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

a study of 97 811 Danish individuals and a meta‐analysis

Helle K.M. Bergholdt, Morten Kranker Larsen, Anette Varbo, Børge G. Nordestgaard, Christina Ellervik

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.
OriginalsprogEngelsk
TidsskriftJournal of Internal Medicine
Vol/bind284
Udgave nummer3
Sider (fra-til)254-269
ISSN0954-6820
DOI
StatusUdgivet - 2018

Bibliografisk note

This article has been found as a 'Free version' of the article. Found at Publishers webpage October 12 2018. Should access to the article close, please notify rucforsk@ruc.dk

Emneord

  • bone mineral density
  • dairy
  • fractures
  • lactase persistence
  • mendelian randomization
  • milk

Citer dette

Bergholdt, Helle K.M. ; Larsen, Morten Kranker ; Varbo, Anette ; Nordestgaard, Børge G. ; Ellervik, Christina. / Lactase persistence, milk intake, hip fracture and bone mineral density : a study of 97 811 Danish individuals and a meta‐analysis. I: Journal of Internal Medicine. 2018 ; Bind 284, Nr. 3. s. 254-269.
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title = "Lactase persistence, milk intake, hip fracture and bone mineral density: a study of 97 811 Danish individuals and a meta‐analysis",
abstract = "BackgroundWhether a causal relationship exists between milk intake and reduced risk of fractures is unclear.ObjectivesWe tested the hypothesis that genetically determined milk intake reduces the risk of fractures and increases bone mineral density (BMD).MethodsWe 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.ResultsIn 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.ConclusionGenetically 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, bone mineral density, dairy, fractures, lactase persistence, mendelian randomization, milk",
author = "Bergholdt, {Helle K.M.} and Larsen, {Morten Kranker} and Anette Varbo and Nordestgaard, {B{\o}rge G.} and Christina Ellervik",
note = "This article has been found as a 'Free version' of the article. Found at Publishers webpage October 12 2018. Should access to the article close, please notify rucforsk@ruc.dk",
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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. / Bergholdt, Helle K.M.; Larsen, Morten Kranker; Varbo, Anette; Nordestgaard, Børge G.; Ellervik, Christina.

I: Journal of Internal Medicine, Bind 284, Nr. 3, 2018, s. 254-269.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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, Helle K.M.

AU - Larsen, Morten Kranker

AU - Varbo, Anette

AU - Nordestgaard, Børge G.

AU - Ellervik, Christina

N1 - This article has been found as a 'Free version' of the article. Found at Publishers webpage October 12 2018. Should access to the article close, please notify rucforsk@ruc.dk

PY - 2018

Y1 - 2018

N2 - BackgroundWhether a causal relationship exists between milk intake and reduced risk of fractures is unclear.ObjectivesWe tested the hypothesis that genetically determined milk intake reduces the risk of fractures and increases bone mineral density (BMD).MethodsWe 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.ResultsIn 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.ConclusionGenetically 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 - BackgroundWhether a causal relationship exists between milk intake and reduced risk of fractures is unclear.ObjectivesWe tested the hypothesis that genetically determined milk intake reduces the risk of fractures and increases bone mineral density (BMD).MethodsWe 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.ResultsIn 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.ConclusionGenetically 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.

KW - bone mineral density

KW - dairy

KW - fractures

KW - lactase persistence

KW - mendelian randomization

KW - milk

KW - bone mineral density

KW - dairy

KW - fractures

KW - lactase persistence

KW - mendelian randomization

KW - milk

UR - https://onlinelibrary.wiley.com/doi/abs/10.1111/joim.12753

U2 - 10.1111/joim.12753

DO - 10.1111/joim.12753

M3 - Journal article

VL - 284

SP - 254

EP - 269

JO - Journal of Internal Medicine

JF - Journal of Internal Medicine

SN - 0954-6820

IS - 3

ER -