Howard Libman, MD; Alan O. Malabanan, MD; Gordon J. Strewler, MD; Eileen E. Reynolds, MD
Acknowledgment: The authors thank the patient for sharing her story.
Grant Support: Beyond the Guidelines receives no external support.
Disclosures: Dr. Libman reports payment for a consultancy with Gilead Sciences, expert testimony, local CME courses, and development of educational presentations from the International Antiviral Society; and royalties from UpToDate. Authors not named here have no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M16-1993.
Requests for Single Reprints: Howard Libman, MD, Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. Libman, Malabanan, and Reynolds: Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215.
Dr. Strewler: University of California, San Franciso, School of Medicine, 533 Parnassus Avenue, San Francisco CA 94117.
Libman H, Malabanan AO, Strewler GJ, Reynolds EE. Should We Screen for Vitamin D Deficiency?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center. Ann Intern Med. 2016;165:800-807. doi: 10.7326/M16-1993
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Published: Ann Intern Med. 2016;165(11):800-807.
The U.S. Preventive Services Task Force (USPSTF) recently issued guidelines on screening for vitamin D deficiency. The guidelines were based on randomized trials of vitamin D deficiency screening and treatment, as well as on case–control studies nested within the Women's Health Initiative. The USPSTF concluded that current evidence is insufficient to assess the benefits and harms of screening for vitamin D deficiency in asymptomatic adults. Compared with placebo or no treatment, vitamin D was associated with decreased mortality; however, benefits were no longer seen after trials of institutionalized persons were excluded. Vitamin D treatment was associated with a possible decreased risk for at least 1 fall and the total number of falls per person but not for fractures. None of the studies examined the effects of vitamin D screening versus not screening on clinical outcomes. In this Grand Rounds, 2 prominent endocrinologists debate the issue of screening for vitamin D deficiency in a 55-year-old, asymptomatic, postmenopausal woman. They review the data on which the USPSTF recommendations are based and discuss the potential benefits and risks, as well as the challenges and controversies, of screening for vitamin D deficiency in primary care practice.
Beyond the Guidelines is an educational feature based on recent guidelines. Each considers a patient who “falls between the cracks” of available evidence and for whom the optimal clinical course in unclear. Presented at Beth Israel Deaconess Medical Center (BIDMC) Grand Rounds, each conference reviews the background evidence and 2 experts then discuss the patient and field audience questions. Videos of the patient and conference, the slide presentation and a CME/MOC activity accompany each article. For more information, visit www.annals.org/GrandRounds.
Series Editor, Annals: Deborah Cotton, MD, MPH
Series Editor, BIDMC: Risa B. Burns, MD, MPH
Series Assistant Editors: Howard Libman, MD; Eileen E. Reynolds, MD; Gerald W. Smetana, MD
This article is based on the Department of Medicine Grand Rounds conference held on 26 May 2016.
Moderator: Eileen E. Reynolds, MD
Discussants: Alan O. Malabanan, MD, and Gordon J. Strewler, MD
Patient interview video
Grand Rounds video
Questions and comments
Screening for vitamin D deficiency in adults: U.S. Preventive Services Task Force recommendation statement.
From reference 2.
Table 1. Risk Factors for Vitamin D Deficiency*
Effect of vitamin D treatment on 25-(OH)D levels for a period greater than 3 months.
To convert nmol/L to ng/mL, divide by 2.5. Modified from reference 18. 25-(OH)D = 25-hydroxyvitamin D.
Changes in 25-(OH)D before and after elective knee surgery.
To convert nmol/L to ng/mL, multiply by 2.5. The dashed line denotes a 25-(OH)D threshold of 20 ng/mL, and the dotted line denotes a threshold of 30 ng/mL. Modified from reference 33. 25-(OH)D = 25-hydroxyvitamin D.
A reverse J-shaped association showing the increase in mortality when 25-(OH)D levels are greater than 40 ng/mL.
From reference 41. 25-(OH)D = 25-hydroxyvitamin D.
Table 2. Vitamin D Questionnaire*
Dr. Libman is Chief of the Education Section in the Division of General Medicine and Primary Care and Director of Ambulatory Residency Training in the Department of Medicine at Beth Israel Deaconess Medical Center and Professor of Medicine at Harvard Medical School, Boston, Massachusetts.
Dr. Malabanan is Program Director of the Beth Israel Deaconess Medical Center—Joslin Clinic Endocrinology Fellowship and Assistant Professor of Medicine at Harvard Medical School, Boston, Massachusetts.
Dr. Strewler is Director of the Inquiry Program and Professor of Medicine at the University of San Francisco School of Medicine, San Francisco, California.
Dr. Reynolds is Vice Chair for Education in the Department of Medicine at Beth Israel Deaconess Medical Center and Associate Professor of Medicine at Harvard Medical School, Boston, Massachusetts.
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Conference Video - Beyond the Guidelines: Should We Screen for Vitamin D Deficiency?
Patient Interview Video - Beyond the Guidelines: Should We Screen for Vitamin D Deficiency?
Case Western Reserve University, MetroHealth Campus
December 8, 2016
Vitamin D is a negative acute phase reactant
TO THE EDITOR: The discussion by Libman and colleagues (1) about whether we should screen for Vitamin D deficiency would be more complete if it took note of the finding that serum 25-(OH)D is a negative acute phase reactant (2, 3), one of the many molecules whose plasma concentration falls during inflammatory states (4). Rather than reflecting Vitamin D deficiency, low levels may merely reflect one of the many conditions associated with low grade inflammation (5).1. Libman H, Malabanan AO, Strewler GJ, Reynolds EE. Should We Screen for Vitamin D Deficiency?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center. 2016 Dec 6;165(11):800-807.2. Reid D, Toole BJ, Knox S, Talwar D, Harten J, O'Reilly DS, et al. The relation between acute changes in the systemic inflammatory response and plasma 25-hydroxyvitamin D concentrations after elective knee arthroplasty. Am J Clin Nutr. 2011 May;93(5):1006-11.3. Waldron JL, Ashby HL, Cornes MP, Bechervaise J, Razavi C, Thomas OL, et al. Vitamin D: a negative acute phase reactant. J Clin Pathol. 2013 Jul;66(7):620-2.4. Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med. 1999 Feb 11;340(6):448-545. Kushner I, Rzewnicki D, Samols D. What does minor elevation of C-reactive protein signify? Am J Med 2006;119: 166.e17–28.
F Ramirez Lafita MD FACP, M Castellà MD, MA Amigó MD
Dept of Occupational Health. ANAV. L'Hospitalet de l'Infant, Tarragona, Spain
December 20, 2016
Screening for vitamin D deficiency
Vitamin D deficiency constitutes a common problem around the world. Beside its effects on bone metabolism, the role of vitamin D in health has become an interesting topic in the last years. Growing evidence associates vitamin D deficiency with several disorders (vascular, inflammatory, neoplastic or neurodegenerative diseases). (1) Interestingly vitamin D deficiency has also been considered a negative acute phase reactant. Therefore, serum 25OHD has been considered an unreliable biomarker of vitamin D status in inflammatory states. Hypovitaminosis D could be a consequence rather than a cause of inflammation. (2)Libman et al bring up an interesting discussion on screening for Vitamin D deficiency where the topic “to screen or not to screen” is discussed. (3)In fact, many providers prescribe vitamin D supplements in nursing home residents while others prefer first to asses vitamin D levels and to prescribe supplements in deficient or in osteoporotic patients (4). However, assessment of VD status is an unsolved issue. There are many available tests to determine levels of vitamin D being 25OHD the preferred marker but, its accuracy is difficult to determine because the lack of studies that use an internationally recognized reference standard and the lack of consensus on laboratory values that define vitamin D deficiency. It has been described that genetic variants play a role on vitamin D metabolism and 25OHD concentrations. New markers of vitamin D status as vitamin D metabolite ratio (VMR), 25OHD not bound to vitamin D binding protein (DBP) and assessment of single nucleotide polymorphism (SNP) in genes of DBP, 7-dehydrocholesterol reductase and vitamin D receptor (VDR) could be helpful to determine actual levels of vitamin D and to identify individuals at risk of vitamin D deficiency who could beneficiate of supplementation. (5) 1. Guillot X, Semerano L, Saidenberg-Kermanach N, Falgarone G, Boissier MC. Vitamin D and inflammation. Joint Bone Spine. 2010 Dec;77(6):552-7. doi: 10.1016/j.jbspin.2010.09.018.2. Waldron JL, Ashby HL, Cornes MP, Bechervaise J, Razavi C, Thomas OL, Chugh S, Deshpande S, Ford C, Gama R. Vitamin D: a negative acute phase reactant. J Clin Pathol. 2013 Jul;66(7):620-2. doi: 10.1136/jclinpath-2012-2013013. Libman H, Malabanan AO, Strewler GJ, Reynolds EE. Should We Screen for Vitamin D Deficiency?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center. Ann Intern Med. 2016 Dec 6;165(11):800-807. doi: 10.7326/M16-1993.4. Buckinx F , Reginster JY , Cavalier E , Petermans J , Ricour C , Dardenne C , Bruyère O. Determinants of vitamin D supplementation prescription in nursing homes: a survey among general practitioners. Osteoporos Int. 2016 Mar;27(3):8816. doi: 10.1007/s00198015346935. Herrmann M, Farrell CL, Pusceddu I, Fabregat-Cabello N, Cavalier E. Assessment of vitamin D status - a changing landscape. Clin Chem Lab Med. 2017 Jan 1;55(1):3-26. doi: 10.1515/cclm-2016-0264
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