Topical glyceryl trinitrate treatment of chronic patellar tendinopathy:
a randomised, double-blind, placebo-controlled clinical trial.
a randomised, double-blind, placebo-controlled clinical trial.
Steunebrink M, Zwerver J, Brandsema R, Groenenboom P, Akker-Scheek IV,
Weir A. Br J Sports Med. 2012 Aug 28. [Epub ahead of print].
Weir A. Br J Sports Med. 2012 Aug 28. [Epub ahead of print].
Chronic patellar
tendinopathy is a common condition seen in elite and recreational athletes,
especially those that participate in sports that involve repetitive jumping and
landing. The prevalence has been shown to be 2.5-14% in non-elite athletes and
as high as 40-50% in elite basketball and volleyball athletes. Eccentric training has become the standard
treatment for chronic tendinopathies, but other treatments are being
investigated that try to stimulate tendon regeneration and modulation of tendon
pain. Some studies, but not all, have
supported the use of continuous topical glyceryl trinitrate (GTN) via patches in chronic
tendinopathies including lateral epicondylosis, non-insertional Achilles
tendinopathy, and supraspinatus tendinopathy.
The objective of the study was to assess if continuous topical GTN
treatment improved outcomes among patients with chronic patellar tendinopathy
compared to placebo, while both groups underwent heavy-load eccentric
training. This study was a randomized,
double-blinded, placebo-controlled trial comparing a 12 week program of using a
5mg/24 hour GTN or placebo patch in combination with eccentric squats on a
decline board. Thirty-three patients
with clinically-diagnosed chronic patellar tendinopathy of at least 3 months
were included in the study, with ages ranging from 18-40 years old. The primary outcome was measured with the Victorian Institute of Sports
Assessment-Patella (VISA-P)
questionnaire at baseline and after 6, 12, and 24 weeks. This questionnaire quantifies pain and
activity level, with scores ranging from 0 (no activity/maximum pain) to 100
(maximum activity/no pain). The authors
found that both groups of patients improved over the study period, but there
was no significant difference found between the two treatment groups. Also, there was no difference found between
the groups for the authors’ secondary outcome measures: patient satisfaction
rate, and visual analog scale pain scores.
tendinopathy is a common condition seen in elite and recreational athletes,
especially those that participate in sports that involve repetitive jumping and
landing. The prevalence has been shown to be 2.5-14% in non-elite athletes and
as high as 40-50% in elite basketball and volleyball athletes. Eccentric training has become the standard
treatment for chronic tendinopathies, but other treatments are being
investigated that try to stimulate tendon regeneration and modulation of tendon
pain. Some studies, but not all, have
supported the use of continuous topical glyceryl trinitrate (GTN) via patches in chronic
tendinopathies including lateral epicondylosis, non-insertional Achilles
tendinopathy, and supraspinatus tendinopathy.
The objective of the study was to assess if continuous topical GTN
treatment improved outcomes among patients with chronic patellar tendinopathy
compared to placebo, while both groups underwent heavy-load eccentric
training. This study was a randomized,
double-blinded, placebo-controlled trial comparing a 12 week program of using a
5mg/24 hour GTN or placebo patch in combination with eccentric squats on a
decline board. Thirty-three patients
with clinically-diagnosed chronic patellar tendinopathy of at least 3 months
were included in the study, with ages ranging from 18-40 years old. The primary outcome was measured with the Victorian Institute of Sports
Assessment-Patella (VISA-P)
questionnaire at baseline and after 6, 12, and 24 weeks. This questionnaire quantifies pain and
activity level, with scores ranging from 0 (no activity/maximum pain) to 100
(maximum activity/no pain). The authors
found that both groups of patients improved over the study period, but there
was no significant difference found between the two treatment groups. Also, there was no difference found between
the groups for the authors’ secondary outcome measures: patient satisfaction
rate, and visual analog scale pain scores.
As previous studies have
looked at other types of tendinopathies, this was the first study to evaluate
the effectiveness of GTN in chronic patellar tendinopathy. The current evidence is conflicting on
whether or not GTN patches are clinically effective for tendinopathies. More supporting evidence for the use of GTN
in tendinopathy would be helpful because currently it is an off-label use of
the medication. Nitric oxide has
exhibited a role in fibroblast proliferation, collagen synthesis, contraction
of collagen lattices, and macrophage angiogenic activity – all important
processes in tendon regeneration. Unfortunately,
this study does not support the use of the nitrate patches or offer any
improvements in clinical outcomes.
Previous studies have reported that about 5-8% of their patients had to
stop treatment due to headaches and 5% due to rash. The headaches are caused by the vasodilation
effect of nitric oxide on the arteries and veins. A positive finding in this study was that
only 3 of the 16 patients receiving GTN patches had a minor rash and they still
continued treatment. This finding leads
to the author’s question of whether the nitric oxide concentrations reached a sufficient
level to stimulate tendon regeneration and may have been a factor for why there
was no significant differences in treatment effects. If the nitric oxide levels were too low to
produce side effects, it may have been too low to reach the injury site for
tendon healing. Even though this study
did not produce the desired outcomes, the results reinforce that eccentric
training needs to be the core of any treatment regimen and more studies are
needed to assess what other treatment options are worth the risk of side
effects and cost. What is your clinical
experience with nitrate patches and chronic tendinopathy?
looked at other types of tendinopathies, this was the first study to evaluate
the effectiveness of GTN in chronic patellar tendinopathy. The current evidence is conflicting on
whether or not GTN patches are clinically effective for tendinopathies. More supporting evidence for the use of GTN
in tendinopathy would be helpful because currently it is an off-label use of
the medication. Nitric oxide has
exhibited a role in fibroblast proliferation, collagen synthesis, contraction
of collagen lattices, and macrophage angiogenic activity – all important
processes in tendon regeneration. Unfortunately,
this study does not support the use of the nitrate patches or offer any
improvements in clinical outcomes.
Previous studies have reported that about 5-8% of their patients had to
stop treatment due to headaches and 5% due to rash. The headaches are caused by the vasodilation
effect of nitric oxide on the arteries and veins. A positive finding in this study was that
only 3 of the 16 patients receiving GTN patches had a minor rash and they still
continued treatment. This finding leads
to the author’s question of whether the nitric oxide concentrations reached a sufficient
level to stimulate tendon regeneration and may have been a factor for why there
was no significant differences in treatment effects. If the nitric oxide levels were too low to
produce side effects, it may have been too low to reach the injury site for
tendon healing. Even though this study
did not produce the desired outcomes, the results reinforce that eccentric
training needs to be the core of any treatment regimen and more studies are
needed to assess what other treatment options are worth the risk of side
effects and cost. What is your clinical
experience with nitrate patches and chronic tendinopathy?
Written by: Kris Fayock,
MD
MD
Reviewed by: Stephen Thomas
Steunebrink M, Zwerver J, Brandsema R, Groenenboom P, Akker-Scheek IV, & Weir A (2012). Topical glyceryl trinitrate treatment of chronic patellar tendinopathy: a randomised, double-blind, placebo-controlled clinical trial. British Journal of Sports Medicine PMID: 22930695
I've had one track athlete with patellar tendinopathy that was not getting better with activity restriction/modification and strengthening exercises alone who was given this type of patch. She exhibited significant reductions in pain over the course of a couple of weeks and stayed at zero to very little pain for the duration of the time that she wore the patch. I moved and am no longer involved with this athlete, but while I was there she was able to overcome and continue running competitively at the division 1 level.
Thanks for the comment Sam. I've heard of many experiences as well that were positive when using nitrate patches for patellar tendinopathy. Hopefully more studies can show which athletes/patients do benefit from this treatment.
Is there a reason why glyceryl trinitrate in the treatment of tendinopathy is administered topically rather than orally in capsule-form?
Thanks for the question. The nitrate is used topically to focus the medicine to the area of concern in the highest concentration that is still safe. One of the problems with topical nitrates that may limit its use are the side effects, with the main one being headaches. With an oral medication the medicine will be distributed to the entire body, just not the area of concern, and the amount the reaches the small part of tendinopathy may be small. The risk of side effects will be higher than the topical, and may also include dizziness, flushing, and rapid heartbeat. Nitrates could also cause low blood pressure,especially if someone is already on blood pressure medications.