Bisphosphonate effects on bone turnover, microdamage, and mechanical properties: What we think we know and what we know that we don't know

Abstract

This is the author's manuscript of the article published in final edited form as: Allen M. R., Burr D.B. (2011 A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT AbstractThe bisphosphonates (BPs) have been useful tools in our understanding of the role that bone remodeling plays in skeletal health. The purpose of this paper is to outline what we know, and what is still unknown, about the role that BPs play in modulating bone turnover, how this affects microdamage accumulation, and ultimately what the effects of these changes elicited by BPs are to the structural and the material biomechanical properties of the skeleton. We know thatBPs suppress remodeling site-specifically, probably do not have a direct effect on formation, and that the individual BPs vary with respect to speed of onset, duration of effect and magnitude of suppression. However, we do not know if these differences are meaningful in a clinical sense, how much remodeling is sufficient, the optimal duration of treatment, or how long it takes to restore remodeling to pre-treatment levels. We also know that suppression is intimately tied to microdamage accumulation, which is also site-specific, that BPs impair targeted repair of damage, and that they can reduce the energy absorption capacity of bone at the tissue level.However, the BPs are clearly effective at preventing fracture, and generally increase bone mineral density and whole bone strength, so we do not know whether these changes in damage accumulation and repair, or the mechanical effects at the tissue level, are clinically meaningful.The mechanical effects of BPs to the fatigue life of bone, or BP effects on bone subject to an impact, are entirely unknown. This paper reviews the literature on these topics, and identifies gaps in knowledge that can be addressed with further research.

Epidemiology, radiology and histology of atypical femoral fractures

“…At the moment there is no consistent evidence that bisphosphonate treatment increases the burden of microdamage in bone in humans (Allen and Burr 2011).…”

Effect of Risedronate on Bone in Renal Transplant Recipients

“…There may be a difference between secondand third-generation bisphosphonate enzyme suppressive activities. [23][24][25] Several studies of parenteral pamidronate reported preservation of BMD [26][27][28] but there were no histomorphometry or sex comparisons. Finally, although we observed a possible risedronate-sex interaction, our study was not designed to assess this.…”

Bisphosphonate-Induced Osteonecrosis of the Jaw: Comparison of Disease Extent on Contrast-Enhanced MR Imaging, [18F] Fluoride PET/CT, and Conebeam CT imaging

“…[ 18 F] fluoride is a radioactive tracer that is incorporated in hydroxyapatite by osteoblasts during bone neoformation. 9 Homeostasis of bone resorption and neoformation is markedly altered in patients with BONJ under bisphosphonate treatment 19 and not only affects the BONJ focus itself but may lead to increased bone sclerosis or periosteal thickening beyond the clinically overt BONJ lesion. 4,6 These often subtle bone changes are hardly perceivable on conventional panoramic radiographs or .…”