Vitamin D, An Issue of Endocrinology and Metabolism Clinics of North America

Sol Epstein

Description

This issue covers essential topics in endocrinology and Vitamin D, providing the most up-to-date information. Subject matter covered includes the extra-skeletal effects, nutritional needs, Vit D. assays, Rickets, osteomalacia, immune properties of Vit. D, oseoporosis, Vit. D analogs and properties, renal disease, Vit D receptor, cancer, and diabetes.

Sujets

• Médecine
• Spécialités médicales
• Medical
• Metabolism
• Endocrinology

Informations

• Publié par: Saunders
• Date de parution: 29 juin 2010
• Nombre de lectures: 0
• EAN13: 9781455700264
• Langue: English
• Poids de l'ouvrage: 2 Mo

Extrait

Endocrinology and Metabolism Clinics , Vol. 39, No. 2, June 2010
ISSN: 0889-8529
doi: 10.1016/S0889-8529(10)00023-X

Contributors
Endocrinology and Metabolism Clinics
Vitamin D
Sol Epstein
231 Jeffery Lane, Newtown Square, PA 19073, USA
ISSN  0889-8529
Volume 39 • Number 2 • June 2010

Contents
Cover
Contributors
Forthcoming Issues
Foreword
Preface
Vitamin D: Metabolism
The Vitamin D Receptor: New Paradigms for the Regulation of Gene Expression by 1,25-Dihydroxyvitamin D 3
Assessment and Interpretation of Circulating 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D in the Clinical Environment
Low Vitamin D Status: Definition, Prevalence, Consequences, and Correction
Maternal Vitamin D Status: Implications for the Development of Infantile Nutritional Rickets
Osteomalacia as a Result of Vitamin D Deficiency
Genetic Disorders and Defects in Vitamin D Action
Vitamin D and Fracture Prevention
Vitamin D in Kidney Disease: Pathophysiology and the Utility of Treatment
Vitamin D and the Immune System: New Perspectives on an Old Theme
Vitamin D: Extraskeletal Health
The Role of Vitamin D in Cancer Prevention and Treatment
Vitamin D and Diabetes
Vitamin D Analogs
Index
Endocrinology and Metabolism Clinics , Vol. 39, No. 2, June 2010
ISSN: 0889-8529
doi: 10.1016/S0889-8529(10)00025-3

Forthcoming Issues
Endocrinology and Metabolism Clinics , Vol. 39, No. 2, June 2010
ISSN: 0889-8529
doi: 10.1016/j.ecl.2010.02.015

Foreword

Derek LeRoith, MD, PhD
Division of Endocrinology, Metabolism, and Bone Diseases, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1055, Altran 4-36, New York, NY 10029, USA
E-mail address: [e-mail]


Derek LeRoith, MD, PhD Consulting Editor
Drs Christakos, Ajibade, Dhawan, Fechner, and Mady review the metabolism of vitamin D. Hydroxylases are involved in converting the parent molecule to 25-OH vitamin D and then to 1,25-OH vitamin D, the active form. The regulation of these hydroxylases is still not well defined, and this area of research may be of value in considering new therapeutic possibilities, especially the possibility that vitamin D may be involved in many nonclassical functions, as described in this issue.
Drs Pike and Meyer describe new information on the vitamin D receptor. The receptor is expressed in cell types, including those of the immune system, skin, pancreas, and bone. This may explain the widespread effects of vitamin D that have recently become known and spurred a large amount of research. When 1,25-OH vitamin D binds its receptor, it activates the receptor that in turn affects varied gene expression in multiple cells and tissues. As the authors outline, new technologies have been instrumental in these new discoveries.
Measurement of vitamin D is important in metabolic bone disease and, we now realize, in many other diseases; this is becoming increasingly clear and is a theme developed in this issue. As described by Dr Hollis, 25-OH vitamin D is the most important indicator of nutritional adequacy, and 1,25-OH vitamin D2 as the active form, which is of concern. Both have stability issues; however, currently available methods for measuring these are reasonably accurate. The methodology to measure circulating levels of the 2 vitamin Ds are discussed, as are currently accepted levels.
In the United States today, it is estimated that almost two-thirds of adults have a level of circulating of 25-OH vitamin below the accepted normal level of 30 ng/mL. The consequences of low levels of vitamin D are under intensive investigation, because many different systems may be affected, including bone, muscle, and cancer. Although the effect on bone has been well established for many decades, the effect on other systems is still poorly defined. It has been advised that the current recommended supplementation of 400 IU per day is far too low and that 800 IU per day is preferable. This dose has raised concerns of hypercalciuria and hypercalcemia occurring, but Drs Binkley, Ramamurthy, and Krueger correctly suggest that vitamin D toxicity from supplementation is uncommon and supplementation is, therefore, essential.
Infantile nutritional rickets was thought to be eradicated in developed countries due to vitamin D supplementation but for several reasons has re-emerged. In underdeveloped countries, breastfeeding is common and continues for many months post partum; this continued widespread practice in immigrants with darker skins in developed countries can result in the appearance of nutritional rickets in offspring, because the mother’s vitamin levels determines the levels in infants. Drs Thandrayen and Pettifor discuss the importance of vitamin supplementation during pregnancy and during lactation to avoid this problem. To maintain normal circulating 25-OH vitamin D levels in high-risk individuals, they recommend 400 IU daily for breastfed infants and 2000 IU per day for pregnant women.
Osteomalacia is usually secondary to vitamin D deficiency. Classically, it was seen in poor countries due to malnutrition or in countries where dark skin pigmentation or lack of sunlight prevented adequate vitamin D synthesis in the skin. With supplementation, the disorder may be prevented or readily treated. As discussed in the article by Drs Bhan, Rao, and Rao, the disorder still exists for many reasons. One cause seen in developed countries is secondary to malabsorption syndromes. More recently, the increase in bariatric surgery may be associated with an increased incidence. Fortunately, diagnosis is still standard and treatment with vitamin D is effective.
There are two rare genetic disorders of vitamin D–related rickets; in one, named vitamin D–dependent rickets type 1, calcitriol can no longer be synthesized, and in the second, hereditary vitamin D–resistant rickets, the vitamin D receptor is defective. Both disorders present with early-onset rickets and hypocalcemia; however, the former has low 1,25-OH vitamin D levels whereas the latter has elevated levels, but the vitamin D receptor mutation prevents it from functioning normally. Drs Malloy and Feldman have been instrumental in characterizing these disorders in humans and animal models.
Dr Bischoff-Ferrari describes the importance of vitamin D supplementation particularly as related to falls and fracture incidence. Clinical trials have demonstrated the efficacy of vitamin D supplementation in preventing falls and fractures at hip and vertebral sites. Given this evidence, it is appropriate to consider 700 to 1000 IU daily as a minimally adequate dose.
Vitamin D metabolism and renal disease are intimately related. Chronic kidney disease (CKD) is commonly associated with low vitamin D levels, leading to secondary hyperparathyroidism and metabolic bone disease. As discussed in the article by Drs Qazi and Martin, CKD is a major risk factor for vitamin D deficiency, and the mechanisms are well studied. Vitamin D therapy at various stages of kidney disease is important to reverse the associated hyperparathyroidism and subsequent renal osteodystrophy, with observational studies suggesting improved survival.
Dr Hewison discusses an interesting topic relating vitamin D to the immune system. Vitamin D, or the active form 1,25-OH, not only is associated with sarcoidosis but also is involved in the normal regulation of innate and adaptive immunity. As described in this article, this effect is mediated by local 1,25-OH vitamin D, derived from the circulation and acting in a local paracrine or autocrine fashion. Therefore, low circulating 25-OH vitamin D, commonly seen as a manifestation of nutritional lack, can perhaps lead to alterations in immune function. The clinical implications are numerous, including infections, such as tuberculosis, and autoimmune disorders, such as type 1 diabetes mellitus.
Dr Holick presents a historical perspective regarding vitamin D, its metabolites, and importance, initially for bone metabolism and more recently for extraskeletal effects. Cancer prevention and even a reduction of metastatic disease, as in the case of prostatic cancer, have been correlated with vitamin D intake. Inhibition of keratinocyte proliferation makes vitamin D a candidate therapeutic approach for psoriasis. Involvement in the autoimmune process suggested a role in type 1 diabetes mellitus, multiple sclerosis, and autoimmune encephalitis. In addition, possible benefits may be seen for patients with hypertension and patients with type 2 diabetes mellitus. Although its role is still being defined, replacement with vitamin D to achieve normal circulating levels is advised.
Is vitamin D, specifically calcitriol, useful in cancer prevention and cancer therapy? As discussed by Krishnan, Trump, Johnson, and Feldman, 1,25-OH vitamin D has been shown in preclinical studies to inhibit cell proliferation, stimulate apoptosis, and inhibit tumor angiogenesis, invasion, and metastasis. This review discusses some of the molecular pathways. The trials currently conducted in human cancer patients have not been completed, however, and its potential has not been fully tested.
The relationship between vitamin D and diabetes is complicated, as described in the article by Drs Takiishi, Gysemans, Bouillon, and Mathieu. Patients with type 1 diabetes mellitus have lower circulating vitamin levels, and vitamin D treatment may reduce insulitis in NOD mice that develop type 1 diabetes; whether or not this will be effective in humans remains to be proved. Treatment of patients with type 2 diabetes mellitus (who also have low circulating 25-OH vitamin D levels) can improve insulin sensitivity and reduce inflammatory processes, most likely due to effects on immune and pancreatic beta cells that express the vitamin D receptor. Thus, the relationship of vitamin D and diabetes is under intense study in preclinical models and in humans.
Vitamin D and its metabolites (25-hydroxyv