Ageing and vitamin D deficiency: effects on calcium homeostasis and considerations for vitamin D supplementation

Vitamin D is a fat-soluble, seco-steroid hormone. In man, the vitamin D receptor is expressed in almost all tissues, enabling effects in multiple systems of the human body. These effects can be endocrine, paracrine and autocrine. The present review summarises the effects of ageing on the vitamin D endocrine system and on Ca homeostasis. Furthermore, consequences for vitamin D supplementation are discussed.

[1]  Mikko P. Björkman,et al.  Responses of parathyroid hormone to vitamin D supplementation: a systematic review of clinical trials. , 2009, Archives of gerontology and geriatrics.

[2]  R. Weggemans,et al.  Naar een toereikende inname van vitamine D , 2009 .

[3]  Sandro Giannini,et al.  Vitamin D status and response to treatment in post-menopausal osteoporosis , 2009, Osteoporosis International.

[4]  H. Morris,et al.  Vitamin D Depletion Induces RANKL‐Mediated Osteoclastogenesis and Bone Loss in a Rodent Model , 2008, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[5]  H. DeLuca,et al.  Altered endocrine and autocrine metabolism of vitamin D in a mouse model of gastrointestinal inflammation. , 2008, Endocrinology.

[6]  K. Olive,et al.  Prevalence of Vitamin D Deficiency and Insufficiency in Northeast Tennessee , 2008, Southern medical journal.

[7]  Gert B. M. Mensink,et al.  Vitamin D status and health correlates among German adults , 2008, European Journal of Clinical Nutrition.

[8]  E. Yetley.  Assessing the vitamin D status of the US population. , 2008, The American journal of clinical nutrition.

[9]  R. Tilvis,et al.  Elevated serum parathyroid hormone predicts impaired survival prognosis in a general aged population. , 2008, European journal of endocrinology.

[10]  J. Adams,et al.  Vitamin D and Innate Immunity , 2009 .

[11]  B. Troen,et al.  Understanding the Mechanisms of Senile Osteoporosis: New Facts for a Major Geriatric Syndrome , 2008, Journal of the American Geriatrics Society.

[12]  J. Holden,et al.  Vitamin D in foods: development of the US Department of Agriculture database. , 2008, The American journal of clinical nutrition.

[13]  M. Holick,et al.  Vitamin D deficiency: a worldwide problem with health consequences. , 2008, The American journal of clinical nutrition.

[14]  J. Zerwekh.  Blood biomarkers of vitamin D status. , 2008, The American journal of clinical nutrition.

[15]  B. Ames,et al.  Is there convincing biological or behavioral evidence linking vitamin D deficiency to brain dysfunction? , 2008, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[16]  R. Jorde,et al.  Serum 1,25-dihydroxy vitamin D is inversely associated with body mass index , 2008, European journal of nutrition.

[17]  M. Holick,et al.  Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. , 2008, The Journal of clinical endocrinology and metabolism.

[18]  F. Coe,et al.  New insights into the pathogenesis of idiopathic hypercalciuria. , 2008, Seminars in nephrology.

[19]  N. G. Tolosa de Talamoni,et al.  Minireview on Regulation of Intestinal Calcium Absorption , 2008, Digestion.

[20]  L. Idolazzi,et al.  Relationship between serum parathyroid hormone, vitamin D sufficiency, age, and calcium intake. , 2008, Bone.

[21]  Y. Nabeshima,et al.  alpha-Klotho: a regulator that integrates calcium homeostasis. , 2008, American journal of nephrology.

[22]  D. Rosene,et al.  Gene profile analysis implicates Klotho as an important contributor to aging changes in brain white matter of the rhesus monkey , 2008, Glia.

[23]  R. Mehta,et al.  25-Hydroxyvitamin D3 is a natural chemopreventive agent against carcinogen induced precancerous lesions in mouse mammary gland organ culture , 2008, Breast Cancer Research and Treatment.

[24]  G. Fuleihan,et al.  Vitamin D: a growing perspective. , 2008, Critical reviews in clinical laboratory sciences.

[25]  E. Giovannucci.  Vitamin D status and cancer incidence and mortality. , 2008, Advances in experimental medicine and biology.

[26]  R. Boland,et al.  Vitamin D receptor levels and binding are reduced in aged rat intestinal subcellular fractions , 2008, Biogerontology.

[27]  Y. Nabeshima,et al.  α-Klotho: A Regulator That Integrates Calcium Homeostasis , 2007, American Journal of Nephrology.

[28]  M. Mohammadi,et al.  The parathyroid is a target organ for FGF23 in rats. , 2007, The Journal of clinical investigation.

[29]  M. Razzaque,et al.  Vitamin D and aging: old concepts and new insights. , 2007, The Journal of nutritional biochemistry.

[30]  N. Stern,et al.  25 hydroxy-vitamin D3-1α hydroxylase expression and activity in cultured human osteoblasts and their modulation by parathyroid hormone, estrogenic compounds and dihydrotestosterone , 2007, The Journal of Steroid Biochemistry and Molecular Biology.

[31]  J. Smit,et al.  Efficacy of different doses and time intervals of oral vitamin D supplementation with or without calcium in elderly nursing home residents , 2007, Osteoporosis International.

[32]  J. Staessen,et al.  Renal versus extrarenal activation of vitamin D in relation to atherosclerosis, arterial stiffening, and hypertension. , 2007, American journal of hypertension.

[33]  M. Razzaque,et al.  Mineral metabolism and aging: the fibroblast growth factor 23 enigma , 2007, Current opinion in nephrology and hypertension.

[34]  D. Bikle.  What is new in vitamin D: 2006–2007 , 2007, Current opinion in rheumatology.

[35]  G. Kantarci,et al.  Klotho: an antiaging protein involved in mineral and vitamin D metabolism. , 2007, Kidney international.

[36]  S. Boonen,et al.  Need for additional calcium to reduce the risk of hip fracture with vitamin d supplementation: evidence from a comparative metaanalysis of randomized controlled trials. , 2007, The Journal of clinical endocrinology and metabolism.

[37]  J. Bernheim,et al.  Parathyroid hormone stimulates endothelial expression of atherosclerotic parameters through protein kinase pathways. , 2007, American journal of physiology. Renal physiology.

[38]  P. Lips.  Vitamin D status and nutrition in Europe and Asia , 2007, The Journal of Steroid Biochemistry and Molecular Biology.

[39]  M. Thorner,et al.  Human studies of growth hormone and aging. , 2007, Pediatric Endocrinology Reviews: diabetes, nutrition, metabolism.

[40]  Y. Helfrich,et al.  Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D-dependent mechanism. , 2007, The Journal of clinical investigation.

[41]  F. Larrea,et al.  Regulation of Vitamin D hydroxylases gene expression by 1,25-dihydroxyvitamin D3 and cyclic AMP in cultured human syncytiotrophoblasts , 2007, The Journal of Steroid Biochemistry and Molecular Biology.

[42]  Ż. Smoleńska,et al.  Klotho—a Common Link in Physiological and Rheumatoid Arthritis-Related Aging of Human CD4+ Lymphocytes1 , 2007, The Journal of Immunology.

[43]  M. Hediger,et al.  Marked Disturbance of Calcium Homeostasis in Mice With Targeted Disruption of the Trpv6 Calcium Channel Gene , 2006, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[44]  A. Shao,et al.  Risk assessment for vitamin D. , 2007, The American journal of clinical nutrition.

[45]  K. Okawa,et al.  Klotho converts canonical FGF receptor into a specific receptor for FGF23 , 2006, Nature.

[46]  J. Hoenderop,et al.  Age-dependent alterations in Ca2+ homeostasis: role of TRPV5 and TRPV6. , 2006, American journal of physiology. Renal physiology.

[47]  R. Poulsom,et al.  Calcium Channel TRPV6 Expression in Human Duodenum: Different Relationships to the Vitamin D System and Aging in Men and Women , 2006, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[48]  A. Uitterlinden,et al.  Evidence for auto/paracrine actions of vitamin D in bone: 1a‐hydroxylase expression and activity in human bone cells , 2006 .

[49]  H. Chiba,et al.  Evidence that both 1α,25‐dihydroxyvitamin D3 and 24‐hydroxylated D3 enhance human osteoblast differentiation and mineralization , 2006, Journal of cellular biochemistry.

[50]  P. Lips.  Vitamin D physiology. , 2006, Progress in biophysics and molecular biology.

[51]  M. Visser,et al.  Low serum concentrations of 25-hydroxyvitamin D in older persons and the risk of nursing home admission. , 2006, The American journal of clinical nutrition.

[52]  K. O̸lgaard,et al.  Klotho, an important new factor for the activity of Ca2+ channels, connecting calcium homeostasis, ageing and uraemia. , 2006, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[53]  M. Razzaque,et al.  Hypervitaminosis D and premature aging: lessons learned from Fgf23 and Klotho mutant mice. , 2006, Trends in molecular medicine.

[54]  W. Willett,et al.  Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. , 2006, The American journal of clinical nutrition.

[55]  Y. Nabeshima.  Toward a better understanding of Klotho. , 2006, Science of aging knowledge environment : SAGE KE.

[56]  G. Tenderich,et al.  Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial. , 2006, The American journal of clinical nutrition.

[57]  Carly M. Kemmis,et al.  Human mammary epithelial cells express CYP27B1 and are growth inhibited by 25-hydroxyvitamin D-3, the major circulating form of vitamin D-3. , 2006, The Journal of nutrition.

[58]  J. Gómez.  The role of insulin-like growth factor I components in the regulation of vitamin D. , 2006, Current pharmaceutical biotechnology.

[59]  J. Welsh,et al.  The Molecular Basis of Vitamin D Receptor and β-Catenin Crossregulation , 2006 .

[60]  L. Rodríguez-Mañas,et al.  Seasonal Variance in Serum Levels of Vitamin D Determines a Compensatory Response by Parathyroid Hormone: Study in an Ambulatory Elderly Population in Quebec , 2006, Gerontology.

[61]  C. Mathieu,et al.  Immune regulation of 25-hydroxyvitamin-D3-1alpha-hydroxylase in human monocytes. , 2006, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[62]  J. Welsh,et al.  The molecular basis of vitamin D receptor and beta-catenin crossregulation. , 2006, Molecular cell.

[63]  H. Weinans,et al.  Hypervitaminosis D mediates compensatory Ca2+ hyperabsorption in TRPV5 knockout mice. , 2005, Journal of the American Society of Nephrology : JASN.

[64]  J. Hoenderop,et al.  The ß-Glucuronidase Klotho Hydrolyzes and Activates the TRPV5 Channel , 2005, Science.

[65]  M. Holick,et al.  Prevalence of Vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy. , 2005, The Journal of clinical endocrinology and metabolism.

[66]  R. Heaney.  The Vitamin D requirement in health and disease , 2005, The Journal of Steroid Biochemistry and Molecular Biology.

[67]  C. Mathieu,et al.  Immune Regulation of 25‐Hydroxyvitamin‐D3‐1α‐Hydroxylase in Human Monocytes , 2005 .

[68]  S. Kato,et al.  Colon-specific regulation of vitamin D hydroxylases--a possible approach for tumor prevention. , 2005, Carcinogenesis.

[69]  U. Fischer,et al.  Vitamin D3 Metabolism in Human Glioblastoma Multiforme: Functionality of CYP27B1 Splice Variants, Metabolism of Calcidiol, and Effect of Calcitriol , 2005, Clinical Cancer Research.

[70]  S. Gallacher,et al.  Prevalence of vitamin D inadequacy in Scottish adults with non-vertebral fragility fractures , 2005, Current medical research and opinion.

[71]  M. Visser,et al.  Adiposity in relation to vitamin D status and parathyroid hormone levels: a population-based study in older men and women. , 2005, The Journal of clinical endocrinology and metabolism.

[72]  N. Stern,et al.  25-Hydroxyvitamin D3-1α-Hydroxylase Is Expressed in Human Vascular Smooth Muscle Cells and Is Upregulated by Parathyroid Hormone and Estrogenic Compounds , 2005, Circulation.

[73]  H. Morris,et al.  Modulation of CYP27B1 and CYP24 mRNA expression in bone is independent of circulating 1,25(OH)2D3 levels. , 2005, Bone.

[74]  C. Barton,et al.  Vitamin D intake: a global perspective of current status. , 2005, The Journal of nutrition.

[75]  B. Nilius,et al.  Calcium absorption across epithelia. , 2005, Physiological reviews.

[76]  H. Stähelin,et al.  A new significant and independent risk factor for falls in elderly men and women: a low creatinine clearance of less than 65 ml/min , 2005, Osteoporosis International.

[77]  M. Horowitz,et al.  Effect of age on calcium absorption in postmenopausal women. , 2004, The American journal of clinical nutrition.

[78]  J. Hoenderop,et al.  Effects of vitamin D compounds on renal and intestinal Ca2+ transport proteins in 25-hydroxyvitamin D3-1alpha-hydroxylase knockout mice. , 2004, Kidney international.

[79]  M. Holick,et al.  The prostate 25-hydroxyvitamin D-1 alpha-hydroxylase is not influenced by parathyroid hormone and calcium: implications for prostate cancer chemoprevention by vitamin D. , 2004, Carcinogenesis.

[80]  H. Adlercreutz,et al.  Phytoestrogens and vitamin D metabolism: a new concept for the prevention and therapy of colorectal, prostate, and mammary carcinomas. , 2004, The Journal of nutrition.

[81]  P. Lips.  Which circulating level of 25-hydroxyvitamin D is appropriate? , 2004, The Journal of Steroid Biochemistry and Molecular Biology.

[82]  M. Holick,et al.  Regulation of 25-hydroxyvitamin D-1α-hydroxylase by epidermal growth factor in prostate cells , 2004, The Journal of Steroid Biochemistry and Molecular Biology.

[83]  Z. Krivošíková,et al.  [Intensive vitamin D supplementation in the treatment of osteoporosis]. , 2004, Vnitrni lekarstvi.

[84]  Y. Takeuchi,et al.  Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism. , 2004, The Journal of clinical investigation.

[85]  F. Gudat,et al.  Vitamin D Receptor Expression in Human Muscle Tissue Decreases With Age , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[86]  J. Wishart,et al.  Relation between calcium absorption and serum calcitriol in normal men: evidence for age-related intestinal resistance to calcitriol , 2004, European Journal of Clinical Nutrition.

[87]  Y. Takeuchi,et al.  FGF‐23 Is a Potent Regulator of Vitamin D Metabolism and Phosphate Homeostasis , 2003, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[88]  A. Russo de Boland.  Age-related changes in the response of intestinal cells to parathyroid hormone. , 2004, Mechanisms of ageing and development.

[89]  F. Kersten,et al.  Renal Ca2+ wasting, hyperabsorption, and reduced bone thickness in mice lacking TRPV5. , 2003, The Journal of clinical investigation.

[90]  K. Fukuda,et al.  Klotho, a gene related to a syndrome resembling human premature aging, functions in a negative regulatory circuit of vitamin D endocrine system. , 2003, Molecular endocrinology.

[91]  Marjolein Visser,et al.  Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): the Longitudinal Aging Study Amsterdam. , 2003, The Journal of clinical endocrinology and metabolism.

[92]  E. Delvin,et al.  Calcitriol regulates the expression of the genes encoding the three key vitamin D3 hydroxylases and the drug‐metabolizing enzyme CYP3A4 in the human fetal intestine , 2003, Clinical endocrinology.

[93]  H. Cross,et al.  Genistein inhibits Vitamin D hydroxylases CYP24 and CYP27B1 expression in prostate cells , 2003, The Journal of Steroid Biochemistry and Molecular Biology.

[94]  S. Kato,et al.  Vitamin D receptor (VDR) knockout mice reveal VDR-independent regulation of intestinal calcium absorption and ECaC2 and calbindin D9k mRNA. , 2003, The Journal of nutrition.

[95]  R. Vieth,et al.  Age-related changes in the 25-hydroxyvitamin D versus parathyroid hormone relationship suggest a different reason why older adults require more vitamin D. , 2003, The Journal of clinical endocrinology and metabolism.

[96]  M. Macoritto,et al.  Estrogens (E2) regulate expression and response of 1,25-dihydroxyvitamin D3 receptors in bone cells: changes with aging and hormone deprivation. , 2002, Biochemical and biophysical research communications.

[97]  J. Welsh,et al.  Impact of the Vitamin D3 receptor on growth-regulatory pathways in mammary gland and breast cancer , 2002, The Journal of Steroid Biochemistry and Molecular Biology.

[98]  W. Miller,et al.  The Mechanism of 1,25-Dihydroxyvitamin D3Autoregulation in Keratinocytes* , 2002, The Journal of Biological Chemistry.

[99]  D. Wheeler,et al.  Synthesis of 1,25-dihydroxyvitamin D(3) by human endothelial cells is regulated by inflammatory cytokines: a novel autocrine determinant of vascular cell adhesion. , 2002, Journal of the American Society of Nephrology : JASN.

[100]  P. Lips,et al.  Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. , 2001, Endocrine reviews.

[101]  A. Howie,et al.  Extrarenal Expression of 25-Hydroxyvitamin D3-1α-Hydroxylase1 , 2001 .

[102]  F. Branca,et al.  Calcium, physical activity and bone health – building bones for a stronger future , 2001, Public Health Nutrition.

[103]  P M Stewart,et al.  Extrarenal expression of 25-hydroxyvitamin d(3)-1 alpha-hydroxylase. , 2001, The Journal of clinical endocrinology and metabolism.

[104]  L. Fried,et al.  Vitamin D deficiency among older women with and without disability. , 2000, The American journal of clinical nutrition.

[105]  N. Itoh,et al.  Identification of a novel fibroblast growth factor, FGF-23, preferentially expressed in the ventrolateral thalamic nucleus of the brain. , 2000, Biochemical and biophysical research communications.

[106]  D. Zehnder,et al.  1alpha-Hydroxylase and the action of vitamin D. , 2000, Journal of molecular endocrinology.

[107]  R. Boland,et al.  Effect of aging on the mechanisms of PTH‐induced calcium influx in rat intestinal cells , 2000, Journal of cellular physiology.

[108]  K. Lau,et al.  Vitamin D Therapy of Osteoporosis: Plain Vitamin D Therapy Versus Active Vitamin D Analog (D-Hormone) Therapy , 1999, Calcified Tissue International.

[109]  H. Armbrecht,et al.  Intestinal plasma membrane calcium pump protein and its induction by 1,25(OH)(2)D(3) decrease with age. , 1999, The American journal of physiology.

[110]  H. Armbrecht,et al.  Intestinal plasma membrane calcium pump protein and its induction by 1,25(OH)2D3 decrease with age. , 1999, American journal of physiology. Gastrointestinal and liver physiology.

[111]  P. Malloy,et al.  Vitamin D resistance. , 1999, The American journal of medicine.

[112]  M. Nanes,et al.  Tumor necrosis factor activates a nuclear inhibitor of vitamin D and retinoid-X receptors , 1998, Molecular and Cellular Endocrinology.

[113]  E. Ritz,et al.  Interaction of IGF-I and 1 alpha, 25(OH)2D3 on receptor expression and growth stimulation in rat growth plate chondrocytes. , 1998, Kidney international.

[114]  John Adams,et al.  Gains in Bone Mineral Density with Resolution of Vitamin D Intoxication , 1997, Annals of Internal Medicine.

[115]  S. Christakos,et al.  Variable in vivo regulation of rat vitamin D-dependent genes (osteopontin, Ca,Mg-adenosine triphosphatase, and 25-hydroxyvitamin D3 24-hydroxylase): implications for differing mechanisms of regulation and involvement of multiple factors. , 1995, Endocrinology.

[116]  S. Blank,et al.  An outbreak of hypervitaminosis D associated with the overfortification of milk from a home-delivery dairy. , 1995, American journal of public health.

[117]  M. Hewison,et al.  Vitamin D resistance , 1994 .

[118]  I. Holm,et al.  Hypervitaminosis D associated with drinking milk. , 1992, The New England journal of medicine.

[119]  B. Ma,et al.  Expression of 25-hydroxyvitamin D 24-hydroxylase cytochrome P450 in kidney and intestine Effect of 1,25-dihydroxyvitamin D and age , 1991 .

[120]  D. Bikle,et al.  Tumor Necrosis Factor-α Regulation of 1,25-Dihydroxy vitamin D Production by Human Keratinocytes* , 1991 .

[121]  D. Bikle,et al.  Tumor necrosis factor-alpha regulation of 1,25-dihydroxyvitamin D production by human keratinocytes. , 1991, Endocrinology.

[122]  J. Delmez,et al.  Extrarenal production of calcitriol in normal and uremic humans. , 1991, The Journal of clinical endocrinology and metabolism.

[123]  H. Armbrecht,et al.  Expression of 25‐hydroxyvitamin D 24‐hydroxylase cytochrome P450 in kidney and intestine Effect of 1,25‐dihydroxyvitamin D and age , 1991, FEBS letters.

[124]  T. Clemens,et al.  Vitamin D supplementation in elderly nursing home residents increases 25(OH)D but not 1,25(OH)2D. , 1990, The American journal of clinical nutrition.

[125]  M. Holick,et al.  AGE, VITAMIN D, AND SOLAR ULTRAVIOLET , 1989, The Lancet.

[126]  D. Bikle,et al.  Regulation of 1,25-dihydroxyvitamin D production in human keratinocytes by interferon-gamma. , 1989, Endocrinology.

[127]  D. Bikle,et al.  1,25-Dihydroxyvitamin D3 production by human keratinocytes. Kinetics and regulation. , 1986, The Journal of clinical investigation.

[128]  M. Holick,et al.  Aging decreases the capacity of human skin to produce vitamin D3. , 1985, The Journal of clinical investigation.

[129]  H. Koeffler,et al.  gamma-Interferon stimulates production of 1,25-dihydroxyvitamin D3 by normal human macrophages. , 1985, Biochemical and biophysical research communications.

[130]  H. DeLuca,et al.  Effect of estrogen on calcium absorption and serum vitamin D metabolites in postmenopausal osteoporosis. , 1980, The Journal of clinical endocrinology and metabolism.

[131]  T. Oppé,et al.  Vitamin D deficiency. , 1979, British medical journal.

[132]  J. Gallagher,et al.  Effect of age on calcium absorption. , 1970, Lancet.