Denosumab reduces lesional fluoride skeletal burden on Na[F-18]F PET-CT in patients with fibrous dysplasia/McCune-Albright syndrome

Abstract

Context: The correlation between fibrous dysplasia/McCune-Albright syndrome (FD/MAS) skeletal disease burden on Na[F-18]F positron emission tomography-computed tomography (PET-CT) and serum bone turnover markers (BTMs) was recently described. The effect of treatment on lesional fluoride burden in FD/MAS is unknown.Objective: To investigate treatment response measurements in patients with FD/MAS who underwent Na[F-18]F-PET-CT and treatment with antiresorptives.Methods: Observational case series at an academic center of expertise for rare bone diseases. Fifteen consecutive patients were observed with FD/MAS with baseline and follow-up Na[F-18]F-PET-CT parameters of healthy bone and FD lesions, BTMs, and pain scores at start of denosumab (n=8) treatment and non-denosumab patients (n=7). On Na[F-18]F-PET-CT the volumetric measures of FD burden (fluoride tumor volume [FTV]) and "fraction affected skeleton" (FAS) represented the portion of the skeleton affected. This was correlated with BTMs and pain.Results: Disease activity decreased significantly, with FTV 361 cm(3) to 97 cm(3) (P=.018) in denosumab-treated patients, but not in non-denosumab patients (P=.249). Serum P1NP and alkaline phosphatase (ALP) decreased significantly: 82 ng/mL vs 55 ng/mL (P=.023) and 119 IU/L vs 84 IU/L (P=.020), respectively. In denosumab-treated patients pain scores improved leading to pain medication reduction. This correlated with lesional uptake, but healthy bone activity did not change. BTMs and FTV correlated positively (P1NP r=0.730, P<.001; and ALP r=0.406, P=.006), as did change in BTMs and FTV: P1NP (P=0.032) and ALP (P=0.024). FAS strongly correlated with treatment-induced decrease in ALP (P=.027) and P1NP (P=.009).Conclusion: Na[F-18]F-PET-CT captured treatment-induced lesional changes which correlated with BTMs and pain reduction. Therefore Na[F-18]F-PET-CT can be used as an objective local parameter of response to denosumab treatment in FD/MAS.