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Muscle force is thought to be one of the main determinants of bone development. Hence, peak muscle growth is expected to precede peak bone growth. In this study, we investigated muscle and bone development in female C57BL/6 J, DBA/2JRj, and C3H/HeOuJ mice. Femoral cortical and trabecular bone structure and the weights of selected muscles were assessed at the ages of 8, 16, and 24 weeks. Muscle mass increased from 8 to 24 weeks in all 3 strains, suggesting peak muscle development at 24 weeks or later. Bone volume fraction, trabecular number, and connectivity density of the femur decreased or remained unchanged, whereas trabecular density and trabecular thickness largely increased. These results suggest a peak in trabecular bone accrual at 8 weeks or earlier followed by further increases in density and structural reorganization of trabeculae. Cortical density, cortical thickness, and cortical cross sectional area increased over time, suggesting a peak in cortical bone accrual at 24 weeks or later. In conclusion, our data provide evidence that growth of muscle lags behind trabecular bone accrual.

<b><i>Introduction:</i></b> Osteoporosis is a frequent age-related disease, which affects millions of people worldwide. Despite significant progress in the treatment of the disease, a high number of patients still are underdiagnosed and undertreated. Therefore, novel animal models for the investigation of the disease are necessary. <i>Nothobranchius furzeri</i> is the shortest-lived vertebrate (with a lifespan of 3–7 months) that can be kept in captivity. Although it is an established model for aging research, studies on bone are lacking. The aim of this study was therefore to characterize <i>N. furzeri</i> as a potential model for age-related osteoporosis<i>.</i> <b><i>Materials and Methods:</i></b> Bone properties of aging <i>N. furzeri</i> were investigated in male and female fish of the Gona Re Zhou strain, which were between 8 and 20 weeks old. Micro-computed tomography (Scanco Medical µCT35) was performed to determine the bone properties of the vertebral bodies. Bone structure and remodeling were investigated by different histological staining techniques and histomorphometry. The chemical composition of fish vertebrae and intervertebral discs was analyzed by Raman microspectroscopy. <b><i>Results:</i></b> Osteoblasts, mono- and multinucleated osteoclasts but no osteocytes could be observed in the vertebral area of <i>N. furzeri</i>. Histomorphometric evaluations revealed a significant decrease of the number of osteoblasts/bone perimeter and for osteoid volume/bone volume (BV) a trend toward a decrease in old male <i>N. furzeri.</i> Comparing male and female fish, males showed higher BV densities and cortical thickness. The relative values of the bone volume density of 20-week-old male <i>N. furzeri</i> were significantly lower than 10-week-old ones. The mineral to matrix ratio increased with age in male and female fish. In the intervertebral discs, proteoglycans in relation to the organic matrix were significantly lower in older female fish. <b><i>Conclusion:</i></b> Our finding of a lack of osteocytes is in agreement with the fact that <i>N. furzeri</i> belongs to the evolutionarily advanced teleost fish. Furthermore, not only age-specific but also sex-specific differences were visible in the bone properties of <i>N. furzeri</i>, which can be taken into consideration for the study of gender aspects of age-related musculoskeletal diseases.

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