IBMS BoneKEy | Perspective

Anabolic plus antiresorptive: Is one plus one more or less two?

Ego Seeman

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DOI:10.1138/20110510

Abstract

The anabolic effect of parathyroid hormone (PTH) 1-34 is remodeling- and modeling-based. Prior or concurrent use of remodeling suppressants may blunt the rise in remodeling markers and bone mineral density (BMD) produced by PTH1-34, perhaps because 70% of the anabolic effect of PTH1-34 is remodeling-based. Cosman et al. report the opposite; PTH1-34 plus zoledronic acid (ZA) initially produced a greater increase in BMD than PTH1-34 alone. While this may be the result of the modeling-based anabolic effect of PTH1-34 (which is not suppressed by ZA), it is unlikely to be the only explanation as modeling-based bone formation probably also occurs when blunting is reported with other combined antiresorptive-anabolic regimens. A more likely explanation is that ZA produces potent remodeling suppression in the first month of parenteral administration which suppresses the appearance of new resorptive cavities allowing refilling of the many resorption cavities present prior to treatment. Whilst evidence is lacking, the net effect is probably a reduction in intracortical porosity and more complete secondary mineralization of osteons that would otherwise have been replaced with less densely mineralized young osteons. In addition, deposition of new under-mineralized bone in the PTH1-34 alone group may decrease or leave BMD unchanged. While evidence for these morphological changes is needed, changes in BMD account for little of the variance in anti-fracture efficacy between treatments, so the use of a greater increase in BMD as a surrogate of better antifracture efficacy is questionable.

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