tial for the gamma carboxylation of three bone matrix proteins (for example, osteocalcin, which facilitates calcium binding to hydroxyapatite). With the exception of boron, deficiencies of these nutrients in growing animals have been associated with bone lesions (Heaney, 1997). In humans, the primary biological function of these nutrients does not appear to be bone metabolism and maintenance of skeletal integrity. Bone fragility in humans related to deficiencies of these trace elements and vitamins has not been well described. Thus, these trace elements and vitamins will be covered in subsequent DRI reports that deal with their major functions.

The roles of boron in human health, in general, and in bone metabolism, in particular, are uncertain. Studies in animals suggest that boron contributes to the composition and strength characteristics of bone (Hunt and Nielsen, 1981). Boron may have an interactive role with vitamin D because it affects steroid hormone metabolism in humans (Nielsen, 1990; Nielsen et al., 1987). In studies in postmenopausal women, boron depletion was not consistently found to alter calcium and vitamin D homeostasis (Nielsen et al., 1987; Peace and Beattie, 1991). Epidemiological evidence of a relationship between dietary boron status and osteoporosis is not available. Thus, it was deemed premature to consider boron as a nutrient functionally related to bone health, and boron was not included in this report.

METHODOLOGICAL CONSIDERATIONS

The scientific data for developing the DRIs have come primarily from clinical, dose-response, balance, depletion-repletion, observational, and case-control studies. In general, only studies published in peer-reviewed journals have been utilized. However, studies published in other scientific journals or readily available reports were considered if they appeared to provide important information on health effects not documented elsewhere. In some cases they were used to estimate intakes. If applicable, original scientific studies were used for the critical determinants of endpoints for deriving the Estimated Average Requirement (EAR), Adequate Intake (AI), and Tolerable Upper Intake Level (UL) for each nutrient at each stage of the lifespan.

Based on a thorough review of the scientific literature, the possible criterion or outcomes of nutrient adequacy were identified for each nutrient and life stage or gender group. The choice of the indicator to utilize in determining the EAR or AI was based on scientific judgment. The strengths and weaknesses of each study



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