The effect of single hyaluronic acid injection into

retrocalcaneal bursa

for the patient with

insertional Achilles tendinopathy.

Tsukasa Kumai1), Masaharu Shiraishi2), Norikazu Matsumoto3) Kazuya Sugimoto4), Norihiro Samoto4), Yasuhito Tanaka1), Yoshinori Takakura1)

1) Nara Medical University 2) Shiraishi Orthopaedic Pain Clinic 3) Higashiosaka City General Hospital 4) Nara Prefectural Hospital

The effect of single hyaluronic acid injection into

retrocalcaneal bursa for the patient with insertional

Achilles tendinopathy

Tsukasa Kumai

• My disclosure is in the Final AOFAS Program Book.

• I have a potential conflict with this presentation due to:

payment for PI on the conduct of the clinical study by Chugai

Pharm

What is “Insertional Achilles tendinopathy (IAT)”?

Achilles tendon

”Enthesis Organ” Concept

Calcaneus

Achilles

tendon

enthesis

Achilles tendon

Retrocalcaneal

bursa

Retromalleolar

fat pad

Synovial

lining cells

Enthesis

fibrocartilage

(EF)

Sesamoid

Fbrocartilage

(SF)

Periosteal

fibrocartilage

(PF)

Enthesis Organ Concept There are bursa and a lot of fat pad around enthesis.

In fat pad which comprised the wall of bursa, there are abundant

blood vessels and nerve tissue leading to symptoms.

The enthesis organ comprised the enthesis itself but also

fibrocaltilages in the walls of the adjacent bursa, together with the

bursal cavity and its associated synovium-covered fat-pad

The concept of an “enthesis organ” is of general significance in

understanding attachment sites and may explained the deverse

pathologic conditions

Histopathologic of IAT A degenarative process characterized by disorganized collagen,

abnormal neovascularization, necrosis, and mucoid degeneration.

IAT is a degenarative disease.

Current conservative treatments Streching exercise, eccentric exercise, shue insoles, NSAIDs and

corticosteroid Injections.

These conservative treatments are effective, but complete resolution

of pain often takes a long time. And these drug may be associated

with side effects

Patients of IAT need more effective and more safe alternative

treatment

The effect of HA injection

We speculate that benefical effect of HA injection in the treatment of IAT is due to…

Inhibition of cartilage degeneration (Kikuchi T et al, Jpn J Rheumatol, 5, 207-15, 1994)

con

t.

Analgesic effect (Tamoto K et al, Jpn J Rheumatol, 5, 227-36, 1994)

Inhibition of blood vessel growth / sensory nerve growth

(Tang T et al, J Med Dent Sci, 33, 951-6, 2006)

2.5 2.5 2.5 0.5 1.5

HA (mg/mL)

30 80 190 190 190

PG

E 2 g

ener

ated

(n

g/5

×1

04 c

ells

) cont. HA

Extended figure

(Safranin-O-staining)

Tibial cartilage

Blood vessel growth Sensory nerve growth

30 : MW 3×105 Da

80 : MW 8×105 Da

190 : MW 1.9×106 Da

Material and Methods

Purpose: To investigate the efficacy and safety of high-molecular-weight hyaluronic acid in patients with IAT.

Design: multicenter, open label study.

Evaluation: Visual Analogue Scale and local symptoms(spontaneous pain, tenderness, pain on exercise) at

baseline and at 1 week after HA 2.5mL single injection.

Patients Inclusion Criteria Diagnosis of IAT depend on clinical symptoms

Depend on pain around the Achilles tendon attachment site on jumping, walking, running

Tenderness in the synovail bursa around the Achilles tendon enthesis

≥20 years and <65 years

Exclusion Criteria Received local injections of HA, corticosteroid or anesthetic or had received corticosteroids (orally, rectally, or

intravenously) within 2 weeks prior to study treatment.

Previously received surgical treatment for the study foot

Acute symptoms due to trauma (fracture or joint sprain etc)

Rheumatic joint disease

【Demographic (n=15)】

Gender Male 10 ( 66.7 % ) Duration of

symptoms

＜12 weeks 9 ( 60.0 % )

Female 5 ( 33.3 % ) ≥12 weeks 6 ( 40.0 % )

Age (years) Mean (range) 38 .0 (21-64) VAS at Baseline mean±SD (cm) 4.58±2.04

Cause

Work 3 ( 20.0 % )

BMI

＜25 4 ( 26.7 % )

Sport 7 ( 46.7 % ) ≥25 11 ( 73.3 % )

Other 5 ( 33.3 % ) mean±SD 26.6±5.61

Method of injection

High-molecular weight (2700 kDa) hyaluronic acid (HA) of non-animal organ in 2.5 mL (Suvenyl®, Chugai Pharmaceutical Co., Ltd) was injected into the RETROCALCANEAL BURSA WITHOUT local anesthetic, NOT the tendon substance

Efficacy and Safety

0

1

2

3

4

5 Spontaneous pain

baseline 1 week

※Data are presented as mean ±SD

Me

an

VA

S s

co

re

(cm

) M

ea

n n

um

erica

l

va

lue

【Safety】

NO serious adverse events were reported.

Injection site pain and discomfort were reported for 2 patients. These adverse event resolved without any intervention.

0

1

2

3

4

5 Tenderness

baseline 1 week 0

1

2

3

4

5 Pain on exercise

baseline 1 week

-1

1

3

5

7

9 VAS

baseline 1 week

VAS score for pain at baseline and at 1 week

baseline 4.58 ± 2.04

1 week 2.78 ± 2.11

Amount of change (cm) -1.80 ± 1.91

Percentage of change (%) -29.4 ± 56.1

Percentage of improvement 12 ( 80.0% )

1 : No pain, 2 : Mild pain, 3 : Moderate pain, 4 : Severe pain, 5 : Intolerable pain

Duration of symptoms

Correlation between VAS score and BMI, duration of symptoms M

ean

VA

S sc

ore

(cm

) M

ean

VA

S sc

ore

(cm

)

BMI

0

1

2

3

4

5

6

7

8

9

< 12 week ≥ 12 week

< 12 week ≥ 12 week

N 9 6

baseline 3.81±1.81 5.73±1.95

1 week 1.91±1.47 4.08±2.37

Amount of change (cm) -1.90±1.93 -1.65±2.04

Percentage of change (%) -30.6±70.3 -28.0±30.0

Percentage of improvement 8 (88.9%) 4 (66.7%)

baseline

1 week

0

1

2

3

4

5

6

7

8

9

< 25 ≥ 25

< 25 ≥ 25

N 4 11

baseline 4.45±2.58 4.63±1.96

1 week 2.18±1.89 3.00±2.23

Amount of change (cm) -2.28±3.35 -1.63±1.27

Percentage of change (%) -7.5±105.3 -37.4±28.7

Percentage of improvement 2 (50.0%) 10 (90.9%)

※Data are presented as mean ±SD

Condition around the insertional Achilles tendon

Mild non-specific synovitis

Detritic synovitis

Inflammatory cells

Enthesis

Achilles tendon

Retrocalcaneal bursa

There is abundant synovial tissue adjacent to entheses, and synovial tissue is richly supplied with blood vessels. (Benjamin M et al, Arthritis Rheum, 50, 3306-13, 2004)

Patient of IAT often have mild non-specific synovitis, and some patients have detritic synovitis and inflammatory cells.

―Symptoms of IAT become worse because of those inflammation and angiogenesis

High HA content was found in the retrocalcaneal bursa. The lubricating properties of HA assure an almost frictionless in-

and-out of the fat body.(Juan J CANOSO et al, The journal of Rheumatology, 25(7), 1254-56, 1998)

It is important to supplement a retrocalcaneal bursa with HA. HA play a something role not only the lubricating.

Delamination of the PF & FC cell clusters

Vasucular proliferation

Detached fragment of PF

PF/SF

histopathology

Conclusion

HA injection into retorcalcaneal bursa improved pain of IAT.

There is a possibility that symptoms of IAT can improve by following HA effect.

• Analgesic effect

• Inhibition of cartilage degeneration

• Inhibition of blood vessel growth / sensory nerve growth

Limitations of this study were the small sample size, lack of a control group, and the short

term results(single injection) so further study is needed. However, HA injection into

retrocalcaneal bursa can become an alternative treatment for patients with IAT without

an serious adverse effects.