Timothy F. Kirn

SNOWMASS, COLO. — The next generation of biological agents will be therapies that capitalize on the ability of regulatory T cells to keep the immune system in check, Randy Noelle, Ph.D., predicted at a symposium sponsored by the American College of Rheumatology.

First discovered 30 years ago, regulatory T-cell research was largely sidelined until interest in the field was renewed about 5 years ago, said Dr. Noelle, a professor of immunology at the Dartmouth-Hitchcock Medical Center, Lebanon, N.H.

“Over the past year, effective strategies have been developed to grow human regulatory T cells in vitro, and I would imagine that within a year you will see groups growing human regulatory T cells for reinfusion into patients for indications such as graft-versus-host disease,” he said.

“They will be the next wave of cell-based therapy that you will use to manage autoimmune disease,” Dr. Noelle told the audience of rheumatologists.

Regulatory T cells are the mechanism by which the body puts the brakes on the immune system functions of attack cells, or executor T cells, Dr. Noelle explained. Both regulatory T cells and executor T cells arise from CD4-positive cells. Research published last fall suggests that expression of the Lag-3 gene in CD4 cells differentiates them into regulatory T cells, which then limit the intensity of the autoimmune response (Immunity 2004;21:503-13).

Regulatory T cells represent about 5%-12% of an individual's CD4-positive T-cell population,

Although it is not known whether regulatory T cells suppress autoimmune activity directly or through cytokine expression, they have been shown to infiltrate tumors and attenuate the immune system response to them.

It has also been shown in mice that if mature, naive effector T cells are infused into immune-deficient mice, they develop inflammatory bowel disease. However, if regulatory T cells are infused at the same time, the mice remain healthy, Dr. Noelle said.

In addition, studies have demonstrated that T cells can prevent allergy and affect graft acceptance.

“I think they will have a resounding impact on our understanding of the development and pathogenesis of autoimmune diseases,” Dr. Noelle said.

Regulatory T cells suppress the functions of both CD4+ and CD8+ T cells. Dr. Randy Noelle

SNOWMASS, COLO. — The next generation of biological agents will be therapies that capitalize on the ability of regulatory T cells to keep the immune system in check, Randy Noelle, Ph.D., predicted at a symposium sponsored by the American College of Rheumatology.

First discovered 30 years ago, regulatory T-cell research was largely sidelined until interest in the field was renewed about 5 years ago, said Dr. Noelle, a professor of immunology at the Dartmouth-Hitchcock Medical Center, Lebanon, N.H.

“Over the past year, effective strategies have been developed to grow human regulatory T cells in vitro, and I would imagine that within a year you will see groups growing human regulatory T cells for reinfusion into patients for indications such as graft-versus-host disease,” he said.

“They will be the next wave of cell-based therapy that you will use to manage autoimmune disease,” Dr. Noelle told the audience of rheumatologists.

Regulatory T cells are the mechanism by which the body puts the brakes on the immune system functions of attack cells, or executor T cells, Dr. Noelle explained. Both regulatory T cells and executor T cells arise from CD4-positive cells. Research published last fall suggests that expression of the Lag-3 gene in CD4 cells differentiates them into regulatory T cells, which then limit the intensity of the autoimmune response (Immunity 2004;21:503-13).

Regulatory T cells represent about 5%-12% of an individual's CD4-positive T-cell population,

Although it is not known whether regulatory T cells suppress autoimmune activity directly or through cytokine expression, they have been shown to infiltrate tumors and attenuate the immune system response to them.

It has also been shown in mice that if mature, naive effector T cells are infused into immune-deficient mice, they develop inflammatory bowel disease. However, if regulatory T cells are infused at the same time, the mice remain healthy, Dr. Noelle said.

In addition, studies have demonstrated that T cells can prevent allergy and affect graft acceptance.

“I think they will have a resounding impact on our understanding of the development and pathogenesis of autoimmune diseases,” Dr. Noelle said.

Regulatory T cells suppress the functions of both CD4+ and CD8+ T cells. Dr. Randy Noelle

SNOWMASS, COLO. — The next generation of biological agents will be therapies that capitalize on the ability of regulatory T cells to keep the immune system in check, Randy Noelle, Ph.D., predicted at a symposium sponsored by the American College of Rheumatology.

First discovered 30 years ago, regulatory T-cell research was largely sidelined until interest in the field was renewed about 5 years ago, said Dr. Noelle, a professor of immunology at the Dartmouth-Hitchcock Medical Center, Lebanon, N.H.

“Over the past year, effective strategies have been developed to grow human regulatory T cells in vitro, and I would imagine that within a year you will see groups growing human regulatory T cells for reinfusion into patients for indications such as graft-versus-host disease,” he said.

“They will be the next wave of cell-based therapy that you will use to manage autoimmune disease,” Dr. Noelle told the audience of rheumatologists.

Regulatory T cells are the mechanism by which the body puts the brakes on the immune system functions of attack cells, or executor T cells, Dr. Noelle explained. Both regulatory T cells and executor T cells arise from CD4-positive cells. Research published last fall suggests that expression of the Lag-3 gene in CD4 cells differentiates them into regulatory T cells, which then limit the intensity of the autoimmune response (Immunity 2004;21:503-13).

Regulatory T cells represent about 5%-12% of an individual's CD4-positive T-cell population,

Although it is not known whether regulatory T cells suppress autoimmune activity directly or through cytokine expression, they have been shown to infiltrate tumors and attenuate the immune system response to them.

It has also been shown in mice that if mature, naive effector T cells are infused into immune-deficient mice, they develop inflammatory bowel disease. However, if regulatory T cells are infused at the same time, the mice remain healthy, Dr. Noelle said.

In addition, studies have demonstrated that T cells can prevent allergy and affect graft acceptance.

“I think they will have a resounding impact on our understanding of the development and pathogenesis of autoimmune diseases,” Dr. Noelle said.

Regulatory T cells suppress the functions of both CD4+ and CD8+ T cells. Dr. Randy Noelle

SNOWMASS, COLO. — Calcium crystals are likely to become a major target for future osteoarthritis therapies, Geraldine M. McCarthy, M.D., predicted at a symposium sponsored by the American College of Rheumatology.

Calcium crystals may actually be related to glucosamine's mechanism of action, said Dr. McCarthy, of the division of rheumatology at Mater Misericordiae Hospital and the Royal College of Surgeons, Dublin, Ireland.

Studies have shown that anywhere from 30% to 70% of patients with osteoarthritis of the knee have calcium crystals in their synovial fluid, Dr. McCarthy said at the meeting.

And yet because the crystals are extremely small, they're difficult to detect, making more precise estimates of their prevalence difficult to obtain.

Dr. McCarthy's interest in arthritis and the role of calcium crystals was spurred by her training at the University of Wisconsin, where Milwaukee shoulder syndrome was identified as the first osteoarthritis entity found to be associated with basic calcium phosphate crystals.

The idea is that these crystals “synergize with other pathogenic mediators of osteoarthritis, thus contributing to the degenerative process,” she said.

Calcium pyrophosphate dihydrate crystals in the synovium are believed to cause pseudogout and pseudo-rheumatoid arthritis.

Basic calcium phosphate crystals, by comparison, are believed to play a role in all osteoarthritis, Dr. McCarthy explained at the meeting.

Research into the role of basic calcium phosphate crystals has been hindered, however, by the size of the crystals. As small as calcium pyrophosphate dihydrate crystals are, basic calcium phosphate crystals are even smaller.

Basic calcium phosphate crystals clump as submicroscopic aggregates ranging in size from 1 μm to 50 μm in diameter.

A radiolabeled bisphosphonate that can detect the crystals has been available at the Medical College of Wisconsin, Milwaukee, but supply is dwindling, and at present no company has stepped up to manufacture more, Dr. McCarthy said.

Studies have shown that as people age basic calcium phosphate crystals tend to accumulate in the synovial fluid, synovial lining, and hyaline cartilage, and that the presence of these crystals correlates strongly with radiographic evidence of cartilage degeneration. In vitro experiments have shown that the crystals induce mitogenesis and increase production of prostaglandins and metalloproteinases.

The presence of crystals also is associated with the increased production and activation of cyclooxygenase-1 and -2.

Interestingly, COX-1 is not usually upregulated by disease processes, so this finding may explain why some osteoarthritis patients do not respond to selective COX-2 inhibitor therapy, Dr. McCarthy suggested.

The crystals appear to be actively generated by articular cartilage matrix vesicles.

“These crystals are not present in other destructive arthropathies,” Dr. McCarthy noted. But they are associated with Milwaukee shoulder syndrome, so it's likely that the crystals are also associated with joint destruction, she continued.

Further investigations are needed to identify therapeutic interventions and to determine why some individuals with basic calcium phosphate crystals have symptomatic degeneration while others do not, she said.

Calcium-chelating agents have been tried in the treatment of Milwaukee shoulder syndrome, but their use has caused severe arthritis flares.

In vitro experiments have shown that misoprostol can inhibit crystal formation, and glucosamine appears to directly inhibit the effects of the calcium crystals on mitogenesis and metalloproteinase production.

SNOWMASS, COLO. — Calcium crystals are likely to become a major target for future osteoarthritis therapies, Geraldine M. McCarthy, M.D., predicted at a symposium sponsored by the American College of Rheumatology.

Calcium crystals may actually be related to glucosamine's mechanism of action, said Dr. McCarthy, of the division of rheumatology at Mater Misericordiae Hospital and the Royal College of Surgeons, Dublin, Ireland.

Studies have shown that anywhere from 30% to 70% of patients with osteoarthritis of the knee have calcium crystals in their synovial fluid, Dr. McCarthy said at the meeting.

And yet because the crystals are extremely small, they're difficult to detect, making more precise estimates of their prevalence difficult to obtain.

Dr. McCarthy's interest in arthritis and the role of calcium crystals was spurred by her training at the University of Wisconsin, where Milwaukee shoulder syndrome was identified as the first osteoarthritis entity found to be associated with basic calcium phosphate crystals.

The idea is that these crystals “synergize with other pathogenic mediators of osteoarthritis, thus contributing to the degenerative process,” she said.

Calcium pyrophosphate dihydrate crystals in the synovium are believed to cause pseudogout and pseudo-rheumatoid arthritis.

Basic calcium phosphate crystals, by comparison, are believed to play a role in all osteoarthritis, Dr. McCarthy explained at the meeting.

Research into the role of basic calcium phosphate crystals has been hindered, however, by the size of the crystals. As small as calcium pyrophosphate dihydrate crystals are, basic calcium phosphate crystals are even smaller.

Basic calcium phosphate crystals clump as submicroscopic aggregates ranging in size from 1 μm to 50 μm in diameter.

A radiolabeled bisphosphonate that can detect the crystals has been available at the Medical College of Wisconsin, Milwaukee, but supply is dwindling, and at present no company has stepped up to manufacture more, Dr. McCarthy said.

Studies have shown that as people age basic calcium phosphate crystals tend to accumulate in the synovial fluid, synovial lining, and hyaline cartilage, and that the presence of these crystals correlates strongly with radiographic evidence of cartilage degeneration. In vitro experiments have shown that the crystals induce mitogenesis and increase production of prostaglandins and metalloproteinases.

The presence of crystals also is associated with the increased production and activation of cyclooxygenase-1 and -2.

Interestingly, COX-1 is not usually upregulated by disease processes, so this finding may explain why some osteoarthritis patients do not respond to selective COX-2 inhibitor therapy, Dr. McCarthy suggested.

The crystals appear to be actively generated by articular cartilage matrix vesicles.

“These crystals are not present in other destructive arthropathies,” Dr. McCarthy noted. But they are associated with Milwaukee shoulder syndrome, so it's likely that the crystals are also associated with joint destruction, she continued.

Further investigations are needed to identify therapeutic interventions and to determine why some individuals with basic calcium phosphate crystals have symptomatic degeneration while others do not, she said.

Calcium-chelating agents have been tried in the treatment of Milwaukee shoulder syndrome, but their use has caused severe arthritis flares.

In vitro experiments have shown that misoprostol can inhibit crystal formation, and glucosamine appears to directly inhibit the effects of the calcium crystals on mitogenesis and metalloproteinase production.

SNOWMASS, COLO. — Calcium crystals are likely to become a major target for future osteoarthritis therapies, Geraldine M. McCarthy, M.D., predicted at a symposium sponsored by the American College of Rheumatology.

Calcium crystals may actually be related to glucosamine's mechanism of action, said Dr. McCarthy, of the division of rheumatology at Mater Misericordiae Hospital and the Royal College of Surgeons, Dublin, Ireland.

Studies have shown that anywhere from 30% to 70% of patients with osteoarthritis of the knee have calcium crystals in their synovial fluid, Dr. McCarthy said at the meeting.

And yet because the crystals are extremely small, they're difficult to detect, making more precise estimates of their prevalence difficult to obtain.

Dr. McCarthy's interest in arthritis and the role of calcium crystals was spurred by her training at the University of Wisconsin, where Milwaukee shoulder syndrome was identified as the first osteoarthritis entity found to be associated with basic calcium phosphate crystals.

The idea is that these crystals “synergize with other pathogenic mediators of osteoarthritis, thus contributing to the degenerative process,” she said.

Calcium pyrophosphate dihydrate crystals in the synovium are believed to cause pseudogout and pseudo-rheumatoid arthritis.

Basic calcium phosphate crystals, by comparison, are believed to play a role in all osteoarthritis, Dr. McCarthy explained at the meeting.

Research into the role of basic calcium phosphate crystals has been hindered, however, by the size of the crystals. As small as calcium pyrophosphate dihydrate crystals are, basic calcium phosphate crystals are even smaller.

Basic calcium phosphate crystals clump as submicroscopic aggregates ranging in size from 1 μm to 50 μm in diameter.

A radiolabeled bisphosphonate that can detect the crystals has been available at the Medical College of Wisconsin, Milwaukee, but supply is dwindling, and at present no company has stepped up to manufacture more, Dr. McCarthy said.

Studies have shown that as people age basic calcium phosphate crystals tend to accumulate in the synovial fluid, synovial lining, and hyaline cartilage, and that the presence of these crystals correlates strongly with radiographic evidence of cartilage degeneration. In vitro experiments have shown that the crystals induce mitogenesis and increase production of prostaglandins and metalloproteinases.

The presence of crystals also is associated with the increased production and activation of cyclooxygenase-1 and -2.

Interestingly, COX-1 is not usually upregulated by disease processes, so this finding may explain why some osteoarthritis patients do not respond to selective COX-2 inhibitor therapy, Dr. McCarthy suggested.

The crystals appear to be actively generated by articular cartilage matrix vesicles.

“These crystals are not present in other destructive arthropathies,” Dr. McCarthy noted. But they are associated with Milwaukee shoulder syndrome, so it's likely that the crystals are also associated with joint destruction, she continued.

Further investigations are needed to identify therapeutic interventions and to determine why some individuals with basic calcium phosphate crystals have symptomatic degeneration while others do not, she said.

Calcium-chelating agents have been tried in the treatment of Milwaukee shoulder syndrome, but their use has caused severe arthritis flares.

In vitro experiments have shown that misoprostol can inhibit crystal formation, and glucosamine appears to directly inhibit the effects of the calcium crystals on mitogenesis and metalloproteinase production.

VANCOUVER, B.C. – At least half of migraine patients who are given a prescription for a medication to abort their attacks wait too long to take their medication, making it less likely to be effective, Roger K. Cady, M.D., reported at the annual meeting of the American Headache Society.

In a pharmacy-based study of migraineurs, 49% of patients with severe migraines and 51% of patients with moderate migraines said they waited more than 2 hours after the onset of the most recent headache before taking the medication, which was either rizatriptan or another oral nontriptan, said Dr. Cady, director of the Headache Care Center, Springfield, Mo.

“You tell patients to treat early, but you really have no idea what that means to them,” Dr. Cady commented.

Rizatriptan is considered to provide effective relief only 35% of the time if a patient waits 2 hours, he said in an interview. “They set themselves up for failure.”

The most common reason that patients gave for delaying their treatment was to see if their headache really was a migraine. Overall, 86% of the study patients had other headaches as well as migraine.

This is probably unrealistic thinking on the patient's part, Dr. Cady commented. Most migraineurs are familiar with their migraines and the signs of an impending migraine.

Patients who had migraines for less than 3 years were one and a half times more likely to delay using the medication than those who had a longer history of migraine, he said.

Other reasons given for delay were wanting to rely on medication only for a severe attack (reported by 46% of those who delayed), having concerns about side effects (37%), having concerns that the drug would become less effective if taken too often (34%), having concerns about becoming dependent (29%), facing limits on supply from the provider (15%), and being worried about cost (9%). Also, 3% of the patients said they had been instructed by their physicians not to take the medication too early.

VANCOUVER, B.C. – At least half of migraine patients who are given a prescription for a medication to abort their attacks wait too long to take their medication, making it less likely to be effective, Roger K. Cady, M.D., reported at the annual meeting of the American Headache Society.

In a pharmacy-based study of migraineurs, 49% of patients with severe migraines and 51% of patients with moderate migraines said they waited more than 2 hours after the onset of the most recent headache before taking the medication, which was either rizatriptan or another oral nontriptan, said Dr. Cady, director of the Headache Care Center, Springfield, Mo.

“You tell patients to treat early, but you really have no idea what that means to them,” Dr. Cady commented.

Rizatriptan is considered to provide effective relief only 35% of the time if a patient waits 2 hours, he said in an interview. “They set themselves up for failure.”

The most common reason that patients gave for delaying their treatment was to see if their headache really was a migraine. Overall, 86% of the study patients had other headaches as well as migraine.

This is probably unrealistic thinking on the patient's part, Dr. Cady commented. Most migraineurs are familiar with their migraines and the signs of an impending migraine.

Patients who had migraines for less than 3 years were one and a half times more likely to delay using the medication than those who had a longer history of migraine, he said.

Other reasons given for delay were wanting to rely on medication only for a severe attack (reported by 46% of those who delayed), having concerns about side effects (37%), having concerns that the drug would become less effective if taken too often (34%), having concerns about becoming dependent (29%), facing limits on supply from the provider (15%), and being worried about cost (9%). Also, 3% of the patients said they had been instructed by their physicians not to take the medication too early.

VANCOUVER, B.C. – At least half of migraine patients who are given a prescription for a medication to abort their attacks wait too long to take their medication, making it less likely to be effective, Roger K. Cady, M.D., reported at the annual meeting of the American Headache Society.

In a pharmacy-based study of migraineurs, 49% of patients with severe migraines and 51% of patients with moderate migraines said they waited more than 2 hours after the onset of the most recent headache before taking the medication, which was either rizatriptan or another oral nontriptan, said Dr. Cady, director of the Headache Care Center, Springfield, Mo.

“You tell patients to treat early, but you really have no idea what that means to them,” Dr. Cady commented.

Rizatriptan is considered to provide effective relief only 35% of the time if a patient waits 2 hours, he said in an interview. “They set themselves up for failure.”

The most common reason that patients gave for delaying their treatment was to see if their headache really was a migraine. Overall, 86% of the study patients had other headaches as well as migraine.

This is probably unrealistic thinking on the patient's part, Dr. Cady commented. Most migraineurs are familiar with their migraines and the signs of an impending migraine.

Patients who had migraines for less than 3 years were one and a half times more likely to delay using the medication than those who had a longer history of migraine, he said.

Other reasons given for delay were wanting to rely on medication only for a severe attack (reported by 46% of those who delayed), having concerns about side effects (37%), having concerns that the drug would become less effective if taken too often (34%), having concerns about becoming dependent (29%), facing limits on supply from the provider (15%), and being worried about cost (9%). Also, 3% of the patients said they had been instructed by their physicians not to take the medication too early.

A single digital rectal exam with a fecal occult blood test performed in the office detects only 5% of important colon neoplasias, and yet at least one-third of primary care physicians rely on this approach for colon cancer screening, two studies have shown.

The studies “send a strong message to primary care physicians to reexamine their colorectal cancer screening practices,” said Harold C. Sox, M.D., editor of the Annals of Internal Medicine.

Even when physicians are doing a fecal occult blood test (FOBT), many are not doing it right, Dr. Sox said in an editorial (Ann. Intern. Med. 2005;142: 146-8).

One study enrolled 2,665 individuals aged 50 to 75 years, most of whom were male. They had a digital rectal examination with a fecal occult blood test, were sent home with Hemoccult II cards to collect six fecal samples from three stools, and also underwent a colonoscopy (Ann. Intern. Med. 2005; 142:81-5).

Colonoscopy identified 284 patients with an advanced neoplasia. The single digital FOBT picked up 5% of those patients, compared with 24% with the six-sample FOBT. The digital FOBT picked up 9% of the cancers; the six-sample FOBT picked up 43%.

The digital FOBT had no negative predictive value, said Judith Collins, M.D., and her colleagues in a Department of Veterans Affairs cooperative study group.

Combining the digital FOBT and the six-sample test did not produce results any more useful than the six-sample test alone. Only five patients with advanced neoplasia had a positive digital FOBT and a negative six-sample FOBT, while 59 had positive six-sample FOBT and negative digital FOBT, said Dr. Collins, of the Portland (Ore.) Veterans Affairs Medical Center.

The second study was a national survey on the use of FOBT by primary care physicians. Of the 1,103 physicians who reported doing a FOBT at least once a month and who indicated what method they used, 26% said they had patients collect six samples at home exclusively, 33% used a single-sample, in-office FOBT method, and 41% used both (Ann. Intern. Med. 2005;142:86-95).

Of the 1,120 physician respondents who indicated how they followed up a positive FOBT, 30% said they repeat it, reported Marion Nadel, Ph.D., of the Centers for Disease Control and Prevention, Atlanta.

Expert panels have recommended having the patient collect two samples from each of three, consecutive-day stools, which is how screening was done in the studies that demonstrated its utility, both study reports noted.

And according to the expert panels, the proper follow-up to a positive test is a colonoscopy, not another FOBT or even a sigmoidoscopy.

In-office tests were used by 66% of internists, 76% of family physicians, 67% of general practice physicians, and 89% of obstetrician/gynecologists.

Although physicians may turn to in-office, single-sample testing because they can be sure of getting the sample and not have to worry about patients returning their stool, the colonoscopy follow-up study totally discredits this approach, Dr. Sox said in his editorial.

Calling those findings “a shocker,” he said that perhaps “we need to put the guaiac cards [for in-office testing] in a locked drawer labeled 'use only in case of emergency.'”

The investigators were a bit more diplomatic. If an in-office screen is done, and it is negative for occult blood, it must be followed up with an in-home FOBT, Dr. Collins said.

“Positive results on digital FOBT performed as part of a primary care physical examination are associated with a trend toward an increased likelihood of advanced neoplasia, and colonoscopy should be performed,” she wrote. “However, negative results do not reduce the likelihood of advanced neoplasia.”

A single digital rectal exam with a fecal occult blood test performed in the office detects only 5% of important colon neoplasias, and yet at least one-third of primary care physicians rely on this approach for colon cancer screening, two studies have shown.

The studies “send a strong message to primary care physicians to reexamine their colorectal cancer screening practices,” said Harold C. Sox, M.D., editor of the Annals of Internal Medicine.

Even when physicians are doing a fecal occult blood test (FOBT), many are not doing it right, Dr. Sox said in an editorial (Ann. Intern. Med. 2005;142: 146-8).

One study enrolled 2,665 individuals aged 50 to 75 years, most of whom were male. They had a digital rectal examination with a fecal occult blood test, were sent home with Hemoccult II cards to collect six fecal samples from three stools, and also underwent a colonoscopy (Ann. Intern. Med. 2005; 142:81-5).

Colonoscopy identified 284 patients with an advanced neoplasia. The single digital FOBT picked up 5% of those patients, compared with 24% with the six-sample FOBT. The digital FOBT picked up 9% of the cancers; the six-sample FOBT picked up 43%.

The digital FOBT had no negative predictive value, said Judith Collins, M.D., and her colleagues in a Department of Veterans Affairs cooperative study group.

Combining the digital FOBT and the six-sample test did not produce results any more useful than the six-sample test alone. Only five patients with advanced neoplasia had a positive digital FOBT and a negative six-sample FOBT, while 59 had positive six-sample FOBT and negative digital FOBT, said Dr. Collins, of the Portland (Ore.) Veterans Affairs Medical Center.

The second study was a national survey on the use of FOBT by primary care physicians. Of the 1,103 physicians who reported doing a FOBT at least once a month and who indicated what method they used, 26% said they had patients collect six samples at home exclusively, 33% used a single-sample, in-office FOBT method, and 41% used both (Ann. Intern. Med. 2005;142:86-95).

Of the 1,120 physician respondents who indicated how they followed up a positive FOBT, 30% said they repeat it, reported Marion Nadel, Ph.D., of the Centers for Disease Control and Prevention, Atlanta.

Expert panels have recommended having the patient collect two samples from each of three, consecutive-day stools, which is how screening was done in the studies that demonstrated its utility, both study reports noted.

And according to the expert panels, the proper follow-up to a positive test is a colonoscopy, not another FOBT or even a sigmoidoscopy.

In-office tests were used by 66% of internists, 76% of family physicians, 67% of general practice physicians, and 89% of obstetrician/gynecologists.

Although physicians may turn to in-office, single-sample testing because they can be sure of getting the sample and not have to worry about patients returning their stool, the colonoscopy follow-up study totally discredits this approach, Dr. Sox said in his editorial.

Calling those findings “a shocker,” he said that perhaps “we need to put the guaiac cards [for in-office testing] in a locked drawer labeled 'use only in case of emergency.'”

The investigators were a bit more diplomatic. If an in-office screen is done, and it is negative for occult blood, it must be followed up with an in-home FOBT, Dr. Collins said.

“Positive results on digital FOBT performed as part of a primary care physical examination are associated with a trend toward an increased likelihood of advanced neoplasia, and colonoscopy should be performed,” she wrote. “However, negative results do not reduce the likelihood of advanced neoplasia.”

A single digital rectal exam with a fecal occult blood test performed in the office detects only 5% of important colon neoplasias, and yet at least one-third of primary care physicians rely on this approach for colon cancer screening, two studies have shown.

The studies “send a strong message to primary care physicians to reexamine their colorectal cancer screening practices,” said Harold C. Sox, M.D., editor of the Annals of Internal Medicine.

Even when physicians are doing a fecal occult blood test (FOBT), many are not doing it right, Dr. Sox said in an editorial (Ann. Intern. Med. 2005;142: 146-8).

One study enrolled 2,665 individuals aged 50 to 75 years, most of whom were male. They had a digital rectal examination with a fecal occult blood test, were sent home with Hemoccult II cards to collect six fecal samples from three stools, and also underwent a colonoscopy (Ann. Intern. Med. 2005; 142:81-5).

Colonoscopy identified 284 patients with an advanced neoplasia. The single digital FOBT picked up 5% of those patients, compared with 24% with the six-sample FOBT. The digital FOBT picked up 9% of the cancers; the six-sample FOBT picked up 43%.

The digital FOBT had no negative predictive value, said Judith Collins, M.D., and her colleagues in a Department of Veterans Affairs cooperative study group.

Combining the digital FOBT and the six-sample test did not produce results any more useful than the six-sample test alone. Only five patients with advanced neoplasia had a positive digital FOBT and a negative six-sample FOBT, while 59 had positive six-sample FOBT and negative digital FOBT, said Dr. Collins, of the Portland (Ore.) Veterans Affairs Medical Center.

The second study was a national survey on the use of FOBT by primary care physicians. Of the 1,103 physicians who reported doing a FOBT at least once a month and who indicated what method they used, 26% said they had patients collect six samples at home exclusively, 33% used a single-sample, in-office FOBT method, and 41% used both (Ann. Intern. Med. 2005;142:86-95).

Of the 1,120 physician respondents who indicated how they followed up a positive FOBT, 30% said they repeat it, reported Marion Nadel, Ph.D., of the Centers for Disease Control and Prevention, Atlanta.

Expert panels have recommended having the patient collect two samples from each of three, consecutive-day stools, which is how screening was done in the studies that demonstrated its utility, both study reports noted.

And according to the expert panels, the proper follow-up to a positive test is a colonoscopy, not another FOBT or even a sigmoidoscopy.

In-office tests were used by 66% of internists, 76% of family physicians, 67% of general practice physicians, and 89% of obstetrician/gynecologists.

Although physicians may turn to in-office, single-sample testing because they can be sure of getting the sample and not have to worry about patients returning their stool, the colonoscopy follow-up study totally discredits this approach, Dr. Sox said in his editorial.

Calling those findings “a shocker,” he said that perhaps “we need to put the guaiac cards [for in-office testing] in a locked drawer labeled 'use only in case of emergency.'”

The investigators were a bit more diplomatic. If an in-office screen is done, and it is negative for occult blood, it must be followed up with an in-home FOBT, Dr. Collins said.

“Positive results on digital FOBT performed as part of a primary care physical examination are associated with a trend toward an increased likelihood of advanced neoplasia, and colonoscopy should be performed,” she wrote. “However, negative results do not reduce the likelihood of advanced neoplasia.”

Scan in a van? From a country club in Austin, Tex., to an evangelical church in Porterville, Calif., to the community hall in Rutherfordton, N.C., people are lining up to be screened for their stroke risk, and maybe even to have their bone density measured.

Mobile ultrasound stroke screening is growing in popularity, and it is being offered by enterprising companies not affiliated with any hospital. The cost: about $109 for the carotid artery sonogram, and generally less than $200 for a more extensive package that might include the bone density or echocardiography.

Everything is paid for out of pocket with cash or a credit card.

And, the perhaps surprising thing about this burgeoning mobile stroke screening business is that it is not being widely challenged by physician groups and the traditional medical establishments, the way coronary calcium screening using electron beam CT has been, for example.

On the contrary, many experts say the time for stroke screening has come, and the vans can offer that screening at a fraction of the cost of a hospital.

Stroke is currently the third leading cause of death in the United States, and, because stroke incidence more than doubles in each successive decade of life beyond age 55 years, the aging of the population means stroke will grow as a problem.

Ultrasound stroke screening may be essential for prevention, and prevention may be necessary to reduce not only stroke mortality but morbidity as well. No one wants to be a stroke survivor, they say.

Up to 30% of stroke survivors become permanently disabled, and 20% require institutionalization within 3 months of the stroke. Between 1992 and 2002, the death rate from stroke dropped 13%, but the actual number of deaths rose 7%.

Ultrasound screening can identify individuals with carotid artery narrowing, and that is a major risk factor, said William Flinn, M.D., professor and head of the vascular surgery division at the University of Maryland, Baltimore.

Moreover, the companies not only seem to be offering a credible service, but their activities educate the public about stroke risk, said Dr. Flinn, who coordinates a free screening program for the American Vascular Association, a group founded to promote stroke awareness and treatment.

A significant number of individuals could benefit from such programs, Dr. Flinn said.

In their screening campaign conducted last May, ultrasound screens were offered at 130 centers in 40 states to individuals older than 55 years with cardiovascular risk factors. Of the first 5,000 persons screened, 8% had carotid stenosis of 50% or greater, and less than half of these at-risk individuals were on either antiplatelet therapy or statin therapy.

Men were more likely than women to have stenosis of 50% or more. At-risk women were less likely than the at-risk men to be receiving any preventive medical treatment.

The companies say that opposition to mobile screening has been minimal because registered technicians perform the tests, board-certified physicians read them, and persons with abnormal tests are referred back to their own physicians.

And there is a market for what they do, because they offer screening tests that Medicare does not routinely reimburse, at affordable prices.

For $109, the mobile units of Cleveland-based Life Line Screening screen for stroke risk, abdominal aortic aneurysm, and peripheral artery disease. For $129, they will also screen for osteoporosis.

According to Paula Motolik, of Life Line, one of the oldest companies in the mobile screening business, the profit margins are low because of the expense of the equipment. But on the plus side, there is a demand. The company has grown from a single van in 1993 to 53 vans in 2004.

HealthFair USA, a relative newcomer, has nine modified buses—each costing about $300,000 with equipment—that offer up to nine screening tests, including the stroke ultrasound, echocardiograms and electrocardiograms. In the 5 years since the company's founding, it has screened about 450,000 persons along the Eastern seaboard.

The company plans to add seven more units before the end of the year, said company president Terrence Diaz, who started his career in medicine as an emergency medical technician. “The technology has come down in cost, allowing us to charge affordable prices.”

Still, concerns remain about the lack of follow-up on the referrals, cost-effectiveness of the widespread screening, and the quality of exams that private companies offer.

Carotid stenosis probably is a good marker for atherosclerosis, and therefore the information that the ultrasound exams provide is probably beneficial, said Colin P. Derdeyn, M.D., program director of endovascular surgical neuroradiology, at the Mallinkcrodt Institute of Radiology at Washington University, St. Louis.

But from a socioeconomic standpoint, the cost-benefit of ultrasound screening for stroke has not been established. A person who is asymptomatic and found to have 60% carotid stenosis, for example, has a 5-year annual stroke risk of 2%. Endarterectomy reduces that risk to 1%, and the person is still at high risk for heart disease.

Screening may be “good for business, but whether it is a good thing for patients is a bit of an open question,” Dr. Derdeyn said. One concern is that the companies will screen people who are too young to seriously be considering their stroke risk, he said.

Ms. Motolik said Life Line tends to be invited to set up screenings at places where individuals are likely to be older, like senior centers. The mean age of its clients is 62 years.

Furthermore, all clients are educated about stroke risk before they pay for anything, and persons younger than 40 are specifically informed that their risk of having any of the conditions that Life Line screens for is extremely low.

Groups such as the American Stroke Association (ASA), a division of the American Heart Association, tend not to have any position on ultrasound screening or the mobile vans.

Blood pressure, pulse, and carotid bruits continue to be the standard of care for assessing stroke risk routinely, said Edgar Kenton, M.D., past chair of ASA's media advisory committee.

But he also noted that half of individuals with hypertension are not treated adequately, and many Americans have no medical insurance. Therefore, he said, he personally cannot be opposed to any activity that increases public access to health services.

Scan in a van? From a country club in Austin, Tex., to an evangelical church in Porterville, Calif., to the community hall in Rutherfordton, N.C., people are lining up to be screened for their stroke risk, and maybe even to have their bone density measured.

Mobile ultrasound stroke screening is growing in popularity, and it is being offered by enterprising companies not affiliated with any hospital. The cost: about $109 for the carotid artery sonogram, and generally less than $200 for a more extensive package that might include the bone density or echocardiography.

Everything is paid for out of pocket with cash or a credit card.

And, the perhaps surprising thing about this burgeoning mobile stroke screening business is that it is not being widely challenged by physician groups and the traditional medical establishments, the way coronary calcium screening using electron beam CT has been, for example.

On the contrary, many experts say the time for stroke screening has come, and the vans can offer that screening at a fraction of the cost of a hospital.

Stroke is currently the third leading cause of death in the United States, and, because stroke incidence more than doubles in each successive decade of life beyond age 55 years, the aging of the population means stroke will grow as a problem.

Ultrasound stroke screening may be essential for prevention, and prevention may be necessary to reduce not only stroke mortality but morbidity as well. No one wants to be a stroke survivor, they say.

Up to 30% of stroke survivors become permanently disabled, and 20% require institutionalization within 3 months of the stroke. Between 1992 and 2002, the death rate from stroke dropped 13%, but the actual number of deaths rose 7%.

Ultrasound screening can identify individuals with carotid artery narrowing, and that is a major risk factor, said William Flinn, M.D., professor and head of the vascular surgery division at the University of Maryland, Baltimore.

Moreover, the companies not only seem to be offering a credible service, but their activities educate the public about stroke risk, said Dr. Flinn, who coordinates a free screening program for the American Vascular Association, a group founded to promote stroke awareness and treatment.

A significant number of individuals could benefit from such programs, Dr. Flinn said.

In their screening campaign conducted last May, ultrasound screens were offered at 130 centers in 40 states to individuals older than 55 years with cardiovascular risk factors. Of the first 5,000 persons screened, 8% had carotid stenosis of 50% or greater, and less than half of these at-risk individuals were on either antiplatelet therapy or statin therapy.

Men were more likely than women to have stenosis of 50% or more. At-risk women were less likely than the at-risk men to be receiving any preventive medical treatment.

The companies say that opposition to mobile screening has been minimal because registered technicians perform the tests, board-certified physicians read them, and persons with abnormal tests are referred back to their own physicians.

And there is a market for what they do, because they offer screening tests that Medicare does not routinely reimburse, at affordable prices.

For $109, the mobile units of Cleveland-based Life Line Screening screen for stroke risk, abdominal aortic aneurysm, and peripheral artery disease. For $129, they will also screen for osteoporosis.

According to Paula Motolik, of Life Line, one of the oldest companies in the mobile screening business, the profit margins are low because of the expense of the equipment. But on the plus side, there is a demand. The company has grown from a single van in 1993 to 53 vans in 2004.

HealthFair USA, a relative newcomer, has nine modified buses—each costing about $300,000 with equipment—that offer up to nine screening tests, including the stroke ultrasound, echocardiograms and electrocardiograms. In the 5 years since the company's founding, it has screened about 450,000 persons along the Eastern seaboard.

The company plans to add seven more units before the end of the year, said company president Terrence Diaz, who started his career in medicine as an emergency medical technician. “The technology has come down in cost, allowing us to charge affordable prices.”

Still, concerns remain about the lack of follow-up on the referrals, cost-effectiveness of the widespread screening, and the quality of exams that private companies offer.

Carotid stenosis probably is a good marker for atherosclerosis, and therefore the information that the ultrasound exams provide is probably beneficial, said Colin P. Derdeyn, M.D., program director of endovascular surgical neuroradiology, at the Mallinkcrodt Institute of Radiology at Washington University, St. Louis.

But from a socioeconomic standpoint, the cost-benefit of ultrasound screening for stroke has not been established. A person who is asymptomatic and found to have 60% carotid stenosis, for example, has a 5-year annual stroke risk of 2%. Endarterectomy reduces that risk to 1%, and the person is still at high risk for heart disease.

Screening may be “good for business, but whether it is a good thing for patients is a bit of an open question,” Dr. Derdeyn said. One concern is that the companies will screen people who are too young to seriously be considering their stroke risk, he said.

Ms. Motolik said Life Line tends to be invited to set up screenings at places where individuals are likely to be older, like senior centers. The mean age of its clients is 62 years.

Furthermore, all clients are educated about stroke risk before they pay for anything, and persons younger than 40 are specifically informed that their risk of having any of the conditions that Life Line screens for is extremely low.

Groups such as the American Stroke Association (ASA), a division of the American Heart Association, tend not to have any position on ultrasound screening or the mobile vans.

Blood pressure, pulse, and carotid bruits continue to be the standard of care for assessing stroke risk routinely, said Edgar Kenton, M.D., past chair of ASA's media advisory committee.

But he also noted that half of individuals with hypertension are not treated adequately, and many Americans have no medical insurance. Therefore, he said, he personally cannot be opposed to any activity that increases public access to health services.

Scan in a van? From a country club in Austin, Tex., to an evangelical church in Porterville, Calif., to the community hall in Rutherfordton, N.C., people are lining up to be screened for their stroke risk, and maybe even to have their bone density measured.

Mobile ultrasound stroke screening is growing in popularity, and it is being offered by enterprising companies not affiliated with any hospital. The cost: about $109 for the carotid artery sonogram, and generally less than $200 for a more extensive package that might include the bone density or echocardiography.

Everything is paid for out of pocket with cash or a credit card.

And, the perhaps surprising thing about this burgeoning mobile stroke screening business is that it is not being widely challenged by physician groups and the traditional medical establishments, the way coronary calcium screening using electron beam CT has been, for example.

On the contrary, many experts say the time for stroke screening has come, and the vans can offer that screening at a fraction of the cost of a hospital.

Stroke is currently the third leading cause of death in the United States, and, because stroke incidence more than doubles in each successive decade of life beyond age 55 years, the aging of the population means stroke will grow as a problem.

Ultrasound stroke screening may be essential for prevention, and prevention may be necessary to reduce not only stroke mortality but morbidity as well. No one wants to be a stroke survivor, they say.

Up to 30% of stroke survivors become permanently disabled, and 20% require institutionalization within 3 months of the stroke. Between 1992 and 2002, the death rate from stroke dropped 13%, but the actual number of deaths rose 7%.

Ultrasound screening can identify individuals with carotid artery narrowing, and that is a major risk factor, said William Flinn, M.D., professor and head of the vascular surgery division at the University of Maryland, Baltimore.

Moreover, the companies not only seem to be offering a credible service, but their activities educate the public about stroke risk, said Dr. Flinn, who coordinates a free screening program for the American Vascular Association, a group founded to promote stroke awareness and treatment.

A significant number of individuals could benefit from such programs, Dr. Flinn said.

In their screening campaign conducted last May, ultrasound screens were offered at 130 centers in 40 states to individuals older than 55 years with cardiovascular risk factors. Of the first 5,000 persons screened, 8% had carotid stenosis of 50% or greater, and less than half of these at-risk individuals were on either antiplatelet therapy or statin therapy.

Men were more likely than women to have stenosis of 50% or more. At-risk women were less likely than the at-risk men to be receiving any preventive medical treatment.

The companies say that opposition to mobile screening has been minimal because registered technicians perform the tests, board-certified physicians read them, and persons with abnormal tests are referred back to their own physicians.

And there is a market for what they do, because they offer screening tests that Medicare does not routinely reimburse, at affordable prices.

For $109, the mobile units of Cleveland-based Life Line Screening screen for stroke risk, abdominal aortic aneurysm, and peripheral artery disease. For $129, they will also screen for osteoporosis.

According to Paula Motolik, of Life Line, one of the oldest companies in the mobile screening business, the profit margins are low because of the expense of the equipment. But on the plus side, there is a demand. The company has grown from a single van in 1993 to 53 vans in 2004.

HealthFair USA, a relative newcomer, has nine modified buses—each costing about $300,000 with equipment—that offer up to nine screening tests, including the stroke ultrasound, echocardiograms and electrocardiograms. In the 5 years since the company's founding, it has screened about 450,000 persons along the Eastern seaboard.

The company plans to add seven more units before the end of the year, said company president Terrence Diaz, who started his career in medicine as an emergency medical technician. “The technology has come down in cost, allowing us to charge affordable prices.”

Still, concerns remain about the lack of follow-up on the referrals, cost-effectiveness of the widespread screening, and the quality of exams that private companies offer.

Carotid stenosis probably is a good marker for atherosclerosis, and therefore the information that the ultrasound exams provide is probably beneficial, said Colin P. Derdeyn, M.D., program director of endovascular surgical neuroradiology, at the Mallinkcrodt Institute of Radiology at Washington University, St. Louis.

But from a socioeconomic standpoint, the cost-benefit of ultrasound screening for stroke has not been established. A person who is asymptomatic and found to have 60% carotid stenosis, for example, has a 5-year annual stroke risk of 2%. Endarterectomy reduces that risk to 1%, and the person is still at high risk for heart disease.

Screening may be “good for business, but whether it is a good thing for patients is a bit of an open question,” Dr. Derdeyn said. One concern is that the companies will screen people who are too young to seriously be considering their stroke risk, he said.

Ms. Motolik said Life Line tends to be invited to set up screenings at places where individuals are likely to be older, like senior centers. The mean age of its clients is 62 years.

Furthermore, all clients are educated about stroke risk before they pay for anything, and persons younger than 40 are specifically informed that their risk of having any of the conditions that Life Line screens for is extremely low.

Groups such as the American Stroke Association (ASA), a division of the American Heart Association, tend not to have any position on ultrasound screening or the mobile vans.

Blood pressure, pulse, and carotid bruits continue to be the standard of care for assessing stroke risk routinely, said Edgar Kenton, M.D., past chair of ASA's media advisory committee.

But he also noted that half of individuals with hypertension are not treated adequately, and many Americans have no medical insurance. Therefore, he said, he personally cannot be opposed to any activity that increases public access to health services.

SAN ANTONIO — If you want to identify the male patients who are most likely to have osteoporosis, look for the thin ones, and then ask them about their calcium intake, Bryan R. Whelan, M.D., said at the annual meeting of the American College of Rheumatology.

Dr. Whelan and his colleagues prospectively screened 350 men referred to an osteoporosis clinic in Cork, Ireland, for assessment using dual x-ray absorptiometry. The aim was to retrospectively assess whether the patients were being properly referred and to identify what, if any, clinical characteristics were associated with a higher risk for fracture.

Overall, 45% of the patients were found to have osteopenia or osteoporosis. Weight turned out to be the most important predictor of who had low bone density, even more so than corticosteroid treatment, said Dr. Whelan of the department of medicine, University College of Cork.

Although 39% of the patients were on or had received corticosteroid treatment, which was why they received the referral, steroid treatment was not correlated with a significantly higher likelihood of a low T score or z score in the study, Dr. Whelan said.

Individuals with a body mass index of less than 25 kg/mg

Patients completed questionnaires on lifestyle factors, such as whether they smoked, how much alcohol they consumed, and the amount of their calcium intake. Participants who took a calcium supplement, ate two or more serving of cheese a day, or drank at least a pint of milk a day were considered to have an adequate calcium intake.

Among men with low BMI and inadequate calcium intake, 70% were found to have a low z score.

“Even though we used such a crude tool to define adequate versus inadequate [calcium intake], it did stratify” patients by their risk, he said.

Even age and daily exercise, which were somewhat related to risk, were not as highly predictive, Dr. Whelan said.

SAN ANTONIO — If you want to identify the male patients who are most likely to have osteoporosis, look for the thin ones, and then ask them about their calcium intake, Bryan R. Whelan, M.D., said at the annual meeting of the American College of Rheumatology.

Dr. Whelan and his colleagues prospectively screened 350 men referred to an osteoporosis clinic in Cork, Ireland, for assessment using dual x-ray absorptiometry. The aim was to retrospectively assess whether the patients were being properly referred and to identify what, if any, clinical characteristics were associated with a higher risk for fracture.

Overall, 45% of the patients were found to have osteopenia or osteoporosis. Weight turned out to be the most important predictor of who had low bone density, even more so than corticosteroid treatment, said Dr. Whelan of the department of medicine, University College of Cork.

Although 39% of the patients were on or had received corticosteroid treatment, which was why they received the referral, steroid treatment was not correlated with a significantly higher likelihood of a low T score or z score in the study, Dr. Whelan said.

Individuals with a body mass index of less than 25 kg/mg

Patients completed questionnaires on lifestyle factors, such as whether they smoked, how much alcohol they consumed, and the amount of their calcium intake. Participants who took a calcium supplement, ate two or more serving of cheese a day, or drank at least a pint of milk a day were considered to have an adequate calcium intake.

Among men with low BMI and inadequate calcium intake, 70% were found to have a low z score.

“Even though we used such a crude tool to define adequate versus inadequate [calcium intake], it did stratify” patients by their risk, he said.

Even age and daily exercise, which were somewhat related to risk, were not as highly predictive, Dr. Whelan said.

SAN ANTONIO — If you want to identify the male patients who are most likely to have osteoporosis, look for the thin ones, and then ask them about their calcium intake, Bryan R. Whelan, M.D., said at the annual meeting of the American College of Rheumatology.

Dr. Whelan and his colleagues prospectively screened 350 men referred to an osteoporosis clinic in Cork, Ireland, for assessment using dual x-ray absorptiometry. The aim was to retrospectively assess whether the patients were being properly referred and to identify what, if any, clinical characteristics were associated with a higher risk for fracture.

Overall, 45% of the patients were found to have osteopenia or osteoporosis. Weight turned out to be the most important predictor of who had low bone density, even more so than corticosteroid treatment, said Dr. Whelan of the department of medicine, University College of Cork.

Although 39% of the patients were on or had received corticosteroid treatment, which was why they received the referral, steroid treatment was not correlated with a significantly higher likelihood of a low T score or z score in the study, Dr. Whelan said.

Individuals with a body mass index of less than 25 kg/mg

Patients completed questionnaires on lifestyle factors, such as whether they smoked, how much alcohol they consumed, and the amount of their calcium intake. Participants who took a calcium supplement, ate two or more serving of cheese a day, or drank at least a pint of milk a day were considered to have an adequate calcium intake.

Among men with low BMI and inadequate calcium intake, 70% were found to have a low z score.

“Even though we used such a crude tool to define adequate versus inadequate [calcium intake], it did stratify” patients by their risk, he said.

Even age and daily exercise, which were somewhat related to risk, were not as highly predictive, Dr. Whelan said.

SEATTLE — Beer and wine increase bone mineral density in a dose-dependent fashion, according to data from the Framingham Offspring Study.

“I think the major effect is an estrogenic or hormonal effect of the alcohol itself,” Katherine L. Tucker, Ph.D., said at the annual meeting of the American Society for Bone and Mineral Research.

The findings are based on 1,631 women and 1,295 men who gave information on their alcohol intake and had bone mineral density measured as part of their participation in the Framingham Offspring study.

At the trochanter, the mean bone mineral density in the men was 0.84–0.86 g/cm

For women, the bone mineral density at the trochanter was a mean 0.68–0.70 g/cm

For both men and women, drinking daily appeared to have the most benefit, Dr. Tucker said.

The beneficial effects were seen for beer among men and wine among women, reflecting the types of alcohol most commonly consumed for each sex. Dr. Tucker added that wine would probably have been equally effective for men and vice versa.

Previous reports have suggested a positive association between alcohol intake and bone density. No other component of the beverages, aside from alcohol, appeared to account totally for the bone density improvement, according to the analysis.

SEATTLE — Beer and wine increase bone mineral density in a dose-dependent fashion, according to data from the Framingham Offspring Study.

“I think the major effect is an estrogenic or hormonal effect of the alcohol itself,” Katherine L. Tucker, Ph.D., said at the annual meeting of the American Society for Bone and Mineral Research.

The findings are based on 1,631 women and 1,295 men who gave information on their alcohol intake and had bone mineral density measured as part of their participation in the Framingham Offspring study.

At the trochanter, the mean bone mineral density in the men was 0.84–0.86 g/cm

For women, the bone mineral density at the trochanter was a mean 0.68–0.70 g/cm

For both men and women, drinking daily appeared to have the most benefit, Dr. Tucker said.

The beneficial effects were seen for beer among men and wine among women, reflecting the types of alcohol most commonly consumed for each sex. Dr. Tucker added that wine would probably have been equally effective for men and vice versa.

Previous reports have suggested a positive association between alcohol intake and bone density. No other component of the beverages, aside from alcohol, appeared to account totally for the bone density improvement, according to the analysis.

SEATTLE — Beer and wine increase bone mineral density in a dose-dependent fashion, according to data from the Framingham Offspring Study.

“I think the major effect is an estrogenic or hormonal effect of the alcohol itself,” Katherine L. Tucker, Ph.D., said at the annual meeting of the American Society for Bone and Mineral Research.

The findings are based on 1,631 women and 1,295 men who gave information on their alcohol intake and had bone mineral density measured as part of their participation in the Framingham Offspring study.

At the trochanter, the mean bone mineral density in the men was 0.84–0.86 g/cm

For women, the bone mineral density at the trochanter was a mean 0.68–0.70 g/cm

For both men and women, drinking daily appeared to have the most benefit, Dr. Tucker said.

The beneficial effects were seen for beer among men and wine among women, reflecting the types of alcohol most commonly consumed for each sex. Dr. Tucker added that wine would probably have been equally effective for men and vice versa.

Previous reports have suggested a positive association between alcohol intake and bone density. No other component of the beverages, aside from alcohol, appeared to account totally for the bone density improvement, according to the analysis.

SEATTLE — Use of selective serotonin reuptake inhibitors is associated with bone loss comparable to that associated with glucocorticoid therapy, according to the findings of two studies.

In the first study (involving nearly 6,000 men), the mean bone mineral density (BMD) at the lumbar spine for the 158 participants using an SSRI at the time of a baseline dual energy x-ray absorptiometry scan was 4.6% lower than in nonusers, Elizabeth McKinstry Haney, M.D., said at the annual meeting of the American Society for Bone and Mineral Research.

By comparison, the 240 glucocorticoid users had a mean baseline BMD 2.9% lower than that of nonusers.

Relative to nonusers, mean total hip BMD was 3.9% lower in the SSRI users and 2.6% lower in the glucocorticoid users, relative to nonusers. At the femoral neck, mean BMD was 4.5% lower for the SSRI users and 2.2% lower for the glucocorticoid users.

Use of tricyclic antidepressants or trazodone was not associated with significantly different BMD findings, compared with nonusers, said Dr. Haney of Oregon Health Sciences University, Portland.

Another study presented at the meeting reported similar findings in women. That study looked at a cohort of 2,556 elderly women who were part of longitudinal investigation of fracture risk. The study compared bone mineral density measurements taken about 5 years apart. The rate of BMD loss among women who reported using an SSRI at the time of one or both of the bone density measurements was almost double that of women who were not taking an SSRI (0.81% vs. 0.47% per year), said Susan J. Diem, of the University of Minnesota, in a poster presentation.

Previous reports have suggested an association between SSRIs, bone loss, and fracture. However, it was unclear in those studies whether the SSRIs caused the bone loss or whether the bone loss was associated with depression, since the mood disorder itself has been tied to a number of factors that might lead to bone loss, such as altered cortisol levels and alcohol abuse, Dr. Haney said.

That is why Dr. Haney's study compared bone density in patients on SSRIs with patients taking other antidepressants.

The cause of the loss is probably related to osteoclasts' and osteoblasts' known expression of functional serotonin transporters, Dr. Haney suggested.

Studies that her group has conducted of SSRIs in mice have confirmed that SSRI treatment led to bone loss.

Dr. Haney said the strength of her study was that it collected very complete data, which permitted the researchers to control for everything from body mass to smoking and vitamin use in their analysis.

Still, the study was limited by the fact that SSRI dosages and duration of use were unknown.

“We don't rule out that other mechanisms might be involved as well, and that deserves further study” she said.

SEATTLE — Use of selective serotonin reuptake inhibitors is associated with bone loss comparable to that associated with glucocorticoid therapy, according to the findings of two studies.

In the first study (involving nearly 6,000 men), the mean bone mineral density (BMD) at the lumbar spine for the 158 participants using an SSRI at the time of a baseline dual energy x-ray absorptiometry scan was 4.6% lower than in nonusers, Elizabeth McKinstry Haney, M.D., said at the annual meeting of the American Society for Bone and Mineral Research.

By comparison, the 240 glucocorticoid users had a mean baseline BMD 2.9% lower than that of nonusers.

Relative to nonusers, mean total hip BMD was 3.9% lower in the SSRI users and 2.6% lower in the glucocorticoid users, relative to nonusers. At the femoral neck, mean BMD was 4.5% lower for the SSRI users and 2.2% lower for the glucocorticoid users.

Use of tricyclic antidepressants or trazodone was not associated with significantly different BMD findings, compared with nonusers, said Dr. Haney of Oregon Health Sciences University, Portland.

Another study presented at the meeting reported similar findings in women. That study looked at a cohort of 2,556 elderly women who were part of longitudinal investigation of fracture risk. The study compared bone mineral density measurements taken about 5 years apart. The rate of BMD loss among women who reported using an SSRI at the time of one or both of the bone density measurements was almost double that of women who were not taking an SSRI (0.81% vs. 0.47% per year), said Susan J. Diem, of the University of Minnesota, in a poster presentation.

Previous reports have suggested an association between SSRIs, bone loss, and fracture. However, it was unclear in those studies whether the SSRIs caused the bone loss or whether the bone loss was associated with depression, since the mood disorder itself has been tied to a number of factors that might lead to bone loss, such as altered cortisol levels and alcohol abuse, Dr. Haney said.

That is why Dr. Haney's study compared bone density in patients on SSRIs with patients taking other antidepressants.

The cause of the loss is probably related to osteoclasts' and osteoblasts' known expression of functional serotonin transporters, Dr. Haney suggested.

Studies that her group has conducted of SSRIs in mice have confirmed that SSRI treatment led to bone loss.

Dr. Haney said the strength of her study was that it collected very complete data, which permitted the researchers to control for everything from body mass to smoking and vitamin use in their analysis.

Still, the study was limited by the fact that SSRI dosages and duration of use were unknown.

“We don't rule out that other mechanisms might be involved as well, and that deserves further study” she said.

SEATTLE — Use of selective serotonin reuptake inhibitors is associated with bone loss comparable to that associated with glucocorticoid therapy, according to the findings of two studies.

In the first study (involving nearly 6,000 men), the mean bone mineral density (BMD) at the lumbar spine for the 158 participants using an SSRI at the time of a baseline dual energy x-ray absorptiometry scan was 4.6% lower than in nonusers, Elizabeth McKinstry Haney, M.D., said at the annual meeting of the American Society for Bone and Mineral Research.

By comparison, the 240 glucocorticoid users had a mean baseline BMD 2.9% lower than that of nonusers.

Relative to nonusers, mean total hip BMD was 3.9% lower in the SSRI users and 2.6% lower in the glucocorticoid users, relative to nonusers. At the femoral neck, mean BMD was 4.5% lower for the SSRI users and 2.2% lower for the glucocorticoid users.

Use of tricyclic antidepressants or trazodone was not associated with significantly different BMD findings, compared with nonusers, said Dr. Haney of Oregon Health Sciences University, Portland.

Another study presented at the meeting reported similar findings in women. That study looked at a cohort of 2,556 elderly women who were part of longitudinal investigation of fracture risk. The study compared bone mineral density measurements taken about 5 years apart. The rate of BMD loss among women who reported using an SSRI at the time of one or both of the bone density measurements was almost double that of women who were not taking an SSRI (0.81% vs. 0.47% per year), said Susan J. Diem, of the University of Minnesota, in a poster presentation.

Previous reports have suggested an association between SSRIs, bone loss, and fracture. However, it was unclear in those studies whether the SSRIs caused the bone loss or whether the bone loss was associated with depression, since the mood disorder itself has been tied to a number of factors that might lead to bone loss, such as altered cortisol levels and alcohol abuse, Dr. Haney said.

That is why Dr. Haney's study compared bone density in patients on SSRIs with patients taking other antidepressants.

The cause of the loss is probably related to osteoclasts' and osteoblasts' known expression of functional serotonin transporters, Dr. Haney suggested.

Studies that her group has conducted of SSRIs in mice have confirmed that SSRI treatment led to bone loss.

Dr. Haney said the strength of her study was that it collected very complete data, which permitted the researchers to control for everything from body mass to smoking and vitamin use in their analysis.

Still, the study was limited by the fact that SSRI dosages and duration of use were unknown.

“We don't rule out that other mechanisms might be involved as well, and that deserves further study” she said.

SAN ANTONIO — Physicians tend to be skeptical of arthritis patients' claims that they can feel bad weather coming on, but maybe they shouldn't be, Timothy E. McAlindon, M.D., said at the annual meeting of the American College of Rheumatology.

Findings from a study conducted by Dr. McAlindon and his colleagues at Tufts-New England Medical Center, Boston, suggest that persons with knee osteoarthritis do indeed have greater pain when there are changes in barometric pressure.

Previous studies probably have failed to document this phenomenon because they have not been able to be as precise in their weather measurements as this study, surmised Dr. McAlindon, chief of the division of rheumatology at Tufts.

The investigators collected data on 205 patients with arthritis who took part in a 3-month trial of glucosamine.

The study tracked patients using the Internet, which enabled them to be from a variety of regions within the U.S.

The participants in the trial lived in 41 different states, which meant that almost all of them experienced very different weather.

During the initial study, which found no positive effect from glucosamine, subjects completed Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index pain questionnaires every 2 weeks.

Corresponding weather data were collected from the National Oceanic and Atmospheric Administration stations, which in some instances were less than a mile from the subject's house, Dr. McAlindon said.

In all, the investigators identified more than 900 pain reports that correlated with weather.

The data indicated that there was no significant association between pain scores and either the dew point or precipitation, which is perhaps another reason previous studies have been confounded, Dr. McAlindon said.

The researchers did, however, find a weak but consistent association between pain and temperature, such that each degree (Fahrenheit) drop was associated with a 1-degree increase in pain on the WOMAC scale.

Similarly, the investigators found that a strong association exists between pain and change in barometric pressure; this association was more pronounced with lower temperatures.

Arthritis patients, anecdotally, have always tended to say that they experience greater pain before the weather changes. It is not uncommon for patients with arthritis to use the phrase, “feel it in your bones” to describe changes in weather.

In keeping with this the pain, barometric pressure association did not occur so much with the drop in barometric pressure that accompanies a change in weather, but rather, it was associated with the increase in barometric pressure that generally precedes a change in weather.

Patients with arthritis also often reported feeling better after a rain, which again is consistent with the fact that barometric pressure drops once a storm arrives, he added.

In a related report comparing 42 control subjects with 92 rheumatic disease patients, 80 of whom had osteoarthritis and 12 of whom had rheumatoid arthritis, Jose Verges, M.D., from Bioiberica SA, a pharmaceutical company in Barcelona, Spain, found that patients with osteoarthritis, in particular, experienced increases in joint pain when atmospheric pressure was low.

Dr. Verges concluded that “it may be possible to modulate pharmacological and nonpharmacological treatments for some osteoarthritic patients, depending on the predictable weather conditions in order to avoid, as much as possible, the disease-associated joint pain and functional incapacity, thus improving patients' quality of life” (Proc. West Pharmacol. Soc. 2004;47:134–6).

SAN ANTONIO — Physicians tend to be skeptical of arthritis patients' claims that they can feel bad weather coming on, but maybe they shouldn't be, Timothy E. McAlindon, M.D., said at the annual meeting of the American College of Rheumatology.

Findings from a study conducted by Dr. McAlindon and his colleagues at Tufts-New England Medical Center, Boston, suggest that persons with knee osteoarthritis do indeed have greater pain when there are changes in barometric pressure.

Previous studies probably have failed to document this phenomenon because they have not been able to be as precise in their weather measurements as this study, surmised Dr. McAlindon, chief of the division of rheumatology at Tufts.

The investigators collected data on 205 patients with arthritis who took part in a 3-month trial of glucosamine.

The study tracked patients using the Internet, which enabled them to be from a variety of regions within the U.S.

The participants in the trial lived in 41 different states, which meant that almost all of them experienced very different weather.

During the initial study, which found no positive effect from glucosamine, subjects completed Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index pain questionnaires every 2 weeks.

Corresponding weather data were collected from the National Oceanic and Atmospheric Administration stations, which in some instances were less than a mile from the subject's house, Dr. McAlindon said.

In all, the investigators identified more than 900 pain reports that correlated with weather.

The data indicated that there was no significant association between pain scores and either the dew point or precipitation, which is perhaps another reason previous studies have been confounded, Dr. McAlindon said.

The researchers did, however, find a weak but consistent association between pain and temperature, such that each degree (Fahrenheit) drop was associated with a 1-degree increase in pain on the WOMAC scale.

Similarly, the investigators found that a strong association exists between pain and change in barometric pressure; this association was more pronounced with lower temperatures.

Arthritis patients, anecdotally, have always tended to say that they experience greater pain before the weather changes. It is not uncommon for patients with arthritis to use the phrase, “feel it in your bones” to describe changes in weather.

In keeping with this the pain, barometric pressure association did not occur so much with the drop in barometric pressure that accompanies a change in weather, but rather, it was associated with the increase in barometric pressure that generally precedes a change in weather.

Patients with arthritis also often reported feeling better after a rain, which again is consistent with the fact that barometric pressure drops once a storm arrives, he added.

In a related report comparing 42 control subjects with 92 rheumatic disease patients, 80 of whom had osteoarthritis and 12 of whom had rheumatoid arthritis, Jose Verges, M.D., from Bioiberica SA, a pharmaceutical company in Barcelona, Spain, found that patients with osteoarthritis, in particular, experienced increases in joint pain when atmospheric pressure was low.

Dr. Verges concluded that “it may be possible to modulate pharmacological and nonpharmacological treatments for some osteoarthritic patients, depending on the predictable weather conditions in order to avoid, as much as possible, the disease-associated joint pain and functional incapacity, thus improving patients' quality of life” (Proc. West Pharmacol. Soc. 2004;47:134–6).

SAN ANTONIO — Physicians tend to be skeptical of arthritis patients' claims that they can feel bad weather coming on, but maybe they shouldn't be, Timothy E. McAlindon, M.D., said at the annual meeting of the American College of Rheumatology.

Findings from a study conducted by Dr. McAlindon and his colleagues at Tufts-New England Medical Center, Boston, suggest that persons with knee osteoarthritis do indeed have greater pain when there are changes in barometric pressure.

Previous studies probably have failed to document this phenomenon because they have not been able to be as precise in their weather measurements as this study, surmised Dr. McAlindon, chief of the division of rheumatology at Tufts.

The investigators collected data on 205 patients with arthritis who took part in a 3-month trial of glucosamine.

The study tracked patients using the Internet, which enabled them to be from a variety of regions within the U.S.

The participants in the trial lived in 41 different states, which meant that almost all of them experienced very different weather.

During the initial study, which found no positive effect from glucosamine, subjects completed Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index pain questionnaires every 2 weeks.

Corresponding weather data were collected from the National Oceanic and Atmospheric Administration stations, which in some instances were less than a mile from the subject's house, Dr. McAlindon said.

In all, the investigators identified more than 900 pain reports that correlated with weather.

The data indicated that there was no significant association between pain scores and either the dew point or precipitation, which is perhaps another reason previous studies have been confounded, Dr. McAlindon said.

The researchers did, however, find a weak but consistent association between pain and temperature, such that each degree (Fahrenheit) drop was associated with a 1-degree increase in pain on the WOMAC scale.

Similarly, the investigators found that a strong association exists between pain and change in barometric pressure; this association was more pronounced with lower temperatures.

Arthritis patients, anecdotally, have always tended to say that they experience greater pain before the weather changes. It is not uncommon for patients with arthritis to use the phrase, “feel it in your bones” to describe changes in weather.

In keeping with this the pain, barometric pressure association did not occur so much with the drop in barometric pressure that accompanies a change in weather, but rather, it was associated with the increase in barometric pressure that generally precedes a change in weather.

Patients with arthritis also often reported feeling better after a rain, which again is consistent with the fact that barometric pressure drops once a storm arrives, he added.

In a related report comparing 42 control subjects with 92 rheumatic disease patients, 80 of whom had osteoarthritis and 12 of whom had rheumatoid arthritis, Jose Verges, M.D., from Bioiberica SA, a pharmaceutical company in Barcelona, Spain, found that patients with osteoarthritis, in particular, experienced increases in joint pain when atmospheric pressure was low.

Dr. Verges concluded that “it may be possible to modulate pharmacological and nonpharmacological treatments for some osteoarthritic patients, depending on the predictable weather conditions in order to avoid, as much as possible, the disease-associated joint pain and functional incapacity, thus improving patients' quality of life” (Proc. West Pharmacol. Soc. 2004;47:134–6).