Cervical vertebrae for early bone loss evaluation in osteoporosis mouse models

Abstract

Background: Osteoporosis (OP), a systemic skeletal disease common in aged population, is an important public health problem worldwide. Animal models are important tools for understanding OP. In ovariectomy (OVX) or orchiectomy (ORX) OP models, lumbar vertebrae are often used for evaluating of the OP progression. However, unlike the bipeds, the lumbar vertebrae are not weight loading bones in quadruped animal, but the head-bearing cervical vertebrae take much higher stress. So, we compared the murine cervical vertebrae with lumbar vertebrae for OP assessment. Methods: OVX and ORX mouse models were established on C57BL/6J mice. Serum estradiol, testosterone and bone related biomarkers were verified. Bone quantity and quality were determined using micro computed tomography (micro-CT) analysis. Hard tissue sections were prepared, stained for histomorphological analyzing, and micro-indentation measured for bone mechanical property evaluation. Results: In OVX and ORX mice, serum estradiol or testosterone levels reduced, bone resorption level and related biomarkers elevated, indicated the successful generation of the OP models. In the early stage, the trabecular bone mineral density (BMD) of cervical vertebrae was already reduced 16.1% (OVX) and 21.7% (ORX) one-month post-gonadectomy, respectively; while this decline in the fifth lumbar vertebra were only 5% and 7.4%, respectively. Six months post-gonadectomy, the reduction of BMD in cervical vertebrae and the fifth lumbar vertebra were 31.2% & 36.1% and 28.5% & 30.7% respectively. In biomechanical aspects, cervical spines showed worse Vickers hardness (HV) and elastic modulus than lumbar spine in six-month OVX and ORX mice. Conclusions: We provide a new OP early-stage evaluation mouse model based on the cervical spine. Through the radiographic, biological and biomechanical assessments, the mouse cervical spine is more suitable for bone remodeling evaluation in OP models than the conventional lumbar vertebrae, especially for early-stage OP study.