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THE RELATION BETWEEN LOADING RATE, STRAIN GRADIENTS, AND BONE ADAPTATION



Abstract

Bones can adapt in response to mechanical stimuli; higher rates of loading have been associated with greater bone formation rates. This study determined where bone accretion was localized in response to high loading rates. Non-invasive loads were applied to mice tibiae at one of three rates for four week. It was found, via calcein labels, that adaptation on the periosteal, but not endosteal, surface exhibited a dose-response relation with loading rate; periosteal and endosteal adaptation was localized to regions of high strain gradients. Understanding the stimuli bone responds to may underpin the development of non-pharmacological treatments to enhance bone mass.

Bones can adapt to mechanical stimuli; higher rates of loading have been linked with greater bone formation rates (BFR).

The purpose of this research was to determine if bone accretion associated with higher loading rates occurs in regions of high strain gradients or strain rates and if adaptation is similar on periosteal and endosteal surfaces.

Periosteal but not endosteal surfaces displayed a dose-response relation with loading rate. Adaptation on both periosteal and endosteal surfaces was localized to sectors with high strain gradients.

Understanding the precise stimuli by which bone responds may underpin the development of non-pharmacological treatments to enhance bone mass.

Tibia loaded at the high rate had significantly greater periosteal BFR, relative to tibiae loaded at medium (> 48 %) and low (> 104 %) rates; adaptation was localized to posterior sectors (high strain gradients). Endosteally, adaptation was localized to regions of high strain gradients (anterior sectors), but did not display a dose-response relation with loading rate.

Forty-three skeletally mature C57BL/6 mice were randomly assigned to one of three groups, based on loading rate; low (0.004 ε/s; n = 14), medium (0.020 ε/s; n = 15), and high (0.100 ε/s; n = 14). Loads were applied so that tibiae experienced non-invasive medio-lateral cantilever bending (peak strain = 1000 με) at 1 Hz, 60 s, 5 d/w, for 4 wk. Calcein bone labels were administered on d one and eighteen. A standardized sector of the tibial middiaphyeal shaft was digitally divided into 45° radial sectors, and prepared for histomorphometry.

Funding: Funded in part by NSERC, and CIHR

Correspondence should be addressed to Cynthia Vezina, Communications Manager, COA, 4150-360 Ste. Catherine St. West, Westmount, QC H3Z 2Y5, Canada