Preclinical models (typically ovariectomized rats and genetically altered mice) have underpinned much of what we know about skeletal biology. They have been pivotal for developing therapies for osteoporosis and monogenic skeletal conditions, including osteogenesis imperfecta, achondroplasia, hypophosphatasia, and craniodysplasias. Further therapeutic advances, particularly to improve cortical strength, require improved understanding and more rigorous use and reporting. We describe here how trabecular and cortical bone structure develop, are maintained, and degenerate with aging in mice, rats, and humans, and how cortical bone structure is changed in some preclinical models of endocrine conditions (eg, postmenopausal osteoporosis, chronic kidney disease, hyperparathyroidism, diabetes). We provide examples of preclinical models used to identify and test current therapies for osteoporosis, and discuss common concerns raised when comparing rodent preclinical models to the human skeleton. We focus especially on cortical bone, because it differs between small and larger mammals in its organizational structure. We discuss mechanisms common to mouse and human controlling cortical bone strength and structure, including recent examples revealing genetic contributors to cortical porosity and osteocyte network configurations during growth, maturity, and aging. We conclude with guidelines for clear reporting on mouse models with a goal for better consistency in the use and interpretation of these models.

中文翻译：

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人类骨疾病的临床前啮齿动物模型，包括重点关注皮质骨。


临床前模型（通常是切除卵巢的大鼠和基因改造的小鼠）支撑了我们对骨骼生物学的大部分了解。它们对于开发骨质疏松症和单基因骨骼疾病（包括成骨不全、软骨发育不全、低磷酸酯酶症和颅骨发育不良）的治疗方法至关重要。进一步的治疗进展，特别是提高皮质强度，需要更好的理解和更严格的使用和报告。我们在这里描述了小鼠、大鼠和人类的小梁骨和皮质骨结构如何随着衰老而发育、维持和退化，以及皮质骨结构在一些内分泌疾病的临床前模型（例如绝经后骨质疏松症、慢性肾病、甲状旁腺功能亢进症、糖尿病）。我们提供了用于识别和测试当前骨质疏松症疗法的临床前模型的示例，并讨论了在将啮齿动物临床前模型与人体骨骼进行比较时提出的常见问题。我们特别关注皮质骨，因为小型和大型哺乳动物的皮质骨在组织结构上有所不同。我们讨论了小鼠和人类控制皮质骨强度和结构的常见机制，包括最近的例子揭示了生长、成熟和衰老过程中皮质孔隙度和骨细胞网络配置的遗传因素。最后，我们提出了关于小鼠模型的清晰报告的指南，目的是使这些模型的使用和解释具有更好的一致性。