1. INJECTABLES FOR OSTEOARTHRITIS
DR BRENDON AUBREY

2. AIM OF THIS TALK What are the injectable options? How do they work?
What is the current evidence?
Are they legal in sport?

3. CORTICOSTEROID WHAT IS IT?
Steroid hormone normally produced by the kidneys
Examples of medical injectable corticosteroids:
Betamethasone (Celestone)
Dexamethasone (Decadron)
Triamcinolone acetonide (Kenacort)
Methylprednisolone (Depo-Medrol)

4. CORTICOSTEROID HOW DOES IT WORK?
Reduce inflammation by inhibiting the body’s normal immunity pathway

5. CORTICOSTEROID WHAT IS THE EVIDENCE?
Cochrane review 2006 (Bellamy et al)
Pain and function significantly better after 1 week (compared to placebo)
Pain still better up to 3 weeks
Lack of evidence for functional improvement after 1 week
Viscosupplementation was better than corticosteroid between 5 and 13 weeks post injection
Triamcinolone acetonide better than betamethasone (but cost is 4x greater)

6. CORTICOSTEROID WHICH PATIENTS MIGHT BENEFIT?
Acute inflammation
Contraindications:
Current infection
Hypersensitivity
Acute haemarthrosis
Osteochondral lesions*
Diabetes*
Side effects:
Facial flushing
Itchy skin

7. VISCOSUPPLEMENTATION WHAT IS IT?
Administration of synthetic hyaluronic acid
Examples
Synvisc/Synvisc One
Orthovisc
Hyalgan
Durolane

8. VISCOSUPPLEMENTATION HOW DOES IT WORK?
Hyaluronic acid is normally found in synovial joints
In osteoarthritis, the concentration of hyaluronic acid in the joint capsule is reduced
Administration of synthetic hyaluronic acid stimulates the synovial lining to produce better quality synovial fluid
Decreased inflammation
Initial lubricant effect
Increased function

9. VISCOSUPPLEMENTATION WHAT IS THE EVIDENCE?
Good evidence for symptom relief up to 6 months (Bellamy et al 2009 – Cochrane Review)
Minimal difference between products
Overall appears to be better than corticosteroid, but inferior to PRP and ACS

10. VISCOSUPPLEMENTATION WHICH PATIENTS MIGHT BENEFIT?
Autologous cellular therapy contraindicated
Current malignancy
Convenience
One injection versus several
Previous success with viscosupplementation
Mild – moderate OA –
Effect is better and more prolonged earlier in the disease
Questionable whether it alters the course of OA progression but does reduce inflammation

11. BEFORE WE GO ANY FURTHER…..

12. PLATELET RICH PLASMA WHAT IS IT
Autologous injection of platelets
Whole blood is taken and placed in centrifuge, platelets then extracted
Concentrated platelet rich plasma is then injected into the affected joint

13. PLATELET RICH PLASMA HOW DOES IT WORK?
Platelets play an important role in wound healing
By injecting activated platelets we initiate the wound healing cascade
Platelets release multiple cytokines and growth factors

14. PRP CYTOKINES AND GROWTH FACTORS

15. PLATELET RICH PLASMA WHAT IS THE EVIDENCE?
Sanchez et al 2008
PRP improved outcome at 5 weeks
Kon et al 2010
PRP improved outcomes at 6 and 12 months (although pain and function scores began to decline after 6 months)
Spakova et al 2012
PRP better than HA at 3 and 6 months
Patel et al 2013
PRP improved outcomes out to 6 months
Symptoms then began to return but not o baseline

16. PLATELET RICH PLASMA WHICH PATIENTS MIGHT BENEFIT?
Mild to moderate arthritis
Patients not suitable for surgery
Failure to respond from more conservative measures
Contraindications
Pregnancy
Cancer
Some bleeding disorders

17. AUTOLOGOUS CONDITIONED SERUM WHAT IS IT?
Administration of autologous serum rich with interlukin 1 receptor antagonist (IL-1ra) into the synovial joint
Autologous blood is taken and incubated by raising the temperature to 37°and exposing the blood to glass beads to activate monocytes
Monocytes are then stimulated to produce large amount of IL- 1ra
Blood is then centrifuged, and the IL-1ra rich serum is injected into the affected joint
Examples:
Orthokine/Regenokine
Cytokine (“generic” version offered at IOP)

18. AUTOLOGOUS CONDITIONED SERUM HOW DOES IT WORK?
Interlukin 1 is a pro-inflammatory cytokine that is thought to be responsible for the progression of arthritis
By injecting large amounts of IL-1ra it is believed we can slow the progression of cartilage destruction

19. AUTOLOGOUS CONDITIONED SERUM WHAT IS THE EVIDENCE?
Baltzer et al – Osteoarthritis and Cartilage 2009
ACS vs HA vs saline injection (knee)
376 patients with knee OA formed 3 treatment groups
All 3 groups showed improvement, but ACS was significantly better at 6 month and 2 year follow up

20. AUTOLOGOUS CONDITIONED SERUM WHICH PATIENTS MIGHT BENEFIT?
Cost can be a factor
Custom synringes ~ $600
Cost of appointment/injection
Recommended 6 injections ~ $4000
**IOP offer course for $1000

21. PRP VS ACS

22. PLATELET-DERIVED GROWTH FACTOR (PDGF) WHAT IS IT?
Synthetic administration of growth factors thought to mediate inflammation and tissue healing
Platelet derived growth factor (PDGF) thought to be the main mediator in tissue healing with this form of treatment

23. PLATELET-DERIVED GROWTH FACTOR (PDGF) HOW DOES IT WORK?
PDGF engineered in a lab
Injected into the affected joint to try and stimulate local anti-inflammatory and tissue healing response
Potentially leads to halt in arthritic process
Essentially the same mechanism as PRP, just acting at a different level in the tissue healing pathway

24. PLATELET-DERIVED GROWTH FACTOR (PDGF) WHAT IS THE EVIDENCE?
Very limited
Some good evidence to assist bone grafting on Orthopaedic Surgery (DiGiovanni et al 2013 JBJS)
Soft tissues and joints mostly studies in animal models
No significant difference between PRP and PDGF
Regranex gel
Topical PDGF for diabetic foot ulcers

25. IS ALL THIS STUFF LEGAL IN SPORT??
Recombinant PDGF
Banned in sport
Thymosin
Cronulla Sharks alledgedly under investigation for its use
Banned under S2 category
Controversial as thymosin is produced naturally by platelets
Currently PRP is legal in sport

26. WADA S2 CATEGORY PEPTIDE HORMONES, GROWTH FACTORS AND RELATED SUBSTANCES
The following substances, and other substances with similar chemical structure or similar biological effect(s), are prohibited:
Erythropoiesis-Stimulating Agents [e.g. erythropoietin (EPO), darbepoetin (dEPO), hypoxia-inducible factor (HIF) stabilizers, methoxy polyethylene glycol-epoetin beta (CERA), peginesatide (Hematide)]
Chorionic Gonadotrophin (CG) and Luteinizing Hormone (LH) and their releasing factors, in males
Corticotrophins and their releasing factors
Growth Hormone (GH) and its releasing factors and Insulin-like Growth Factor-1 (IGF-1)

27. In addition, the following growth factors are prohibited:
WADA S2 CATEGORY PEPTIDE HORMONES, GROWTH FACTORS AND RELATED SUBSTANCES
In addition, the following growth factors are prohibited:
Fibroblast Growth Factors (FGFs), Hepatocyte Growth Factor (HGF), Mechano Growth Factors (MGFs), Platelet-Derived Growth Factor (PDGF), Vascular- Endothelial Growth Factor (VEGF) as well as any other growth factor affecting muscle, tendon or ligament protein synthesis/degradation, vascularisation, energy utilization, regenerative capacity or fibre type switching;
and other substances with similar chemical structure or similar biological effect(s).

28. SUMMARY
Corticosteroid is still a good option for acute exacerbations, but will not alter long term symptoms
Newer injectable options (PRP, ACS, GF’s) have all shown promise
Unable to rank in terms of efficacy, all seem to work
Cost is a major factor
More research required
All injectables can be used in advanced disease to buy time
STEM CELLS ON THE HORIZON……..