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OSTEOARTHRITIS by: Dr. JO Serrentino Cytokine Therapy series 3/21/2012

By Dr JO Serrentino

This seminar/webinar is for the purposes of continuing education and available to registrants only. No part of this material may be duplicated in any format without the expressed written permission of the author. No part of this presentation can be used in any form or medium, and is not for unauthorized distribution. The information and suggestions in this document are for informational purposes only; for continuing education registrants only Copyrighted material any duplication or unauthorized use is prohibited. 2012 JO Serrentino.

Signs and stats

-DISORDER OF ARTICULAR CARTILAGE associated with hypertrophic bone changes -AFFECTS ALL JOINTS ESP. HIP AND KNEE -AGE-RELATED DISEASE -EXERCISE/SPORTS RELATED CONDITION -METABOLIC CAUSES CAN INDUCE OSTEOARTHRITIS

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OSTEOARTHRITIS by: Dr. JO Serrentino Cytokine Therapy series 3/21/2012

DECREASE OF CHONDROCYTES IN ARTICULAR CARTILAGE CHONDROCYTIC APOPTOSIS DECREASE OF IGF IN ARTICULAR CHONDROCYTES LOSS OF ARTICULAR CARTILAGE STRUCTURAL CHANGES IN ADJACENT BONE MARGINS FORMATION OF OSTEOPHYTES IMBALANCE OFCARTILAGE HOMEOSTASIS HYPERPLASIA OF SYNOVIAL LINING

LOSS OF ARTICULAR CARTILAGE STRUCTURAL CHANGES IN ADJACENT BONE MARGINS FORMATION OF OSTEOPHYTES

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OSTEOARTHRITIS by: Dr. JO Serrentino Cytokine Therapy series 3/21/2012

Cartilage has low repair capacity because of low mitotic potential of chondrocytes and relative lack of innervation and vascularization. TNF main degrading agent OA cartilage expresses large concentrations of IL-1 OA cartilage produces more TACE OA cartilage contains reduced IGF-1

Macrophage and lymphocyte infiltration, neoangeogenesis and fibrosis cause synovitis - Synovitis correlates with degradation of cartilage, severity of osteoarthritis and joint pain

IL-7 considered marker for ageing joint IL-7 high in synovial fluid of older patients IL-7 low in synovial fluid of severe OA joints Il-7 correlates with BMI Cytokines differ in initial stages of OA to progressive stage

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IL-1 and TNF DRIVE OA PATHOPHYSIOLOGY TACE stimulates TNF TNF inhibits chondrocyte biosynthesis pathways
interaction between expressed cytokines causes different pathways according to the combination expressed

Proteoglycans and collagen-rich cartilage form a matrix designed to endure mechanical stresses and weight bearing on the joint; for example Aggrecan serves to resist compression Type ll collagen fibers contribute tensile strength The proteoglycan/cartilage complex is maintained by the extracellular matrix; synthesis and maintenance comes from cytokine signaling. Chondrocytes control the rates of synthesis of matrix proteins

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OSTEOARTHRITIS by: Dr. JO Serrentino Cytokine Therapy series 3/21/2012

IMPORTANT MATRIX MOLECULE DEGRADATION OF TYPE ll COLLAGEN OCCURS IN INITIAL EVENT OF INJURY OR POSTSURGICALLY DEGRADATION OF COLLAGEN LEADS TO OA FRAGMENTS FROM DEGRADING COLLAGEN TYPE ll SEEN IN SYNOVIAL FLUID OF OA PATIENTS

OA can develop from metabolic dysregulation such as:

High cholesterol and triglycerides hyperinsulemia Insulin resistance Metabolic syndrome Dysregulated non-esterified fatty acids (NEFA) Low adiponectin

Infrapatellar fat pad and other adipose tissues in arthritic joints produce leptin leading to cartilage degeneration

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HYPERTROPHIC BONE CHANGES

Structural changes in peri-articular bone and bone margins and formation of osteophytes DISREGULATION OF OSTEOCLASTOGENIC AND ANTI-OSTEOCLASTOGENIC PATHWAYS

Mesenchymal stem cells derived from progenitor cells are now being targeted for therapeutic options in osteoarthritis Events and pathways parallel cytokine expression Similar to PRP

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- peri-prosthetic osteolysis due to deterioration around bone - chronic inflammation and loosening of prosthesis - metalosis causing immune response - release of PGE2 - osteolysis and cell death - cytokine therapy can help prevent and manage these events in a post-surgical protocol

COMMON IN CATS EQUIVALENT TO DJD IN HORSES AND DOGS SYNOVITIS IS COMMON PAIN MEDS COUNTERACT REPAIR MECHANISMS, CAUSING APOPTOSIS OF CHONDROCYTES

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The main mediators for osteoarthitis are: IGF-1: anti-inflammatory & anti-apoptotic AIL-1: neutralizes IL-1 and TNF IL-4: suppresses synthesis of TNF and IL-1 IL-10: anti-inflammatory (increases antiinflammatory effect of protocol esp. with IL-4) The combination of cytokines is most important in osteoarthritic protocols.

IGF-1 is the main mediator in osteoarthitis because of its role in cartilage homeostasis Anti-inflammatory Anti-apoptotic Scavenges IL-1 and stimulates proteoglycan and collagen ll Stimulates chondrocyte differentiation Activates glycoprotein synthesis Low in synovial fluid of aging joints

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COMPLEXES APPLICABLE TO OA:

OSTEOBIOS: for PTH factor in bone therapy OMEOSPORT: supportive therapy for CTM strengthens and supports during physio or re-entry to sports after injury, to reduce recovery time after workout. Mainly muscular support. NATUR 4 & 5 CREAM: to prepare cytokine topicals TAMANU ARNICA CREAM: to prepare cytokine topicals ARTHRO: support and analgesia during repair FLAM: extra analgesia with Arthro VIRUS: for pain control while preventing infection SPASM: extra analgesia and supportive analgesia for muscles and CTM in general BASIC: to reduce acidity associated with oxidative stress

Protocol
TOPICAL
50 g of NATUR 4, 5 or TAMANU ARNICA + IGF: 60 drops + AIL-1: 60 drops + IL-4 : 45 drops + IL-10: 50 drops + FGF: 30 drops + TGF: 20drops

GENERAL PROTOCOL FOR OSTEOARTHRITIS To manage and prevent further degradation of cartilage and chronic inflammation.

GM EA N I EN RT AE LN A N C E

IGF: 20 drops bid for 2 months,then sid for 2 months, then 3 x week for 3-4 months + AIL-1: 20 drops bid for 3 months, then 3 x week for 3-4 months + IL-10: 20 drops bid for 1 month, then sid for 2 months, then 3 x (at sid) for 2 months + Il-4 : 20 drops sid for 2 months, then 3 x week for 2-3 months + FGF: 10 drops sid for 1 month, then 3 x week for a month.

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Protocol

To prevent further degradation of cartilage or for high stress on joints due to sports

P R E V E N I O N

IGF: 20 DROPS BID FOR 2 MONTHS, THEN SID FOR 1 MONTH, THEN 3 X WEEK FOR 1-2 MONTHS. STOP + AIL-1: 20 DROPS BID FOR 2 MONTHS, THEN 3 X WEEK FOR 2-3 MONTHS. + IL-10: 20 DROPS SID FOR 2 MONTHS, THEN 3 X WEEK FOR 1 MONTH + Il-4 : 20 DROPS SID FOR 2 MONTHS, THEN 3 X WEEK FOR 1 MONTH. STOP + FGF: 20 DROPS SID FOR 2 MONTHS, THEN 3 X WEEK FOR 2 MONTHS

VITAMIN D: 2000 IU DAILY take with FGF

Protocol
TOPICAL
50 g of NATUR 4, 5 or TAMANU ARNICA + 60 drops IGF + 60 drops AIL-1 + 40 drops IL-4 + 50 drops IL-10

This is a short-term protocol immediately following surgery to counteract anabolic pathways . It can be given with pain Rx IGF: 20 drops bid for 2 weeks (14 days), then 3 x week for 2 weeks. + AIL-1: 20 drops tid for 10 days, then bid for 1 month + IL-4: 10 drops bid for 2 weeks, then sid for 2 weeks. + OSTEOBIOS: 20 drops bid for 1 month + VIRUS: 5 pellets tid for 10 days

P O S T S U R G I C A L

Topical can be continued for 3-6 months

OPTIONAL for added analgesia: ARTHRO + FLAM: 20 DROPS OF EACH QID

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Protocol
TOPICAL

When associated with lipidosis, insulin resistance, metabolic syndrome, obesity. IGF: 20 drops bid for 2 months, then 3 x week for 2 months + AIL-1: 20 drops bid for 2 months, then 3 x week for 2 months + IL-10: 20 drops bid for 2 months, then 3 x week for 2 months + Il-4 : 10 drops bid for 1 month, then sid for 1 month.
OPTIONAL: BASIC: 1 PACKET 3 X WEEK FOR 2-4 MONTHS.

M E T A B O L I C

50 g of NATUR 4, 5 or TAMANU ARNICA + IGF: 50 DROPS + AIL-1: 50 DROPS + IL-10: 60 DROPS

Protocol
TOPICAL
50 g of NATUR 4, 5 or TAMANU ARNICA + IGF: 50 DROPS + AIL-1: 50 DROPS + IL-10: 60 DROPS + IL-4: 35 DROPS + FGF: 30 DROPS

Post PRP or stem cell injection or Intraarticular injection such as with steroids or hyaluronic acid.

P o s t s t e

c e l l
o r

IGF: 20 drops bid for 2 weeks, then 3 x week for 1-2 months + AIL-1: 20 drops bid for 1 month, then 3 x week for 1-2 months + FGF:20 drops bid for 2 weeks, then 3 x week for 1-2 months. OPTION: VIRUS: 5 PELLETS BID FOR 2 WEEKS.

I m A

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Protocol
TOPICAL
PP OR SO T S - T H E S I S

When complications of metalosis, or to prevent the possibility of this type or reaction

50 g of NATUR 4, 5 or TAMANU ARNICA + IL-4: 40 DROPS + IL-10: 60 DROPS

IGF: 20 DROPS BID FOR 1 MONTH, THEN SID FOR 2 MONTHS + AIL-1: 20 DROPS BID FOR 2 MONTHS, THEN 3 X WEEK FOR 1 MONTH + IL-10: 20 DROPS BID FOR 2 MONTHS, THEN 3 X WEEK FOR 1 MONTH + Il-4 : 20 DROPS BID FOR 1 MONTH, THEN SID FOR 2 MONTHS, THEN 3 X WEEK FOR 1 MONTH

Protocol
TOPICAL
P e r i p r o s t h e t i c

FOR PERI-PROSTHETIC OSTEOLYSIS WITH PROGRESSIVE DETERIORATION OF PERIARTICULAR BONE. Can be used after surgical revision
IGF: 20 DROPS BID FOR 1 MONTH, THEN SID FOR 1 MONTH, THEN 3 X WEEK FOR 2 MONTHS + AIL-1: 20 DROPS BID FOR 2 MONTHS, THEN 3 X WEEK FOR 1 MONTH + OSTEOBIOS: 20 DROPS BID FOR 3 MONTHS, THEN 3 X WEEK FOR 2-3 MONTHS + IL-3: 10 DROPS SID FOR 2-3 MONTHS + Il-4 : 10 DROPS SID FOR 1 MONTH, THEN 3 X WEEK FOR 1-2 MONTHS + FGF: 20 DROPS SID FOR 1 MONTH, THEN 3 X WEEK FOR 1 MONTH + TGF: 20 DROPS 3 X WEEK FOR 1 MONTH VITAMIN D: 2000 IU taken with Osteobios and IL-3

o s t e o l y s i s

50 g of NATUR 4, 5 or TAMANU ARNICA + IL-4: 40 DROPS + IL-10: 60 DROPS + FGF: 35 DROPS + TGF: 30 DROPS + AIL-1: 20 DROPS

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OSTEOARTHRITIS by: Dr. JO Serrentino Cytokine Therapy series 3/21/2012

Protocol
TOPICAL S Y N O V I T I S
50 g of NATUR 4, 5 or TAMANU ARNICA + AIL-1: 60 drops + IL-4: 60 drops + IL-10: 50 drops

For inflammation of synovial lining. Can be used post clinical therapy such as after aa injection of steroid or in lieu of. For best results use with topical.

IGF: 20 drops bid for 1 month, then 3 x week for 2 months + AIL-1: 20 drops tid for 1-2 months, then bid for 2 months, then 3 xweek (at bid) for 1-2 months + IL-10: 20 drops tid for 1 month, then bid for 1 month, then 3 x week for 2 months + IL-4: 20 drops bid for 2 months, then sid for 1 month, then 3 x week for 1 month + FGF: 10 drops sid for 1 month, then 3 x week for 1 month.

Protocol
Dosage chart for systemic therapy (per dose):
10 lbs or less = 1-2 drops 10-50 lbs = 3-5 drops 50-100 lbs = 8 drops 100-120 lbs = 10 drops Giant dogs = 12 drops Horses = 1 mL (35 drops)

For repair and blunting of cartilage degeneration . For analgesia and to promote mobility and quality of life.

V E T E R I N A R Y

IGF: bid for 1-2 months, then 3 x week for 2-4 months. + AIL-1: bid for 2 months, then 3 x week for 2-4 months + IL-10: bid for 2 months, then 3 x week for 2 months + Il-4 : bid for 1 month, then sid for 1-2 months, then 3 x week for 2 months.

Then assess to continue 3 x week for another 1-2 months. Or stop for 2-4 months, then repeat, but use Arthro for maintenance.

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