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A positive dose-response effect of vitamin D supplementation on site-specific bone mineral augmentation in adolescent girls: a double-blinded randomized placebo-controlled 1-year intervention. Viljakainen HT, Natri AM, Kärkkäinen M, Huttunen MM, Palssa A, Jakobsen J, Cashman KD, Mølgaard C, Lamberg-Allardt C. J Bone Miner Res. 2006 Jun;21(6):836-44. PMID: 16753014 doi: 10.1359/jbmr.060302 We conclude that the current vitamin D recommendation for adolescent girls, at least in the northern latitudes, is too low to ensure sufficient vitamin D status during winter. Intake of vitamin D at rates of 10-15 μg/day aids to maintain stable S-25(OH)D concentrations during winter. Vitamin D induced BMC augmentation by decreasing bone resorption, but not affecting bone formation, which was reflected by the biochemical markers of bone turnover. Optimizing bone mineral gain in adolescence is crucial to the prevention of osteoporosis later in life. Increasing vitamin D intake to 10-15 μg/day aids in attaining this goal.

Measurement of vitamin D levels in inflammatory bowel disease patients reveals a subset of Crohn's disease patients with elevated 1,25-dihydroxyvitamin D and low bone mineral density. Abreu MT, Kantorovich V, Vasiliauskas EA, Gruntmanis U, Matuk R, Daigle K, Chen S, Zehnder D, Lin YC, Yang H, Hewison M, Adams JS. Gut. 2004 Aug;53(8):1129-36. PMID: 15247180 doi: 10.1136/gut.2003.036657. Conclusions: These data demonstrate that elevated 1,25(OH)2D is more common in CD than previously appreciated and is independently associated with low bone mineral density. The source of the active vitamin D may be the inflamed intestine. Treatment of the underlying inflammation may improve metabolic bone disease in this subgroup of patients.

Relation of body fat indexes to vitamin D status and deficiency among obese adolescents. Lenders CM, Feldman HA, Von Scheven E, Merewood A, Sweeney C, Wilson DM, Lee PD, Abrams SH, Gitelman SE, Wertz MS, Klish WJ, Taylor GA, Chen TC, Holick MF; Elizabeth Glaser Pediatric Research Network Obesity Study Group. Am J Clin Nutr. 2009 Sep;90(3):459-67. Epub 2009 Jul 29. PMID: 19640956 RESULTS: The mean (+/-SD) age of the adolescents was 14.9 +/- 1.4 y; 38 (66%) were female, and 8 (14%) were black. The mean (+/-SD) body mass index (in kg/m(2)) was 36 +/- 5, FM was 40.0 +/- 5.5%, and VAT was 12.4 +/- 4.3%. Seventeen of the adolescents were vitamin D deficient, but none had elevated PTH concentrations. Bone mineral content and bone mineral density were within 2 SDs of national standards. In a multivariate analysis, 25(OH)D decreased by 0.46 +/- 0.22 ng/mL per 1% increment in FM (beta +/- SE, P = 0.05), whereas PTH decreased by 0.78 +/- 0.29 pg/mL per 1% increment in VAT (P = 0.01). CONCLUSIONS: To the best of our knowledge, our results show for the first time that obese adolescents with 25(OH)D deficiency, but without elevated PTH concentrations, have a bone mass within the range of national standards (+/-2 SD). The findings provide initial evidence that the distribution of fat may be associated with vitamin D status, but this relation may be dependent on metabolic factors

Summary of evidence-based review on vitamin D efficacy and safety in relation to bone health. Cranney A, Weiler HA, O'Donnell S, Puil L. Am J Clin Nutr. 2008 Aug;88(2):513S-519S. Review. PMID: 18689393 We found inconsistent evidence of an association between serum 25-hydroxyvitamin D [25(OH)D] concentration and bone mineral content in infants and fair evidence of an association with bone mineral content or density in older children and older adults. The evidence of an association between serum 25(OH)D concentration and some clinical outcomes (fractures, performance measures) in postmenopausal women and older men was inconsistent, and the evidence of an association with falls was fair. We found good evidence of a positive effect of consuming vitamin D-fortified foods on 25(OH)D concentrations. The evidence for a benefit of vitamin D on falls and fractures varied. We found fair evidence that adults tolerated vitamin D at doses above current dietary reference intake levels, but we had no data on the association between long-term harms and higher doses of vitamin D.

Acid-base balance has an effect on bone turnover, especially on the rates of bone resorption and calcium mobilization. Bone mineral participates in the defense against acid-base disturbances, especially against metabolic acidosis (Lemann et al. 1966, Green & Kleeman 1991). The role of the bone mineral is important in the acid-base disorders, as no appreciable change in the intestinal calcium absorption occurs (Bichara et al. 1990). In the mammalian body, mainly three hormones regulate the calcium metabolism and the bone turnover. 1,25-dihydroxycholecalciferol (vitamin D derivative) increases calcium absorption from the intestine and, indirectly, from bone. Parathyroid hormone mobilizes calcium from the bone and increases the urinary phosphate excretion. Calcitonin inhibits bone resorption (Ganong 1981). Used as drugs, these hormones are also capable of inducing acid-base disorders. Calcitonin administration (Escanero et al. 1991) and vitamin D excess (Bichara et al. 1990) have been reported to cause metabolic alkalosis.

Bioactive vitamin D or calcitriol is a steroid hormone that has long been known for its important role in regulating body levels of calcium and phosphorus, and in mineralization of bone. More recently, it has become clear that receptors for vitamin D are present in a wide variety of cells, and that this hormone has biologic effects which extend far beyond control of mineral metabolism. The active form of vitamin D binds to intracellular receptors that then function as transcription factors to modulate gene expression. Like the receptors for other steroid hormones and thyroid hormones, the vitamin D receptor has hormone-binding and DNA-binding domains. The vitamin D receptor forms a complex with another intracellular receptor, the retinoid-X receptor, and that heterodimer is what binds to DNA. In most cases studied, the effect is to activate transcription, but situations are also known in which vitamin D suppresses transcription. Each of the forms of vitamin D is hydrophobic, and is transported in blood bound to carrier proteins. The major carrier is called, appropriately, vitamin D-binding protein. The halflife of 25-hydroxycholecalciferol is several weeks, while that of 1,25-dihydroxycholecalciferol is only a few hours. The vitamin D receptor binds several forms of cholecalciferol. Its affinity for 1,25-dihydroxycholecalciferol is roughly 1000 times that for 25-hydroxycholecalciferol, which explains their relative biological potencies

In 1945, Dr. Weston Price described "a new vitamin-like activator" that played an influential role in the utilization of minerals, protection from tooth decay, growth and development, reproduction, protection against heart disease and the function of the brain. Using a chemical test, he determined that this compound-which he called Activator X-occurred in the butterfat, organs and fat of animals consuming rapidly growing green grass, and also in certain sea foods such as fish eggs. Vitamin K2 is produced by animal tissues, including the mammary glands, from vitamin K1, which occurs in rapidly growing green plants. A growing body of published research confirms Dr. Price's discoveries, namely that vitamin K2 is important for the utilization of minerals, protects against tooth decay, supports growth and development, is involved in normal reproduction, protects against calcification of the arteries leading to heart disease, and is a major component of the brain

The Linus Pauling Institute's Micronutrient Information Center is a source for scientifically accurate information regarding the roles of vitamins, minerals, other nutrients, dietary phytochemicals (plant chemicals that may affect health), and some foods

Wintertime vitamin D supplementation inhibits seasonal variation of calcitropic hormones and maintains bone turnover in healthy men. Viljakainen HT, Väisänen M, Kemi V, Rikkonen T, Kröger H, Laitinen EK, Rita H, Lamberg-Allardt C. J Bone Miner Res. 2009 Feb;24(2):346-52. PMID: 18847321

Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. Bischoff HA, Stähelin HB, Dick W, Akos R, Knecht M, Salis C, Nebiker M, Theiler R, Pfeifer M, Begerow B, Lew RA, Conzelmann M. J Bone Miner Res. 2003 Feb;18(2):343-51. PMID: 12568412 A single intervention with vitamin D plus calcium over a 3-month period reduced the risk of falling by 49% compared with calcium alone. Over this short-term intervention, recurrent fallers seem to benefit most by the treatment. The impact of vitamin D on falls might be explained by the observed improvement in musculoskeletal function.

Vitamin D and skin physiology: a D-lightful story. Holick MF, Chen TC, Lu Z, Sauter E. J Bone Miner Res. 2007 Dec;22 Suppl 2:V28-33. PMID: 18290718 doi: 10.1359/jbmr.07s211 Very few foods naturally contain vitamin D, and those that do have a very variable vitamin D content. Recently it was observed that wild caught salmon had between 75% and 90% more vitamin D(3) compared with farmed salmon. The associations regarding increased risk of common deadly cancers, autoimmune diseases, infectious diseases, and cardiovascular disease with living at higher latitudes and being prone to vitamin D deficiency should alert all health care professionals about the importance of vitamin D for overall health and well being. Humans have depended on sunlight for their vitamin D requirement. The impact of season, time of day, and latitude on vitamin D synthesis is well documented.(2,3) We now report that altitude also has a dramatic influence on vitamin D3 production and that living at altitudes above 3500 m permits previtamin D3 production at a time when very little is produced at latitudes below 3400 m. It was surprising that, at 27° N in Agra (169 M), little previtamin D3 production was observed. However, there was significant air pollution that caused a haze over the city. It is likely the ozone and other UVB-absorbing pollutants in the air prevented the solar UVB photons from reaching the earth's surface to produce previtamin D3.

A seasonal variation of calcitropic hormones, bone turnover and bone mineral density in early and mid-puberty girls - a cross-sectional study. Viljakainen HT, Palssa A, Kärkkäinen M, Jakobsen J, Cashman KD, Mølgaard C, Lamberg-Allardt C. Br J Nutr. 2006 Jul;96(1):124-30. PMID: 16870000 Seasonal variation in S-25-OHD and bone remodelling markers accompanied by negative correlation between S-25-OHD and S-iPTH was seen in this cross-sectional study of adolescent girls. In addition, the seasonal rhythm contributed 7.0-7.6 % difference in the BMD of lumbar vertebrae and left femur in early puberty girls. This variation should be avoided since it could hamper peak bone mass attainment.

Calcium and vitamin d supplementation decreases incidence of stress fractures in female navy recruits. Lappe J, Cullen D, Haynatzki G, Recker R, Ahlf R, Thompson K. J Bone Miner Res. 2008 May;23(5):741-9. PMID: 18433305 doi: 10.1359/jbmr.080102 Conclusions: Generalizing the findings to the population of 14,416 women who entered basic training at the Great Lakes during the 24 mo of recruitment, calcium and vitamin D supplementation for the entire cohort would have prevented 187 persons from fracturing. Such a decrease in SFx would be associated with a significant decrease in morbidity and financial costs.

Association between serum 25(OH)D concentrations and bone stress fractures in Finnish young men. Ruohola JP, Laaksi I, Ylikomi T, Haataja R, Mattila VM, Sahi T, Tuohimaa P, Pihlajamäki H. J Bone Miner Res. 2006 Sep;21(9):1483-8. doi: 10.1359/jbmr.060607 Conclusions: A lower level of serum 25(OH)D concentration may be a generally predisposing element for bone stress fractures. Considering the obvious need of additional vitamin D in prevention of stress fractures, the effects of vitamin D fortification of foods and supplementation will be subjects of interest for future research PMID: 16939407

[Low levels of 25-hydroxyvitamin D (25OHD) in patients with inflammatory bowel disease and its correlation with bone mineral density] Souza HN, Lora FL, Kulak CA, Mañas NC, Amarante HM, Borba VZ. Arq Bras Endocrinol Metabol. 2008 Jun;52(4):684-91. Portuguese. PMID: 18604382

Vitamin D status affects serum parathyroid hormone concentrations during winter in female adolescents: associations with forearm bone mineral density. Outila TA, Kärkkäinen MU, Lamberg-Allardt CJ. Am J Clin Nutr. 2001 Aug;74(2):206-10. PMID: 11470722 Conclusion: A large percentage of adolescent females have low vitamin D status during the winter in Finland, which seems to have negative effects on bone health.

Vitamin D deficiency and bone health in healthy adults in Finland: could this be a concern in other parts of Europe? Lamberg-Allardt CJ, Outila TA, Kärkkainen MU, Rita HJ, Valsta LM. J Bone Miner Res. 2001 Nov;16(11):2066-73. PMID: 11697803 Low vitamin D status was prevalent in these young adults in northern Europe in winter, although the vitamin D intake met the recommendation. This probably is not a local problem for northern Europe, because the natural sources of vitamin D are scarce and fortification is not very common in Europe, and with the exception of the southern part of Europe, sunshine is not very abundant in this part of the world. Thus, the results of this study indicate that more attention should be focused on vitamin D status and the sources of vitamin D in these countries.

Vitamin D toxicity, policy, and science. Vieth R. J Bone Miner Res. 2007 Dec;22 Suppl 2:V64-8. Review. PMID: 18290725 doi: 10.1359/jbmr.07s221

Vitamin D and skin physiology: a D-lightful story.\nHolick MF, Chen TC, Lu Z, Sauter E.\nJ Bone Miner Res. 2007 Dec;22 Suppl 2:V28-33.\nPMID: 18290718 \ndoi: 10.1359/jbmr.07s211\n

P.T. Liu, S. Stenger, H. Li, L. Wenzel, B.H. Tan, S.R. Krutzik, M.T. Ochoa, J. Schauber, K. Wu, C. Meinken, et al.\nVitamin D3-Triggered Antimicrobial Response--Another Pleiotropic Effect beyond Mineral and Bone Metabolism: Toll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response. Science 311: 1770-1773, 2006\nJ. Am. Soc. Nephrol., November 1, 2006; 17(11): 2949 - 2953.