Ionized calcium (Ca2+), phosphate, albumin, total calcium, and pH measurements taken from participants in a large population-based epidemiological study were examined to determine the change in physiological variation with age for persons over 43 years old. Only Ca2+ showed a statistically significant increase in SD with age (p < 0.0001). The Ca2+ coefficients of variation (CV) increased from 2.92% in the youngest age group (43-54 years) to 3.69% in the oldest age group (75-86 years of age). In females, the increase in Ca2+ variability was nearly complete by age 55. Males also showed a significant (p = 0.006) increase in SD between the 43-54 age group and the 55-64 age group, however, Ca2+ variability did not plateau after age 55 in men as it did in women. In the 43-54 (p = 0.04) and 55-64 (p = 0.03) age group men showed significantly better physiological control of Ca2+ than women. Phosphate showed a slight decrease in CV with age. These data suggest that Ca2+ homeostasis is disrupted in the same age groups that are most vulnerable to osteoporosis.