In a healthy body, homeostatic actions of osteoclasts and osteoblasts maintain the integrity of the skeletal system. When cellular activities of osteoclasts and osteoblasts become abnormal, pathological bone conditions, such as osteoporosis, can occur. Traditional imaging modalities, such as radiographs, are insensitive to the early cellular changes that precede gross pathological findings, often leading to delayed disease diagnoses and suboptimal therapeutic strategies. ¹⁸F-sodium fluoride (¹⁸F-NaF)-positron emission tomography (PET) is an emerging imaging modality with the potential for early diagnosis and monitoring of bone diseases through the detection of subtle metabolic changes. Specifically, the dissociated ¹⁸F^- is incorporated into hydroxyapatite, and its uptake reflects osteoblastic activity and bone perfusion, allowing for the quantification of bone turnover. While ¹⁸F-NaF-PET has traditionally been used to detect metastatic bone disease, recent literature corroborates the use of ¹⁸F-NaF-PET in benign osseous conditions as well. In this review, we discuss the cellular mechanisms of ¹⁸F-NaF-PET and examine recent findings on its clinical application in diverse metabolic, autoimmune, and osteogenic bone disorders.

Positron emission tomography (PET) imaging with ¹⁸F-fluorodeoxyglucose (FDG) represents a method of detecting and characterizing arterial wall inflammation, with potential applications in the early assessment of vascular disorders such as atherosclerosis. By portraying early-stage molecular changes, FDG-PET findings have previously been shown to correlate with atherosclerosis progression. In addition, recent studies have suggested that microcalcification revealed by ¹⁸F-sodium fluoride (NaF) may be more sensitive at detecting atherogenic changes compared to FDG-PET. In this review, we summarize the roles of FDG and NaF in the assessment of atherosclerosis and discuss the role of global assessment in quantification of the vascular disease burden. Furthermore, we will review the emerging applications of FDG-PET in various vascular disorders, including pulmonary embolism, as well as inflammatory and infectious vascular diseases.

Osteoclasts are the sole bone-resorbing cells that play an essential role in homeostatic bone remodeling and pathogenic bone destruction such as inflammatory arthritis. Pharmacologically targeting osteoclasts has been a promising approach to alleviating bone disease, but there remains room for improvement in mitigating drug side effects and enhancing cell specificity. Recently, we demonstrated the crucial role of MYC and its downstream effectors in driving osteoclast differentiation. Despite these advances, upstream regulators of MYC have not been well defined. In this study, we identify nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor known to regulate the expression of phase II antioxidant enzymes, as a novel upstream regulator of MYC. NRF2 negatively regulates receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis through the ERK and p38 signaling-mediated suppression of MYC transcription. Furthermore, the ablation of MYC in osteoclasts reverses the enhanced osteoclast differentiation and activity in NRF2 deficiency in vivo and in vitro in addition to protecting NRF2-deficient mice from pathological bone loss in a murine model of inflammatory arthritis. Our findings indicate that this novel NRF2-MYC axis could be instrumental for the fine-tuning of osteoclast formation and provides additional ways in which osteoclasts could be therapeutically targeted to prevent pathological bone erosion.

A quantification technique for costal cartilage calcification using ¹⁸F-sodium fluoride–positron emission tomography/computed tomography (¹⁸F-NaF-PET/CT) has yet to be established, and the effects of aging and other demographic variables on costal cartilage calcification remain understudied. This study aims to introduce a quantification methodology for assessing costal cartilage calcification using ¹⁸F-NaF-PET/CT, assess age-related changes in its ¹⁸F-NaF uptake in females and males, and examine the relationship between its ¹⁸F-NaF uptake and CT attenuation as well as ¹⁸F-NaF uptake and coronary artery calcification. In this retrospective study, we analyzed subjects from the Cardiovascular Molecular Calcification Assessed by ¹⁸F-NaF PET/CT (CAMONA) clinical trial. This study evaluated 130 subjects (mean age 48.7 ± 14.5 years; n = 67 females). We manually generated regions of interest overlying the costal cartilages from ribs 8 to 10 on the left side, carefully avoiding osseous uptake from adjacent ribs and sternum, to measure cartilaginous ¹⁸F-NaF uptake. Non-parametric statistical analyses (Spearman correlations, Mann–Whitney U tests, Kruskal–Wallis tests) and receiver operating characteristic analysis were performed to evaluate sex-specific age-related changes in uptake, correlations between imaging parameters, and associations with coronary artery calcium (CAC) score. In females, the mean ¹⁸F-NaF uptake (as assessed by average SUV_mean) was 0.69 ± 0.38 while the corresponding mean Hounsfield Unit (HU) was 108.0 ± 40.0. In males, the mean ¹⁸F-NaF uptake (as assessed by average SUV_mean) was 0.63 ± 0.22, and the mean HU was 104.0 ± 24.0. There was a significant correlation between ¹⁸F-NaF uptake and age in both females (p = 0.003, r = 0.36) and males (p < 0.0001, r = 0.63). The correlation was significantly stronger in males than females (Fisher’s z-test, p = 0.040). There was a significant correlation between CAC score and costal cartilage SUV_mean in both females (r = 0.26, p = 0.036) and males (r = 0.51, p < 0.0001). This study introduces a quantification technique to assess costal cartilage calcification using ¹⁸F-NaF-PET/CT and demonstrates that the calcification increases with age, more strongly in males than in females, and ¹⁸F-NaF uptake is correlated with CAC score. This technique can be applied to other cartilages of interest, in both physiological and pathological conditions, to assess the effects of aging and various demographic variables on cartilage calcification.