4. Discussion
fractures, hypophosphatemia
HYPOPHOSPHATEMIA, STILL, MINERALIZATION
This study revealed significant differences in serum phosphate levels as well as in serum ferritin levels two and four weeks after intravenous iron substitution therapy when comparing ferric carboxymaltose and iron sucrose treatments. Patients treated with ferric carboxymaltose presented with transient hypophosphatemia as rapidly as two weeks after drug administration, which normalized 12 weeks after intravenous iron substitution therapy. However, P1NP remained upregulated at the final follow-up after treatment with ferric carboxymaltose.In healthy adults, the serum phosphate level ranges between 0.8 mmol/L and 1.45 mmol/L, with changes across the day in relation to dietary phosphate consumption [Under intravenous iron substitution therapy with ferric carboxymaltose, patients presented with hypophosphatemia two weeks after drug administration. This was not observed under iron substitution with iron sucrose. Four weeks after iron substitution therapy, serum phosphate levels were within the therapeutic threshold in both study groups; however, significant differences were still observed when comparing ferric carboxymaltose and iron sucrose. These observations are consistent with those from the literature. A new systematic review by Glaspy et al. showed a higher incidence of hypophosphatemia after treatment with ferric carboxymaltose (up to 92%) compared to after treatment with iron sucrose (up to 40%) [Ferritin represents an indirect reflection of the total body iron stores [In this study, serum ferritin levels were markedly above the reference value two weeks after iron substitution therapy with ferric carboxymaltose. Four weeks after drug administration, significant differences were still observed between both study groups. However, median ferritin levels were within the therapeutic threshold in both study groups. Indeed, elevated ferritin levels after iron substitution therapy with ferric carboxymaltose were only observed for two weeks. These observations must be treated with caution since the patient’s ferritin levels before the baseline measurements were unknown.P1NP and CTX are both so-called bone turnover markers (BTM), which are generated during bone remodeling. Using serum P1NP, bone formation can be monitored, whereas CTX is a BTM for the bone resorption process [In this study, no significant differences in P1NP and CTX were observed between both study groups at any timepoint. The reference value for P1NP is between 15–59 µg/L, and for CTX it is <57 ng/mL. However, patients treated with iron sucrose had increased serum levels, being 68.71 µg/L for P1NP and 0.60 ng/mL for CTX two weeks after iron substitution therapy. Since both values for bone formation and for bone resorption were elevated, this can theoretically imply balanced bone remodeling. Still, as already stated by Nagy et al., the increased bone remodeling rate can result in a decrease in bone quality [Previous studies demonstrated that intravenous administration of iron carboxymaltose causes hypophosphatemia in up to 75% of cases [The potential impact of phosphate on bone fractures is still under investigation [Vitamin D is crucial for physiological musculoskeletal function as it ensures the absorption of calcium, promotes osteoid tissue mineralization in bones, and preserves muscle function [Interestingly, in our study, serum 25(OH)D levels remained within the therapeutic threshold within both study groups throughout the whole study period. However, 25(OH)D values continually declined in both study groups until the last follow-up.There are several limitations to this study. Due to the small sample sizes, the results must be interpreted with caution. However, even with this small sample size, such highly significant differences in serum phosphate levels could be detected by comparing both drugs. Even if a longitudinal assessment of serum markers, including baseline values, was performed, no information was available regarding the previous serum values of all patients, previous iron substitution therapies, and clinical symptoms of hypophosphatemia or elevated ferritin levels. Furthermore, no data on FGF23 levels were available. This may be of great interest for future studies, since FGF23 levels are expected to drastically change after intravenous iron substitution therapy, along with the resulting changes in serum phosphate levels and transient hypophosphatemia.