Heredity and environmental factors contribute to the development of osteoporosis. Because calcium is the major mineral in bone and adolescence is a key period in bone acquisition, we hypothesized that bone turnover would be less responsive to alterations in dietary calcium intake in both girls and adult women from families with histories of osteoporosis. To address this issue, we studied calcium kinetics in the maternal grandmother (age range 56–81 years), mother (age range 32–47 years), and granddaughter (age range 8–15 years) in 10 multigenerational families. In five families, the mother and/or grandmother had osteoporosis (bone mineral density ≥ 2 SD below the age-specific mean). To examine both active and passive calcium absorption, families consumed low- (279 ± 64 mg/day) and high- (1580 ± 385) calcium diets for 10 days prior to administration of oral (46Ca) and intravenous (42Ca) stable isotopes. Using repeated measures analysis of variance, fractional calcium absorption, true calcium absorption, bone calcium deposition, and the balance in bone calcium turnover were all significantly affected by diet (p < 0.01). Females from nonosteoporotic families had decreased bone calcium resorption with little change in bone calcium deposition during the high-calcium study. In contrast, girls and adult women from osteoporotic families had increased both bone calcium deposition and resorption during the high-calcium period, leading to a less positive balance in bone calcium turnover. A significant interaction between bone status and diet was found for bone calcium resorption (p < 0.05) and approached significance for bone calcium deposition (p < 0.07), effects which were independent of generation. We conclude that girls and women from osteoporotic families have a significantly altered bone turnover response to acute changes in calcium intake.