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Effects of Antiresorptive Therapy on Bone Microarchitecture

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The Duration and Safety of Osteoporosis Treatment

Abstract

Dual-energy X-ray absorptiometry (DXA) is widely used to measure bone mineral density (BMD) for both clinical and research use. While DXA is well validated as a predictor of fracture, density is only one determinant of bone quality. Other potential major contributors to fracture risk reduction include bone morphology, bone microarchitecture, and the intrinsic physical properties of bone tissue. This chapter focuses on the effect of antiresorptive therapy on bone microarchitecture as assessed by (1) traditional two-dimensional histomorphometry of iliac crest bone biopsies and three-dimensional ex vivo micro-CT of biopsies and (2) imaging methods including high-resolution peripheral quantitative CT (HR-pQCT) that assess bone microarchitecture in vivo. Studies show that trabecular microarchitecture is generally preserved or improved with antiresorptive treatment as assessed by histomorphometry and micro-CT of iliac crest biopsies. However, trabecular microarchitectural changes as assessed by HR-pQCT are generally not detected, possibly due to limited imaging resolution and modest reproducibility for trabecular microarchitecture measurements. Cortical microarchitecture is generally preserved or improved as assessed by both iliac crest bone biopsy histomorphometry with micro-CT and by HR-pQCT of the distal radius and distal tibia. These studies highlight the important positive effects of antiresorptive treatment on trabecular and cortical microarchitecture at axial and peripheral sites.

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Notes

  1. 1.

    *Important References

    **Very important References

Abbreviations

DXA:

Dual-energy X-ray absorptiometry

HR-pQCT:

High-resolution peripheral quantitative CT

BMD:

Bone mineral density

2-D:

Two-dimensional

BV/TV:

Trabecular bone volume fraction

3-D:

Three-dimensional

vBMD:

Volumetric bone mineral density

ITS:

Individual trabecula segmentation

References

*Important References

**Very important References

  1. Delmas PD. How does antiresorptive therapy decrease the risk of fracture in women with osteoporosis? Bone. 2000;27(1):1–3. PubMed.

    Article  PubMed  CAS  Google Scholar 

  2. Delmas PD, Seeman E. Changes in bone mineral density explain little of the reduction in vertebral or nonvertebral fracture risk with anti-resorptive therapy. Bone. 2004;34(4):599–604. PubMed.

    Article  PubMed  CAS  Google Scholar 

  3. Schuit SC, van der Klift M, Weel AE, de Laet CE, Burger H, Seeman E, et al. Fracture incidence and association with bone mineral density in elderly men and women: the Rotterdam study. Bone. 2004;34(1):195–202. PubMed.

    Article  PubMed  CAS  Google Scholar 

  4. Siris ES, Miller PD, Barrett-Connor E, Faulkner KG, Wehren LE, Abbott TA, et al. Identification and fracture outcomes of undiagnosed low bone mineral density in postmenopausal women: results from the national osteoporosis risk assessment. JAMA. 2001;286(22):2815–22. PubMed.

    Article  PubMed  CAS  Google Scholar 

  5. Stone KL, Seeley DG, Lui LY, Cauley JA, Ensrud K, Browner WS, et al. BMD at multiple sites and risk of fracture of multiple types: long-term results from the study of osteoporotic fractures. J Bone Miner Res. 2003;18(11):1947–54. PubMed.

    Article  PubMed  Google Scholar 

  6. Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, et al. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture intervention trial research group. Lancet. 1996;348(9041):1535–41. PubMed.

    Article  PubMed  CAS  Google Scholar 

  7. Feldkamp LA, Goldstein SA, Parfitt AM, Jesion G, Kleerekoper M. The direct examination of three-dimensional bone architecture in vitro by computed tomography. J Bone Miner Res. 1989;4(1):3–11. PubMed.

    Article  PubMed  CAS  Google Scholar 

  8. Ruegsegger P, Koller B, Muller R. A microtomographic system for the nondestructive evaluation of bone architecture. Calcif Tissue Int. 1996;58(1):24–9. PubMed.

    Article  PubMed  CAS  Google Scholar 

  9. *Boutroy S, Bouxsein ML, Munoz F, Delmas PD. In vivo assessment of trabecular bone microarchitecture by high-resolution peripheral quantitative computed tomography. J Clin Endocrinol Metab. 2005;90(12):6508–15. PubMed. *This cross-sectional study was the first to demonstrate that alterations of trabecular structure as measured by HR-pQCT discriminate between postmenopausal osteopenic women with and without a history of fragility fracture, whereas hip and spine areal BMD were no different between those with and without a history of fracture.

    Article  PubMed  CAS  Google Scholar 

  10. *Khosla S, Riggs BL, Atkinson EJ, Oberg AL, McDaniel LJ, Holets M, et al. Effects of sex and age on bone microstructure at the ultradistal radius: a population-based noninvasive in vivo assessment. J Bone Miner Res. 2006;21(1):124–31. PubMed Pubmed Central PMCID: 1352156. *By examining differences in microarchitecture, this large population-based study proposes an explanation for the difference in age-related radial fracture risk between men and women.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, et al. Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR histomorphometry nomenclature committee. J Bone Miner Res. 1987;2(6):595–610. PubMed.

    Article  PubMed  CAS  Google Scholar 

  12. Chavassieux PM, Arlot ME, Reda C, Wei L, Yates AJ, Meunier PJ. Histomorphometric assessment of the long-term effects of alendronate on bone quality and remodeling in patients with osteoporosis. J Clin Invest. 1997;100(6):1475–80. PubMed Pubmed Central PMCID: 508326.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Roschger P, Rinnerthaler S, Yates J, Rodan GA, Fratzl P, Klaushofer K. Alendronate increases degree and uniformity of mineralization in cancellous bone and decreases the porosity in cortical bone of osteoporotic women. Bone. 2001;29(2):185–91. PubMed.

    Article  PubMed  CAS  Google Scholar 

  14. Recker RR, Weinstein RS, Chesnut 3rd CH, Schimmer RC, Mahoney P, Hughes C, et al. Histomorphometric evaluation of daily and intermittent oral ibandronate in women with postmenopausal osteoporosis: results from the BONE study. Osteoporos Int. 2004;15(3):231–7. PubMed.

    Article  PubMed  CAS  Google Scholar 

  15. Arlot M, Meunier PJ, Boivin G, Haddock L, Tamayo J, Correa-Rotter R, et al. Differential effects of teriparatide and alendronate on bone remodeling in postmenopausal women assessed by histomorphometric parameters. J Bone Miner Res. 2005;20(7):1244–53. PubMed.

    Article  PubMed  CAS  Google Scholar 

  16. Recker R, Masarachia P, Santora A, Howard T, Chavassieux P, Arlot M, et al. Trabecular bone microarchitecture after alendronate treatment of osteoporotic women. Curr Med Res Opin. 2005;21(2):185–94. PubMed.

    Article  PubMed  CAS  Google Scholar 

  17. Recker RR, Delmas PD, Halse J, Reid IR, Boonen S, Garcia-Hernandez PA, et al. Effects of intravenous zoledronic acid once yearly on bone remodeling and bone structure. J Bone Miner Res. 2008;23(1):6–16. PubMed.

    Article  PubMed  CAS  Google Scholar 

  18. Recker RR, Ste-Marie LG, Langdahl B, Masanauskaite D, Ethgen D, Delmas PD. Oral ibandronate preserves trabecular microarchitecture: micro-computed tomography findings from the oral iBandronate osteoporosis vertebral fracture trial in North America and Europe study. J Clin Densitom. 2009;12(1):71–6. PubMed.

    Article  PubMed  Google Scholar 

  19. Brixen K, Chapurlat R, Cheung AM, Keaveny TM, Fuerst T, Engelke K, et al. Bone density, turnover, and estimated strength in postmenopausal women treated with odanacatib: a randomized trial. J Clin Endocrinol Metab. 2013;98(2):571–80. PubMed.

    Article  PubMed  CAS  Google Scholar 

  20. Reid IR, Miller PD, Brown JP, Kendler DL, Fahrleitner-Pammer A, Valter I, et al. Effects of denosumab on bone histomorphometry: the FREEDOM and STAND studies. J Bone Miner Res. 2010;25(10):2256–65. PubMed Epub 2010/06/10. eng.

    Article  PubMed  CAS  Google Scholar 

  21. Bravenboer N, Papapoulos SE, Holzmann P, Hamdy NA, Netelenbos JC, Lips P. Bone histomorphometric evaluation of pamidronate treatment in clinically manifest osteoporosis. Osteoporos Int. 1999;9(6):489–93. PubMed.

    Article  PubMed  CAS  Google Scholar 

  22. Prestwood KM, Gunness M, Muchmore DB, Lu Y, Wong M, Raisz LG. A comparison of the effects of raloxifene and estrogen on bone in postmenopausal women. J Clin Endocrinol Metab. 2000;85(6):2197–202. PubMed.

    PubMed  CAS  Google Scholar 

  23. Eriksen EF, Melsen F, Sod E, Barton I, Chines A. Effects of long-term risedronate on bone quality and bone turnover in women with postmenopausal osteoporosis. Bone. 2002;31(5):620–5. PubMed.

    Article  PubMed  CAS  Google Scholar 

  24. Ott SM, Oleksik A, Lu Y, Harper K, Lips P. Bone histomorphometric and biochemical marker results of a 2-year placebo-controlled trial of raloxifene in postmenopausal women. J Bone Miner Res. 2002;17(2):341–8. PubMed.

    Article  PubMed  CAS  Google Scholar 

  25. Dufresne TE, Chmielewski PA, Manhart MD, Johnson TD, Borah B. Risedronate preserves bone architecture in early postmenopausal women in 1 year as measured by three-dimensional microcomputed tomography. Calcif Tissue Int. 2003;73(5):423–32. PubMed.

    Article  PubMed  CAS  Google Scholar 

  26. Borah B, Dufresne TE, Chmielewski PA, Johnson TD, Chines A, Manhart MD. Risedronate preserves bone architecture in postmenopausal women with osteoporosis as measured by three-dimensional microcomputed tomography. Bone. 2004;34(4):736–46. PubMed.

    Article  PubMed  CAS  Google Scholar 

  27. Ste-Marie LG, Sod E, Johnson T, Chines A. Five years of treatment with risedronate and its effects on bone safety in women with postmenopausal osteoporosis. Calcif Tissue Int. 2004;75(6):469–76. PubMed.

    Article  PubMed  CAS  Google Scholar 

  28. Borah B, Dufresne T, Nurre J, Phipps R, Chmielewski P, Wagner L, et al. Risedronate reduces intracortical porosity in women with osteoporosis. J Bone Miner Res. 2010;25(1):41–7. PubMed.

    Article  PubMed  CAS  Google Scholar 

  29. Borah B, Dufresne TE, Ritman EL, Jorgensen SM, Liu S, Chmielewski PA, et al. Long-term risedronate treatment normalizes mineralization and continues to preserve trabecular architecture: sequential triple biopsy studies with micro-computed tomography. Bone. 2006;39(2):345–52. PubMed.

    Article  PubMed  CAS  Google Scholar 

  30. Ulrich D, Rietbergen B, Laib A, Ruegsegger P. Mechanical analysis of bone and its microarchitecture based on in vivo voxel images. Technol Health Care. 1998;6(5–6):421–7. PubMed.

    PubMed  CAS  Google Scholar 

  31. *Cheung AM, Adachi JD, Hanley DA, Kendler DL, Davison KS, Josse R, et al. High-resolution peripheral quantitative computed tomography for the assessment of bone strength and structure: a review by the Canadian bone strength working group. Current Osteoporos Rep. 2013;11(2):136–46. PubMed Pubmed Central PMCID: 3641288. *This is an excellent review of HR-pQCT for assessment of bone microarchitecture in vivo.

    Article  Google Scholar 

  32. Boutroy S, Van Rietbergen B, Sornay-Rendu E, Munoz F, Bouxsein ML, Delmas PD. Finite element analysis based on in vivo HR-pQCT images of the distal radius is associated with wrist fracture in postmenopausal women. J Bone Miner Res. 2008;23(3):392–9. PubMed.

    Article  PubMed  Google Scholar 

  33. *Liu XS, Stein EM, Zhou B, Zhang CA, Nickolas TL, Cohen A, et al. Individual trabecula segmentation (ITS)-based morphological analyses and microfinite element analysis of HR-pQCT images discriminate postmenopausal fragility fractures independent of DXA measurements. J Bone Miner Res. 2012;27(2):263–72. PubMed Pubmed Central PMCID: 3290758. *This case-control study demonstrates the utility of advanced individual trabecular segmentation (ITS), independent of DXA BMD measurements, to discriminate fracture subjects from controls..

    Article  PubMed  PubMed Central  Google Scholar 

  34. Melton 3rd LJ, Christen D, Riggs BL, Achenbach SJ, Muller R, van Lenthe GH, et al. Assessing forearm fracture risk in postmenopausal women. Osteoporos Int. 2010;21(7):1161–9. PubMed Pubmed Central PMCID: 2889027.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Nishiyama KK, Macdonald HM, Hanley DA, Boyd SK. Women with previous fragility fractures can be classified based on bone microarchitecture and finite element analysis measured with HR-pQCT. Osteoporos Int. 2013;24(5):1733–40. PubMed.

    Article  PubMed  CAS  Google Scholar 

  36. Pialat JB, Vilayphiou N, Boutroy S, Gouttenoire PJ, Sornay-Rendu E, Chapurlat R, et al. Local topological analysis at the distal radius by HR-pQCT: application to in vivo bone microarchitecture and fracture assessment in the OFELY study. Bone. 2012;51(3):362–8. PubMed.

    Article  PubMed  CAS  Google Scholar 

  37. **Sornay-Rendu E, Boutroy S, Chapurlat R. Bone Microarchitecture assessed by HR-pQCT as predictor of fracture risk in postmenopausal women: the OFELY study. J Bone Miner Metab Res. 2014;29 Suppl 1. ** This recently presented abstract is the first study to prospectively show the utility of bone microarchitecture measurements by HR-pQCT for fracture risk assessment.

    Google Scholar 

  38. Rozental TD, Deschamps LN, Taylor A, Earp B, Zurakowski D, Day CS, et al. Premenopausal women with a distal radial fracture have deteriorated trabecular bone density and morphology compared with controls without a fracture. J Bone Joint Surg Am. 2013;95(7):633–42. PubMed Pubmed Central PMCID: 3748976.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Sornay-Rendu E, Boutroy S, Munoz F, Delmas PD. Alterations of cortical and trabecular architecture are associated with fractures in postmenopausal women, partially independent of decreased BMD measured by DXA: the OFELY study. J Bone Miner Res. 2007;22(3):425–33. PubMed.

    Article  PubMed  Google Scholar 

  40. Sornay-Rendu E, Cabrera-Bravo JL, Boutroy S, Munoz F, Delmas PD. Severity of vertebral fractures is associated with alterations of cortical architecture in postmenopausal women. J Bone Miner Res. 2009;24(4):737–43. PubMed.

    Article  PubMed  Google Scholar 

  41. Stein EM, Liu XS, Nickolas TL, Cohen A, Thomas V, McMahon DJ, et al. Abnormal microarchitecture and stiffness in postmenopausal women with ankle fractures. J Clin Endocrinol Metab. 2011;96(7):2041–8. PubMed Pubmed Central PMCID: 3135193.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Vico L, Zouch M, Amirouche A, Frere D, Laroche N, Koller B, et al. High-resolution pQCT analysis at the distal radius and tibia discriminates patients with recent wrist and femoral neck fractures. J Bone Miner Res. 2008;23(11):1741–50. PubMed.

    Article  PubMed  Google Scholar 

  43. Burghardt AJ, Kazakia GJ, Ramachandran S, Link TM, Majumdar S. Age- and gender-related differences in the geometric properties and biomechanical significance of intracortical porosity in the distal radius and tibia. J Bone Miner Res. 2010;25(5):983–93. PubMed Pubmed Central PMCID: 3153365.

    PubMed  PubMed Central  Google Scholar 

  44. Nishiyama KK, Macdonald HM, Buie HR, Hanley DA, Boyd SK. Postmenopausal women with osteopenia have higher cortical porosity and thinner cortices at the distal radius and tibia than women with normal aBMD: an in vivo HR-pQCT study. J Bone Miner Res. 2010;25(4):882–90. PubMed.

    PubMed  Google Scholar 

  45. *Zebaze R, Ghasem-Zadeh A, Mbala A, Seeman E. A new method of segmentation of compact-appearing, transitional and trabecular compartments and quantification of cortical porosity from high resolution peripheral quantitative computed tomographic images. Bone. 2013;54(1):8–20. PubMed. *This study introduces a new approach to assess intracortical porosity. Using a non-thresholding or “segmentation-free” method, this approach distinguishes cortical bone from trabecular bone and is unique in defining an inner and outer transitional zone.

    Article  PubMed  CAS  Google Scholar 

  46. Zebaze RM, Libanati C, Austin M, Ghasem-Zadeh A, Hanley DA, Zanchetta JR, et al. Differing effects of denosumab and alendronate on cortical and trabecular bone. Bone. 2014;59:173–9. PubMed.

    Article  PubMed  CAS  Google Scholar 

  47. Bala Y, Chapurlat R, Cheung AM, Felsenberg D, LaRoche M, Morris E, et al. Risedronate slows or partly reverses cortical and trabecular microarchitectural deterioration in postmenopausal women. J Bone Miner Res. 2014;29(2):380–8. PubMed.

    Article  PubMed  CAS  Google Scholar 

  48. Chapurlat RD, Laroche M, Thomas T, Rouanet S, Delmas PD, de Vernejoul MC. Effect of oral monthly ibandronate on bone microarchitecture in women with osteopenia-a randomized placebo-controlled trial. Osteoporos Int. 2013;24(1):311–20. PubMed.

    Article  PubMed  CAS  Google Scholar 

  49. Burghardt AJ, Kazakia GJ, Sode M, de Papp AE, Link TM, Majumdar S. A longitudinal HR-pQCT study of alendronate treatment in postmenopausal women with low bone density: relations among density, cortical and trabecular microarchitecture, biomechanics, and bone turnover. J Bone Miner Res. 2010;25(12):2558–71. PubMed Pubmed Central PMCID: 3179276.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Rizzoli R, Chapurlat RD, Laroche JM, Krieg MA, Thomas T, Frieling I, et al. Effects of strontium ranelate and alendronate on bone microstructure in women with osteoporosis. Results of a 2-year study. Osteoporos Int. 2012;23(1):305–15. PubMed.

    Article  PubMed  CAS  Google Scholar 

  51. **Seeman E, Delmas PD, Hanley DA, Sellmeyer D, Cheung AM, Shane E, et al. Microarchitectural deterioration of cortical and trabecular bone: differing effects of denosumab and alendronate. J Bone Miner Res. 2010;25(8):1886–94. PubMed. **This placebo-controlled trial is the first longitudinal study to describe effects of antiresorptive treatment on bone microarchitecture as assessed in vivo by HR-pQCT. This study is one of the first multi-center trials conducted with HR-pQCT..

    Article  PubMed  PubMed Central  Google Scholar 

  52. Cheung AM, Majumdar S, Brixen K, Chapurlat R, Fuerst T, Engelke K, et al. Effects of odanacatib on the radius and tibia of postmenopausal women: improvements in bone geometry, microarchitecture, and estimated bone strength. J Bone Miner Res. 2014;29(8):1786–94. PubMed.

    Article  PubMed  CAS  Google Scholar 

  53. Hansen S, Hauge EM, Beck Jensen JE, Brixen K. Differing effects of PTH 1-34, PTH 1-84, and zoledronic acid on bone microarchitecture and estimated strength in postmenopausal women with osteoporosis: an 18-month open-labeled observational study using HR-pQCT. J Bone Miner Res. 2013;28(4):736–45. PubMed.

    Article  PubMed  CAS  Google Scholar 

  54. *Tsai JN, Uihlein AV, Burnett-Bowie SA, Neer RM, Zhu Y, Derrico N, et al. Comparative effects of teriparatide, denosumab, and combination therapy on peripheral compartmental bone density, microarchitecture, and estimated strength: the DATA-HRpQCT study. J Bone Miner Res. 2014; Epub 2014 Jul 7. *This is the first clinical trial to assess the effects of combination therapy—denosumab plus PTH, compared to either therapy alone—on bone microarchitecture, assessed by HR-pQCT.

    Google Scholar 

  55. Tjong W, Kazakia GJ, Burghardt AJ, Majumdar S. The effect of voxel size on high-resolution peripheral computed tomography measurements of trabecular and cortical bone microstructure. Med Phys. 2012;39(4):1893–903. PubMed Pubmed Central PMCID: 3316694.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Ellouz R, Chapurlat R, van Rietbergen B, Christen P, Pialat JB, Boutroy S. Challenges in longitudinal measurements with HR-pQCT: evaluation of a 3D registration method to improve bone microarchitecture and strength measurement reproducibility. Bone. 2014;63:147–57. PubMed.

    Article  PubMed  Google Scholar 

  57. Nishiyama KK, Pauchard Y, Nikkel LE, Iyer S, Zhang C, McMahon DJ, et al. Longitudinal HR-pQCT and image registration detects endocortical bone loss in kidney transplantation patients. J Bone Miner Res. 2014;11:554–61. PubMed.

    Google Scholar 

  58. *Liu XS, Sajda P, Saha PK, Wehrli FW, Bevill G, Keaveny TM, et al. Complete volumetric decomposition of individual trabecular plates and rods and its morphological correlations with anisotropic elastic moduli in human trabecular bone. J Bone Miner Res. 2008;23(2):223–35. PubMed Pubmed Central PMCID: 2665696. *This study utilizes an advanced method to assess trabecular morphology (plates or rods). This technique has the potential to improve non-invasive assessment of trabecular microarchitecture changes in response to treatment.

    PubMed  PubMed Central  Google Scholar 

  59. Nishiyama KK, Cohen A, Young P, Wang J, Lappe JM, Guo XE, et al. Teriparatide increases strength of the peripheral skeleton in premenopausal women with idiopathic osteoporosis: a pilot HR-pQCT study. J Clin Endocrinol Metab. 2014;99(7):2418–25. PubMed Pubmed Central PMCID: 4079304.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Poole, KE, Treece GM, Gee AH, Brown JP, McClung MR, Wang A, et al. Denosumab rapidly increases cortical bone in key locations of the femur: a 3D bone mapping study in women with osteoporosis. J Bone Miner Res. 2015;30(1):46–54.

    Google Scholar 

  61. Schafer AL, Burghardt AJ, Sellmeyer DE, Palermo L, Shoback DM, Majumdar S, et al. Postmenopausal women treated with combination parathyroid hormone (1-84) and ibandronate demonstrate different microstructural changes at the radius vs. tibia: the PTH and ibandronate combination study (PICS). Osteoporos Int. 2013;24(10):2591–601. PubMed.

    Article  PubMed  CAS  Google Scholar 

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Tsai, J.N., Bouxsein, M.L. (2016). Effects of Antiresorptive Therapy on Bone Microarchitecture. In: Silverman, S., Abrahamsen, B. (eds) The Duration and Safety of Osteoporosis Treatment. Springer, Cham. https://doi.org/10.1007/978-3-319-23639-1_10

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