Previous studies have shown that TBS can assess the bone quality of secondary osteoporosis and predict fracture risk independently of BMD and FRAX scores. When combined with any method, it can increase the accuracy of fracture prediction. However, there is a lack of research on TBS about PHPT in China. Therefore, the present study studied the role of TBS in assessing bone quality in PHPT patients.
In the present study, it was found that sixty-two per cent of PHPT patients exhibited bone microstructural deterioration. Moreover, thirty-nine per cent of patients were diagnosed with osteoporosis by DXA. Similarly, seventy per cent of hypercortisolism patients had bone microstructural deterioration, and only twenty-two per cent were diagnosed with osteoporosis by DXA. A retrospective study involving 72 PHPT patients by Manuel et al. obtained similar findings. Accordingly, 73.6% of PHPT patients had a decrease in TBS, and 37.5% of patients were diagnosed with osteoporosis based on BMD. Silva and colleagues and Vinolas et al. also obtained similar findings in PHPT patients and hypercortisolism patients, respectively. In combination with the results of the current study, there is sufficient evidence to claim that a difference between TBS and BMD exists when assessing patients’ bone health. Moreover, studies have suggested that the combined application of TBS and BMD increases the sensitivity of bone strength assessment in patients with secondary osteoporosis. So, the aim is to draw conclusions which index has higher sensitivity or specificity for the occurrence of fragility fractures of clinical concern.
In this study, it was found that the BMD of the lumbar spine, femoral neck, and total hip of PHPT patients were significantly lower than that of the patients in the hypercortisolism group. However, there was no statistical difference in the TBS and fracture rate between the two groups. Hypercortisolism patients have higher BMD than PHPT patients. However, the incidence of fractures was similar in the two groups, suggesting that hypercortisolism patients are more prone to fractures and BMD is less sensitive to predict fracture occurrence in these patients.
Furthermore, a logistics regression analysis was conducted on the occurrence of osteoporosis and it was found that TBS is a predictive factor for osteoporosis in PHPT patients. After adjusting for confounding factors such as age, gender, and BMI, TBS still had a similar predictive effect. On the contrary, for patients with hypercortisolism, TBS is meaningless, even after adjusting for confounding factors. The reason could be that hypercortisolism patients may have a longer medical history than those in the PHPT group. Reportedly, TBS is an early predictor in hypercortisolism patients. Considering that some of the participating patients had hypercortisolism with a longer medical history, it could be considered as the reason why TBS is a non-osteoporotic predictor for hypercortisolism patients.
The correlation between TBS and BMD is not consistent in different populations[21, 22, 23]. The difference could be related to the difference of the race. The findings indicate TBS was positively correlated with lumbar, femoral neck, and total hip BMD at moderate strength. Moreover, it was also observed that the correlation could lead to a reduction in the capacity of TBS to predict fractures. Therefore, it cannot be concluded that TBS is completely independent of bone density, and there is not sufficient evidence to consider supporting the replacement of BMD with TBS. On the contrary, the combined use of these two measurement methods may be more meaningful for the assessment of bone mass with underestimated bone density. Similarly, the present analysis also found that TBS was negatively correlated with AKP and serum osteocalcin levels. Increased AKP and bone turnover indices suggest that the high bone turnover is related to bone microstructure damage.
BMD is a crucial indicator in the assessment of future fracture risk, and FRAX scores are used for people with reduced bone mass. A study examining the fracture risk of patients with hypercortisolism and TBS involved 182 patients with Cushing’s syndrome and found that TBS was not associated with fractures, and the 24-hour urine cortisol level was a predictor of fracture. Similar results were obtained from the present study. Among patients with hypercortisolism, there was no statistically significant difference in TBS between the fracture group and the non-fracture group. Two European studies have shown that TBS is associated with vertebral fractures commonly found in PHPT[5, 6]. When compared with PHPT patients in the non-fracture group, there was no statistical difference in TBS in the fracture group of the present study, which conform with the results of Liu MH, et al.. Analysis of the fracture sites of the PHPT patients in this study showed that only 2 patients had vertebral fractures, and whether the prediction of fracture by TBS is related to the fracture site is still inconclusive. Therefore, it is unknown whether the different fracture sites will affect the results of the present analysis.
In order to explore the sensitivity of FRAX and TBS in predicting future fractures, the current analysis employed a ROC curve on the sensitivity of FRAX, TBS, and TBS adjusted FRAX for fracture prediction. Accordingly, it was found that the sensitivity of FRAX for predicting fracture risk in patients with PHPT and hypercortisolism in the next ten years is higher than that of TBS alone, and the sensitivity of TBS and FRAX combined prediction is not significantly different from FRAX alone. The result indicates that TBS is not as effective as FRAX in assessing fracture risk in patients with PHPT and hypercortisolism.
Several limitations of this study should be acknowledged. Firstly, the sample size is relatively small, which might restrict the wide applicability of the findings. It may require further validation in a larger cohort. Nevertheless, the fracture sites of fracture patients are not typical enough, and more prospective studies of patients with vertebral fractures are needed in the future.
In summary, TBS and BMD have differences in evaluating bone quality. TBS appears to be associated with bone microarchitecture, and when combined with BMD, the combination increases the diagnostic accuracy of secondary osteoporosis, including primary hyperparathyroidism and hypercortisolism. Moreover, in patients with PHPT or hypercortisolism, FRAX is more sensitive to fracture prediction than TBS. Nevertheless, extensive longitudinal studies are required to recommend this tool in clinical practice guidelines for this population.