18F-Sodium Fluoride PET as a Diagnostic Modality for Metabolic, Autoimmune, and Osteogenic Bone Disorders: Cellular Mechanisms and Clinical Applications

Abstract

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.

Keywords: 18F-NaF; 18F-sodium fluoride; PET; Paget’s disease; ankylosing spondylitis; hyperparathyroidism; osteoporosis; osteosarcoma; rheumatoid arthritis.

Figure 1

Schematic graph and representation of changes in bone disease with aging in osteoporosis. Molecular changes that favor bone resorption over bone formation such as decreased estrogen, increased RANKL/OPG ratio, and increased inflammatory cytokines such as TNF-α, IL-1, and IL-6 precede structural changes in the bone. Structural changes associated with osteoporotic bone include decreased cortical thickness, increased trabecular spacing, and decreased bone mass density.

Figure 2

Cellular mechanisms that influence observed ¹⁸F-NaF activity. ¹⁸F-NaF-PET depicts bone turnover by detecting direct alterations in osteoblasts, impaired osteoblast–osteoclast coupling, and abnormal bone perfusion.

Figure 3

Aging and ¹⁸F-NaF uptake in the bone. Maximum intensity projection ¹⁸F-NaF-PET images of two healthy subjects, (A) a 26-year-old female and (B) a 62-year-old female. The difference in ¹⁸F-NaF uptake is visible particularly in the spine, pelvis, and proximal femur, which can be quantified in longitudinal studies to monitor disease progression and therapeutic response.