COX-2 Inhibition Mitigates Cytokine-Mediated Suppression of Matrix Proteoglycan and Collagen...

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STUDY DESIGN/SETTING: We used data from the nationwide SWISSspine BKP registry for finding predictors for a pain alleviation of at least 41 points (group mean). Inclusion criteria were a single-level ver- tebral fracture and availability of at least one followup within 6 months af- ter surgery. PATIENT SAMPLE: There were 194 female and 82 males with an aver- age age of 70.4 and 65.3 years, respectively. 61% of cases were treated for an osteoporotic fracture, 36.4% for a traumatic one, and 2.6% for a lytic fracture. Stratified by sex, 68.3% of women had an osteoporotic fracture, 29.1% a traumatic one and 2.6% a lytic fracture. In men the distribution was 43.8%, 53.8% and 2.4%, respectively. OUTCOME MEASURES: Back pain on COMI VAS score (Core Out- come Measures Index) METHODS: A logistic regression model was built with pain alleviation greater or smaller 41 points on VAS as the outcome. The following cova- riates were fed into the model and the significant ones were identified with backward elimination. Patient age was used as a continuous and gender as a categorized variable. The level of the monosegmental fracture respec- tively localization of the treatment was categorized into three groups: 1) thoracic vertebral bodies Th4-Th10, 2) thoraco-lumbar vertebrae Th11- L2 3) lumbar vertebrae L3-L5. Diagnosis was categorized as osteoporotic, traumatic and lytic. Pain was used as continuous co-variate 0-100. Fracture types were categorized as A.1.1, A.1.2, A.3.1 and other. Fracture age was detailed as lesser or more than 8 weeks. Cement extrusions were recorded as present or not present, independent of direction of extrusion or several extrusions from one and the same fracture site. Cement volumes were cat- egorized according to the SWISSspine BKP case report forms into !3 ml, 3-4.5 ml, 4.6-6 ml, 6.1-7.5 ml, and O7.5 ml but for the final model they were converted into a binary format with !54.5 ml and O 4.5 ml. The level of significance was set to a 5 0.05. All statistical analyses were con- ducted using SAS 9.2 (SAS Institute Inc, Cary, NC, USA). RESULTS: The average followup time was 106 days. Mean preoperative pain levels were 69.3 points on VAS 0-100, postoperative ones were 28.7 points. Stratified by sex mean preoperative pain levels were 71 (female) and 65.2 (male) points. The mean postoperative pain was 27.1 (female) and 32.4 (male) points. There were cement extrusion in 27.2% of cases. The location of fractures broke down in the following way: 10.6% of frac- tures were located between Th4-10, 71.8% between Th11-L2, and 17.6% between L3-L5. There were 200 fractures treated earlier than 8 weeks after their occurrence, and 76 treated later than 8 weeks. While patient age or diagnosis did not have a significant influence on achieving the average pain relief of 41 points, patient sex did. Female patients were about twice as likely for achieving this amount of pain relief compared to males (p50.04). The preoperative pain level was the strongest predictor in that the likelihood for achieving an at least 41 point pain relief increased by about 8% with each additional point of preoperative pain (p !0.001). Frac- ture characteristics: the location of fracture, simplified as thoracic, thoraco- lumbar or lumbar, did not have an influence on pain relief. The fracture type, however, did. An A3.1 fracture did only have about a third of the probability for achieving the average pain relief compared with an A1.1 fracture (p50.01). Fracture age in its binary outcome did not have a signif- icant influence. Operator dependent co-variates A cement extrusion did not influence the odds for achieving the average pain relief. Cement volume, however did. Volumes below 4.5 ml did only bring with them an about 40% chance for an at least 41 point pain alleviation as compared with ce- ment volumes of at least 4.5 ml (p50.009). The relationship between ce- ment volume and pain alleviation follows a dose dependent pattern With each category increase in cement volume and up to 7.5 ml, the proportion of patients with a pain relief of at least 41 points increases from 20% to 68.1%. Also, mean and median pain alleviation levels increased with each cement volume category and were the highest in the volume class of 6-7.5 ml. Cement volumes between 4.5 ml and 7.5 ml seem to be the ideal filling volumes for pain alleviation in BKP. CONCLUSIONS: After preoperative pain, cement volume was the second most important and operator dependent predictor for pain alleviation in BKP. Cement volumes of 4.5-7.5 ml should be targeted. FDA DEVICE/DRUG STATUS: Ballon kyphoplasty (Approved for this indication) http://dx.doi.org/10.1016/j.spinee.2012.08.290 P17. COX-2 Inhibition Mitigates Cytokine-Mediated Suppression of Matrix Proteoglycan and Collagen Syntheses in Human Disc Cells Nam Vo, PhD 1 , Gwendolyn A. Sowa, MD, PhD 2 , James D. Kang, MD 3 , Rebecca Studer, PhD 4 ; 1 LJPMC/Ferguson Lab, Pittsburgh, PA, US; 2 University of Pittsburgh, Pittsburgh, PA, US; 3 University of Pittsburg Medical Center, Pittsburgh, PA, US; 4 Pittsburgh, PA, US BACKGROUND CONTEXT: Back pain, often inflammatory and disco- genic in origin 1,2, is frequently treated with nonsteroidal anti-inflamma- tory drugs (NSAIDs). Most NSAIDs act to inhibit cyclooxygenase (COX), the biosynthetic enzyme that catalytically convert arachidonic acid into prostaglandins. Prostaglandins act as messenger molecules in the process of inflammation. However, little is still known about the effects of limiting prostaglandins on disc extracellular matrix of the prostaglandins whose synthesis and accumulation is diminished by these drugs 3. PURPOSE: To delineate prostaglandin actions in cytokine activated inter- vertebral disc cells by comparing matrix synthesis of disc cells in response to the pro-inflammatory cytokine IL-1beta with and without COX-2 inhibition. STUDY DESIGN/SETTING: Human disc cell cultures activated by IL- 1beta were treated with a chemical inhibitor of COX-2 to block prostaglan- din synthesis. OUTCOME MEASURES: Proteoglycan (PG) and collagen syntheses. METHODS: Human nucleus pulposus cells in alginate beads were acti- vated with IL-1beta 6 the COX-2 inhibitor Sc-58125. Proteoglycan syn- thesis (35S-sulfate incorporation), collagen synthesis (collagenase sensitive incorporation of 3H-L-proline) were measured. Conditioned me- dia were analyzed for the prostaglandin PGE2 and PGF2a. RESULTS: IL-1beta increased COX-2 expression and culture media PGE2 and PGF2a. IL-1beta decreased proteoglycan and collagen synthe- ses to 40% and 90% of the levels of untreated control, respectively. COX-2 inhibition in IL-1beta activated cells blocked PGE2 and PGF2a production and partially rescued proteoglycan synthesis (10%) and greatly increased collagen synthesis (50%). CONCLUSIONS: COX-2 inhibition alters matrix metabolism of disc cells in response to IL-1beta, suggesting IL-1beta action on disc cells is mediated at least in part through COX-2 and its prostaglandins. Blocking COX-2 might be beneficial for maintaining disc matrix since it provides an overall rescue of IL-1 induced loss of matrix protein synthesis. This impor- tant finding laid the groundwork for future studies to determine whether inhibiting prostaglandin synthesis can affect the course of disc degenera- tion and back pain. REFERENCES: 1. Freemont, AJ. Rheumatology 2009; 48(1):5-10.2. LeMaitre CL, et al., Arthritis Res & Therapy 2007; 9:R77.3. Vo, N et al., J Ortho Res 2010, 28(10):1259-66. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs. http://dx.doi.org/10.1016/j.spinee.2012.08.291 P18. Psychosocial Factors and Expectancy Contribute Separately to Spine Surgery Outcome Andrew R. Block, PhD 1 , Yossef S. Ben-Porath, PhD 2 , Donna D. Ohnmeiss, PhD 3 , Richard D. Guyer, MD 1 , Ryan J. Marek, BS 4 ; 1 Texas Back Institute, Plano, TX, US; 2 Copley, OH, US; 3 Texas Back Institute Research Foundation, Plano, TX, US; 4 Parma, OH, US BACKGROUND CONTEXT: Spine surgery is not always effective in providing pain relief and improvement in function. A growing body of re- search demonstrates that failure of surgical intervention may be predicted on the basis of an established presurgical psychosocial screening (PPS) 106S Proceedings of the NASS 27th Annual Meeting / The Spine Journal 12 (2012) 99S–165S All referenced figures and tables will be available at the Annual Meeting and will be included with the post-meeting online content.

Transcript of COX-2 Inhibition Mitigates Cytokine-Mediated Suppression of Matrix Proteoglycan and Collagen...

106S Proceedings of the NASS 27th Annual Meeting / The Spine Journal 12 (2012) 99S–165S

STUDY DESIGN/SETTING: We used data from the nationwide

SWISSspine BKP registry for finding predictors for a pain alleviation of

at least 41 points (group mean). Inclusion criteria were a single-level ver-

tebral fracture and availability of at least one followup within 6 months af-

ter surgery.

PATIENT SAMPLE: There were 194 female and 82 males with an aver-

age age of 70.4 and 65.3 years, respectively. 61% of cases were treated for

an osteoporotic fracture, 36.4% for a traumatic one, and 2.6% for a lytic

fracture. Stratified by sex, 68.3% of women had an osteoporotic fracture,

29.1% a traumatic one and 2.6% a lytic fracture. In men the distribution

was 43.8%, 53.8% and 2.4%, respectively.

OUTCOME MEASURES: Back pain on COMI VAS score (Core Out-

come Measures Index)

METHODS: A logistic regression model was built with pain alleviation

greater or smaller 41 points on VAS as the outcome. The following cova-

riates were fed into the model and the significant ones were identified with

backward elimination. Patient age was used as a continuous and gender as

a categorized variable. The level of the monosegmental fracture respec-

tively localization of the treatment was categorized into three groups: 1)

thoracic vertebral bodies Th4-Th10, 2) thoraco-lumbar vertebrae Th11-

L2 3) lumbar vertebrae L3-L5. Diagnosis was categorized as osteoporotic,

traumatic and lytic. Pain was used as continuous co-variate 0-100. Fracture

types were categorized as A.1.1, A.1.2, A.3.1 and other. Fracture age was

detailed as lesser or more than 8 weeks. Cement extrusions were recorded

as present or not present, independent of direction of extrusion or several

extrusions from one and the same fracture site. Cement volumes were cat-

egorized according to the SWISSspine BKP case report forms into!3 ml,

3-4.5 ml, 4.6-6 ml, 6.1-7.5 ml, and O7.5 ml but for the final model they

were converted into a binary format with !54.5 ml and O4.5 ml. The

level of significance was set to a 5 0.05. All statistical analyses were con-

ducted using SAS 9.2 (SAS Institute Inc, Cary, NC, USA).

RESULTS: The average followup time was 106 days. Mean preoperative

pain levels were 69.3 points on VAS 0-100, postoperative ones were 28.7

points. Stratified by sex mean preoperative pain levels were 71 (female)

and 65.2 (male) points. The mean postoperative pain was 27.1 (female)

and 32.4 (male) points. There were cement extrusion in 27.2% of cases.

The location of fractures broke down in the following way: 10.6% of frac-

tures were located between Th4-10, 71.8% between Th11-L2, and 17.6%

between L3-L5. There were 200 fractures treated earlier than 8 weeks after

their occurrence, and 76 treated later than 8 weeks. While patient age or

diagnosis did not have a significant influence on achieving the average pain

relief of 41 points, patient sex did. Female patients were about twice as

likely for achieving this amount of pain relief compared to males

(p50.04). The preoperative pain level was the strongest predictor in that

the likelihood for achieving an at least 41 point pain relief increased by

about 8% with each additional point of preoperative pain (p!0.001). Frac-

ture characteristics: the location of fracture, simplified as thoracic, thoraco-

lumbar or lumbar, did not have an influence on pain relief. The fracture

type, however, did. An A3.1 fracture did only have about a third of the

probability for achieving the average pain relief compared with an A1.1

fracture (p50.01). Fracture age in its binary outcome did not have a signif-

icant influence. Operator dependent co-variates A cement extrusion did not

influence the odds for achieving the average pain relief. Cement volume,

however did. Volumes below 4.5 ml did only bring with them an about

40% chance for an at least 41 point pain alleviation as compared with ce-

ment volumes of at least 4.5 ml (p50.009). The relationship between ce-

ment volume and pain alleviation follows a dose dependent pattern With

each category increase in cement volume and up to 7.5 ml, the proportion

of patients with a pain relief of at least 41 points increases from 20% to

68.1%. Also, mean and median pain alleviation levels increased with each

cement volume category and were the highest in the volume class of

6-7.5 ml. Cement volumes between 4.5 ml and 7.5 ml seem to be the ideal

filling volumes for pain alleviation in BKP.

CONCLUSIONS: After preoperative pain, cement volume was the second

most important and operator dependent predictor for pain alleviation in

BKP. Cement volumes of 4.5-7.5 ml should be targeted.

All referenced figures and tables will be available at the Annual Mee

FDA DEVICE/DRUG STATUS: Ballon kyphoplasty (Approved for this

indication)

http://dx.doi.org/10.1016/j.spinee.2012.08.290

P17. COX-2 Inhibition Mitigates Cytokine-Mediated Suppression of

Matrix Proteoglycan and Collagen Syntheses in Human Disc Cells

Nam Vo, PhD1, Gwendolyn A. Sowa, MD, PhD2, James D. Kang, MD3,

Rebecca Studer, PhD4; 1LJPMC/Ferguson Lab, Pittsburgh, PA, US;2University of Pittsburgh, Pittsburgh, PA, US; 3University of Pittsburg

Medical Center, Pittsburgh, PA, US; 4Pittsburgh, PA, US

BACKGROUND CONTEXT: Back pain, often inflammatory and disco-

genic in origin 1,2, is frequently treated with nonsteroidal anti-inflamma-

tory drugs (NSAIDs). Most NSAIDs act to inhibit cyclooxygenase (COX),

the biosynthetic enzyme that catalytically convert arachidonic acid into

prostaglandins. Prostaglandins act as messenger molecules in the process

of inflammation. However, little is still known about the effects of limiting

prostaglandins on disc extracellular matrix of the prostaglandins whose

synthesis and accumulation is diminished by these drugs 3.

PURPOSE: To delineate prostaglandin actions in cytokine activated inter-

vertebral disc cells by comparing matrix synthesis of disc cells in response

to the pro-inflammatory cytokine IL-1beta with and without COX-2

inhibition.

STUDY DESIGN/SETTING: Human disc cell cultures activated by IL-

1beta were treated with a chemical inhibitor of COX-2 to block prostaglan-

din synthesis.

OUTCOME MEASURES: Proteoglycan (PG) and collagen syntheses.

METHODS: Human nucleus pulposus cells in alginate beads were acti-

vated with IL-1beta 6 the COX-2 inhibitor Sc-58125. Proteoglycan syn-

thesis (35S-sulfate incorporation), collagen synthesis (collagenase

sensitive incorporation of 3H-L-proline) were measured. Conditioned me-

dia were analyzed for the prostaglandin PGE2 and PGF2a.

RESULTS: IL-1beta increased COX-2 expression and culture media

PGE2 and PGF2a. IL-1beta decreased proteoglycan and collagen synthe-

ses to 40% and 90% of the levels of untreated control, respectively. COX-2

inhibition in IL-1beta activated cells blocked PGE2 and PGF2a production

and partially rescued proteoglycan synthesis (10%) and greatly increased

collagen synthesis (50%).

CONCLUSIONS: COX-2 inhibition alters matrix metabolism of disc

cells in response to IL-1beta, suggesting IL-1beta action on disc cells is

mediated at least in part through COX-2 and its prostaglandins. Blocking

COX-2 might be beneficial for maintaining disc matrix since it provides an

overall rescue of IL-1 induced loss of matrix protein synthesis. This impor-

tant finding laid the groundwork for future studies to determine whether

inhibiting prostaglandin synthesis can affect the course of disc degenera-

tion and back pain. REFERENCES: 1. Freemont, AJ. Rheumatology

2009; 48(1):5-10.2. LeMaitre CL, et al., Arthritis Res & Therapy 2007;

9:R77.3. Vo, N et al., J Ortho Res 2010, 28(10):1259-66.

FDA DEVICE/DRUG STATUS: This abstract does not discuss or include

any applicable devices or drugs.

http://dx.doi.org/10.1016/j.spinee.2012.08.291

P18. Psychosocial Factors and Expectancy Contribute Separately to

Spine Surgery Outcome

Andrew R. Block, PhD1, Yossef S. Ben-Porath, PhD2, Donna D. Ohnmeiss,

PhD3, Richard D. Guyer, MD1, Ryan J. Marek, BS4; 1Texas Back Institute,

Plano, TX, US; 2Copley, OH, US; 3Texas Back Institute Research

Foundation, Plano, TX, US; 4Parma, OH, US

BACKGROUND CONTEXT: Spine surgery is not always effective in

providing pain relief and improvement in function. A growing body of re-

search demonstrates that failure of surgical intervention may be predicted

on the basis of an established presurgical psychosocial screening (PPS)

ting and will be included with the post-meeting online content.