Osteoporosis International

, Volume 29, Issue 10, pp 2323–2333 | Cite as

Effects of osteoporosis drug treatments on cortical and trabecular bone in the femur using DXA-based 3D modeling

  • R. Winzenrieth
  • L. Humbert
  • S. Di Gregorio
  • E. Bonel
  • M. García
  • L. Del Rio
Original Article



Effects of osteoporosis drugs on proximal femur cortical and trabecular bone were studied using dual-energy x-ray absorptiometry (DXA)-based 3D modeling method. Changes observed in this head-to-head study were consistent with those obtained using computed tomography in the literature.


The aim of the present study was to assess the effects of osteoporosis drugs on cortical and trabecular bone at the proximal femur using DXA-based 3D modeling.


We retrospectively analyzed 155 patients stratified by treatments: naive of treatment (NAIVE), alendronate (AL), denosumab (DMAB), and teriparatide (TPTD). DXA scans were performed at baseline and after treatment, and areal bone mineral density at spine and femur were measured. A software algorithm (3D-SHAPER) was used to derive 3D models from hip DXA scans and compute: trabecular and cortical volumetric BMD (vBMD), cortical thickness (Cth), and cortical surface BMD (cortical sBMD). Changes from baseline were normalized at 24 months and evaluated in terms or percentage.


After 24 months, a non-significant decrease was observed for trabecular vBMD, Cortical sBMD, Cth, and cortical vBMD (− 2.3, − 0.8, − 0.3, and − 0.5%) in the NAIVE group. Under AL and DMAB, significant increases were observed in trabecular vBMD (3.8 and 7.3%), cortical vBMD (1.4 and 2.0%), and cortical sBMD (1.5 and 3.6%). An increase in Cth was observed in patients under DMAB (1.8%). Under TPTD, a significant increase in Trabecular vBMD was observed (5.9%) associated with a non-significant increase of Cth (+ 1%) concomitant with a decrease in cortical vBMD (− 1.1%).


Results obtained in this head-to-head study are consistent with those obtained using computed tomography in the literature. DXA-based modeling techniques could complement standard DXA examination to monitor treatment effects on trabecular and cortical compartments.


3D modeling Cortical and trabecular bones DXA Femur Osteoporosis treatments 



Areal bone mineral density at lumbar spine in grams per square centimeter


Areal bone mineral density at femoral neck in grams per square centimeter


Areal bone mineral density at total femur in grams per square centimeter

Trabecular vBMD

Trabecular volumetric bone mineral density in milligrams per cubic centimeter

Cortical vBMD

Cortical volumetric bone mineral density in milligrams per cubic centimeter

Cortical sBMD

Cortical surface bone mineral density in milligrams per square centimeter


Cortical thickness in millimeters



The work of Renaud Winzenrieth is supported by: Programa Estatal de Promoción del Talento y su Empleabilidad - Torres Quevedo, Ministerio de Economía y Competitividad (Reference: PTQ-16-08627).

Compliance with ethical standards

Conflicts of interest

R. Winzenrieth is an employee of Galgo Medical. L. Humbert is a stockholder of Galgo Medical. S. Di Gregorio; E. Bonel, M. García, and L. Del Rio have no conflict of interest.


  1. 1.
    Chan CKY, Mason A, Cooper C, Dennison E (2017) Novel advances in the treatment of osteoporosis. Br Med Bull 119:129–142. CrossRefGoogle Scholar
  2. 2.
    Austin M, Yang Y, Vittinghoff E et al (2012) Relationship between bone mineral density changes with Denosumab treatment and risk reduction for vertebral and nonvertebral fractures. J Bone Miner Res 27:687–693. CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, Bauer DC, Genant HK, Haskell WL, Marcus R, Ott SM, Torner JC, Quandt SA, Reiss TF, Ensrud KE (1996) Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 348:1535–1541CrossRefPubMedGoogle Scholar
  4. 4.
    Small RE (2005) Uses and limitations of bone mineral density measurements in the management of osteoporosis. MedGenMed 7:3PubMedPubMedCentralGoogle Scholar
  5. 5.
    Moseley KF (2012) Type 2 diabetes and bone fractures. Curr Opin Endocrinol Diabetes Obes 19:128–135. CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Lewiecki EM, Miller PD (2013) Skeletal effects of primary hyperparathyroidism: bone mineral density and fracture risk. J Clin Densitom 16:28–32. CrossRefPubMedGoogle Scholar
  7. 7.
    McClung MR, Martin JS, Miller PD et al (2005) Opposite bone remodeling effects of Teriparatide and alendronate in increasing bone mass. Arch Intern Med 165:1762–1769CrossRefPubMedGoogle Scholar
  8. 8.
    Van Staa TP, Leufkens HG, Abenhaim L et al (2000) Use of oral corticosteroids and risk of fractures. J Bone Miner Res 15:993–1000. CrossRefPubMedGoogle Scholar
  9. 9.
    Dempster DW, Müller R, Zhou H, Kohler T, Shane E, Parisien M, Silverberg SJ, Bilezikian JP (2007) Preserved three-dimensional cancellous bone structure in mild primary hyperparathyroidism. Bone 41:19–24. CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Reid IR (1997) Glucocorticoid osteoporosis—mechanisms and management. Eur J Endocrinol 137:209–217CrossRefPubMedGoogle Scholar
  11. 11.
    Genant HK, Libanati C, Engelke K, Zanchetta JR, Høiseth A, Yuen CK, Stonkus S, Bolognese MA, Franek E, Fuerst T, Radcliffe HS, McClung MR (2013) Improvements in hip trabecular , subcortical , and cortical density and mass in postmenopausal women with osteoporosis treated with denosumab. Bone 56:482–488. CrossRefPubMedGoogle Scholar
  12. 12.
    Keaveny TM, Hoffmann PF, Singh M, Palermo L, Bilezikian JP, Greenspan SL, Black DM (2008) Femoral bone strength and its relation to cortical and trabecular changes after treatment with PTH, alendronate, and their combination as assessed by finite element analysis of quantitative CT scans. J Bone Miner Res 23:1974–1982. CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Engelke K, Lang T, Khosla S, Qin L, Zysset P, Leslie WD, Shepherd JA, Schousboe JT (2015) 2015 ISCD position development conference clinical use of quantitative computed tomography (QCT) of the hip in the management of osteoporosis in adults: the 2015 ISCD official positions d part I. J Clin Densitom 18:338–358. CrossRefPubMedGoogle Scholar
  14. 14.
    Johannesdottir F, Aspelund T, Reeve J, Poole KE, Sigurdsson S, Harris TB, Gudnason VG, Sigurdsson G (2013) Similarities and differences between sexes in regional loss of cortical and trabecular bone in the mid-femoral neck: the AGES - Reykjavik longitudinal study. J Bone Miner Res 28:2165–2176. CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Nicks KM, Amin S, Melton LJ et al (2013) Three-dimensional structural analysis of the proximal femur in an age-stratified sample of women. Bone 55:179–188. CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Bousson D, Adams J, Engelke K et al (2011) In vivo discrimination of hip fracture with quantitative computed tomography: results from the prospective European femur fracture study (EFFECT ). J Bone Miner Res 26:881–893. CrossRefPubMedGoogle Scholar
  17. 17.
    Black DM, Bouxsein ML, Marshall LM, Cummings SR, Lang TF, Cauley JA, Ensrud KE, Nielson CM, Orwoll ES, Osteoporotic Fractures in Men (MrOS) Research Group (2008) Proximal femoral structure and the prediction of hip fracture in men: a large prospective study using QCT. J Bone Miner Res 23:1326–1333. CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Keaveny TM, Donley DW, Hoffmann PF, Mitlak BH, Glass EV, San Martin JA (2007) Effects of teriparatide and alendronate on vertebral strength as assessed by finite element modeling of QCT scans in women with osteoporosis. J Bone Miner Res 22:149–157. CrossRefPubMedGoogle Scholar
  19. 19.
    Genant HK, Engelke K, Hanley DA, Brown JP, Omizo M, Bone HG, Kivitz AJ, Fuerst T, Wang H, Austin M, Libanati C (2010) Denosumab improves density and strength parameters as measured by QCT of the radius in postmenopausal women with low bone mineral density. Bone 47:131–139. CrossRefPubMedGoogle Scholar
  20. 20.
    Zebaze R, Libanati C, MR M et al (2016) Denosumab reduces cortical porosity of the proximal femoral shaft in postmenopausal women with osteoporosis. J Bone Miner Res 31:1827–1834. CrossRefPubMedGoogle Scholar
  21. 21.
    Zysset P, Pahr D, Engelke K, Genant HK, McClung MR, Kendler DL, Recknor C, Kinzl M, Schwiedrzik J, Museyko O, Wang A, Libanati C (2015) Comparison of proximal femur and vertebral body strength improvements in the FREEDOM trial using an alternative finite element methodology. Bone 81:122–130. CrossRefPubMedGoogle Scholar
  22. 22.
    Poole KES, Treece GM, Gee AH, Brown JP, McClung MR, Wang A, Libanati C (2014) Denosumab rapidly increases cortical bone in key locations of the femur: a 3D bone mapping study in women with osteoporosis. J Bone Miner Res 30:46–54. CrossRefGoogle Scholar
  23. 23.
    Keaveny TM, Mcclung MR, Wan X et al (2012) Femoral strength in osteoporotic women treated with teriparatide. Bone 50:165–170. CrossRefPubMedGoogle Scholar
  24. 24.
    Whitmarsh T, Treece GM, Gee AH, Poole KES (2016) The effects on the femoral cortex of a 24 month treatment compared to an 18 month treatment with teriparatide: a multi-trial retrospective analysis. PLoS One 11:1–9. CrossRefGoogle Scholar
  25. 25.
    Borggrefe J, Graeff C, Nickelsen TN, Marin F, Glüer CC (2010) Quantitative computed tomographic assessment of the effects of 24 months of teriparatide treatment on 3D femoral neck bone distribution, geometry, and bone strength: results from the EUROFORS study. J Bone Miner Res 25:472–481. CrossRefPubMedGoogle Scholar
  26. 26.
    Zysset P, Qin L, Lang T, Khosla S, Leslie WD, Shepherd JA, Schousboe JT, Engelke K (2015) 2015 ISCD position development conference clinical use of quantitative computed tomography e based finite element analysis of the hip and spine in the management of osteoporosis in adults: the 2015 ISCD official positions d part II. J Clin Densitom 18:359–392. CrossRefPubMedGoogle Scholar
  27. 27.
    Humbert L, Martelli Y, Fonollà R et al (2016) 3D-DXA: analyzing the femoral shape, the trabecular macrostructure and the cortical layer in 3D from DXA images. IEEE Trans Med Imaging 0062:1–12. CrossRefGoogle Scholar
  28. 28.
    Väänänen SP, Grassi L, Flivik G, Jurvelin JS, Isaksson H (2015) Generation of 3D shape, density, cortical thickness and finite element mesh of proximal femur from a DXA image. Med Image Anal 24:125–134. CrossRefPubMedGoogle Scholar
  29. 29.
    Clotet J, Martelli Y, Di Gregorio S, et al (2017) Structural parameters of the proximal femur by 3-dimensional dual-energy x-ray absorptiometry software: comparison with quantitative computed tomography. J Clin Densitom 1–13.
  30. 30.
    Ahmad O, Ramamurthi K, Wilson KE, Engelke K, Prince RL, Taylor RH (2010) Volumetric DXA (VXA): a new method to extract 3D information from multiple in vivo DXA images. J Bone Miner Res 25:2468–2475. CrossRefGoogle Scholar
  31. 31.
    Humbert L, Hazrati Marangalou J, del Río Barquero LM, van Lenthe GH, van Rietbergen B (2016) Technical note: cortical thickness and density estimation from clinical CT using a prior thickness-density relationship. Med Phys 43:1945–1954. CrossRefPubMedGoogle Scholar
  32. 32.
    Treece GM, Gee AH (2015) Independent measurement of femoral cortical thickness and cortical bone density using clinical CT. Med Image Anal 20:249–264CrossRefPubMedGoogle Scholar
  33. 33.
    Lewiecki EM, Miller PD, Mcclung MR et al (2007) Two-year treatment with Denosumab (AMG 162) in a randomized phase 2 study of postmenopausal women with low BMD. J Bone Miner Res 22:1832–1841. CrossRefPubMedGoogle Scholar
  34. 34.
    Brown JP, Prince R, Deal C et al (2009) Comparison of the effect of denosumab and alendronate on BMD and biochemical markers of bone turnover in postmenopausal women with low bone mass: a randomized, blinded, phase 3 trial. J Bone Miner Res 24:153–161. CrossRefPubMedGoogle Scholar
  35. 35.
    Bolognese MA, Teglbjærg CS, Zanchetta JR, Lippuner K, McClung MR, Brandi ML, Høiseth A, Lakatos P, Moffett AH, Lorenc RS, Wang A, Libanati C (2013) Denosumab significantly increases DXA BMD at both trabecular and cortical sites: results from the FREEDOM study. J Clin Densitom 16:147–153. CrossRefPubMedGoogle Scholar
  36. 36.
    Sánchez A, Brun LR, Salerni H, Costanzo PR, González D, Bagur A, Oliveri B, Zanchetta MB, Farías V, Maffei L, Premrou V, Mansur JL, Larroudé MS, Sarli MA, Rey P, Ulla MR, Pavlove MM, Karlsbrum S, Brance ML (2016) Effect of denosumab on bone mineral density and markers of bone turnover among postmenopausal women with osteoporosis. J Osteoporos 2016:1–6. CrossRefGoogle Scholar
  37. 37.
    Senn C, Günther B, Popp AW, Perrelet R (2014) Comparative effects of teriparatide and ibandronate on spine bone mineral density (BMD) and microarchitecture (TBS) in postmenopausal women with osteoporosis: a 2-year open-label study. Osteoporos Int 25:1945–1951. CrossRefPubMedGoogle Scholar
  38. 38.
    Miyauchi A, Matsumoto T, Sugimoto T, Tsujimoto M, Warner MR, Nakamura T (2010) Effects of teriparatide on bone mineral density and bone turnover markers in Japanese subjects with osteoporosis at high risk of fracture in a 24-month clinical. Bone 47:493–502. CrossRefPubMedGoogle Scholar
  39. 39.
    Roschger P, Rinnerthaler S, Yates J, Rodan GA, Fratzl P, Klaushofer K (2001) Alendronate increases degree and uniformity of mineralization in cancellous bone and decreases the porosity in cortical bone of osteoporotic women. Bone 29:185–191CrossRefPubMedGoogle Scholar
  40. 40.
    Boivin GY, Chavassieux PM, Santora AC, Yates J, Meunier PJ (2000) Alendronate increases bone strength by increasing the mean degree of mineralization of bone tissue in osteoporotic women. Bone 27:687–694CrossRefPubMedGoogle Scholar
  41. 41.
    Zebaze RM, Libanati C, Austin M, Ghasem-Zadeh A, Hanley DA, Zanchetta JR, Thomas T, Boutroy S, Bogado CE, Bilezikian JP, Seeman E (2014) Differing effects of denosumab and alendronate on cortical and trabecular bone. Bone 59:173–179. CrossRefPubMedGoogle Scholar
  42. 42.
    Unnanuntana A, Ashfaq K, Ton QV, Kleimeyer JP, Lane JM (2012) The effect of long-term alendronate treatment on cortical thickness of the proximal femur. Clin Orthop Relat Res 470:291–298. CrossRefPubMedGoogle Scholar
  43. 43.
    Niimi R, Kono T, Nishihara A, Hasegawa M, Matsumine A, Kono T, Sudo A (2015) Cortical thickness of the femur and long-term bisphosphonate use. J Bone Miner Res 30:225–231. CrossRefPubMedGoogle Scholar
  44. 44.
    Seeman E, Delmas PD, Hanley DA, Sellmeyer D, Cheung AM, Shane E, Kearns A, Thomas T, Boyd SK, Boutroy S, Bogado C, Majumdar S, Fan M, Libanati C, Zanchetta J (2010) Microarchitectural deterioration of cortical and trabecular bone: differing effects of denosumab and alendronate. J Bone Miner Res 25:1886–1894. CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Ma YL, Zeng QQ, Chiang AY, Burr D, Li J, Dobnig H, Fahrleitner-Pammer A, Michalská D, Marin F, Pavo I, Stepan JJ (2014) Effects of teriparatide on cortical histomorphometric variables in postmenopausal women with or without prior alendronate treatment. Bone 59:139–147. CrossRefPubMedGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2018

Authors and Affiliations

  1. 1.Musculoskeletal UnitGalgo MedicalBarcelonaSpain
  2. 2.Department of UrologyHospital Universitario de Bellvitgel’HospitaletSpain
  3. 3.Cetir Grup MèdicBarcelonaSpain

Personalised recommendations