title: Population data on calcium in drinking water and hip fracture: An association may depend on other minerals in water. A NOREPOS study.
abstract: BACKGROUND
  The Norwegian population has among the highest hip fracture rates in the world. The incidence varies geographically, also within Norway. Calcium in drinking water has been found to be beneficially associated with bone health in some studies, but not in all. In most previous studies, other minerals in water have not been taken into account. Trace minerals, for which drinking water can be an important source and even fulfill the daily nutritional requirement, could act as effect-modifiers in the association between calcium and hip fracture risk. The aim of the present study was to investigate the association between calcium in drinking water and hip fracture, and whether other water minerals modified this association.
  
  
  METHODS
  A survey of trace metals in 429 waterworks, supplying 64% of the population in Norway, was linked geographically to the home addresses of patients with incident hip fractures (1994-2000). Drinking water mineral concentrations were divided into "low" (below and equal waterworks average) and "high" (above waterworks average). Poisson regression models were fitted, and all incidence rate ratios (IRRs) were adjusted for age, geographic region, urbanization degree, type of water source, and pH of the water. Effect modifications were examined by stratification, and interactions between calcium and magnesium, copper, zinc, iron and manganese were tested both on the multiplicative and the additive scale. Analyses were stratified on gender.
  
  
  RESULTS
  Among those supplied from the 429 waterworks (2,110,916 person-years in men and 2,397,217 person-years in women), 5433 men and 13,493 women aged 50-85 years suffered a hip fracture during 1994-2000. Compared to low calcium in drinking water, a high level was associated with a 15% lower hip fracture risk in men (IRR=0.85, 95% CI: 0.78, 0.91) but no significant difference was found in women (IRR=0.98, 95%CI: 0.93-1.02). There was interaction between calcium and copper on hip fracture risk in men (p=0.051); the association between calcium and hip fracture risk was stronger when the copper concentration in water was high (IRR=0.52, 95% CI: 0.35, 0.78) as opposed to when it was low (IRR=0.88, 95% CI: 0.81, 0.94). This pattern persisted also after including potential confounding factors and other minerals in the model. No similar variation in risk was found in women.
  
  
  CONCLUSIONS
  In this large, prospective population study covering two thirds of the Norwegian population and comprising 19,000 hip fractures, we found an inverse association between calcium in drinking water and hip fracture risk in men. The association was stronger when the copper concentration in the water was high.
authors.affiliation: Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway. Electronic address: Cecilie.Dahl@fhi.no.
authors.forename: Cecilie
authors.initials: C
authors.lastname: Dahl
authors.affiliation: Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Anne Johanne
authors.initials: AJ
authors.lastname: Søgaard
authors.affiliation: Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; Department of Health Registries, Norwegian Institute of Public Health, Bergen, Norway.
authors.forename: Grethe S
authors.initials: GS
authors.lastname: Tell
authors.affiliation: Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway; Women and Children's Division, Norwegian Resource Centre for Women's Health, Oslo University Hospital, Norway.
authors.forename: Lisa
authors.initials: L
authors.lastname: Forsén
authors.affiliation: Department of Chemistry, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Trond Peder
authors.initials: TP
authors.lastname: Flaten
authors.affiliation: Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Dag
authors.initials: D
authors.lastname: Hongve
authors.affiliation: Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway; Department of Community Medicine (Institute of Health and Society), University of Oslo, Oslo, Norway.
authors.forename: Tone Kristin
authors.initials: TK
authors.lastname: Omsland
authors.affiliation: Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Kristin
authors.initials: K
authors.lastname: Holvik
authors.affiliation: Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway; Department of Community Medicine (Institute of Health and Society), University of Oslo, Oslo, Norway.
authors.forename: Haakon E
authors.initials: HE
authors.lastname: Meyer
authors.affiliation: Department of Landscape Architecture and Spatial Planning (ILP), Norwegian University of Life Sciences, Ås, Norway.
authors.forename: Geir
authors.initials: G
authors.lastname: Aamodt
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002136:Calcium, Dietary / Q000008:administration & dosage*; D015331:Cohort Studies; D016208:Databases, Factual / Q000639:trends; D060766:Drinking Water / Q000008:administration & dosage* / Q000032:analysis*; D005260:Female; D006620:Hip Fractures / Q000453:epidemiology* / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D011159:Population Surveillance / Q000379:methods; D011446:Prospective Studies; D012307:Risk Factors; D014131:Trace Elements / Q000008:administration & dosage / Q000032:analysis
chemical_list: D002136:Calcium, Dietary; D060766:Drinking Water; D014131:Trace Elements
keywords: Calcium; Drinking water; Epidemiology; Hip fracture; Interaction; Water minerals