Osteoporosis International

, Volume 20, Issue 5, pp 793–800 | Cite as

Spectroscopic markers of bone quality in alendronate-treated postmenopausal women

Original Article



Comparison of infrared spectroscopic images of sections from biopsies of placebo-treated post-menopausal women and women treated for 3 years with 10 mg/day alendronate demonstrated significant increases in cortical bone mineral content, no alterations in other spectroscopic markers of “bone quality,” but a decrease in tissue heterogeneity.


The material properties of thick sections from iliac crest biopsies of seven alendronate-treated women were compared to those from ten comparably aged post-menopausal women without bone disease, using infrared spectroscopic imaging at ∼7 μm spatial resolution. Parameters evaluated were mineral/matrix ratio, crystallinity, carbonate/amide I ratio, and collagen maturity. The line widths at half maximum of the pixel histograms for each parameter were used as measures of heterogeneity.


The mineral content (mineral/matrix ratio) in the cortical bone of the treated women’s biopsies was higher than that in the untreated control women. Crystallinity, carbonate/protein, and collagen maturity indices were not significantly altered; however, the pixel distribution was significantly narrowed for all cortical and trabecular parameters with the exception of collagen maturity in the alendronate treatment group.


The increases in mineral density and decreased fracture risk associated with bisphosphonate treatment may be counterbalanced by a decrease in tissue heterogeneity, which could impair tissue mechanical properties. These consistent data suggest that alendronate treatment, while increasing the bone mass, decreases the tissue heterogeneity.


Alendronate Bone heterogeneity Infrared spectroscopic imaging Osteoporosis 



This study was supported by NIH grant AR043125 and Core Center grant AR046121 to A.L.B. and by AR046191 to R.S.W. This investigation was conducted in a facility constructed with support from Research Facilities Improvement Program grant number C06-RR12538-01 from the National Center for Research Resources, National Institutes of Health.

Conflicts of interest



  1. 1.
    Boskey AL, Mendelsohn R (2005) Infrared spectroscopic characterization of mineralized tissues. Vib Spectrosc 38:107–114PubMedCrossRefGoogle Scholar
  2. 2.
    Paschalis EP, DiCarlo E, Betts F et al (1996) FTIR microspectroscopic analysis of human osteonal bone. Calcif Tissue Int 59:480–487PubMedGoogle Scholar
  3. 3.
    Paschalis EP, Betts F, DiCarlo E et al (1997) FTIR microspectroscopic analysis of normal human cortical and trabecular bone. Calcif Tissue Int 61:480–486PubMedCrossRefGoogle Scholar
  4. 4.
    Paschalis EP, Betts F, DiCarlo E et al (1997) FTIR microspectroscopic analysis of human iliac crest biopsies from untreated osteoporotic bone. Calcif Tissue Int 61:487–492PubMedCrossRefGoogle Scholar
  5. 5.
    Paschalis EP, Verdelis K, Doty SB et al (2001) Spectroscopic characterization of collagen cross-links in bone. J Bone Miner Res 16:1821–1828PubMedCrossRefGoogle Scholar
  6. 6.
    Paschalis EP, Boskey AL, Kassem M, Eriksen EF (2003) Effect of hormone replacement therapy on bone quality in early postmenopausal women. J Bone Miner Res 18:955–959PubMedCrossRefGoogle Scholar
  7. 7.
    Paschalis EP, Recker R, DiCarlo E et al (2003) Distribution of collagen cross-links in normal human trabecular bone. J Bone Miner Res 18:1942–1946PubMedCrossRefGoogle Scholar
  8. 8.
    Paschalis EP, Shane E, Lyritis G et al (2004) Bone fragility and collagen cross-links. J Bone Miner Res 19:2000–2004PubMedCrossRefGoogle Scholar
  9. 9.
    Boskey AL, DiCarlo E, Paschalis E et al (2005) Comparison of mineral quality and quantity in iliac crest biopsies from high- and low-turnover osteoporosis: an FT-IR microspectroscopic investigation. Osteoporos Int 16:2031–2038PubMedCrossRefGoogle Scholar
  10. 10.
    Durchschlag E, Paschalis EP, Zoehrer R et al (2006) Bone material properties in trabecular bone from human iliac crest biopsies after 3- and 5-year treatment with risedronate. J Bone Miner Res 21:1581–1590PubMedCrossRefGoogle Scholar
  11. 11.
    Miller LM, Little W, Schirmer A et al (2007) Accretion of bone quantity and quality in the developing mouse skeleton. J Bone Miner Res 22:1037–1045PubMedCrossRefGoogle Scholar
  12. 12.
    Busa B, Miller LM, Rubin CT et al (2005) Rapid establishment of chemical and mechanical properties during lamellar bone formation. Calcif Tissue Int 77:386–394PubMedCrossRefGoogle Scholar
  13. 13.
    Silva MJ, Brodt MD, Wopenka B et al (2006) Decreased collagen organization and content are associated with reduced strength of demineralized and intact bone in the SAMP6 mouse. J Bone Miner Res 21:78–88PubMedCrossRefGoogle Scholar
  14. 14.
    Lane NE, Yao W, Balooch M et al (2006) Glucocorticoid-treated mice have localized changes in trabecular bone material properties and osteocyte lacunar size that are not observed in placebo-treated or estrogen-deficient mice. J Bone Miner Res 21:466–476PubMedCrossRefGoogle Scholar
  15. 15.
    Tumanov AT, Gunyaev GM, Lyutsau VG, Stepanychev EI (1975) Structure, properties, and tests of carbon-reinforced plastics. Mech Compos Mater 11:167–327Google Scholar
  16. 16.
    National Materials Advisory Board Committee on high-performance synthetic fibers for composites; Commission on Engineering and Technical Systems; National Research Council (1992) High-performance synthetic fibers for composites publication NMAB-458. National Academy Press, Washington, DC, pp 49–103Google Scholar
  17. 17.
    Smith EJ, McEvoy A, Little DG et al (2004) Transient retention of endochondral cartilaginous matrix with bisphosphonate treatment in a long-term rabbit model of distraction osteogenesis. J Bone Miner Res 19:1698–1705PubMedCrossRefGoogle Scholar
  18. 18.
    Burr DB (2002) Bone material properties and mineral matrix contributions to fracture risk or age in women and men. J Musculoskelet Neuronal Interact 2:201–204PubMedGoogle Scholar
  19. 19.
    Zoehrer R, Roschger P, Paschalis EP et al (2006) Effects of 3- and 5-year treatment with risedronate on bone mineralization density distribution in triple biopsies of the iliac crest in postmenopausal women. J Bone Miner Res 21:1106–1112PubMedCrossRefGoogle Scholar
  20. 20.
    Roschger P, Dempster DW, Zhou H et al (2007) New observations on bone quality in mild primary hyperparathyroidism as determined by quantitative backscattered electron imaging. J Bone Miner Res 22:717–723PubMedCrossRefGoogle Scholar
  21. 21.
    Ruffoni D, Fratzl P, Roschger P et al (2007) The bone mineralization density distribution as a fingerprint of the mineralization process. Bone 40:1308–1319PubMedCrossRefGoogle Scholar
  22. 22.
    Roschger P, Pascalis EP, Fratzl P, Klaushofer K (2008) Bone mineralization density distribution in health and disease. Bone 42:456–466PubMedCrossRefGoogle Scholar
  23. 23.
    Roschger P, Fratl P, Klaushofer K, Rodan G (1997) Mineralization of cancellous bone after alendronate and sodium fluoride treatment: a quantitative backscattered electron imaging study on minipig ribs. Bone 20:393–397PubMedCrossRefGoogle Scholar
  24. 24.
    Roschger P, Rinnerthaler S, Yates J, Rodan GA et al (2001) Alendronate increases degree and uniformity of mineralization in cancellous bone and decreases the porosity in cortical bone of osteoporotic women. Bone 29:185–191PubMedCrossRefGoogle Scholar
  25. 25.
    McClung M, Clemmesen B, Daifotis A et al (1998) Alendronate prevents postmenopausal bone loss in women without osteoporosis. A double-blind, randomized, controlled trial. Alendronate Osteoporosis Prevention Study Group. Ann Intern Med 128:253–261PubMedGoogle Scholar
  26. 26.
    Finkelstein JS, Brockwell SE, Mehta V, Greendale GA et al (2008) Bone mineral density changes during the menopause transition in a multiethnic cohort of women. J Clin Endocrinol Metab 93:861–868PubMedCrossRefGoogle Scholar
  27. 27.
    Misof BM, Roschger P, Baldini T et al (2005) Differential effects of alendronate treatment on bone from growing osteogenesis imperfecta and wild-type mouse. Bone 36:150–158PubMedCrossRefGoogle Scholar
  28. 28.
    Fratzl P, Roschger P, Fratzl-Zelman N, Paschalis EP et al (2007) Evidence that treatment with risedronate in women with postmenopausal osteoporosis effects bone mineralization and bone volume. Calciif Tissue Int 81:73–80CrossRefGoogle Scholar
  29. 29.
    Keaveny TM, Hayes WC (1993) A 20-year perspective on the mechanical properties of trabecular bone. Transact ASME 115:534–554Google Scholar
  30. 30.
    Goldstein SA (1987) The mechanical properties of trabecular bone: dependence on anatomic location and function. J Biomech 20:1055–1061PubMedCrossRefGoogle Scholar
  31. 31.
    Zoehrer R, Roschger P, Duschschlag E, Fratzl P et al (2006) Bone mineralization density distribution in triple biopsies of the iliac crest in post-menopausal women. J Bone Miner Res 21:1106–1112PubMedCrossRefGoogle Scholar
  32. 32.
    Boivin GY, Chavassieux PM, Santora AC et al (2000) Alendronate increases bone strength by increasing the mean degree of mineralization of bone tissue in osteoporotic women. Bone 27:687–694PubMedCrossRefGoogle Scholar
  33. 33.
    Black DM, Cummings SR, Karpf DB et al (1996) Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures: Fracture Intervention Trial Research Group. Lancet 348:1535–1541PubMedCrossRefGoogle Scholar
  34. 34.
    Bone HG, Hosking D, Devogelaer JP et al (2004) Ten years’ experience with alendronate for osteoporosis in post menopausal women. N Engl J Med 350:1189–1199PubMedCrossRefGoogle Scholar
  35. 35.
    Chavassieux PM, Arlot ME, Reda C et al (1997) Histomorphometric assessment of the long-term effects of alendronate on bone quality and remodeling in patients with osteoporosis. J Clin Invest 100:1475–1480PubMedCrossRefGoogle Scholar
  36. 36.
    Black DM, Schwartz AV, Ensrud KE et al (2006) Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA 296:2927–2938PubMedCrossRefGoogle Scholar
  37. 37.
    Goh SK, Yang KY, Koh JS et al (2007) Subtrochanteric insufficiency fractures in patients on alendronate therapy: a caution. J Bone Joint Surg Br 2007 89:349–353CrossRefGoogle Scholar
  38. 38.
    Lenart B, Lorich DG, Lane JM (2008) Atypical fractures of the femoral diaphysis in postmenopausal women taking alendronate. NEJM 358:1304PubMedCrossRefGoogle Scholar
  39. 39.
    Lee P, van der Wall H, Seibel MJ (2007) Looking beyond low bone mineral density: multiple insufficiency fractures in a woman with post-menopausal osteoporosis on alendronate therapy. J Endocrinol Invest 30:590–597PubMedGoogle Scholar
  40. 40.
    Imai K, Yamamoto S, Anamizu Y, Horiuchi T (2007) Pelvic insufficiency fracture associated with severe suppression of bone turnover by alendronate therapy. J Bone Miner Metab 25:333–336PubMedCrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2008

Authors and Affiliations

  1. 1.Musculoskeletal Integrity ProgramHospital for Special SurgeryNew YorkUSA
  2. 2.Division of Endocrinology and Metabolism, Center for Osteoporosis and Metabolic Bone Diseases, Department of Internal Medicine and the Central Arkansas Veterans Healthcare SystemUniversity of Arkansas for Medical SciencesLittle RockUSA
  3. 3.Hospital for Special SurgeryNew YorkUSA

Personalised recommendations