Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 12/2019

Open Access 01-11-2019 | Original Article

Assessment of acute bone loading in humans using [18F]NaF PET/MRI

Authors: Bryan Haddock, Audrey P. Fan, Scott D. Uhlrich, Niklas R. Jørgensen, Charlotte Suetta, Garry Evan Gold, Feliks Kogan

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 12/2019

Login to get access

Abstract

Purpose

The acute effect of loading on bone tissue and physiology can offer important information with regard to joint function in diseases such as osteoarthritis. Imaging studies using [18F]-sodium fluoride ([18F]NaF) have found changes in tracer kinetics in animals after subjecting bones to strain, indicating an acute physiological response. The aim of this study is to measure acute changes in NaF uptake in human bone due to exercise-induced loading.

Methods

Twelve healthy subjects underwent two consecutive 50-min [18F]NaF PET/MRI examinations of the knees, one baseline followed by one post-exercise scan. Quantification of tracer kinetics was performed using an image-derived input function from the popliteal artery. For both scans, kinetic parameters of KiNLR, K1, k2, k3, and blood volume were mapped parametrically using nonlinear regression with the Hawkins model. The kinetic parameters along with mean SUV and SUVmax were compared between the pre- and post-exercise examinations. Differences in response to exercise were analysed between bone tissue types (subchondral, cortical, and trabecular bone) and between regional subsections of knee subchondral bone.

Results

Exercise induced a significant (p < <0.001) increase in [18F]NaF uptake in all bone tissues in both knees, with mean SUV increases ranging from 47% in trabecular bone tissue to 131% in subchondral bone tissue. Kinetic parameters involving vascularization (K1 and blood volume) increased, whereas the NaF extraction fraction [k3/(k2 + k3)] was reduced.

Conclusions

Bone loading induces an acute response in bone physiology as quantified by [18F]NaF PET kinetics. Dynamic imaging after bone loading using [18F]NaF PET is a promising diagnostic tool in bone physiology and imaging of biomechanics.
Appendix
Available only for authorised users
Literature
1.
Pasco JA, Mohebbi M, Holloway KL, Brennan-Olsen SL, Hyde NK, Kotowicz MA. Musculoskeletal decline and mortality: prospective data from the Geelong Osteoporosis Study. J Cachexia Sarcopenia Muscle. 2017;8:482–9.CrossRefPubMed
2.
Ray R, Clement ND, Aitken SA, McQueen MM, Court-Brown CM, Ralston SH. High mortality in younger patients with major osteoporotic fractures. Osteoporos Int. 2017;28:1047–52.CrossRefPubMed
3.
Milte R, Crotty M. Musculoskeletal health, frailty and functional decline. Best Pract Res Clin Rheumatol. 2014;28:395–410.CrossRefPubMed
4.
Bliuc D, Alarkawi D, Nguyen TV, Eisman JA, Center JR. Risk of subsequent fractures and mortality in elderly women and men with fragility fractures with and without osteoporotic bone density: the Dubbo Osteoporosis Epidemiology Study. J Bone Miner Res. 2015;30:637–46.CrossRefPubMed
5.
Burr DB, Robling AG, Turner CH. Effects of biomechanical stress on bones in animals. Bone. 2002;30:781–6.CrossRefPubMed
6.
Hart NH, Nimphius S, Rantalainen T, Ireland A, Siafarikas A, Newton RU. Mechanical basis of bone strength: influence of bone material, bone structure and muscle action. J Musculoskelet Neuronal Interact. 2017;17:114–39.PubMedPubMedCentral
7.
Rosa N, Simoes R, Magalhães FD, Marques AT. From mechanical stimulus to bone formation: a review. Med Eng Phys. 2015;37:719–28.CrossRefPubMed
8.
Weatherholt AM, Fuchs RK, Warden SJ. Cortical and trabecular bone adaptation to incremental load magnitudes using the mouse tibial axial compression loading model. Bone. 2013;52:372–9.CrossRefPubMed
9.
10.
Tyrovola JB. The “mechanostat theory” of frost and the OPG/RANKL/RANK system. J Cell Biochem. 2015;116:2724–9.CrossRefPubMed
11.
Klein-Nulend J, Bakker AD, Bacabac RG, Vatsa A, Weinbaum S. Mechanosensation and transduction in osteocytes. Bone. 2013;54:182–90.CrossRefPubMed
12.
Savic D, Pedoia V, Seo Y, Yang J, Bucknor M, Franc BL, et al. Imaging bone-cartilage interactions in osteoarthritis using [(18)F]-NaF PET-MRI. Mol Imaging. 2016;15:1–12.CrossRefPubMed
13.
14.
Kogan F, Fan AP, McWalter EJ, Oei EHG, Quon A, Gold GE. PET/MRI of metabolic activity in osteoarthritis: a feasibility study. J Magn Reson Imaging. 2017;45:1736–45.CrossRefPubMed
15.
Draper CE, Quon A, Fredericson M, Besier TF, Delp SL, Beaupre GS, et al. Comparison of MRI and 18F-NaF PET/CT in patients with patellofemoral pain. J Magn Reson Imaging. 2012;36:928–32.CrossRefPubMedPubMedCentral
16.
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.CrossRefPubMed
17.
Blake GM, Siddique M, Frost ML, Moore AEB, Fogelman I. Imaging of site specific bone turnover in osteoporosis using positron emission tomography. Curr Osteoporos Rep. 2014;12:475–85.CrossRefPubMed
18.
Heinonen I, Kemppainen J, Fujimoto T, Knuuti J, Kalliokoski KK. Increase of glucose uptake in human bone marrow with increasing exercise intensity. Int J Sport Nutr Exerc Metab. 2019;29:254–8.CrossRefPubMed
19.
Heinonen I, Kemppainen J, Kaskinoro K, Langberg H, Knuuti J, Boushel R, et al. Bone blood flow and metabolism in humans: effect of muscular exercise and other physiological perturbations. J Bone Miner Res. 2013;28:1068–74.CrossRefPubMed
20.
Heinonen I, Boushel R, Hellsten Y, Kalliokoski K. Regulation of bone blood flow in humans: the role of nitric oxide, prostaglandins, and adenosine. Scand J Med Sci Sports. 2018;28:1552–8.CrossRefPubMed
21.
Silva MJ, Uthgenannt BA, Rutlin JR, Wohl GR, Lewis JS, Welch MJ. In vivo skeletal imaging of 18F-fluoride with positron emission tomography reveals damage- and time-dependent responses to fatigue loading in the rat ulna. Bone. 2006;39:229–36.CrossRefPubMed
22.
Muir P, Sample SJ, Barrett JG, McCarthy J, Vanderby R, Markel MD, et al. Effect of fatigue loading and associated matrix microdamage on bone blood flow and interstitial fluid flow. Bone. 2007;40:948–56.CrossRefPubMed
23.
De Souza RL, Matsuura M, Eckstein F, Rawlinson SCF, Lanyon LE, Pitsillides AA. Non-invasive axial loading of mouse tibiae increases cortical bone formation and modifies trabecular organization: a new model to study cortical and cancellous compartments in a single loaded element. Bone. 2005;37:810–8.CrossRefPubMed
24.
Tomlinson RE, Silva MJ, Shoghi KI. Quantification of skeletal blood flow and fluoride metabolism in rats using PET in a pre-clinical stress fracture model. Mol Imaging Biol. 2012;14:348–54.CrossRefPubMedPubMedCentral
25.
26.
Kogan F, Levine E, Chaudhari AS, Monu UD, Epperson K, Oei EHG, et al. Simultaneous bilateral-knee MR imaging. Magn Reson Med. 2018;80:529–37.CrossRefPubMed
27.
Wagenknecht G, Kaiser H-J, Mottaghy FM, Herzog H. MRI for attenuation correction in PET: methods and challenges. MAGMA. 2013;26:99–113.CrossRefPubMed
28.
Haddock B, Fan AP, Jørgensen NR, Suetta C, Gold GE, Kogan F. Kinetic [18F]-fluoride of the knee in Normal volunteers. Clin Nucl Med. 2019;44(5):377–85.
29.
Blake GM, Siddique M, Puri T, Frost ML, Moore AE, Cook GJR, et al. A semipopulation input function for quantifying static and dynamic 18F-fluoride PET scans. Nucl Med Commun. 2012;33:881–8.CrossRefPubMed
30.
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. 1992;33:633–42.PubMed
31.
Patlak CS, Blasberg RG, Fenstermacher JD. Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. J Cereb Blood Flow Metab. 1983;3:1–7.CrossRefPubMed
32.
Draghici AE, Potart D, Hollmann JL, Pera V, Fang Q, DiMarzio CA, et al. Near infrared spectroscopy for measuring changes in bone hemoglobin content after exercise in individuals with spinal cord injury. J Orthop Res. 2018;36:183–91.PubMed
33.
Heinonen I, Wendelin-Saarenhovi M, Kaskinoro K, Knuuti J, Scheinin M, Kalliokoski KK. Inhibition of α-adrenergic tone disturbs the distribution of blood flow in the exercising human limb. Am J Physiol Heart Circ Physiol. 2013;305:H163–72.CrossRefPubMed
34.
McCarthy I. The physiology of bone blood flow: a review. J Bone Joint Surg Am. 2006;88(Suppl 3):4–9.PubMed
35.
Knothe Tate ML, Steck R, Forwood MR, Niederer P. In vivo demonstration of load-induced fluid flow in the rat tibia and its potential implications for processes associated with functional adaptation. J Exp Biol. 2000;203:2737–45.PubMed
36.
Tami AE, Nasser P, Verborgt O, Schaffler MB, Knothe Tate ML. The role of interstitial fluid flow in the remodeling response to fatigue loading. J Bone Miner Res. 2002;17:2030–7.CrossRefPubMed
37.
Martelli S, Pivonka P, Ebeling PR. Femoral shaft strains during daily activities: implications for atypical femoral fractures. Clin Biomech (Bristol, Avon). 2014;29:869–76.CrossRef
38.
Haddock BT, Francis ST, Larsson HBW, Andersen UB. Assessment of perfusion and oxygenation of the human renal cortex and medulla by quantitative MRI during handgrip exercise. J Am Soc Nephrol. 2018;29:2510–7.CrossRefPubMedPubMedCentral
39.
Wu Q, Sample SJ, Baker TA, Thomas CF, Behan M, Muir P. Mechanical loading of a long bone induces plasticity in sensory input to the central nervous system. Neurosci Lett. 2009;463:254–7.CrossRefPubMedPubMedCentral
40.
Umemura Y, Ishiko T, Yamauchi T, Kurono M, Mashiko S. Five jumps per day increase bone mass and breaking force in rats. J Bone Miner Res. 1997;12:1480–5.CrossRefPubMed
41.
Aznar MC, Sersar R, Saabye J, Ladefoged CN, Andersen FL, Rasmussen JH, et al. Whole-body PET/MRI: the effect of bone attenuation during MR-based attenuation correction in oncology imaging. Eur J Radiol. 2014;83:1177–83.CrossRefPubMed
42.
Klein-Nulend J, van Oers RFM, Bakker AD, Bacabac RG. Bone cell mechanosensitivity, estrogen deficiency, and osteoporosis. J Biomech. 2015;48:855–65.CrossRefPubMed
43.
Bakker AD, Klein-Nulend J, Tanck E, Heyligers IC, Albers GH, Lips P, et al. Different responsiveness to mechanical stress of bone cells from osteoporotic versus osteoarthritic donors. Osteoporos Int. 2006;17:827–33.CrossRefPubMed
44.
Torvinen S, Kannus P, Sievänen H, Järvinen TAH, Pasanen M, Kontulainen S, et al. Effect of four-month vertical whole body vibration on performance and balance. Med Sci Sports Exerc. 2002;34:1523–8.CrossRefPubMed
45.
Ireland A, Maden-Wilkinson T, Ganse B, Degens H, Rittweger J. Effects of age and starting age upon side asymmetry in the arms of veteran tennis players: a cross-sectional study. Osteoporos Int. 2014;25:1389–400.CrossRefPubMed
46.
47.
Barry DW, Kohrt WM. Exercise and the preservation of bone health. J Cardiopulm Rehabil Prev. 2008;28:153–62.CrossRefPubMed
48.
Qin YX, Lam H, Ferreri S, Rubin C. Dynamic skeletal muscle stimulation and its potential in bone adaptation. J Musculoskelet Neuronal Interact. 2010;10:12–24.PubMed
49.
50.
Frost ML, Blake GM, Cook GJR, Marsden PK, Fogelman I. Differences in regional bone perfusion and turnover between lumbar spine and distal humerus: (18)F-fluoride PET study of treatment-naïve and treated postmenopausal women. Bone. 2009;45:942–8.CrossRefPubMed
51.
Hart NH, Newton RU, Spry NA, Taaffe DR, Chambers SK, Feeney KT, et al. Can exercise suppress tumour growth in advanced prostate cancer patients with sclerotic bone metastases? A randomised, controlled study protocol examining feasibility, safety and efficacy. BMJ Open. 2017;7:e014458.CrossRefPubMedPubMedCentral
52.
Lynch ME, Fischbach C. Biomechanical forces in the skeleton and their relevance to bone metastasis: biology and engineering considerations. Adv Drug Deliv Rev. 2014;79–80:119–34.CrossRefPubMed
53.
Frost ML, Blake GM, Park-Holohan S-J, Cook GJR, Curran KM, Marsden PK, et al. Long-term precision of 18F-fluoride PET skeletal kinetic studies in the assessment of bone metabolism. J Nucl Med. 2008;49:700–7.CrossRefPubMed
54.
Al-Beyatti Y, Siddique M, Frost ML, Fogelman I, Blake GM. Precision of 18F-fluoride PET skeletal kinetic studies in the assessment of bone metabolism. Osteoporos Int. 2012;23:2535–41.CrossRefPubMed
55.
Blake GM, Siddique M, Frost ML, Moore AEB, Fogelman I. Quantitative PET imaging using (18)F sodium fluoride in the assessment of metabolic bone diseases and the monitoring of their response to therapy. PET Clin. 2012;7:275–91.CrossRefPubMed
Metadata
Title
Assessment of acute bone loading in humans using [18F]NaF PET/MRI
Authors
Bryan Haddock
Audrey P. Fan
Scott D. Uhlrich
Niklas R. Jørgensen
Charlotte Suetta
Garry Evan Gold
Feliks Kogan
Publication date
01-11-2019
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 12/2019
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-019-04424-2

Other articles of this Issue 12/2019

European Journal of Nuclear Medicine and Molecular Imaging 12/2019 Go to the issue

Letter to the Editor

Hepatic supraselective radioembolization, today and new horizons

Original Article

Long-term outcome of rare oncocytic papillary (Hürthle cell) thyroid carcinoma following (adjuvant) initial radioiodine therapy

Review Article

Somatostatin receptor imaging by SPECT and PET in patients with chronic inflammatory disorders: a systematic review

Editorial

The 70th anniversary of automated radionuclide imaging

Image of the Month

Atypical gouty mediastinal tophus mimicking thymoma on 18F-FDG PET/CT

Guidelines

Joint EANM/ESNR and ESCMID-endorsed consensus document for the diagnosis of spine infection (spondylodiscitis) in adults