Lactase persistence, milk intake, hip fracture and bone mineral density: a study of 97 811 Danish individuals and a meta-analysis

Background: Whether a causal relationship exists between milk intake and reduced risk of fractures is unclear. Objectives: We tested the hypothesis that genetically determined milk intake reduces the risk of fractures and increases bone mineral density (BMD). Methods: We investigated the association between milk intake, LCT-13910 C/T (rs4988235), which is associated with lactase persistence (TT/TC) in Northern Europeans, and hip fractures in three Danish prospective studies (N = 97 811, age ≥20 years). We added meta-analyses of LCT-13910 and fractures and BMD from five published Northern European population studies. Results: In the Danish studies, the adjusted hazard ratio (HR) for hip fracture per one glass per week higher milk intake was 1.00 (95% CI: 0.99–1.01). The per T-allele milk intake was 0.58 (0.49–0.68) glasses per week, but HR was 1.01 (0.94–1.09) for hip fracture. In meta-analyses of Danish studies with published Northern European population studies, the random effects odds ratio for any fracture was 0.86 (0.61–1.21; I ² = 73%) for TT vs. CC and 0.90 (0.68–1.21; I ² = 63%) for TC vs. CC. The standardized mean difference in femoral neck BMD was 0.10 (0.02–0.18; I ² = 0%) g cm ⁻² for TT vs. CC and 0.06 (−0.04 to 0.17; I ² = 17%) g cm ⁻² for TC vs. CC. There were no differences in lumbar spine or total hip BMD comparing TT or TC with CC. Conclusion: Genetically lifelong lactase persistence with high milk intake was not associated with hip fracture in Danish population-based cohorts. A meta-analysis combining Danish studies with published Northern European population studies also showed that lactase persistence was not associated with fracture risk. Genetic lactase persistence was associated with a higher femoral neck BMD, but not lumbar spine or total hip BMD.