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Effect of zoledronic acid on vertebral marrow adiposity in postmenopausal osteoporosis assessed by MR spectroscopy

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Abstract

Objective

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.

Materials and methods

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.

Results

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.

Conclusions

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.

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References

  1. Recknor C. Zoledronic acid for prevention and treatment of osteoporosis. Expert Opin Pharmacother. 2011;12:807–15.

    Article  CAS  PubMed  Google Scholar 

  2. Black DM, Delmas PD, Eastell R, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356:1809–22.

    Article  CAS  PubMed  Google Scholar 

  3. Basso FG, Silveira TAP, Hebling J, de Souza Costa CA. Zoledronic acid inhibits human osteoblast activities. Gerontology. 2013;59:534–41.

    Article  CAS  PubMed  Google Scholar 

  4. Patntirapong S, Singhatanadgit W, Chanruangvanit C, Lavanrattanakul K, Satravaha Y. Zoledronic acid suppresses mineralization through direct cytotoxicity and osteoblast differentiation inhibition. J Oral Pathol Med. 2012;41:713–20.

    Article  CAS  PubMed  Google Scholar 

  5. Koch FP, Merkel C, Ziebart T, Smeets R, Walter C, Al-Nawas B. Influence of bisphosphonates on the osteoblast RANKL and OPG gene expression in vitro. Clin Oral Investig. 2012;16:79–86.

    Article  PubMed  Google Scholar 

  6. Duque G, Li W, Adams M, Xu S, Phipps R. Effects of risedronate on bone marrow adipocytes in postmenopausal women. Osteoporos Int. 2011;22:1547–53.

    Article  CAS  PubMed  Google Scholar 

  7. Patel JJ, Butters OR, Arnett TR. PPAR agonists stimulate adipogenesis at the expense of osteoblast differentiation while inhibiting osteoclast formation and activity. Cell Biochem Funct. 2014;32:368–77.

    Article  CAS  PubMed  Google Scholar 

  8. Casado-Diaz A, Santiago-Mora R, Dorado G, Quesada-Gomez JM. Risedronate positively affects osteogenic differentiation of human mesenchymal stromal cells. Arch Med Res. 2013;44:325–34.

    Article  CAS  PubMed  Google Scholar 

  9. Jin J, Wang L, Wang XK, et al. Risedronate inhibits bone marrow mesenchymal stem cell adipogenesis and switches RANKL/OPG ratio to impair osteoclast differentiation. J Surg Res. 2013;180:e21–9.

    Article  CAS  PubMed  Google Scholar 

  10. Duque G, Rivas D. Alendronate has an anabolic effect on bone through the differentiation of mesenchymal stem cells. J Bone Miner Res. 2007;22:1603–11.

    Article  CAS  PubMed  Google Scholar 

  11. Fu L, Tang T, Miao Y, Zhang S, Qu Z, Dai K. Stimulation of osteogenic differentiation and inhibition of adipogenic differentiation in bone marrow stromal cells by alendronate via ERK and JNK activation. Bone. 2008;43:40–7.

    Article  CAS  PubMed  Google Scholar 

  12. Li GW, Xu Z, Chang SX, et al. Influence of early zoledronic acid administration on bone marrow fat in ovariectomized rats. Endocrinology. 2014;155:4731–8.

    Article  PubMed  Google Scholar 

  13. Li GW, Chang SX, Fan JZ, Tian YN, Xu Z, He YM. Marrow adiposity recovery after early zoledronic acid treatment of glucocorticoid-induced bone loss in rabbits assessed by magnetic resonance spectroscopy. Bone. 2013;52:668–75.

    Article  CAS  PubMed  Google Scholar 

  14. Roldan-Valadez E, Pina-Jimenez C, Favila R, Rios C. Gender and age groups interactions in the quantification of bone marrow fat content in lumbar spine using 3T MR spectroscopy: a multivariate analysis of covariance (Mancova). Eur J Radiol. 2013.

  15. Li GW, Xu Z, Chen QW, Chang SX, Tian YN, Fan JZ. The temporal characterization of marrow lipids and adipocytes in a rabbit model of glucocorticoid-induced osteoporosis. Skeletal Radiol. 2013;42:1235–44.

    Article  PubMed  Google Scholar 

  16. Hwang JS, Chin LS, Chen JF, et al. The effects of intravenous zoledronic acid in Chinese women with postmenopausal osteoporosis. J Bone Miner Metab. 2011;29:328–33.

    Article  CAS  PubMed  Google Scholar 

  17. Eastell R, Boonen S, Cosman F, et al. Relationship between pretreatment rate of bone loss and bone density response to once-yearly ZOL: HORIZON-PFT extension study. J Bone Miner Res. 2015;30:483–7.

    Article  CAS  Google Scholar 

  18. Blake GM, Griffith JF, Yeung DK, Leung PC, Fogelman I. Effect of increasing vertebral marrow fat content on BMD measurement, T-Score status and fracture risk prediction by DXA. Bone. 2009;44:495–501.

    Article  CAS  PubMed  Google Scholar 

  19. Svendsen OL, Hassager C, Skodt V, Christiansen C. Impact of soft tissue on in vivo accuracy of bone mineral measurements in the spine, hip, and forearm: a human cadaver study. J Bone Miner Res. 1995;10:868–73.

    Article  CAS  PubMed  Google Scholar 

  20. Sorenson JA. Effects of nonmineral tissues on measurement of bone mineral content by dual-photon absorptiometry. Med Phys. 1990;17:905–12.

    Article  CAS  PubMed  Google Scholar 

  21. Jacques RM, Boonen S, Cosman F, et al. Relationship of changes in total hip bone mineral density to vertebral and nonvertebral fracture risk in women with postmenopausal osteoporosis treated with once-yearly zoledronic acid 5 mg: the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res. 2012;27:1627–34.

    Article  CAS  PubMed  Google Scholar 

  22. Li GW, Tang GY, Liu Y, Tang RB, Peng YF, Li W. MR spectroscopy and micro-CT in evaluation of osteoporosis model in rabbits: comparison with histopathology. Eur Radiol. 2012;22:923–9.

    Article  PubMed  Google Scholar 

  23. Bredella MA, Fazeli PK, Daley SM, et al. Marrow fat composition in anorexia nervosa. Bone. 2014;66:199–204.

    Article  CAS  PubMed  Google Scholar 

  24. Bredella MA, Gerweck AV, Barber LA, et al. Effects of growth hormone administration for 6 months on bone turnover and bone marrow fat in obese premenopausal women. Bone. 2014;62:29–35.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Carmona R, Pritz J, Bydder M, et al. Fat composition changes in bone marrow during chemotherapy and radiation therapy. Int J Radiat Oncol Biol Phys. 2014;90:155–63.

    Article  PubMed  Google Scholar 

  26. Bernard CP, Liney GP, Manton DJ, Turnbull LW, Langton CM. Comparison of fat quantification methods: a phantom study at 3.0 T. J Magn Reson Imaging. 2008;27:192–7.

    Article  PubMed  Google Scholar 

  27. Duque G, Li W, Vidal C, Bermeo S, Rivas D, Henderson J. Pharmacological inhibition of PPARgamma increases osteoblastogenesis and bone mass in male C57BL/6 mice. J Bone Miner Res. 2013;28:639–48.

    Article  CAS  PubMed  Google Scholar 

  28. Li X, Kuo D, Schafer AL, et al. Quantification of vertebral bone marrow fat content using 3 Tesla MR spectroscopy: reproducibility, vertebral variation, and applications in osteoporosis. J Magn Reson Imaging. 2011;33:974–9.

    Article  PubMed Central  PubMed  Google Scholar 

  29. Karampinos DC, Melkus G, Baum T, Bauer JS, Rummeny EJ, Krug R. Bone marrow fat quantification in the presence of trabecular bone: Initial comparison between water-fat imaging and single-voxel MRS. Magn Reson Med. 2014;71:1158–65.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Conflict of interest

The authors have no conflicts of interest to declare.

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Authors and Affiliations

  1. Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin Er Road, Shanghai, 200025, China

    Yi Yang, Xianfu Luo & Fuhua Yan

  2. Department of Radiology, The Second Affiliated Hospital of Soochow University, No. 1055, Sanxiang Road, Suzhou, 215004, China

    Yi Yang, Zheng Jiang, Yong Li & Junkang Shen

  3. Departments of Radiology, Northern Jiangsu People’s Hospital and Clinical Medical College of Yangzhou University, Yangzhou, 225001, China

    Xianfu Luo

  4. Departments of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China

    Chen Fang

Authors
  1. Yi Yang
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  2. Xianfu Luo
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  3. Fuhua Yan
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  4. Zheng Jiang
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  5. Yong Li
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  6. Chen Fang
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  7. Junkang Shen
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Correspondence to Fuhua Yan or Junkang Shen.

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Yang, Y., Luo, X., Yan, F. et al. Effect of zoledronic acid on vertebral marrow adiposity in postmenopausal osteoporosis assessed by MR spectroscopy. Skeletal Radiol 44, 1499–1505 (2015). https://doi.org/10.1007/s00256-015-2200-y

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  • DOI: https://doi.org/10.1007/s00256-015-2200-y

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