Nancy Walsh

BIRMINGHAM, ENGLAND — No important differences in rates of serious infections have been reported among patients treated with etanercept, infliximab, or adalimumab, according to a report from the British Society for Rheumatology Biologics Register (BSRBR).

Since January 2002 all patients in the United Kingdom with rheumatic diseases who are treated with biologic agents have been enrolled in the register. They are being followed with the goal of determining the incidence and nature of any short- or long-term adverse effects, Will Dixon, Ph.D., said at the joint meeting of the British Society for Rheumatology and the German Society for Rheumatology.

To date, data have been analyzed for 2,602 patients who have received etanercept, 2,871 treated with infliximab, and 915 given adalimumab with follow-up for at least 6 months, he said.

Patients in the three groups had similar demographics: The mean age in all groups was 54 years, and median disease duration was 12 years. Three-quarters were women.

Thus far, there have been 132 serious infections among patients on etanercept, 205 in those on infliximab, and 40 in those on adalimumab.

Incidence rates for the three groups were 52.6, 52.1, and 62.4 per 1,000 patient years, respectively. The differences in incidence rates were not statistically significant, said Dr. Dixon of the BSRBR Arthritis Research Campaign epidemiology unit at the University of Manchester (England).

Serious infections were defined as those requiring intravenous antibiotics, leading to a hospital admission, or being in any way life threatening, he said. The most common sites of serious infections also were broadly similar (see the chart).

All three drugs are inhibitors of tumor necrosis factor (TNF)-α, which is a cytokine with a central role in the inflammatory process of rheumatoid arthritis, Dr. Dixon explained. However, it also has a role in infection control, acting synergistically with interferon-γ. In its anti-infection capacity, TNF-α is particularly crucial for the control of intracellular infections such as tuberculosis, where its inhibition can lead to dissemination of the infection.

With regard to these types of infection, there have been 11 cases of tuberculosis, 9 in patients on infliximab and 2 in patients on etanercept; incidence rates for tuberculosis were 2.3 and 0.8 per 1,000 patient-years for the two drugs, respectively. Despite the fact that the rate was more than 2.5-fold higher with infliximab, the difference was not statistically significant because of the small numbers, he said.

There were two cases of Salmonella septic arthritis and one of Salmonella gastroenteritis, all in patients receiving etanercept, Dr. Dixon said. One case of Legionella pneumonia was reported following treatment with infliximab.

When an audience member asked if concurrent steroid therapy might be a contributing factor to the development of infection, Dr. Dixon replied that the strongest predictor of infection was diabetes, followed by a high Health Assessment Questionnaire score, and then steroid use. About 50% of patients were on steroids at baseline.

BIRMINGHAM, ENGLAND — No important differences in rates of serious infections have been reported among patients treated with etanercept, infliximab, or adalimumab, according to a report from the British Society for Rheumatology Biologics Register (BSRBR).

Since January 2002 all patients in the United Kingdom with rheumatic diseases who are treated with biologic agents have been enrolled in the register. They are being followed with the goal of determining the incidence and nature of any short- or long-term adverse effects, Will Dixon, Ph.D., said at the joint meeting of the British Society for Rheumatology and the German Society for Rheumatology.

To date, data have been analyzed for 2,602 patients who have received etanercept, 2,871 treated with infliximab, and 915 given adalimumab with follow-up for at least 6 months, he said.

Patients in the three groups had similar demographics: The mean age in all groups was 54 years, and median disease duration was 12 years. Three-quarters were women.

Thus far, there have been 132 serious infections among patients on etanercept, 205 in those on infliximab, and 40 in those on adalimumab.

Incidence rates for the three groups were 52.6, 52.1, and 62.4 per 1,000 patient years, respectively. The differences in incidence rates were not statistically significant, said Dr. Dixon of the BSRBR Arthritis Research Campaign epidemiology unit at the University of Manchester (England).

Serious infections were defined as those requiring intravenous antibiotics, leading to a hospital admission, or being in any way life threatening, he said. The most common sites of serious infections also were broadly similar (see the chart).

All three drugs are inhibitors of tumor necrosis factor (TNF)-α, which is a cytokine with a central role in the inflammatory process of rheumatoid arthritis, Dr. Dixon explained. However, it also has a role in infection control, acting synergistically with interferon-γ. In its anti-infection capacity, TNF-α is particularly crucial for the control of intracellular infections such as tuberculosis, where its inhibition can lead to dissemination of the infection.

With regard to these types of infection, there have been 11 cases of tuberculosis, 9 in patients on infliximab and 2 in patients on etanercept; incidence rates for tuberculosis were 2.3 and 0.8 per 1,000 patient-years for the two drugs, respectively. Despite the fact that the rate was more than 2.5-fold higher with infliximab, the difference was not statistically significant because of the small numbers, he said.

There were two cases of Salmonella septic arthritis and one of Salmonella gastroenteritis, all in patients receiving etanercept, Dr. Dixon said. One case of Legionella pneumonia was reported following treatment with infliximab.

When an audience member asked if concurrent steroid therapy might be a contributing factor to the development of infection, Dr. Dixon replied that the strongest predictor of infection was diabetes, followed by a high Health Assessment Questionnaire score, and then steroid use. About 50% of patients were on steroids at baseline.

BIRMINGHAM, ENGLAND — No important differences in rates of serious infections have been reported among patients treated with etanercept, infliximab, or adalimumab, according to a report from the British Society for Rheumatology Biologics Register (BSRBR).

Since January 2002 all patients in the United Kingdom with rheumatic diseases who are treated with biologic agents have been enrolled in the register. They are being followed with the goal of determining the incidence and nature of any short- or long-term adverse effects, Will Dixon, Ph.D., said at the joint meeting of the British Society for Rheumatology and the German Society for Rheumatology.

To date, data have been analyzed for 2,602 patients who have received etanercept, 2,871 treated with infliximab, and 915 given adalimumab with follow-up for at least 6 months, he said.

Patients in the three groups had similar demographics: The mean age in all groups was 54 years, and median disease duration was 12 years. Three-quarters were women.

Thus far, there have been 132 serious infections among patients on etanercept, 205 in those on infliximab, and 40 in those on adalimumab.

Incidence rates for the three groups were 52.6, 52.1, and 62.4 per 1,000 patient years, respectively. The differences in incidence rates were not statistically significant, said Dr. Dixon of the BSRBR Arthritis Research Campaign epidemiology unit at the University of Manchester (England).

Serious infections were defined as those requiring intravenous antibiotics, leading to a hospital admission, or being in any way life threatening, he said. The most common sites of serious infections also were broadly similar (see the chart).

All three drugs are inhibitors of tumor necrosis factor (TNF)-α, which is a cytokine with a central role in the inflammatory process of rheumatoid arthritis, Dr. Dixon explained. However, it also has a role in infection control, acting synergistically with interferon-γ. In its anti-infection capacity, TNF-α is particularly crucial for the control of intracellular infections such as tuberculosis, where its inhibition can lead to dissemination of the infection.

With regard to these types of infection, there have been 11 cases of tuberculosis, 9 in patients on infliximab and 2 in patients on etanercept; incidence rates for tuberculosis were 2.3 and 0.8 per 1,000 patient-years for the two drugs, respectively. Despite the fact that the rate was more than 2.5-fold higher with infliximab, the difference was not statistically significant because of the small numbers, he said.

There were two cases of Salmonella septic arthritis and one of Salmonella gastroenteritis, all in patients receiving etanercept, Dr. Dixon said. One case of Legionella pneumonia was reported following treatment with infliximab.

When an audience member asked if concurrent steroid therapy might be a contributing factor to the development of infection, Dr. Dixon replied that the strongest predictor of infection was diabetes, followed by a high Health Assessment Questionnaire score, and then steroid use. About 50% of patients were on steroids at baseline.

BIRMINGHAM, ENGLAND — One promising strategy for holding down the cost of biologic therapy for patients with rheumatic diseases is to prescribe low doses when possible, results from two new studies have suggested.

With infliximab, for example, the typical dosage regimen in ankylosing spondylitis (AS) is 5 mg/kg given by infusion at weeks 1, 2, and 6 and then every 8 weeks. This is higher than the usual regimen for rheumatoid arthritis (RA).

“Because of cost pressures, we tried using conventional RA doses of 3 mg/kg in 13 AS patients,” Ramesh N. Jois, M.D., said at the joint meeting of the British Society for Rheumatology and the German Society for Rheumatology.

All patients had Bath AS Disease Activity Index (BASDAI) scores greater than 4 at baseline. Mean disease duration of these patients, 12 of whom were male, was 16.9 years.

Clinical response was judged to be a 50% or greater reduction in the BASDAI score at 3 months.

One patient did not respond to the low-dose regimen and required an increase to the higher dose. All other patients showed statistically significant improvements across multiple measures of efficacy, said Dr. Jois of the department of rheumatology, Norfolk and Norwich (England) University Hospital.

Some patients now have been on the regimen for 12 months, with persisting benefits. (See chart.)

Five patients have been able to reduce their methotrexate dose (mean reduction 14 mg/wk). One stopped cyclosporine, another stopped sulfasalazine, and five discontinued nonsteroidal anti-inflammatory drugs altogether, he said.

No side effects were seen with the low-dose infliximab therapy.

Use of this regimen has led to a significant cost savings of approximately $29,000 per patient per year, for a total cost savings of $315,000 to the unit in the past year, Dr. Jois said in a poster session. “We advise starting all AS patients on low-dose infliximab. Consider increasing to the higher dose only if they fail to respond,” he said.

Dr. Jois disclosed that his department has received research grant support from Wyeth, Schering-Plough, and Abbott Pharmaceuticals.

In a second study, 36 patients with RA and 3 patients with AS were treated with the standard etanercept regimen of 25 mg twice weekly for at least 3 months. Those with RA who achieved a Disease Activity Score (DAS)-28 below 3.2 and those with AS who achieved a very good response then were asked to gradually increase the interval between their etanercept injections from twice weekly to once weekly, said Veronica E. Abernethy, M.D., of the rheumatology practice development unit, St. Helens and Knowsley NHS Hospitals, Merseyside, England.

Currently, 7 of the 39 have successfully reduced their etanercept to once weekly without any deterioration in disease activity, which has resulted in a cost savings of $67,675 per year. This figure represents 9% of the total etanercept cost for the 39 patients, Dr. Abernethy said in a poster session.

BIRMINGHAM, ENGLAND — One promising strategy for holding down the cost of biologic therapy for patients with rheumatic diseases is to prescribe low doses when possible, results from two new studies have suggested.

With infliximab, for example, the typical dosage regimen in ankylosing spondylitis (AS) is 5 mg/kg given by infusion at weeks 1, 2, and 6 and then every 8 weeks. This is higher than the usual regimen for rheumatoid arthritis (RA).

“Because of cost pressures, we tried using conventional RA doses of 3 mg/kg in 13 AS patients,” Ramesh N. Jois, M.D., said at the joint meeting of the British Society for Rheumatology and the German Society for Rheumatology.

All patients had Bath AS Disease Activity Index (BASDAI) scores greater than 4 at baseline. Mean disease duration of these patients, 12 of whom were male, was 16.9 years.

Clinical response was judged to be a 50% or greater reduction in the BASDAI score at 3 months.

One patient did not respond to the low-dose regimen and required an increase to the higher dose. All other patients showed statistically significant improvements across multiple measures of efficacy, said Dr. Jois of the department of rheumatology, Norfolk and Norwich (England) University Hospital.

Some patients now have been on the regimen for 12 months, with persisting benefits. (See chart.)

Five patients have been able to reduce their methotrexate dose (mean reduction 14 mg/wk). One stopped cyclosporine, another stopped sulfasalazine, and five discontinued nonsteroidal anti-inflammatory drugs altogether, he said.

No side effects were seen with the low-dose infliximab therapy.

Use of this regimen has led to a significant cost savings of approximately $29,000 per patient per year, for a total cost savings of $315,000 to the unit in the past year, Dr. Jois said in a poster session. “We advise starting all AS patients on low-dose infliximab. Consider increasing to the higher dose only if they fail to respond,” he said.

Dr. Jois disclosed that his department has received research grant support from Wyeth, Schering-Plough, and Abbott Pharmaceuticals.

In a second study, 36 patients with RA and 3 patients with AS were treated with the standard etanercept regimen of 25 mg twice weekly for at least 3 months. Those with RA who achieved a Disease Activity Score (DAS)-28 below 3.2 and those with AS who achieved a very good response then were asked to gradually increase the interval between their etanercept injections from twice weekly to once weekly, said Veronica E. Abernethy, M.D., of the rheumatology practice development unit, St. Helens and Knowsley NHS Hospitals, Merseyside, England.

Currently, 7 of the 39 have successfully reduced their etanercept to once weekly without any deterioration in disease activity, which has resulted in a cost savings of $67,675 per year. This figure represents 9% of the total etanercept cost for the 39 patients, Dr. Abernethy said in a poster session.

BIRMINGHAM, ENGLAND — One promising strategy for holding down the cost of biologic therapy for patients with rheumatic diseases is to prescribe low doses when possible, results from two new studies have suggested.

With infliximab, for example, the typical dosage regimen in ankylosing spondylitis (AS) is 5 mg/kg given by infusion at weeks 1, 2, and 6 and then every 8 weeks. This is higher than the usual regimen for rheumatoid arthritis (RA).

“Because of cost pressures, we tried using conventional RA doses of 3 mg/kg in 13 AS patients,” Ramesh N. Jois, M.D., said at the joint meeting of the British Society for Rheumatology and the German Society for Rheumatology.

All patients had Bath AS Disease Activity Index (BASDAI) scores greater than 4 at baseline. Mean disease duration of these patients, 12 of whom were male, was 16.9 years.

Clinical response was judged to be a 50% or greater reduction in the BASDAI score at 3 months.

One patient did not respond to the low-dose regimen and required an increase to the higher dose. All other patients showed statistically significant improvements across multiple measures of efficacy, said Dr. Jois of the department of rheumatology, Norfolk and Norwich (England) University Hospital.

Some patients now have been on the regimen for 12 months, with persisting benefits. (See chart.)

Five patients have been able to reduce their methotrexate dose (mean reduction 14 mg/wk). One stopped cyclosporine, another stopped sulfasalazine, and five discontinued nonsteroidal anti-inflammatory drugs altogether, he said.

No side effects were seen with the low-dose infliximab therapy.

Use of this regimen has led to a significant cost savings of approximately $29,000 per patient per year, for a total cost savings of $315,000 to the unit in the past year, Dr. Jois said in a poster session. “We advise starting all AS patients on low-dose infliximab. Consider increasing to the higher dose only if they fail to respond,” he said.

Dr. Jois disclosed that his department has received research grant support from Wyeth, Schering-Plough, and Abbott Pharmaceuticals.

In a second study, 36 patients with RA and 3 patients with AS were treated with the standard etanercept regimen of 25 mg twice weekly for at least 3 months. Those with RA who achieved a Disease Activity Score (DAS)-28 below 3.2 and those with AS who achieved a very good response then were asked to gradually increase the interval between their etanercept injections from twice weekly to once weekly, said Veronica E. Abernethy, M.D., of the rheumatology practice development unit, St. Helens and Knowsley NHS Hospitals, Merseyside, England.

Currently, 7 of the 39 have successfully reduced their etanercept to once weekly without any deterioration in disease activity, which has resulted in a cost savings of $67,675 per year. This figure represents 9% of the total etanercept cost for the 39 patients, Dr. Abernethy said in a poster session.

BIRMINGHAM, ENGLAND — Tumor necrosis factor antagonists are the most effective treatment available for ankylosing spondylitis, according to the results of a systematic review of randomized placebo-controlled trials comparing the biologics with conventional drugs.

Prior to the introduction of biologic agents, treatment for ankylosing spondylitis (AS) was largely limited to physiotherapy and nonsteroidal antiinflammatory drugs (NSAIDs). Other drugs such as methotrexate and sulfasalazine have not shown the same efficacy for ankylosing spondylitis as they have for rheumatoid arthritis, Sarah Levy, M.D., said at the joint meeting of the British Society for Rheumatology and the German Society for Rheumatology.

From a search on Medline and Embase, Dr. Levy and her associates at University Hospital Lewisham, London, identified 14 trials of pharmacologic management of AS; 9 of the trials were of adequate quality and produced data that were comparable across all studies, she said. Two of the studies evaluated NSAIDs, three evaluated sulfasalazine, and four evaluated TNF-α blocking agents.

Spinal pain visual analog scale scores were available for all treatments, but the Bath Ankylosing Spondylitis Functional Index (BASFI) was available only for NSAIDs and anti-TNF-α treatment, said Dr. Levy, a rheumatologist at the hospital.

Treatment with NSAIDs and sulfasalazine did show significant benefit in BASFI and spinal pain, but the effect sizes were small. (See box.) Most of the effect of treatment with sulfasalazine was seen in patients with both axial and peripheral disease, rather than in those with axial disease alone. In contrast, anti-TNF-α treatment showed highly significant benefits and the largest effect size on both BASFI and spinal pain scores, she said in a poster session.

Four trials evaluating physical exercise regimens also were identified and showed no benefit in spinal pain scores compared with placebo.

BIRMINGHAM, ENGLAND — Tumor necrosis factor antagonists are the most effective treatment available for ankylosing spondylitis, according to the results of a systematic review of randomized placebo-controlled trials comparing the biologics with conventional drugs.

Prior to the introduction of biologic agents, treatment for ankylosing spondylitis (AS) was largely limited to physiotherapy and nonsteroidal antiinflammatory drugs (NSAIDs). Other drugs such as methotrexate and sulfasalazine have not shown the same efficacy for ankylosing spondylitis as they have for rheumatoid arthritis, Sarah Levy, M.D., said at the joint meeting of the British Society for Rheumatology and the German Society for Rheumatology.

From a search on Medline and Embase, Dr. Levy and her associates at University Hospital Lewisham, London, identified 14 trials of pharmacologic management of AS; 9 of the trials were of adequate quality and produced data that were comparable across all studies, she said. Two of the studies evaluated NSAIDs, three evaluated sulfasalazine, and four evaluated TNF-α blocking agents.

Spinal pain visual analog scale scores were available for all treatments, but the Bath Ankylosing Spondylitis Functional Index (BASFI) was available only for NSAIDs and anti-TNF-α treatment, said Dr. Levy, a rheumatologist at the hospital.

Treatment with NSAIDs and sulfasalazine did show significant benefit in BASFI and spinal pain, but the effect sizes were small. (See box.) Most of the effect of treatment with sulfasalazine was seen in patients with both axial and peripheral disease, rather than in those with axial disease alone. In contrast, anti-TNF-α treatment showed highly significant benefits and the largest effect size on both BASFI and spinal pain scores, she said in a poster session.

Four trials evaluating physical exercise regimens also were identified and showed no benefit in spinal pain scores compared with placebo.

BIRMINGHAM, ENGLAND — Tumor necrosis factor antagonists are the most effective treatment available for ankylosing spondylitis, according to the results of a systematic review of randomized placebo-controlled trials comparing the biologics with conventional drugs.

Prior to the introduction of biologic agents, treatment for ankylosing spondylitis (AS) was largely limited to physiotherapy and nonsteroidal antiinflammatory drugs (NSAIDs). Other drugs such as methotrexate and sulfasalazine have not shown the same efficacy for ankylosing spondylitis as they have for rheumatoid arthritis, Sarah Levy, M.D., said at the joint meeting of the British Society for Rheumatology and the German Society for Rheumatology.

From a search on Medline and Embase, Dr. Levy and her associates at University Hospital Lewisham, London, identified 14 trials of pharmacologic management of AS; 9 of the trials were of adequate quality and produced data that were comparable across all studies, she said. Two of the studies evaluated NSAIDs, three evaluated sulfasalazine, and four evaluated TNF-α blocking agents.

Spinal pain visual analog scale scores were available for all treatments, but the Bath Ankylosing Spondylitis Functional Index (BASFI) was available only for NSAIDs and anti-TNF-α treatment, said Dr. Levy, a rheumatologist at the hospital.

Treatment with NSAIDs and sulfasalazine did show significant benefit in BASFI and spinal pain, but the effect sizes were small. (See box.) Most of the effect of treatment with sulfasalazine was seen in patients with both axial and peripheral disease, rather than in those with axial disease alone. In contrast, anti-TNF-α treatment showed highly significant benefits and the largest effect size on both BASFI and spinal pain scores, she said in a poster session.

Four trials evaluating physical exercise regimens also were identified and showed no benefit in spinal pain scores compared with placebo.

BIRMINGHAM, ENGLAND — A newly identified human endogenous retrovirus that is much more prevalent in Africa than in other parts of the world may place its carriers at risk for certain autoimmune diseases, David Moyes, Ph.D., said at the joint meeting of the British Society for Rheumatology and the German Society for Rheumatology.

Patients with autoimmune diseases often have elevated antibody levels to certain structural proteins of human endogenous retroviruses (HERVs), suggesting a possible role for these viruses in autoimmune disease, Dr. Moyes said.

Until recently it was thought that HERVs were ubiquitous and fixed in the population, having been incorporated into the genome before the initial wave of human migration out of Africa some 200,000 years ago. But two of these viruses, HERV-K113 and HERV-K115 are now known to vary widely in prevalence across different populations. “This means that both viruses are likely to have been incorporated into the genome during more recent human evolution and that both could potentially induce an autoimmune response,” he said.

The mean prevalence of HERV-K113 identified by polymerase chain reaction testing in a sample of 174 subjects from Kenya, Malawi, and Côte d'Ivoire was 21.8%, compared with 4.2% in a sample of 96 subjects from the United Kingdom, said Dr. Moyes of the Kennedy Institute of Rheumatology, Imperial College, London.

Similarly, HERV-K115 was present in 34% of subjects from Africa and in only 1% of those in the United Kingdom.

“When you move off the African continent to the Arabian peninsula the prevalence drops off markedly. Neither virus was detected in any of 54 samples from Papua New Guinea,” he said.

“Because of the possibility that one or both of these retroviruses could be involved in autoimmune disease, we went on to analyze their prevalence in two U.K. disease cohorts,” he said. Among 96 patients with Sjögren's syndrome, the prevalence of the K113 allele was significantly increased, at 15.6%, compared with 4.2% among 96 normal controls. The allele also was more prevalent among 100 patients with multiple sclerosis, at 11.6%, he said.

Increases in these diseases were not associated with K115, however, which is a defective virus. “Both are full length proviruses, but HERV-K113 is a complete virus that has open reading frames and can fully express all its genes. HERV-K115 has a single deletion that prevents the expression of the Pro/Pol genes,” he said.

An audience member asked if there was any evidence that these viruses were pathogenic, and whether there was an association with the autoantibodies Ro and La that are present in many autoimmune diseases. Dr. Moyes replied that there does not appear to be an association with Ro and La specifically, but that there is an increase in many other autoantibodies seen in patients with scleroderma, rheumatoid arthritis, and Sjögren's syndrome.

“The exact relevance of those increases is open to question, but there is also a degree of evidence suggesting that proteins from these viruses can induce inflammation,” he said.

The prevalence of HERV-K113 and HERV-K115 varies widely across countries. The top number is the prevalence of HERV-K113 in each country. Underneath is the prevalence of HERV-K115. Courtesy Dr. David Moyes

BIRMINGHAM, ENGLAND — A newly identified human endogenous retrovirus that is much more prevalent in Africa than in other parts of the world may place its carriers at risk for certain autoimmune diseases, David Moyes, Ph.D., said at the joint meeting of the British Society for Rheumatology and the German Society for Rheumatology.

Patients with autoimmune diseases often have elevated antibody levels to certain structural proteins of human endogenous retroviruses (HERVs), suggesting a possible role for these viruses in autoimmune disease, Dr. Moyes said.

Until recently it was thought that HERVs were ubiquitous and fixed in the population, having been incorporated into the genome before the initial wave of human migration out of Africa some 200,000 years ago. But two of these viruses, HERV-K113 and HERV-K115 are now known to vary widely in prevalence across different populations. “This means that both viruses are likely to have been incorporated into the genome during more recent human evolution and that both could potentially induce an autoimmune response,” he said.

The mean prevalence of HERV-K113 identified by polymerase chain reaction testing in a sample of 174 subjects from Kenya, Malawi, and Côte d'Ivoire was 21.8%, compared with 4.2% in a sample of 96 subjects from the United Kingdom, said Dr. Moyes of the Kennedy Institute of Rheumatology, Imperial College, London.

Similarly, HERV-K115 was present in 34% of subjects from Africa and in only 1% of those in the United Kingdom.

“When you move off the African continent to the Arabian peninsula the prevalence drops off markedly. Neither virus was detected in any of 54 samples from Papua New Guinea,” he said.

“Because of the possibility that one or both of these retroviruses could be involved in autoimmune disease, we went on to analyze their prevalence in two U.K. disease cohorts,” he said. Among 96 patients with Sjögren's syndrome, the prevalence of the K113 allele was significantly increased, at 15.6%, compared with 4.2% among 96 normal controls. The allele also was more prevalent among 100 patients with multiple sclerosis, at 11.6%, he said.

Increases in these diseases were not associated with K115, however, which is a defective virus. “Both are full length proviruses, but HERV-K113 is a complete virus that has open reading frames and can fully express all its genes. HERV-K115 has a single deletion that prevents the expression of the Pro/Pol genes,” he said.

An audience member asked if there was any evidence that these viruses were pathogenic, and whether there was an association with the autoantibodies Ro and La that are present in many autoimmune diseases. Dr. Moyes replied that there does not appear to be an association with Ro and La specifically, but that there is an increase in many other autoantibodies seen in patients with scleroderma, rheumatoid arthritis, and Sjögren's syndrome.

“The exact relevance of those increases is open to question, but there is also a degree of evidence suggesting that proteins from these viruses can induce inflammation,” he said.

The prevalence of HERV-K113 and HERV-K115 varies widely across countries. The top number is the prevalence of HERV-K113 in each country. Underneath is the prevalence of HERV-K115. Courtesy Dr. David Moyes

BIRMINGHAM, ENGLAND — A newly identified human endogenous retrovirus that is much more prevalent in Africa than in other parts of the world may place its carriers at risk for certain autoimmune diseases, David Moyes, Ph.D., said at the joint meeting of the British Society for Rheumatology and the German Society for Rheumatology.

Patients with autoimmune diseases often have elevated antibody levels to certain structural proteins of human endogenous retroviruses (HERVs), suggesting a possible role for these viruses in autoimmune disease, Dr. Moyes said.

Until recently it was thought that HERVs were ubiquitous and fixed in the population, having been incorporated into the genome before the initial wave of human migration out of Africa some 200,000 years ago. But two of these viruses, HERV-K113 and HERV-K115 are now known to vary widely in prevalence across different populations. “This means that both viruses are likely to have been incorporated into the genome during more recent human evolution and that both could potentially induce an autoimmune response,” he said.

The mean prevalence of HERV-K113 identified by polymerase chain reaction testing in a sample of 174 subjects from Kenya, Malawi, and Côte d'Ivoire was 21.8%, compared with 4.2% in a sample of 96 subjects from the United Kingdom, said Dr. Moyes of the Kennedy Institute of Rheumatology, Imperial College, London.

Similarly, HERV-K115 was present in 34% of subjects from Africa and in only 1% of those in the United Kingdom.

“When you move off the African continent to the Arabian peninsula the prevalence drops off markedly. Neither virus was detected in any of 54 samples from Papua New Guinea,” he said.

“Because of the possibility that one or both of these retroviruses could be involved in autoimmune disease, we went on to analyze their prevalence in two U.K. disease cohorts,” he said. Among 96 patients with Sjögren's syndrome, the prevalence of the K113 allele was significantly increased, at 15.6%, compared with 4.2% among 96 normal controls. The allele also was more prevalent among 100 patients with multiple sclerosis, at 11.6%, he said.

Increases in these diseases were not associated with K115, however, which is a defective virus. “Both are full length proviruses, but HERV-K113 is a complete virus that has open reading frames and can fully express all its genes. HERV-K115 has a single deletion that prevents the expression of the Pro/Pol genes,” he said.

An audience member asked if there was any evidence that these viruses were pathogenic, and whether there was an association with the autoantibodies Ro and La that are present in many autoimmune diseases. Dr. Moyes replied that there does not appear to be an association with Ro and La specifically, but that there is an increase in many other autoantibodies seen in patients with scleroderma, rheumatoid arthritis, and Sjögren's syndrome.

“The exact relevance of those increases is open to question, but there is also a degree of evidence suggesting that proteins from these viruses can induce inflammation,” he said.

The prevalence of HERV-K113 and HERV-K115 varies widely across countries. The top number is the prevalence of HERV-K113 in each country. Underneath is the prevalence of HERV-K115. Courtesy Dr. David Moyes

NEW YORK — While bone mineral density T scores clearly are predictive of a postmenopausal woman's osteoporotic fracture risk, treatment decisions should take into account other factors, including her overall health and history of previous fractures, Stephen Honig, M.D., said at a rheumatology meeting sponsored by New York University.

“We have to do better than the T score in deciding who needs treatment for osteoporosis, because the long-term use of bisphosphonates has not been determined to be safe,” said Dr. Honig, director of the osteoporosis center at the Hospital for Joint Diseases Spine Center in New York.

Very long-term bisphosphonate therapy may lead to oversuppression of bone turnover, he said. This superhardening can hinder subsequent fracture healing, as was seen in a recent report of nine patients who sustained spontaneous, nonhealing fractures while on alendronate therapy (J. Clin. Endocrinol. Metab. 2005;90:1294–301).

These patients showed histomorphometric evidence of markedly suppressed bone formation, Dr. Honig said.

This new finding has heightened interest in targeting osteoporosis treatment. Research findings have begun to provide guidance on which patients can most benefit from treatment.

Most notable was the National Osteoporosis Risk Assessment (NORA) study, which enrolled 200,160 postmenopausal women aged 50 and older. In that study, bone mineral density (BMD) measurements were obtained at baseline, and the participants were followed for 1 year.

At follow up, one-third of all fractures and one-fifth of all hip fractures in particular occurred in women aged 50–64. Although the majority of fractures did occur in women 65 and older, the high number in the younger cohort “was a little surprising,” said Dr. Honig.

In addition, 80% of the women who had fractures during NORA had T scores that were higher than −2.5 and therefore did not meet the World Health Organization definition of osteoporosis. Most fell between −1 and −2.5, the osteopenic range, he said.

“We want to identify patients at risk in this middle range and not wait until they have obvious fractures,” he said.

The NORA investigators subsequently followed 57,421 osteopenic women and developed an algorithm for determining risk. As it turns out, identifying patients with a previous fracture, a T score below −1.8, a self-reported health status of fair or poor, and poor mobility were all factors significantly predictive of fracture risk (Arch. Intern. Med. 2004;164:1113–20).

Another prospective study conducted in France followed 672 healthy postmenopausal women for more than 5 years, and found an annual incidence of osteoporotic fractures of 21 per 1,000 women per year (Bone 2003;32:78–85). The French investigators identified the key risk factors (in order of importance) to be: a past fracture, hip BMD, low physical activity, low grip strength, age over 65, maternal fracture history, and past falls.

Based on the available data and tools at hand, Dr. Honig recommends that clinicians now consider treatment for the following patients:

▸ Women 65 and older, with or without a history of fracture, who have low BMD or other risk factors, such as low BMI and family history.

▸ Women 50 and older with a previous fracture and a T score of −1.8 or less.

▸ Women in poor overall health with mobility problems and low BMD.

▸ Women with low BMD and increased markers of bone resorption.

But some key questions still remain unanswered, Dr. Honig said. How long can a bisphosphonate be used? When should teriparatide or a selective estrogen receptor modulator be used? And what place does hormone therapy have in treatment strategies?

Dr. Honig disclosed that he receives support from Eli Lilly & Co. and is on the speakers' bureau of Sanofi-Aventis.

NEW YORK — While bone mineral density T scores clearly are predictive of a postmenopausal woman's osteoporotic fracture risk, treatment decisions should take into account other factors, including her overall health and history of previous fractures, Stephen Honig, M.D., said at a rheumatology meeting sponsored by New York University.

“We have to do better than the T score in deciding who needs treatment for osteoporosis, because the long-term use of bisphosphonates has not been determined to be safe,” said Dr. Honig, director of the osteoporosis center at the Hospital for Joint Diseases Spine Center in New York.

Very long-term bisphosphonate therapy may lead to oversuppression of bone turnover, he said. This superhardening can hinder subsequent fracture healing, as was seen in a recent report of nine patients who sustained spontaneous, nonhealing fractures while on alendronate therapy (J. Clin. Endocrinol. Metab. 2005;90:1294–301).

These patients showed histomorphometric evidence of markedly suppressed bone formation, Dr. Honig said.

This new finding has heightened interest in targeting osteoporosis treatment. Research findings have begun to provide guidance on which patients can most benefit from treatment.

Most notable was the National Osteoporosis Risk Assessment (NORA) study, which enrolled 200,160 postmenopausal women aged 50 and older. In that study, bone mineral density (BMD) measurements were obtained at baseline, and the participants were followed for 1 year.

At follow up, one-third of all fractures and one-fifth of all hip fractures in particular occurred in women aged 50–64. Although the majority of fractures did occur in women 65 and older, the high number in the younger cohort “was a little surprising,” said Dr. Honig.

In addition, 80% of the women who had fractures during NORA had T scores that were higher than −2.5 and therefore did not meet the World Health Organization definition of osteoporosis. Most fell between −1 and −2.5, the osteopenic range, he said.

“We want to identify patients at risk in this middle range and not wait until they have obvious fractures,” he said.

The NORA investigators subsequently followed 57,421 osteopenic women and developed an algorithm for determining risk. As it turns out, identifying patients with a previous fracture, a T score below −1.8, a self-reported health status of fair or poor, and poor mobility were all factors significantly predictive of fracture risk (Arch. Intern. Med. 2004;164:1113–20).

Another prospective study conducted in France followed 672 healthy postmenopausal women for more than 5 years, and found an annual incidence of osteoporotic fractures of 21 per 1,000 women per year (Bone 2003;32:78–85). The French investigators identified the key risk factors (in order of importance) to be: a past fracture, hip BMD, low physical activity, low grip strength, age over 65, maternal fracture history, and past falls.

Based on the available data and tools at hand, Dr. Honig recommends that clinicians now consider treatment for the following patients:

▸ Women 65 and older, with or without a history of fracture, who have low BMD or other risk factors, such as low BMI and family history.

▸ Women 50 and older with a previous fracture and a T score of −1.8 or less.

▸ Women in poor overall health with mobility problems and low BMD.

▸ Women with low BMD and increased markers of bone resorption.

But some key questions still remain unanswered, Dr. Honig said. How long can a bisphosphonate be used? When should teriparatide or a selective estrogen receptor modulator be used? And what place does hormone therapy have in treatment strategies?

Dr. Honig disclosed that he receives support from Eli Lilly & Co. and is on the speakers' bureau of Sanofi-Aventis.

NEW YORK — While bone mineral density T scores clearly are predictive of a postmenopausal woman's osteoporotic fracture risk, treatment decisions should take into account other factors, including her overall health and history of previous fractures, Stephen Honig, M.D., said at a rheumatology meeting sponsored by New York University.

“We have to do better than the T score in deciding who needs treatment for osteoporosis, because the long-term use of bisphosphonates has not been determined to be safe,” said Dr. Honig, director of the osteoporosis center at the Hospital for Joint Diseases Spine Center in New York.

Very long-term bisphosphonate therapy may lead to oversuppression of bone turnover, he said. This superhardening can hinder subsequent fracture healing, as was seen in a recent report of nine patients who sustained spontaneous, nonhealing fractures while on alendronate therapy (J. Clin. Endocrinol. Metab. 2005;90:1294–301).

These patients showed histomorphometric evidence of markedly suppressed bone formation, Dr. Honig said.

This new finding has heightened interest in targeting osteoporosis treatment. Research findings have begun to provide guidance on which patients can most benefit from treatment.

Most notable was the National Osteoporosis Risk Assessment (NORA) study, which enrolled 200,160 postmenopausal women aged 50 and older. In that study, bone mineral density (BMD) measurements were obtained at baseline, and the participants were followed for 1 year.

At follow up, one-third of all fractures and one-fifth of all hip fractures in particular occurred in women aged 50–64. Although the majority of fractures did occur in women 65 and older, the high number in the younger cohort “was a little surprising,” said Dr. Honig.

In addition, 80% of the women who had fractures during NORA had T scores that were higher than −2.5 and therefore did not meet the World Health Organization definition of osteoporosis. Most fell between −1 and −2.5, the osteopenic range, he said.

“We want to identify patients at risk in this middle range and not wait until they have obvious fractures,” he said.

The NORA investigators subsequently followed 57,421 osteopenic women and developed an algorithm for determining risk. As it turns out, identifying patients with a previous fracture, a T score below −1.8, a self-reported health status of fair or poor, and poor mobility were all factors significantly predictive of fracture risk (Arch. Intern. Med. 2004;164:1113–20).

Another prospective study conducted in France followed 672 healthy postmenopausal women for more than 5 years, and found an annual incidence of osteoporotic fractures of 21 per 1,000 women per year (Bone 2003;32:78–85). The French investigators identified the key risk factors (in order of importance) to be: a past fracture, hip BMD, low physical activity, low grip strength, age over 65, maternal fracture history, and past falls.

Based on the available data and tools at hand, Dr. Honig recommends that clinicians now consider treatment for the following patients:

▸ Women 65 and older, with or without a history of fracture, who have low BMD or other risk factors, such as low BMI and family history.

▸ Women 50 and older with a previous fracture and a T score of −1.8 or less.

▸ Women in poor overall health with mobility problems and low BMD.

▸ Women with low BMD and increased markers of bone resorption.

But some key questions still remain unanswered, Dr. Honig said. How long can a bisphosphonate be used? When should teriparatide or a selective estrogen receptor modulator be used? And what place does hormone therapy have in treatment strategies?

Dr. Honig disclosed that he receives support from Eli Lilly & Co. and is on the speakers' bureau of Sanofi-Aventis.

NEW YORK — With revisions to the consensus guidelines for the management of women with cervical cytological abnormalities expected in 2006, experts are taking a hard look at ways the guidelines might be tailored to be more age specific.

Much less is known about the natural history of cervical intraepithelial neoplasia (CIN) in young women, compared with older women. The 2001 guidelines do not provide specific recommendations for adolescents and young women, and the result today “is that we are probably doing a lot more harm than good,” Thomas C. Wright, M.D., said at a gynecology conference sponsored by Mount Sinai School of Medicine.

Screening as it is practiced today is generating a large number of false positives, particularly among younger women. In adolescents aged 16–18 years, 1 in 10 will have a false-positive result, and the cost implications are significant, Dr. Wright said.

Why all the false positives? High-risk strains of HPV are “essentially ubiquitous” among sexually active young women. “I have looked at young women serially over a period of 2–3 years, and found that two-thirds became HPV-DNA positive,” said Dr. Wright, director of the division of gynecologic and obstetric pathology, Columbia University College of Physicians and Surgeons, New York City.

In another study, more than 80% of college-aged women were HPV positive when tested monthly, but the vast majority are transient infections and clear spontaneously. In a study from Rutgers University, New Brunswick, N.J., where two-thirds of the female participants were HPV positive, by 1 year, 70% of infections had cleared, and by 2 years, 92% had spontaneously cleared. Other studies have shown similar results, he said.

Certain aspects of follow-up and management have been evolving differently for younger women. Among 18-year-olds with Pap smears classified as atypical squamous cells of undetermined significance (ASCUS), 71% will be positive for high-risk HPV and two-thirds will continue to be abnormal on a repeat Pap smear. “So anything you do in this population means that the bulk of them are going to end up getting sent for colposcopy,” he said.

“We don't have a recommendation on how you should manage ASCUS, but I can tell you that in an 18-year-old it is probably not wise to be doing HPV-DNA testing. What we are doing at Columbia is following up with repeat cytology,” he said.

For low-grade squamous intraepithelial lesions (LSIL), the options are to repeat the Pap smear, perform HPV testing, or to do a colposcopy. “HPV testing in a young woman with LSIL is a complete waste of time, as 87% are going to be HPV-DNA positive. If you repeat the Pap smear, 81% are going to remain abnormal unless you wait years for the infection to clear,” he said. Therefore, most [physicians] believe adolescents with LSIL should undergo colposcopy, he said.

Colposcopy is also advised for high-grade squamous intraepithelial lesions. “But if the lesions are not biopsy-confirmed CIN 2 or 3, rather than doing a loop electrosurgical excisional procedure, we can follow them by doing colposcopy and cytology at 4- to 6-month intervals provided the colposcopy is satisfactory, the endocervical curettage findings are essentially negative, and the patient accepts the risk of possible occult disease,” Dr. Wright said.

NEW YORK — With revisions to the consensus guidelines for the management of women with cervical cytological abnormalities expected in 2006, experts are taking a hard look at ways the guidelines might be tailored to be more age specific.

Much less is known about the natural history of cervical intraepithelial neoplasia (CIN) in young women, compared with older women. The 2001 guidelines do not provide specific recommendations for adolescents and young women, and the result today “is that we are probably doing a lot more harm than good,” Thomas C. Wright, M.D., said at a gynecology conference sponsored by Mount Sinai School of Medicine.

Screening as it is practiced today is generating a large number of false positives, particularly among younger women. In adolescents aged 16–18 years, 1 in 10 will have a false-positive result, and the cost implications are significant, Dr. Wright said.

Why all the false positives? High-risk strains of HPV are “essentially ubiquitous” among sexually active young women. “I have looked at young women serially over a period of 2–3 years, and found that two-thirds became HPV-DNA positive,” said Dr. Wright, director of the division of gynecologic and obstetric pathology, Columbia University College of Physicians and Surgeons, New York City.

In another study, more than 80% of college-aged women were HPV positive when tested monthly, but the vast majority are transient infections and clear spontaneously. In a study from Rutgers University, New Brunswick, N.J., where two-thirds of the female participants were HPV positive, by 1 year, 70% of infections had cleared, and by 2 years, 92% had spontaneously cleared. Other studies have shown similar results, he said.

Certain aspects of follow-up and management have been evolving differently for younger women. Among 18-year-olds with Pap smears classified as atypical squamous cells of undetermined significance (ASCUS), 71% will be positive for high-risk HPV and two-thirds will continue to be abnormal on a repeat Pap smear. “So anything you do in this population means that the bulk of them are going to end up getting sent for colposcopy,” he said.

“We don't have a recommendation on how you should manage ASCUS, but I can tell you that in an 18-year-old it is probably not wise to be doing HPV-DNA testing. What we are doing at Columbia is following up with repeat cytology,” he said.

For low-grade squamous intraepithelial lesions (LSIL), the options are to repeat the Pap smear, perform HPV testing, or to do a colposcopy. “HPV testing in a young woman with LSIL is a complete waste of time, as 87% are going to be HPV-DNA positive. If you repeat the Pap smear, 81% are going to remain abnormal unless you wait years for the infection to clear,” he said. Therefore, most [physicians] believe adolescents with LSIL should undergo colposcopy, he said.

Colposcopy is also advised for high-grade squamous intraepithelial lesions. “But if the lesions are not biopsy-confirmed CIN 2 or 3, rather than doing a loop electrosurgical excisional procedure, we can follow them by doing colposcopy and cytology at 4- to 6-month intervals provided the colposcopy is satisfactory, the endocervical curettage findings are essentially negative, and the patient accepts the risk of possible occult disease,” Dr. Wright said.

NEW YORK — With revisions to the consensus guidelines for the management of women with cervical cytological abnormalities expected in 2006, experts are taking a hard look at ways the guidelines might be tailored to be more age specific.

Much less is known about the natural history of cervical intraepithelial neoplasia (CIN) in young women, compared with older women. The 2001 guidelines do not provide specific recommendations for adolescents and young women, and the result today “is that we are probably doing a lot more harm than good,” Thomas C. Wright, M.D., said at a gynecology conference sponsored by Mount Sinai School of Medicine.

Screening as it is practiced today is generating a large number of false positives, particularly among younger women. In adolescents aged 16–18 years, 1 in 10 will have a false-positive result, and the cost implications are significant, Dr. Wright said.

Why all the false positives? High-risk strains of HPV are “essentially ubiquitous” among sexually active young women. “I have looked at young women serially over a period of 2–3 years, and found that two-thirds became HPV-DNA positive,” said Dr. Wright, director of the division of gynecologic and obstetric pathology, Columbia University College of Physicians and Surgeons, New York City.

In another study, more than 80% of college-aged women were HPV positive when tested monthly, but the vast majority are transient infections and clear spontaneously. In a study from Rutgers University, New Brunswick, N.J., where two-thirds of the female participants were HPV positive, by 1 year, 70% of infections had cleared, and by 2 years, 92% had spontaneously cleared. Other studies have shown similar results, he said.

Certain aspects of follow-up and management have been evolving differently for younger women. Among 18-year-olds with Pap smears classified as atypical squamous cells of undetermined significance (ASCUS), 71% will be positive for high-risk HPV and two-thirds will continue to be abnormal on a repeat Pap smear. “So anything you do in this population means that the bulk of them are going to end up getting sent for colposcopy,” he said.

“We don't have a recommendation on how you should manage ASCUS, but I can tell you that in an 18-year-old it is probably not wise to be doing HPV-DNA testing. What we are doing at Columbia is following up with repeat cytology,” he said.

For low-grade squamous intraepithelial lesions (LSIL), the options are to repeat the Pap smear, perform HPV testing, or to do a colposcopy. “HPV testing in a young woman with LSIL is a complete waste of time, as 87% are going to be HPV-DNA positive. If you repeat the Pap smear, 81% are going to remain abnormal unless you wait years for the infection to clear,” he said. Therefore, most [physicians] believe adolescents with LSIL should undergo colposcopy, he said.

Colposcopy is also advised for high-grade squamous intraepithelial lesions. “But if the lesions are not biopsy-confirmed CIN 2 or 3, rather than doing a loop electrosurgical excisional procedure, we can follow them by doing colposcopy and cytology at 4- to 6-month intervals provided the colposcopy is satisfactory, the endocervical curettage findings are essentially negative, and the patient accepts the risk of possible occult disease,” Dr. Wright said.

NEW YORK — With revisions to the consensus guidelines for the management of women with cervical cytological abnormalities expected in 2006, experts are taking a hard look at ways the guidelines might be tailored to be more age specific.

Much less is known about the natural history of cervical intraepithelial neoplasia (CIN) in young women, compared with older women. The 2001 guidelines do not provide specific recommendations for adolescents and young women, and the result today “is that we are probably doing a lot more harm than good,” Thomas C. Wright, M.D., said at a gynecology conference sponsored by Mount Sinai School of Medicine.

Screening as it is practiced today is generating a large number of false positives, particularly among younger women. In adolescents aged 16-18 years, 1 in 10 will have a false positive result, and the cost implications of that are significant, he said.

Of course, false positives generate tremendous anxiety. “Today's 18-year-olds go on the Web, they know about HPV [human papillomavirus], they're afraid they are going to develop invasive cervical cancer. They are afraid they will be transmitting a disease to their boyfriends. There is a huge amount of concern associated with abnormal results in this population,” he said.

Why all the false positives? High-risk strains of HPV are “essentially ubiquitous” among sexually active young women. “I have looked at young women serially over a period of 2-3 years, and found that two-thirds became HPV-DNA positive,” said Dr. Wright, director of the division of gynecologic and obstetric pathology, Columbia University College of Physicians and Surgeons, New York City.

In another study, more than 80% of college-aged women were HPV positive when tested monthly, but the vast majority are transient infections and clear spontaneously. In a study from Rutgers University, New Brunswick, N.J., where two-thirds of the participants were HPV positive, by 1 year, 70% of infections had cleared, and by 2 years, 92% had spontaneously cleared. Other studies have shown similar results.

Certain aspects of follow-up and management have been evolving differently for younger women. Among 18-year-olds with Pap smears classified as atypical squamous cells of undetermined significance (ASCUS), 71% will be positive for high-risk HPV and two-thirds will continue to be abnormal on a repeat Pap smear. “Anything you do in this population means that the bulk of them are going to end up getting sent for colposcopy,” he said.

“We don't have a recommendation on how you should manage ASCUS, but I can tell you that in an 18-year-old it is probably not wise to be doing HPV-DNA testing. What we are doing at Columbia is following up with repeat cytology,” he said.

For low-grade squamous intraepithelial lesions (LSIL), the options are to repeat the Pap smear, perform HPV testing, or to do a colposcopy. “HPV testing in a young woman with LSIL is a complete waste of time, as 87% are going to be HPV-DNA positive. If you repeat the Pap smear, 81% are going to remain abnormal unless you wait years for the infection to clear,” he said. Most [physicians] believe adolescents with LSIL should undergo colposcopy, he said.

For high-grade squamous intraepithelial lesions (HSIL) in adolescents or young women colposcopy is recommended. “But if the lesions are not biopsy-confirmed cervical intraepithelial neoplasia (CIN) 2 or 3, rather than doing a loop electrosurgical excisional procedure, we can follow them by doing colposcopy and cytology at 4- to 6-month intervals provided the colposcopy is satisfactory, the endocervical curettage findings are essentially negative, and the patient accepts the risk of possible occult disease,” Dr. Wright said.

NEW YORK — With revisions to the consensus guidelines for the management of women with cervical cytological abnormalities expected in 2006, experts are taking a hard look at ways the guidelines might be tailored to be more age specific.

Much less is known about the natural history of cervical intraepithelial neoplasia (CIN) in young women, compared with older women. The 2001 guidelines do not provide specific recommendations for adolescents and young women, and the result today “is that we are probably doing a lot more harm than good,” Thomas C. Wright, M.D., said at a gynecology conference sponsored by Mount Sinai School of Medicine.

Screening as it is practiced today is generating a large number of false positives, particularly among younger women. In adolescents aged 16-18 years, 1 in 10 will have a false positive result, and the cost implications of that are significant, he said.

Of course, false positives generate tremendous anxiety. “Today's 18-year-olds go on the Web, they know about HPV [human papillomavirus], they're afraid they are going to develop invasive cervical cancer. They are afraid they will be transmitting a disease to their boyfriends. There is a huge amount of concern associated with abnormal results in this population,” he said.

Why all the false positives? High-risk strains of HPV are “essentially ubiquitous” among sexually active young women. “I have looked at young women serially over a period of 2-3 years, and found that two-thirds became HPV-DNA positive,” said Dr. Wright, director of the division of gynecologic and obstetric pathology, Columbia University College of Physicians and Surgeons, New York City.

In another study, more than 80% of college-aged women were HPV positive when tested monthly, but the vast majority are transient infections and clear spontaneously. In a study from Rutgers University, New Brunswick, N.J., where two-thirds of the participants were HPV positive, by 1 year, 70% of infections had cleared, and by 2 years, 92% had spontaneously cleared. Other studies have shown similar results.

Certain aspects of follow-up and management have been evolving differently for younger women. Among 18-year-olds with Pap smears classified as atypical squamous cells of undetermined significance (ASCUS), 71% will be positive for high-risk HPV and two-thirds will continue to be abnormal on a repeat Pap smear. “Anything you do in this population means that the bulk of them are going to end up getting sent for colposcopy,” he said.

“We don't have a recommendation on how you should manage ASCUS, but I can tell you that in an 18-year-old it is probably not wise to be doing HPV-DNA testing. What we are doing at Columbia is following up with repeat cytology,” he said.

For low-grade squamous intraepithelial lesions (LSIL), the options are to repeat the Pap smear, perform HPV testing, or to do a colposcopy. “HPV testing in a young woman with LSIL is a complete waste of time, as 87% are going to be HPV-DNA positive. If you repeat the Pap smear, 81% are going to remain abnormal unless you wait years for the infection to clear,” he said. Most [physicians] believe adolescents with LSIL should undergo colposcopy, he said.

For high-grade squamous intraepithelial lesions (HSIL) in adolescents or young women colposcopy is recommended. “But if the lesions are not biopsy-confirmed cervical intraepithelial neoplasia (CIN) 2 or 3, rather than doing a loop electrosurgical excisional procedure, we can follow them by doing colposcopy and cytology at 4- to 6-month intervals provided the colposcopy is satisfactory, the endocervical curettage findings are essentially negative, and the patient accepts the risk of possible occult disease,” Dr. Wright said.

NEW YORK — With revisions to the consensus guidelines for the management of women with cervical cytological abnormalities expected in 2006, experts are taking a hard look at ways the guidelines might be tailored to be more age specific.

Much less is known about the natural history of cervical intraepithelial neoplasia (CIN) in young women, compared with older women. The 2001 guidelines do not provide specific recommendations for adolescents and young women, and the result today “is that we are probably doing a lot more harm than good,” Thomas C. Wright, M.D., said at a gynecology conference sponsored by Mount Sinai School of Medicine.

Screening as it is practiced today is generating a large number of false positives, particularly among younger women. In adolescents aged 16-18 years, 1 in 10 will have a false positive result, and the cost implications of that are significant, he said.

Of course, false positives generate tremendous anxiety. “Today's 18-year-olds go on the Web, they know about HPV [human papillomavirus], they're afraid they are going to develop invasive cervical cancer. They are afraid they will be transmitting a disease to their boyfriends. There is a huge amount of concern associated with abnormal results in this population,” he said.

Why all the false positives? High-risk strains of HPV are “essentially ubiquitous” among sexually active young women. “I have looked at young women serially over a period of 2-3 years, and found that two-thirds became HPV-DNA positive,” said Dr. Wright, director of the division of gynecologic and obstetric pathology, Columbia University College of Physicians and Surgeons, New York City.

In another study, more than 80% of college-aged women were HPV positive when tested monthly, but the vast majority are transient infections and clear spontaneously. In a study from Rutgers University, New Brunswick, N.J., where two-thirds of the participants were HPV positive, by 1 year, 70% of infections had cleared, and by 2 years, 92% had spontaneously cleared. Other studies have shown similar results.

Certain aspects of follow-up and management have been evolving differently for younger women. Among 18-year-olds with Pap smears classified as atypical squamous cells of undetermined significance (ASCUS), 71% will be positive for high-risk HPV and two-thirds will continue to be abnormal on a repeat Pap smear. “Anything you do in this population means that the bulk of them are going to end up getting sent for colposcopy,” he said.

“We don't have a recommendation on how you should manage ASCUS, but I can tell you that in an 18-year-old it is probably not wise to be doing HPV-DNA testing. What we are doing at Columbia is following up with repeat cytology,” he said.

For low-grade squamous intraepithelial lesions (LSIL), the options are to repeat the Pap smear, perform HPV testing, or to do a colposcopy. “HPV testing in a young woman with LSIL is a complete waste of time, as 87% are going to be HPV-DNA positive. If you repeat the Pap smear, 81% are going to remain abnormal unless you wait years for the infection to clear,” he said. Most [physicians] believe adolescents with LSIL should undergo colposcopy, he said.

For high-grade squamous intraepithelial lesions (HSIL) in adolescents or young women colposcopy is recommended. “But if the lesions are not biopsy-confirmed cervical intraepithelial neoplasia (CIN) 2 or 3, rather than doing a loop electrosurgical excisional procedure, we can follow them by doing colposcopy and cytology at 4- to 6-month intervals provided the colposcopy is satisfactory, the endocervical curettage findings are essentially negative, and the patient accepts the risk of possible occult disease,” Dr. Wright said.

NEW YORK — A vulvar injury in a child is likely to heal without major intervention, even if a large hematoma is present and the patient complains of severe pain, David Muram, M.D., said at a gynecology conference sponsored by Mount Sinai School of Medicine.

Typical vulvar injuries are accidental deceleration injuries, occurring when the child falls on the crossbar of a bicycle or while climbing fences or playground equipment. The vagina, urethra, and hymen are usually spared because of the protection provided by the overlying labia, Dr. Muram said.

If there is no evidence of hymeneal injury—which is unlikely to result from an accident—the main concern is ensuring the child can void. If not, she should be kept for observation, and a suprapubic catheter should be placed, he said.

It's also a good idea to check whether there is a fracture of the pubic bone. “Tell her to stand up and raise one foot at a time. If this causes pain, get an x-ray. Not that you are going to do anything about it, but you won't be sued for missing it,” said Dr. Muram of the department of obstetrics and gynecology at the University of Tennessee, Memphis, and consultant to Eli Lilly & Co., Indianapolis.

In most cases, contusion of the vulva does not require special treatment, other than cold packs. Drainage is required only if bleeding persists and there is a large hematoma that continues to grow. Any clotted blood should be removed and the bleeding points identified and ligated, he said.

If the source of the bleeding in a large hematoma cannot be identified, pack the cavity with gauze and apply a firm pressure dressing. The pack can be removed the next day, but watch for possible renewed bleeding, he said.

It's also wise to prescribe a broad-spectrum antibiotic prophylactically, particularly if the hematoma is incised.

“Sitz baths are wonderful in this situation, and make sure the child lies on an air-filled doughnut to prevent pressure necrosis of the external genitalia,” he said.

NEW YORK — A vulvar injury in a child is likely to heal without major intervention, even if a large hematoma is present and the patient complains of severe pain, David Muram, M.D., said at a gynecology conference sponsored by Mount Sinai School of Medicine.

Typical vulvar injuries are accidental deceleration injuries, occurring when the child falls on the crossbar of a bicycle or while climbing fences or playground equipment. The vagina, urethra, and hymen are usually spared because of the protection provided by the overlying labia, Dr. Muram said.

If there is no evidence of hymeneal injury—which is unlikely to result from an accident—the main concern is ensuring the child can void. If not, she should be kept for observation, and a suprapubic catheter should be placed, he said.

It's also a good idea to check whether there is a fracture of the pubic bone. “Tell her to stand up and raise one foot at a time. If this causes pain, get an x-ray. Not that you are going to do anything about it, but you won't be sued for missing it,” said Dr. Muram of the department of obstetrics and gynecology at the University of Tennessee, Memphis, and consultant to Eli Lilly & Co., Indianapolis.

In most cases, contusion of the vulva does not require special treatment, other than cold packs. Drainage is required only if bleeding persists and there is a large hematoma that continues to grow. Any clotted blood should be removed and the bleeding points identified and ligated, he said.

If the source of the bleeding in a large hematoma cannot be identified, pack the cavity with gauze and apply a firm pressure dressing. The pack can be removed the next day, but watch for possible renewed bleeding, he said.

It's also wise to prescribe a broad-spectrum antibiotic prophylactically, particularly if the hematoma is incised.

“Sitz baths are wonderful in this situation, and make sure the child lies on an air-filled doughnut to prevent pressure necrosis of the external genitalia,” he said.

NEW YORK — A vulvar injury in a child is likely to heal without major intervention, even if a large hematoma is present and the patient complains of severe pain, David Muram, M.D., said at a gynecology conference sponsored by Mount Sinai School of Medicine.

Typical vulvar injuries are accidental deceleration injuries, occurring when the child falls on the crossbar of a bicycle or while climbing fences or playground equipment. The vagina, urethra, and hymen are usually spared because of the protection provided by the overlying labia, Dr. Muram said.

If there is no evidence of hymeneal injury—which is unlikely to result from an accident—the main concern is ensuring the child can void. If not, she should be kept for observation, and a suprapubic catheter should be placed, he said.

It's also a good idea to check whether there is a fracture of the pubic bone. “Tell her to stand up and raise one foot at a time. If this causes pain, get an x-ray. Not that you are going to do anything about it, but you won't be sued for missing it,” said Dr. Muram of the department of obstetrics and gynecology at the University of Tennessee, Memphis, and consultant to Eli Lilly & Co., Indianapolis.

In most cases, contusion of the vulva does not require special treatment, other than cold packs. Drainage is required only if bleeding persists and there is a large hematoma that continues to grow. Any clotted blood should be removed and the bleeding points identified and ligated, he said.

If the source of the bleeding in a large hematoma cannot be identified, pack the cavity with gauze and apply a firm pressure dressing. The pack can be removed the next day, but watch for possible renewed bleeding, he said.

It's also wise to prescribe a broad-spectrum antibiotic prophylactically, particularly if the hematoma is incised.

“Sitz baths are wonderful in this situation, and make sure the child lies on an air-filled doughnut to prevent pressure necrosis of the external genitalia,” he said.

NEW YORK — While bone mineral density T scores clearly are predictive of a postmenopausal woman's osteoporotic fracture risk, treatment decisions should take into account other factors, including her overall health and history of previous fractures, Stephen Honig, M.D., said at a rheumatology meeting sponsored by New York University.

“We have to do better than the T score in deciding who needs treatment for osteoporosis, because the long-term use of bisphosphonates has not been determined to be safe,” said Dr. Honig, director of the osteoporosis center at the Hospital for Joint Diseases Spine Center in New York.

Very long-term bisphosphonate therapy may lead to oversuppression of bone turnover, he said. This superhardening can hinder subsequent fracture healing, as was seen in a recent report of nine patients who sustained spontaneous, nonhealing fractures while on alendronate therapy (J. Clin. Endocrinol. Metab. 2005;90:1294-301).

These patients showed histomorphometric evidence of markedly suppressed bone formation, Dr. Honig said.

This new finding has heightened interest in targeting osteoporosis treatment. Research findings have begun to provide guidance on which patients can most benefit from treatment.

Most notable was the National Osteoporosis Risk Assessment (NORA) study, which enrolled 200,160 postmenopausal women aged 50 and older. In that study, bone mineral density (BMD) measurements were obtained at baseline, and the participants were followed for 1 year.

At follow up, one-third of all fractures and one-fifth of all hip fractures in particular occurred in women aged 50-64. Although the majority of fractures did occur in women 65 and older, the high number in the younger cohort “was a little surprising,” said Dr. Honig.

Another finding that emerged from NORA was that 80% of the women who had fractures during the yearlong study had T scores that were higher than -2.5 and therefore did not meet the World Health Organization definition of osteoporosis. Most fell between -1 and -2.5, the osteopenic range, he said.

“We want to identify patients at risk in this middle range and not wait until they have obvious fractures,” he said.

The NORA investigators subsequently followed 57,421 osteopenic women and developed an algorithm for determining risk. As it turns out, identifying patients with a previous fracture, a T score below -1.8, a self-reported health status of fair or poor, and poor mobility were all factors significantly predictive of fracture risk (Arch. Intern. Med. 2004;164:1113-20).

Another prospective study conducted in France followed 672 healthy postmenopausal women for more than 5 years, and found an annual incidence of osteoporotic fractures of 21 per 1,000 women per year (Bone 2003;32:78-85). The French investigators identified the key risk factors (in order of importance) to be: a past fracture, hip BMD, low physical activity, low grip strength, age over 65, maternal fracture history, and past falls.

Other studies have also suggested additional risk factors, including smoking, low body mass index, and increased markers of bone absorption.

Based on the available data and tools at hand, Dr. Honig recommends that clinicians now consider treatment for the following patients:

▸ Women 65 and older, with or without a history of fracture, who have low BMD or other risk factors, such as low BMI and family history.

▸ Women 50 and older with a previous fracture and a T score of -1.8 or less.

▸ Women in poor overall health with mobility problems and low BMD.

▸ Women with low BMD and increased markers of bone resorption.

But questions remain, he said. How long can a bisphosphonate be used? When should teriparatide or a selective estrogen receptor modulator be used? What place does hormone replacement therapy have in treatment strategies? “There is some new evidence that postmenopausal women with certain levels of endogenous estradiol have a lower incidence of fractures. This may translate into using very low-dose [hormone therapy], which conceivably could be safer than what was seen in the Women's Health Initiative,” he said.

Dr. Honig disclosed that he receives support from Eli Lilly & Co. and is on the speakers' bureau of Sanofi-Aventis.

NEW YORK — While bone mineral density T scores clearly are predictive of a postmenopausal woman's osteoporotic fracture risk, treatment decisions should take into account other factors, including her overall health and history of previous fractures, Stephen Honig, M.D., said at a rheumatology meeting sponsored by New York University.

“We have to do better than the T score in deciding who needs treatment for osteoporosis, because the long-term use of bisphosphonates has not been determined to be safe,” said Dr. Honig, director of the osteoporosis center at the Hospital for Joint Diseases Spine Center in New York.

Very long-term bisphosphonate therapy may lead to oversuppression of bone turnover, he said. This superhardening can hinder subsequent fracture healing, as was seen in a recent report of nine patients who sustained spontaneous, nonhealing fractures while on alendronate therapy (J. Clin. Endocrinol. Metab. 2005;90:1294-301).

These patients showed histomorphometric evidence of markedly suppressed bone formation, Dr. Honig said.

This new finding has heightened interest in targeting osteoporosis treatment. Research findings have begun to provide guidance on which patients can most benefit from treatment.

Most notable was the National Osteoporosis Risk Assessment (NORA) study, which enrolled 200,160 postmenopausal women aged 50 and older. In that study, bone mineral density (BMD) measurements were obtained at baseline, and the participants were followed for 1 year.

At follow up, one-third of all fractures and one-fifth of all hip fractures in particular occurred in women aged 50-64. Although the majority of fractures did occur in women 65 and older, the high number in the younger cohort “was a little surprising,” said Dr. Honig.

Another finding that emerged from NORA was that 80% of the women who had fractures during the yearlong study had T scores that were higher than -2.5 and therefore did not meet the World Health Organization definition of osteoporosis. Most fell between -1 and -2.5, the osteopenic range, he said.

“We want to identify patients at risk in this middle range and not wait until they have obvious fractures,” he said.

The NORA investigators subsequently followed 57,421 osteopenic women and developed an algorithm for determining risk. As it turns out, identifying patients with a previous fracture, a T score below -1.8, a self-reported health status of fair or poor, and poor mobility were all factors significantly predictive of fracture risk (Arch. Intern. Med. 2004;164:1113-20).

Another prospective study conducted in France followed 672 healthy postmenopausal women for more than 5 years, and found an annual incidence of osteoporotic fractures of 21 per 1,000 women per year (Bone 2003;32:78-85). The French investigators identified the key risk factors (in order of importance) to be: a past fracture, hip BMD, low physical activity, low grip strength, age over 65, maternal fracture history, and past falls.

Other studies have also suggested additional risk factors, including smoking, low body mass index, and increased markers of bone absorption.

Based on the available data and tools at hand, Dr. Honig recommends that clinicians now consider treatment for the following patients:

▸ Women 65 and older, with or without a history of fracture, who have low BMD or other risk factors, such as low BMI and family history.

▸ Women 50 and older with a previous fracture and a T score of -1.8 or less.

▸ Women in poor overall health with mobility problems and low BMD.

▸ Women with low BMD and increased markers of bone resorption.

But questions remain, he said. How long can a bisphosphonate be used? When should teriparatide or a selective estrogen receptor modulator be used? What place does hormone replacement therapy have in treatment strategies? “There is some new evidence that postmenopausal women with certain levels of endogenous estradiol have a lower incidence of fractures. This may translate into using very low-dose [hormone therapy], which conceivably could be safer than what was seen in the Women's Health Initiative,” he said.

Dr. Honig disclosed that he receives support from Eli Lilly & Co. and is on the speakers' bureau of Sanofi-Aventis.

NEW YORK — While bone mineral density T scores clearly are predictive of a postmenopausal woman's osteoporotic fracture risk, treatment decisions should take into account other factors, including her overall health and history of previous fractures, Stephen Honig, M.D., said at a rheumatology meeting sponsored by New York University.

“We have to do better than the T score in deciding who needs treatment for osteoporosis, because the long-term use of bisphosphonates has not been determined to be safe,” said Dr. Honig, director of the osteoporosis center at the Hospital for Joint Diseases Spine Center in New York.

Very long-term bisphosphonate therapy may lead to oversuppression of bone turnover, he said. This superhardening can hinder subsequent fracture healing, as was seen in a recent report of nine patients who sustained spontaneous, nonhealing fractures while on alendronate therapy (J. Clin. Endocrinol. Metab. 2005;90:1294-301).

These patients showed histomorphometric evidence of markedly suppressed bone formation, Dr. Honig said.

This new finding has heightened interest in targeting osteoporosis treatment. Research findings have begun to provide guidance on which patients can most benefit from treatment.

Most notable was the National Osteoporosis Risk Assessment (NORA) study, which enrolled 200,160 postmenopausal women aged 50 and older. In that study, bone mineral density (BMD) measurements were obtained at baseline, and the participants were followed for 1 year.

At follow up, one-third of all fractures and one-fifth of all hip fractures in particular occurred in women aged 50-64. Although the majority of fractures did occur in women 65 and older, the high number in the younger cohort “was a little surprising,” said Dr. Honig.

Another finding that emerged from NORA was that 80% of the women who had fractures during the yearlong study had T scores that were higher than -2.5 and therefore did not meet the World Health Organization definition of osteoporosis. Most fell between -1 and -2.5, the osteopenic range, he said.

“We want to identify patients at risk in this middle range and not wait until they have obvious fractures,” he said.

The NORA investigators subsequently followed 57,421 osteopenic women and developed an algorithm for determining risk. As it turns out, identifying patients with a previous fracture, a T score below -1.8, a self-reported health status of fair or poor, and poor mobility were all factors significantly predictive of fracture risk (Arch. Intern. Med. 2004;164:1113-20).

Another prospective study conducted in France followed 672 healthy postmenopausal women for more than 5 years, and found an annual incidence of osteoporotic fractures of 21 per 1,000 women per year (Bone 2003;32:78-85). The French investigators identified the key risk factors (in order of importance) to be: a past fracture, hip BMD, low physical activity, low grip strength, age over 65, maternal fracture history, and past falls.

Other studies have also suggested additional risk factors, including smoking, low body mass index, and increased markers of bone absorption.

Based on the available data and tools at hand, Dr. Honig recommends that clinicians now consider treatment for the following patients:

▸ Women 65 and older, with or without a history of fracture, who have low BMD or other risk factors, such as low BMI and family history.

▸ Women 50 and older with a previous fracture and a T score of -1.8 or less.

▸ Women in poor overall health with mobility problems and low BMD.

▸ Women with low BMD and increased markers of bone resorption.

But questions remain, he said. How long can a bisphosphonate be used? When should teriparatide or a selective estrogen receptor modulator be used? What place does hormone replacement therapy have in treatment strategies? “There is some new evidence that postmenopausal women with certain levels of endogenous estradiol have a lower incidence of fractures. This may translate into using very low-dose [hormone therapy], which conceivably could be safer than what was seen in the Women's Health Initiative,” he said.

Dr. Honig disclosed that he receives support from Eli Lilly & Co. and is on the speakers' bureau of Sanofi-Aventis.