vitamin D deficiency
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Etiology
- diminished vitamin D absorption
- nutritional deficiency
- gastrointestinal abnormalities
- gastrectomy
- ileal bypass or resection
- pancreatic insufficiency
- tropical & non-tropical sprue (celiac disease)
- disorders in vitamin D metabolism
- liver disease
- nephrotic range proteinuria
- inability to hydroxylate 25-hydroxyvitamin D
- vitamin D resistance
- renal disorders
- oncogenic osteomalacia
- unsual tumors of mesenchymal origin
- generally benign
- tumor in close association with bone
- adenocarcinoma of the prostate
- small cell carcinoma of the lung
- unsual tumors of mesenchymal origin
- pharmacologic causes:
Epidemiology
- 93% of patients with non-specific musculoskeletal pain in Minneapolis[5]
- 23% of whites, 38% of hispanics, 56% of blacks in Southern Arizona[8]
- uncommon in those who report significant sun-exposure[8]
Pathology
- secondary hyperparathyroidism if prolonged & severe
- etiology of osteomalacia
- vitamin D may suppress pathways leading to anemia of chronic inflammation[13]
Clinical manifestations
- non-specific bone pain is common
- aching pain with weight-bearing (osteomalacia)
- no simple relationship between pain & vit D status[9]
- proximal muscle weakness, gait ataxia
- fatigue
Laboratory
- diminished serum 25-hydroxyvitamin D3
- best indicator of total body vitamin D [7, 8]
- < 20 ng/mL defines vitamin D deficiency[14]*
- optimal level still a matter of dispute*
- neither 800 IU vit D QD nor 50,000 IU twice monthly increases bone mineral density or reduces falls in elderly with serum 25-OH vitamin D of 14-27 ng/mL[22]
- serum 1,25-dihydroxyvitamin D3 may be normal or diminished
- serum Ca+2 may be low normal or slightly diminished
- ionized Ca+2 is low or normal
- serum PTH is normal or increased
- serum phosphate may be low normal or slightly diminished
- mild to moderately elevated serum alkaline phosphatase
- urine chemistry
- urine calcium is normal
- urine phosphate is increased
- aminoaciduria may be present
- tissue transglutaminase IgA in serum for celiac disease if deficiency refractory to treatment[2]
- bone biopsy for definitive diagnosis of osteomalacia
* no consensus on the definition of vitamin D deficiency. or agreement on optimal blood level of 25-hydroxyvitamin D[21]
Radiology
- bone mineral density is low
- plain radiographs may show osteopenia & pseudofractures
Complications
- pulmonary:[11]
- increased risk of reactive airway disease
- increased likelihood of hospitalization for asthma
- neurological disorders
- cognitive impairment[12]
- increased risk of dementia & Alzheimer's disease (RR=1.5-2.2)[20][31]
- may increase risk of multiple sclerosis[31]
- vitamin D levels inversely correlate with motor symptoms of Parkinson disease[31]
- cognitive impairment[12]
- low maternal serum vitamin D levels are associated with adverse pregnancy outcomes[15]
- maternal vitamin D deficiency duing pregnancy associated with increased risk of multiple sclerosis in offsrping[24]
- even seasonal serum 25-hydroxyvitamin D3 < 20 ng//mL is associated with increased risk of death in older adults (HR = 1.32)[16]
- vitamin D deficiency is associated with increased severity of Covid-19 & mortality (RR=14)[30]
Management
- vitamin D
- 50,000 IU (1.25 g) as ergocalciferol weekly for 6-12 weeks[4][18][32]
- check serum 25-hydroxyvitamin D after loading dose; target > 30 ug/L
- maintenance vitamin D 800-1000 IU/day
- supplementation of no benefit in preventing bone loss[26]. falls[28], or cognitive decline in elderly black women[27]
- vitamin D3 without benefit for vitamin D-deficient critically ill patients[29]
- 50,000 IU (1.25 g) as ergocalciferol weekly for 6-12 weeks[4][18][32]
- calcium carbonate
- correction of Mg+2 deficiency
- sunlight
- USPSTF says not enough evidence to recommend for or against screening for vitamin D deficiency[29]
- screening for vitamin D deficiency not recommended[2]
- USPSTF says not enough evidence to recommend for or against vitamin D & calcium supplementation each alone or in combination for prevention of bone fractures in men or postmenopausal women[2]
More general terms
More specific terms
Additional terms
References
- ↑ Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook, Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 829-39
- ↑ 2.0 2.1 2.2 2.3 Medical Knowledge Self Assessment Program (MKSAP) 11, 15, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2009, 2015, 2018, 2022.
Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022 - ↑ Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 1328
- ↑ 4.0 4.1 4.2 Geriatrics Review Syllabus, American Geriatrics Society, 5th edition, 2002-2004
Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
Geriatric Review Syllabus, 9th edition (GRS9) Medinal-Walpole A, Pacala JT, Porter JF (eds) American Geriatrics Society, 2016
Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022 - ↑ 5.0 5.1 Journal Watch 24(2):17, 2004 Plotnikoff GA & Quigley JM, Mayo Clin Proc 78:1463, 2003 http://www.mayo.edu/proceedings/2003/dec/7812e1.pdf PMID: https://www.ncbi.nlm.nih.gov/pubmed/14661675
Holick MF, Mayo Clin Proc 78:1457, 2003 http://www.mayo.edu/proceedings/2003/dec/7812a1.pdf PMID: https://www.ncbi.nlm.nih.gov/pubmed/14661673 - ↑ Prescriber's Letter 11(2):11 2004 Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=200211&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Prescriber's Letter 15(3): 2008 Prevention and treatment of vitamin D deficiency Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=240311&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 8.0 8.1 8.2 Jacobs ET et al, Vitamin D deficiency in southern Arizona. Am J Clin Nutr 2008, 87:608 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18326598
- ↑ 9.0 9.1 Hicks GE et al. Associations between vitamin D status and pain in older adults: The Invecchiare in Chianti Study. J Am Geriatr Soc 2008 May; 56:785. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18331295
- ↑ 10.0 10.1 Zhu K et al. Randomized controlled trial of the effects of calcium with or without vitamin D on bone structure and bone-related chemistry in elderly women with vitamin D insufficiency. J Bone Miner Res 2008 Aug; 23:1343 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18410225
- ↑ 11.0 11.1 Brehm JM et al Serum vitamin D levels and markers of severity of childhood asthma in Costa Rica. Am J Respir Crit Care Med. 2009 May 1;179(9):765-71 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19179486
Devereux G et al. Vitamin D and asthma: Time for intervention? Am J Respir Crit Care Med 2009 May 1; 179:739. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19383926 - ↑ 12.0 12.1 Annweiler C et al. Association of vitamin D deficiency with cognitive impairment in older women: Cross-sectional study. Neurology 2009 Sep 30 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/19794127 <Internet> http://dx.doi.org/10.1212/WNL.0b013e3181beecd3
Buell JS et al. 25-hydroxyvitamin D, dementia, and cerebrovascular pathology in elders receiving home services. Neurology 2010 Jan 5; 74:18. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19940273
Slinin Y et al. 25-hydroxyvitamin D levels and cognitive performance and decline in elderly men. Neurology 2010 Jan 5; 74:33. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19940271
Miller JW. Vitamin D and cognitive function in older adults: Are we concerned about vitamin D-mentia? PMID: https://www.ncbi.nlm.nih.gov/pubmed/19940269 Neurology 2010 Jan 5; 74:13. - ↑ 13.0 13.1 Perlstein TS et al. Prevalence of 25-hydroxyvitamin D deficiency in subgroups of elderly persons with anemia: Association with anemia of inflammation. Blood 2011 Mar 10; 117:2800. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21239700
- ↑ 14.0 14.1 Holick MF et al Evaluation, Treatment, and Prevention of Vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline Journal of Clinical Endocrinology & Metabolism June 6, 2011 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21646368 <Internet> http://jcem.endojournals.org/content/early/2011/06/03/jc.2011-0385.abstract
- ↑ 15.0 15.1 Aghajafari F et al Association between maternal serum 25-hydroxyvitamin D level and pregnancy and neonatal outcomes: systematic review and meta-analysis of observational studies. BMJ 2013;346:f1169 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23533188 <Internet> http://www.bmj.com/content/346/bmj.f1169
Lucas R et al Vitamin D sufficiency in pregnancy. BMJ 2013;346:f1675 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23533189 <Internet> http://www.bmj.com/content/346/bmj.f1675 - ↑ 16.0 16.1 de Boer IH e al Serum 25-hydroxyvitamin D concentration and risk for major clinical disease events in a community-based population of older adults: a cohort study. Ann Intern Med. 2012 May 1;156(9):627-34 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22547472
- ↑ Holick MF, Binkley NC, Bischoff-Ferrari HA et al Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011 Jul;96(7):1911-30 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21646368 corresponding NGC guideline withdrawn Feb 2017
Holick MF, Binkley NC, Bischoff-Ferrari HA et al Guidelines for preventing and treating vitamin D deficiency and insufficiency revisited. J Clin Endocrinol Metab. 2012 Apr;97(4):1153-8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22442274 - ↑ 18.0 18.1 Prescriber's Letter 17(7): 2010 Vitamin D Dosing: An Update Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=260707&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Rosen CJ. Clinical practice. Vitamin D insufficiency. N Engl J Med. 2011 Jan 20;364(3):248-54. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21247315
- ↑ 20.0 20.1 Littlejohns TJ et al. Vitamin D and the risk of dementia and Alzheimer disease. Neurology 2014 Sep 2; 83:1 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25098535 <Internet> http://www.neurology.org/content/83/10/920
- ↑ 21.0 21.1 LeFevre ML for the U.S. Preventive Services Task Force Screening for Vitamin D Deficiency in Adults: U.S. Preventive Services Task Force Recommendation Statement. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25419853 <Internet> http://annals.org/article.aspx?articleid=1938935
LeBlanc ES et al Screening for Vitamin D Deficiency: A Systematic Review for the U.S. Preventive Services Task Force. Ann Intern Med. Published online 25 November 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25419719 <Internet> http://annals.org/article.aspx?articleid=1938934
US Preventive Services Task Force Screening for Vitamin D Deficiency in Adults. US Preventive Services Task Force Recommendation Statement JAMA. 2021;325(14):1436-1442. April 13. PMID: https://www.ncbi.nlm.nih.gov/pubmed/33847711 https://jamanetwork.com/journals/jama/fullarticle/2778487
Kahwati LC, LeBlanc E, Weber RP et al Screening for Vitamin D Deficiency in AdultsUpdated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2021;325(14):1443-1463. April 13. PMID: https://www.ncbi.nlm.nih.gov/pubmed/33847712 https://jamanetwork.com/journals/jama/fullarticle/2778488
Burnett-Bowie SAM, Cappola AR The USPSTF 2021 Recommendations on Screening for Asymptomatic Vitamin D Deficiency in Adults. The Challenge for Clinicians Continues. JAMA. 2021;325(14):1401-1402 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33847724 https://jamanetwork.com/journals/jama/fullarticle/2778507 - ↑ 22.0 22.1 Hansen KE et al Treatment of Vitamin D Insufficiency in Postmenopausal Women. A Randomized Clinical Trial. JAMA Intern Med. Published online August 03, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26237520 <Internet> http://archinte.jamanetwork.com/article.aspx?articleid=2422066
Grady D How Much Vitamin D Is Enough? JAMA Intern Med. Published online August 03, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26237006 <Internet> http://archinte.jamanetwork.com/article.aspx?articleid=2422063 - ↑ Holick MF Vitamin D deficiency. N Engl J Med. 2007 Jul 19;357(3):266-81. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17634462
- ↑ 24.0 24.1 Munger KL, Aivo J, Hongell K et al Vitamin D Status During Pregnancy and Risk of Multiple Sclerosis in Offspring of Women in the Finnish Maternity Cohort. JAMA Neurol. Published online March 07, 2016. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/2695377 <Internet> http://archneur.jamanetwork.com/article.aspx?articleid=2499458
- ↑ 25.0 25.1 Shah S, Chiang C, Sikaris K, Lu Z, Bui M, Zebaze R, Seeman E. Serum 25-hydroxyvitamin D insufficiency in search of a bone disease. J Clin Endocrinol Metab 2017 Mar 30; 102:2321 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28379394
- ↑ 26.0 26.1 Aloia J, Fazzari M, Islam S et al. Vitamin D supplementation in elderly black women does not prevent bone loss: A randomized controlled trial. J Bone Miner Res 2018 Nov; 33:1916. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29905969
- ↑ 27.0 27.1 Owusu JE, Islam S, Katumuluwa SS et al. Cognition and vitamin D in older African-American women - Physical performance and osteoporosis prevention with vitamin D in older African Americans trial and dementia. J Am Geriatr Soc 2019 Jan; 67:81. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30359476
- ↑ 28.0 28.1 Aloia JF, Rubinova R, Fazzari M, Vitamin D and Falls in Older African American Women: The PODA Randomized Clinical Trial. J Am Geriatr Soc. 2019 Jan 30. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30698279
- ↑ 29.0 29.1 29.2 U.S. Preventive Services Task Force (USPSTF) Vitamin D Deficiency in Adults: Screening. Draft Recommendation Statement. Sept 22, 2020 https://www.uspreventiveservicestaskforce.org/uspstf/draft-recommendation/vitamin-d-deficiency-screening-2021
U.S. Preventive Services Task Force (USPSTF) Vitamin D Deficiency in Adults: Screening. Draft Evidence Review. Sept 22, 2020 https://www.uspreventiveservicestaskforce.org/uspstf/document/draft-evidence-review/vitamin-d-deficiency-screening-2021 - ↑ 30.0 30.1 Crist C Study: Vitamin D Deficiency Linked to Severe COVID. Medscape. February 08, 2022 https://www.medscape.com/viewarticle/968121
Dorr AA, Morozov N, Daoud A et al Pre-infection 25-hydroxyvitamin D3 levels and association with severity of COVID-19 illness. PLOS One. 2022. Feb 3. https://doi.org/10.1371/journal.pone.0263069 - ↑ 31.0 31.1 31.2 31.3 Miles DS Vitamin D Deficiency Linked to Neurologic Disorders. Clinical Advisor. December 15, 2022 https://www.clinicaladvisor.com/home/topics/neurology-information-center/vitamin-d-deficiency-neurologic-disorders/
- ↑ 32.0 32.1 NEJM Knowledge+ Endocrinology
- ↑ The National Heart, Lung, and Blood Institute PETAL Clinical Trials Network. Early high-dose vitamin D3 for critically ill, vitamin D-deficient patients. N Engl J Med 2019 Dec 26; 381:2529 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31826336 https://www.nejm.org/doi/10.1056/NEJMoa1911124