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Paschalis E.P.,Ludwig Boltzmann Research Institute | Mendelsohn R.,Rutgers University | Boskey A.L.,Musculoskeletal Integrity Program
Clinical Orthopaedics and Related Research | Year: 2011

Background: Bone strength depends on both bone quantity and quality. The former is routinely estimated in clinical settings through bone mineral density measurements but not the latter. Bone quality encompasses the structural and material properties of bone. Although its importance is appreciated, its contribution in determining bone strength has been difficult to precisely quantify partly because it is multifactorial and requires investigation of all bone hierarchical levels. Fourier transform infrared spectroscopy provides one way to explore these levels. Questions/purposes: The purposes of our review were to (1) provide a brief overview of Fourier transform infrared spectroscopy as a way to establish bone quality, (2) review the major bone material parameters determined from Fourier transform infrared spectroscopy, and (3) review the role of Fourier transform infrared microspectroscopic analysis in establishing bone quality. Methods: We used the ISI Web of Knowledge database initially to identify articles containing the Boolean term "infrared" AND "bone." We then focused on articles on infrared spectroscopy in bone-related journals. Results: Infrared spectroscopy provides information on bone material properties. Their microspectroscopic versions allow one to establish these properties as a function of anatomic location, mineralization extent, and bone metabolic activity. It provides answers pertaining to the contribution of mineral to matrix ratio, mineral maturity, mineral carbonate substitution, and collagen crosslinks to bone strength. Alterations of bone material properties have been identified in disease (especially osteoporosis) not attainable by other techniques. Conclusions: Infrared spectroscopic analysis is a powerful tool for establishing the important material properties contributing to bone strength and thus has helped better understand changes in fragile bone. © 2011 The Association of Bone and Joint Surgeons®. Source


Boskey A.L.,Musculoskeletal Integrity Program | Villarreal-Ramirez E.,National Autonomous University of Mexico
Matrix Biology | Year: 2016

In vertebrates and invertebrates, biomineralization is controlled by the cell and the proteins they produce. A large number of these proteins are intrinsically disordered, gaining some secondary structure when they interact with their binding partners. These partners include the component ions of the mineral being deposited, the crystals themselves, the template on which the initial crystals form, and other intrinsically disordered proteins and peptides. This review speculates why intrinsically disordered proteins are so important for biomineralization, providing illustrations from the SIBLING (small integrin binding N-glycosylated) proteins and their peptides. It is concluded that the flexible structure, and the ability of the intrinsically disordered proteins to bind to a multitude of surfaces is crucial, but details on the precise-interactions, energetics and kinetics of binding remain to be determined. © 2016 International Society of Matrix Biology. Source


Burket J.C.,Cornell University | Brooks D.J.,Cornell University | MacLeay J.M.,Colorado State University | Baker S.P.,Cornell University | And 3 more authors.
Bone | Year: 2013

Osteoporosis and treatment may affect both composition and nanomechanical properties and their spatial distributions within the individual trabeculae of cancellous bone at length scales that cannot be captured by bulk measurements. This study utilized 25 mature adult ewes divided into 5 treatment groups. Four treatment groups were given a dietary model for human high-turnover osteoporosis, and two of these were treated with antiresorptive drugs, either zoledronate (ZOL) or raloxifene (RAL), to examine their effects on bulk tissue properties and nanoscale tissue composition and mechanical properties within trabeculae. Treatment effects were most pronounced at the nanoscale, where RAL increased indentation modulus and hardness throughout trabeculae by 10% relative to the osteoporosis model. In comparison, ZOL increased these properties exclusively at the surfaces of trabeculae (indentation modulus +. 12%, hardness +. 16%). Nanomechanical alterations correlated with changes in tissue mineralization, carbonate substitution, crystallinity, and aligned collagen. Despite only minimal changes in bulk tissue tBMD, the nanomechanical improvements within trabeculae with both treatments greatly improved the predicted theoretical bending stiffness of individual trabeculae when idealized as cylindrical struts. Hence, small tissue-level alterations in critical locations for resisting trabecular failure could account for some of the discrepancy between the large reductions in fracture risk and the only modest changes in BMD with antiresorptive treatments. © 2012 Elsevier Inc. Source


Donnelly E.,Cornell University | Chen D.X.,Cornell University | Boskey A.L.,Musculoskeletal Integrity Program | Boskey A.L.,Cornell University | And 2 more authors.
Calcified Tissue International | Year: 2010

Bone geometry and tissue material properties jointly govern whole-bone structural behavior. While the role of geometry in structural behavior is well characterized, the contribution of the tissue material properties is less clear, partially due to the multiple tissue constituents and hierarchical levels at which these properties can be characterized. Our objective was to elucidate the contribution of the mineral phase to bone mechanical properties across multiple length scales, from the tissue material level to the structural level. Vitamin D and calcium deficiency in 6-week-old male rats was employed as a model of reduced mineral content with minimal collagen changes. The structural properties of the humeri were measured in three-point bending and related to the mineral content and geometry from microcomputed tomography. Whole-cortex and local bone tissue properties were examined with infrared (IR) spectroscopy, Raman spectroscopy, and nanoindentation to understand the role of altered mineral content on the constituent material behavior. Structural stiffness (-47%) and strength (-50%) were reduced in vitamin D-deficient (-D) humeri relative to controls. Moment of inertia (-38%), tissue mineral density (TMD, -9%), periosteal mineralization (-28%), and IR mineral:matrix ratio (-19%) were reduced in -D cortices. Thus, both decreased tissue mineral content and changes in cortical geometry contributed to impaired skeletal load-bearing function. In fact, 97% of the variability in humeral strength was explained by moment of inertia, TMD, and IR mineral:matrix ratio. The strong relationships between structural properties and cortical material composition demonstrate a critical role of the microscale material behavior in skeletal load-bearing performance. © 2010 Springer Science+Business Media, LLC. Source


Roy R.,Cornell University | Boskey A.,Musculoskeletal Integrity Program | Bonassar L.J.,Cornell University
Journal of Biomedical Materials Research - Part A | Year: 2010

This study focuses on the development of a novel method of nonenzymatic glycation of fibrillar collagen gels. In contrast to previous studies in which type I collagen gels were glycated in the solid state, this study presents a method for glycation in solution. The type I collagen in solution or gels was exposed to a range of ribose concentrations from 0 to 250 mM. The binding of ribose to collagen was documented using Fourier transform infrared (FTIR) spectroscopy. formation of advanced glycation end products (AGEs) was quantified by fluorescence measurement. The bulk compressive modulus and viscoelastic time constant of processed gels were determined in stress relaxation studies. Both methods of glycation enhanced ribose addition and AGE formation in a dose-dependent manner, with glycation in the gel state being more efficient. Both methods enhanced mechanical properties similarly, with 250 mM ribose treatment resulting in a 10-fold increase in bulk modulus. © 2009 Wiley Periodicals, Inc. Source

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