Objectively-Verified Parental Non-Hip Major Osteoporotic Fractures and Offspring Osteoporotic Fracture Risk: A Population-Based Familial Linkage Study.

Parental hip fracture (HF) is associated with increased risk of offspring major osteoporotic fractures (MOFs; comprising hip, forearm, clinical spine or humerus fracture). Whether other sites of parental fracture should be used for fracture risk assessment is uncertain. The current study tested the association between objectively-verified parental non-hip MOF and offspring incident MOF. Using population-based administrative healthcare data for the province of Manitoba, Canada, we identified 255,512 offspring with linkage to at least one parent (238,054 mothers and 209,423 fathers). Parental non-hip MOF (1984-2014) and offspring MOF (1997-2014) were ascertained with validated case definitions. Time-dependent multivariable Cox proportional hazards regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs). During a median of 12 years of offspring follow-up, we identified 7045 incident MOF among offspring (3.7% and 2.5% for offspring with and without a parental non-hip MOF, p < 0.001). Maternal non-hip MOF (HR 1.27; 95% CI, 1.19 to 1.35), paternal non-hip MOF (HR 1.33; 95% CI, 1.20 to 1.48), and any parental non-hip MOF (HR 1.28; 95% CI, 1.21 to 1.36) were significantly associated with offspring MOF after adjusting for covariates. The risk of MOF was even greater for offspring with both maternal and paternal non-hip MOF (adjusted HR 1.61; 95% CI, 1.27 to 2.02). All HRs were similar for male and female offspring (all pinteraction >0.1). Risks associated with parental HF only (adjusted HR 1.26; 95% CI, 1.13 to 1.40) and non-hip MOF only (adjusted HR 1.26; 95% CI, 1.18 to 1.34) were the same. The strength of association between any parental non-hip MOF and offspring MOF decreased with older parental age at non-hip MOF (ptrend  = 0.028). In summary, parental non-hip MOF confers an increased risk for offspring MOF, but the strength of the relationship decreases with older parental age at fracture. © 2016 American Society for Bone and Mineral Research.