16.7: Interpretive criteria (18b.8)
- Page ID
- 117079
\( \newcommand{\vecs}[1]{\overset { \scriptstyle \rightharpoonup} {\mathbf{#1}} } \)
\( \newcommand{\vecd}[1]{\overset{-\!-\!\rightharpoonup}{\vphantom{a}\smash {#1}}} \)
\( \newcommand{\dsum}{\displaystyle\sum\limits} \)
\( \newcommand{\dint}{\displaystyle\int\limits} \)
\( \newcommand{\dlim}{\displaystyle\lim\limits} \)
\( \newcommand{\id}{\mathrm{id}}\) \( \newcommand{\Span}{\mathrm{span}}\)
( \newcommand{\kernel}{\mathrm{null}\,}\) \( \newcommand{\range}{\mathrm{range}\,}\)
\( \newcommand{\RealPart}{\mathrm{Re}}\) \( \newcommand{\ImaginaryPart}{\mathrm{Im}}\)
\( \newcommand{\Argument}{\mathrm{Arg}}\) \( \newcommand{\norm}[1]{\| #1 \|}\)
\( \newcommand{\inner}[2]{\langle #1, #2 \rangle}\)
\( \newcommand{\Span}{\mathrm{span}}\)
\( \newcommand{\id}{\mathrm{id}}\)
\( \newcommand{\Span}{\mathrm{span}}\)
\( \newcommand{\kernel}{\mathrm{null}\,}\)
\( \newcommand{\range}{\mathrm{range}\,}\)
\( \newcommand{\RealPart}{\mathrm{Re}}\)
\( \newcommand{\ImaginaryPart}{\mathrm{Im}}\)
\( \newcommand{\Argument}{\mathrm{Arg}}\)
\( \newcommand{\norm}[1]{\| #1 \|}\)
\( \newcommand{\inner}[2]{\langle #1, #2 \rangle}\)
\( \newcommand{\Span}{\mathrm{span}}\) \( \newcommand{\AA}{\unicode[.8,0]{x212B}}\)
\( \newcommand{\vectorA}[1]{\vec{#1}} % arrow\)
\( \newcommand{\vectorAt}[1]{\vec{\text{#1}}} % arrow\)
\( \newcommand{\vectorB}[1]{\overset { \scriptstyle \rightharpoonup} {\mathbf{#1}} } \)
\( \newcommand{\vectorC}[1]{\textbf{#1}} \)
\( \newcommand{\vectorD}[1]{\overrightarrow{#1}} \)
\( \newcommand{\vectorDt}[1]{\overrightarrow{\text{#1}}} \)
\( \newcommand{\vectE}[1]{\overset{-\!-\!\rightharpoonup}{\vphantom{a}\smash{\mathbf {#1}}}} \)
\( \newcommand{\vecs}[1]{\overset { \scriptstyle \rightharpoonup} {\mathbf{#1}} } \)
\(\newcommand{\longvect}{\overrightarrow}\)
\( \newcommand{\vecd}[1]{\overset{-\!-\!\rightharpoonup}{\vphantom{a}\smash {#1}}} \)
\(\newcommand{\avec}{\mathbf a}\) \(\newcommand{\bvec}{\mathbf b}\) \(\newcommand{\cvec}{\mathbf c}\) \(\newcommand{\dvec}{\mathbf d}\) \(\newcommand{\dtil}{\widetilde{\mathbf d}}\) \(\newcommand{\evec}{\mathbf e}\) \(\newcommand{\fvec}{\mathbf f}\) \(\newcommand{\nvec}{\mathbf n}\) \(\newcommand{\pvec}{\mathbf p}\) \(\newcommand{\qvec}{\mathbf q}\) \(\newcommand{\svec}{\mathbf s}\) \(\newcommand{\tvec}{\mathbf t}\) \(\newcommand{\uvec}{\mathbf u}\) \(\newcommand{\vvec}{\mathbf v}\) \(\newcommand{\wvec}{\mathbf w}\) \(\newcommand{\xvec}{\mathbf x}\) \(\newcommand{\yvec}{\mathbf y}\) \(\newcommand{\zvec}{\mathbf z}\) \(\newcommand{\rvec}{\mathbf r}\) \(\newcommand{\mvec}{\mathbf m}\) \(\newcommand{\zerovec}{\mathbf 0}\) \(\newcommand{\onevec}{\mathbf 1}\) \(\newcommand{\real}{\mathbb R}\) \(\newcommand{\twovec}[2]{\left[\begin{array}{r}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\ctwovec}[2]{\left[\begin{array}{c}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\threevec}[3]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\cthreevec}[3]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\fourvec}[4]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\cfourvec}[4]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\fivevec}[5]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\cfivevec}[5]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\mattwo}[4]{\left[\begin{array}{rr}#1 \amp #2 \\ #3 \amp #4 \\ \end{array}\right]}\) \(\newcommand{\laspan}[1]{\text{Span}\{#1\}}\) \(\newcommand{\bcal}{\cal B}\) \(\newcommand{\ccal}{\cal C}\) \(\newcommand{\scal}{\cal S}\) \(\newcommand{\wcal}{\cal W}\) \(\newcommand{\ecal}{\cal E}\) \(\newcommand{\coords}[2]{\left\{#1\right\}_{#2}}\) \(\newcommand{\gray}[1]{\color{gray}{#1}}\) \(\newcommand{\lgray}[1]{\color{lightgray}{#1}}\) \(\newcommand{\rank}{\operatorname{rank}}\) \(\newcommand{\row}{\text{Row}}\) \(\newcommand{\col}{\text{Col}}\) \(\renewcommand{\row}{\text{Row}}\) \(\newcommand{\nul}{\text{Nul}}\) \(\newcommand{\var}{\text{Var}}\) \(\newcommand{\corr}{\text{corr}}\) \(\newcommand{\len}[1]{\left|#1\right|}\) \(\newcommand{\bbar}{\overline{\bvec}}\) \(\newcommand{\bhat}{\widehat{\bvec}}\) \(\newcommand{\bperp}{\bvec^\perp}\) \(\newcommand{\xhat}{\widehat{\xvec}}\) \(\newcommand{\vhat}{\widehat{\vvec}}\) \(\newcommand{\uhat}{\widehat{\uvec}}\) \(\newcommand{\what}{\widehat{\wvec}}\) \(\newcommand{\Sighat}{\widehat{\Sigma}}\) \(\newcommand{\lt}{<}\) \(\newcommand{\gt}{>}\) \(\newcommand{\amp}{&}\) \(\definecolor{fillinmathshade}{gray}{0.9}\)Table 18b.3 shows a lack of consensus in defining cutoff points for serum total 25(OH)D (nmol/L) (i.e., the sum of serum 25(OH)D2 and 25(OH)D3 concentrations). The uncertainty is attributed in part to the lack of standardization of the laboratory measurement of serum total 25(OH)D and the lack of potential functional biomarkers of vitamin D status. Only three of the numerous meta-analyses completed to date are based on standardized serum total 25(OH)D levels (Sempos and Binkley, 2020).
Table 18b.3. Recommendations for interpreting serum levels of 25‑hydroxyvitamin D. Colour code: red denotes a state of severe deficiency (danger) that has to be corrected without exception; orange denotes a state of mild deficiency (modest concern), in which intervention is desirable; green denotes a state of sufficient supply that does not benefit from additional supplementation. AAP, American Academy of Pediatrics; AGS, American Geriatrics Society; DACH, Deutschland, Austria and Confoederatio Helvetica; IOF, International Osteoporosis Foundation; IOM, Institute of Medicine; SACN, Scientific Advisory Committee on Nutrition. Modified from Bouillon (2017)
Agreement exists Table 18b.3 between two groups of nations (i.e., United Kingdom, the Netherlands with Australia/New Zealand, European Union, USA) for the cutoff point to define severe deficiency (i.e., 25–30nmol/L, 10–12ng/mL), but there is much less agreement for cutoff points to define vitamin D insufficiency, vitamin D sufficiency, and vitamin D toxicity. Conflicting recommendations have been compiled by some non-governmental medical societies and organizations.
In 2011, the US Institute of Medicine (IOM) published cut-off points for serum total 25(OH)D that represent public health guidelines for generally healthy non-diseased populations Table 18b.4
| Interpretation | IOM (ng/mL) | Endocine Society (ng/mL) |
|---|---|---|
| Deficient | <12 | <20 |
| Insufficient | 12–20 | 21–29 |
| Sufficient | 20–30 | 30–100 |
| No added benefit | 30–50 | |
| Possible harm | >50 | >100 |
(IOM, 2011). A summary report is available in Ross et al. (2011). The lower limit of adequacy, interpreted as deficiency (i.e.,< 12ng/mL; 30nmol/L), was based on relationships to biomarkers of bone health. Cutoff points for insufficiency, sufficiency, no added benefit, and possible harm were also defined by IOM, and have been adopted by several other organizations, including the Global Consensus Recommendations on the Prevention and Management of Nutritional Rickets (Munns et al., 2016, Sempos and Binkley, 2020).
Note the levels set by IOM differ from those set for clinical practice by the Endocrine Society in 2011, and presented in Table 18b.4 (Holick et al., 2011).However, these are intended as guidance for clinicians for the evaluation, treatment, and prevention of vitamin D deficiency, with emphasis on the care of patients who are at high risk of deficiency (e.g., those with rickets, osteomalacia, osteoporosis, chronic kidney disease, etc). Such practice guidelines to treat disease should not be applied to the apparently healthy population. Clearly, more research is urgently required using assays that meet the standardized criteria developed by the Vitamin D Standardization Program (VDSP) (Section 18b.9) to develop a consensus on a single set of rigorous interpretive criteria for serum total 25(OH)D levels relative to vitamin D status and interventions that are appropriate for both public health and clinical needs. In the meantime, readers are advised to use the IOM (2011) cutoffs proposed and listed in Table 18b.4 for public health use.