The Scientific Case for Animal Models: A Perspective From Musculoskeletal Researchers.

Area of Science:

• Musculoskeletal Biology and Biomedical Research

Background:

• The National Institutes of Health (NIH) promotes New Approach Methodologies (NAMs) to reduce animal model reliance.
• Animal research is indispensable for understanding complex musculoskeletal processes, disease progression, and therapy development.
• Foundational knowledge in development, disease mechanisms, regeneration, gene function, and pharmacology originates from animal models.

Purpose of the Study:

• To review the essential role of animal models in musculoskeletal biology.
• To examine New Approach Methodologies (NAMs) and their limitations.
• To advocate for the integration of NAMs as complementary tools alongside animal research.

Main Methods:

• Review of existing literature on animal models and NAMs in musculoskeletal science.
• Analysis of the strengths and limitations of NAMs (organoids, engineered scaffolds, organ-on-chip, AI/computational modeling).
• Focus on five key musculoskeletal areas: osteoporosis, osteoarthritis, fracture repair, bone cancer, and inherited skeletal disorders.

Main Results:

• Animal models are crucial for understanding complex in vivo processes, disease mechanisms, and preclinical testing.
• NAMs offer strengths in mechanistic and high-throughput studies but cannot replicate in vivo complexity.
• Animal research is essential for developing and translating therapies for musculoskeletal conditions.

Conclusions:

• Animal models remain the gold standard for exploring disease mechanisms and testing therapeutic efficacy and safety.
• NAMs should complement, not replace, animal research to advance musculoskeletal science.
• Ethically conducted animal research is a cornerstone of musculoskeletal health, essential for medical progress.