16000644-01

Importance of Fracture Reduction and Anatomy Restoration in Patients with Vertebral Compression Fractures

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Common Beliefs and Practices

1. “No one has shown that vertebral deformity causes problems.”2. “I manage patients non-operatively for one to three months because the pain might

go away. I am performing balloon kyphoplasty to address pain.”3. “There is no evidence that kyphoplasty restores height.”4. “Sometimes I can restore height with balloon kyphoplasty, but it is not reliable.”5. “Vertebroplasty restores height.”6. “I perform balloon kyphoplasty because it is safer than vertebroplasty. I do not care

about fracture reduction.”7. “I do not perform balloon kyphoplasty on a fracture older than three months

because you cannot restore height in old fractures.”8. “Balloon kyphoplasty and vertebroplasty are pain operations. No one has shown

any difference in the pain benefit, so why should I spend more money or time to perform balloon kyphoplasty?”

9. “Ballon kyphoplasty increases the rate of adjacent fractures more than vertebroplasty, because bone cement stiffens the vertebral body, while vertebroplasty is better because it preserves the bone and only fills the trabeculae.”

10. “No one has shown any benefit to balloon kyphoplasty.”

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Consequences are independent of acute fracture pain

Impact of Deformity due to VCFs

Spinal deformity correlates with:• Impaired gait, poor balance (Gold 1996, Sinaki 2004)

• Disability, reduced quality of life (Leidig-Bruckner 1997)

• Reduced lung function (Leech 1990, Culham 1994, Schlaich 1998)

• Early satiety, gastric distress (Gold 1996)

• Future facture risk (Kado 2003)

• Excess mortality (Kado 1998, Kado 2004, Huang 2005)

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Kyphotic Deformity, Not Acute Back Pain, Accounts for Long-term Consequences

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Deformity Impairs Pulmonary Function

• Medically stable kyphotic patients with no acute back pain versus age-matched controls (n=30)

• Excluded patients with pre-existing pulmonary disease, previous spine surgery

*All differences p<0.05

Culham - Spine 1994

  Normal Osteoporosis % Diff

T1-T12 kyphosis (º) 34.9 58.3* 67%

Rib mobility (centimeters)

Anterior expansion 3.5 2.3* 34%

Lung volume (liters)

Total lung capacity 4.4 3.8* 14%

Vital capacity 2.7 2.2* 19%

Inspiratory capacity 2.2 1.6* 27%

Significant negative correlation between kyphosis angle and lung function measures

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Chronic Low Back Pain

Osteoporosis (≥1 VCF)

P value

Patients (n) 51 34 -

% Vital Capacity 105 94 <0.05

% Forced Expiratory Vol (1 sec) 92 85 <0.05

Schlaich – Osteoporos Int 1998

Kyphotic deformity reduces pulmonary function compared to chronic low back pain patients matched for back pain

Deformity Impairs Pulmonary Function

Adjusted for age, sex and height at age 25No acute back pain

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Lindsay – Osteoporos Int 2005

Prior Fracture Increases Future Fracture Risk

Lindsay 2001

• Lindsay 2001 analyzed VCF risk within one year in patients with 0, 1 or 2 or more prior VCFs. (JAMA 2001)

• Lindsay 2005 used the same patient cohort to analyze VCF risk within one year in patients with 0, 1, 2, 3, 4, 5, 6, 7, or 8 prior VCFs. (Osteoporos Int 2005)

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Black – J Bone Min Res 1999

Fracture Deformity and Risk

Increasing fracture risk with increasing deformity

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Future VCF Risk Predicted by Biomechanics

According to mechanical principles, kyphosis increases anterior stress, predicting increases in future fracture risk

W = body’s center of gravity M = muscles and ligaments in the back = vertebral body

Figures from Yuan – J Spinal Disord Tech 2004

16000644-01 10Silverman – Arthr Rheum 2000

1,425 women on 2 doses of an osteoporosisdrug or placebo, followed for 3 years

Correlation between Number of VCFs and Progressive Decrease in QOL

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Van Schoor – Osteo Int 2005

The Profound Impact of Radiographically-Detected VCF on QOL (SF-12)

• Study of 334 people ≥ 65 y.o. assessed by radiographs and SF-12

• Loss of quality of life in patients with radiographic vertebral fractures was comparable to that of patients with CHRONIC OBSTRUCTIVE PULMONARY DISORDER (COPD) OR CARDIAC DISEASE

• Patients with 3 or more VCFs had a loss of quality of life comparable to that of patients with STROKE OR CANCER

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Patients With Acute VCFs Do Not “Get Better”

• SF-36 Physical Function Scores unchanged at 2 years (Hallberg 2004)

• VCF patients treated with non-surgical management did not show improvement in pain and function compared to balloon kyphoplasty patients (Komp 2004, Grafe 2005)

• Worse SF-36 outcomes than hip fx patients at 2 and 5 years (Hallberg 2004, Hall 1999, Zethraeus 2002)

• Mortality greater than hip fx pts at 4-5 years (Cauley 2000, Johnell 2004)

• VCFs are NOT stable– Not always apparent on initial X-ray, collapse can take 18

months (Lyritis 1989, Heggeness 1993, Heggeness 1994, Komp 2004, Grafe 2005)

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• The highest standard of non-surgical management does not prevent deformity, leading to:– Future fracture– Impaired health – Loss of physical function– Loss of QOL

Reginster – Osteoporos Int 2002

Deformity alone leads to serious health consequences

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Orthopaedic Principles of Fracture Management

• Anatomy restoration• Rigid fixation• Minimal tissue disruption• Safe and early mobilization

Conservative management does not fulfill Orthopaedic principles of fracture management

Helfet – J Bone Joint Surg Am 2003

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Patient Outcomes After Balloon Kyphoplasty: Literature Summary

Number or Rate

Studies 35

Prospective 19 (54%)

Concurrently Controlled (with NSM) 2 (5.7%)

Retrospective 14 (40%)

Balloon Kyphoplasty Patients 1,888

Osteoporosis 1658 (88%)

Cancer 203 (12%)

Procedure-Related Complications, PMMA 0.32%

Procedure-Related Complications, All 1.06 %

Data on file at Kyphon. Studies reported in analysis provided at end of presentation.

Analysis current as of 04/2006

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Balloon Kyphoplasty Studies Consistently Show Positive Outcomes

Outcome

Osteoonly

Canceronly

Both Total

Pain (NRS or Descriptive) 18 3 7 28/28

Ambulation / Activities of Daily Living 6 0 3 9/9

Oswestry or Roland Morris Disability Indices 4 1 3 8/8

Karnofsky Score 1 0 0 1/1

SF-36 QOL Medical Outcomes Survey 1 1 2 4/4

Vertebral Height Restoration 11 4 7 22/23

Angular Deformity Correction (Kyphosis) 10 2 4 16/16

Data on file at Kyphon. Studies reported in analysis referenced at end of presentation.

Analysis current as of 04/2006

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Komp – J Miner Stoffwechs 2004

Prospective concurrently controlled studyN=19 KP, 17 NSM; mean fracture age 1 month

0

2

4

6

8

10

Baseline 6 wks 6 mo

VA

S P

ain

Rat

ing

Balloon Kyphoplasty

Non-surgical Management

* *

* p < 0.05, difference BK - NSM

0

20

40

60

80

100

Baseline 6 wks 6 mo

Osw

estr

y D

isab

ilit

y In

dex

Balloon KyphoplastyNon-surgical Management

* p < 0.05, difference BK - NSM

* *

VAS Pain Scores Oswestry Back Disability Index

Balloon Kyphoplasty Improved Pain and Function Compared to NSM in Pts with ACUTE Fxs

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Prospective concurrently controlled studyN=60 KP, 30 NSM; all fractures at least one year old

Balloon Kyphoplasty Improved Pain and Function Compared to NSM in Pts with CHRONIC Fxs

Similar results reported at one-year follow-up(Grafe – Osteoporos Int 2005)

* statistically significant difference BK-NSM (p = 0.007)** Scale: 0 = severe pain; 100 = no pain

(Kasperk - J Bone Miner Res 2005)

* statistically significant difference BK-NSM (p = 0.03)

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Crandall – Spine J 2004, Gaitanis – Eur Spine J 2005, Ledlie – Spine 2006

Anatomy Restoration with Balloon Kyphoplasty:Recent Height Restoration Results

Paper

% of Estimated Pre-Fracture Height%

ReduciblePre-op Post-op 2 yrs

Crandall-acute

Crandall-chronic

58%

56%

86%

79%

N/R

N/R

92%

80%

Gaitanis-midline

Gaitanis-anterior

71%

73%

87%

87%

N/R

N/R

92%

92%

Ledlie-midline

Ledlie-anterior

61%

61%

87%

81%

88%

81%

90%

N/R

N/R = Not Reported

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Anatomy Restoration With Balloon Kyphoplasty:Recent Angular Deformity Correction Results

Paper

Local Angulation (°) Last Follow-upReducible

(%)Pre (°) Post (°)

Corrected (%)

Follow-up (°)

Follow-up (%)

Gaitanis 16° 8° 53% N/R N/R 90%

Crandall-acute

Crandall-chronic

15°

15°

8°

10°

47%

34%

N/R

N/R

N/R

N/R

N/R

N/R

Open surgery 14° 4° 72% 10° 29% N/R

Crandall – Spine J 2004; Gaitanis – Eur Spine J 2005; Ledlie – Spine 2006Open surgery, 11 papers with modern pedicles screws published 1990-2003 (References provided at end of presentation)

N/R = Not Reported

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Anatomy Restoration With Balloon Kyphoplasty:Comparison to Postural Reduction

• Postural reduction through patient positioning provides some improvement

• Balloon kyphoplasty doubled improvement, and final height achieved after balloon kyphoplasty was maintained.

Voggenreiter – Spine 2006

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Anatomy Restoration with Balloon Kyphoplasty: Correction of Vertebral Morphology

* Definitions according to Genant – J Bone Miner Res 1993: Vertebral Fracture Assessment Using a Semiquantitative Technique

VBs abnormalities predict future fracture risk (Ismail – Osteoporos Int 2003)

Using osteoporosis literature definitions*, nearly 50% of VBs were normalized by KP (Ledlie – Spine 2006)

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Adjacent Fractures and Bone Cement

• Theory– Bone cement stiffness alters load transfer

in the spine– This leads to adjacent fractures

• Facts– Not true on mechanical principles– Not shown in biomechanical studies– Not demonstrated in clinical studies

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Functional Spine Unit (FSU)

VB

Disc

VB

Bone is MORE STIFF ~100 MPa

Disc is LESS STIFF < 3 MPa

Bone is MORE STIFF ~100 MPa

The Functional Spine Unit is Mechanically Equivalent to Three Springs in a Series

The Functional Spine Unit is Mechanically Equivalent to Three Springs in a Series

Biomechanics of the Spine

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The Response of the FSU to a Load is Driven byits Least Stiff Component, the Disc

The Response of the FSU to a Load is Driven byits Least Stiff Component, the Disc

Functional Spine Unit (FSU)

VB

Disc

VB

Load transfer is primarily

through the disc

Biomechanics of the Spine

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VB

Disc

VB

Stiffening the Stiffer Component Does Not Alter Load TransferStiffening the Stiffer Component Does Not Alter Load Transfer

Functional Spine Unit (FSU) with STIFF BIOMATERIAL

PMMA

PMMA

=

Vertebral augmentation helps restore normal mechanics to a fractured VB

PMMA

Biomechanics of the Spine

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Fusion Does Alter Load Transfer because the Least Stiff Component (the disc) has been stiffened

Fusion Does Alter Load Transfer because the Least Stiff Component (the disc) has been stiffened

FUSEDFunctional Spine Unit (FSU)

VB

VB PMMA

Biomechanics of the Spine

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Biomechanics: Stiffness

Table 3 from Kyphon’s White Paper – Feb 2006

Bone cement does not

increase VB stiffness beyond

prefracture state

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• Rates vary by study, not by method

• Cannot compare rates in these studies due to:– Different fracture definitions– Different time spans– Influence of confounding

factors: age, sex, BMD, prior fracture, and bone-affecting drugs (steroids)

Subsequent fracture rates cannot be interpreted unless the study population “controls” for all

important risk factors

Subsequent VCF Rates after using PMMA

Table 2 from Kyphon’s White Paper – Feb 2006

m

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Natural History of Subsequent VCFs

• 58% of patients had adjacent fractures (Silverman 2001)

• Likely explanations for adjacent fractures– Biomechanics: Stresses highest at apex of curve– Forces on index VB likely to damage nearby VBs– Adjacent fracture underway but overlooked

Silverman – Arthrit & Rheum 2001

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Balloon Kyphoplasty Reduced the Subsequent VCF Rate in Prospective Concurrently Controlled Studies

The only two prospective concurrently controlled balloon kyphoplasty vs. non-surgical mgmt studies show significant decrease in new fractures after balloon kyphoplasty

% Pts With Subsequent Fracture

65%50%

0%

10%

20%

30%

40%

50%

60%

70%

NSM KP

**

*

18%

38%

*p < 0.05**p < 0.02

Grafe Komp 1 yr 6 mo

Komp – J Miner Stoffwechs 2004; Grafe – Osteoporos Int 2005

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Collection of Level 1 Evidencefrom Clinical Studies in Progress

FREE (300 patient enrollment complete)

– Objective: Level I evidence that osteoporosis patients significantly benefit from balloon kyphoplasty compared to non-surgical management

CAFE (enrollment ongoing)

– Objective: Level I evidence that cancer patients significantly benefit from balloon kyphoplasty compared to non-surgical management

KAVIAR (study in development)

– Objective: Level I evidence that correcting spinal deformity results in balloon kyphoplasty superiority over vertebroplasty

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Meanwhile, the Clinical Literature Reports that Deformity Correction is Important

• Deformity

• Debilitation

• Disability

• Depression

• Death

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Although the complication rate with Balloon Kyphoplasty has been demonstrated to be low, as with most surgical procedures, there are risks associated with Balloon Kyphoplasty, including serious complications. For complete information regarding indications for use, warnings, precautions, adverse events and methods of use, please reference the devices’ Instructions for Use.

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References

Slide 3Gold – Bone. 1996;18(3 suppl):185S-189S

Sinaki et al. – Osteoporos Int. 2005;16(8):1004-10

Leidig-Bruckner et al. – J Bone Miner Res. 1997;12:663-675

Leech et al. – Am Rev Respir Dis. 1990;141:68-71

Culham et al. – Spine. 1994;19:1250-1255

Schlaich et al. – Osteoporos Int. 1998;8:261-267

Kado et al. – Osteoporos Int. 2003 Jul;14(7):589-94

Kado et al. – Arch Inter Med. 1999;159:1215-1220

Kado et al. – J Am Geriatr Soc. 2004;52(10):1662-1667

Huang et al. – J Bone Miner Res. 200621(3):419-423Slide 5

Culham et al. – Spine. 1994;19:1250-1255Slide 6

Schlaich et al. – Osteoporos Int. 1998;8:261-267Slide 7

Lindsay et al. – Osteoporos Int. 2005;16:306-312Slide 8

Black et al. – J Bone Miner Res. 1999;14:821-828Slide 9

Yuan et al. – J Spinal Disord Tech. 2004;17:236-242

Slide 10Silverman et al. – Arthritis Rheum. 2001 Nov;44(11):2611-9

Slide 11van Schoor et al. – Osteoporos Int. 2005;16(7):749-756

Slide 12Hallberg et al. – Osteoporos Int. 2004;15:834-841Hall et al. – Osteoporos Int. 1999;9:508-515Zethraeus et al. – SSE/EFI Working Paper Series in Economics

and Finance, No 512, October 2002Cauley et al. – Osteoporos Int. 2000;11:556-561Johnell et al. – Osteoporos Int. 2004;15:175-179Lyritis et al. – Clin Rheumatol. 1989;8(Suppl 2):66-69Heggeness et al. – Osteoporos Int. 1993;3(4):215-221Heggeness MH & Mathis KB – Chapter 57: An Orthopedic

Perspective of Osteoporosis. In Osteoporosis. Academic Press, Inc. 1996

Komp et al. – J Miner Stoffwech. 2004;(11(Suppl 1):13-15Grafe et al. – Osteoporos Int. 2005;16:2005-2012

Slide 13Reginster et al. – Osteoporos Int. 2000;11:83-91

Slide 14Helfet et al. – J Bone Joint Surg Am. 2003;85-A(6):1156-1160

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References (cont.)

Slides 15 and 161. Kasperk et al. – J Bone Miner Res. 2005;20(4):604-122. Komp et al. – J Miner Stoffwechs. 2004;11 (Suppl 1):13-53. Berlemann et al. Eur Spine J. 2004;13(6):496-5014. Coumans et al. – J Neurosurg. 2003;99(1):44-505. Crandall et al. – Spine J. 2004;4(4):418-246. Gaitanis et al. – Eur Spine J. 2005;14(3):250-2607. Garfin et al. – Spine. 2006;In press8. Gerszten et al. – Neurosurg Focus. 2005;18(3):e89. Grohs et al. – J Spinal Disord Tech. 2005;18(3):238-4210. Hillmeier et al. – Orthopade. 2004;33(1):31-911. Lane et al. – In: North American Spine Society; 2004;

Chicago, IL; 200412. Lieberman et al. – Spine. 2001;26(14):1631-813. Lieberman et al. – Clin Orthop Relat Res. 2003(415

Suppl):S176-8614. Phillips et al. – Spine. 2002;27(19):2173-8; discussion 8-915. Phillips et al. – Spine. 2003;28(19):2260-5; discussion 5-716. Villavicencio et al. – Neurosurg Focus. 2005;18(3):e3

17. Voggenreiter et al. – Med Review. 2004;1:7-818. Voggenreiter – Spine. 2005;30(24):2806-1219. Wilhelm et al. – Rofo. 2003;175(12):1690-620. Atalay et al. – Surg Neurol. 2005;64 Suppl 2:S72-621. Boszczyk et al. – Eur Spine J. 2005;14(10):992-922. Choe et al. – AJR Am J Roentgenol. 2004;183(4):1097-

10223. de Falco et al. – J Neurosurg Sci. 2005;49(4):147-5324. Feltes et al. – Neurosurg Focus. 2005;18(3):e525. Fourney et al. – J Neurosurg. 2003;98(1):21-3026. Fribourg et al. – Spine. 2004;29(20):2270-627. Garfin et al. – Spine. 2001;26(14):1511-528. Heini et al. – Eur Spine J. 2004;13(3):184-9229. Lane et al. – Orthop Clin North Am. 2002;33(2):431-8, viii30. Ledlie et al. – Spine. 2006;31(1):57-6431. Majd et al. – Spine J. 2005;5(3):244-5532. Masala et al. – In Vivo. 2004;18(2):149-5333. Masala et al. – Radiol Med (Torino). 2005;110(1-2):97-

10534. Rhyne et al. – J OrthopTrauma. 2004;18(5):294-935. Theodorou et al. – J Clin Imag. 2002;26:1-5

16000644-01 37

References (cont.)

Slide 17Komp et al. – J Miner Stoffwech. 2004;(11(Suppl 1):13-

15

Slide 18Kasperk et al. – J Bone Miner Res. 2005;20:604-612

Slides 19Crandall et al. – Spine J. 2004 Jul-Aug;4(4):418-24Gaitanis et al. – Eur Spine J. 2005;14(3):250-260Ledlie – Spine. 2006;31:57-64

Slide 20Crandall et al. – Spine J. 2004 Jul-Aug;4(4):418-24Gaitanis et al. – Spine J. 2005;5:45-54Ledlie – Spine. 2006;31:57-64Open Surgery papers (12):

1) Akahn et al. – Eur Spine J. 1994;3:1022) Alanay et al. – Spine. 2001;26:213-73) Bernucci et al. – Surg Neurol. 1994;42:234) Knop et al. – Spine. 2001;26:88-995) Leferink et al. – Eur Spine J. 2001;10:5176) Lindsey et al. – Spine. 1991;16:S140

Slide 20 (cont.)7) Oner et al. – Spine. 2002 Mar 15;27(6):629-36.8) Liu et al. – Zhonghua Yi Xue Za Zhi (Taipei).

1991;62:619-259) Muller et al. – Eur Spine J. 1999;8(4):284-910) Shen et al. – Spine. 2001;26:103811) Speth et al. – Acta Orthop Scand. 1995;66:406-1012) Wood et al. – J Bone Joint Surg Am. 2003;85-A:773-81.

Erratum in: J BoneJoint Surg Am. (2004) 86-A:1283

Slide 21Voggenreiter et al. – Spine. 2005;30:2806-2812

Slide 22Genant et al. – J Bone Miner Res. 1993 Sep;8(9):1137-48Ismail et al. – Osteoporos Int. 1999;9:206-213

Slide 30Silverman et al. – Arthritis Rheum. 2001 Nov;44(11):2611-9

Slide 31Komp et al. – J Miner Stoffwech. 2004;(11(Suppl 1):13-15Grafe et al. - Osteoporos Int. 2005;16:2005-2012.