Genetic predisposition for adult lactose intolerance and relation to diet, bone density, and bone fractures

J Bone Miner Res. 2004 Jan;19(1):42-7. doi: 10.1359/JBMR.0301207.


Evidence that genetic disposition for adult lactose intolerance significantly affects calcium intake, bone density, and fractures in postmenopausal women is presented. PCR-based genotyping of lactase gene polymorphisms may complement diagnostic procedures to identify persons at risk for both lactose malabsorption and osteoporosis.

Introduction: Lactase deficiency is a common autosomal recessive condition resulting in decreased intestinal lactose degradation. A -13910 T/C dimorphism (LCT) near the lactase phlorizin hydrolase gene, reported to be strongly associated with adult lactase nonpersistence, may have an impact on calcium supply, bone density, and osteoporotic fractures in the elderly.

Materials and methods: We determined LCT genotypes TT, TC, and CC in 258 postmenopausal women using a polymerase chain reaction-based assay. Genotypes were related to milk intolerance, nutritional calcium intake, intestinal calcium absorption, bone mineral density (BMD), and nonvertebral fractures.

Results: Twenty-four percent of all women were found to have CC genotypes and genetic lactase deficiency. Age-adjusted BMD at the hip in CC genotypes and at the spine in CC and TC genotypes was reduced by -7% to -11% depending on the site measured (p = 0.04). LCT(T/C-13910) polymorphisms alone accounted for 2-4% of BMD in a multiple regression model. Bone fracture incidence was significantly associated with CC genotypes (p = 0.001). Milk calcium intake was significantly lower (-55%, p = 0.004) and aversion to milk consumption was significantly higher (+166%, p = 0.01) in women with the CC genotype, but there were no differences in overall dietary calcium intake or in intestinal calcium absorption test values.

Conclusion: The LCT(T/C-13910) polymorphism is associated with subjective milk intolerance, reduced milk calcium intake, and reduced BMD at the hip and the lumbar spine and may predispose to bone fractures. Genetic testing for lactase deficiency may complement indirect methods in the detection of individuals at risk for both lactose malabsorption and osteoporosis.

MeSH terms

  • Age Factors
  • Aged
  • Animals
  • Bone Density*
  • Calcifediol / blood
  • Calcium, Dietary / administration & dosage
  • Calcium, Dietary / metabolism
  • Collagen / blood
  • Diet*
  • Female
  • Femur Neck / chemistry
  • Fractures, Bone / complications*
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Intestinal Absorption
  • Lactase-Phlorizin Hydrolase / genetics
  • Lactose Intolerance / complications
  • Lactose Intolerance / genetics*
  • Lumbar Vertebrae / chemistry
  • Middle Aged
  • Milk
  • Osteocalcin / blood
  • Pelvic Bones / chemistry
  • Peptide Fragments / blood
  • Polymorphism, Genetic / genetics
  • Postmenopause / blood
  • Postmenopause / genetics
  • Postmenopause / metabolism
  • Regression Analysis
  • Yogurt


  • Calcium, Dietary
  • Peptide Fragments
  • glutamyl-lysyl-alanyl-histidyl-aspartyl-glycyl-glycyl-arginine
  • Osteocalcin
  • Collagen
  • Lactase-Phlorizin Hydrolase
  • Calcifediol