1. Sr. Consultant Orthopedics Apollo Hospital, New Delhi
IN KNEE OSTEOARTHRITIS
Dr(Prof) Raju Vaishya
MS, MCh, FRCS
Sr. Consultant Orthopedics
Apollo Hospital, New Delhi

2. Pathophysiology of OA
Pathophysiology of OA involves a combination of mechanical, cellular, and biochemical processes
In osteoarthritis, the concentration and molecular weight of hyaluronic acid in synovial fluid is reduced by a factor of 2 or 3 by both degradation and dilution leads to dramatic changes in the viscoelastic properties and altered joint mechanics.
Hyaluronic acid also influence a variety of leukocyte functions and is chondroprotective - inhibiting degradation of cartilage as well as encouraging its healing and repair.
Progression of OA -imbalance of proinflammatory and anti-inflammatory cytokines, proteolytic enzymes and destroys
Recent treatments for OA are concentrating on resolving these cytokine imbalances.

4. Operative options for OA Bone marrow stimulation (microfracture)
Treatment
Non-operative treatment for OA and pain NSAIDs Glucosamine Chondroitin sulfate IA inj. of steroids IA inj. of sod. hyaluronate Prolotherapy
Operative options for OA
Bone marrow stimulation (microfracture)
Chondrocyte implantation
Osteochondral transplantation
Osteotomy
Arthroplasty
Treatment for late and early OA
Recent adv- Regenrative treatment (PRP)

5. Why PRP for Knee OA?
NSAIDs, glucosamine, chondroitin sulfate and hyaluronic acid - used for their anti-inflammatory and analgesic action.
Have limited effect on reducing chondrocyte degeneration and improving regeneration.
Medications protecting or healing the cartilage include cytokine inhibitors, gene therapy, artificial chondrocytes - still at experimental stage.
Autologous platelet rich plasma (PRP) application has emerged as a treatment option for OA.

6. PRP for Knee OA
Kon et al reported that 80% of 91 patients, receiving weekly PRP, were satisfied with the treatment.
Chang et al, in systematic review, reported PRP applications to be more effective in functional improvement in OA compared to HA administration.

7. PRP
Contains a mean of 3-5 fold higher platelet counts compared with whole blood.
No widely accepted and quantified values of platelet concentrations in PRP.
Number of platelets which exist in whole blood ranges from 150,000/µl to 350,000/µl
The aim is to maintain the concentration of platelets in PRP at least 200% compared with whole blood.

8. Preparation of PRP No standard technique
Can be prepared manually, there are also various commercial PRP preparation kits.
PRP substrates consisting of different concentrations and counts of platelets are obtained by these kits using different cloting activators.
Platelet concentrations in PRP varies according to the preparation method, ranging from 2.5 to 8 fold higher compared to whole blood.
Therapeutic effects of PRP may vary due to different preparation techniques.
High-cost of these commercial kits are disadvantages to be used frequently.

9. PRP Preparation
Prepared by centrifuging autologous, anticoagulated (citrated) whole blood. Centrifugation separates the following: (1) plasma (top layer) from (2) platelets and white blood cells (buffy coat, middle layer) and (3) red blood cells (bottom layer) as a result of differences in specific gravity. The volume of platelet rich plasma and concentration of platelets yielded from a volume of whole blood can differ based on the preparation system used
Absolute contraindications for PRP administration include platelet dysfunction syndrome, critical thrombocytopenia, hemodynamic instability, septicemia, local infection at the site of the procedure and patient unwilling to accept risks.

10. PLATELET RICH PLASMA

11. Growth factors in PLATE RICH PLASMA
PRP
platelets contain an abundance of growth factors and cytokines that are crucial in soft tissue healing and bone mineralization
Platelet rich plasma is composed of 3-8 times the concentration of platelets contained in whole blood Safe from immune reaction and blood diseases, outpatient clinic, cheap and effective, and no additional procedures
PRP treatment was more effective than hyaluronic acid intra-articular injections Advantage - on clotting, platelets form three-dimensional scaffolds to fill the cartilage defect and act as a guide for neochondrogenesis in situ

12. Properties of Growth factors
Increases the synthesis of chondrocyte matrix and stimulates chondrogenic cell proliferation.
Reduces the activation of nuclear factor kappa B which has an important role in the pathogenesis of OA, by inhibition of inflammatory process which is induced by interleukin-1 beta.
Platelet alpha granules contain significant amount of GF.
PRP also includes plasma proteins that act as mesenchymal cell adhesion molecules like fibrin, fibronectin and vitronectin.

13. PRP for Knee OA Known to be used for the last 20 years.
Sánchez et al (2008) - 60 patients treated with PRP injections to 30 patients treated with HA injections for knee OA. Application of GF rich PRP was more effective than HA injections on pain management.
Wang-Saegusa et al demonstrated significantly improved WOMAC, VAS, Lequesne Index, and SF-36 values at the 6 months follow-up in 261 patients with unilateral or bilateral knee OA.

14. Effectiveness of PRP in knee OA
Kwon et al - PRP was efficient in all stages of degeneration; but PRP injections had stronger regenerative effects in mid- or mild-mid level OA.
Kon et al found PRP injections were more efficient compared to HA injections in the long-term decreasing of pain and symptoms and improving articular functions. They achieved better results in younger patients and patients with lower cartilage degeneration.
Calis et al (2014) showed short and long term clinical, functional and radiological improvement even in patients with Gr II/IV OA.

15. Efficacy of Intra-articular Platelet-Rich Plasma Injections in Knee Osteoarthritis: A Systematic Review (Meheux et al. Arthroscopy (2015)
Six articles (739 patients, 817 knees)
PRP injection results in significant clinical improvements up to 12 months post injection.
Clinical outcomes and WOMAC scores are significantly better after PRP versus HA at 3 to 12 months post injection.
Limited evidence for comparing leukocyte-rich versus leukocyte- poor PRP or PRP versus steroids in this study.

16. Does intra-articular PRP inj
Does intra-articular PRP inj. provide clinically superior outcomes compared with other therapies in the treatment of Knee OA? A Systematic Review of Overlapping Meta-analyses. (Campbell et al. Arthroscopy (2015)
Literature searched for meta-analyses examining use of PRP versus corticosteroids, hyaluronic acid, oral NSAIDs, or placebo. 
Three meta-analyses included ranged in quality from Level II to Level IV evidence.
Conclusions:
IA-PRP is a viable treatment for knee OA and may provide symptomatic relief for up to 12 months.
IA-PRP offers better symptomatic relief to patients with early knee degenerative changes.
Increased risk of local adverse reactions after multiple PRP injections.

17. PRP Intra-articular Knee Injections Show No Superiority V/s Viscosupplementation: A RCT. Filardo et al. AJSM (2015)
A total of 443 patients were screened, and 192 of them were enrolled in the study
PRP presented overall significantly more post injection swelling and pain.
Both treatments proved to be effective in improving knee functional status and reducing symptoms
The comparative analysis of the 2 treatments showed no significant intergroup difference at any follow-up evaluation in any of the clinical scores adopted.

18. Single or multiple injections?
For patients with early OA, multiple (3) PRP injections are useful in achieving better clinical results.
For patients with advanced OA, multiple injections do not significantly improve the results of patients in any group.
(Gormelli et al, KSSTA, 2015)

19. Unanswered questions about PRP
Best PRP separation technique?
Single or multiple injections?
Optimal frequency of injections?
Does it stop/reverse the degenerative process?

20. Consensus about PRP injections for Knee OA
Effective in pain relief for up to 1 year
Superior (or similar) to HA in effectiveness
May cause increase pain and swelling post injection
Useful therapy in early OA (LK grade I/II)

21. CONCLUSION
Treatment is most effective in younger male patients, with lower body mass index and lower degrees of chondral degeneration.
Very good result regarding the safety, feasibility, and short- term efficacy of this treatment suggest that it may represent a minimally invasive and safe procedure.
Treatment is most effective in younger male patients, with lower body mass index and lower degrees of chondral degeneration. The interesting results obtained regarding the safety, feasibility, and short-term efficacy of this treatment suggest that it may represent a minimally invasive and safe procedure