chapter 11 case study low serum vitamin d

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INTRODUCTION

Overt vitamin D deficiency, characterized by hypocalcemia and/or hypophosphatemia and rickets and osteomalacia in children and osteomalacia in adults, is now uncommon in most developed countries (see "Epidemiology and etiology of osteomalacia" and "Clinical manifestations, diagnosis, and treatment of osteomalacia in adults" ). However, subclinical vitamin D deficiency occurs even in developed countries and is associated with osteoporosis and possibly fractures. Vitamin D stores decline with age, especially in the winter [ 1-3 ]. In temperate areas such as Boston and Edmonton, for example, cutaneous production of vitamin D virtually ceases in winter [ 2 ]. Thus, identification and treatment of vitamin D deficiency is important for musculoskeletal health and possibly even extraskeletal health, including the immune and cardiovascular systems. (See "Vitamin D and extraskeletal health" .)

This topic will review the definition, clinical manifestations, and treatment of vitamin D deficiency in adults. The causes of vitamin D deficiency, vitamin D supplementation in osteoporosis, and the treatment of vitamin D deficiency in children are reviewed separately. (See "Causes of vitamin D deficiency and resistance" and "Calcium and vitamin D supplementation in osteoporosis" and "Vitamin D insufficiency and deficiency in children and adolescents" .)

DEFINING VITAMIN D SUFFICIENCY

Serum 25-hydroxyvitamin D  —  Vitamin D sufficiency is estimated by measuring 25-hydroxyvitamin D (25[OH]D or calcidiol) concentrations. The optimal serum 25(OH)D concentration for skeletal health is controversial. Based upon the trials of vitamin D supplementation [ 4-7 ] and National Academy of Medicine (NAM), formerly called the Institute of Medicine (IOM), systematic review [ 8 ], we favor maintaining the serum 25(OH)D concentration between 20 and 40 ng/mL (50 to 100 nmol/L). Experts agree that levels lower than 20 ng/mL are suboptimal for skeletal health. The optimal serum 25(OH)D concentrations for extraskeletal health have not been established. (See "Vitamin D and extraskeletal health" .)

The NAM supports 25(OH)D concentrations above 20 ng/mL (50 nmol/L) [ 8 ]. These recommendations are based upon evidence related to bone health. Other experts (the National Osteoporosis Foundation [NOF], the International Osteoporosis Foundation [IOF], the American Geriatric Society [AGS]) suggest that a minimum level of 30 ng/mL (75 nmol/L) is necessary in older adults to minimize the risk of falls and fracture [ 9-12 ]. The systematic review by the NAM concluded there are insufficient data to determine the safe upper limit of serum 25(OH)D [ 8 ]. However, there was some concern at serum 25(OH)D concentrations above 50 ng/mL (125 nmol/L). These concerns were based upon the increase in fracture in patients treated with high-dose vitamin D [ 7 ] and conflicting studies describing a potential increased risk for some cancers (eg, pancreatic, prostate) and mortality with levels above 30 to 48 ng/mL (75 to 120 nmol/L). (See "Vitamin D and extraskeletal health", section on 'Cancer' and "Vitamin D and extraskeletal health", section on 'Mortality' .)

Given the controversy surrounding optimal serum 25(OH)D concentrations, the definitions of vitamin D sufficiency, insufficiency, and deficiency are only approximate. The majority of groups currently use the following values to categorize the vitamin D status in adults [ 13 ].

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Screening for Vitamin D Deficiency in Adults: An Evidence Review for the U.S. Preventive Services Task Force

Evidence Synthesis, No. 201

Investigators: Leila C. Kahwati , MD, MPH, Erin LeBlanc , MD, MPH, Rachel Palmieri Weber , PhD, Kayla Giger , BS, Rachel Clark , BA, Kara Suvada , BS, Amy Guisinger , BS, and Meera Viswanathan , PhD.

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Structured Abstract

To review the evidence about screening for vitamin D deficiency in adults.

Data Sources:

MEDLINE, Embase, the Cochrane Library, trial registries, and other sources through March 12, 2020; bibliographies from retrieved articles, outside experts, and surveillance of the literature through November 30, 2020.

Study Selection:

Two investigators independently selected studies using a priori inclusion and exclusion criteria. We selected randomized, controlled trials (RCTs) that evaluated the benefits or harms of screening or treatment of vitamin D deficiency in adults; observational studies were also eligible for selection if they reported eligible harms. For treatment, we selected studies for which at least 90 percent of the population had serum vitamin D levels less than 30 ng/ml. We excluded studies with poor methodological quality and studies conducted in developing countries.

Data Extraction and Analysis:

One investigator extracted data and a second checked accuracy. Two reviewers independently rated methodological quality for all included studies using predefined criteria. When at least three similar studies were available, meta-analyses were conducted.

Data Synthesis:

We did not identify any studies directly evaluating health benefits or harms of screening. We included 46 studies (45 RCTs and 1 nested case-control study within a RCT) that evaluated various doses, frequency, and duration of treatment with vitamin D (with or without calcium). We assessed 13 studies as good quality; the rest were fair quality.

Twenty-six RCTs and one nested case-control study reported on the effectiveness of treatment on health outcomes; half enrolled or reported on participants with serum vitamin D levels less than 20 ng/ml. Overall, the evidence suggests treatment with vitamin D (with or without calcium) had no effect on most health outcomes, though the evidence is limited for some outcomes. Among community-dwelling populations, treatment had no effect on mortality (pooled absolute risk difference [ARD] 0.3% [95% confidence interval [CI], −0.6% to 1.1%]; 8 RCTs), fractures (pooled ARD −0.3% [95% CI, −2.1% to 1.6%]; 6 RCTs), incidence of diabetes (pooled ARD 0.1% [95% CI, −1.3% to 1.6%]; 5 RCTs), incidence of cardiovascular disease (2 RCTs, relative risk 1.00 [95% CI, 0.74 to 1.35] and 1.09 [95% CI, 0.68 to 1.76]), incidence of cancer (2 RCTs, hazard ratio 0.97 [95% CI, 0.68 to 1.39] and 1.01 [95% CI, 0.65 to 1.58] , or depression (3 RCTs, various measures reported). The evidence for the impact of treatment on falls was inconclusive. The pooled ARD for incidence of participants with one or more falls was −4.3% (95% CI, −11.6% to 2.9%; 6 RCTs), and the pooled incidence rate difference for the total number of falls per group was −0.10 (95% CI, −0.19 to −0.002). The evidence was mixed for the impact of treatment on physical functioning (2 RCTs) and limited for the impact on infection (1 RCT).

The incidence of total adverse events, serious adverse events, discontinuations due to adverse events, kidney stones, and other harms was similar between active treatment and control groups.

Limitations:

Only English-language studies were included. Most studies were primarily designed to assess intermediate health outcomes; some studies were conducted in nondeficient populations but reported on subgroups with deficiency. We did not assess comparative effectiveness or harms of various doses or formulations of vitamin D or assess the impact of vitamin D treatment for specific clinical conditions.

Conclusions:

No studies have evaluated the direct benefit or harms of screening for vitamin D deficiency. Among asymptomatic, community-dwelling populations with low vitamin D levels, the evidence suggests that treatment with vitamin D (with or without calcium) has no effect on mortality or the incidence of fractures, falls, depression, diabetes, cardiovascular disease, cancer, or adverse events. The evidence is inconclusive about the impact of treatment on physical functioning and infection.

• Collapse All
• Acknowledgments
• Condition Definition
• Prevalence and Burden of Disease/Illness
• Etiology and Risk Factors
• Rationale for Screening/Screening Strategies
• Current Clinical Practice
• Key Questions and Analytic Framework
• Data Sources and Searches
• Study Selection
• Quality Assessment and Data Extraction
• Data Synthesis and Analysis
• U.S. Preventive Services Task Force Involvement
• Expert Review and Public Comment
• Benefits of Screening (Key Question 1)
• Harms of Screening (Key Question 2)
• Benefits of Treatment (Key Question 3)
• Harms of Treatment (Key Question 4)
• Summary of Evidence
• Limitations
• Future Research Needs
• Conclusions
• Appendix A. Contextual Questions
• Appendix B. Additional Methods Information
• Appendix C. Excluded Studies
• Appendix D. Evidence Tables
• Appendix E. Assessment of Study Quality
• Appendix F. Additional Results

Suggested citation:

Kahwati LC, LeBlanc E, Weber RP, Giger K, Clark R, Suvada K, Guisinger A, Viswanathan M. Screening for Vitamin D Deficiency in Adults: An Evidence Review for the U.S. Preventive Services Task Force. Evidence Synthesis No. 201. AHRQ Publication No. 20-05270-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2021.

This report is based on research conducted by the RTI International–University of North Carolina at Chapel Hill Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. HHSA-290-2015-00011-I, Task Order No. 11). The findings and conclusions in this document are those of the authors, who are responsible for its contents, and do not necessarily represent the views of AHRQ. Therefore, no statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services.

The information in this report is intended to help health care decision makers—patients and clinicians, health system leaders, and policymakers, among others—make well-informed decisions and thereby improve the quality of healthcare services. This report is not intended to be a substitute for the application of clinical judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information (i.e., in the context of available resources and circumstances presented by individual patients).

This report may be used, in whole or in part, as the basis for development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.

None of the investigators have any affiliations or financial involvement that conflicts with the material presented in this report.

• Cite this Page Kahwati LC, LeBlanc E, Weber RP, et al. Screening for Vitamin D Deficiency in Adults: An Evidence Review for the U.S. Preventive Services Task Force [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2021 Apr. (Evidence Synthesis, No. 201.)
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Question: Case Study: Low Serum Vitamin D Martha is a 90-year-old Caucasian woman who has recently been diagnosed with osteoporosis after a recent fall that broke her hip. She is 64 inches tall and weighs 115 pounds. Lately she has been complaining about muscle pain in her legs. She eats a limited diet due to a chronic low appetite. A recent blood test shows Martha's

Breakfast: Cereal with milk, one egg  L …

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Chapter 11 Case Study: Low Serum Vitamin D

1. Which of the following is NOT a likely cause of vitamin D deficiency in the elderly?

Reduced absorption of magnesium

6. Joan has been taking a multivitamin supplement every day that provides 1,500 µg of vitamin A. The RDA for Vitamin A for a woman of Joan's age is 700 ug/day and the Upper Limit (UL) for vitamin A is 3000 ug/day. Joan's supplement supplies what percent of the RDA for Vitamin A?

3. Because Joan is concerned about skin cancer, she uses a sunscreen when she is outside. At what SPF level will sunscreen start to interfere with vitamin D synthesis?

4. Joan's low serum vitamin D levels and low dietary vitamin D intake indicate that she is vitamin D-deficient. She needs a vitamin D supplement to raise blood vitamin D levels and to lower the risk of fractures. Based on her vitamin D Recommended Dietary Allowance, or RDA, what supplement dose should she take daily?

8. Which of the following food groups is rich in vitamin K?

Dark green, leafy vegetables

2. Of the foods Joan eats, which is the best source of vitamin D?

Fortified milk

7. Analyzing Joan's diet and supplement use, what might explain why she now has osteoporosis?

Her low vitamin D and calcium intakes and her history of taking a multivitamin pill containing 5000 IU of vitamin A per day can all lead to the development of osteoporosis.

5. If Joan wants to increase her intake of vitamin A, which of the following foods would be best?

Sweet potatoes

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