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

TY - JOUR

T1 - Lactase persistence, milk intake, hip fracture and bone mineral density

T2 - a study of 97 811 Danish individuals and a meta-analysis

AU - Bergholdt, H K M

AU - Larsen, M K

AU - Varbo, A

AU - Nordestgaard, B G

AU - Ellervik, C

PY - 2018/9

Y1 - 2018/9

N2 - 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; I2 = 73%) for TT vs. CC and 0.90 (0.68-1.21; I2 = 63%) for TC vs. CC. The standardized mean difference in femoral neck BMD was 0.10 (0.02-0.18; I2 = 0%) g cm-2 for TT vs. CC and 0.06 (-0.04 to 0.17; I2 = 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.

AB - 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; I2 = 73%) for TT vs. CC and 0.90 (0.68-1.21; I2 = 63%) for TC vs. CC. The standardized mean difference in femoral neck BMD was 0.10 (0.02-0.18; I2 = 0%) g cm-2 for TT vs. CC and 0.06 (-0.04 to 0.17; I2 = 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.

U2 - 10.1111/joim.12753

DO - 10.1111/joim.12753

M3 - Journal article

C2 - 29537719

SN - 0955-7873

VL - 284

SP - 254

EP - 269

JO - Journal of Internal Medicine, Supplement

JF - Journal of Internal Medicine, Supplement

IS - 3

ER -