Low Prevalence of Exploratory Biochemical Patterns Compatible with Osteomalacia in a Large Cohort of Participants...

The threshold for vitamin D deficiency is mainly based on osteomalacia prevention. Osteomalacia is diagnosed by bone biopsy, but may potentially also be identified biochemically. Our objective was to examine the prevalence of exploratory biochemical patterns compatible with osteomalacia in a population with low vitamin D status, as well as the effect of vitamin D supplementation on the biochemical parameters. The study was cross-sectional followed by a randomized controlled trial (trial registration number: NCT02750293). The participants were recruited from the population-based Tromsø study. Plasma parathyroid hormone, serum calcium, alkaline phosphatase and bone-specific alkaline phosphatase were measured. 423 participants were included in the cross-sectional part and 382 completed the randomized controlled trial (194 given vitamin D (100,000 IU as a loading dose followed by 20,000 IU per week for four months) and 188 given placebo). The mean serum 25-hydroxyvitamin D level in the cohort was 34 nmol/L. None of the participants had a combination of high (above reference range) serum parathyroid hormone, high alkaline phosphatase, and low (below reference range) serum calcium. With the most permissive exploratory biochemical pattern the prevalence was 8.3%. In the intervention study vitamin D significantly reduced plasma parathyroid hormone and alkaline phosphatase and increased serum calcium as compared to placebo. In conclusion, the prevalence of the explored biochemical patterns compatible with ostemalacia was low and strongly dependent on the analytical thresholds applied. In the absence of validation against bone histomorphometry, these findings cannot determine the prevalence of osteomalacia or establish an appropriate serum 25OHD threshold.