The purpose of this systematic evidence-based review, referred to as AHRQ-Ottawa,¹ requested by the Office of Dietary Supplements, National Institutes of Health and conducted by the University of Ottawa Evidence-based Practice Center (UO-EPC) was to review and synthesize the published literature on five key questions.

1. Are specific circulating concentrations of 25 hydroxyvitamin D (25[OH]D) associated with bone health outcomes in:
   1. Children: rickets, bone mineral density (BMD), bone mineral content (BMC), fractures, or parathyroid hormone (PTH)?
   2. Women of reproductive age (including pregnant and lactating women): BMD, calcaneal ultrasound, fractures, PTH?
   3. Elderly men and postmenopausal women: BMD, fractures, falls?
2. Do food fortification, sun exposure, and/or vitamin D supplementation affect circulating concentrations of 25(OH)D?
3. What is the evidence regarding the effect of supplemental doses of vitamin D on bone mineral density and fracture or fall risk and does this vary with age groups, ethnicity, body mass index, or geography?
4. Is there a level of sunlight exposure that is sufficient to maintain adequate vitamin D levels but does not increase the risk of non-melanoma or melanoma skin cancer?
5. Does intake of vitamin D above current reference intakes lead to toxicities (e.g., hypercalcemia, hypercalciuria, and calcification of soft tissue or major organs)?

The review focused on electronic searches of the medical literature to identify publications addressing the aforementioned questions. Out of 9,150 citations, 112 RCTs, 19 prospective cohorts, 30 case–control studies, and 6 before-after studies were systematically reviewed, and each was rated on quality and used to assess the strength of evidence for each outcome.

The methods and results chapters of the AHRQ-Ottawa evidence review are reprinted below. The report in its entirety, including appendices and evidence tables, can be accessed and viewed at http://www.ahrq.gov/clinic/tp/vitadtp.htm#Report.