Hyaluronans in the Shoulder

L Funk, 2005

Hyaluronan (HA) is a naturally occurring polymer found in high concentrations in joints. It has a number of functions in the joint of which the main being it action as lubricant and shock absorber (6). HA, which is highly viscous, may provide an important lubrication role in the movement of soft tissues, as well as joints. Such as with the movement of adjacent synovial folds over each other(8), as in the subacromial bursa.

Hyaluronans have been used for treatment of pain relief and inflammation associated with degenerative joint disorders of the knee mainly (1)(2). HA is a proven adjunct to the treatment armamentarium of general practitioners and surgeons. Numerous  clinical  trials  have evaluated the efficacy and safety of intra-articular hyaluronic acid injections. The reports of these studies were among those presented to the Food and Drug Administration (FDA) in the course of the process that resulted in the release of this treatment modality. The American College of Rheumatology has included viscosupplementation in the treatment algorithm for osteoarthritis of the knee.

Mechanisms of Action
Postulated mechanisms of the long-term efficacy of HA include possible action on pain receptors and action on inflammatory cells (see below). It forms a viscous coating over the synovial and cartilage linings, acting as a mechanical barrier over pain receptors and inflammatory cells [ Figure 1 ].

Figure 1: Barrier effect of Hyaluronan

1. Anti-inflammatory Effect
HA has both in vivo and in vitro effects on leukocyte function. These include inhibition of phagocytosis, adherence and mitogen-induced stimulation. These properties are dependant on the molecular size of haluronic acid. Intra-articular administration of hyaluronic acid reduces levels of inflammatory mediators, including prostaglandin and cyclic adenosine monophosphate, in the synovial fluid of patients with arthritis (9).

HA also forms a mesh-like network in synovial fluid solution. This network has 'pores' allowing the free passage of small molecules, such as nutrients, but blocking the passage of larger molecules, such as inflammatory cells and proteins [Figure 2].

Figure2: Hyaluronan Mesh in Synovial Fluid

2. Restoration of Joint Homeostasis
The synthesis of HA by synovial fibroblast cells is influenced by the concentration and molecular weight of the HA in their extra cellular environment. Instilling exogenous HA with a molecular weight >5X10 5 stimulates HA synthesis in a concentration dependant manner.

3. Analgesic Effect
Intra-articular HA modulates pain perception directly through inhibition of nociceptors or indirectly through binding of substance P - a small peptide involved in the transmission of pain signals (9).

4. Chondroprotective Potential
There is data from human and animal studies to suggest that HA could have a chondroprotective effect. Listrat et al. suggest that repeated intra-articular injections of HA might delay the structural progression of osteoarthritis. (10). However, the chondroprotective effect of HA remains unproven. More research is needed to evaluate whether or not viscosupplementation has disease-altering properties in addition to its apparent palliative characteristics. (9).

Hyaluronans in the Shoulder
HA does not have the know detrimental effects on tendons that corticosteroids have (14) (See Shoulder Injections ) and therefore is an attractive alternative to corticosteroids around the sensitive rotator cuff. It has been shown to be moderately more effective to corticosteroids without the side-effects of steroids (15).

Shibata et al [8] prospectively compared HA and steroid injections in patients with rotator cuff tears. There was no difference with respect to the pain relief experienced, range of motion and surgical requirements between the two groups. However, biopsies from the rotator cuff stumps were examined from patients who underwent surgery and showed that the collagen fibres from those injected with HA pre-operatively were significantly denser than those treated with steroid. HA injected patients were more responsive to rotator cuff repair with better outcomes. There was also a link between the number of steroid injections and the outcome of surgery. Repeated steroid injections may cause severe local destruction. They concluded that although local steroid injection is often used for pain, since it has a good analgesic effect, repeated injections are associated with a softer residual cuff, and poor surgical results may be due to the giving way of this soft tissue (7).

HA is particularly beneficial for arthritis, particularly in those patients that are unfit for a shoulder replacement (11) or where a replacement is not indicated. HA is also useful for athletes and does not require a TUE form.

HA can be mixed with local anaesthetics and injected into the subacromial bursa or gleno-humeral joint. We have used Ostenil from TRB Chemedica , which is licensed for use in the shoulder in the UK. Our clinical experience after one year is that it is a useful alternative to corticosteroids and provides similar pain relief, without the concern of complications such as rotator cuff damage and fat necrosis.  It also seems to be a useful alternative for the Neer injection test (reduction of impingement pain following injection into the subacromial space). So far, we have had no complications related to the Ostenil injections and have published on this subject (11, 12). Other authors have found similar rexults with other hyaluronans (13).



1) Leardini G., Perbellini A., et al. "Intra-Articular Injections of Hyaluronic Acid in the Treatment of Painful Shoulder," Clinical Therapeutics 1988/ Vol 10.No.5.

 2) Raynauld J,P., Choquette D., et al. " Hylan versus Triamcinolone Acetonide Injection for Acute Supraspinatus Tendinitis:  Early Report of a Randomised Controlled Trial," Arthritis Rheum (1994) 37 Supp. 9 (S346)

 3)Hayes PR, Flatlow EL. "Attrition sign in impingement syndrome." Arthroscopy 2002 Nov-Dec; 18(9): E44

 4) www.orthoteers.co.uk

 5) Biberthaler., P et al, " Microcirculation Associated with Degenerative Rotator Cuff Lesion," J Bone Joint Surg AM (2003) 85; 475-480

 6)Abatangelo G., O'Regan M. "Hyaluronan: Biological role and Function in Articular Joints"
European Journal of Rheumatology and Inflammation 1995; 15: 9-16

 7) Shibata et al. Presented at the AAOS, Anaheim, Ca. Feb 1999. Press release from the Academy News Newsletter. 05/02/1999. "Hyaluronate Sodium Eases Pain of Rotator Cuff Tear."

 8) Simon LS. Viscosupplementation therapy with intra-articular hyaluronic acid - fact or fantasy? Rheum Dis Clin N Am. 1999. 25(2): 345-357.

9) Watterson JR, Esdaile JM. Viscosupplementation: Therapeutic Mechanisms and Clinical Potential in Osteoarthritis of the Knee. J Am Acad Orthop Surg 2000;8:277-284.

10) Listrat V, Ayral X, Patarnello F, Bonvarlet JP, Simonnet J, Amor B, Dougados M. Arthroscopic evaluation of potential structure modifying activity of hyaluronan (Hyalgan) in osteoarthritis of the knee. Osteoarthritis Cart 1997;5:153-160.

11) Funk L. Ostenil Hyaluronan for Inoperable Arthritis of the shoulder. Osteoarthritis & Cartilage 2004; 12(Suppl B)

12) Funk L. Hyaluronan vs corticosteroids for subacromial impingement of the shoulder. Osteoarthritis & Cartilage 2005; 13(Suppl A)

13) RD Altman, RW Moskowitz, S Jacobs, M Daley, J Udell, R Levin. Treatment of chronic shoulder pain: Intra-articular injection (IA) of sodium hyaluronate (Hyalgan). Osteoarthritis & Cartilage 2005; 13(Suppl A)

14) Nichols AW. Complications Associated With the Use of Corticosteroids in the Treatment of Athletic Injuries. Clinical Journal of Sport Medicine. 15(5):E370, September 2005.

15) Saito S, Furuya T, Kotake S. Therapeutic effects of hyaluronate injections in patients with chronic painful shoulder: A meta-analysis of randomized controlled trials. Arthritis Care Res (Hoboken). 2010 Jul 8;62(7):1009-18.


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