Role of NaF-PET/CT in detecting age-associated changes in the trabecular bone metabolism

Introduction: Osteoporosis is a metabolic bone disease characterized by the loss of bone mineral density and increased susceptibility to fractures, ultimately decreasing the quality of life. Risk factors for developing osteoporosis include age and sex, which influence molecular pathways and alterations that lead to bone metabolism imbalance and increased bone degradation over formation. Using molecular imaging modalities such as 18F-sodium fluoride (NaF)- positron emission tomography (PET) to detect such pathological cellular changes preceding structural deterioration could be critical for the early diagnosis and monitoring of osteoporosis. In this study, we examine the effect of aging and sex on the bone metabolism of lumbar spines and femoral neck using NaF-PET and assess the correlation between the Hounsfield unit and NaF uptake.

Methods: The analysis was performed retrospectively with NaF-PET/CT scans of 88 healthy subjects (43 females and 45 males, mean age 44.6 years, range 21-75) from the Cardiovascular Molecular Calcification Assessed by 18FNaF PET/CT (CAMONA) study. The regions of interest were defined as the trabecular bones from the L1 to the L4 vertebrae and the femoral necks at both left and right sides (OsiriX software, Pixmeo, Bernex, Switzerland). The global mean standardized uptake value (NaF SUVmean) was calculated, and Hounsfield Unit (HU) measurements were derived from the CT scans of the same ROI sections. All the statistical tests and graphs were performed and plotted using GraphPad Prism 8 (San Diego, CA, USA).

Results: For the L1-L4 vertebrae, there was a negative correlation between NaF SUVmean and age for both females (p < 0.0001, r = -0.59) and males (p = 0.03, r = -0.32). A strong decreasing correlation between HU and aging was found as well for both sexes (female: p < 0.0001, r = -0.70; males: p < 0.0001, r = -0.58). Furthermore, NaF SUVmean and HU positively correlated for both females (p < 0.0001, r =0.75) and males (p = 0.006, r = 0.41). For the femoral neck, a negative correlation between NaF SUVmean and age was found in males only, but for both the left (p = 0.01, r = -0.38) and right (p = 0.006, r = -0.40) sides. However, a strong negative correlation between HU and age was found in both females (left: p < 0.0001, r = -0.76; right: p < 0.0001, r = -0.82) and males (left: p <0.0001, r = -0.66; right: p < 0.0001, r = -0.69). Similar to the results from L1-L4, significant positive correlations between NaF SUVmean and HU were found in both sexes on both sides.

Conclusions: In the trabecular bones of L1-L4 vertebrae, HU and NaF uptake significantly decreased with age in both sexes. For the femoral neck, however, NaF uptake decreased with age in males only. Lack of such negative correlation in females could be indicative of the differential effect of menopause, estrogen deficiency, or earlier onset of osteoporosis on the femoral neck bone metabolism. Meanwhile, all NaF SUVmean values positively correlated with HU, emphasizing the close association between molecular bone turnover and structural changes in bone density. Overall, our results suggest that NaF-PET/CT is a promising imaging modality for measuring molecular bone alterations that occur with aging in the trabecular bone, regardless of sex. Further studies elaborating the use of NaF-PET/CT to measure NaF uptake in the trabecular bone in pathological or treatment conditions could be critical for defining the next steps for its clinical implementation.