COLLAGEN CROSS-LINKS AND BONE STRENGTH
1627
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Limitations and strengths of the study
The main limitation of this study is the relatively small
number of subjects used to collect the samples (n ϭ 9). We
increased the number of samples by coring and analyzing
eight samples in each spine. Consequently, the validity of
the regression analysis on the overall number of cylinders
(n ϭ 63) is reduced by the repeated nature of the data.
Conclusions from such regressions have to be limited to the
relationship between the nature of a given cylinder (density
and biochemical composition of the matrix) and its own
mechanical behavior. After reduction of the data to a single
mean value for a given subject (using n ϭ 9), the correlation
also was significant but the regression with two predictors
on such a small number of values is questionable.
However, our study was strong in that we carried out all
the measurements on human vertebral cancellous bone. The
use of human material from an anatomical site that has the
highest risk of fracture with aging certainly is important if
we ultimately are to draw clinically relevant conclusions.
This is much more difficult with animal models. The bio-
chemical and mechanical analyses were performed on the
same samples. Our sampling strategy was rigorous and
proved its sensitivity to the within-subject variations in the
structure or density.(25) The end-cap technique was used for
measurement of properties of vertebral cancellous bone
because it was designed specially to eliminate end artifacts
thus allowing a precise measurement of the stiffness.(24)
In this study, we improved the prediction of the biome-
chanical properties of vertebral cancellous bone by combin-
ing pQCT (density) data and direct collagen cross-link
assessment. Because both density measurements and pyr-
idinoline levels (HP/LP in urine) are accessible in clinical
practice, our observations open an interesting way of
progress in the prediction of fracture risk.
15. Knott L, Whitehead CC, Fleming RH, Bailey AJ 1995 Bio-
chemical changes in the collagenous matrix of osteoporotic
avian bone. Biochem J 310:1045–1051.
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CR 1993 Impaired mechanical strength of bone in experimen-
tal copper deficiency. Ann Nutr Metab 37:245–252.
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of mature crosslinking in bone matrix collagen of rabbit com-
pact bone: Corresponding variation of sonic velocity and equa-
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Howell DS, Boskey AL 1996 Pyridoxine deficiency affects
biomechanical properties of chick tibial bone. Bone 18:567–
574.
19. Oxlund H, Barckman M, Ortoft G, Andreassen TT 1995 Re-
duced concentrations of collagen cross-links are associated
with reduced strength of bone. Bone 17(Suppl 4):365S–371S.
20. Bailey AJ, Sims TJ, Ebbesen EN, Mansell JP, Thomsen JS,
Mosekilde L 1999 Age-related changes in the biochemical
properties of human cancellous bone collagen: Relationship to
bone strength. Calcif Tissue Int 65:203–210.
ACKNOWLEDGMENTS
This work was supported by the National Funds for
Scientific Research (FNRS, Belgium).
21. Bailey AJ, Wotton SF, Sims TJ, Thompson PW 1992 Post-
translational modifications in the collagen of human osteopo-
rotic femoral head. Biochem Biophys Res Commun 185:801–
805.
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