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 Sep;284(3):254-269. doi: 10.1111/joim.12753. Epub 2018 Apr 10.

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.

Keywords: bone mineral density; dairy; fractures; lactase persistence; mendelian randomization; milk.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Animals
  • Bone Density / genetics*
  • Cohort Studies
  • Correlation of Data
  • Denmark
  • Female
  • Genotype
  • Hip Fractures / enzymology
  • Hip Fractures / genetics*
  • Hip Fractures / prevention & control
  • Humans
  • Lactase / blood*
  • Lactase / deficiency
  • Lactase / genetics
  • Lactase-Phlorizin Hydrolase / blood
  • Lactose Intolerance / enzymology
  • Lactose Intolerance / genetics
  • Lactose Intolerance / prevention & control
  • Lumbar Vertebrae / injuries
  • Male
  • Middle Aged
  • Milk / adverse effects*
  • Odds Ratio
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • Spinal Fractures / enzymology
  • Spinal Fractures / genetics
  • Spinal Fractures / prevention & control
  • Young Adult

Substances

  • Lactase
  • Lactase-Phlorizin Hydrolase

Supplementary concepts

  • Lactose Intolerance, Adult Type