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

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 vol...

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Veröffentlicht in:Nature reviews. Rheumatology 2019-04, Vol.15 (4), p.225-236
Hauptverfasser: Seeman, Ego, Martin, T. J.
Format: Artikel
Sprache:eng
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Zusammenfassung: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. Bone turnover and risk of fracture are orchestrated by homeostatic functions of osteoclast–osteoblast bone remodelling units. Anabolic and antiresorptive drugs used to treat and prevent fractures have differing effects on remodelling defects, but which class of drug is the preferred front-line therapy? Key points Slowness of the formation phases of bone remodelling produces a systemically ever-present deficit in bone volume that is transient and focally reversible. The size of the reversible deficit in bone volume is remodelling-rate-dependent. During early menopause, the rapid increase in remodelling rate enlarges the reversible deficit, causing a rapid decrease in bone mineral density (BMD). Remodelling imbalance occurs around the ages of 45–50 years, producing irreversible deficits in bone volume, microstructural deterioration and bone fragility. Antiresorptive agents slow remodelling, thereby reducing the reversible deficit in bone volume, resulting in an early rapid increase in BMD, but the irreversible deficit in bone volume responsible for microstructural deterioration
ISSN:1759-4790
1759-4804
DOI:10.1038/s41584-019-0172-3