Dextrose Prolotherapy for Knee Osteoarthritis: A Randomized Controlled Trial

David Rabago; Jeffrey J. Patterson; Marlon Mundt; Richard Kijowski; Jessica Grettie; Neil A. Segal; Aleksandra Zgierska

doi:10.1370/afm.1504

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Figure 1
Screening, enrollment, and randomization.
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Figure 2
Change in WOMAC composite scores over 52 weeks (± standard error).

WOMAC = Western Ontario McMaster University Osteoarthritis Index.

Note: WOMAC is scored on a range of 0 to 100 points, with higher scores indicating better knee-related quality of life. Nonoverlapping confidence intervals indicate significance of change in dextrose scores compared with change in scores of both saline (P <.05) and exercise (P <.05) groups.

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Table 1

Injection Solutions and Injection Techniques

Injection Type	Solution	Injection Technique
Dextrose
Intra-articular 25% dextrose	In a 10-mL syringe: 5 mL 50% dextrose 5 mL lidocaine 1% saline	6.0 mL was injected using an inferomedial approach
Extra-articular 15% dextrose	22.5 mL distributed in 3, 10-mL syringes (7.5 mL each) using the following recipe: 6.75 mL 50% dextrose 4.5 mL 1% lidocaine 11.25 mL 0.9% saline	Up to 15 subdermal injections were placed, and 0.5 mL of 15% solution was injected using a peppering technique with a 25-gauge needle at each ligament-bone insertion. Each puncture site allowed for placement of solution at up to 3 ligament-bone insertions using a skin-sliding technique (withdrawing the needle to just below the skin and reinserting into an adjacent area without removing from the initial puncture site), allowing for the placement of up to 22.5 mL of solution
Saline control
Intra-articular	5 mL 0.9% sodium chloride 5 mL 1% lidocaine	Injection technique identical to intra-articular injections above
Extra-articular	22.5 mL distributed in 3, 10-mL syringes (7.5 mL each) using the following recipe: 18 mL 0.9% sodium chloride 4.5 mL 1% lidocaine	Injection technique identical to extra-articular above

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Table 2

Baseline Participant Characteristics by Treatment Group

Characteristic	Dextrose	Saline	Exercise	P Value
No.	30	29	31
Female, No. (%)	19 (63)	20 (69)	21 (68)	0.82
Age, mean (SD), y	56.8 (7.9)	56.8 (6.7)	56.4 (7.0)	0.97
Duration of knee pain, No. (SD), mo	79.8 (62.9)	108.0 (99.5)	60.4 (71.6)	0.08
Body mass index, No. (%)
≤25	10 (33)	8 (28)	6 (19)
25–30	6 (20)	11 (38)	12 (39)	0.44
≥30	14 (47)	10 (34)	13 (42)
Prior knee intervention, No. (%)
History of arthroscopic surgery	7 (23)	5 (17)	7 (23)	0.84
Physical therapy	6 (20)	3 (27)	16 (52)	0.08
Hyaluronic acid injection	3 (10)	0 (0)	2 (6)	0.62
Corticosteroid injection	4 (13)	1 (9)	2 (6)	0.79
Glucosamine	7 (23)	5 (17)	8 (26)	0.82

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Table 3

Baseline Participant Knee Osteoarthritis Severity Scores by Treatment Group

Characteristic	Dextrose		Saline		Exercise		P Value
X-ray Kellgren-Lawrence osteoarthritis severity score^a
1–2 (mild osteoarthritis)	11		12		9		.35
3–4 (moderate to severe osteoarthritis)	14		9		14
WOMAC total score (SD) [range]^b	63.1 (15.0) [34.6–93.1]		62.7 (14.3) [34.3–90.8]		60.5 (11.3) [35.7–77.0]		.73
Pain score (SD) [range]	66.8 (14.9) [35.0–95.0]		66.7 (16.1) [30.0–95.0]		63.2 (13.1) [35.0–90.0]		.49
Stiffness score (SD) [range]	57.1 (19.9) [25.0–87.5]		53.9 (14.2) [25.0–87.5]		55.3 (18.0) [12.5–100.0]		.73
Function score (SD) [range]	65.2 (15.8) [39.7–96.9]		67.6 (17.5) [35.3–100.0]		61.9 (12.7) [36.8–86.8]		.36
Knee pain scale^c	Treated Knee n=43	Untreated Knee n=17	Treated Knee n=41	Untreated Knee n=17	Treated Knee n=47	Untreated Knee n=15	TreatedPValue	UntreatedPValue

Pain frequency score (SD)	2.5 (0.9)	0.6 (1.1)	2.4 (0.9)	0.9 (0.9)	2.5(0.9)	0.7 (1.0)	.52	.69
Pain severity score (SD)	1.8 (0.8)	0.5 (1.1)	1.7 (0.7)	0.6 (0.8)	1.7(0.8)	0.4 (0.7)	.42	.74

WOMAC = Western Ontario McMaster University Osteoarthritis Index.
↵a Kellgren-Lawrence scores range from 1 to 4.
↵b The theoretical range in this study is 0 to 100, with higher values indicating better knee-related quality of life.
↵c The theoretical range of scores for knee pain frequency is 0 to 4 and for knee pain severity is 0 to 5, with higher values indicating worse symptoms.

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Table 4

Change in the WOMAC Composite and Subscale Scores Over Time

Score	Week 5	Week 9	Week 12	Week 24	Week 52
WOMAC composite score change, mean (SE)
Dextrose	7.94 (3.21)	13.91 (3.23)^a	13.31 (3.32)^b	15.85 (3.26)^a	15.32 (3.32)^a
Saline	5.22 (3.21)	6.75 (3.27)^a	8.19 (3.37)^b	8.12 (3.33)^a	7.59 (3.36)^a
Exercise	4.42 (3.21)	2.51 (3.26)^a	4.26 (3.36)^b	8.48 (3.28)^a	8.24 (3.33)^a
Subscale score change, mean (SE)
Pain
Dextrose	8.17 (3.49)	14.00 (3.52)^a	11.78 (3.62)^b	15.50 (3.56)^a	14.18 (3.62)
Saline	3.28 (3.50)	5.29 (3.56)^a	5.79 (3.67)^b	6.40 (3.63)^a	7.38 (3.67)
Exercise	4.53 (3.51)	3.44 (3.55)^a	4.89 (3.66)^b	8.07 (3.60)^a	9.24 (3.63)
Stiffness
Dextrose	7.08 (4.50)	14.17 (4.53)^c	13.49 (4.67)^b	14.85 (4.58)	15.55 (4.66)
Saline	8.62 (4.51)	9.12 (4.59)^c	12.22 (4.73)^b	10.40 (4.67)	9.97 (4.72)
Exercise	3.63 (4.51)	0.14 (4.58)^c	3.13 (4.71)^b	8.18 (4.61)	8.31 (4.68)
Function
Dextrose	8.57 (3.27)	13.58 (3.30)^a	14.61 (3.40)^a	17.19 (3.33)^a	16.25 (3.39)^a
Saline	3.77 (3.28)	5.85 (3.34)^a	6.63 (3.44)^a	7.62 (3.40)^a	5.46 (3.44)^a
Exercise	5.10 (3.28)	4.00 (3.33)^a	4.89 (3.43)^a	9.30 (3.35)^a	7.31 (3.40)^a

WOMAC = Western Ontario McMaster University Osteoarthritis Index.
Notes: Numbers of participants for measurement points are as follows. Week 5: n = 30 dextrose, n = 29 saline, n = 28 exercise. Week 9: n = 30 dextrose, n = 26 saline, n = 27 exercise. Week 12: n = 27 dextrose, n = 24 saline, n = 25 exercise. Week 24: n = 28 dextrose, n = 25 saline, n = 27 exercise. Week 52: n = 26 dextrose, n = 25 saline, n = 26 exercise. Repeated measures analysis of variance compared between-group total and subscale WOMAC scores after adjusting for baseline scores, age, sex, and body mass index.
↵a Dextrose outperformed saline (P <.05) and exercise (P <.05); no statistically significant differences between saline and exercise.
↵b Dextrose outperformed exercise (P <.05); no statistically significant differences between dextrose and saline, and between saline and exercise.
↵c Dextrose outperformed exercise (P <.05); saline outperformed exercise (P <.05); no statistically significant differences between dextrose and saline.

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Table 5

Change in Knee Pain Scale Pain Frequency and Pain Severity Scores in Individual Treated Knees Over Time

Measure	Week 5	Week 9	Week 12	Week 24	Week 52
KPS pain frequency score, mean (SE) [No.]
Dextrose	−0.55 (0.26) [43]	−0.84^a (0.25) [42]	−0.87^a (0.27) [38]	−1.19^a (0.25) [40]	−1.20^a (0.21) [37]
Saline	−0.26 (0.26) [40]	−0.32 (0.25) [37]	−0.31 (0.27) [36]	−0.48 (0.25) [37]	−0.60 (0.21) [38]
Exercise	−0.15 (0.25) [38]	−0.22 (0.24) [40]	−0.12 (0.26) [37]	−0.49 (0.24) [39]	−0.40 (0.21) [38]
KPS pain severity score, mean (SE)
Dextrose	−0.25 (0.26)	−0.48 (0.25)	−0.51 (0.27)	−0.92^a (0.25)	−0.92^a (0.21)
Saline	−0.07 (0.26)	−0.19 (0.25)	−0.16 (0.27)	−0.26 (0.25)	−0.32 (0.21)
Exercise	−0.07 (0.25)	−0.15 (0.24)	−0.06 (0.26)	−0.33 (0.24)	−0.11 (0.21)

KPS=knee pain scale.
Repeated measures analysis of variance compared between-group KPS scores after adjusting for baseline scores, age, sex, and body mass index.
↵a Change in dextrose score was greater than change in saline (P <.05) and exercise (P <.05) scores, and there were no statistically significant differences between saline and exercise scores.

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The Article in Brief

Dextrose Prolotherapy for Knee Osteoarthritis: A Randomized Controlled Trial

David Rabago , and colleagues

Background Knee osteoarthritis is a common, debilitating, chronic disease. This study tests the effectiveness of prolotherapy-an injection using a sugar solution to relieve musculoskeletal pain-for knee osteoarthritis.

What This Study Found Dextrose prolotherapy offers sustained improvement of pain, function, and stiffness for patients with knee osteoarthritis. Ninety adults with at least 3 months of painful knee osteoarthritis received dextrose prolotherapy injections, saline injections, or at-home exercise. Injections were done at 1, 5, and 9 weeks with as-needed additional treatments at weeks 13 and 17. Patients receiving dextrose prolotherapy improved more at 52 weeks and reported significantly better function than patients receiving saline and exercise. Individual knee pain scores also improved more in the prolotherapy group. Patient satisfaction with prolotherapy was high and no adverse events were reported.

Implications

With most of the population showing evidence of osteoarthritis by the age of 65 years, the authors call for larger studies to compare the effectiveness of prolotherapy for knee osteoarthritis with other therapies.
Correction

In Table 1, under Solution, the components for intra-articular 25% dextrose erroneously contained 1% saline. There is no saline in the intra-articular injection, just the specified 5 mL 50% dextrose and 5 mL 1% lidocaine.