Age-related changes in physicochemical properties of mineral crystals are related to impaired mechanical function of cortical bone.

The measures of bone mass and architecture need to be supplemented with physicochemical and compositional measures for better assessment of fracture risk. In the current studies, we investigated the effects of physicochemical properties of mineral crystals on tissue and organ-level mechanical function of aging rat cortical bone. Our hypothesis was that age-related changes in physicochemical properties of mineral crystals are related to impaired elastic deformability of cortical bone tissue. Raman microspectroscopy was used to investigate the age-related changes in mineralization (relative amounts of mineral and organic matrix), the substitution of carbonate ions in phosphate positions (type-B carbonate substitution) and mineral crystallinity (the orderliness of crystal lattice) of femurs from young adult (3-month old), middle-aged (8-month old) and aged (24-month old) female Sprague-Dawley rats. Cross-sectional properties, the area and the moment of inertia at the mid-diaphysis, were histomorphometrically quantified and the elastic deformation capacity of femurs was quantified via three-point bending tests. It was observed that the elastic deformation capacity of aged rats was significantly impaired both at the tissue and the organ levels with increasing age. In parallel with this impairment in the elastic deformability and in support of our hypothesis, we found that increasing mineralization, increasing crystallinity and increasing type-B carbonate substitution were significantly correlated with decreasing elastic deformation capacity with age. We conclude that the measure of bone mass needs to be supplemented with measures reflecting the physicochemical status of mineral crystals for improved assessment of fracture susceptibility.

[1]  T. Wilkin.  Changing perceptions in osteoporosis. , 1999 .

[2]  A. S. Posner,et al.  Infra-Red Determination of the Percentage of Crystallinity in Apatitic Calcium Phosphates , 1966, Nature.

[3]  Michael D. Morris,et al.  Chemical Microstructure of Cortical Bone Probed by Raman Transects , 1999 .

[4]  A. Boskey,et al.  FTIR Microspectroscopic Analysis of Normal Human Cortical and Trabecular Bone , 1997, Calcified Tissue International.

[5]  W. Walsh,et al.  Compressive properties of cortical bone: mineral-organic interfacial bonding. , 1994, Biomaterials.

[6]  D. Felsenberg,et al.  Comments on the Hypotheses Underlying Fracture Risk Assessment in Osteoporosis as Proposed by the World Health Organization , 1999, Calcified Tissue International.

[7]  M. Glimcher,et al.  X-ray diffraction studies of the crystallinity of bone mineral in newly synthesized and density fractionated bone , 2006, Calcified Tissue International.

[8]  O. Akkus,et al.  Aging of Microstructural Compartments in Human Compact Bone , 2003, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[9]  H J Donahue,et al.  Aged bone displays an increased responsiveness to low-intensity resistance exercise. , 2001, Journal of applied physiology.

[10]  S. Goldstein,et al.  Targeted disruption of the biglycan gene leads to an osteoporosis-like phenotype in mice , 1998, Nature Genetics.

[11]  C. Rey,et al.  MicroRaman Spectral Study of the PO4 and CO3 Vibrational Modes in Synthetic and Biological Apatites , 1998, Calcified Tissue International.

[12]  C. M. Agrawal,et al.  Age-related changes in the collagen network and toughness of bone. , 2002, Bone.

[13]  R. Martin,et al.  Studies of skeletal remodeling in aging men. , 1980, Clinical orthopaedics and related research.

[14]  Glimcher Mj.  The nature of the mineral component of bone and the mechanism of calcification. , 1987 .

[15]  R. L. Cain,et al.  Changes in Geometry and Cortical Porosity in Adult, Ovary-Intact Rabbits after 5 Months Treatment with LY333334 (hPTH 1-34) , 2000, Calcified Tissue International.

[16]  J. J. Freeman,et al.  Raman Spectroscopic Detection of Changes in Bioapatite in Mouse Femora as a Function of Age and In Vitro Fluoride Treatment , 2001, Calcified Tissue International.

[17]  H. Wahner,et al.  Updated Data on Proximal Femur Bone Mineral Levels of US Adults , 1998, Osteoporosis International.

[18]  H. Genant,et al.  Models of spinal trabecular bone loss as determined by quantitative computed tomography , 1989, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[19]  J A McGeough,et al.  Age-Related Changes in the Compressive Strength of Cancellous Bone. The Relative Importance of Changes in Density and Trabecular Architecture* , 1997, The Journal of bone and joint surgery. American volume.

[20]  Ontogenetic changes in the mechanical properties of the femur of the polar bear Ursus maritimus , 1990 .

[21]  P Zioupos,et al.  The effects of ageing and changes in mineral content in degrading the toughness of human femora. , 1997, Journal of biomechanics.

[22]  D. Felsenberg,et al.  Discriminability of fracture and nonfracture cases based on the spatial distribution of spinal bone mineral. , 1997, Journal of computer assisted tomography.

[23]  D. Carrier,et al.  Skeletal growth and function in the California gull (Larus californicus) , 1990 .

[24]  A. Boskey,et al.  FTIR microspectroscopic analysis of human osteonal bone , 1996, Calcified Tissue International.

[25]  R. Cook.  Detection of influential observation in linear regression , 2000 .

[26]  W. Sontag.  Quantitative measurements of periosteal and cortical-endosteal bone formation and resorption in the midshaft of male rat femur. , 1986, Bone.

[27]  J A McGeough,et al.  Age-related changes in the tensile properties of cortical bone. The relative importance of changes in porosity, mineralization, and microstructure. , 1993, The Journal of bone and joint surgery. American volume.

[28]  A. Boskey,et al.  Osteopontin-hydroxyapatite interactions in vitro: inhibition of hydroxyapatite formation and growth in a gelatin-gel. , 1993, Bone and mineral.

[29]  A. Boskey.  Variations in bone mineral properties with age and disease. , 2002, Journal of musculoskeletal & neuronal interactions.

[30]  A. Bailey,et al.  Age-Related Changes in the Biochemical Properties of Human Cancellous Bone Collagen: Relationship to Bone Strength , 1999, Calcified Tissue International.

[31]  Handschin Rg,et al.  Crystallographic and chemical analysis of human bone apatite (Crista Iliaca). , 1994 .

[32]  S. Stover,et al.  Calcium buffering is required to maintain bone stiffness in saline solution. , 1996, Journal of biomechanics.

[33]  J. Koenig,et al.  Raman scattering of collagen, gelatin, and elastin , 1975, Biopolymers.

[34]  S. Cummings.  Are patients with hip fractures more osteoporotic? Review of the evidence. , 1985, The American journal of medicine.

[35]  O. Johnell,et al.  Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures , 1996 .

[36]  W. Kalender,et al.  Global and regional variations in the spinal trabecular bone: single and dual energy examinations. , 1991, The Journal of clinical endocrinology and metabolism.

[37]  F. Severcan,et al.  A biomechanical and spectroscopic study of bone from rats with selenium deficiency and toxicity , 1998, Biometals.

[38]  Douglas C. Montgomery,et al.  Applied Statistics and Probability for Engineers, Third edition , 1994 .

[39]  A. Boskey,et al.  The effects of noncollagenous matrix proteins on hydroxyapatite formation and proliferation in a collagen gel system. , 1989, Connective tissue research.

[40]  W. B. Stern,et al.  Crystallographic lattice refinement of human bone , 1992, Calcified Tissue International.

[41]  C. Rimnac,et al.  Effect of abnormal mineralization on the mechanical behavior of X-linked hypophosphatemic mice femora. , 1995, Bone.

[42]  C. Rimnac,et al.  A physical, chemical, and mechanical study of lumbar vertebrae from normal, ovariectomized, and nandrolone decanoate-treated cynomolgus monkeys (Macaca fascicularis). , 2000, Bone.

[43]  G. Daculsi,et al.  Ultrastructural Properties of Bone Mineral of Control and Tiludronate-Treated Osteoporotic Rat , 2000, Calcified Tissue International.

[44]  G. Rodan,et al.  Type beta transforming growth factor regulates expression of genes encoding bone matrix proteins. , 1989, Connective tissue research.

[45]  W. Walsh,et al.  The role of ions and mineral-organic interfacial bonding on the compressive properties of cortical bone. , 1993, Bio-medical materials and engineering.

[46]  J. Currey,et al.  The effects of strain rate, reconstruction and mineral content on some mechanical properties of bovine bone. , 1975, Journal of biomechanics.

[47]  P Zioupos,et al.  The role of collagen in the declining mechanical properties of aging human cortical bone. , 1999, Journal of biomedical materials research.

[48]  C H Turner,et al.  Basic biomechanical measurements of bone: a tutorial. , 1993, Bone.

[49]  A Hofman,et al.  Bone density and risk of hip fracture in men and women: cross sectional analysis , 1997, BMJ.

[50]  Ming Ding,et al.  Age variations in the properties of human tibial trabecular bone. , 1997, The Journal of bone and joint surgery. British volume.

[51]  A. S. Posner,et al.  Infrared Analysis of Rat Bone: Age Dependency of Amorphous and Crystalline Mineral Fractions , 1966, Science.

[52]  M. Morris,et al.  Application of vibrational spectroscopy to the study of mineralized tissues (review). , 2000, Journal of biomedical optics.

[53]  M. J. Silva,et al.  In vitro sodium fluoride exposure decreases torsional and bending strength and increases ductility of mouse femora. , 2000, Journal of biomechanics.

[54]  J. Fox,et al.  Relationships Among Carbonated Apatite Solubility, Crystallite Size, and Microstrain Parameters , 1999, Calcified Tissue International.

[55]  T J Wilkin,et al.  Bone densitometry is not a good predictor of hip fracture. , 2001, BMJ : British Medical Journal.

[56]  T. Tait,et al.  A clinical and biochemical assessment of methotrexate in rheumatoid arthritis , 1994, Clinical Rheumatology.

[57]  C C Glueer,et al.  Quantitative computed tomography in assessment of osteoporosis. , 1987, Seminars in nuclear medicine.

[58]  S A Goldstein,et al.  Biomechanics of Fracture: Is Bone Mineral Density Sufficient to Assess Risk? , 2000, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[59]  Toru Hirano,et al.  Anabolic Effects of Human Biosynthetic Parathyroid Hormone Fragment (1–34), LY333334, on Remodeling and Mechanical Properties of Cortical Bone in Rabbits , 1999, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.