JBiSE  Vol.7 No.9 , July 2014
Bone Mineral “Quality”: Differing Characteristics of Calcified Microsphere Populations at the Osteoporotic and Osteoarthritic Femoral Articulation Front
Abstract: The mineral front consists of large populations of organically enshrouded calcified microspheres (filamentous clusters) about 1 micron in diameter and associated smaller numbers of variably dense nanospheres, 30 - 40 nm in diameter. The discrete objects persist and modulate in maturity, and may constitute a variable “qualitative” factor in the skeletal inorganic phase, exemplified by the biomechanically contrasting pathologies of osteoporosis (OP; fracture, low stress condition) and osteoarthritis (OA; non fracture, high stress condition). The aim was to compare the articulation front material for morphological and trace element diversity using fresh female femoral head discards (from Dewsbury District Hospital NHS Mid-Yorkshire Trust). These were prepared for histology of the cartilage/bone interface region by immersion in hydrazine hydrate to expose the anorganic mineral topography for microscopy and FEGSEM microanalysis. 1) Mineral microsphere morphology (compared to animals as arbitrary controls) suggested that calcified microspheres from OP (n = 19) tended to be small (0.5 - 0.7 microns), smooth and compacted; those from OA (n = 19) were large (0.5 - 4.0 microns), uneven and irregularly dispersed. Respective calcified nanospheres from OP were similarly smaller (30 - 50 nm) than those from OA (>100 nm). In subchondral bone a proportion of the filamentous microspheres had fused into a fine-textured phase in OP and a coarse-textured phase in OA. 2) Trace element analysis (compared to positive porcine Si and Mg and other peaks) suggested a diminution with mineral maturity, and also with age effecting OP and OA similarly, with minor differences detected between them. It was concluded that calcified objects constituting the inorganic phase vary regionally with age and in fracture and nonfracture, being diminished in size (not number) in weak OP and enlarged (compared to porcine control) in stronger OA, with Si or Mg “doping” diminishing with time, perhaps influencing their individual bioactivity and matrix dynamics.
Cite this paper: Linton, K. , Hordon, L. , Shore, R. and Aaron, J. (2014) Bone Mineral “Quality”: Differing Characteristics of Calcified Microsphere Populations at the Osteoporotic and Osteoarthritic Femoral Articulation Front. Journal of Biomedical Science and Engineering, 7, 739-755. doi: 10.4236/jbise.2014.79073.

[1]   Miller, L.M., Tetenbaum Novatt, J., Hamerman, D. and Carlson, C.S. (2004) Alterations in Mineral Composition Observed in Osteoarthritic Joints of Cynomolgus Monkeys. Bone, 35, 498-506.

[2]   Cooper, C., Cook, P.L., Osmond, C., Fisher, L. and Cawley. M.I.D. (1991) Osteoarthritis of the Hip and Osteoporosis of the Proximal Femur. Annals of the Rheumatic Diseases, 50, 540-542.

[3]   Hordon, L.D., Wright, V. and Smith, M.A. (1992) Bone Mass in Osteoarthritis. Annals of the Rheumatic Diseases, 51, 823-825.

[4]   Mattei, J.P. and Roux, H. (1999) New Potential Therapeutic Goals: Subchondral Bone and Progression of Osteoarthritis. Osteoarthritis Cartilage, 7, 329-330.

[5]   Bergink, A.P., Uitterlinden, A.G., van Leeuwen, J.P.T.M., Hofman, A., Verhaar, J.A.N. and Pols, H.A.P. (2005) Bone Mineral Density and Progressive Radiographic Knee Osteoarthritis in Elderly Men and Women: the Rotterdam Study. Bone, 37, 446-456.

[6]   Marcus, R. (1996) The Nature of Osteoporosis. The Journal of Clinical Endocrinology and Metabolism, 81, 1-5.

[7]   Aaron, J.E. (2003) Bone Turnover and Microdamage. Advances in Osteoporotic Fracture Management, 2, 102-110.

[8]   Loveridge, N., Power, J., Reeve, J. and Boyde, A. (2004) Bone Mineralization Density and Femoral Neck Fragility. Bone, 35, 929-941.

[9]   Dmitrovsky, E., Lane, L.B. and Bullough, P.G. (1978) The Characterization of the Tidemark in Human Articular Cartilage. Metabolic Bone Disease and Related Research, 1, 115-118.

[10]   Bullough, P.G. and Jagannath, A. (1983) The Morphology of the Calcification Front in Articular Cartilage. Journal of Bone and Joint Surgery, 65B, 72-78.

[11]   Burr, D.B. and Schaffler, M.B. (1997) The Involvement of Subchondral Mineralised Tissues in Osteoarthrosis: Quantitative Microscopic Evidence. Microscopy Research and Technique, 37, 343-357.<343::AID-JEMT9>3.0.CO;2-L

[12]   Kuettner, K.E. and Thonar, E.J.M.A. (1998) Cartilage Integrity and Homeostasis. In: Klippel, J.H. and Dieppe, P., Eds., Rheumatology, 2nd Edition, Mosby, St Louis, 8.6.1-8.6.18.

[13]   Boyde, A. (1980) Electron Microscopy of the Mineralizing Front. Metabolic Bone Disease and Related Research, 25, 69-78.

[14]   Carter, D.H., Hatton, P.V. and Aaron, J.E. (1997) The Ultrastructure of Slam-Frozen Bone Mineral. The Histochemical Journal, 29, 783-793.

[15]   Termine, J.D. and Posner, A.S. (1967) Amorphous/Crystalline Interrelationships in Bone Mineral. Calcified Tissue Research, 1, 8-23.

[16]   Eanes, E.D., Termine, J. and Posner, A. (1967) Amorphous Calcium Phosphate in Skeletal Tissues. Clinical Orthopaedics and Related Research, 53, 223-235.

[17]   Aaron, J.E. (1981) Alkaline Phosphatase, Vesicles and Calcification. Metabolic Bone Disease and Related Research, 25, 151-157.

[18]   Lester, K.S. and Ash Jr., M.M. (1980) Scanning Electron Microscopy of Mineralized Cartilage in Rat Mandibular Condyle. Journal of Ultrastructure Research, 72, 141-150.

[19]   Aaron, J.E., Oliver, B., Clarke, N. and Carter, D.H. (1999) Calcified Microspheres as Biological Entities and Their Isolation from Bone. The Histochemical Journal, 31, 455-470.

[20]   Carter, D.H., Scully, A.J., Davies, R.M. and Aaron, J.E. (1998) Evidence for Phosphoprotein Microspheres in Bone. The Histochemical Journal, 30, 677-686.

[21]   Carter, D.H., Scully, A.J., Heaton, D.A., Young, M.P. and Aaron, J.E. (2002) Effect of Deproteination on Bone Mineral Morphology: Implications for Biomaterials and Aging. Bone, 31, 389-395.

[22]   Clark, I. and Belanger, L. (1967) The Effects of Alterations in Dietary Magnesium on Calcium, Phosphate and Skeletal Metabolism. Calcified Tissue Research, 1, 204-218.

[23]   Linton, K.M., Tapping, C.R., Adams, D.G., Carter, D.H., Shore, R.C. and Aaron, J.E. (2013) A Silicon Cell Cycle in a Bacterial Model of Calcium Phosphate Mineralogenesis. Micron, 44, 419-432.

[24]   Ereiba, K.M.T., Mostafa, A.G., Gamal, G.A. and Said, A.H. (2013) In Vitro Study of Iron Doped Hydroxyapatite. Journal of Biophysical Chemistry, 4, 122-130.

[25]   Williams, R.J.P. (1978) Introduction. In: Williams, R.J.P. and Da Silva, J.R.R.F., Eds., New Trends in Bioinorganic Chemistry, Academic Press, London, 1-10.

[26]   Aaron, J.E. and Shore, P.A. (2004) Histomorphometry. In: Langton, C.M. and Njeh, C.F., Eds., The Physical Measurement of Bone, Institute of Physics Publishing, Bristol, 185-224.

[27]   Termine, J.D., Eanes, E.D., Greenfield, D.J., Nylen, M.U. and Harper, R.A. (1973) Hydrazine-Deproteinated Bone Mineral. Calcified Tissue Research, 12, 73-90.

[28]   Termine, J.D. (1972) Mineral Chemistry and Skeletal Biology. Clinical Orthopaedics and Related Research, 85, 207-241.

[29]   Carter, D.H., Scully, A.J., Hatton, P.V., Davies, R.M. and Aaron, J.E. (2000) Cryopreservation and Image Enhancement of Juvenile and Adult Dentine Mineral. Histochemical Journal, 32, 253-261.

[30]   Aaron, J.E., Shore, P.A., Itoda, M., Morrison, R.J.M., Hartopp, A., Hensor, E.M.A. and Hordon, L.D. (2014) Mapping Trabecular Disconnection “Hotspots” in Aged Spine and Hip. Submitted.

[31]   Li, B. and Aspden, R.M. (1997) Mechanical and Material Properties of the Subchondral Bone Plate from the Femoral Head of Patients with Osteoporosis or Osteoarthritis. Annals of the Rheumatic Diseases, 56, 247-254.

[32]   Matsui, H., Shimizu, M. and Tsuji, H. (1997) Cartilage and Subchondral Bone Interaction in Osteoarthrosis of Human Knee Joint: A Histological and Histomorphometric Study. Microscopy Research and Technique, 37, 333-342.<333::AID-JEMT8>3.0.CO;2-L

[33]   Boyd, S.K., Müller, R., Matyas, J.R., Wohl, G.R. and Zernicke, R.F. (2000) Early Morphometric and Anisotropic Change in Periarticular Cancellous Bone in a Model of Experimental Knee Osteoarthritis Quantified Using Microcomputed Tomography. Clinical Biomechanics, 15, 624-631.

[34]   Fazzalari, N.L., Darracott, J. and Vernon-Roberts, B. (1988) Histomorphometric Changes in the Trabecular Structure of a Selected Stress Region in the Femur in Patients with Osteoarthritis and Fracture of the Femoral Neck. Bone, 6, 125-133.

[35]   Oegema, T.R., Carpenter, R.J., Hofmeister, F. and Thompson Jr., R.C. (1997) The Interaction of the Zone of Calcified Cartilage and Subchondral Bone in Osteoarthritis. Microscopy Research and Technique, 37, 324-332.<324::AID-JEMT7>3.0.CO;2-K

[36]   Burr, D.B. (1998) The Importance of Subchondral Bone in Osteoarthrosis. Current Opinion in Rheumatology, 10, 256-262.

[37]   Lajeunesse, D., Hilal, G., Pelletier, J. and Martel-Pelletier, J. (1999) Subchondral Bone Morphological and Biochemical Alterations in Osteoarthritis. Osteoarthritis and Cartilage, 7, 321-322.

[38]   Macys, J.R., Bullough, P.G. and Wilson Jr., P.D. (1980) Coxarthrosis: A Study of the Natural History Based on a Correlation of Clinical, Radiographic and Pathological Findings. Seminars in Arthritis and Rheumatism, 10, 66-80.

[39]   Ho, A.M., Johnson, M.D. and Kingsley, D.M. (2000) Role of the Mouse ank Gene in Control of Tissue Calcification and Arthritis. Science, 289, 265-270.

[40]   Aaron, J.E. and Pautard, F.G. (1972) Ultrastructural Features of Phosphate in Developing Bone Cells. Israel Journal of Medical Sciences, 81, 625-629.

[41]   Pautard, F.G.E. (1966) A Biomolecular Survey of Calcification. In: Fleisch, H., Blackwood, J. and Owen, M., Eds., Calcified Tissues, Springer, Berlin, 108-118.

[42]   Pautard, F.G.E. (1981) Calcium Phosphate Microspheres in Biology. Progress in Crystal Growth and Characterization, 4, 89-98.

[43]   Little, K. (1973) Bone Behaviour. Academic Press, London.

[44]   Kashiwa, H.K. (1970) Mineralized Spherules in Cartilage of Bone Revealed by Cytochemical Methods. American Journal of Anatomy, 129, 459-465.

[45]   Koshihara, Y., Kawamura, M., Oda, H. and Higaki, S. (1987) In Vitro Calcification in Human Osteoblastic Cell Line Derived from Periosteum. Biochemical and Biophysical Research Communications, 145, 651-657.

[46]   Aaron, J.E. (1973) Osteocyte Types in the Developing Mouse Calvarium. Calcified Tissue Research, 12, 259-279.

[47]   Roach, H.I. (1997) New Aspects of Endochondral Ossification in the Chick: Chondrocyte Apoptosis, Bone Formation by Former Chondrocytes, and Acid Phosphatase Activity in the Endochondral Bone Matrix. Journal of Bone and Mineral Research, 12, 795-805.

[48]   Chang, Y.L., Stanford, C.M. and Keller, J.C. (2000) Calcium and Phosphate Supplementation Promotes Bone Cell Mineralization: Implications for Hydroxyapatite (HA)-Enhanced Bone Formation. Journal of Biomedical Materials Research, 52, 270-278.<270::AID-JBM5>3.0.CO;2-1

[49]   Kato, Y., Boskey, A., Spevak, L., Dallas, M., Hori, M. and Bonewald, L.F. (2001) Establishment of an Osteoid Preosteocyte-Like Cell MLO-A5 that Spontaneously Mineralizes in Culture. Journal of Bone and Mineral Research, 16, 1622-1633.

[50]   Barragan-Adjemian, C., Nicolella, D., Dusevich, V., Dallas, M.R., Eick, J.D. and Bonewald, L.F. (2006) Mechanism by Which MLO-A5 Late Osteoblasts/Early Osteocytes Mineralize in Culture: Similarities with Mineralization of Lamellar Bone. Calcified Tissue International, 79, 340-353.

[51]   Feng, J.Q., Ward, L.M., Liu, S., Lu, Y., Xie, Y., Yuan, B., Yu, X., Rauch, F., Davis, S.I., Zhang, S., Rios, H., Drezner, M.K., Quarles, L.D., Bonewald, L.F. and White, K.E. (2006) Loss of DMP1 Causes Rickets and Osteomalacia and Identifies a Role for Osteocytes in Mineral Metabolism. Nature Genetics, 38, 1310-1315.

[52]   Mahamid, J., Aichmeyer, B., Shimoni, E., Ziblat, R., Li, C., Siegel, S., Paris, O., Fratzl, P., Weiner, S. and Addadi, L. (2010) Mapping Amorphous Calcium Phosphate Transformation into Crystalline Mineral from the Cell to the Bone in Zebrafish Fin Rays. Proceedings of the National Academy of Sciences of the United States of America, 107, 6316-6321.

[53]   Aaron, J.E. and Pautard, F.G.E. (1978) A Cell Cycle in Bone Mineralization. In: Balls, M. and Billett, F.S., Eds., The Cell Cycle in Development and Differentiation, University Press, Cambridge, 325-330.

[54]   Fallon, V. (2006) The Fabrication of Mineral Particles by Bone Cells and Unicellular Organisms. Ph.D. Dissertation, University of Leeds, Leeds.

[55]   Fallon, V., Carter, D.H. and Aaron, J.E. (2014) Mineral Fabrication and Golgi Apparatus Activity in the Mouse Calvarium. Journal of Biomedical Science and Engineering, in press.

[56]   Carlisle, E. (1974) Silicon as an Essential Element. Federation Proceedings, 33, 1758-1766.

[57]   Birchall, J.D. (1978) Silicon in the Biosphere. In: Williams, R.J.P. and da Silva, J.R.R.F., Eds., New Trends in Bioinorganic Chemistry, Academic Press, London, 209-252.

[58]   Bernard, G.W. and Pease, D.C. (1969) An Electron Microscope Study of Initial Intramembranous Osteogenesis. American Journal of Anatomy, 125, 271-290.

[59]   Reffitt, D.M., Ogston, N., Jugdaohsingh, R., Cheung, H.F.J., Evans, B.A.J., Thompson, R.P.H., Powell, J.J. and Hampson, G.N. (2003) Orthosilicic Acid Stimulates Collagen Type I Synthesis and Osteoblastic Differentiation in Human Osteoblast-Like Cells in Vitro. Bone, 32, 127-135.

[60]   Jugdaohsingh, R., Tucker, K.L., Qiao, N., Cupples, A., Kiel, D.P. and Powell, J.J. (2004) Dietary Silicon Intake Is Positively Associated with Bone Mineral Density in Men and Premenopausal Women of the Framingham Offspring Cohort. Journal of Bone and Mineral Research, 19, 297-307.

[61]   McNaughton, S.A., Bolton-Smith, C., Mishra, G.D., Jugdaohsingh, R. and Powell, J.J. (2005) Dietary Silicon Intake in Postmenopausal Women. British Journal of Nutrition, 94, 813-817.

[62]   Powell, J.J., McNaughton, S.A., Jugdaohsingh, R., Anderson, S.H.C., Dear, J., Khot, F., Mowatt, L., Gleason, K.L., Sykes, M., Thompson, R.P.H., Bolton-Smith, C. and Hodson, M.J. (2005) A Provisional Database for the Silicon Content of Foods in the United Kingdom. British Journal of Nutrition, 94, 804-812.

[63]   Jugdaohsingh, R., Anderson, S.H.C., Tucker, K.L., Elliott, H., Kiel, D.P., Thompson, R.P.H. and Powell, J.J. (2002) Dietary Silicon Intake and Absorption. American Journal of Clinical Nutrition, 75, 887-893.

[64]   Linton, K.M. (2007) Calcium Phosphate Morphology in Bone and Bacteria. Ph.D. Dissertation. University of Leeds, Leeds.

[65]   Exley, C. (2012) Reflections upon a Recent Insight into the Mechanism of Formation of Hydroxyaluminosilicates and the Therapeutic Potential of Silicic Acid. Coordination Chemistry Reviews, 256, 82-88.

[66]   Olszta, M.J., Cheng, X., Jee, S.S., Kumar, R., Kim, Y.Y., Kaufman, M.J., Douglas, E.P. and Gower, L.B. (2007) Bone Structure and Formation: A New Perspective. Materials Science and Engineering: R: Reports, 58, 77-116.

[67]   Pautard, F.G.E. (1978) Phosphorous and Bone. In: Williams, R.J.P. and Da Silva, J.R.R.F., Eds., New Trends in Bio-Inorganic Chemistry, Academic Press, London, New York, San Fransisco, 261-354.