Association of sugar rationing during the first 1000 days with long-term risk of osteoporosis: A natural experiment study

BACKGROUND: The first 1000 days, from conception to approximately the second birthday, are important for skeletal development. We examined whether lower sugar availability during this period was associated with osteoporosis in adulthood. METHODS: We studied 65,346 UK-born UK Biobank participants born between October 1951 and March 1956 (mean baseline age, 54.6 years; 55.9% women). Birth month defined four categories of early-life sugar rationing exposure: never exposed, in utero only, in utero plus up to 1year, and in utero plus up to 2 years. Cox models estimated associations with hospital-recorded incident osteoporosis. We also examined differences by sex and polygenic risk score (PRS) and tested alternative time scales. RESULTS: During a median 13.8 years of follow-up, 1606 incident cases occurred. Compared with never exposed participants, fully adjusted hazard ratios were 0.94 (95% CI, 0.80-1.11), 0.78 (0.66-0.93), and 0.77 (0.63-0.95) across the three progressively longer exposure categories (P for trend=0.006). We found no evidence of interaction with sex (P=0.385) or PRS tertile (P=0.816). When attained age was the time scale, the estimate for the longest exposure was 0.93 (0.81-1.06). CONCLUSIONS: Sugar rationing exposure extending into infancy was associated with a lower hazard of adult osteoporosis in the primary analysis. The association weakened when attained age was the time scale, limiting causal interpretation. We found no evidence of greater benefit among participants with higher genetic risk.