The longitudinal effects of ovariectomy on the morphometric, densitometric and mechanical properties in the murine tibia: A comparison between two mouse strains

Abstract Oestrogen deficiency-related bone loss in the ovariectomized (OVX) mouse is a common model for osteoporosis. However, a comprehensive in vivo assessment of intervention-related changes in multiple bone properties, and in multiple mouse strains, is required in order to identify an appropriate model for future evaluation of novel anti-osteoporotic therapies. The aim of this study was to evaluate the effect of OVX on the morphometric and densitometric properties measured in the microCT images and the mechanical properties estimated with finite element models of the tibia in two mouse strains, C57BL/6 and BALB/c. 14-weeks-old female C57BL/6 and BALB/c mice were divided into two groups per strain: (1) ovariectomized, (2) non-operated control. The right tibia was scanned at baseline (14 weeks) and then every two weeks thereafter, until 24-weeks-old, using in vivo microCT. Changes in trabecular and cortical bone morphometry, spatiotemporal changes in densitometric properties and in mechanical properties (from micro-finite element (μFE) analysis) were computed. Differences between OVX and non-operated controls were evaluated by ANCOVA, adjusted for 14-weeks baseline. In morphometry, trabecular bone mass was significantly reduced in both C57BL/6 and BALB/c from four weeks following surgery. Though the OVX-effect was transient in BALB/c as bone mass reached skeletal homeostasis. OVX inhibited the age-related thickening of cortical bone only in C57BL/6. In both strains, increments in bone mineral content were significantly lower with OVX only in the proximal tibia, with intervention-related differences increasing with time. OVX had no effect on μFE estimates of stiffness nor failure load in either strain. The results of this study show strain-, time- and region-(trabecular or cortical) dependent changes in morphometric and densitometric properties. These findings highlight the importance of choosing an appropriate mouse model and time points for research of treatments against accelerated bone resorption.