Effects of Alendronate on Bone Metabolism in Glucocorticoid-Induced Osteoporosis Measured by¹⁸F-Fluoride PET: A Prospective Study

Abstract

Osteoporosis represents a significant side effect of glucocorticoid therapy, and alendronate has been reported to prevent this glucocorticoid-induced osteoporosis. Functional imaging with 18 F-fluoride PET allows quantitative analysis of bone metabolism in specific skeletal regions. However, only a few studies have quantitatively determined bone turnover and metabolism in glucocorticoid-induced osteoporosis by radiologic imaging techniques including PET. The aim of this study was to examine changes in regional bone remodeling and turnover as measured by 18 F-fluoride PET, the relationship between these measured changes and conventional bone metabolism parameters, and the effect of alendronate treatment. Methods: The study group consisted of 24 postmenopausal women (mean age, 59.7 y) who had various diseases, excluding rheumatoid arthritis, and had been treated with 10 mg or more of oral glucocorticoids (prednisolone equivalent) per day for more than 6 mo. Treatment with 5 mg of alendronate per day began at the time of study entry and continued for 12 mo. 18 F-fluoride PET was performed at baseline, 3 mo, and 12 mo to determine localized bone turnover, and the results were compared with other bone metabolism parameters. Results: Lumbar spine standardized uptake values (SUVs) were significantly lower (P , 0.05) in the osteoporotic group (T-score # 22.5) than in the group that was healthy or osteopenic (T-score . 22.5). Patients treated with alendronate for 12 mo exhibited significant decreases in serum bone-specific alkaline phosphate (P , 0.05), urinary N-telopeptide for type I collagen (P , 0.01), lumbar spine SUV (P , 0.01), and femoral neck SUV (P , 0.01) in association with a gradual increase in bone mineral density (BMD) of the lumbar spine relative to the baseline value (P , 0.05). Although there was a significant correlation between BMD and SUV in the lumbar spine at baseline (P , 0.05), there was no correlation between the 2 variables at 12 mo of treatment with alendronate. Conclusion: Alendronate treatment resulted in significant decreases in bone metabolism and turnover in the lumbar spine. It also led to an increase in BMD of the lumbar spine in patients with glucocorticoid-induced osteoporosis. Our findings suggest that antiresorptive therapy has a direct bone-metabolism effect on skeletal kinetics in glucocorticoid-induced osteoporosis at the clinically important site of the lumbar spine.

Differential effects of teriparatide on regional bone formation using 18F-fluoride positron emission tomography

“…In the only other study we are aware of that used 18 F À PET to examine the regional effects of an osteoporosis therapy, Uchida et al reported a 14% decrease in SUVs at the spine and a 24% decrease at the femoral neck in 24 postmenopausal women treated with alendronate for 12 months for glucocorticoid-induced osteoporosis. (27) In the present study, although there was a highly significant change in 18 F À plasma clearance at the lumbar spine, SUVs at this site were almost unchanged. The 3% increase in SUVs after 6 months of treatment with teriparatide was explained by the 24% increase in spine plasma clearance being almost canceled by a 20% decrease in 18 F À plasma concentration.…”

“…An example is the gamma camera method of measuring the skeletal uptake of 99m Tc-methylene diphosphonate ( 99m Tc-MDP) described by Brenner et al (26) For 18 F À PET studies, an equivalent measurement of bone uptake is provided by standardized uptake values (SUVs), which normalize the concentration in the bone region of interest for injected activity and body weight (SUV ¼ mean kBq/ mL x body weight [kg]/injected activity [MBq]). (27) The only previous studies that used 18 F À PET to examine the regional effects of an osteoporosis treatment were a report by Frost et al (21) on the effect of risedronate on bone turnover at the lumbar spine and a study by Uchida et al (27) on the effects of alendronate on bone metabolism at the spine and femoral neck in glucocorticoid-induced osteoporosis. To date, no studies of an anabolic agent have been reported.…”

Quantitative imaging methods in osteoporosis

“…Zooming in further, in 18 F-Fluoride PET scanning it is believed that PET intensity reflects the activities of osteoblasts and osteoclasts, and at least in animal experiments, microdamage can be detected (147). Regional bone perfusion and turnover studies with bone turnover markers as a reference have been performed comparing different skeletal sites in treatment-naïve and patients with osteoporosis on treatment with various antiosteoporotic agents (148)(149)(150)(151)(152)(153)(154). The long term precision reflected by the coefficients of variation (12.2-26.6%) and intraclass correlation (0.44-0.85) for 18 F-Fluoride PET parameters has been reported to be equivalent to that observed for biochemical bone turnover markers (155).…”

The Precision and Sensitivity of 18F-Fluoride PET for Measuring Regional Bone Metabolism: A Comparison of Quantification Methods

“…Quant itative radionuclide imaging of the skeleton using 18 F-fluoride PET ( 18 F 2 PET) (1,2) is a valuable tool for research studies examining the pathophysiology of metabolic bone diseases and the response of patients to treatment (3)(4)(5)(6)(7). Treatments for osteoporosis and Paget disease generally have a profound effect on bone remodeling (8)(9)(10)(11), and studies of bone metabolism have an important role in the evaluation of the effect of treatment on bone tissue (12).…”