H K M Bergholdt1,2, M K Larsen2,3, A Varbo4,5, B G Nordestgaard6,4,5,7, C Ellervik2,6,8,9. 1. Department of Clinical Biochemistry, Copenhagen University Hospital Naestved Slagelse Ringsted, Naestved, Denmark. 2. The Danish General Suburban Population Study, Copenhagen University Hospital Naestved Slagelse Ringsted, Naestved, Denmark. 3. Department of Science and Environment, University of Roskilde, Roskilde, Denmark. 4. Department of Clinical Biochemistry, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark. 5. The Copenhagen General Population Study, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark. 6. The Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 7. The Copenhagen City Heart Study, Copenhagen University Hospital, Frederiksberg Hospital, Frederiksberg, Denmark. 8. Department of Production, Research and Innovation, Region Zealand, Sorø, Denmark. 9. Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA, USA.
Abstract
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.
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.
Authors: Susanna C Larsson; Amy M Mason; Siddhartha Kar; Mathew Vithayathil; Paul Carter; John A Baron; Karl Michaëlsson; Stephen Burgess Journal: BMC Med Date: 2020-12-02 Impact factor: 8.775
Authors: Jie Zheng; Monika Frysz; John P Kemp; David M Evans; George Davey Smith; Jonathan H Tobias Journal: Front Endocrinol (Lausanne) Date: 2019-11-21 Impact factor: 5.555