The Journal of Bone and Joint Surgery (American) 86:916-922 (2004)
© 2004 The Journal of Bone and Joint Surgery, Inc.
Topical Glyceryl Trinitrate Treatment of Chronic Noninsertional Achilles Tendinopathy
A Randomized, Double-Blind, Placebo-Controlled Trial
Justin A. Paoloni, MBBS1,
Richard C. Appleyard, PhD1,
Janis Nelson, MCLinPharm1 and
George A.C. Murrell, MBBS, DPhil1
1 Orthopaedic Research Institute, St. George Hospital Campus, University of New
South Wales, 2nd Floor, 4 South Street, Kogarah, NSW, 2217, Australia. E-mail
address for J.A. Paoloni:
pao_26{at}hotmail.com
Investigation performed at Orthopaedic Research Institute, St. George
Hospital Campus, University of New South Wales, New South Wales,
Australia
In support of their research or preparation of this manuscript, one or more
of the authors received grants or outside funding from Schering-Plough
Australia (a one-time monetary payment was made to the lead author [J.A.P.] to
fund the pretrial pilot study). No further monetary or other payments were
received in relation to this clinical trial. In addition, one or more of the
authors received payments or other benefits or a commitment or agreement to
provide such benefits from a commercial entity (G.A.C.M. holds a patent for
using nitric oxide to aid tendon healing). No commercial entity paid or
directed, or agreed to pay or direct, any benefits to any research fund,
foundation, educational institution, or other charitable or nonprofit
organization with which the authors are affiliated or associated.
Background: Noninsertional Achilles tendinopathy is a degenerative
overuse disorder. No method has been universally successful in treating this
condition. Topically applied nitric oxide has been shown, in animal models, to
be effective for the treatment of fractures and cutaneous wounds through
mechanisms that may include stimulation of collagen synthesis in fibroblasts.
The goal of the present study was to determine if topical glyceryl trinitrate
improves clinical outcome measures in patients with Achilles tendinopathy.
Methods: A prospective, randomized, double-blind, placebo-controlled
trial involving a total of sixty-five patients (eighty-four Achilles tendons)
was performed to compare continuous application of topical glyceryl trinitrate
(at a dosage of 1.25 mg per twenty-four hours) with rehabilitation alone for
the treatment of noninsertional Achilles tendinopathy.
Results: Compared with the control group, the glyceryl trinitrate
group showed reduced pain with activity at twelve weeks (p = 0.02) and
twenty-four weeks (p = 0.03), reduced night pain at twelve weeks (p = 0.04),
reduced tenderness at twelve weeks (p = 0.02), decreased pain scores after the
hop test at twenty-four weeks (p = 0.005), and increased ankle plantar flexor
mean total work compared with the baseline level at twenty-four weeks (p =
0.04). Twenty-eight (78%) of thirty-six tendons in the glyceryl trinitrate
group were asymptomatic with activities of daily living at six months,
compared with twenty (49%) of forty-one tendons in the placebo group (p =
0.001, chi-square analysis). The mean effect size for all outcome measures was
0.14.
Conculsions: Topical glyceryl trinitrate significantly reduced pain
with activity and at night, improved functional measures, and improved
outcomes in patients with Achilles tendinopathy.
Level of Evidence: Therapeutic study, Level I-1a
(randomized controlled trial [significant difference]). See Instructions to
Authors for a complete description of levels of evidence.
 CiteULike  Connotea  Del.icio.us  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
A. M. Ball and K. M. Smith
Optimizing transdermal drug therapy
Am. J. Health Syst. Pharm.,
July 15, 2008;
65(14):
1337 - 1346.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. P. C. Kane, M. Ismail, and J. D. F. Calder
Topical Glyceryl Trinitrate and Noninsertional Achilles Tendinopathy: A Clinical and Cellular Investigation
Am. J. Sports Med.,
June 1, 2008;
36(6):
1160 - 1163.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Maffulli and U. G. Longo
Conservative management for tendinopathy: is there enough scientific evidence?
Rheumatology,
April 1, 2008;
47(4):
390 - 391.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. D. Rompe, J. Furia, and N. Maffulli
Eccentric Loading Compared with Shock Wave Treatment for Chronic Insertional Achilles Tendinopathy. A Randomized, Controlled Trial
J. Bone Joint Surg. Am.,
January 1, 2008;
90(1):
52 - 61.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. G. Silbernagel, R. Thomee, B. I. Eriksson, and J. Karlsson
Continued Sports Activity, Using a Pain-Monitoring Model, During Rehabilitation in Patients With Achilles Tendinopathy: A Randomized Controlled Study
Am. J. Sports Med.,
June 1, 2007;
35(6):
897 - 906.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. A C Murrell
Using nitric oxide to treat tendinopathy
Br. J. Sports Med.,
April 1, 2007;
41(4):
227 - 231.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Alfredson and J Cook
A treatment algorithm for managing Achilles tendinopathy: new treatment options
Br. J. Sports Med.,
April 1, 2007;
41(4):
211 - 216.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J C Reeser, E Verhagen, W W Briner, T I Askeland, R Bahr, M Walden, and K Knobloch
Strategies for the prevention of volleyball related injuries * Commentary 1 * Commentary 2.
Br. J. Sports Med.,
July 1, 2006;
40(7):
594 - 600.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. D. Rees, A. M. Wilson, and R. L. Wolman
Current concepts in the management of tendon disorders
Rheumatology,
May 1, 2006;
45(5):
508 - 521.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R Brown, J Orchard, M Kinchington, A Hooper, and G Nalder
Aprotinin in the management of Achilles tendinopathy: a randomised controlled trial.
Br. J. Sports Med.,
March 1, 2006;
40(3):
275 - 279.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Miller, T. A. DeCoster, and M. S. Mizel
What's New in Foot and Ankle Surgery?
J. Bone Joint Surg. Am.,
April 1, 2005;
87(4):
909 - 917.
[Full Text]
[PDF]
|
|
|
|
|
|
|
Other articles noted
Evid. Based Med.,
September 1, 2004;
9(5):
e5 - e5.
[Full Text]
[PDF]
|
|
|
|
|
|
|
Other articles noted
Evid. Based Med.,
September 1, 2004;
9(5):
159 - 160.
[Full Text]
[PDF]
|
|
|
|
