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16.10: Other vitamin D meta­bolites (18b.11)

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    Alkaline phos­phat­ase (EC 3.1.1.1) activ­ity in serum can be used as an indirect measure of vitamin D status. Activity inc­reases in osteo­malacia in adults and child­hood rickets but is gener­ally normal in osteoporosis. Increases in the activ­ity of alkaline phos­phat­ase are usually pro­por­tion­al to the severity of vitamin D deple­tion. For exam­ple, elderly Irish indiv­iduals with serum 25(OH)D levels indic­ative of severe or marg­inal vitamin D deple­tion had slightly higher serum alkaline phos­phat­ase activ­ity than those with 25(OH)D levels classified as replete (Figure 18b.4).

    Scatter plot showing serum alkaline phosphatase levels for young adults, replete, borderline, and depleted elderly subjects. The chart includes individual data points and shaded reference ranges.

    Figure 18b.4. Comparison of mean plasma 25(OH)D levels by season for free-living elderly men and women and participants in institutions. Data from Finch et al., 1998, National Diet and Nutrition Survey: People Aged 65 Years or Over. The Stationery Office, London.

    Seasonal changes in serum alkaline phos­phat­ase activ­ity have also been obser­ved in cross-sectional studies, with levels decreasing with seasonal rises in serum 25(OH)D levels (McKenna et al., 1985).

    Serum alkaline phos­phat­ase activ­ity is also affected by sex and age, again in the opposite direction to changes in the levels of serum 25(OH)D. Serum alkaline phos­phat­ase activ­ity is sig­nif­icantly higher in females relative to males and in older versus younger adults; activ­ity is also higher in growing chil­dren and pregnant women, espe­cially during the third trimester (McKenna, 1992). In older surveys such as the U.K. nat­ional survey of young people 4–18y, mean alkaline phosphatase activ­ity was meas­ured. The lowest level was found in the oldest adol­es­cents (15–18y), espe­cially among the girls (Gregory et al., 2000).

    The activ­ity of serum alkaline phos­phat­ase is also altered by various dis­ease states such as hyper­para­thyroid­ism, Paget's dis­ease, sec­ond­ary bone cancer, and cholestasis (Sauberlich, 1999). Serum alkaline phos­phat­ase activ­ity may de­crease in zinc de­fi­ciency but, as noted earlier, appears to be close to normal in osteoporosis in con­trast to osteo­malacia where it is high (Uday and Högler, 2019).

    In general, measure­ment of alkaline phos­phat­ase activ­ity in serum is best used to con­firm a clin­ical diag­nosis of vitamin D de­fi­ciency, or as a screen­ing tool, but it is not very useful for detecting subclin­ical vitamin D de­fi­ciency. The diag­nosis of osteo­malacia can be made in the presence of high alkaline phos­phat­ase activ­ity accompanied by high PTH, low diet­ary calcium intake (< 300mg/d) and/or low serum 25(OH)D (< 30nmol/L) (Uday and Högler, 2019).

    18b.12.1 Interpretive cri­teria

    Serum alkaline phos­phat­ase activ­ity is normally expressed as U/L. The refer­ence range for normal adults is 30–135U/L (Gregory et al., 2000). Total plasma alkaline phos­phat­ase activ­ity was meas­ured in the past U.K. nat­ional surveys (Gregory et al., 2000, Finch et al., 1998) , with the excep­tion of the survey on pre-school chil­dren. Mean, median, and lower and upper 2.5 or 5th per­cen­tiles by age and sex are presented.

    18b.12.2 Measurement of alkaline phos­phat­ase

    Several methods are avail­able for the assay of serum or plasma alkaline phos­phat­ase (ALP); for plasma, heparin­ized blood sam­ples should be used (Bessey et al., 1946). Total alkaline phosphatase meas­ures all sources of en­zyme activ­ity includ­ing liver, while bone-specific alkaline phosphatase (BALP) meas­ures activ­ity derived from osteoblast activ­ity. Higher total or bone alkaline phos­phat­ase levels accompanied by low urin­ary calcium could prompt inves­tigation of vitamin D de­fi­ciency (Kennel et al., 2010). The assay of total alkaline phosphatase activity is sufficient evi­dence as long as other liver en­zymes are normal. The activ­ity of serum or plasma alkaline phos­phat­ase should be expressed as U/L. The within-sub­ject coef­fic­ient of vari­ation for serum/plasma alkaline phos­phat­ase activ­ity ranges from 4.6% to 9.2%, depend­ing on the time frame and diet­ary regimen (Gallagher et al., 1989). The en­zyme is reasonably stable in frozen serum or plasma.

    This page titled 16.10: Other vitamin D meta­bolites (18b.11) is shared under a CC BY 4.0 license and was authored, remixed, and/or curated by Rosalind S. Gibson via source content that was edited to the style and standards of the LibreTexts platform.