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an increased risk of fracture independent of other predictors of fracture, and also avoid some trabecular perforations. Prolongation of the secondary
including their rate of bone turnover.
mineralisation may lead to higher tissular mineralisation and, consequently,
improvement of the mechanical resistance of bone – i.e. higher stiffness.
Decrease in Biomechanical Markers of Bone Turnover Level Longer periods between metabolic cycles leave more time for the enzymatic
and Antifracture Efficacy of the Antiresorptive Treatment post-translational modifications of bone matrix proteins (described above),
which may increase the stiffness of bone. However, concomitant
Clinical Data nonenzymatic post-translational modifications of collagen, such as the
The association between changes in BMD induced by antiresorptive formation of advanced glycation end-products (pentosidine), may decrease
therapy and their antifracture efficacy is very weak.
Moreover, for any bone toughness – i.e. bone will break after absorption of lower energy.
change in BMD compared with baseline, fracture risk is lower in the treated
than in the placebo group.
These data show that BMD is a poor surrogate Association Between Biochemical Markers of
parameter of the antifracture efficacy of antiresorptive treatment. In Bone Turnover Measurement and Persistence with
contrast, a significant association was found between a decrease in BTM Antiresorptive Treatment
levels and antifracture efficacy during antiresorptive treatment.
Women Measurement of BTM levels may also influence the persistence with
who had the greatest decrease in BTM levels had the lowest fracture antiresorptive treatment using risedronate.
Women who received
incidence during treatment, whereas in women who had stable BTM positive information – >30% decrease in NTX-I urinary excretion – had a
fracture incidence was comparable to that in the placebo group.
lower risk of discontinuation of treatment (higher persistence);
Moreover, for a given decrease in BTM levels and for a given BTM level contrast, women who received negative information – >30% increase in
during treatment, fracture incidence was similar regardless of the group NTX-I urinary excretion – had a higher risk of discontinuation of
(active treatment or placebo).
Thus, rate of bone turnover and any treatment (lower persistence). Such an association was not found in
change of that rate may be important determinants of fracture risk. women who were not informed about the change in NTX-I level induced
by treatment. Thus, measurement of BTM does influence persistence
The association between the decrease in BTM levels and antifracture efficacy with antiresorptive treatment and is not merely a method of identifying
is stronger for spine than for non-spine fractures and for women with lower compliant and non-compliant patients. However, these data are only
baseline BMD versus those with higher BMD.
This observation is plausible preliminary and it has not been established how BTM measurements
because spine fractures and fractures in individuals with very low BMD should be used in the global clinical monitoring of patients receiving anti-
depend more on BMD and the rate of bone turnover. In contrast, non-spine osteoporotic treatment. These data are limited to women on
fractures and vertebral fractures in women with higher BMD may depend antiresorptive treatment. Data on the relationship between BTMs and the
more strongly on the frequency and intensity of traumas. fracture risk during teriparatide therapy are scarce and no such data are
available for strontium. In addition, data in men are scant.
Mechanisms of the Association Between the Decreases in
Bone Turnover and Fracture Incidence Induced by Conclusions
Antiresorptive Therapy Measurement of BTMs may improve the prevention of fragility fractures in
The pathophysiological mechanisms that underlie the association between post-menopausal and elderly women. From a pathophysiological point of
the inhibition of bone turnover and the antifracture efficacy of the view, the rate of bone turnover (spontaneous or modified by treatment)
antiresorptive therapy remain speculative. The inhibition of bone resorption seems to be a major determinant of bone fragility. From a clinical point of
reduces the creation of new resorptive cavities, which preserves the existing view, measurement of BTMs may improve the identification of post-
bone mass, reduces the formation of stress risers (sites of local weakening menopausal women at high risk of fracture. Moreover, if properly utilised,
of the trabeculae) and decreases the risk of perforation and loss of BTMs may improve persistence with antiresorptive treatment; however, data
trabeculae (especially in women with high bone turnover).
The are still limited. Finally, from the economic point of view, preliminary data
continuing bone formation in the pre-existing BMUs may also decrease the suggest that use of BTMs may improve the cost-effectiveness of anti-
number of stress risers, because osteoblasts fill up the resorptive cavities, osteoporotic treatment in women. ■
1. Dempster DW, American Society for Bone and Mineral Research, 11. Sambrook P, Chen C, March L, et al., J Bone Miner Res, 2002;17:826–33.
2006;7–11. 2006;21:549–55. 22. Delmas PD, Seeman E, Bone, 2004;34:599–604.
2. Garnero P, Delmas PD, Osteoporosis, Academic Press, 2001;2: 12. Delmas PD, Licata AA, Reginster JY, et al., Bone, 23. Sarkar S, Mitlak BH, Wong M, et al., J Bone Miner Res,
459–77. 2006;39:237–43. 2002;17:1–10.
3. Garnero P, Hausher E, Chapuy MC, et al., J Bone Miner Res, 13. Schousboe JT, Bauer DC, Nyman JA, et al., Osteoporos Int, 24. Bauer DC, Black DM, Garnero P, et al., J Bone Miner Res,
1996;11:1531–8. 2007;18:201–10. 2004;19:1250–58.
4. Garnero P, Sornay-Rendu E, Claustrat B, Delmas PD, J Bone 14. Garnero P, Sornay-Rendu E, Chapuy MC, Delmas PD, J Bone 25. Reginster JY, Sarkar S, Zegels B, et al., Bone, 2004;34:344–51.
Miner Res, 2000;15:1526–36. Miner Res, 1996;11:337–49. 26. Eastell R, Barton I, Hannon RA, et al., J Bone Miner Res,
5. Chapurlat RD, Garnero P, Bréart G, et al., Bone, 2000;27: 15. Borah B, Dufresne TE, Chmielewski PA, et al., Bone, 2003;18:1051–6.
283–6. 2004;34:736–46. 27. Bjarnasson NH, Sarkar S, Duong T, et al., Osteoporos Int,
6. Gerdhem P, Ivaska KK, Alatalo SL, et al., J Bone Miner Res, 16. Garnero P, Sornay-Rendu E, Duboeuf F, Delmas PD, J Bone 2001;12:922–30.
2004;19:386–93. Miner Res, 1999;14:1614–21. 28. Recker R, Masarachia P, Santora A, et al., Curr Mer Res Opin,
7. Sornay-Rendu E, Munoz F, Garnero P, et al., J Bone Miner Res, 17. Dempster DW, J Bone Miner Res, 2000;15:20–23. 2005;21:185–94.
2005;20:1813–19. 18. Follet H, Boivin G, Rumelhart C, Meunier PJ, Bone, 29. Wang X, Shen X, Li X, Mauli Agrawal C, Bone, 2002;31:1–7.
8. Ross PD, Kress BC, Parson RE, et al., Osteoporos Int, 2004;34:783–9. 30. Clowes JA, Peel NFA, Eastell R, J Clin Endocrinol Metab,
2000;11:76–82. 19. Viguet-Carin S, Roux JP, Arlot ME, et al., Bone, 2004;89:1117–23.
9. Johnell O, Oden A, de Laet C, et al., Osteoporos Int, 2002;13: 2006;39:1073–9. 31. Delmas PD, Vrijens B, Eastell R, et al., J Clin Endocrinol Metab,
523–6. 20. Oxlund H, Barckman M, Ortoft G, Andreassen TT, Bone, 2007; online.
10. Daele PLA van, Seibel MJ, Burger H, et al., Br Med J, 1995;17(Suppl. 4):365S–371S.
1996;312:482–3. 21. Garnero P, Cloos P, Sornay-Rendu E, et al., J Bone Miner Res,
94 EUROPEAN MUSCULOSKELETAL REVIEW 2007
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