Effect of zoledronic acid on vertebral marrow adiposity in postmenopausal osteoporosis assessed by MR spectroscopy
Zoledronic acid (ZOL) has a suppressive effect on marrow adiposity in ovariectomized rats. Currently, however, data on the effect of ZOL on marrow fat in humans are unavailable. The purpose of this work was to determine the in vivo effect of ZOL on bone remodeling and marrow adipogenesis in postmenopausal osteoporosis. In a 12-month, randomized, double-blind, placebo-controlled trial, we studied 100 postmenopausal women with osteoporosis who were randomly given either a single dose of intravenous infusion of ZOL (5 mg) or placebo. All subjects received adequate dietary calcium and vitamin D3. Main outcome measures included bone mineral density by dual-energy X-ray absorptiometry, vertebral marrow fat content by proton MR spectroscopy, serum markers of bone turnover by biochemical analysis. Ninety percent of the participants completed the 12-month follow-up. With respect to baselines, marrow fat content reduced by 8.1 % in the ZOL-treated women and increased by 3.0 % in the controls (all p < 0.05). In addition, there were significant increases of bone mineral density by 2.8, 2.0, and 1.7 % in the lumbar spine, femoral neck, and total hip, respectively, in the ZOL group compared with the placebo group. Serum levels of bone resorption marker CTX and bone formation marker BALP decreased by 33 and 18 % in postmenopausal women receiving ZOL. In postmenopausal women with osteoporosis, a single dose of ZOL therapy significantly reduced marrow adiposity. MR spectroscopy of vertebral marrow fat may therefore serve as a novel tool for BMD-independent efficacy assessment.