Preclinical Rodent Models for Human Bone Disease, Including a Focus on Cortical Bone

Area of Science:

• Skeletal Biology and Disease
• Preclinical Research Models
• Bone Physiology

Background:

• Preclinical models, primarily rats and mice, are foundational to skeletal biology research.
• These models have been instrumental in developing therapies for osteoporosis and genetic bone disorders.
• Advances in treating skeletal conditions, especially cortical bone strength, necessitate improved understanding and reporting of preclinical models.

Purpose of the Study:

• To describe bone structure development, maintenance, and degeneration in mice, rats, and humans.
• To examine cortical bone changes in preclinical models of endocrine conditions.
• To provide guidelines for consistent use and interpretation of mouse models in skeletal research.

Main Methods:

• Review of trabecular and cortical bone development, maintenance, and aging in mice, rats, and humans.
• Analysis of cortical bone structure in preclinical models of endocrine conditions (osteoporosis, CKD, hyperparathyroidism, diabetes).
• Discussion of common concerns in comparing rodent models to the human skeleton, with a focus on cortical bone differences.

Main Results:

• Cortical bone structure differs between small and large mammals.
• Mechanisms controlling cortical bone strength and structure are common to mice and humans.
• Recent findings highlight genetic contributors to cortical porosity and osteocyte networks across lifespan stages.

Conclusions:

• Improved understanding and rigorous reporting of preclinical models are essential for therapeutic advances in skeletal biology.
• Guidelines are provided to enhance consistency in the use and interpretation of mouse models.
• Focusing on cortical bone in preclinical research is critical due to its distinct structure in different mammals.