Introduction:​ Bisphosphonate treatment in adults with hypophosphatasia (HPP) may increase fracture risk. PLP is a useful marker in biochemically differentiating HPP from osteoporosis in adults. In order to identify elevated PLP, robust reference intervals are needed which are calculated in a large, representative sample population.

Methods:​ Complete data from 9069 individuals (ages 20–80, 50.6% female) from two years of the NHANES Survey (2007–2008 and 2009–2010) were investigated. Differences in PLP in the presence of four factors;​ inflammation (CRP ≥5.0 mg/L), low ALP (lt;​36 IU/L), chronic kidney disease (eGFR <60 mL/min/1.732), and daily vitamin B6 supplementation, were investigated. Race, gender and age differences in PLP were then investigated;​ 95% reference intervals were calculated that reflected these differences.

Results:​ Inflammation and chronic kidney disease were associated with lower PLP (p < .0001 and p = .0005 respectively), while low ALP and vitamin B6 supplementation were associated with higher PLP (both p < .0001). Individuals were excluded based on the presence of these factors;​ a reference interval population (n = 4463) was established. There were significant differences in PLP depending on race and gender (p < .0001) Increasing age was correlated with decreasing PLP (spearman's rho −0.204, p < .0001). Race- and gender-specific 95% reference intervals were calculated. In male patients, these were also calculated according to age groups:​ young and older adults (ages 20–49 years and ≥50 years respectively).

Conclusions:​ In order to identify adult hypophosphatasia based on elevated PLP, considerations must be made depending on the race, gender and age of the individual. Factors associated with significant differences in PLP must also be considered when assessing biochemical measurements.