Elsevier

Bone

Volume 31, Issue 1, July 2002, Pages 1-7
Bone

Original article
Age-related changes in the collagen network and toughness of bone

https://doi.org/10.1016/S8756-3282(01)00697-4Get rights and content

Abstract

The hypothesis of this study is that the mechanical integrity of the collagen network in bone deteriorates with age, and such adverse changes correlate with the decreased toughness of aged bone. To test the hypothesis, 30 human cadaveric femurs from donors ranging from 19 to 89 years of age were tested to determine the age-related changes in the mechanical properties of demineralized bone and fresh bone samples. Along with bone porosity, bone density, and weight fractions of the mineral and organic phases, collagen denaturation and concentrations of collagen cross-links (HP, hydroxylysylpyridinoline; LP, lysylpyridinoline; PE, pentosidine) were determined for these bone specimens as a function age. Analysis of variance (ANOVA) showed that age-dependent changes were reflected in the decreased strength, work to fracture, and fracture toughness of bone; in the decreased strength, elastic modulus, and work to fracture of the collagen network; as well as in the increased concentration of pentosidine (a marker of nonenzymatic glycation) and increased bone porosity. Regression analyses of the measured parameters showed that the age-related decrease in work to fracture of bone (especially its postyield portion) correlated significantly with deterioration in the mechanical integrity of the collagen network. The results of this study indicate that the adverse changes in the collagen network occur as people age and such changes may lead to the decreased toughness of bone. Also, the results suggest that nonenzymatic glycation may be an important contributing factor causing changes in collagen and, consequently, leading to the age-related deterioration of bone quality.

Introduction

Over the years, loss of bone mineral or bone mass has been considered the major cause of age-related bone fractures.36, 38 However, the large overlap in bone density that exists between healthy individuals and patients who sustain bone fractures suggests that low bone density is not the only reason for the weakening of bone.37 A recent study reported that the risk of bone fracture for older women (average 75 years old) is about 7%, whereas such a risk is only 1% for much younger individuals (average 45 years old), although they have a similar bone density level.23 In addition, it has been found that, although elderly black Gambian women also experience loss of bone mass, they rarely suffer osteoporotic bone fractures as compared with their white counterparts.2

Bone is a natural composite comprising mineral (mainly hydroxyapatite), organic (mostly type I collagen), and water phases.25, 28 Thus, the biomechanical properties of bone are dependent on the quality and spatial arrangement of these constituents.35 Recent studies have shown that the mineral predominantly contributes to bone stiffness,42, 43 whereas the quality of collagen matrix may predominantly determine the toughness of bone.10, 12, 15, 47, 49 In addition, it was found that osteoporosis is not just a simple loss of bone mass, but involves significant changes in the biochemical and physical properties of the collagen network.27 Thus far, only a few studies on the age-related changes in collagen and their correlation with the toughness of bone have been reported in the literature.47, 49 Although these studies have demonstrated the involvement of collagen in age-related changes in bone quality, the underlying mechanisms are still not clear.

The hypothesis of this study is that the mechanical integrity of the collagen network in human bone deteriorates with age, and such adverse changes correlate with the decreased toughness of aged bone. To test this hypothesis, we examined age-related changes in collagen molecular structures, the mechanical integrity of the collagen network, and the mechanical properties of bone. Finally, we attempted to explore the correlation of age-related changes in the collagen network with the toughness of bone.

Section snippets

Materials and methods

Thirty fresh frozen human cadaveric femurs were acquired from the Musculoskeletal Transplant Foundation (Edison, NJ) and a local tissue bank, ranging between 19 and 89 years of age. All samples were screened carefully to avoid the influence of any bone-related pathologies. These samples were divided into three age groups: young adults (19–49 years old); middle-aged (50–69 years old); and elderly (>70 years old). Each group included ten samples (n = 10). Eight men and two women were included in

Results

ANOVA analyses indicated that age had significant effects on the mechanical integrity of bone (Table 1). Although neither the ultimate nor yield strength (σs and σy) of bone showed any significant difference for the young and middle-aged groups, they decreased significantly for the elderly group. In contrast, aging exhibited little effect on the elastic modulus (E) of bone. The work to fracture (Wf) of bone decreased with increasing age. Interestingly, it was observed that the resilience of

Discussion

To test the hypothesis that the mechanical integrity of the collagen network in bone deteriorates with age, and such changes correlate with the age-related decrease in the toughness of bone, we measured the mechanical properties of the demineralized bone and bone samples (n = 30) acquired from a broad range of ages (19–89 years), and determined their compositional and microstructural characteristics. The experimental results of this study indicate that the mechanical integrity of the collagen

Acknowledgements

This study was supported by grants from the Whitaker Foundation (RG-99-0440), NIAMS/NIH (R03 AR46428), and the San Antonio Area Foundation.

References (49)

  • M.B. Schaffler et al.

    Stiffness of compact boneEffects of porosity and density

    J Biomech

    (1988)
  • K. Singer et al.

    Prediction of thoracic and lumbar vertebral body compressive strengthCorrelations with bone mineral density and vertebral region

    Bone

    (1995)
  • M. Takahashi et al.

    Direct measurement of crosslinks, pyridinoline, deoxypyridinoline, and pentosidine, in the hydrolysate of tissues using high-performance liquid chromatography

    Anal Biochem

    (1995)
  • D. Vashishth et al.

    Crack growth resistance in cortical boneConcept of microcrack toughening

    J Biomech

    (1997)
  • D. Vashishth et al.

    Influence of nonenzymatic glycation on biomechanical properties of cortical bone

    Bone

    (2001)
  • S. Weiner et al.

    Rotated plywood structure of primary lamellar bone in the ratOrientations of the collagen fibril arrays

    Bone

    (1997)
  • A. Alho et al.

    Bone mineral content and mechanical strength. An ex vivo study on human femora at autopsy

    Clin Orthop

    (1988)
  • T.J. Aspray et al.

    Low bone mineral content is common but osteoporotic fractures are rare in elderly rural Gambian women

    J Bone Miner Res

    (1996)
  • ASTM Standard and D790-86. Standard Test Methods for Flexural Properties of Unreinforced and Reinforced Plastics and...
  • ASTM Standard and E399-90. Standard Test Method for Plane Strain Fracture Toughness of Metallic Materials....
  • A.J. Bailey et al.

    Age-related changes in the biochemical properties of human cancellous bone collagenRelationship to bone strength

    Calcif Tissue Int

    (1999)
  • A.J. Bailey et al.

    Biochemical changes in the collagen of human osteoporotic bone matrix

    Connect Tissue Res

    (1993)
  • R.A. Bank et al.

    Ageing and zonal variation in post-translational modification of collagen in normal human articular cartilage. The age-related increase in non-enzymatic glycation affects biomechanical properties of cartilage

    Biochem J

    (1998)
  • A.L. Boskey et al.

    Collagen and bone strength

    J Bone Miner Res

    (1999)
  • Cited by (0)

    View full text