title: Calcium intake and bone mineral density as an example of non-linearity and threshold analysis.
abstract: Non-linearity is a likely phenomenon in bone metabolism, but is often ignored in pertinent epidemiological studies. Using NHANES III data on calcium intake and bone mineral density, the most important non-linear methods are introduced and discussed. The results should motivate researchers to consider non-linearity in this field more frequently.
  
  
  BACKGROUND
  Many relationships in bone metabolism and homeostasis are likely to follow non-linear patterns. Detailed dose-response analyses allowing for non-linear associations nonetheless remain scarce in this field.
  
  
  METHODS
  A detailed analysis of NHANES III data on dietary calcium intake and bone mineral density was used to demonstrate the application and some of the challenges of the most important dose-response methods, including LOESS, categorical analysis, fractional polynomials, restricted cubic splines, and segmented regression.
  
  
  RESULTS
  The spline estimate suggested increasing bone mineral density up to a calcium intake of about 1 g/day and a plateau thereafter. In segmented regression, the break-point marking the beginning of the plateau was placed at an intake of 0.58 (95 % confidence interval, 0.33 to 0.82) g/day. Sensitivity analyses suggested a less curved dose-response in women.
  
  
  CONCLUSIONS
  Knowing about the possibilities and limitations of non-linear dose-response approaches should encourage researchers to consider these methods more frequently in studies on bone health and disease. The example analysis suggested bone mineral density to reach a plateau slightly below current calcium intake recommendations, with fairly pronounced differences of the dose-response shape by sex and menopausal status.
authors: German Cancer Research Center, Division C070 Clinical Epidemiology and Aging Research, PO Box 101949, 69009, Heidelberg, Germany, lutz.breitling@gmail.com.
authors: L P
authors: LP
authors: Breitling
mesh_terms: D000328:Adult; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology; D001842:Bone and Bones / Q000378:metabolism; D002136:Calcium, Dietary / Q000008:administration & dosage* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017711:Nonlinear Dynamics; D009749:Nutrition Surveys
chemical_list: D002136:Calcium, Dietary
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