Patrice Wendling

CHICAGO — Current hormone therapy use in postmenopausal women reduces cartilage turnover, Joanne M. Jordan, M.D., said at the 2004 World Congress on Osteoarthritis.

The study included 168 postmenopausal women, of whom 49% were African American, 23% were current hormone therapy (HT) users, and 63% had knee osteoarthritis (OA).

Rates of type II collagen cleavage measured by levels of the cartilage degradation assay and collagen II synthesis measured by type II procollagen (CPII) synthesis were lower in current HT users than in nonusers.

Taken together, these results demonstrate reduced collagen II turnover in HT users with and without osteoarthritis, Dr. Jordan reported in a poster at the meeting, sponsored by the Osteoarthritis Research Society International.

Dr. Jordan and colleagues at the Thurston Arthritis Research Center at the University of North Carolina at Chapel Hill previously reported that current HT use is associated with lower levels of serum cartilage oligomeric matrix protein, another marker of cartilage degradation.

In the current study, led by doctoral student Anca D. Dragomir, separate analyses of covariance models were used to evaluate the relationship between current HRT use and biomarker levels.

After controlling for ethnicity, age, body mass index, and knee OA status, only the reduction in mean CPII associated with current HT use was significantly associated with collagen II synthesis.

There was evidence of an association between current HT use and knee OA status for another biomarker, chondroitin sulphate epitope 846 (CSE 846), thought to be a marker of newly synthesized cartilage proteoglycan. HT users without OA had higher levels of CSE 846, compared with HT users with OA. This suggests that HT use could increase proteoglycan aggrecan production in postmenopausal women with no radiographic evidence of knee or hip OA.

CHICAGO — Current hormone therapy use in postmenopausal women reduces cartilage turnover, Joanne M. Jordan, M.D., said at the 2004 World Congress on Osteoarthritis.

The study included 168 postmenopausal women, of whom 49% were African American, 23% were current hormone therapy (HT) users, and 63% had knee osteoarthritis (OA).

Rates of type II collagen cleavage measured by levels of the cartilage degradation assay and collagen II synthesis measured by type II procollagen (CPII) synthesis were lower in current HT users than in nonusers.

Taken together, these results demonstrate reduced collagen II turnover in HT users with and without osteoarthritis, Dr. Jordan reported in a poster at the meeting, sponsored by the Osteoarthritis Research Society International.

Dr. Jordan and colleagues at the Thurston Arthritis Research Center at the University of North Carolina at Chapel Hill previously reported that current HT use is associated with lower levels of serum cartilage oligomeric matrix protein, another marker of cartilage degradation.

In the current study, led by doctoral student Anca D. Dragomir, separate analyses of covariance models were used to evaluate the relationship between current HRT use and biomarker levels.

After controlling for ethnicity, age, body mass index, and knee OA status, only the reduction in mean CPII associated with current HT use was significantly associated with collagen II synthesis.

There was evidence of an association between current HT use and knee OA status for another biomarker, chondroitin sulphate epitope 846 (CSE 846), thought to be a marker of newly synthesized cartilage proteoglycan. HT users without OA had higher levels of CSE 846, compared with HT users with OA. This suggests that HT use could increase proteoglycan aggrecan production in postmenopausal women with no radiographic evidence of knee or hip OA.

CHICAGO — Current hormone therapy use in postmenopausal women reduces cartilage turnover, Joanne M. Jordan, M.D., said at the 2004 World Congress on Osteoarthritis.

The study included 168 postmenopausal women, of whom 49% were African American, 23% were current hormone therapy (HT) users, and 63% had knee osteoarthritis (OA).

Rates of type II collagen cleavage measured by levels of the cartilage degradation assay and collagen II synthesis measured by type II procollagen (CPII) synthesis were lower in current HT users than in nonusers.

Taken together, these results demonstrate reduced collagen II turnover in HT users with and without osteoarthritis, Dr. Jordan reported in a poster at the meeting, sponsored by the Osteoarthritis Research Society International.

Dr. Jordan and colleagues at the Thurston Arthritis Research Center at the University of North Carolina at Chapel Hill previously reported that current HT use is associated with lower levels of serum cartilage oligomeric matrix protein, another marker of cartilage degradation.

In the current study, led by doctoral student Anca D. Dragomir, separate analyses of covariance models were used to evaluate the relationship between current HRT use and biomarker levels.

After controlling for ethnicity, age, body mass index, and knee OA status, only the reduction in mean CPII associated with current HT use was significantly associated with collagen II synthesis.

There was evidence of an association between current HT use and knee OA status for another biomarker, chondroitin sulphate epitope 846 (CSE 846), thought to be a marker of newly synthesized cartilage proteoglycan. HT users without OA had higher levels of CSE 846, compared with HT users with OA. This suggests that HT use could increase proteoglycan aggrecan production in postmenopausal women with no radiographic evidence of knee or hip OA.

CHICAGO — Tidal irrigation leads to more sustained benefits than intraarticular corticosteroid injections in patients with knee osteoarthritis, particularly in those without an effusion, Nigel K. Arden, M.D., said at the 2004 World Congress on Osteoarthritis.

Both treatments significantly improved pain and function at 2 weeks, according to results from a randomized, single-blinded, parallel group trial involving patients with symptomatic knee OA. But the benefits were maintained only in the irrigation group at 26 weeks.

Tidal irrigation, which involves infusing saline into the knee under local anesthesia to repeatedly distend the capsule, is thought to provide benefit by disrupting intraarticular adhesions and by cleansing away debris and inflammatory cytokines, said Dr. Arden of Southampton (England) University Hospitals NHS Trust.

The 150 study participants were randomized to intraarticular corticosteroid injections with 40 mg triamcinolone and 2 mL of 1% lidocaine or irrigation of the knee with 500–1,000 mL of normal saline.

At 2 weeks, pain scores had improved significantly from baseline, and there were no significant differences between treatment groups. The mean pain score for both groups was 243 at baseline, on a 0–500 scale. At 2 weeks scores fell to 168 in the steroid group and 155 in the irrigation group. At 26 weeks, significant pain relief was maintained only in the irrigation group (mean 173 vs. 232 for the steroid group). A similar pattern was seen for function at 26 weeks.

At baseline, 61% of patients had an effusion, and at 2 weeks' follow-up, there was little difference between treatment groups in this subset of patients.

By 26 weeks, however, only patients treated with tidal irrigation had significant improvement, and this was more marked in patients without an effusion.

Among patients without an effusion, the mean pain score for those treated with irrigation was 164 vs. 262 for patients treated with injections. Among patients with an effusion, the mean pain score for those treated with irrigation was 180 vs. 214 for patients treated with injections.

Patients' overall assessment of treatment was similar at 2 weeks' and 4 weeks' follow-up. But patients' self-assessments significantly favored tidal irrigation at 12 and 24 weeks, Dr. Arden said at the meeting, sponsored by the Osteoarthritis Research Society International.

Such findings in no way account for the placebo effect of the interventions, John D. Bradley, M.D., told this newspaper. Generally, “the more elaborate the intervention, the more potent the placebo effect.”

In their investigation, Dr. Bradley and colleagues at Indiana University, Indianapolis, tracked 180 randomized subjects with knee OA for up to 12 months following randomization to tidal irrigation or a sham procedure, which involved placement of a needle through the soft tissue and down to, but not through, the joint capsule. Both groups received intraarticular anesthesia with bupivacaine.

The investigators concluded that after adjusting for baseline differences between groups, there were no differences between outcomes from the real and the sham procedures (Arthritis Rheum. 2002; 46:100–8).

Dr. Bradley noted that psychological factors and the subjects' guesses regarding the identity of their treatment correlated with their response to treatment.

The controversial procedure is thought to disrupt intraarticular adhesions, and clear away debris and inflammatory cytokines. Courtesy Dr. Nigel K. Arden

CHICAGO — Tidal irrigation leads to more sustained benefits than intraarticular corticosteroid injections in patients with knee osteoarthritis, particularly in those without an effusion, Nigel K. Arden, M.D., said at the 2004 World Congress on Osteoarthritis.

Both treatments significantly improved pain and function at 2 weeks, according to results from a randomized, single-blinded, parallel group trial involving patients with symptomatic knee OA. But the benefits were maintained only in the irrigation group at 26 weeks.

Tidal irrigation, which involves infusing saline into the knee under local anesthesia to repeatedly distend the capsule, is thought to provide benefit by disrupting intraarticular adhesions and by cleansing away debris and inflammatory cytokines, said Dr. Arden of Southampton (England) University Hospitals NHS Trust.

The 150 study participants were randomized to intraarticular corticosteroid injections with 40 mg triamcinolone and 2 mL of 1% lidocaine or irrigation of the knee with 500–1,000 mL of normal saline.

At 2 weeks, pain scores had improved significantly from baseline, and there were no significant differences between treatment groups. The mean pain score for both groups was 243 at baseline, on a 0–500 scale. At 2 weeks scores fell to 168 in the steroid group and 155 in the irrigation group. At 26 weeks, significant pain relief was maintained only in the irrigation group (mean 173 vs. 232 for the steroid group). A similar pattern was seen for function at 26 weeks.

At baseline, 61% of patients had an effusion, and at 2 weeks' follow-up, there was little difference between treatment groups in this subset of patients.

By 26 weeks, however, only patients treated with tidal irrigation had significant improvement, and this was more marked in patients without an effusion.

Among patients without an effusion, the mean pain score for those treated with irrigation was 164 vs. 262 for patients treated with injections. Among patients with an effusion, the mean pain score for those treated with irrigation was 180 vs. 214 for patients treated with injections.

Patients' overall assessment of treatment was similar at 2 weeks' and 4 weeks' follow-up. But patients' self-assessments significantly favored tidal irrigation at 12 and 24 weeks, Dr. Arden said at the meeting, sponsored by the Osteoarthritis Research Society International.

Such findings in no way account for the placebo effect of the interventions, John D. Bradley, M.D., told this newspaper. Generally, “the more elaborate the intervention, the more potent the placebo effect.”

In their investigation, Dr. Bradley and colleagues at Indiana University, Indianapolis, tracked 180 randomized subjects with knee OA for up to 12 months following randomization to tidal irrigation or a sham procedure, which involved placement of a needle through the soft tissue and down to, but not through, the joint capsule. Both groups received intraarticular anesthesia with bupivacaine.

The investigators concluded that after adjusting for baseline differences between groups, there were no differences between outcomes from the real and the sham procedures (Arthritis Rheum. 2002; 46:100–8).

Dr. Bradley noted that psychological factors and the subjects' guesses regarding the identity of their treatment correlated with their response to treatment.

The controversial procedure is thought to disrupt intraarticular adhesions, and clear away debris and inflammatory cytokines. Courtesy Dr. Nigel K. Arden

CHICAGO — Tidal irrigation leads to more sustained benefits than intraarticular corticosteroid injections in patients with knee osteoarthritis, particularly in those without an effusion, Nigel K. Arden, M.D., said at the 2004 World Congress on Osteoarthritis.

Both treatments significantly improved pain and function at 2 weeks, according to results from a randomized, single-blinded, parallel group trial involving patients with symptomatic knee OA. But the benefits were maintained only in the irrigation group at 26 weeks.

Tidal irrigation, which involves infusing saline into the knee under local anesthesia to repeatedly distend the capsule, is thought to provide benefit by disrupting intraarticular adhesions and by cleansing away debris and inflammatory cytokines, said Dr. Arden of Southampton (England) University Hospitals NHS Trust.

The 150 study participants were randomized to intraarticular corticosteroid injections with 40 mg triamcinolone and 2 mL of 1% lidocaine or irrigation of the knee with 500–1,000 mL of normal saline.

At 2 weeks, pain scores had improved significantly from baseline, and there were no significant differences between treatment groups. The mean pain score for both groups was 243 at baseline, on a 0–500 scale. At 2 weeks scores fell to 168 in the steroid group and 155 in the irrigation group. At 26 weeks, significant pain relief was maintained only in the irrigation group (mean 173 vs. 232 for the steroid group). A similar pattern was seen for function at 26 weeks.

At baseline, 61% of patients had an effusion, and at 2 weeks' follow-up, there was little difference between treatment groups in this subset of patients.

By 26 weeks, however, only patients treated with tidal irrigation had significant improvement, and this was more marked in patients without an effusion.

Among patients without an effusion, the mean pain score for those treated with irrigation was 164 vs. 262 for patients treated with injections. Among patients with an effusion, the mean pain score for those treated with irrigation was 180 vs. 214 for patients treated with injections.

Patients' overall assessment of treatment was similar at 2 weeks' and 4 weeks' follow-up. But patients' self-assessments significantly favored tidal irrigation at 12 and 24 weeks, Dr. Arden said at the meeting, sponsored by the Osteoarthritis Research Society International.

Such findings in no way account for the placebo effect of the interventions, John D. Bradley, M.D., told this newspaper. Generally, “the more elaborate the intervention, the more potent the placebo effect.”

In their investigation, Dr. Bradley and colleagues at Indiana University, Indianapolis, tracked 180 randomized subjects with knee OA for up to 12 months following randomization to tidal irrigation or a sham procedure, which involved placement of a needle through the soft tissue and down to, but not through, the joint capsule. Both groups received intraarticular anesthesia with bupivacaine.

The investigators concluded that after adjusting for baseline differences between groups, there were no differences between outcomes from the real and the sham procedures (Arthritis Rheum. 2002; 46:100–8).

Dr. Bradley noted that psychological factors and the subjects' guesses regarding the identity of their treatment correlated with their response to treatment.

The controversial procedure is thought to disrupt intraarticular adhesions, and clear away debris and inflammatory cytokines. Courtesy Dr. Nigel K. Arden

CHICAGO — A new study suggests that three of the five criteria for inclusion in the pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, or PANDAS, subgroup could be narrowed and still provide clinically useful benchmarks.

The first criteria for this subgroup is that the children must meet a lifetime diagnostic criteria for obsessive-compulsive disorder (OCD) or a tic disorder, Lisa Snider, M.D., said at the annual meeting of the Society for Developmental and Behavioral Pediatrics.

“Some people are suggesting that anorexia nervosa, attention-deficit hyperactivity disorder, possibly even bipolar disorder could be triggered by infections like streptococcal infection,” Dr. Snider said. “Our research came out of a predisposition to thinking that OCD and tics are secondary to a dysfunction within the basal ganglia.

“Our original research was on patients with Sydenham's chorea, which is triggered by streptococcal infection, and felt to be a basal ganglia disorder.”

The criteria were defined in 1998 by colleague Susan Swedo, M.D., of the National Institute of Mental Health in Bethesda, Md. The criteria also have been used successfully to study the pathophysiology and clinical course of the PANDAS subgroup. But, some researchers have criticized the criteria as being too broad.

PANDAS is now defined by the presence of OCD and/or tic disorder, prepubertal onset, unique clinical course, association of neuropsychiatric symptoms with group A β-hemolytic streptococcal infections, and association with neurologic abnormalities during symptomatic periods.

Dr. Snider, along with some colleagues have suggested the three new criteria should be:

▸ A primary diagnosis of OCD or prominent obsessive-compulsive features (criterion 1).

▸ Abrupt onset of neuropsychiatric symptoms reaching clinical impairment in less than 48 hours or a period of complete neuropsychiatric symptom remission (criterion 2).

▸ A positive throat culture in the 2 months prior to or elevated antistreptococcal titers drawn between 3 weeks and 3 months after neuropsychiatric symptom onset or exacerbation (criterion 3).

“The criteria haven't radically changed, but they are tighter and much more specific, she said. That should help clinicians and researchers,” Dr. Snider told this publication. “If you see someone for the first time, you have a better chance now of saying if this is PANDAS or not, because we don't have a blood test for this disorder.”

The latest study included 30 boys and 20 girls, who met the original PANDAS criteria.

The mean age for the group was 8.2 years.

Thirty-eight of the patients (76%) had a primary diagnosis of OCD and 12 patients (24%) had a primary diagnosis of tic disorder.

Of the 12 patients with a primary tic disorder, 9 (75%) had comorbid OCD or significant obsessive-compulsive symptoms. Only three patients had a tic disorder without obsessive-compulsive features.

The results were equally clear with regard to criterion 2, Dr. Snider said. Forty-four of the 50 patients (88%) had an abrupt onset of symptoms reaching clinical impairment in less than 48 hours. Of the remaining six patients, four had at least one period of complete symptom remission.

Finally, each of the 50 patients reportedly had a group A β-hemolytic streptococcal infection, which was associated with onset or exacerbation. Infection was identified in 23% of patients at presentation. “Three of the five criteria for inclusion in the PANDAS subgroup could be narrowed and still include 95% of this cohort,” Dr. Snider said.

CHICAGO — A new study suggests that three of the five criteria for inclusion in the pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, or PANDAS, subgroup could be narrowed and still provide clinically useful benchmarks.

The first criteria for this subgroup is that the children must meet a lifetime diagnostic criteria for obsessive-compulsive disorder (OCD) or a tic disorder, Lisa Snider, M.D., said at the annual meeting of the Society for Developmental and Behavioral Pediatrics.

“Some people are suggesting that anorexia nervosa, attention-deficit hyperactivity disorder, possibly even bipolar disorder could be triggered by infections like streptococcal infection,” Dr. Snider said. “Our research came out of a predisposition to thinking that OCD and tics are secondary to a dysfunction within the basal ganglia.

“Our original research was on patients with Sydenham's chorea, which is triggered by streptococcal infection, and felt to be a basal ganglia disorder.”

The criteria were defined in 1998 by colleague Susan Swedo, M.D., of the National Institute of Mental Health in Bethesda, Md. The criteria also have been used successfully to study the pathophysiology and clinical course of the PANDAS subgroup. But, some researchers have criticized the criteria as being too broad.

PANDAS is now defined by the presence of OCD and/or tic disorder, prepubertal onset, unique clinical course, association of neuropsychiatric symptoms with group A β-hemolytic streptococcal infections, and association with neurologic abnormalities during symptomatic periods.

Dr. Snider, along with some colleagues have suggested the three new criteria should be:

▸ A primary diagnosis of OCD or prominent obsessive-compulsive features (criterion 1).

▸ Abrupt onset of neuropsychiatric symptoms reaching clinical impairment in less than 48 hours or a period of complete neuropsychiatric symptom remission (criterion 2).

▸ A positive throat culture in the 2 months prior to or elevated antistreptococcal titers drawn between 3 weeks and 3 months after neuropsychiatric symptom onset or exacerbation (criterion 3).

“The criteria haven't radically changed, but they are tighter and much more specific, she said. That should help clinicians and researchers,” Dr. Snider told this publication. “If you see someone for the first time, you have a better chance now of saying if this is PANDAS or not, because we don't have a blood test for this disorder.”

The latest study included 30 boys and 20 girls, who met the original PANDAS criteria.

The mean age for the group was 8.2 years.

Thirty-eight of the patients (76%) had a primary diagnosis of OCD and 12 patients (24%) had a primary diagnosis of tic disorder.

Of the 12 patients with a primary tic disorder, 9 (75%) had comorbid OCD or significant obsessive-compulsive symptoms. Only three patients had a tic disorder without obsessive-compulsive features.

The results were equally clear with regard to criterion 2, Dr. Snider said. Forty-four of the 50 patients (88%) had an abrupt onset of symptoms reaching clinical impairment in less than 48 hours. Of the remaining six patients, four had at least one period of complete symptom remission.

Finally, each of the 50 patients reportedly had a group A β-hemolytic streptococcal infection, which was associated with onset or exacerbation. Infection was identified in 23% of patients at presentation. “Three of the five criteria for inclusion in the PANDAS subgroup could be narrowed and still include 95% of this cohort,” Dr. Snider said.

CHICAGO — A new study suggests that three of the five criteria for inclusion in the pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, or PANDAS, subgroup could be narrowed and still provide clinically useful benchmarks.

The first criteria for this subgroup is that the children must meet a lifetime diagnostic criteria for obsessive-compulsive disorder (OCD) or a tic disorder, Lisa Snider, M.D., said at the annual meeting of the Society for Developmental and Behavioral Pediatrics.

“Some people are suggesting that anorexia nervosa, attention-deficit hyperactivity disorder, possibly even bipolar disorder could be triggered by infections like streptococcal infection,” Dr. Snider said. “Our research came out of a predisposition to thinking that OCD and tics are secondary to a dysfunction within the basal ganglia.

“Our original research was on patients with Sydenham's chorea, which is triggered by streptococcal infection, and felt to be a basal ganglia disorder.”

The criteria were defined in 1998 by colleague Susan Swedo, M.D., of the National Institute of Mental Health in Bethesda, Md. The criteria also have been used successfully to study the pathophysiology and clinical course of the PANDAS subgroup. But, some researchers have criticized the criteria as being too broad.

PANDAS is now defined by the presence of OCD and/or tic disorder, prepubertal onset, unique clinical course, association of neuropsychiatric symptoms with group A β-hemolytic streptococcal infections, and association with neurologic abnormalities during symptomatic periods.

Dr. Snider, along with some colleagues have suggested the three new criteria should be:

▸ A primary diagnosis of OCD or prominent obsessive-compulsive features (criterion 1).

▸ Abrupt onset of neuropsychiatric symptoms reaching clinical impairment in less than 48 hours or a period of complete neuropsychiatric symptom remission (criterion 2).

▸ A positive throat culture in the 2 months prior to or elevated antistreptococcal titers drawn between 3 weeks and 3 months after neuropsychiatric symptom onset or exacerbation (criterion 3).

“The criteria haven't radically changed, but they are tighter and much more specific, she said. That should help clinicians and researchers,” Dr. Snider told this publication. “If you see someone for the first time, you have a better chance now of saying if this is PANDAS or not, because we don't have a blood test for this disorder.”

The latest study included 30 boys and 20 girls, who met the original PANDAS criteria.

The mean age for the group was 8.2 years.

Thirty-eight of the patients (76%) had a primary diagnosis of OCD and 12 patients (24%) had a primary diagnosis of tic disorder.

Of the 12 patients with a primary tic disorder, 9 (75%) had comorbid OCD or significant obsessive-compulsive symptoms. Only three patients had a tic disorder without obsessive-compulsive features.

The results were equally clear with regard to criterion 2, Dr. Snider said. Forty-four of the 50 patients (88%) had an abrupt onset of symptoms reaching clinical impairment in less than 48 hours. Of the remaining six patients, four had at least one period of complete symptom remission.

Finally, each of the 50 patients reportedly had a group A β-hemolytic streptococcal infection, which was associated with onset or exacerbation. Infection was identified in 23% of patients at presentation. “Three of the five criteria for inclusion in the PANDAS subgroup could be narrowed and still include 95% of this cohort,” Dr. Snider said.

CHICAGO —A patient's psychological state appears more predictive than physical abnormalities of outcomes from persistent benign low back pain following herniated disk surgery, according to the conclusions of a prospective, longitudinal study.

The hypothesis from the outset was that physical findings such as disk degeneration, annular disruption, and end-plate changes would most strongly predict serious future low back pain events.

However, the data did not support that theory, lead investigator Eugene J. Carragee, M.D., said at the annual meeting of the North American Spine Society.

In fact, psychosocial variables were strongly predictive of both long- and short-term disability events and health care visits for low back pain problems. Smoking and a previous workers' compensation claim also were predictive of outcomes, said Dr. Carragee of Stanford (Calif.) University.

Patients most likely to have periods of remission from their low back pain were those who were psychologically healthy, as well as those who stopped working a heavy labor job, and those who did not have chronic nonlumbar pain.

Of the physical findings, only moderate or severe Modic changes of the vertebral end plate were weakly associated with an adverse outcome.

The cohort of 100 patients had known risk factors for degenerative lumbar disk disease and a history of mild, persistent, but nondisabling, low back pain lasting more than 2 years after herniated disk surgery.

Patient selection was biased (ratio 2:1) to subjects with a history of chronic nonlumbar pain, as this group is known to be at greater risk for both increased psychosocial and neurophysiologic complications.

At baseline, 22% of patients were distressed or at risk of being distressed according to blinded psychometric testing, and 69% had other chronic pain syndromes, he said.

Physical exams and MRI studies revealed that 70% of patients had degenerated disks and 30% had annular fissures.

During the 5-year follow-up period, there were 134 back pain episodes without disability and 17 episodes with disability including four patients who went on long-term disability.

Positive findings observed in 12 of 25 patients who underwent experimental discography at baseline were not predictive of future episodes of back pain.

Instead, distress at baseline was associated with all the major adverse events.

Distressed patients had more weeks of long-term disability, and suffered additional short-term work loss (0.42 episodes versus 0.015 episodes among the nondistressed patients).

Remission of 6 months or longer was reported by 26 patients, and was strongly associated with a decrease in performing heavy labor. The distressed group did not report any 6-month periods of remission, Dr. Carragee said.

Distressed patients used considerably more medical resources, compared with nondistressed patients (3.25 visits per year vs. 0.003 visits, respectively).

During the study, there were 12 new workers' compensation or litigation claims made for low back conditions, half of which were filed by distressed patients early in the study, three by patients deemed at risk of being distressed, and three by patients with normal psychometric scores.

Workers' compensation claims for low back problems were strongly associated with long-term disability, severe back pain episodes, short-term disability, and medical care utilization, Dr. Carragee said at the meeting.

Current smoking status increased the likelihood of short-term disability, long-term disability, and the frequency of back pain episodes, but there was no significant association between smoking and health care visits or remission rates.

CHICAGO —A patient's psychological state appears more predictive than physical abnormalities of outcomes from persistent benign low back pain following herniated disk surgery, according to the conclusions of a prospective, longitudinal study.

The hypothesis from the outset was that physical findings such as disk degeneration, annular disruption, and end-plate changes would most strongly predict serious future low back pain events.

However, the data did not support that theory, lead investigator Eugene J. Carragee, M.D., said at the annual meeting of the North American Spine Society.

In fact, psychosocial variables were strongly predictive of both long- and short-term disability events and health care visits for low back pain problems. Smoking and a previous workers' compensation claim also were predictive of outcomes, said Dr. Carragee of Stanford (Calif.) University.

Patients most likely to have periods of remission from their low back pain were those who were psychologically healthy, as well as those who stopped working a heavy labor job, and those who did not have chronic nonlumbar pain.

Of the physical findings, only moderate or severe Modic changes of the vertebral end plate were weakly associated with an adverse outcome.

The cohort of 100 patients had known risk factors for degenerative lumbar disk disease and a history of mild, persistent, but nondisabling, low back pain lasting more than 2 years after herniated disk surgery.

Patient selection was biased (ratio 2:1) to subjects with a history of chronic nonlumbar pain, as this group is known to be at greater risk for both increased psychosocial and neurophysiologic complications.

At baseline, 22% of patients were distressed or at risk of being distressed according to blinded psychometric testing, and 69% had other chronic pain syndromes, he said.

Physical exams and MRI studies revealed that 70% of patients had degenerated disks and 30% had annular fissures.

During the 5-year follow-up period, there were 134 back pain episodes without disability and 17 episodes with disability including four patients who went on long-term disability.

Positive findings observed in 12 of 25 patients who underwent experimental discography at baseline were not predictive of future episodes of back pain.

Instead, distress at baseline was associated with all the major adverse events.

Distressed patients had more weeks of long-term disability, and suffered additional short-term work loss (0.42 episodes versus 0.015 episodes among the nondistressed patients).

Remission of 6 months or longer was reported by 26 patients, and was strongly associated with a decrease in performing heavy labor. The distressed group did not report any 6-month periods of remission, Dr. Carragee said.

Distressed patients used considerably more medical resources, compared with nondistressed patients (3.25 visits per year vs. 0.003 visits, respectively).

During the study, there were 12 new workers' compensation or litigation claims made for low back conditions, half of which were filed by distressed patients early in the study, three by patients deemed at risk of being distressed, and three by patients with normal psychometric scores.

Workers' compensation claims for low back problems were strongly associated with long-term disability, severe back pain episodes, short-term disability, and medical care utilization, Dr. Carragee said at the meeting.

Current smoking status increased the likelihood of short-term disability, long-term disability, and the frequency of back pain episodes, but there was no significant association between smoking and health care visits or remission rates.

CHICAGO —A patient's psychological state appears more predictive than physical abnormalities of outcomes from persistent benign low back pain following herniated disk surgery, according to the conclusions of a prospective, longitudinal study.

The hypothesis from the outset was that physical findings such as disk degeneration, annular disruption, and end-plate changes would most strongly predict serious future low back pain events.

However, the data did not support that theory, lead investigator Eugene J. Carragee, M.D., said at the annual meeting of the North American Spine Society.

In fact, psychosocial variables were strongly predictive of both long- and short-term disability events and health care visits for low back pain problems. Smoking and a previous workers' compensation claim also were predictive of outcomes, said Dr. Carragee of Stanford (Calif.) University.

Patients most likely to have periods of remission from their low back pain were those who were psychologically healthy, as well as those who stopped working a heavy labor job, and those who did not have chronic nonlumbar pain.

Of the physical findings, only moderate or severe Modic changes of the vertebral end plate were weakly associated with an adverse outcome.

The cohort of 100 patients had known risk factors for degenerative lumbar disk disease and a history of mild, persistent, but nondisabling, low back pain lasting more than 2 years after herniated disk surgery.

Patient selection was biased (ratio 2:1) to subjects with a history of chronic nonlumbar pain, as this group is known to be at greater risk for both increased psychosocial and neurophysiologic complications.

At baseline, 22% of patients were distressed or at risk of being distressed according to blinded psychometric testing, and 69% had other chronic pain syndromes, he said.

Physical exams and MRI studies revealed that 70% of patients had degenerated disks and 30% had annular fissures.

During the 5-year follow-up period, there were 134 back pain episodes without disability and 17 episodes with disability including four patients who went on long-term disability.

Positive findings observed in 12 of 25 patients who underwent experimental discography at baseline were not predictive of future episodes of back pain.

Instead, distress at baseline was associated with all the major adverse events.

Distressed patients had more weeks of long-term disability, and suffered additional short-term work loss (0.42 episodes versus 0.015 episodes among the nondistressed patients).

Remission of 6 months or longer was reported by 26 patients, and was strongly associated with a decrease in performing heavy labor. The distressed group did not report any 6-month periods of remission, Dr. Carragee said.

Distressed patients used considerably more medical resources, compared with nondistressed patients (3.25 visits per year vs. 0.003 visits, respectively).

During the study, there were 12 new workers' compensation or litigation claims made for low back conditions, half of which were filed by distressed patients early in the study, three by patients deemed at risk of being distressed, and three by patients with normal psychometric scores.

Workers' compensation claims for low back problems were strongly associated with long-term disability, severe back pain episodes, short-term disability, and medical care utilization, Dr. Carragee said at the meeting.

Current smoking status increased the likelihood of short-term disability, long-term disability, and the frequency of back pain episodes, but there was no significant association between smoking and health care visits or remission rates.

CHICAGO — Waist circumference appears to be an important and previously unrecognized indicator of knee osteoarthritis risk in men, Lauren M. Abbate reported at the 2004 World Congress on Osteoarthritis.

Men with a waist circumference greater than 108 cm were twice as likely to have knee osteoarthritis (OA) than were men with a waist circumference less than 95 cm, according to findings from the Johnston County Osteoarthritis Project, which involved a randomly selected group of 849 women and 458 men from Johnston County in North Carolina.

Among women there was a stronger association between body mass index (BMI) or weight and knee OA compared with men, added Ms. Abbate, an epidemiology doctoral student at the University of North Carolina at Chapel Hill.

Large waist circumference among women was associated with an increased risk of knee OA in the study, but not independently of BMI. This finding is similar to data reported from the population-based Chingford Study.

Previous OA studies have shown that the effect of BMI differs by gender, but have not evaluated the effect using measures of body fat distribution or composition.

Investigators at UNC's Thurston Arthritis Research Center assessed body composition using dual-energy X-ray absorptiometry (DXA), and assessed body fat distribution using waist and hip circumferences. Radiographic knee OA was defined as a Kellgren-Lawrence grade of 2 or more.

The mean age of the participants was 65 years for both men and women; 27% of the women and 16% of the men were African American.

In women, the mean BMI was 30 kg/m2 and mean weight was 77 kg, and in men, mean BMI was 29 kg/m2 and mean weight 89 kg.

Body composition variables associated with higher odds of knee OA in women included fat mass (OR 4.47), percent fat mass (OR 3.25), and lean mass (OR 3.18).

By contrast, in men, waist circumference was the only variable significantly associated with the knee OA (2.47). Waist size was also significantly associated with the disease in women (OR 4.33).

Waist-to-hip ratio was not significantly associated with knee OA in women (OR 1.56) or men (OR 1.21). After adjustment for BMI, none of the associations with body composition or body fat distribution variables and knee OA in women remained significant. Waist circumference in men, however, remained a statistically significant predictor of knee OA (OR 3.46).

The findings underscore the importance of weight management for OA, particularly among women, Ms. Abbate said at the meeting, which was sponsored by the Osteoarthritis Research Society International.

Waist circumference in men is a previously overlooked risk factor for knee OA, above and beyond BMI, senior author and UNC associate professor of medicine Joanne M. Jordan, M.D., told this newspaper.

“This study suggests that in women, BMI is highly associated with radiographic knee osteoarthritis, and that other measures of obesity such as body composition may not be necessary beyond BMI,” Dr. Jordan said. “It also suggests that BMI may not be the best measurement of obesity when assessing risk among men, and that we should investigate the waist circumference measurements in more detail.”

CHICAGO — Waist circumference appears to be an important and previously unrecognized indicator of knee osteoarthritis risk in men, Lauren M. Abbate reported at the 2004 World Congress on Osteoarthritis.

Men with a waist circumference greater than 108 cm were twice as likely to have knee osteoarthritis (OA) than were men with a waist circumference less than 95 cm, according to findings from the Johnston County Osteoarthritis Project, which involved a randomly selected group of 849 women and 458 men from Johnston County in North Carolina.

Among women there was a stronger association between body mass index (BMI) or weight and knee OA compared with men, added Ms. Abbate, an epidemiology doctoral student at the University of North Carolina at Chapel Hill.

Large waist circumference among women was associated with an increased risk of knee OA in the study, but not independently of BMI. This finding is similar to data reported from the population-based Chingford Study.

Previous OA studies have shown that the effect of BMI differs by gender, but have not evaluated the effect using measures of body fat distribution or composition.

Investigators at UNC's Thurston Arthritis Research Center assessed body composition using dual-energy X-ray absorptiometry (DXA), and assessed body fat distribution using waist and hip circumferences. Radiographic knee OA was defined as a Kellgren-Lawrence grade of 2 or more.

The mean age of the participants was 65 years for both men and women; 27% of the women and 16% of the men were African American.

In women, the mean BMI was 30 kg/m2 and mean weight was 77 kg, and in men, mean BMI was 29 kg/m2 and mean weight 89 kg.

Body composition variables associated with higher odds of knee OA in women included fat mass (OR 4.47), percent fat mass (OR 3.25), and lean mass (OR 3.18).

By contrast, in men, waist circumference was the only variable significantly associated with the knee OA (2.47). Waist size was also significantly associated with the disease in women (OR 4.33).

Waist-to-hip ratio was not significantly associated with knee OA in women (OR 1.56) or men (OR 1.21). After adjustment for BMI, none of the associations with body composition or body fat distribution variables and knee OA in women remained significant. Waist circumference in men, however, remained a statistically significant predictor of knee OA (OR 3.46).

The findings underscore the importance of weight management for OA, particularly among women, Ms. Abbate said at the meeting, which was sponsored by the Osteoarthritis Research Society International.

Waist circumference in men is a previously overlooked risk factor for knee OA, above and beyond BMI, senior author and UNC associate professor of medicine Joanne M. Jordan, M.D., told this newspaper.

“This study suggests that in women, BMI is highly associated with radiographic knee osteoarthritis, and that other measures of obesity such as body composition may not be necessary beyond BMI,” Dr. Jordan said. “It also suggests that BMI may not be the best measurement of obesity when assessing risk among men, and that we should investigate the waist circumference measurements in more detail.”

CHICAGO — Waist circumference appears to be an important and previously unrecognized indicator of knee osteoarthritis risk in men, Lauren M. Abbate reported at the 2004 World Congress on Osteoarthritis.

Men with a waist circumference greater than 108 cm were twice as likely to have knee osteoarthritis (OA) than were men with a waist circumference less than 95 cm, according to findings from the Johnston County Osteoarthritis Project, which involved a randomly selected group of 849 women and 458 men from Johnston County in North Carolina.

Among women there was a stronger association between body mass index (BMI) or weight and knee OA compared with men, added Ms. Abbate, an epidemiology doctoral student at the University of North Carolina at Chapel Hill.

Large waist circumference among women was associated with an increased risk of knee OA in the study, but not independently of BMI. This finding is similar to data reported from the population-based Chingford Study.

Previous OA studies have shown that the effect of BMI differs by gender, but have not evaluated the effect using measures of body fat distribution or composition.

Investigators at UNC's Thurston Arthritis Research Center assessed body composition using dual-energy X-ray absorptiometry (DXA), and assessed body fat distribution using waist and hip circumferences. Radiographic knee OA was defined as a Kellgren-Lawrence grade of 2 or more.

The mean age of the participants was 65 years for both men and women; 27% of the women and 16% of the men were African American.

In women, the mean BMI was 30 kg/m2 and mean weight was 77 kg, and in men, mean BMI was 29 kg/m2 and mean weight 89 kg.

Body composition variables associated with higher odds of knee OA in women included fat mass (OR 4.47), percent fat mass (OR 3.25), and lean mass (OR 3.18).

By contrast, in men, waist circumference was the only variable significantly associated with the knee OA (2.47). Waist size was also significantly associated with the disease in women (OR 4.33).

Waist-to-hip ratio was not significantly associated with knee OA in women (OR 1.56) or men (OR 1.21). After adjustment for BMI, none of the associations with body composition or body fat distribution variables and knee OA in women remained significant. Waist circumference in men, however, remained a statistically significant predictor of knee OA (OR 3.46).

The findings underscore the importance of weight management for OA, particularly among women, Ms. Abbate said at the meeting, which was sponsored by the Osteoarthritis Research Society International.

Waist circumference in men is a previously overlooked risk factor for knee OA, above and beyond BMI, senior author and UNC associate professor of medicine Joanne M. Jordan, M.D., told this newspaper.

“This study suggests that in women, BMI is highly associated with radiographic knee osteoarthritis, and that other measures of obesity such as body composition may not be necessary beyond BMI,” Dr. Jordan said. “It also suggests that BMI may not be the best measurement of obesity when assessing risk among men, and that we should investigate the waist circumference measurements in more detail.”

CHICAGO — Use of a laterally wedged insole with strapping of the subtalar joint can improve pain and correct abnormal biomechanics due to varus alignment in medial compartment osteoarthritis of the knee, Yoshitaka Toda, M.D., said at the 2004 World Congress on Osteoarthritis.

The idea is that an insole can correct varus alignment by creating valgus correction, resulting in a reduction of medial knee joint surface loading, said Dr. Toda, who has an orthopedic rheumatology practice in Osaka, Japan.

Previous attempts to achieve such a correction with a shoe insert haven't been successful, he said, perhaps because of movement of the talus.

Instead, an insole that's fixed in place with subtalar strapping prevents the talus from moving and creates tension to correct the femorotibial angle, he explained.

In a study designed to assess the optimal daily usage of the device, which was developed and patented by Dr. Toda, 81 women with knee osteoarthritis were randomly assigned to wear the insole for less than 5 hours a day (short group), between 5 hours and 10 hours (medium group), for more than 10 hours (long group), or to wear a placebo subtalar strapping band without the wedge insert. Both of the groups were treated for 2 weeks.

All patients also were treated with oral NSAIDs twice a day as adjunctive therapy. There were no differences between groups in terms of age, disease duration, body mass, height, or femorotibial angle.

All patients with varus knee osteoarthritis who wore the orthotic device daily had a significantly greater valgus correction of the femorotibial angle on standing radiographs than did patients in the placebo group.

The average time spent actually wearing the device was 3.5 hours in the short group, 6.9 hours in the medium group, and 14.2 hours in the long group, according to patient diaries.

The optimal time for wearing the device appears to be between 5 and 10 hours a day, Dr. Toda said at the congress, which was sponsored by the Osteoarthritis Research Society International.

In the short, medium, and long groups, the femorotibial angle was reduced by an average of 2.4 degrees, 2.2 degrees, and 2.5 degrees, respectively. The femorotibial angle in the placebo group increased by 1.8 degrees.

Pain remission scores on the Lequesne Functional Severity Index at 2 weeks were significantly improved from baseline in the medium group (−5.9) compared with the placebo (−1.9) and long groups (−2.3). The short group score was −4.6.

Maximum improvement on the severity index occurred among patients who wore the device for 8 hours per day, Dr. Toda said.

“A possible reason for the reduced improvement in the long group might be that the continuing reduction in the femorotibial angle resulted in fatigue of surrounding muscles, which had been compensating for the deformity,” Dr. Toda said.

The poor results in the placebo group suggest that the improvements seen in patients wearing the device for 5–10 hours were due to changes in the femorotibial angle and not to the effects of NSAIDs.

The insole offers a possible alternative for patients with knee osteoarthritis who are hesitant to undergo pharmacologic or surgical treatment, Dr. Toda added. Follow-up studies are planned to determine if the device alters or delays OA progression.

Patients would be wise to consult their physicians before using devices such as Dr. Toda's, said Neil Segal, M.D., of the department of orthopedics and rehabilitation at the University of Iowa, Iowa City. “We're still studying the biomechanics of what leads to OA,” he said.

This device may help patients with medial compartment OA who have varus forces on that compartment. But it won't help patients with lateral compartment OA, and it might even make them worse.

The femorotibial angle, formed by the axes of the femur and tibia, before treatment with the insole. Courtesy Dr. Yoshitaka Toda

After treatment with the strapped insole, the femorotibial angle was reduced by about 5 degrees. Courtesy Dr. Yoshitaka Toda

The insole is secured with straps around the subtalar joint, preventing the talus from moving. James Reinaker

CHICAGO — Use of a laterally wedged insole with strapping of the subtalar joint can improve pain and correct abnormal biomechanics due to varus alignment in medial compartment osteoarthritis of the knee, Yoshitaka Toda, M.D., said at the 2004 World Congress on Osteoarthritis.

The idea is that an insole can correct varus alignment by creating valgus correction, resulting in a reduction of medial knee joint surface loading, said Dr. Toda, who has an orthopedic rheumatology practice in Osaka, Japan.

Previous attempts to achieve such a correction with a shoe insert haven't been successful, he said, perhaps because of movement of the talus.

Instead, an insole that's fixed in place with subtalar strapping prevents the talus from moving and creates tension to correct the femorotibial angle, he explained.

In a study designed to assess the optimal daily usage of the device, which was developed and patented by Dr. Toda, 81 women with knee osteoarthritis were randomly assigned to wear the insole for less than 5 hours a day (short group), between 5 hours and 10 hours (medium group), for more than 10 hours (long group), or to wear a placebo subtalar strapping band without the wedge insert. Both of the groups were treated for 2 weeks.

All patients also were treated with oral NSAIDs twice a day as adjunctive therapy. There were no differences between groups in terms of age, disease duration, body mass, height, or femorotibial angle.

All patients with varus knee osteoarthritis who wore the orthotic device daily had a significantly greater valgus correction of the femorotibial angle on standing radiographs than did patients in the placebo group.

The average time spent actually wearing the device was 3.5 hours in the short group, 6.9 hours in the medium group, and 14.2 hours in the long group, according to patient diaries.

The optimal time for wearing the device appears to be between 5 and 10 hours a day, Dr. Toda said at the congress, which was sponsored by the Osteoarthritis Research Society International.

In the short, medium, and long groups, the femorotibial angle was reduced by an average of 2.4 degrees, 2.2 degrees, and 2.5 degrees, respectively. The femorotibial angle in the placebo group increased by 1.8 degrees.

Pain remission scores on the Lequesne Functional Severity Index at 2 weeks were significantly improved from baseline in the medium group (−5.9) compared with the placebo (−1.9) and long groups (−2.3). The short group score was −4.6.

Maximum improvement on the severity index occurred among patients who wore the device for 8 hours per day, Dr. Toda said.

“A possible reason for the reduced improvement in the long group might be that the continuing reduction in the femorotibial angle resulted in fatigue of surrounding muscles, which had been compensating for the deformity,” Dr. Toda said.

The poor results in the placebo group suggest that the improvements seen in patients wearing the device for 5–10 hours were due to changes in the femorotibial angle and not to the effects of NSAIDs.

The insole offers a possible alternative for patients with knee osteoarthritis who are hesitant to undergo pharmacologic or surgical treatment, Dr. Toda added. Follow-up studies are planned to determine if the device alters or delays OA progression.

Patients would be wise to consult their physicians before using devices such as Dr. Toda's, said Neil Segal, M.D., of the department of orthopedics and rehabilitation at the University of Iowa, Iowa City. “We're still studying the biomechanics of what leads to OA,” he said.

This device may help patients with medial compartment OA who have varus forces on that compartment. But it won't help patients with lateral compartment OA, and it might even make them worse.

The femorotibial angle, formed by the axes of the femur and tibia, before treatment with the insole. Courtesy Dr. Yoshitaka Toda

After treatment with the strapped insole, the femorotibial angle was reduced by about 5 degrees. Courtesy Dr. Yoshitaka Toda

The insole is secured with straps around the subtalar joint, preventing the talus from moving. James Reinaker

CHICAGO — Use of a laterally wedged insole with strapping of the subtalar joint can improve pain and correct abnormal biomechanics due to varus alignment in medial compartment osteoarthritis of the knee, Yoshitaka Toda, M.D., said at the 2004 World Congress on Osteoarthritis.

The idea is that an insole can correct varus alignment by creating valgus correction, resulting in a reduction of medial knee joint surface loading, said Dr. Toda, who has an orthopedic rheumatology practice in Osaka, Japan.

Previous attempts to achieve such a correction with a shoe insert haven't been successful, he said, perhaps because of movement of the talus.

Instead, an insole that's fixed in place with subtalar strapping prevents the talus from moving and creates tension to correct the femorotibial angle, he explained.

In a study designed to assess the optimal daily usage of the device, which was developed and patented by Dr. Toda, 81 women with knee osteoarthritis were randomly assigned to wear the insole for less than 5 hours a day (short group), between 5 hours and 10 hours (medium group), for more than 10 hours (long group), or to wear a placebo subtalar strapping band without the wedge insert. Both of the groups were treated for 2 weeks.

All patients also were treated with oral NSAIDs twice a day as adjunctive therapy. There were no differences between groups in terms of age, disease duration, body mass, height, or femorotibial angle.

All patients with varus knee osteoarthritis who wore the orthotic device daily had a significantly greater valgus correction of the femorotibial angle on standing radiographs than did patients in the placebo group.

The average time spent actually wearing the device was 3.5 hours in the short group, 6.9 hours in the medium group, and 14.2 hours in the long group, according to patient diaries.

The optimal time for wearing the device appears to be between 5 and 10 hours a day, Dr. Toda said at the congress, which was sponsored by the Osteoarthritis Research Society International.

In the short, medium, and long groups, the femorotibial angle was reduced by an average of 2.4 degrees, 2.2 degrees, and 2.5 degrees, respectively. The femorotibial angle in the placebo group increased by 1.8 degrees.

Pain remission scores on the Lequesne Functional Severity Index at 2 weeks were significantly improved from baseline in the medium group (−5.9) compared with the placebo (−1.9) and long groups (−2.3). The short group score was −4.6.

Maximum improvement on the severity index occurred among patients who wore the device for 8 hours per day, Dr. Toda said.

“A possible reason for the reduced improvement in the long group might be that the continuing reduction in the femorotibial angle resulted in fatigue of surrounding muscles, which had been compensating for the deformity,” Dr. Toda said.

The poor results in the placebo group suggest that the improvements seen in patients wearing the device for 5–10 hours were due to changes in the femorotibial angle and not to the effects of NSAIDs.

The insole offers a possible alternative for patients with knee osteoarthritis who are hesitant to undergo pharmacologic or surgical treatment, Dr. Toda added. Follow-up studies are planned to determine if the device alters or delays OA progression.

Patients would be wise to consult their physicians before using devices such as Dr. Toda's, said Neil Segal, M.D., of the department of orthopedics and rehabilitation at the University of Iowa, Iowa City. “We're still studying the biomechanics of what leads to OA,” he said.

This device may help patients with medial compartment OA who have varus forces on that compartment. But it won't help patients with lateral compartment OA, and it might even make them worse.

The femorotibial angle, formed by the axes of the femur and tibia, before treatment with the insole. Courtesy Dr. Yoshitaka Toda

After treatment with the strapped insole, the femorotibial angle was reduced by about 5 degrees. Courtesy Dr. Yoshitaka Toda

The insole is secured with straps around the subtalar joint, preventing the talus from moving. James Reinaker

CHICAGO — The presence of an impaired metabolism exacerbates the impact of obesity as a risk factor for developing knee osteoarthritis and is associated with reduced physical functioning, Mary Fran Sowers, Ph.D., reported at the 2004 World Congress on Osteoarthritis.

Such findings suggest that “the role of obesity with respect to osteoarthritis and functioning may extend mechanistically beyond that of just simple joint loading,” said Dr. Sowers, an epidemiology professor at the University of Michigan, Ann Arbor.

Current OA treatments should be evaluated for their potential to exacerbate these metabolic derangements, because this exacerbation is likely to diminish treatment efficacy.

“An understanding of the added contribution of the obesity subtypes could be very useful in guiding primary and secondary treatment efforts,” Dr. Sowers added at the meeting, sponsored by the Osteoarthritis Research Society International.

Researchers have identified several obesity subtypes, including individuals who are obese but metabolically healthy. This may occur in about 20% of obese persons and is characterized by large amounts of fat mass but normal insulin levels and favorable cardiovascular risk factor profiles.

Another risk group comprises individuals of normal weight but who have metabolic profiles more typically seen in the obese.

This risk group may account for about 15% of the general population and is characterized by low HDL cholesterol, higher triglyceride levels, and higher levels of inflammatory markers.

A community-based cohort of 775 women aged 43–53 years was evaluated for metabolic obesity, defined on the basis of three body mass index (BMI) cutoff points and the presence of two or more of the following metabolic derangements: diabetes or fasting glucose greater than 125 mg/dL, serum C-reactive protein greater than 2 mg/L, HDL less than 45 mg/dL, triglycerides greater than 200 mg/dL, or a waist-hip ratio greater than 0.81 cm.

The investigators found that 34% of the women were not obese (BMI less than 26 kg/m2) and had no metabolic derangements.

Another 31% of the participants were overweight to obese (BMI 26–34 kg/m2) without a metabolic derangement, and an additional 15% were overweight/obese women who did have a metabolic derangement.

Finally, 12% were very obese (BMI greater than 34 kg/m2) without a metabolic derangement, and 8% were very obese women who did have a metabolic derangement.

Among those without a metabolic derangement, the odds of having knee OA were increased among women who were either overweight/obese (odds ratio 1.9) or very obese (OR 7.0), compared with women who were not obese and had no metabolic derangement.

But when obesity was associated with a metabolic derangement, the risk of knee OA was three times higher in overweight or obese women (OR 3.3) and nine times higher in very obese women (OR 9.0), compared with women who were not obese and had no metabolic derangement.

The impact of metabolic disorders and weight on OA risk was consistent across all four of the physical tests: speed measured during walking on gait mats, grip strength, timed walk, and timed stair climbing, Dr. Sowers said.

There was no loss in leg strength unless women had an impaired metabolism, and then the loss was most pronounced in individuals with the highest BMI.

Dr. Sowers proposed that metabolic disorders and obesity may affect leg strength by altering glycation products in the muscles, by allowing fatty infiltration of muscle tissue and compromising selective muscle fibers, or by causing innervation problems.

CHICAGO — The presence of an impaired metabolism exacerbates the impact of obesity as a risk factor for developing knee osteoarthritis and is associated with reduced physical functioning, Mary Fran Sowers, Ph.D., reported at the 2004 World Congress on Osteoarthritis.

Such findings suggest that “the role of obesity with respect to osteoarthritis and functioning may extend mechanistically beyond that of just simple joint loading,” said Dr. Sowers, an epidemiology professor at the University of Michigan, Ann Arbor.

Current OA treatments should be evaluated for their potential to exacerbate these metabolic derangements, because this exacerbation is likely to diminish treatment efficacy.

“An understanding of the added contribution of the obesity subtypes could be very useful in guiding primary and secondary treatment efforts,” Dr. Sowers added at the meeting, sponsored by the Osteoarthritis Research Society International.

Researchers have identified several obesity subtypes, including individuals who are obese but metabolically healthy. This may occur in about 20% of obese persons and is characterized by large amounts of fat mass but normal insulin levels and favorable cardiovascular risk factor profiles.

Another risk group comprises individuals of normal weight but who have metabolic profiles more typically seen in the obese.

This risk group may account for about 15% of the general population and is characterized by low HDL cholesterol, higher triglyceride levels, and higher levels of inflammatory markers.

A community-based cohort of 775 women aged 43–53 years was evaluated for metabolic obesity, defined on the basis of three body mass index (BMI) cutoff points and the presence of two or more of the following metabolic derangements: diabetes or fasting glucose greater than 125 mg/dL, serum C-reactive protein greater than 2 mg/L, HDL less than 45 mg/dL, triglycerides greater than 200 mg/dL, or a waist-hip ratio greater than 0.81 cm.

The investigators found that 34% of the women were not obese (BMI less than 26 kg/m2) and had no metabolic derangements.

Another 31% of the participants were overweight to obese (BMI 26–34 kg/m2) without a metabolic derangement, and an additional 15% were overweight/obese women who did have a metabolic derangement.

Finally, 12% were very obese (BMI greater than 34 kg/m2) without a metabolic derangement, and 8% were very obese women who did have a metabolic derangement.

Among those without a metabolic derangement, the odds of having knee OA were increased among women who were either overweight/obese (odds ratio 1.9) or very obese (OR 7.0), compared with women who were not obese and had no metabolic derangement.

But when obesity was associated with a metabolic derangement, the risk of knee OA was three times higher in overweight or obese women (OR 3.3) and nine times higher in very obese women (OR 9.0), compared with women who were not obese and had no metabolic derangement.

The impact of metabolic disorders and weight on OA risk was consistent across all four of the physical tests: speed measured during walking on gait mats, grip strength, timed walk, and timed stair climbing, Dr. Sowers said.

There was no loss in leg strength unless women had an impaired metabolism, and then the loss was most pronounced in individuals with the highest BMI.

Dr. Sowers proposed that metabolic disorders and obesity may affect leg strength by altering glycation products in the muscles, by allowing fatty infiltration of muscle tissue and compromising selective muscle fibers, or by causing innervation problems.

CHICAGO — The presence of an impaired metabolism exacerbates the impact of obesity as a risk factor for developing knee osteoarthritis and is associated with reduced physical functioning, Mary Fran Sowers, Ph.D., reported at the 2004 World Congress on Osteoarthritis.

Such findings suggest that “the role of obesity with respect to osteoarthritis and functioning may extend mechanistically beyond that of just simple joint loading,” said Dr. Sowers, an epidemiology professor at the University of Michigan, Ann Arbor.

Current OA treatments should be evaluated for their potential to exacerbate these metabolic derangements, because this exacerbation is likely to diminish treatment efficacy.

“An understanding of the added contribution of the obesity subtypes could be very useful in guiding primary and secondary treatment efforts,” Dr. Sowers added at the meeting, sponsored by the Osteoarthritis Research Society International.

Researchers have identified several obesity subtypes, including individuals who are obese but metabolically healthy. This may occur in about 20% of obese persons and is characterized by large amounts of fat mass but normal insulin levels and favorable cardiovascular risk factor profiles.

Another risk group comprises individuals of normal weight but who have metabolic profiles more typically seen in the obese.

This risk group may account for about 15% of the general population and is characterized by low HDL cholesterol, higher triglyceride levels, and higher levels of inflammatory markers.

A community-based cohort of 775 women aged 43–53 years was evaluated for metabolic obesity, defined on the basis of three body mass index (BMI) cutoff points and the presence of two or more of the following metabolic derangements: diabetes or fasting glucose greater than 125 mg/dL, serum C-reactive protein greater than 2 mg/L, HDL less than 45 mg/dL, triglycerides greater than 200 mg/dL, or a waist-hip ratio greater than 0.81 cm.

The investigators found that 34% of the women were not obese (BMI less than 26 kg/m2) and had no metabolic derangements.

Another 31% of the participants were overweight to obese (BMI 26–34 kg/m2) without a metabolic derangement, and an additional 15% were overweight/obese women who did have a metabolic derangement.

Finally, 12% were very obese (BMI greater than 34 kg/m2) without a metabolic derangement, and 8% were very obese women who did have a metabolic derangement.

Among those without a metabolic derangement, the odds of having knee OA were increased among women who were either overweight/obese (odds ratio 1.9) or very obese (OR 7.0), compared with women who were not obese and had no metabolic derangement.

But when obesity was associated with a metabolic derangement, the risk of knee OA was three times higher in overweight or obese women (OR 3.3) and nine times higher in very obese women (OR 9.0), compared with women who were not obese and had no metabolic derangement.

The impact of metabolic disorders and weight on OA risk was consistent across all four of the physical tests: speed measured during walking on gait mats, grip strength, timed walk, and timed stair climbing, Dr. Sowers said.

There was no loss in leg strength unless women had an impaired metabolism, and then the loss was most pronounced in individuals with the highest BMI.

Dr. Sowers proposed that metabolic disorders and obesity may affect leg strength by altering glycation products in the muscles, by allowing fatty infiltration of muscle tissue and compromising selective muscle fibers, or by causing innervation problems.

MINNEAPOLIS — A gene therapy appears to block the spread of HIV virus in humans, according to a study presented at the annual meeting of the American Society of Gene Therapy.

Three patients with drug-resistant strains of HIV have undergone the experimental treatment, which involves taking T cells from patients and reengineering them so they can paralyze HIV and prevent it from spreading to other cells.

“Preliminary analysis has shown a lower level of HIV in their blood stream than predosing levels, which, given the nature of a phase I clinical trial, is very encouraging,” Boro Dropulic, Ph.D., chief scientific officer and founder, VIRxSYS Corp., Gaithersburg, Md., said in an interview.

The therapy consists of an HIV-1-based lentiviral vector that contains a 937-base antisense gene against the HIV envelope, VRX496, for autologous T-cell therapy, said Dr. Dropulic, who is conducting the research in collaboration with Johns Hopkins University in Baltimore and the University of Pennsylvania in Philadelphia.

Patients undergo leukopheresis with CD4-cell isolation. The vector that is used is based on a debilitated form of a lentivirus, which contains an antisense sequence that is targeted to the envelope gene.

Its expression should inhibit the replication of HIV in a transduced cell.

The antisense virus inhibited HIV in cultures by more than 93% over controls, regardless of patient status or the tropism of the infecting virus.

CD4 cells are transduced with the vector and subsequently expanded in culture for 8–11 days to more than 10 billion cells prior to reintroduction into the patient. The cells are given intravenously over 30 minutes.

Preclinical studies showed the feasibility of the approach in normal CD4 cells and in CD4 cells taken from 20 early- and late-stage patients. This is noteworthy, given the rapid emergence of drug-resistant strains of HIV, Dr. Dropulic said.

About 15% of newly transmitted virus is already resistant to at least one antiretroviral drug, which brings into question whether highly active antiretroviral therapy is a long-term solution to the AIDS crisis.

In the United States, where highly active antiretroviral therapy has become the standard of care, there are issues surrounding the toxicity of antiretroviral therapy and the spread of drug-resistant forms of HIV through the population, which limit the utility of these drugs, Dr. Dropulic said.

In the phase I, open-label clinical trial, five highly active antiretroviral therapy-resistant patients with CD4-cell counts between 200 and 500 cells/μL were serially enrolled to receive about 10 billion modified autologous CD4 cells in a single dose.

To date, three subjects have been infused and have completed early monitoring.

Adverse events were defined in part by a sustained 0.5-log increase in viral load or sustained 0.5-log increase in CD4 count within 3 weeks post dose.

Patients were monitored for the emergence of any replication-competent lentivirus. At baseline, subject one had an average viral load of 188,500, which fell to 70,006 by day 266.

Subject two's average viral loads were 54,000 at baseline and 8,600 at day 180; subject three's were 46,150 at baseline and 43,612 at day 90, Dr. Dropulic said.

There have been no adverse events, and all replication-competent lentivirus assays have been negative.

CD4 counts remain steady in all three patients, and there has been no evidence of change in the patients' T-cell repertoire, Dr. Dropulic said.

The second phase of the trial is designed to evaluate efficacy, and future trials are planned to examine the impact of single as well as multiple infusions.

MINNEAPOLIS — A gene therapy appears to block the spread of HIV virus in humans, according to a study presented at the annual meeting of the American Society of Gene Therapy.

Three patients with drug-resistant strains of HIV have undergone the experimental treatment, which involves taking T cells from patients and reengineering them so they can paralyze HIV and prevent it from spreading to other cells.

“Preliminary analysis has shown a lower level of HIV in their blood stream than predosing levels, which, given the nature of a phase I clinical trial, is very encouraging,” Boro Dropulic, Ph.D., chief scientific officer and founder, VIRxSYS Corp., Gaithersburg, Md., said in an interview.

The therapy consists of an HIV-1-based lentiviral vector that contains a 937-base antisense gene against the HIV envelope, VRX496, for autologous T-cell therapy, said Dr. Dropulic, who is conducting the research in collaboration with Johns Hopkins University in Baltimore and the University of Pennsylvania in Philadelphia.

Patients undergo leukopheresis with CD4-cell isolation. The vector that is used is based on a debilitated form of a lentivirus, which contains an antisense sequence that is targeted to the envelope gene.

Its expression should inhibit the replication of HIV in a transduced cell.

The antisense virus inhibited HIV in cultures by more than 93% over controls, regardless of patient status or the tropism of the infecting virus.

CD4 cells are transduced with the vector and subsequently expanded in culture for 8–11 days to more than 10 billion cells prior to reintroduction into the patient. The cells are given intravenously over 30 minutes.

Preclinical studies showed the feasibility of the approach in normal CD4 cells and in CD4 cells taken from 20 early- and late-stage patients. This is noteworthy, given the rapid emergence of drug-resistant strains of HIV, Dr. Dropulic said.

About 15% of newly transmitted virus is already resistant to at least one antiretroviral drug, which brings into question whether highly active antiretroviral therapy is a long-term solution to the AIDS crisis.

In the United States, where highly active antiretroviral therapy has become the standard of care, there are issues surrounding the toxicity of antiretroviral therapy and the spread of drug-resistant forms of HIV through the population, which limit the utility of these drugs, Dr. Dropulic said.

In the phase I, open-label clinical trial, five highly active antiretroviral therapy-resistant patients with CD4-cell counts between 200 and 500 cells/μL were serially enrolled to receive about 10 billion modified autologous CD4 cells in a single dose.

To date, three subjects have been infused and have completed early monitoring.

Adverse events were defined in part by a sustained 0.5-log increase in viral load or sustained 0.5-log increase in CD4 count within 3 weeks post dose.

Patients were monitored for the emergence of any replication-competent lentivirus. At baseline, subject one had an average viral load of 188,500, which fell to 70,006 by day 266.

Subject two's average viral loads were 54,000 at baseline and 8,600 at day 180; subject three's were 46,150 at baseline and 43,612 at day 90, Dr. Dropulic said.

There have been no adverse events, and all replication-competent lentivirus assays have been negative.

CD4 counts remain steady in all three patients, and there has been no evidence of change in the patients' T-cell repertoire, Dr. Dropulic said.

The second phase of the trial is designed to evaluate efficacy, and future trials are planned to examine the impact of single as well as multiple infusions.

MINNEAPOLIS — A gene therapy appears to block the spread of HIV virus in humans, according to a study presented at the annual meeting of the American Society of Gene Therapy.

Three patients with drug-resistant strains of HIV have undergone the experimental treatment, which involves taking T cells from patients and reengineering them so they can paralyze HIV and prevent it from spreading to other cells.

“Preliminary analysis has shown a lower level of HIV in their blood stream than predosing levels, which, given the nature of a phase I clinical trial, is very encouraging,” Boro Dropulic, Ph.D., chief scientific officer and founder, VIRxSYS Corp., Gaithersburg, Md., said in an interview.

The therapy consists of an HIV-1-based lentiviral vector that contains a 937-base antisense gene against the HIV envelope, VRX496, for autologous T-cell therapy, said Dr. Dropulic, who is conducting the research in collaboration with Johns Hopkins University in Baltimore and the University of Pennsylvania in Philadelphia.

Patients undergo leukopheresis with CD4-cell isolation. The vector that is used is based on a debilitated form of a lentivirus, which contains an antisense sequence that is targeted to the envelope gene.

Its expression should inhibit the replication of HIV in a transduced cell.

The antisense virus inhibited HIV in cultures by more than 93% over controls, regardless of patient status or the tropism of the infecting virus.

CD4 cells are transduced with the vector and subsequently expanded in culture for 8–11 days to more than 10 billion cells prior to reintroduction into the patient. The cells are given intravenously over 30 minutes.

Preclinical studies showed the feasibility of the approach in normal CD4 cells and in CD4 cells taken from 20 early- and late-stage patients. This is noteworthy, given the rapid emergence of drug-resistant strains of HIV, Dr. Dropulic said.

About 15% of newly transmitted virus is already resistant to at least one antiretroviral drug, which brings into question whether highly active antiretroviral therapy is a long-term solution to the AIDS crisis.

In the United States, where highly active antiretroviral therapy has become the standard of care, there are issues surrounding the toxicity of antiretroviral therapy and the spread of drug-resistant forms of HIV through the population, which limit the utility of these drugs, Dr. Dropulic said.

In the phase I, open-label clinical trial, five highly active antiretroviral therapy-resistant patients with CD4-cell counts between 200 and 500 cells/μL were serially enrolled to receive about 10 billion modified autologous CD4 cells in a single dose.

To date, three subjects have been infused and have completed early monitoring.

Adverse events were defined in part by a sustained 0.5-log increase in viral load or sustained 0.5-log increase in CD4 count within 3 weeks post dose.

Patients were monitored for the emergence of any replication-competent lentivirus. At baseline, subject one had an average viral load of 188,500, which fell to 70,006 by day 266.

Subject two's average viral loads were 54,000 at baseline and 8,600 at day 180; subject three's were 46,150 at baseline and 43,612 at day 90, Dr. Dropulic said.

There have been no adverse events, and all replication-competent lentivirus assays have been negative.

CD4 counts remain steady in all three patients, and there has been no evidence of change in the patients' T-cell repertoire, Dr. Dropulic said.

The second phase of the trial is designed to evaluate efficacy, and future trials are planned to examine the impact of single as well as multiple infusions.

CHICAGO — High folate intake may lower the risk of hypertension, particularly in young women, according to data presented at a conference of the Council for High Blood Pressure Research.

Young women who consumed at least 800 mcg/day of folate reduced their risk of developing high blood pressure by almost a third, compared with those who consumed less than 200 mcg/day. Folate also reduced the risk in older women to a lesser degree, reported John P. Forman, M.D., a research and clinical fellow at Brigham and Women's Hospital in Boston.

The most striking effects of folate intake were seen among women aged 35 years or younger, he said. Supplemental folic acid also contributed to this decrease in risk, as most of the women in the higher range of folate intake obtained much of their intake from supplements.

Dr. Forman and colleagues based their findings on data from the Nurses' Health Study I (NHS I), comprising 62,260 women aged 43–70 years, and the Nurses' Health Study II (NHS II), comprising 93,034 women aged 26–46 years. None of the women had high blood pressure at baseline.

Semiquantitative food-frequency questionnaires were used to gather information about dietary and supplemental folate intake at baseline, and were followed up with additional questionnaires every 4 years. Information about physician-diagnosed high blood pressure was self-reported every 2 years.

Cox regression analysis was used to estimate relative risk after the investigators controlled for age, body mass index, smoking, exercise, family history of hypertension, and intake of alcohol, caffeine, salt, calcium, magnesium, potassium, fiber, methionine, and vitamins B6, B12, and D.

Over 8 years of follow-up, there were 12,347 incident cases of hypertension in NHS I and 7,373 incident cases in NHS II.

Young women who consumed at least 800 mcg/day of folate had a 29% lower risk of high blood pressure, compared with those who consumed less than 200 mcg/day. Older women who consumed at least 800 mcg/day had a 13% lower risk than did those who consumed less than 200 mcg/day.

Although the most striking effects of folate were seen in women younger than 35, there was no significant interaction between age and reduced risk among women in the older cohort when divided into three additional subgroups.

One hypothesis as for why the effect of folate varies by age is that the pathogenesis of hypertension may be different in older versus younger women, Dr. Forman said at the meeting, sponsored by the American Heart Association.

The Food and Drug Administration began requiring folate supplementation of several foods including bread and cereals in 1998. But fortification had begun in 1996, spanning the last 2 years of the NHS I and the last 3 years of the NHS II.

The researchers did not directly measure serum folate, which was a limitation of the study, Dr. Forman said. However, the food-frequency questionnaires used in the cohort have been previously validated and are highly correlated with both dietary records and serum folate levels. In addition, all of the study participants were registered nurses, and self-reported hypertension was thought to be reliable.

CHICAGO — High folate intake may lower the risk of hypertension, particularly in young women, according to data presented at a conference of the Council for High Blood Pressure Research.

Young women who consumed at least 800 mcg/day of folate reduced their risk of developing high blood pressure by almost a third, compared with those who consumed less than 200 mcg/day. Folate also reduced the risk in older women to a lesser degree, reported John P. Forman, M.D., a research and clinical fellow at Brigham and Women's Hospital in Boston.

The most striking effects of folate intake were seen among women aged 35 years or younger, he said. Supplemental folic acid also contributed to this decrease in risk, as most of the women in the higher range of folate intake obtained much of their intake from supplements.

Dr. Forman and colleagues based their findings on data from the Nurses' Health Study I (NHS I), comprising 62,260 women aged 43–70 years, and the Nurses' Health Study II (NHS II), comprising 93,034 women aged 26–46 years. None of the women had high blood pressure at baseline.

Semiquantitative food-frequency questionnaires were used to gather information about dietary and supplemental folate intake at baseline, and were followed up with additional questionnaires every 4 years. Information about physician-diagnosed high blood pressure was self-reported every 2 years.

Cox regression analysis was used to estimate relative risk after the investigators controlled for age, body mass index, smoking, exercise, family history of hypertension, and intake of alcohol, caffeine, salt, calcium, magnesium, potassium, fiber, methionine, and vitamins B6, B12, and D.

Over 8 years of follow-up, there were 12,347 incident cases of hypertension in NHS I and 7,373 incident cases in NHS II.

Young women who consumed at least 800 mcg/day of folate had a 29% lower risk of high blood pressure, compared with those who consumed less than 200 mcg/day. Older women who consumed at least 800 mcg/day had a 13% lower risk than did those who consumed less than 200 mcg/day.

Although the most striking effects of folate were seen in women younger than 35, there was no significant interaction between age and reduced risk among women in the older cohort when divided into three additional subgroups.

One hypothesis as for why the effect of folate varies by age is that the pathogenesis of hypertension may be different in older versus younger women, Dr. Forman said at the meeting, sponsored by the American Heart Association.

The Food and Drug Administration began requiring folate supplementation of several foods including bread and cereals in 1998. But fortification had begun in 1996, spanning the last 2 years of the NHS I and the last 3 years of the NHS II.

The researchers did not directly measure serum folate, which was a limitation of the study, Dr. Forman said. However, the food-frequency questionnaires used in the cohort have been previously validated and are highly correlated with both dietary records and serum folate levels. In addition, all of the study participants were registered nurses, and self-reported hypertension was thought to be reliable.

CHICAGO — High folate intake may lower the risk of hypertension, particularly in young women, according to data presented at a conference of the Council for High Blood Pressure Research.

Young women who consumed at least 800 mcg/day of folate reduced their risk of developing high blood pressure by almost a third, compared with those who consumed less than 200 mcg/day. Folate also reduced the risk in older women to a lesser degree, reported John P. Forman, M.D., a research and clinical fellow at Brigham and Women's Hospital in Boston.

The most striking effects of folate intake were seen among women aged 35 years or younger, he said. Supplemental folic acid also contributed to this decrease in risk, as most of the women in the higher range of folate intake obtained much of their intake from supplements.

Dr. Forman and colleagues based their findings on data from the Nurses' Health Study I (NHS I), comprising 62,260 women aged 43–70 years, and the Nurses' Health Study II (NHS II), comprising 93,034 women aged 26–46 years. None of the women had high blood pressure at baseline.

Semiquantitative food-frequency questionnaires were used to gather information about dietary and supplemental folate intake at baseline, and were followed up with additional questionnaires every 4 years. Information about physician-diagnosed high blood pressure was self-reported every 2 years.

Cox regression analysis was used to estimate relative risk after the investigators controlled for age, body mass index, smoking, exercise, family history of hypertension, and intake of alcohol, caffeine, salt, calcium, magnesium, potassium, fiber, methionine, and vitamins B6, B12, and D.

Over 8 years of follow-up, there were 12,347 incident cases of hypertension in NHS I and 7,373 incident cases in NHS II.

Young women who consumed at least 800 mcg/day of folate had a 29% lower risk of high blood pressure, compared with those who consumed less than 200 mcg/day. Older women who consumed at least 800 mcg/day had a 13% lower risk than did those who consumed less than 200 mcg/day.

Although the most striking effects of folate were seen in women younger than 35, there was no significant interaction between age and reduced risk among women in the older cohort when divided into three additional subgroups.

One hypothesis as for why the effect of folate varies by age is that the pathogenesis of hypertension may be different in older versus younger women, Dr. Forman said at the meeting, sponsored by the American Heart Association.

The Food and Drug Administration began requiring folate supplementation of several foods including bread and cereals in 1998. But fortification had begun in 1996, spanning the last 2 years of the NHS I and the last 3 years of the NHS II.

The researchers did not directly measure serum folate, which was a limitation of the study, Dr. Forman said. However, the food-frequency questionnaires used in the cohort have been previously validated and are highly correlated with both dietary records and serum folate levels. In addition, all of the study participants were registered nurses, and self-reported hypertension was thought to be reliable.

CHICAGO – Spine specialists have traditionally focused on specific degenerative pathology in the spine as the main determinant of back pain, but science now suggests that the central nervous system ultimately modulates chronic low back pain.

Acceptance of the new evidence will require a fundamental shift in thinking by spine surgeons and could lessen the role of surgery and increase the role of exercise in the management of low back pain at a time when critics are assailing the overuse of spinal fusion surgery in the United States.

“We've been looking for decades for where the smoking gun is as to why these people are having back pain, and so far we haven't found it,” James Rainville, M.D., said at the annual meeting of the North American Spine Society. “There is now some information coming out to show what is going on, and [pain processing] may not be where we thought it was. It may be happening in the central nervous system.”

Less well known than the spinal cord's role in pain production is the part the spinal cord plays in pain augmentation, said Dr. Rainville, chief of rehabilitation at New England Baptist Hospital, Boston.

Wide dynamic range neurons have been identified in the spine as responsible for “windup,” or the accentuation of painful stimuli.

A recent study found evidence of central nervous system augmentation of pain processing in patients with chronic low back pain (Arthritis Rheum. 2004;50:613–23). Experimental pain testing at the thumb revealed hyperalgesia in patients with idiopathic chronic low back pain as well as in patients with fibromyalgia, compared with controls.

Moreover, functional magnetic resonance imaging detected five common regions of neuronal activation in pain-related cortical areas in the low back pain and fibromyalgia groups. The areas are responsible for the transmission of neurologic information into the conscious experience of pain and included the contralateral primary and secondary somatosensory cortices, inferior parietal lobule, cerebellum, and ipsilateral secondary somatosensory cortex. The same stimulus resulted in only a single activation in controls in the contralateral secondary somatosensory cortex.

Finally, these studies' findings are strengthened by research that suggests that thoughts can change brain activity induced by peripheral stimulation (J. Neurosci. 2004;24:7199–203).

“Could our thoughts, ideas, and feelings that we have all be acting through central mechanisms to change our central sensitization to pain? If that's the case, then we're in trouble if we're trying to treat it in the periphery always,” observed Dr. Rainville, of Harvard Medical School.

This has important implications for understanding the successes and failures of spinal surgery. Spine surgeons came under fire recently in an editorial (N. Engl. J. Med. 2004;350:722–6) that charged fusion surgery was being overused in the United States. NASS fired back with an editorial of its own (Spine J. 2004;4[suppl. 5]:S129–38) and a high-profile panel discussion at the annual meeting.

Still, several studies presented at the same meeting validated a different approach. The rehabilitation model suggests that pain can be stopped by desensitizing the pain-producing tissue and improving central processing.

Exercise can improve muscle strength and flexibility, reduce disability, and even reduce pain intensity by 10%–50%. Exercise also can alter a patient's pain attitudes and beliefs.

A recent study by Dr. Rainville and colleagues showed that exercise reduced both the pain anticipated before and induced with exercise.

Significant improvements were observed for global back pain, leg pain, disability, and performance on each physical testing in 70 patients with chronic low back pain who completed an intensive 2-hour exercise program delivered up to three times per week for 6 weeks.

Performances on all physical testing correlated with anticipated and induced pain for all tests at baseline, but only for measures of flexibility at discharge. The correlation between disability and pain attitudes and beliefs was extremely high, at 0.79.

“Something about the pain process has been changed,” Dr. Rainville said. “What, I don't know. Where, I don't know. But it's a fascinating observation. In addition, people improved their strength. They have less pain with lifting a lot more. Something has been learned differently within the central nervous system, because we didn't change their anatomy in any positive way.”

Finally, exercise may help wean patients with chronic low back pain from narcotics. After 6 weeks of exercise therapy, one-half of patients in the study who regularly used narcotics were able to stop taking them.

CHICAGO – Spine specialists have traditionally focused on specific degenerative pathology in the spine as the main determinant of back pain, but science now suggests that the central nervous system ultimately modulates chronic low back pain.

Acceptance of the new evidence will require a fundamental shift in thinking by spine surgeons and could lessen the role of surgery and increase the role of exercise in the management of low back pain at a time when critics are assailing the overuse of spinal fusion surgery in the United States.

“We've been looking for decades for where the smoking gun is as to why these people are having back pain, and so far we haven't found it,” James Rainville, M.D., said at the annual meeting of the North American Spine Society. “There is now some information coming out to show what is going on, and [pain processing] may not be where we thought it was. It may be happening in the central nervous system.”

Less well known than the spinal cord's role in pain production is the part the spinal cord plays in pain augmentation, said Dr. Rainville, chief of rehabilitation at New England Baptist Hospital, Boston.

Wide dynamic range neurons have been identified in the spine as responsible for “windup,” or the accentuation of painful stimuli.

A recent study found evidence of central nervous system augmentation of pain processing in patients with chronic low back pain (Arthritis Rheum. 2004;50:613–23). Experimental pain testing at the thumb revealed hyperalgesia in patients with idiopathic chronic low back pain as well as in patients with fibromyalgia, compared with controls.

Moreover, functional magnetic resonance imaging detected five common regions of neuronal activation in pain-related cortical areas in the low back pain and fibromyalgia groups. The areas are responsible for the transmission of neurologic information into the conscious experience of pain and included the contralateral primary and secondary somatosensory cortices, inferior parietal lobule, cerebellum, and ipsilateral secondary somatosensory cortex. The same stimulus resulted in only a single activation in controls in the contralateral secondary somatosensory cortex.

Finally, these studies' findings are strengthened by research that suggests that thoughts can change brain activity induced by peripheral stimulation (J. Neurosci. 2004;24:7199–203).

“Could our thoughts, ideas, and feelings that we have all be acting through central mechanisms to change our central sensitization to pain? If that's the case, then we're in trouble if we're trying to treat it in the periphery always,” observed Dr. Rainville, of Harvard Medical School.

This has important implications for understanding the successes and failures of spinal surgery. Spine surgeons came under fire recently in an editorial (N. Engl. J. Med. 2004;350:722–6) that charged fusion surgery was being overused in the United States. NASS fired back with an editorial of its own (Spine J. 2004;4[suppl. 5]:S129–38) and a high-profile panel discussion at the annual meeting.

Still, several studies presented at the same meeting validated a different approach. The rehabilitation model suggests that pain can be stopped by desensitizing the pain-producing tissue and improving central processing.

Exercise can improve muscle strength and flexibility, reduce disability, and even reduce pain intensity by 10%–50%. Exercise also can alter a patient's pain attitudes and beliefs.

A recent study by Dr. Rainville and colleagues showed that exercise reduced both the pain anticipated before and induced with exercise.

Significant improvements were observed for global back pain, leg pain, disability, and performance on each physical testing in 70 patients with chronic low back pain who completed an intensive 2-hour exercise program delivered up to three times per week for 6 weeks.

Performances on all physical testing correlated with anticipated and induced pain for all tests at baseline, but only for measures of flexibility at discharge. The correlation between disability and pain attitudes and beliefs was extremely high, at 0.79.

“Something about the pain process has been changed,” Dr. Rainville said. “What, I don't know. Where, I don't know. But it's a fascinating observation. In addition, people improved their strength. They have less pain with lifting a lot more. Something has been learned differently within the central nervous system, because we didn't change their anatomy in any positive way.”

Finally, exercise may help wean patients with chronic low back pain from narcotics. After 6 weeks of exercise therapy, one-half of patients in the study who regularly used narcotics were able to stop taking them.

CHICAGO – Spine specialists have traditionally focused on specific degenerative pathology in the spine as the main determinant of back pain, but science now suggests that the central nervous system ultimately modulates chronic low back pain.

Acceptance of the new evidence will require a fundamental shift in thinking by spine surgeons and could lessen the role of surgery and increase the role of exercise in the management of low back pain at a time when critics are assailing the overuse of spinal fusion surgery in the United States.

“We've been looking for decades for where the smoking gun is as to why these people are having back pain, and so far we haven't found it,” James Rainville, M.D., said at the annual meeting of the North American Spine Society. “There is now some information coming out to show what is going on, and [pain processing] may not be where we thought it was. It may be happening in the central nervous system.”

Less well known than the spinal cord's role in pain production is the part the spinal cord plays in pain augmentation, said Dr. Rainville, chief of rehabilitation at New England Baptist Hospital, Boston.

Wide dynamic range neurons have been identified in the spine as responsible for “windup,” or the accentuation of painful stimuli.

A recent study found evidence of central nervous system augmentation of pain processing in patients with chronic low back pain (Arthritis Rheum. 2004;50:613–23). Experimental pain testing at the thumb revealed hyperalgesia in patients with idiopathic chronic low back pain as well as in patients with fibromyalgia, compared with controls.

Moreover, functional magnetic resonance imaging detected five common regions of neuronal activation in pain-related cortical areas in the low back pain and fibromyalgia groups. The areas are responsible for the transmission of neurologic information into the conscious experience of pain and included the contralateral primary and secondary somatosensory cortices, inferior parietal lobule, cerebellum, and ipsilateral secondary somatosensory cortex. The same stimulus resulted in only a single activation in controls in the contralateral secondary somatosensory cortex.

Finally, these studies' findings are strengthened by research that suggests that thoughts can change brain activity induced by peripheral stimulation (J. Neurosci. 2004;24:7199–203).

“Could our thoughts, ideas, and feelings that we have all be acting through central mechanisms to change our central sensitization to pain? If that's the case, then we're in trouble if we're trying to treat it in the periphery always,” observed Dr. Rainville, of Harvard Medical School.

This has important implications for understanding the successes and failures of spinal surgery. Spine surgeons came under fire recently in an editorial (N. Engl. J. Med. 2004;350:722–6) that charged fusion surgery was being overused in the United States. NASS fired back with an editorial of its own (Spine J. 2004;4[suppl. 5]:S129–38) and a high-profile panel discussion at the annual meeting.

Still, several studies presented at the same meeting validated a different approach. The rehabilitation model suggests that pain can be stopped by desensitizing the pain-producing tissue and improving central processing.

Exercise can improve muscle strength and flexibility, reduce disability, and even reduce pain intensity by 10%–50%. Exercise also can alter a patient's pain attitudes and beliefs.

A recent study by Dr. Rainville and colleagues showed that exercise reduced both the pain anticipated before and induced with exercise.

Significant improvements were observed for global back pain, leg pain, disability, and performance on each physical testing in 70 patients with chronic low back pain who completed an intensive 2-hour exercise program delivered up to three times per week for 6 weeks.

Performances on all physical testing correlated with anticipated and induced pain for all tests at baseline, but only for measures of flexibility at discharge. The correlation between disability and pain attitudes and beliefs was extremely high, at 0.79.

“Something about the pain process has been changed,” Dr. Rainville said. “What, I don't know. Where, I don't know. But it's a fascinating observation. In addition, people improved their strength. They have less pain with lifting a lot more. Something has been learned differently within the central nervous system, because we didn't change their anatomy in any positive way.”

Finally, exercise may help wean patients with chronic low back pain from narcotics. After 6 weeks of exercise therapy, one-half of patients in the study who regularly used narcotics were able to stop taking them.