Previous research has demonstrated significant age‐ and sex‐related differences in bone loss in European populations. This study utilizes metacarpal radiogrammetry to analyze cortical bone thickness and bone loss for a sample of indigenous individuals (n = 120) from the Hospital Real San José de los Naturales (HSJN) skeletal collection in Colonial Mexico City. The results indicate statistically significant differences between males and females in total length, total width, and cortical thickness, but no difference in the standardized cortical index measure. There are significant differences in age groups for all measures except total length and the population follows a similar pattern of decreased cortical index over the life course. When age and sex are considered together, females begin this bone loss from young to middle adulthood with continued loss in old adulthood; however, males do not see a decrease in cortical index until old adulthood. While these results are consistent with previously reported patterns of bone loss, the HSJN population has higher levels of peak cortical bone in young adulthood than any archeological European populations. We suggest that this increased peak bone mass may reflect differences in diet that include higher levels of calcium and magnesium as a result of the traditional practice of softening corn by boiling it in limewater (nixtamalization). Similarly, a small sample of African descendant individuals (n = 5) from the HSJN population was compared with the averages for indigenous individuals in the collection and indicated a variation in bone size, though predominantly higher levels of cortical index that may also suggest important population differences that should be further explored. This research provides important comparative data on bone maintenance and loss that supports previous hypotheses that a higher nutrient diet in modern populations may be the key factor in increased peak bone mass compared with archeological populations.