ICEOS: Nov. 19th – Nov. 20th 2015

1 École Polytechnique of Montreal (Canada)2 Sainte-Justine Research Hospital Center (Canada)

3 Faculty of Dentistry, University of Montreal (Canada)4 École des Mines de Saint-Étienne (France)

Presenting author

1,2MÉNARD A-L, 2GRIMARD G, 1,2,4MASSOL E, 2LONDONO I, 2,3MOLDOVAN F, 1,2VILLEMURE I

Static versus Dynamic Compression Applied and Subsequently Removed on Growing Rat

Tails: Effects on Intervertebral Discs

2

Intro

M&MResults

Discussion

Disclosures

Authors Disclosure Information a. Consultantb. Stock/Shareholder

Presenter: Anne-Laure Ménard No Relationships

Co-Authors: Guy Grimard (a,b) Emovi, IncÉlise Massol No RelationshipsIrène Londono No Relationships Florina Moldovan No RelationshipsIsabelle Villemure No Relationships

Presenter: Anne-Laure Ménard No Relationships

Co-Authors: Guy Grimard (a,b) Emovi, IncÉlise Massol No RelationshipsIrène Londono No Relationships Florina Moldovan No RelationshipsIsabelle Villemure No Relationships

3

Clinical context: fusionless devices

Research evidence: compression on the disc Mechanical loading:

• Causing factor of disc degeneration (Aronsson et al., 2011)

Disc degeneration: • disc height (Wuertz et al., 2009)

• proteoglycan in the nucleus (Sivan et al., 2014)

Compression-based fusionless devices (Skaggs et al., 2013) Span the intervertebral disc Can possibly be removed following spinal correction

(Hunt et al., 2010)

Intervertebral disc integrity in young growing individuals after physiological compression removal ?

Intro

M&MResults

Discussion

4

Clinical research question

4

Staples : compression Growth plate (GP)

(*) Is the intervertebral disc still healthy ?

RESEARCH QUESTION

Intro

M&MResults

Discussion

Intervertebral disc

Fusionless approaches

Growth

Device removal

(*)

5

Hypothesis & Objectives

5

OBJECTIVES

To assess and compare the effects of subsequently applying and removing static/dynamic compression on the intervertebral disc:

(1) Structure: disc height(2) Composition: nucleus proteoglycan content

Intro

M&MResults

Discussion

HYPOTHESIS

Dynamic compression better preserves long-term disc integrity and functionality

In vivo protocol: rat tail

Growth modulation Growth resumption?

28 43 53Rat age in Days

Loading (15 days) No loading (10 days)

Surgery

6

Cd7

Cd7

Proximal Distal

Cd7

Cd7

Control (n = 6)

Sham(n = 6)

Static(n = 6)

Dynamic(n = 6)

StaticCompression

DynamicCompression

Intro

M&MResults

Discussion

(inspired by Walsh et al., 2004 ; Cancel et al., 2009 ; Valteau et al., 2011)

Micro-loading deviceDissection of4-week group

Dissection of2-week group

Dissection & measures

7

Intervertebral disc height

Intro

M&MResults

Discussion

Analyzed discs

Cd4 Cd5 Cd6 Cd7 Cd8

D45 D78

Collecting tissus

3D reconstruction of ex-vivo samples using microCT images

Disc height = mean value of six images cut through vertebra

Intervertebral disc measurements

Safranine-O staining (2.5X)Intensity level (ImageJ software)

8

Proteoglycan content in the nucleus

(Nb pixels) proteoglycanProteoglycan =

(Nb pixels) nucleus

Intro

M&MResults

Discussion

Nucleus/Annulus proportion: stereological method (Griffiths, 1993)

(Nb points) nucleusProportion =

(Nb points) annulus

Toluidine blue staining (2.5X)Grid (Gimp) + cell counter (ImageJ)

0.0

0.2

0.4

0.6

0.8

1.0

1.2

Intervertebral disc height

9

Both static and dynamic compressions disc height

Summary

Intro

M&MResults

Discussion

Disc height D78 normalized with D45 [μm/μm]

* **

4-week group2-week group

p = 0.056 & p = 0.052

One-way ANOVA, Tukey post-hoc comparisons, *p < 0.05 and **p < 0.01

Control ShamStatic Dynamic

Cd4 Cd5 Cd6 Cd7 Cd8

D78

Intervertebral disc composition

10

No difference observed for nucleus/annulus proportion After loading removal, proteoglycan for static but remained for dynamic

Intro

M&MResults

Discussion

Nucleus/Annulus proportion of D78 [μm/μm] Proteoglycan content in the nucleus for D78

2-week group 4-week group0.00

0.20

0.40

0.60

0.80

1.00

1.20

One-way ANOVA, Tukey post-hoc comparisons, **p < 0.01

0.00

0.05

0.10

0.15

0.20

0.25

0.30

0.35

0.40

0.45

0.50 **

2-week group 4-week group

**

Summary

Control ShamStatic Dynamic

Discussion

11

Intro

M&MResults

Discussion

Limitations One range of loading (magnitude/frequency) Rat discs: conservative model with more notochordal cells, therefore

better adaptation capabilities

Future work Inflammatory pathways within disc

Physiological loading range Magnitude below 1.0MPa &

frequency above 0.01Hz and below 1.0Hz preserve disc integrity (Iatridis et al., 2006)

Dynamic loading: preserve nucleus PG content even following compression removal

PG in the nucleus

COMPRESSION2-week group

REMOVING COMPRESSION4-week group

STAT

ICDY

NAM

IC

Funding & References

12

Intro

M&MResults

Discussion

Hunt KJ, Braun JT, Christensen BA. The Effect of Two Clinically Relevant Fusionless Scoliosis Implant Strategies on the Health of the Intervertebral Disc. Spine 2010;35: 371-7.

Aronsson DD, Stokes IAF. Nonfusion Treatment of Adolescent Idiopathic Scoliosis by Growth Modulation and Remodeling. J Pediatr Orthop 2011;31: S99-106.

Wuertz K, Godburn K, MacLean JJ, Barbir A, Stinnett Donnelly J, Roughley PJ, Alini, M, Iatridis JC. In Vivo Remodeling of Intervertebral Discs in Response to Short- and Long-Term Dynamic Compression. J Orthop Res 2009;27: 1235-42.

Sivan SS, Wachtel E, Roughley PJ. Structure, Function, Aging and Turnover of Aggrecan in the Intervertebral Disc. Biochimica et Biophysica Acta 2014;1840: 3181-9.

Walsh AJ, Lotz JC. Biological Response of the Intervertebral Disc to Dynamic Loading. J Biomech 2004;37: 329-37. Cancel M, Grimard G, Thuillard-Crisinel D, Moldovan F, Villemure I. Effects of In Vivo Static Compressive Loading on

Aggrecan and Type II and X Collagens in the Rat Growth Plate Extracellular Matrix. Bone 2009;44: 306-15. Valteau B, Grimard G, Londono I, Moldovan F, Villemure I. In Vivo Dynamic Bone Growth Modulation is Less Detrimental

but as Effective as Static Growth Modulation. Bone 2011;49: 996-1004. Griffiths G. Quantitative Aspects of Immunocytochemistry. In Fine Structure Immunocytochemistry. 1993: 371-445. Iatridis JC, MacLean JJ, Roughley PJ, Alini M. Effects of Mechanical Loading on Intervertebral Disc Metabolism In Vivo. J

Bone Joint Surg Am 2006;88: 41-46.

Funding sources:

References: