Palnitkar S, Parfitt AM. Differences in osteocyte and lacunar density between Black and White American women. Bone 2006; 38 (01) 130-135.
  • 67 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.
  • 68 Singh IJ, Tonna EA, Gandel CP. A comparative histological study of mammalian bone. J Morphol 1974; 144 (04) 421-437.
  • 69 Power J, Loveridge N, Rushton N. et al. Osteocyte density in aging subjects is enhanced in bone adjacent to remodeling Haversian systems. Bone 2002; 30 (06) 859-865.
  • 70 Qiu S, Rao DS, Palnitkar S, Parfitt AM. Relationships between osteocyte density and bone formation rate in human cancellous bone. Bone 2002; 31 (06) 709-711.
  • 71 Qiu S, Fyhrie DP, Palnitkar S, Rao DS. Histomorphometric assessment of Haversian canal and osteocyte lacunae in different-sized osteons in human rib. Anat Rec 2003; 272A (02) 520-525.
  • 72 Skedros JG, Hunt KJ, Bloebaum RD. Relationships of loading history and structural and material characteristics of bone: development of the mule deer calcaneus. J Morphol 2004; 259: 281-307.
  • 73 Vashishth D, Gibson GJ, Fyhrie DP. Sexual dimorphism and age dependence of osteocyte lacunar density for human vertebral cancellous bone. Anat Rec A Discov Mol Cell Evol Biol 2005; 282 (02) 157-162.
  • 74 Hedgecock NL, Hadi T, Chen AA. et al. Quantitative regional associations between remodeling, modeling, and osteocyte apoptosis and density in rabbit tibial midshafts. Bone 2007; 40 (03) 627-637.
  • 75 Skedros JG, Hunt KJ, Bloebaum RD. Erratum: Relationships of loading history and structural and material characteristics of bone: development of the mule deer calcaneus. J Morphol 2005; 265 (02) 244-247.
  • 76 Metz LN, Martin RB, Turner AS. Histomorphometric analysis of the effects of osteocyte density on osteonal morphology and remodeling. Bone 2003; 33 (05) 753-759.
  • 77 Carter Y, Suchorab JL, Thomas CD. et al. Normal variation in cortical osteocyte lacunar parameters in healthy young males. J Anat 2014; 225 (03) 328-336.
  • 78 Hesse B, Mannicke N, Pacureanu A. et al. Accessing osteocyte lacunar geometrical properties in human jaw bone on the submicron length scale using synchrotron radiation muCT. J Microsc 2014; 255 (03) 158-168.
  • 79 Carter Y, Thomas CD, Clement JG. et al. Variation in osteocyte lacunar morphology and density in the human femur – a synchrotron radiation micro-CT study. Bone 2013; 52 (01) 126-132.
  • 80 Bach-Gansmo FL, Weaver JC, Jensen MH. et al. Osteocyte lacunar properties in rat cortical bone: differences between lamellar and central bone. J Struct Biol 2015; 191 (01) 59-67.
  • 81 Karsdal MA, Andersen TA, Bonewald L, Christiansen C. Matrix metalloproteinases (MMPs) safeguard osteoblasts from apoptosis during transdifferentiation into osteocytes: MT1-MN maintains osteocyte viability. DNA Cell Biol 2004; 23 (03) 155-156.
  • 82 Erlebacher A, Filvaroff EH, Ye JQ, Derynck R. Osteoblastic responses to TGF-beta during bone remodeling. Mol Biol Cell 1998; 09 (07) 1903-1918.
  • 83 Bellido T, Plotkin LI, Bruzzaniti A. Bone cells. In Burr DB, Allen MR. editors Basic and applied bone biology. London: Academic Press/Elsevier; 2014: 27-45.