Dissociation Between Global Markers of Bone Formation and Direct Measurement of Spinal Bone Formation in Osteoporosis

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Abstract
Regional bone metabolism measured using 18F-fluoride PET was assessed in 72 postmenopausal women classified as normal, osteopenic, or osteoporotic. Lower values of regional bone formation activity at the lumbar spine were seen in osteoporotic women, whereas global markers of bone formation were significantly increased. Evaluations of global bone remodeling have revealed that increased bone turnover is a feature of patients with osteoporosis. The noninvasive functional imaging technique of 18F-fluoride positron emission tomography (PET) allows the direct quantitative assessment of bone metabolism at specific sites in the skeleton, including the clinically important site of the lumbar spine. The aim of this study was to compare regional skeletal kinetics in 72 postmenopausal women (mean age, 61 years) classified as normal, osteopenic, or osteoporotic according to their BMD T score at the lumbar spine. Each woman had a dynamic PET scan of the lumbar spine after injection of 90 MBq 18F-fluoride ion and measurements of biochemical markers of bone formation and resorption. The arterial plasma input function was derived using aorta arterial activity from the PET image. Time-activity curves were obtained by placing regions of interest over the lumbar vertebrae. A three-compartmental model was used to calculate bone blood flow (K1) and the net plasma clearance of tracer to bone mineral (Ki), reflecting regional osteoblastic activity (ml/minutes/ml). Rate constants k2, k3, and k4, which describe transport between plasma, the extracellular fluid (ECF) compartment, and the bone mineral compartment, were also measured. The net uptake of fluoride to the bone mineral compartment (Ki) was significantly lower in the osteoporotic group compared with both the osteopenic and normal groups, with a mean difference of 0.005 ml/minutes/ml (16.7%). The fraction of the tracer in the extravascular tissue space that underwent specific binding to bone mineral (k3/k2 + k3) was also significantly reduced in the women classified as osteoporotic. In contrast, levels of bone-specific alkaline phosphatase (BSALP) were significantly higher in the osteoporotic group compared with the normal and osteopenic groups by 35% and 27%, respectively. A significant negative correlation (r = -0.41) was observed between levels of BSALP and the fraction of the tracer that underwent specific binding to bone mineral. Lower values of Ki, a measurement of regional bone formation activity, were seen in women classified as osteoporotic, whereas levels of BSALP, a measure of global bone formation, were significantly increased. These findings are suggestive of increased global skeletal bone turnover in women with postmenopausal osteoporosis but with relatively reduced regional bone formation at the predominantly trabecular site of the lumbar spine.

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