D-galactose-induced osteoporosis in rodents—Model development, skeletal characteristics, and optimal dosing regimens: A scoping review

D-galactose has been extensively utilized as a compound to accelerate aging and induce osteoporosis in rodent models. However, variations in dosage, administration routes, and experimental protocols have resulted in inconsistent findings. This scoping review aims to compile preclinical evidence on the use of D-galactose to induce bone loss, with a particular focus on identifying optimal dosing regimens and their specific impacts on skeletal indices. A systematic literature search was conducted in PubMed, Scopus, and Web of Science using predefined terms related to D-galactose-induced osteoporosis in rodents. Eligible studies were selected based on inclusion criteria, concentrating on both in vivo and in vitro models. A total of 44 studies met these criteria, primarily involving rats and mice. D-galactose was administered via subcutaneous, intraperitoneal, or oral routes, with doses ranging from 10 to 10,000 mg/kg/day for durations spanning 20 days to 5 months. The most commonly employed regimen was 200 mg/kg/day for 8 weeks. D-galactose consistently induced osteoporotic changes, including reduced bone mineral density, compromised microarchitecture, decreased biomechanical strength, and alterations in bone turnover markers. These skeletal changes were associated with oxidative stress, cellular senescence, and ferroptosis. Susceptibility to these effects was influenced by sex, species, and age, with male rodents generally exhibiting greater sensitivity. In conclusion, D-galactose serves as an effective model for age-related osteoporosis in rodents, primarily mediated by oxidative stress and accelerated cellular senescence. A regimen of 200 mg/kg/day administered subcutaneously or intraperitoneally for 8 weeks is commonly used to replicate osteoporotic phenotypes. Greater standardization of protocols is necessary to enhance reproducibility and translational relevance in future studies.