Short Term Tissue Response to Current Treatments for Rotator Cuff Tendinopathy
+1Murphy, R J; 1Kliskey, K; 1Wheway, K; 1Beard, D J; 1Carr, A J
+1Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK
[email protected]
INTRODUCTION
Shoulder pain is the third commonest presentation of musculoskeletal
pain in general practice and rotator cuff tendinopathy accounts for the
majority of cases.(1) Common interventions for rotator cuff
tendinopathy include glucocorticoid injections (GCI) into the
subacromial
bursa,
physiotherapy,
arthroscopic
subacromial
decompression (SAD) and rotator cuff repair surgery (RCR). The
efficacy of these and many other interventions used to treat rotator cuff
tendinopathy is equivocal and there is growing clinical evidence to
suggest that the use of steroid injections in the treatment of tendinopathy
may have a negative long term effect.(2)(3)(4) Despite the lack of
evidence to support the effectiveness of these interventions, the use of
GCI is widespread and in the NHS in England the rates of SAD and
RCR surgery have increased by 746% and 544% respectively in the last
ten years.(5)
In the past it has not been possible to evaluate the impact of current
treatments upon tendinopathic rotator cuff tissue due to an inability to
sample the tendon tissue before and after treatment. Undertaking serial
tissue sampling pre- and post-intervention would allow assessment of
the impact of current therapies for the condition and inform the
development of novel future therapeutic options.
The aim of this study was evaluate the short-term rotator cuff tendon
tissue response to GCI, SAD and RCR.
METHODS
Ethical approval for the study was granted by the local Research
Ethics Committee prior to recruitment of participants.
Patients with a history of rotator cuff tendinopathy were recruited
into groups defined by the treatments being undertaken and the
structural integrity of the rotator cuff was assessed using ultrasound or
arthroscopic diagnosis. Three groups were recruited:
1. GCI – patients with a history of rotator cuff tendinopathy without a
full thickness tear undergoing subacromial injection of glucocorticoid.
2. SAD – patients with a history of rotator cuff tendinopathy without a
full thickness tear undergoing arthroscopic subacromial
decompression due to failed glucocorticoid injection therapy.
3. RCR – patients with a full thickness rotator cuff tear undergoing
rotator cuff repair surgery.
Tissue Sampling: biopsies of the supraspinatus tendon were taken on
the day of intervention, prior to treatment, and repeated at initial follow
up 7-weeks post-intervention. These paired samples were then analyzed
to evaluate the tissue response to the intervention undertaken.
Ultrasound guided biopsy: samples were taken under ultrasound
guidance using a BARD Magnum 14G core biopsy needle. Biopsies
were sampled from the supraspinatus tendon 5mm posterior to the
rotator interval in a plane parallel to the footprint of the tendon and as
close to the tuberosity as possible. The biopsies were obtained in clinic
under local anaesthetic for the GCI group and in the operating theatre for
the surgical and control groups.
Tissue processing: the tendon samples were fixed in 10% formalin
solution before wax-embedding. Three micron sections were mounted
onto slides and stained using the following immunohistochemical (IHC)
stains to evaluate changes is tissue characteristics:
1. CD34 – to identify vascular endothelial tissue.
2. CD45 Leucocyte common antigen – to identify CD45 positive white
cells as a marker of inflammation.
3. MIB-1 – to identify proliferating cells.
4. Active Caspase-3 – to identify cells undergoing apoptosis.
Image Processing: all slides were imaged under consistent
conditions using a Zeiss Axio Imager M1 light microscope. Analysis
used computer software to calculate the proportion of positively stained
tissue from the IHC images. Images were standardized using a control
slide to ensure consistency in analysis of staining.
RESULTS
Table 1 details the composition of the study groups. The
immunohistochemical results (Figure 1) show a comparison of tissue
characteristics on the day of intervention (pre-) and 7-weeks post-
intervention. A significant increase in vascularity is seen in the RCR
group at 7-weeks post intervention. There is a significant increase in
inflammatory cells post treatment in the SAD and RCR groups.
Proliferation is significantly reduced post treatment in the GCI group.
No difference was seen in apoptosis after any of the interventions.
Figure 1. Histological analyses
(* denotes significant difference between
pre- and post-intervention groups using a
paired t-test, P<0.05)
Table 1.
Group Sizes
DISCUSSION
This study has demonstrated the principle of obtaining pre- and postintervention tissue samples from the supraspinatus tendon and has
shown changes in tissue characteristics in response to treatment. The
results show increased vascularity in the RCR group, supporting a theory
of a healing response from the tendon. Both surgical groups showed
increased inflammation within the tissue, although this may simply
reflect the early post-operative sampling time point. Perhaps the most
significant finding was the reduction in proliferation within the tendon
tissue in response to glucocorticoid injection supporting the theory of the
negative effects of steroid treatment in tendinopathy. Further work is
needed to define other biomarkers of tissue response and to investigate
the tissue effects of treatment at other time points post-intervention.
SIGNIFICANCE
This is the first study to have collected samples of supraspinatus
tendon tissue before and after treatment for rotator cuff tendinopathy.
This work has begun to describe the tissue response to current treatments
and opens the door to a much wider area of potential investigation into
rotator cuff tendinopathy, the assessment of current treatments and the
development and evaluation of novel therapies.
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tendinopathy: a systematic review of randomised controlled trials.
Lancet. 2010 Nov. 20;376(9754):1751–1767.
5. Murphy RJ, Maxwell R, Kulkarni R, et al. Rates of Arthroscopic
Subacromial Decompression and Rotator Cuff Repair Surgery in the
NHS in England from 2000 to 2010. In: British Elbow and Shoulder
Society Conference 2011. Newcastle: 2011.
Poster No. 2332 • ORS 2012 Annual Meeting