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Lactase persistence, milk intake, hip fracture and bone mineral density: a study of 97 811 Danish individuals and a meta-analysis.
J Intern Med 2018; 284(3):254-269JI

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.

Authors+Show Affiliations

Department of Clinical Biochemistry, Copenhagen University Hospital Naestved Slagelse Ringsted, Naestved, Denmark. The Danish General Suburban Population Study, Copenhagen University Hospital Naestved Slagelse Ringsted, Naestved, Denmark.The Danish General Suburban Population Study, Copenhagen University Hospital Naestved Slagelse Ringsted, Naestved, Denmark. Department of Science and Environment, University of Roskilde, Roskilde, Denmark.Department of Clinical Biochemistry, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark. The Copenhagen General Population Study, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark.The Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Department of Clinical Biochemistry, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark. The Copenhagen General Population Study, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark. The Copenhagen City Heart Study, Copenhagen University Hospital, Frederiksberg Hospital, Frederiksberg, Denmark.The Danish General Suburban Population Study, Copenhagen University Hospital Naestved Slagelse Ringsted, Naestved, Denmark. The Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Department of Production, Research and Innovation, Region Zealand, Sorø, Denmark. Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA, USA.

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29537719

Citation

Bergholdt, H K M., et al. "Lactase Persistence, Milk Intake, Hip Fracture and Bone Mineral Density: a Study of 97 811 Danish Individuals and a Meta-analysis." Journal of Internal Medicine, vol. 284, no. 3, 2018, pp. 254-269.
Bergholdt HKM, Larsen MK, Varbo A, et al. Lactase persistence, milk intake, hip fracture and bone mineral density: a study of 97 811 Danish individuals and a meta-analysis. J Intern Med. 2018;284(3):254-269.
Bergholdt, H. K. M., Larsen, M. K., Varbo, A., Nordestgaard, B. G., & Ellervik, C. (2018). Lactase persistence, milk intake, hip fracture and bone mineral density: a study of 97 811 Danish individuals and a meta-analysis. Journal of Internal Medicine, 284(3), pp. 254-269. doi:10.1111/joim.12753.
Bergholdt HKM, et al. Lactase Persistence, Milk Intake, Hip Fracture and Bone Mineral Density: a Study of 97 811 Danish Individuals and a Meta-analysis. J Intern Med. 2018;284(3):254-269. PubMed PMID: 29537719.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lactase persistence, milk intake, hip fracture and bone mineral density: 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, Y1 - 2018/04/10/ PY - 2018/3/15/pubmed PY - 2018/3/15/medline PY - 2018/3/15/entrez KW - bone mineral density KW - dairy KW - fractures KW - lactase persistence KW - mendelian randomization KW - milk SP - 254 EP - 269 JF - Journal of internal medicine JO - J. Intern. Med. VL - 284 IS - 3 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. SN - 1365-2796 UR - https://www.unboundmedicine.com/medline/citation/29537719/Lactase_persistence_milk_intake_hip_fracture_and_bone_mineral_density:_a_study_of_97_811_Danish_individuals_and_a_meta_analysis_ L2 - https://doi.org/10.1111/joim.12753 DB - PRIME DP - Unbound Medicine ER -