Skip to main content

Advertisement

SpringerLink
Log in

Assessing the effects of body weight on subchondral bone formation with quantitative 18F-sodium fluoride PET

  • Original Article
  • Published:
Annals of Nuclear Medicine Aims and scope Submit manuscript

Abstract

Objectives

The aim of this study was to quantify subchondral bone remodeling in the elbows, hands, knees, and feet using volumetric and metabolic parameters derived from 18F-sodium fluoride positron emission tomography (NaF-PET) and to assess the convergent validity of these parameters as an index of joint degeneration and preclinical osteoarthritis.

Methods

A retrospective analysis was conducted in 34 subjects (32 males, 2 females) with metastatic bone disease who underwent full-body NaF-PET/CT scans. An adaptive contrast-oriented thresholding algorithm was applied to segment NaF-avid regions in the bilateral elbows, hands, knees, and feet of each subject, and metabolically active volume (MAV), maximum standardized uptake value (SUVmax), mean metabolic volumetric product (MVPmean), and partial volume-corrected MVPmean (cMVPmean) of the segmented regions were calculated. Global parameters for MAV, SUVmax, MVPmean, and cMVPmean were defined as the sum of the corresponding values in all the joints of a subject. Inter-rater reliability was determined with Lin’s concordance correlation, and associations of global values with subject body weight and age were assessed with Pearson correlation and Spearman correlation analyses.

Results

Inter-rater reliability was observed to be the highest in SUVmax (ρc = 0.99), followed by MVPmean (ρc = 0.96), cMVPmean (ρc = 0.93), and MAV (ρc = 0.93). MAV, MVPmean, and cMVPmean were observed to significantly increase with weight (all p < 0.0001) determined by Pearson correlation. In addition, Spearman rank-order analysis demonstrated a significant correlation between SUVmax and weight in addition to MAV, MVPmean, and cMVPmean and weight (all p < 0.01). No significant association between age and any PET parameter was observed.

Conclusions

These preliminary data demonstrate the feasibility and reliability of assessing bone turnover at the joints using quantitative NaF-PET. Our findings corroborate the fact that biomechanical factors including mechanical loading and weight-bearing are contributors to osteoarthritis disease progression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Bijlsma JWJ, Berenbaum F, Lafeber FPJG. Osteoarthritis: an update with relevance for clinical practice. Lancet Lond Engl. 2011;377:2115–266. https://doi.org/10.1016/S0140-6736(11)60243-2.

    Article  Google Scholar 

  2. Murphy L, Schwartz TA, Helmick CG, Renner JB, Tudor G, Koch G, et al. Lifetime risk of symptomatic knee osteoarthritis. Arthritis Rheum. 2008;59:1207–13. https://doi.org/10.1002/art.24021.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Burr DB, Gallant MA. Bone remodelling in osteoarthritis. Nat Rev Rheumatol. 2012;8:665–73. https://doi.org/10.1038/nrrheum.2012.130.

    Article  CAS  PubMed  Google Scholar 

  4. Raynor W, Houshmand S, Gholami S, Emamzadehfard S, Rajapakse CS, Blomberg BA, et al. Evolving role of molecular imaging with (18)F-sodium fluoride PET as a biomarker for calcium metabolism. Curr Osteoporos Rep. 2016;14:115–25. https://doi.org/10.1007/s11914-016-0312-5.

    Article  PubMed  Google Scholar 

  5. Swagerty DL, Hellinger D. Radiographic assessment of osteoarthritis. Am Fam Phys. 2001;64:279–86.

    Google Scholar 

  6. Zhang W, Doherty M, Peat G, Bierma-Zeinstra MA, Arden NK, Bresnihan B, et al. EULAR evidence-based recommendations for the diagnosis of knee osteoarthritis. Ann Rheum Dis. 2010;69:483–9. https://doi.org/10.1136/ard.2009.113100.

    Article  CAS  PubMed  Google Scholar 

  7. Möller I, Bong D, Naredo E, Filippucci E, Carrasco I, Moragues C, et al. Ultrasound in the study and monitoring of osteoarthritis. Osteoarthr Cartil. 2008;16(Suppl 3):S4–7. https://doi.org/10.1016/j.joca.2008.06.005.

    Article  PubMed  Google Scholar 

  8. Saltzherr MS, Coert JH, Selles RW, van Neck JW, Jaquet J-B, van Osch GJVM, et al. Accuracy of magnetic resonance imaging to detect cartilage loss in severe osteoarthritis of the first carpometacarpal joint: comparison with histological evaluation. Arthritis Res Ther. 2017;19:55. https://doi.org/10.1186/s13075-017-1262-8.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Menashe L, Hirko K, Losina E, Kloppenburg M, Zhang W, Li L, et al. The diagnostic performance of MRI in osteoarthritis: a systematic review and meta-analysis. Osteoarthr Cartil. 2012;20:13–211. https://doi.org/10.1016/j.joca.2011.10.003.

    Article  CAS  PubMed  Google Scholar 

  10. Al-Zaghal A, Raynor W, Khosravi M, Guermazi A, Werner TJ, Alavi A. Applications of PET imaging in the evaluation of musculoskeletal diseases among the geriatric population. Semin Nucl Med. 2018;48(6):525–34.

    Article  Google Scholar 

  11. Raynor WY, Al-Zaghal A, Zadeh MZ, Seraj SM, Alavi A. Metastatic seeding attacks bone marrow. Not Bone. PET Clin. 2019;14(1):135–44.

    Article  Google Scholar 

  12. Kobayashi N, Inaba Y, Tateishi U, Ike H, Kubota S, Inoue T, et al. Comparison of 18F-fluoride positron emission tomography and magnetic resonance imaging in evaluating early-stage osteoarthritis of the hip. Nucl Med Commun. 2015;36:84–9. https://doi.org/10.1097/MNM.0000000000000214.

  13. Savic D, Pedoia V, Seo Y, Yang J, Bucknor M, Franc BL, et al. Imaging bone-cartilage interactions in osteoarthritis using [18F]-NaF PET-MRI. Mol Imaging. 2016;15:1–12. https://doi.org/10.1177/1536012116683597.

    Article  CAS  PubMed  Google Scholar 

  14. Guilak F. Biomechanical factors in osteoarthritis. Best Pract Res Clin Rheumatol. 2011;25:815–23. https://doi.org/10.1016/j.berh.2011.11.013.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Høilund-Carlsen PF, Edenbrandt L, Alavi A. Global disease score (GDS) is the name of the game! Eur J Nucl Med Mol Imaging. 2019;46:1768–72.

    Article  Google Scholar 

  16. Borja A, Werner T, Alavi A. Role of PET/CT in vascular dementia. J Nucl Med. 2019;60:1153–1153.

    Google Scholar 

  17. Hofheinz F, Langner J, Petr J, Beuthien-Baumann B, Oehme L, Steinbach J, et al. A method for model-free partial volume correction in oncological PET. EJNMMI Res. 2012;2:16. https://doi.org/10.1186/2191-219X-2-16.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Hofheinz F, Pötzsch C, Oehme L, Beuthien-Baumann B, Steinbach J, Kotzerke J, et al. Automatic volume delineation in oncological PET. Evaluation of a dedicated software tool and comparison with manual delineation in clinical data sets. Nukl Nucl Med. 2012;51:9–16. https://doi.org/10.3413/Nukmed-0419-11-07.

    Article  CAS  Google Scholar 

  19. Torigian DA, Lopez RF, Alapati S, Bodapati G, Hofheinz F, van den Hoff J, et al. Feasibility and performance of novel software to quantify metabolically active volumes and 3D partial volume corrected SUV and metabolic volumetric products of spinal bone marrow metastases on 18F-FDG-PET/CT. Hell J Nucl Med. 2011;14:8–14.

    PubMed  Google Scholar 

  20. Costeas A, Woodard HQ, Laughlin JS. Depletion of 18F from blood flowing through bone. J Nucl Med Off Publ Soc Nucl Med. 1970;11:43–5.

    CAS  Google Scholar 

  21. Nawata S, Kaneta T, Ogawa M, Ishiwata Y, Kobayashi N, Shishikura-Hino A, et al. Differences in sodium fluoride-18 uptake in the normal skeleton depending on the location and characteristics of the bone. Nukl Nucl Med. 2017;56:91–6. https://doi.org/10.3413/Nukmed-0867-16-12.

    Article  Google Scholar 

  22. Hawkins RA, Choi Y, Huang SC, Hoh CK, Dahlbom M, Schiepers C, et al. Evaluation of the skeletal kinetics of fluorine-18-fluoride ion with PET. J Nucl Med Off Publ Soc Nucl Med. 1992;33:633–42.

    CAS  Google Scholar 

  23. Bastawrous S, Bhargava P, Behnia F, Djang DSW, Haseley DR. Newer PET application with an old tracer: role of 18F-NaF skeletal PET/CT in oncologic practice. RadioGraphics. 2014;34:1295–316. https://doi.org/10.1148/rg.345130061.

    Article  PubMed  Google Scholar 

  24. Knapik DM, Perera P, Nam J, Blazek AD, Rath B, Leblebicioglu B, et al. Mechanosignaling in bone health, trauma and inflammation. Antioxid Redox Signal. 2014;20:970–85. https://doi.org/10.1089/ars.2013.5467.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Cao JJ. Effects of obesity on bone metabolism. J Orthop Surg. 2011;6:30. https://doi.org/10.1186/1749-799X-6-30.

    Article  Google Scholar 

  26. Sartori-Cintra AR, Aikawa P, Cintra DEC. Obesity versus osteoarthritis: beyond the mechanical overload. Einstein Sao Paulo Braz. 2014;12:374–9. https://doi.org/10.1590/s1679-45082014rb2912.

    Article  Google Scholar 

  27. Simpfendorfer CS. Radiologic approach to musculoskeletal infections. Infect Dis Clin North Am. 2017;31:299–32424. https://doi.org/10.1016/j.idc.2017.01.004.

    Article  PubMed  Google Scholar 

  28. Yellanki DP, Kothekar E, Al-Zaghal A, Cheng N, Werner TJ, Høilund-Carlsen PF, et al. Efficacy of 18F-FDG and 18F-NaF PET/CT imaging: a novel semi-quantitative assessment of the effects of age and obesity on hip joint inflammation and bone degeneration. Hell J Nucl Med. 2018;21:181–5. https://doi.org/10.1967/s002449910903.

    Article  PubMed  Google Scholar 

  29. Sellam J, Berenbaum F. Is osteoarthritis a metabolic disease? Jt Bone Spine. 2013;80:568–73. https://doi.org/10.1016/j.jbspin.2013.09.007.

    Article  CAS  Google Scholar 

  30. Kothekar E, Yellanki D, Borja AJ, Al-Zaghal A, Werner TJ, Revheim M-E, et al. 18F-FDG-PET/CT in measuring volume and global metabolic activity of thigh muscles: a novel CT-based tissue segmentation methodology. Nucl Med Commun. 2020;41:162–8. https://doi.org/10.1097/MNM.0000000000001127.

    Article  PubMed  Google Scholar 

  31. Kothekar E, Raynor WY, Al-Zaghal A, Jonnakuti VS, Werner TJ, Alavi A. Evolving role of PET/CT-MRI in assessing muscle disorders. PET Clin. 2019;14:71–9. https://doi.org/10.1016/j.cpet.2018.08.010.

    Article  PubMed  Google Scholar 

  32. Raynor WY, Jonnakuti VS, Zadeh MZ, Werner TJ, Cheng G, Zhuang H, Høilund-Carlsen PF, Alavi A, Baker JF. Comparison of methods of quantifying global synovial metabolic activity with FDG-PET/CT in rheumatoid arthritis. Int J Rheum Dis. 2019;22(12):2191–8.

    Article  CAS  Google Scholar 

  33. Høilund-Carlsen PF, Hess S, Werner TJ, Alavi A. Cancer metastasizes to the bone marrow and not to the bone: time for a paradigm shift! Eur J Nucl Med Mol Imaging. 2018;45:893–7. https://doi.org/10.1007/s00259-018-3959-6.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Laor T, Jaramillo D. MR imaging insights into skeletal maturation: what is normal? Radiology. 2009;250:28–38. https://doi.org/10.1148/radiol.2501071322.

    Article  PubMed  Google Scholar 

  35. Basu S, Torigian D, Alavi A. Evolving concept of imaging bone marrow metastasis in the twenty-first century: critical role of FDG-PET. Eur J Nucl Med Mol Imaging. 2008;35:465–71. https://doi.org/10.1007/s00259-007-0593-0.

    Article  PubMed  Google Scholar 

  36. Ricci C, Cova M, Kang YS, Yang A, Rahmouni A, Scott WW, et al. Normal age-related patterns of cellular and fatty bone marrow distribution in the axial skeleton: MR imaging study. Radiology. 1990;177:83–8. https://doi.org/10.1148/radiology.177.1.2399343.

    Article  CAS  PubMed  Google Scholar 

  37. Kricun ME. Red-yellow marrow conversion: its effect on the location of some solitary bone lesions. Skeletal Radiol. 1985;14:10–9. https://doi.org/10.1007/bf00361188.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

None.

Author information

Author notes

  1. Tiffany H. Khaw and William Y. Raynor share co-first authorship.

Authors and Affiliations

  1. Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce St, Philadelphia, PA, 19104, USA

    Tiffany H. Khaw, William Y. Raynor, Austin J. Borja, Abdullah Al-Zaghal, Venkata S. Jonnakuti, Nina Cheng, Sina Houshmand, Thomas J. Werner & Abass Alavi

  2. Drexel University College of Medicine, Philadelphia, PA, USA

    Tiffany H. Khaw & William Y. Raynor

  3. Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Austin J. Borja

Authors
  1. Tiffany H. Khaw
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. William Y. Raynor
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Austin J. Borja
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Abdullah Al-Zaghal
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Venkata S. Jonnakuti
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nina Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sina Houshmand
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Thomas J. Werner
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Abass Alavi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Abass Alavi.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Khaw, T.H., Raynor, W.Y., Borja, A.J. et al. Assessing the effects of body weight on subchondral bone formation with quantitative 18F-sodium fluoride PET. Ann Nucl Med 34, 559–564 (2020). https://doi.org/10.1007/s12149-020-01482-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12149-020-01482-7

Keywords

Search

Navigation