Three-Month Randomized Clinical Trial of Nasal Calcitonin in Adults with X-linked Hypophosphatemia

Abstract

Previous work has demonstrated that a single subcutaneous dose of salmon calcitonin leads to a transient decline in circulating levels of FGF23 in patients with X-linked hypophosphatemia (XLH). Since the calcitonin receptor is expressed on osteocytes, this raises the possibility that interdicting signals through that receptor could modulate circulating levels of FGF23 in XLH. In the present study, 21 subjects with XLH were randomly assigned to receive either placebo nasal spray or 400 IU of nasal salmon calcitonin daily for three months. On the first and last day of the study, serial measurements of FGF23, 1,25-dihydroxyvitamin D, and TmP/GFR were made over 27 h. At the beginning of Visit 2 (the first day of month 2) and the beginning of Visit 3 (the first day of month 3), single, first-morning, fasting measurements of these same parameters were made before the next administered dose of study drug. Following the initial or final dose of study drug, there were no differences in area under the curve, based on treatment assignment, for the three principal outcome variables. Similarly, there were no differences in the fasting measures taken at the beginning of Visit 2 or Visit 3 compared to the fasting values on either day 2 of Visit 1 or the fasting values on day 2 of Visit 4. There were also no significant changes over time in serum phosphorus, serum calcium, circulating levels of PTH, CTx, or P1NP. The reasons why nasal salmon calcitonin did not recapitulate the findings with subcutaneously administered drug may relate to the kinetics of drug delivery, the bioavailability of drug or peak drug dose achieved. It remains possible, however, that other means of altering calcitonin receptor signaling may still provide an opportunity for regulating FGF23 production.

New Developments in the Treatment of X-Linked Hypophosphataemia: Implications for Clinical Management

“…No significant change in FGF23 was noted in controls [48]. A similar biochemical effect was not demonstrated in a randomised, controlled, 3-month trial of 400 IU of nasal calcitonin in adult patients with XLH [49].…”

FGF23, Hypophosphatemia, and Emerging Treatments

“…However, calcitonin also decreased FGF23 in patients with XLH after a single injection . A three‐month trial of calcitonin nasal spray did not improve serum FGF23 or phosphate, lowering enthusiasm for this as an alternate therapy …”

“…(80) A three-month trial of calcitonin nasal spray did not improve serum FGF23 or phosphate, lowering enthusiasm for this as an alternate therapy. (83) Additional potential strategies to manage FGF23 excess include trying to decrease FGF23 production or blocking FGF23 activity at its receptor. Most of these strategies have only been studied in mouse models.…”

Pharmacological management of X‐linked hypophosphataemia

“…To make the calcitonin story more confusing, case reports indicate calcitonin increases urinary phosphorus excretion in hyperphosphatemic tumoural calcinosis (a condition of FGF23 deficiency rather than excess) , which would be opposite of the goal of XLH management. A 3‐month‐long blinded randomized controlled clinical trial of monotherapy with nasal calcitonin 400 units daily for XLH failed to demonstrate improvements in serum phosphorus, TmP/GFR or FGF23 . Given the current lack of data indicating benefit, calcitonin should not be used for XLH.…”