Rapid Decrease in Dextrose Concentration After Intra-Articular Knee Injection: Implications for Mechanism of Action of Dextrose Prolotherapy

Background: D-glucose (dextrose) is used as a 5000–25,000 mg% solution in the injection-based pain therapy known as dextrose prolotherapy (DPT). The number of peer-reviewed clinical trials supporting its use is growing. However, the mechanism of action is unknown, limiting further research. A common...

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Main Authors: Kenneth Dean Reeves, Jordan R. Atkins, Clare R. Solso, Chin-I Cheng, Ian M. Thornell, King Hei Stanley Lam, Yung-Tsan Wu, Thomas Motyka, David Rabago
Format: Article
Language:English
Published: MDPI AG 2025-02-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/2/350
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author Kenneth Dean Reeves
Jordan R. Atkins
Clare R. Solso
Chin-I Cheng
Ian M. Thornell
King Hei Stanley Lam
Yung-Tsan Wu
Thomas Motyka
David Rabago
author_facet Kenneth Dean Reeves
Jordan R. Atkins
Clare R. Solso
Chin-I Cheng
Ian M. Thornell
King Hei Stanley Lam
Yung-Tsan Wu
Thomas Motyka
David Rabago
author_sort Kenneth Dean Reeves
collection DOAJ
description Background: D-glucose (dextrose) is used as a 5000–25,000 mg% solution in the injection-based pain therapy known as dextrose prolotherapy (DPT). The number of peer-reviewed clinical trials supporting its use is growing. However, the mechanism of action is unknown, limiting further research. A commonly expressed theory is that hyperosmotic dextrose injection induces inflammation, initiating a healing-specific inflammatory cascade. In vitro study models have used continuous exposure to high concentration dextrose. But the rate of dextrose clearance after intra-articular injection, and, therefore, the duration of exposure of tissues to any particular dextrose concentration, remains unknown. We therefore determined the rate of dextrose concentration diminution in one human participant’s knees after intra-articular dextrose knee injection. Method: In this pre–post N-of-1 study, the first author (KDR), a well 70-year-old male without knee-related pathology, injected his own knees with 30 mL of 12,500 mg% dextrose on three occasions; performed serial aspirations of 1.2 mL of intra-articular fluid from 7 to 360 min post-injection; and assessed synovial dextrose concentration. Dextrose clearance kinetics were determined using Minitab and GraphPad Prism software. Results: Dextrose concentration dropped rapidly in all three trials, approximating an exponential or steep S curve. A third order chemical reaction pattern was found, suggesting factors other than dilution or glucose transporter activity, such as rapid diffusion of dextrose across the synovial membrane, may have contributed to the rapid drop in dextrose concentration. Conclusion: This pre-post N-of-1 study shows that, after intraarticular injection of 30 mL of 12,500 mg% dextrose injection into a well knee, the concentration of dextrose diminished rapidly, suggesting that intra-articular cells, tissue, and anatomic structures are exposed to an initially high dextrose concentration for a very short time. This likely affects the mechanism of action of DPT and should inform in vitro study methods.
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spelling doaj-art-a80a3dbfb8784936980ea1d4f9cf4d332025-08-20T03:12:10ZengMDPI AGBiomedicines2227-90592025-02-0113235010.3390/biomedicines13020350Rapid Decrease in Dextrose Concentration After Intra-Articular Knee Injection: Implications for Mechanism of Action of Dextrose ProlotherapyKenneth Dean Reeves0Jordan R. Atkins1Clare R. Solso2Chin-I Cheng3Ian M. Thornell4King Hei Stanley Lam5Yung-Tsan Wu6Thomas Motyka7David Rabago8Independent Researcher, Roeland Park, KS 66205, USAMedical School, DeBusk College of Osteopathic Medicine, Lincoln Memorial University, Harrogate, TN 37752, USAIndependent Researcher, Mission, KS 66202, USADepartment of Statistics, Actuarial and Data Science, Central Michigan University, Mt. Pleasant, MI 48859, USADepartment of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAThe Hong Kong Institute of Musculoskeletal Medicine, Hong Kong 999077, ChinaDepartment of Physical Medicine and Rehabilitation, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei 11490, TaiwanDepartment of Osteopathic Manipulative Medicine, School of Osteopathic Medicine, Campbell University, Lillington, NC 27506, USADepartment of Family and Community Medicine, Penn State College of Medicine, Hershey, PA 17003, USABackground: D-glucose (dextrose) is used as a 5000–25,000 mg% solution in the injection-based pain therapy known as dextrose prolotherapy (DPT). The number of peer-reviewed clinical trials supporting its use is growing. However, the mechanism of action is unknown, limiting further research. A commonly expressed theory is that hyperosmotic dextrose injection induces inflammation, initiating a healing-specific inflammatory cascade. In vitro study models have used continuous exposure to high concentration dextrose. But the rate of dextrose clearance after intra-articular injection, and, therefore, the duration of exposure of tissues to any particular dextrose concentration, remains unknown. We therefore determined the rate of dextrose concentration diminution in one human participant’s knees after intra-articular dextrose knee injection. Method: In this pre–post N-of-1 study, the first author (KDR), a well 70-year-old male without knee-related pathology, injected his own knees with 30 mL of 12,500 mg% dextrose on three occasions; performed serial aspirations of 1.2 mL of intra-articular fluid from 7 to 360 min post-injection; and assessed synovial dextrose concentration. Dextrose clearance kinetics were determined using Minitab and GraphPad Prism software. Results: Dextrose concentration dropped rapidly in all three trials, approximating an exponential or steep S curve. A third order chemical reaction pattern was found, suggesting factors other than dilution or glucose transporter activity, such as rapid diffusion of dextrose across the synovial membrane, may have contributed to the rapid drop in dextrose concentration. Conclusion: This pre-post N-of-1 study shows that, after intraarticular injection of 30 mL of 12,500 mg% dextrose injection into a well knee, the concentration of dextrose diminished rapidly, suggesting that intra-articular cells, tissue, and anatomic structures are exposed to an initially high dextrose concentration for a very short time. This likely affects the mechanism of action of DPT and should inform in vitro study methods.https://www.mdpi.com/2227-9059/13/2/350glucoseprolotherapymonosaccharide transport proteins
spellingShingle Kenneth Dean Reeves
Jordan R. Atkins
Clare R. Solso
Chin-I Cheng
Ian M. Thornell
King Hei Stanley Lam
Yung-Tsan Wu
Thomas Motyka
David Rabago
Rapid Decrease in Dextrose Concentration After Intra-Articular Knee Injection: Implications for Mechanism of Action of Dextrose Prolotherapy
Biomedicines
glucose
prolotherapy
monosaccharide transport proteins
title Rapid Decrease in Dextrose Concentration After Intra-Articular Knee Injection: Implications for Mechanism of Action of Dextrose Prolotherapy
title_full Rapid Decrease in Dextrose Concentration After Intra-Articular Knee Injection: Implications for Mechanism of Action of Dextrose Prolotherapy
title_fullStr Rapid Decrease in Dextrose Concentration After Intra-Articular Knee Injection: Implications for Mechanism of Action of Dextrose Prolotherapy
title_full_unstemmed Rapid Decrease in Dextrose Concentration After Intra-Articular Knee Injection: Implications for Mechanism of Action of Dextrose Prolotherapy
title_short Rapid Decrease in Dextrose Concentration After Intra-Articular Knee Injection: Implications for Mechanism of Action of Dextrose Prolotherapy
title_sort rapid decrease in dextrose concentration after intra articular knee injection implications for mechanism of action of dextrose prolotherapy
topic glucose
prolotherapy
monosaccharide transport proteins
url https://www.mdpi.com/2227-9059/13/2/350
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