Abstract
Excess of bone remodeling is still the major pathogenic factor in involutional osteoporosis. This phenomenon is linked to an imbalance between neoformation (by osteoblasts) and resorption (by osteoclasts). Recently, research in drug development is focused on new and more “physiological” approach to balance bone remodeling. The efficacy of denosumab was proved in the prevention of vertebral and non-vertebral fractures and related to the ability of the drug to penetrate in cortical and trabecular bone. Recently, data from several clinical studies confirm that denosumab improves fracture outcomes, also at skeletal sites rich in cortical bone.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Borah B, Dufresne TE, Chmielewski PA, Johnson TD, Chines A, Manhart MD (2004) Risedronate preserves bone architecture in postmenopausal women with osteoporosis as measured by three-dimensional microcomputed tomography. Bone 34(4):736–746
Zebaze RM, Ghasem-Zadeh A, Bohte A, Iuliano-Burns S, Mirams M, Price RI, Mackie EJ, Seeman E (2010) Intracortical remodelling and porosity in the distal radius and post-mortem femurs of women: a cross-sectional study. Lancet 375(9727):1729–1736
Sambrook P, Cooper C (2006) Osteoporosis. Lancet 367(9527):2010–2018
Boyle WJ, Simonet WS, Lacey DL (2003) Osteoclast differentiation and activation. Nature 423(6937):337–342
Lacey DL, Boyle WJ, Simonet WS, Kostenuik PJ, Dougall WC, Sullivan JK, San Martin J, Dansey R (2012) Bench to bedside: elucidation of the OPG–RANK–RANK-L pathway and the development of denosumab. Nat Rev Drug Discov. 11(5):401–419
Russell RG, Xia Z, Dunford JE, Oppermann U, Kwaasi A, Hulley PA, Kavanagh KL, Triffitt JT, Lundy MW, Phipps RJ, Barnett BL, Coxon FP, Rogers MJ, Watts NB, Ebetino FH (2007) Bisphosphonates: an update on mechanisms of action and how these relate to clinical efficacy. Ann N Y Acad Sci 1117:209–257
Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C, FREEDOM Trial (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361(8):756–765
Papapoulos S, Chapurlat R, Libanati C, Brandi ML, Brown JP, Czerwiński E, Krieg MA, Man Z, Mellström D, Radominski SC, Reginster JY, Resch H, Román Ivorra JA, Roux C, Vittinghoff E, Austin M, Daizadeh N, Bradley MN, Grauer A, Cummings SR, Bone HG (2012) Five years of denosumab exposure in women with postmenopausal osteoporosis: results from the first two years of the FREEDOM extension. J Bone Miner Res 27(3):694–701
Austin M, Yang YC, Vittinghoff E, Adami S, Boonen S, Bauer DC, Bianchi G, Bolognese MA, Christiansen C, Eastell R, Grauer A, Hawkins F, Kendler DL, Oliveri B, McClung MR, Reid IR, Siris ES, Zanchetta J, Zerbini CA, Libanati C, Cummings SR, FREEDOM Trial (2012) Relationship between bone mineral density changes with denosumab treatment and risk reduction for vertebral and nonvertebral fractures. J Bone Miner Res 27(3):687–693
Beck TJ, Lewiecki EM, Miller PD, Felsenberg D, Liu Y, Ding B, Libanati C (2008) Effects of denosumab on the geometry of the proximal femur in postmenopausal women in comparison with alendronate. J Clin Densitom. 11(3):351–359
Brown JP, Prince RL, Deal C, Recker RR, Kiel DP, de Gregorio LH, Hadji P, Hofbauer LC, Alvaro-Gracia JM, Wang H, Austin M, Wagman RB, Newmark R, Libanati C, San Martin J, Bone HG (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(1):153–161
Kendler DL, Roux C, Benhamou CL et al (2010) Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy. J Bone Miner Res 25:72–81
Reid IR, Miller PD, Brown JP, Kendler DL, Fahrleitner-Pammer A, Valter I, Maasalu K, Bolognese MA, Woodson G, Bone H, Ding B, Wagman RB, San Martin J, Ominsky MS, Dempster DW, Denosumab Phase 3 Bone Histology Study Group (2010) Effects of denosumab on bone histomorphometry: the FREEDOM and STAND studies. J Bone Miner Res 25(10):2256–2265
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(2):147–153
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(8):1886–1894
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(1):131–139
Adami S, Libanati C, Boonen S, Cummings SR, Ho PR, Wang A, Siris E, Lane J, FREEDOM Fracture-Healing Writing Group, Adachi JD, Bhandari M, de Gregorio L, Gilchrist N, Lyritis G, Moller G, Palacios S, Pavelka K, Heinrich R, Roux C, Uebelhart D (2012) Denosumab treatment in postmenopausal women with osteoporosis does not interfere with fracture-healing: results from the FREEDOM trial. J Bone Joint Surg Am 94(23):2113–2119
Conflict of interest
The authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Iolascon, G., Resmini, G. & Tarantino, U. Effects of denosumab on cortical and trabecular microarchitecture: evidences from clinical studies. Aging Clin Exp Res 25 (Suppl 1), 19–22 (2013). https://doi.org/10.1007/s40520-013-0086-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40520-013-0086-x