We conducted a study aimed at estimating the feasibility of utilizing 18F-NaF PET/CT for evaluating bone metabolism and BMD for DTC patients with long-term TSH suppression therapy. We hypothesis that quantitative parameters of 18F-NaF PET/CT could serve as the additional valuable indicators of bone metabolic activity and indirectly reflect the BMD status in these patients. We also investigated the incidence of osteopenia or osteoporosis in different patient group, and the difference of 18F-NaF uptake in these groups. Our data suggested that postmenopausal female rank the highest incidence rate of osteopenia or osteoporosis, accomplished by decreased 18F-NaF uptake. Furthermore, patients with higher duration of TSH suppression depicted lower BMD and 18F-NaF uptake than that of short duration of TSH suppression patients.
Osteoporosis is the most common metabolic bone disorder, with an estimated prevalence of 13.1–27.1% of women and 3.3–5.7% of men over the age of 50 affected[10]. In line with this study, our cohort illustrated positive correlation between age and incidence of osteopenia or osteoporosis, as well as a similar prevalence of osteoporosis in postmenopausal female patients with TSH suppression therapy (29%), which is higher than that of postmenopausal female and male patients. Interestingly, the prevalence of osteopenia or osteoporosis was higher in patient with longer TSH suppression therapy than that of shorter patients (32% vs 29%, 13% vs 10%, respectively). This finding is consistent with that of Park who indicated TSH suppression after surgery for DTC has adverse effects on BMD from 1 year postoperatively[11], especially in women ≥ 50 years of age. Previous study also found that the decreased baseline BMD level is the key determinant of whether DTC patients with TSH suppression are progressively shortened from osteopenia to osteoporosis. In general, therefore, shorter TSH suppression patients should pay more attention to the decreased BMD level, because these patients are easier to transit from osteopenia to osteoporosis, resulting in a series of adverse events. Apparently, the proportion of these patients is not small in this cohort (29%).
18F-NaF is a positron-emitting radiopharmaceutical used for skeletal imaging. It provides diagnostic information superior to that of 99mTc-MDP bone scans due to higher sensitivity and specificity in a wide variety of osseous metastasis[8, 12]. Nonetheless, given its ability to evaluate bone turnover at the molecular level,18F-NaF-PET/CT has the potential to provide an alternative superior modality to imaging of metabolic bone disorders to track changes with higher sensitivity[13], and previous studies have shown the feasibility in evaluation of bone metabolism and formation[14, 15]. Whether there is difference in 18F-NaF uptake between different BMD levels, and patients, as well as the 18F-NaF PET/CT can provide additional information for assessing BMD in DTC patient with TSH suppression have not been reported. Firstly, our study indicated that there is significant difference of lumbar vertebral 18F-NaF uptake between different BMD groups, and lumbar vertebral 18F-NaF uptake was decreased as the BMD decreased[14, 16, 17]. In accordance with the present results, previous studies have demonstrated that quantitative evaluation of 99mTc‑MDP in the lumbar spine with SPECT/CT was significantly different among subjects with different BMD, and the SUV was positively correlated with BMD [16]. Although quantitative SPECT can serve as the similar role in evaluation of BMD, the penetration of rate of such equipment is relatively low, as well as traditional SPECT have conventionally been analyzed in a nonquantitative manner that were interpreted using relative intensity values instead of absolute values of tracer concentration. Thus, our study alluded 18F-NaF PET/CT is an applicable tool for clinical quantification of bone metabolism in osteoporosis patients[18]. In addition, our study also demonstrated that 18F-NaF uptake of lumbar vertebra was diminished in postmenopausal female and DTC patient with longer TSH suppression than that of other groups that supports evidence from BMD of DXA[16, 19–21].
Secondly, our study revealed an intriguing finding regarding the comparison of 18F-NaF uptake in the femoral neck. Interestingly, we observed no significant differences in 18F-NaF uptake among subjects with varying BMD and genders (P > 0.05). Nevertheless, the value of 18F-NaF uptake is still reduced in osteoporosis and postmenopausal female compared with other groups. Another result of our study indicates that 18F-NaF and mean bone density in the lumbar spine decreased significantly with age (All P < 0.05), it is consistent with the description of previous findings[22–24]. But our study did not analyze the rate of loss of bone density in different sites, previous another study illustrated that BMD of the femoral neck has been shown to decrease more rapidly with age in comparison with other skeletal sites[25]. Thus, further studies are needed to investigate whether descent rate of 18F-NaF and BMD is different with age. Another interesting finding of our study was the 18F-NaF uptake of femoral neck increasing in DTC patients with longer TSH suppression duration than that of shorter patients (SUVmax, 2.90 ± 1.25 vs. 2.7 ± 1.12, P = 0.026). This manifestation of discrepancy in 18F-NaF uptake is possible that there are biological differences between skeletal sites. Bones within the lumbar spine consist predominantly of trabecular bone with a thin sheet of cortical bone surrounding them. By contrast, long bones, similar to those of the femur, are comprised predominantly of a thicker sheet of cortical bone and a thin inner layer of trabecular bone[26]. Cortical and trabecular bone differ in their material and mechanical and functional properties that also cause the difference of metabolism. However, the exact mechanism is not clear, which may be the direction of future research.
In order to expand the use of 18F-NaF PET/CT for distinguishing normal BMD from abnormality, our study calculated the sensitivity, specificity and optimal cut-off value of each lumbar spine by ROC curves. The results showed that SUVmean of L2 lumbar vertebra in L1-L4 had the best predictive ability to differentiate the BMD level, and a combined model based on the SUVmean of L1-L4 can significantly improve the predictive ability for identification of DTC patients with abnormal BMD. Hence, 18F-NaF PET/CT may offer an added function for DTC patients with TSH suppression to monitor the BMD level, apart from detection of metastatic bone. Additionally, based on the bone metabolism from 18F-NaF PET/CT, further examinations or therapy should be considered for patients with low lumbar spine 18F-NaF uptake, in particular postmenopausal female.
We aware that our research may have several limitations. Firstly, because of the design of retrospective study, there are confounding factors inevitably were included in this study, such as the supplement of vitamin D, which has a determined effect on vertebral bone density and metabolism. Our study used the relatively large sample size than previous studies in order to diminish the bias. The second is SUV measurements from 18F-NaF PET/CT is not the best measure when comparing dynamic 18F-NaF PET whose kinetic modeling parameters can provided more accurate indexes[24]. However, we would like to expand the range of functions of 18F-NaF PET/CT when it is used to detect bone metastases in DTC patients with TSH suppression. For this reason, static SUV measurements are advantageous as they allow for shorter scan times, making it more comfortable for the patient and less technically demanding on clinical staff. As shown above, the static 18F-NaF uptake of different sites exhibited different patterns between DTC patients receiving different TSH suppression duration. We believe further studies are needed to explain this weird phenomenon by dynamic 18F-NaF PET/CT.