A review of treatment and papers of AO in horses 2012-2014

1. Joint Therapy
House officers rounds
2/11/15

6. OSTEOARTHRITIS

8. OPTIONS OF TREATMENT
●
Corticosteroids (TA-MP)
●
HA+GAG
●
Pentosan polysulfate
●
Standing Arthroscopy
●
Stem cells + PRP

9. Corticosteroids

10. • Objectives: To describe the plasma pharmacokinetics
of TA and time-related urine and synovial fluid
concentrations following i.m. and intra-articular
administration to exercised Thoroughbred horses.

11. •
• 12 TB horses
• Exercise:
Ø3 days/ week: Walker,
Ø2 days/ week: treadmill
• Triamcinolone acetonide
ØIM 0.1 mg/kg
ØIA: 9 mg antebrachiocarpal joint.
Ø
• Samples:
ØBlood: every other day until 60 days post administration
ØSynovial fluid: once a week until 56 days
ØUrine: Various times until 60 days

12. • IA: LOQ 0.75 ng/ml LOD approximately 0.5 ng/ml

13. The primary goal: knowledge of the disposition of
MP in plasma, urine, and synovial fluid following
intra-articular administration in the horse.
Relate MP plasma and synovial fluid concentrations
following intra-articular administration of MPA to
exercised horses

14. •
• 16 healthy TB
• Exercise:
Ø3 days/week horse walkers
Ø2 days/week treadmill
• Methylprednisolone acetate 100 mg
•
• Samples:
ØBlood: until day 44.
ØSynovial: R-L antebrachiocarpal and middle carpal joints, once a week
until 77 days
ØUrine: until day 49
•

15. • LOQ 1.0 ng/mL LOD 0.15 ng/mL.

16. HA + GAG

17. • Goal: Report findings of some potential clinical sign
or disease modifying action of this compound
administered IA at the tested dose and frequency.

18. • 16 horses ( 8 placebo/ 8 treatment)
• Arthroscopic of the middle carpal joints. One OC fragment
created
• Day 15: exercised treadmill 5 days/week
• Treatment: Days 0, 7, 14 and 28
ØPCB: 125 mg amikacin + 5 mL 0.9% saline.
ØIA PG: 5 mL IA PG plus +amikacin Days 0, 7, 14 and 28 OA
affected joint and amikacin + 5 mL 0.9% saline sham
operated joint
Ø

19. • Carpal flexion: joint pain-Efussion
• Lameness
• Radiographic
• Synovial fluid: 1/week, TP and WBC. 2 biomarker (GAG
andPGE2)
• Gross pathological examination
• Histologic examination

20. • Improve lameness (pain)
• No xr difference

21. • Increase full thickness erosion

22. Modest clinical sign and potential disease modifying
effects of a hyaluronan, sodium chondroitin sulfate
and N-acetyl-D-glucosamine combination when
administered IA at the time of disease creation

23. Pentosan polysulfate

24. How they administer pentosan polysulfate (PPS) to
horses and their perceptions of the efficacy of PPS for:
the prevention and treatment of osteoarthritis (OA),
PPS is combined with other drugs, and the efficacy of
PPS compared with other osteoarthritic drugs.

25. • Survey 76 equine vets use PPS

27. • The most common reason for using PPS was as
prophylactic therapy prior to upcoming
equestrian events (90%). Respondents also
perceived that PPS was more effective as a
prophylactic therapy than as treatment for horses
with clinical signs of OA

28. Standing Surgery

31. Regenerative therapies

32. • Evaluate the clinical response of horses treated with
PRP, MSC or combination of treatment

33. 1) 20 horses AO fetlock joint were divided in 4 groups
• Injected: 1) PRP; 2) MSCs; 3) MSCs and PRP; or 4)
chondrogenic induced MSCs and PRP.
• Evaluated: Clinical scoring after 6 weeks (T1), 12 weeks
(T2), 6 months (T3) and 12 months (T4) post
2) 30 horses randomly assigned combination therapies
and evaluated at T1

35. • Objective—To evaluate intra-articular autologous
protein solution (APS) for the treatment of
osteoarthritis in horses.

37. • 40 horses, vary high motion joints AO
• 20 injected/ 20 placebo
• Lameness exam
• Force plate
• Joint fluid analysis
• Xr
• Train 2/week treatmill

38. • Increase of number sound gate

39. • No significant changes

40. • Evaluate the efficacy of bilayer gelatin/b-
tricalcium phosphate (GT) sponges loaded with
mesenchymal stem cells (MSCs), chondrocytes,
bone morphogenetic protein-2 (BMP-2), and
platelet rich plasma (PRP) for the repair of
osteochondral defects of the talus in horses

41. • 6 horses
• Sponges: Bone Narrow  PRP, MS, chondrogenic
differentiation
• Lateral trochlear ridge of the talus by surgical drilling
through the incision, the MSC/BMP2/GT was inserted
into the lower part of the defect, and the
Ch/MSC/PRP/GT was inserted into the upper part of the
defect
• Medial oblique xr 0, 1, 2, 3, and 4. osteochondral
regeneration scored % area filled
• CT : 4 months
• Macroscopic evaluation
• Histology

44. • No remaining implant material and no
inflammatory reactions in or near the defects

46. • Investigate the blood and synovial immune and
histologic response to intra-articular injection of
autologous, allogeneic, and xenogeneic bone
marrow-derived mesenchymal stem cells (MSC) in
horses

47. • 6 Horses fetlock joints injected BMDMSC
treatments 60days previously
• BMDMSC treatments (1) auto, (2) auto-BMP2,(3)
allo, or (4) xeno.
• Synovial biopsies histologic and molecu-lar
analyses.
• Peripheral venous blood 60 day safter synovial
biopsy
•
•

48. • No abnormalities were observed in the synovium or
the articular cartilage

49. • increased cellularity with some small caliber vessels.
Inflamatory cell severity

50. • increase in number of CD4 positive cells days 3 and 6 upon re-exposure of PBMC to the xenoMSC
• Cytokine analysis:
• increases in IL-6 PBMCplus xeno group compared to all other groups
• IL-2 concentrations not significantly different among the groups at any timepoints.
• Interferon gamma concentrations were significantly greater in the PBMC
• IL-10 significantly greater in PBMCplus auto, allo and xeno groups compared to the PBMC orMSC
alone

51. A xenogeneic cell-mediated immune response was
generated that may produce a more significant immune
response if a second injection was performed in vivo.
Allogeneic MSC may not induce a detectable immune
response after intra-articular injection, but further work
may be needed to identify a more subtle response.

52. Questions???