Immersion in Raloxifene does not significantly improve bone toughness or screw pull-out strength in multiple in vitro models

Abstract

Background Failure of surgical fixation in orthopaedic fractures occurs at a significantly higher rate in osteoporotic patients due to weakened osteoporotic bone. A therapy to acutely improve the mechanical properties of bone during fracture repair would have profound clinical impact. A previous study has demonstrated an increase in mechanical properties of acellular cortical canine bone after immersion in raloxifene. The goal of this study was to determine if similar treatment yields the same results in cancellous fetal bovine bone and whether this translates into a difference in screw pull-out strength in human cadaveric tissue. Methods Cancellous bone from fetal bovine distal femora underwent quasi-static four-point bending tests after being immersed in either raloxifene (20 μM) or phosphate-buffered saline as a control for 7 days (n = 10). Separately, 5 matched pairs of human osteoporotic cadaveric humeral heads underwent the same procedure. Five 3.5 mm unicortical cancellous screws were then inserted at standard surgical fixation locations to a depth of 30 mm and quasi-static screw pull-out tests were performed. Results In the four-point bending tests, there were no significant differences between the raloxifene and control groups for any of the mechanical properties - including stiffness (p = 0.333) and toughness (p = 0.546). In the screw pull-out tests, the raloxifene soaked samples and control samples had pullout strengths of 122 ± 74.3 N and 89.5 ± 63.8 N, respectively. Conclusions Results from this study indicate that cancellous fetal bovine samples did not demonstrate an increase in toughness with raloxifene treatment, which is in contrast to previously published data that studied canine cortical bone. In vivo experiments are likely required to determine whether raloxifene will improve implant fixation.

Bone hydration: How we can evaluate it, what can it tell us, and is it an effective therapeutic target?

“…12 D) ( Allen et al, 2017 ). This suite of beagle studies using clinically relevant doses of raloxifene has since spurred several important pre-clinical studies looking at the efficacy of raloxifene across animal and disease models and in combination with other bone therapeutics ( Eby et al, 2021 ; Powell et al, 2019 ; Tastad et al, 2021 ; Wang et al, 2021a ).

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