Familial risks of hospital treated osteoporosis and fractures in first-, second- and third-degree relatives - A Swedish nationwide real-world family study

OBJECTIVE: Osteoporosis (OP) is a common degenerative disorder. This is the first real-world nationwide study aimed to determine the familial risks of hospital treated OP and fractures in first-, second- and third-degree relatives. DESIGN: The Swedish Multigeneration register was linked to the National Patient Register to investigate the familial risks of OP between 1997 and 2018. Offspring born to Swedish parents were included. The adjusted familial hazard ratios (afHRs) with 95% confidence interval (CI) were determined for hospital treated OP and fractures at common osteoporotic fracture sites among twins, full-siblings, half-siblings, and cousins. There was no information about zygosity of the twins. Adjustments were made for birth year, sex, educational level, and comorbidities. RESULTS: 6,548,562 individuals (48.77% women) were included with a mean age of 41 years (range 0-87 years) at the end of follow-up. 57,869 (0.88%) individuals were affected with hospital treated OP, and 403,660 (6.16%) individuals with fractures. The afHRs were increased for both OP and fractures in twins, full-siblings, half-siblings, and cousins. The afHR for OP were for twins 2.92 (95%CI 2.32-3.67), full-siblings 2.22 (95%CI 2.14-2.31), half-siblings 1.74 (95%CI 1.55-1.94), cousins 1.81 (95%CI 1.55-2.11). Age-stratified analysis showed age-dependent familial associations with highest afHR in young individuals (<20 years): among full-siblings afHR was 125.70 (95%CI 59.44-265.84) for OP and 2.34 (95%CI 2.28-2.39) for fractures. CONCLUSIONS: Heredity is associated with risk of hospital treated OP and fractures in the Swedish population. The familial risk of hospital treated OP or fractures is related to the genetic closeness of the affected relative(s).