Antiresorptive and anabolic agents in the prevention and reversal of bone fragility

Journal article

Seeman, Ego and Martin, T. J.. (2019). Antiresorptive and anabolic agents in the prevention and reversal of bone fragility. Nature Reviews Rheumatology. 15(4), pp. 225 - 236. https://doi.org/10.1038/s41584-019-0172-3

Authors	Seeman, Ego and Martin, T. J.
Abstract	Bone volume, microstructure and its material composition are maintained by bone remodelling, a cellular activity carried out by bone multicellular units (BMUs). BMUs are focally transient teams of osteoclasts and osteoblasts that respectively resorb a volume of old bone and then deposit an equal volume of new bone at the same location. Around the time of menopause, bone remodelling becomes unbalanced and rapid, and an increased number of BMUs deposit less bone than they resorb, resulting in bone loss, a reduction in bone volume and microstructural deterioration. Cortices become porous and thin, and trabeculae become thin, perforated and disconnected, causing bone fragility. Antiresorptive agents reduce fracture risk by reducing the rate of bone remodelling so that fewer BMUs are available to remodel bone. Bone fragility is not abolished by these drugs because existing microstructural deterioration is not reversed, unsuppressed remodelling continues producing microstructural deterioration and unremodelled bone that becomes more mineralized can become brittle. Anabolic agents reduce fracture risk by stimulating new bone formation, which partly restores bone volume and microstructure. To guide fracture prevention, this Review provides an overview of the structural basis of bone fragility, the mechanisms of remodelling and how anabolic and antiresorptive agents target remodelling defects.
Year	2019
Journal	Nature Reviews Rheumatology
Journal citation	15 (4), pp. 225 - 236
Publisher	Nature Publishing Group
ISSN	1759-4790
Digital Object Identifier (DOI)	https://doi.org/10.1038/s41584-019-0172-3
Scopus EID	2-s2.0-85061515592
Page range	225 - 236
Research Group	Mary MacKillop Institute for Health Research
Publisher's version	File Access Level Controlled
Place of publication	United Kingdom

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A. Michael Parfitt: Enlightened scholar and revered mentor: May 10, 1930-May 18, 2015

Manolagas, Stavros C., Compston, Juliet, Rao, Sudhaker and Seeman, Ego. (2015). A. Michael Parfitt: Enlightened scholar and revered mentor: May 10, 1930-May 18, 2015. Journal of Bone and Mineral Research. 30(8), pp. 1349 - 1355. https://doi.org/10.1002/jbmr.2576

Co-administration of antiresorptive and anabolic agents: A missed opportunity

Seeman, Ego and Martin, T. John. (2015). Co-administration of antiresorptive and anabolic agents: A missed opportunity. Journal of Bone and Mineral Research. 30(5), pp. 753 - 764. https://doi.org/10.1002/jbmr.2496

The ABC of writing a grant proposal

Seeman, Ego. (2015). The ABC of writing a grant proposal. Osteoporosis International. 26(6), pp. 1665 - 1666. https://doi.org/10.1007/s00198-015-3085-2

Growth and age-related abnormalities in cortical structure and fracture risk

Seeman, Ego. (2015). Growth and age-related abnormalities in cortical structure and fracture risk. Endocrinology and Metabolism. 30(4), pp. 419 - 428. https://doi.org/10.3803/EnM.2015.30.4.419

High-resolution in vivo imaging of bone and joints: a window to microarchitecture

Geusens, P., Geusens, P., Chapurlat, Roland D., Chapurlat, Roland D., Schett, G., Ghasem-Zadeh, Ali, Ghasem-Zadeh, Ali, Seeman, Ego, De Jong, J. and Van Den Bergh, J.. (2014). High-resolution in vivo imaging of bone and joints: a window to microarchitecture. Nature Reviews Rheumatology. 10(5), pp. 304 - 313. https://doi.org/10.1038/nrrheum.2014.23

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

Zebaze, Roger M., Ghasem-Zadeh, Ali, Mbala, A. and Seeman, Ego. (2013). 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. 54(1), pp. 8 - 20. https://doi.org/10.1016/j.bone.2013.01.007

Teriparatide improves bone quality and healing of atypical femoral fractures associated with bisphosphonate therapy

Chiang, Cherie Ying, Zebaze, Roger M.D., Ghasem-Zadeh, Ali, Iuliano-Burns, Sandra, Hardidge, Andrew and Seeman, Ego. (2013). Teriparatide improves bone quality and healing of atypical femoral fractures associated with bisphosphonate therapy. Bone. 52(1), pp. 360 - 365. https://doi.org/10.1016/j.bone.2012.10.006

Predictors of new and severe vertebral fractures: Results from the HoRIZoN Pivotal Fracture Trial

Wustrack, R., Seeman, Ego, Bucci-Rechtweg, C. and Burch, S.. (2012). Predictors of new and severe vertebral fractures: Results from the HoRIZoN Pivotal Fracture Trial. Osteoporosis International. 23(1), pp. 53 - 58. https://doi.org/10.1007/s00198-011-1664-4

The effect of acute exercise on undercarboxylated osteocalcin in obese men

Levinger, Itamar, Zebaze, Roger M., Jeru, G., Hare, David L., Selig, Steve and Seeman, Ego. (2011). The effect of acute exercise on undercarboxylated osteocalcin in obese men. Osteoporosis International. 22(5), pp. 1621 - 1626. https://doi.org/10.1007/s00198-010-1370-7