osteoartrita

Copyrighted material . Not for distribution

For continuing education registrants only.

OSTEOARTHRITIS by:

Dr. JO Serrentino

Cytokine Therapy series 3/21/2012

2012 © JO Serrentino. Duplication is

prohibited without the permission of

author/publisher.

Osteoarthritis by Dr JO Serrentino

For registrants only. 1

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 onlyCopyrighted 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



OSTEOARTHRITIS by:

Dr. JO Serrentino




author/publisher.



� 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



OSTEOARTHRITIS by:

Dr. JO Serrentino




author/publisher.



� 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 β� 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



OSTEOARTHRITIS by:

Dr. JO Serrentino




author/publisher.



� 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



OSTEOARTHRITIS by:

Dr. JO Serrentino




author/publisher.



� IMPORTANT MATRIX MOLECULE

� DEGRADATION OF TYPE ll COLLAGEN OCCURS IN INITIAL EVENT OF INJURY OR POST-SURGICALLY

� 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



OSTEOARTHRITIS by:

Dr. JO Serrentino




author/publisher.



� 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



OSTEOARTHRITIS by:

Dr. JO Serrentino




author/publisher.



- 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



OSTEOARTHRITIS by:

Dr. JO Serrentino




author/publisher.



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 anti-

inflammatory 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 α and β� stimulates proteoglycan and collagen ll� Stimulates chondrocyte differentiation� Activates glycoprotein synthesis� Low in synovial fluid of aging joints



OSTEOARTHRITIS by:

Dr. JO Serrentino




author/publisher.



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

G

E

N

E

R

A

L

M

A

I

N

T

E

N

A

N

C

E

GENERAL PROTOCOL FOR OSTEOARTHRITIS

To manage and prevent further degradation

of cartilage and chronic inflammation.

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.

TOPICAL50 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



OSTEOARTHRITIS by:

Dr. JO Serrentino




author/publisher.



Protocol

P

R

E

V

E

N

I

O

N

To prevent further degradation of cartilage or

for high stress on joints due to sports

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

P

O

S

T

-

S

U

R

G

I

C

A

L

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

Topical can be continued for 3-6 months

OPTIONAL for added analgesia:

ARTHRO + FLAM: 20 DROPS OF EACH QID

TOPICAL50 g of

NATUR 4,

5 or

TAMANU

ARNICA

+

60 drops

IGF

+

60 drops

AIL-1

+

40 drops

IL-4

+

50 drops

IL-10



OSTEOARTHRITIS by:

Dr. JO Serrentino




author/publisher.



Protocol

M

E

T

A

B

O

L

I

C

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.

TOPICAL50 g of

NATUR 4,

5 or

TAMANU

ARNICA

+

IGF: 50

DROPS

+

AIL-1: 50

DROPS

+

IL-10: 60

DROPS

Protocol

P

o

s

t

-

s

t

e

m

c

e

l

l

o

r

I

A

Post PRP or stem cell injection or Intra-

articular injection such as with steroids or

hyaluronic acid.

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.

TOPICAL50 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



OSTEOARTHRITIS by:

Dr. JO Serrentino




author/publisher.



Protocol

P

O

S

T

-

P

R

O

S

T

H

E

S

I

S

When complications of metalosis, or to

prevent the possibility of this type or

reaction

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

TOPICAL50 g of

NATUR 4,

5 or

TAMANU

ARNICA

+

IL-4: 40

DROPS

+

IL-10: 60

DROPS

Protocol

P

e

r

i

-

p

r

o

s

t

h

e

t

i

c

o

s

t

e

o

l

y

s

i

s

FOR PERI-PROSTHETIC OSTEOLYSIS WITH

PROGRESSIVE DETERIORATION OF PERI-

ARTICULAR 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

TOPICAL50 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



OSTEOARTHRITIS by:

Dr. JO Serrentino




author/publisher.



Protocol

S

Y

N

O

V

I

T

I

S

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.

TOPICAL50 g of

NATUR 4,

5 or

TAMANU

ARNICA

+

AIL-1: 60

drops

+

IL-4: 60

drops

+

IL-10: 50

drops

Protocol

V

E

T

E

R

I

N

A

R

Y

For repair and blunting of cartilage

degeneration . For analgesia and to promote

mobility and quality of life.

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.

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)



OSTEOARTHRITIS by:

Dr. JO Serrentino




author/publisher.



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