Damian McNamara

FORT LAUDERDALE, FLA. – The walk of a patient with osteoarthritis differs by which knee compartments are affected, according to researchers who linked radiographic findings with sophisticated motion analysis.

Knee osteoarthritis (OA) leads to alterations in gait that can further impair function for patients, Dr. William F. Harvey said at the World Congress on Osteoarthritis. To find out if there are gait alterations unique to the compartments of the knee that are affected by OA, Dr. Harvey and his associates assessed 448 patients in North Carolina enrolled in the Observational Arthritis Study in Seniors (OASIS).

Participants' mean age was 72 years and all were more than 65 years old; all reported knee pain. Just more than half, 51%, were women; 83% were white; and the mean body mass index was 30 kg/m

At baseline, researchers found that 166 patients had grade 0 Kellgren-Lawrence (KL), 51 patients had grade 1 KL, 47 patients had grade 2 KL, 126 patients had grade 3 KL, and 58 patients had grade 4 KL; in general, the higher the KL grade, the worse the meniscal pathology and chondral degradation, Dr. Harvey, a fellow in rheumatology at Boston University, said at the meeting, which was sponsored by the Osteoarthritis Research Society International.

Kinematic measures of gait were performed during self-paced walking in the sagittal plane only, with outcomes based on an average of three trials. Peak angular range of motion, mean angular velocity (of the hip, knee, and ankle joints), stride length, walking velocity, cadence, and stance and swing times were measured. Mean values were compared between groups. Results were adjusted for age, race, gender, body mass index, and walking velocity.

Patients with isolated tibio-femoral (159 participants), and both tibiofemoral and patellofemoral osteoarthritis (72 participants) had a significantly lower knee range of motion and mean angular velocity, compared with those with no osteoarthritis (206 participants), Dr. Harvey said. The mean knee range of motion angle was 54 degrees in the tibiofemoral group and 53 degrees in the combined group, compared with 57 degrees in the unaffected group. The mean value for the patellofemoral osteoarthritis group, 58 degrees, was not statistically significant because of the small number of patients in the category.

In addition, there was a statistically significant difference in mean angular velocity of the knee between the same groups. Those with tibiofemoral osteoarthritis and both compartments affected had a lower mean angular velocity, compared with those without osteoarthritis, Dr. Harvey said. Expressed as degrees per second, the values were 104 in the tibiofemoral group, 100 in the group with both compartments affected, and 117 in the comparison, disease-free, group without disease. Again, the 110 degrees per second finding in the patellofemoral group was not significant.

Stance time was another variable that was significantly different between groups. The patellofemoral group and doubly affected group spent more time in stance versus swing, compared with the tibiofemoral osteoarthritis group or the unaffected patients.

The study was funded by Wake Forest University and a grant from the National Institutes of Health.

ELSEVIER GLOBAL MEDICAL NEWS

FORT LAUDERDALE, FLA. – The walk of a patient with osteoarthritis differs by which knee compartments are affected, according to researchers who linked radiographic findings with sophisticated motion analysis.

Knee osteoarthritis (OA) leads to alterations in gait that can further impair function for patients, Dr. William F. Harvey said at the World Congress on Osteoarthritis. To find out if there are gait alterations unique to the compartments of the knee that are affected by OA, Dr. Harvey and his associates assessed 448 patients in North Carolina enrolled in the Observational Arthritis Study in Seniors (OASIS).

Participants' mean age was 72 years and all were more than 65 years old; all reported knee pain. Just more than half, 51%, were women; 83% were white; and the mean body mass index was 30 kg/m

At baseline, researchers found that 166 patients had grade 0 Kellgren-Lawrence (KL), 51 patients had grade 1 KL, 47 patients had grade 2 KL, 126 patients had grade 3 KL, and 58 patients had grade 4 KL; in general, the higher the KL grade, the worse the meniscal pathology and chondral degradation, Dr. Harvey, a fellow in rheumatology at Boston University, said at the meeting, which was sponsored by the Osteoarthritis Research Society International.

Kinematic measures of gait were performed during self-paced walking in the sagittal plane only, with outcomes based on an average of three trials. Peak angular range of motion, mean angular velocity (of the hip, knee, and ankle joints), stride length, walking velocity, cadence, and stance and swing times were measured. Mean values were compared between groups. Results were adjusted for age, race, gender, body mass index, and walking velocity.

Patients with isolated tibio-femoral (159 participants), and both tibiofemoral and patellofemoral osteoarthritis (72 participants) had a significantly lower knee range of motion and mean angular velocity, compared with those with no osteoarthritis (206 participants), Dr. Harvey said. The mean knee range of motion angle was 54 degrees in the tibiofemoral group and 53 degrees in the combined group, compared with 57 degrees in the unaffected group. The mean value for the patellofemoral osteoarthritis group, 58 degrees, was not statistically significant because of the small number of patients in the category.

In addition, there was a statistically significant difference in mean angular velocity of the knee between the same groups. Those with tibiofemoral osteoarthritis and both compartments affected had a lower mean angular velocity, compared with those without osteoarthritis, Dr. Harvey said. Expressed as degrees per second, the values were 104 in the tibiofemoral group, 100 in the group with both compartments affected, and 117 in the comparison, disease-free, group without disease. Again, the 110 degrees per second finding in the patellofemoral group was not significant.

Stance time was another variable that was significantly different between groups. The patellofemoral group and doubly affected group spent more time in stance versus swing, compared with the tibiofemoral osteoarthritis group or the unaffected patients.

The study was funded by Wake Forest University and a grant from the National Institutes of Health.

ELSEVIER GLOBAL MEDICAL NEWS

FORT LAUDERDALE, FLA. – The walk of a patient with osteoarthritis differs by which knee compartments are affected, according to researchers who linked radiographic findings with sophisticated motion analysis.

Knee osteoarthritis (OA) leads to alterations in gait that can further impair function for patients, Dr. William F. Harvey said at the World Congress on Osteoarthritis. To find out if there are gait alterations unique to the compartments of the knee that are affected by OA, Dr. Harvey and his associates assessed 448 patients in North Carolina enrolled in the Observational Arthritis Study in Seniors (OASIS).

Participants' mean age was 72 years and all were more than 65 years old; all reported knee pain. Just more than half, 51%, were women; 83% were white; and the mean body mass index was 30 kg/m

At baseline, researchers found that 166 patients had grade 0 Kellgren-Lawrence (KL), 51 patients had grade 1 KL, 47 patients had grade 2 KL, 126 patients had grade 3 KL, and 58 patients had grade 4 KL; in general, the higher the KL grade, the worse the meniscal pathology and chondral degradation, Dr. Harvey, a fellow in rheumatology at Boston University, said at the meeting, which was sponsored by the Osteoarthritis Research Society International.

Kinematic measures of gait were performed during self-paced walking in the sagittal plane only, with outcomes based on an average of three trials. Peak angular range of motion, mean angular velocity (of the hip, knee, and ankle joints), stride length, walking velocity, cadence, and stance and swing times were measured. Mean values were compared between groups. Results were adjusted for age, race, gender, body mass index, and walking velocity.

Patients with isolated tibio-femoral (159 participants), and both tibiofemoral and patellofemoral osteoarthritis (72 participants) had a significantly lower knee range of motion and mean angular velocity, compared with those with no osteoarthritis (206 participants), Dr. Harvey said. The mean knee range of motion angle was 54 degrees in the tibiofemoral group and 53 degrees in the combined group, compared with 57 degrees in the unaffected group. The mean value for the patellofemoral osteoarthritis group, 58 degrees, was not statistically significant because of the small number of patients in the category.

In addition, there was a statistically significant difference in mean angular velocity of the knee between the same groups. Those with tibiofemoral osteoarthritis and both compartments affected had a lower mean angular velocity, compared with those without osteoarthritis, Dr. Harvey said. Expressed as degrees per second, the values were 104 in the tibiofemoral group, 100 in the group with both compartments affected, and 117 in the comparison, disease-free, group without disease. Again, the 110 degrees per second finding in the patellofemoral group was not significant.

Stance time was another variable that was significantly different between groups. The patellofemoral group and doubly affected group spent more time in stance versus swing, compared with the tibiofemoral osteoarthritis group or the unaffected patients.

The study was funded by Wake Forest University and a grant from the National Institutes of Health.

ELSEVIER GLOBAL MEDICAL NEWS

FORT LAUDERDALE, FLA. – Symmetrical bilateral progression of knee osteoarthritis was a surprising result of a genetic study of people with hand osteoarthritis and their relatives.

“[This finding] indicates to me that there is probably a strong genetic factor for progression,” Dr. Virginia Byers Kraus said in an interview during a poster session at the World Congress on Osteoarthritis.

Dr. Byers Kraus and her associates studied 1,333 patients with hand osteoarthritis for a median of 3.8 years. Participants whose osteoarthritis progressed in either the medial or lateral compartment of one knee were significantly more likely to show progression in the same compartments of the other knee.

There are clinical implications to the findings. For example, “if you see these individuals [with hand osteoarthritis], if they have an affected knee, the other is likely to be affected with osteoarthritis and they are likely to progress in parallel,” said Dr. Byers Kraus, an internist in the division of rheumatology, Duke University Medical Center, Durham, N.C. “It's a probable prognostic factor for patients.”

What makes the conclusions “particularly intriguing” is that the knee progression symmetry was observed in this study of people with hand osteoarthritis, Dr. Byers Kraus said at the meeting, which was sponsored by the Osteoarthritis Research Society International.

The cohort came from the Genetics of Generalized Osteoarthritis (GOGO) study. In all, 79% were women and the mean age was 69 years. Researchers scored baseline and follow-up radiographs for changes in Kellgren-Lawrence grade, minimal joint space, presence of osteophytes, and joint space narrowing of the medial and lateral knee compartments. They also assessed at least two affected siblings with three-joint bilateral bony enlargements in their hands to assess any genetic correlations.

“In a cohort with hand osteoarthritis, they were more likely to have osteoarthritis [in other joints] if family members have hand osteoarthritis,” Dr. Byers Kraus said. And “when you have a patient with hand osteoarthritis and relatives with hand osteoarthritis, there is an increased likelihood of bilateral knee osteoarthritis.”

These findings support a strong genetic or constitutional risk for progression in knee osteoarthritis, Dr. Byers Kraus said.

The results also could have research implications, especially in studying people with osteoarthritis but in whom there is no progression, Dr. Byers Kraus said. This makes it difficult to assess the efficacy of a particular treatment compared with a control group. “This was responsible for the failure of a major trial on Actonel. Age, female gender, obesity–outside of these, we are not good at identifying definite progressors.”

FORT LAUDERDALE, FLA. – Symmetrical bilateral progression of knee osteoarthritis was a surprising result of a genetic study of people with hand osteoarthritis and their relatives.

“[This finding] indicates to me that there is probably a strong genetic factor for progression,” Dr. Virginia Byers Kraus said in an interview during a poster session at the World Congress on Osteoarthritis.

Dr. Byers Kraus and her associates studied 1,333 patients with hand osteoarthritis for a median of 3.8 years. Participants whose osteoarthritis progressed in either the medial or lateral compartment of one knee were significantly more likely to show progression in the same compartments of the other knee.

There are clinical implications to the findings. For example, “if you see these individuals [with hand osteoarthritis], if they have an affected knee, the other is likely to be affected with osteoarthritis and they are likely to progress in parallel,” said Dr. Byers Kraus, an internist in the division of rheumatology, Duke University Medical Center, Durham, N.C. “It's a probable prognostic factor for patients.”

What makes the conclusions “particularly intriguing” is that the knee progression symmetry was observed in this study of people with hand osteoarthritis, Dr. Byers Kraus said at the meeting, which was sponsored by the Osteoarthritis Research Society International.

The cohort came from the Genetics of Generalized Osteoarthritis (GOGO) study. In all, 79% were women and the mean age was 69 years. Researchers scored baseline and follow-up radiographs for changes in Kellgren-Lawrence grade, minimal joint space, presence of osteophytes, and joint space narrowing of the medial and lateral knee compartments. They also assessed at least two affected siblings with three-joint bilateral bony enlargements in their hands to assess any genetic correlations.

“In a cohort with hand osteoarthritis, they were more likely to have osteoarthritis [in other joints] if family members have hand osteoarthritis,” Dr. Byers Kraus said. And “when you have a patient with hand osteoarthritis and relatives with hand osteoarthritis, there is an increased likelihood of bilateral knee osteoarthritis.”

These findings support a strong genetic or constitutional risk for progression in knee osteoarthritis, Dr. Byers Kraus said.

The results also could have research implications, especially in studying people with osteoarthritis but in whom there is no progression, Dr. Byers Kraus said. This makes it difficult to assess the efficacy of a particular treatment compared with a control group. “This was responsible for the failure of a major trial on Actonel. Age, female gender, obesity–outside of these, we are not good at identifying definite progressors.”

FORT LAUDERDALE, FLA. – Symmetrical bilateral progression of knee osteoarthritis was a surprising result of a genetic study of people with hand osteoarthritis and their relatives.

“[This finding] indicates to me that there is probably a strong genetic factor for progression,” Dr. Virginia Byers Kraus said in an interview during a poster session at the World Congress on Osteoarthritis.

Dr. Byers Kraus and her associates studied 1,333 patients with hand osteoarthritis for a median of 3.8 years. Participants whose osteoarthritis progressed in either the medial or lateral compartment of one knee were significantly more likely to show progression in the same compartments of the other knee.

There are clinical implications to the findings. For example, “if you see these individuals [with hand osteoarthritis], if they have an affected knee, the other is likely to be affected with osteoarthritis and they are likely to progress in parallel,” said Dr. Byers Kraus, an internist in the division of rheumatology, Duke University Medical Center, Durham, N.C. “It's a probable prognostic factor for patients.”

What makes the conclusions “particularly intriguing” is that the knee progression symmetry was observed in this study of people with hand osteoarthritis, Dr. Byers Kraus said at the meeting, which was sponsored by the Osteoarthritis Research Society International.

The cohort came from the Genetics of Generalized Osteoarthritis (GOGO) study. In all, 79% were women and the mean age was 69 years. Researchers scored baseline and follow-up radiographs for changes in Kellgren-Lawrence grade, minimal joint space, presence of osteophytes, and joint space narrowing of the medial and lateral knee compartments. They also assessed at least two affected siblings with three-joint bilateral bony enlargements in their hands to assess any genetic correlations.

“In a cohort with hand osteoarthritis, they were more likely to have osteoarthritis [in other joints] if family members have hand osteoarthritis,” Dr. Byers Kraus said. And “when you have a patient with hand osteoarthritis and relatives with hand osteoarthritis, there is an increased likelihood of bilateral knee osteoarthritis.”

These findings support a strong genetic or constitutional risk for progression in knee osteoarthritis, Dr. Byers Kraus said.

The results also could have research implications, especially in studying people with osteoarthritis but in whom there is no progression, Dr. Byers Kraus said. This makes it difficult to assess the efficacy of a particular treatment compared with a control group. “This was responsible for the failure of a major trial on Actonel. Age, female gender, obesity–outside of these, we are not good at identifying definite progressors.”

Calcium supplementation significantly increased the risk of a myocardial infarction among healthy postmenopausal women, compared with those taking placebo, in a secondary analysis of an osteoporosis study.

Physicians should consider this increased cardiovascular risk against other clinical benefits of calcium supplementation in older women until confirmatory studies can be completed, the authors suggested.

“It is an important finding because so many women are prescribed calcium supplements,” Dr. Rita F. Redberg said in an interview. “I would not recommend calcium supplementation based on this finding. This raises enough concern. With any supplement, you have to show evidence of benefit without risk,” said Dr. Redberg, who was not involved in the study.

The HDL to LDL cholesterol ratios improved among the 732 women who took daily calcium supplementation, compared with the 739 participants who took placebo. This suggests that a different mechanism spurred the increase in myocardial infarction.

“This is an interesting point. It shows that just improving cholesterol does not reduce the risk of a heart attack,” said Dr. Redberg, a Robert Wood Johnson Foundation health policy fellow and director of women's cardiovascular services at the University of California, San Francisco. “It was the same finding with estrogen: It lowered LDL, increased HDL, but did not reduce the number of heart attacks in studies.”

The current findings contrast with previous suggestions of cardiovascular benefit from calcium supplementation. One study found that calcium increases the HDL:LDL cholesterol ratio by almost 20% (Am. J. Med. 2002;112:343-7).

In addition, a one-third decrease in deaths from cardiovascular events was observed among women who had the greatest intake of calcium from either diet or supplements in the Iowa Women's Health Study (Am. J. Epidemiol. 1999;149:151-61).

Following completion of a 5-year osteoporosis study (Am. J. Med. 2006;1119:777-85), Dr. Mark J. Bolland and his associates at the University of Auckland (New Zealand) reassessed their data to compare cardiovascular events. Women were randomized to 1 g/day of elemental calcium (Citracal) or placebo. All of the 1,471 participants were postmenopausal for at least 5 years and older than age 55 years at baseline, and 10% of those were older than age 80 at baseline.

Death, sudden death, myocardial infarction, angina, other chest pain, stroke, and transient ischemic attacks events were recorded every 6 months. In all, 336 women stopped taking the calcium and 296 stopped taking the placebo before the study end.

A total of 21 of the 732 women in the calcium group experienced 24 myocardial infarctions, a statistically significant difference vs. 10 of the 739 in the placebo group who had 10 such events. A composite end point of sudden death, myocardial infarction, angina, or chest pain was also higher in the calcium group (155 events among 87 women) vs. the placebo group (135 events among 93 women).

No significant differences were found in angina, chest pain, transient ischemic attack, stroke, or sudden death events between groups. There were 34 deaths in the calcium group and 29 in the placebo, a nonsignificant difference.

Dr. Redberg was not surprised by the elevated MI risk. She said research by Dr. Linda Demer, vice chair of medicine at the University of California, Los Angeles, has indicated increased cardiovascular risk associated with calcium.

“It's called the calcium paradox. Women lose calcium from their bones as they get older and it ends up in their arteries and the lining of their vessel walls, leading to accelerated atherosclerosis,” Dr. Redberg said. “This study is a confirmation of that hypothesis, that calcium can end up in the walls of your arteries.” Dr. Redberg is also a professor of medicine at the University of California, San Francisco.

The mean age was 74 years and participants were white, a possible limitation for generalizing results to other ages or racial groups, the authors said.

However, Dr. Redberg said that the inclusion of older women in the study is a strength because they are the most likely to be prescribed calcium supplements. It is very unusual for studies to include people older than age 80, she added.

'It is an important finding because so many women are prescribed calcium supplements.' DR. REDBERG

Calcium supplementation significantly increased the risk of a myocardial infarction among healthy postmenopausal women, compared with those taking placebo, in a secondary analysis of an osteoporosis study.

Physicians should consider this increased cardiovascular risk against other clinical benefits of calcium supplementation in older women until confirmatory studies can be completed, the authors suggested.

“It is an important finding because so many women are prescribed calcium supplements,” Dr. Rita F. Redberg said in an interview. “I would not recommend calcium supplementation based on this finding. This raises enough concern. With any supplement, you have to show evidence of benefit without risk,” said Dr. Redberg, who was not involved in the study.

The HDL to LDL cholesterol ratios improved among the 732 women who took daily calcium supplementation, compared with the 739 participants who took placebo. This suggests that a different mechanism spurred the increase in myocardial infarction.

“This is an interesting point. It shows that just improving cholesterol does not reduce the risk of a heart attack,” said Dr. Redberg, a Robert Wood Johnson Foundation health policy fellow and director of women's cardiovascular services at the University of California, San Francisco. “It was the same finding with estrogen: It lowered LDL, increased HDL, but did not reduce the number of heart attacks in studies.”

The current findings contrast with previous suggestions of cardiovascular benefit from calcium supplementation. One study found that calcium increases the HDL:LDL cholesterol ratio by almost 20% (Am. J. Med. 2002;112:343-7).

In addition, a one-third decrease in deaths from cardiovascular events was observed among women who had the greatest intake of calcium from either diet or supplements in the Iowa Women's Health Study (Am. J. Epidemiol. 1999;149:151-61).

Following completion of a 5-year osteoporosis study (Am. J. Med. 2006;1119:777-85), Dr. Mark J. Bolland and his associates at the University of Auckland (New Zealand) reassessed their data to compare cardiovascular events. Women were randomized to 1 g/day of elemental calcium (Citracal) or placebo. All of the 1,471 participants were postmenopausal for at least 5 years and older than age 55 years at baseline, and 10% of those were older than age 80 at baseline.

Death, sudden death, myocardial infarction, angina, other chest pain, stroke, and transient ischemic attacks events were recorded every 6 months. In all, 336 women stopped taking the calcium and 296 stopped taking the placebo before the study end.

A total of 21 of the 732 women in the calcium group experienced 24 myocardial infarctions, a statistically significant difference vs. 10 of the 739 in the placebo group who had 10 such events. A composite end point of sudden death, myocardial infarction, angina, or chest pain was also higher in the calcium group (155 events among 87 women) vs. the placebo group (135 events among 93 women).

No significant differences were found in angina, chest pain, transient ischemic attack, stroke, or sudden death events between groups. There were 34 deaths in the calcium group and 29 in the placebo, a nonsignificant difference.

Dr. Redberg was not surprised by the elevated MI risk. She said research by Dr. Linda Demer, vice chair of medicine at the University of California, Los Angeles, has indicated increased cardiovascular risk associated with calcium.

“It's called the calcium paradox. Women lose calcium from their bones as they get older and it ends up in their arteries and the lining of their vessel walls, leading to accelerated atherosclerosis,” Dr. Redberg said. “This study is a confirmation of that hypothesis, that calcium can end up in the walls of your arteries.” Dr. Redberg is also a professor of medicine at the University of California, San Francisco.

The mean age was 74 years and participants were white, a possible limitation for generalizing results to other ages or racial groups, the authors said.

However, Dr. Redberg said that the inclusion of older women in the study is a strength because they are the most likely to be prescribed calcium supplements. It is very unusual for studies to include people older than age 80, she added.

'It is an important finding because so many women are prescribed calcium supplements.' DR. REDBERG

Calcium supplementation significantly increased the risk of a myocardial infarction among healthy postmenopausal women, compared with those taking placebo, in a secondary analysis of an osteoporosis study.

Physicians should consider this increased cardiovascular risk against other clinical benefits of calcium supplementation in older women until confirmatory studies can be completed, the authors suggested.

“It is an important finding because so many women are prescribed calcium supplements,” Dr. Rita F. Redberg said in an interview. “I would not recommend calcium supplementation based on this finding. This raises enough concern. With any supplement, you have to show evidence of benefit without risk,” said Dr. Redberg, who was not involved in the study.

The HDL to LDL cholesterol ratios improved among the 732 women who took daily calcium supplementation, compared with the 739 participants who took placebo. This suggests that a different mechanism spurred the increase in myocardial infarction.

“This is an interesting point. It shows that just improving cholesterol does not reduce the risk of a heart attack,” said Dr. Redberg, a Robert Wood Johnson Foundation health policy fellow and director of women's cardiovascular services at the University of California, San Francisco. “It was the same finding with estrogen: It lowered LDL, increased HDL, but did not reduce the number of heart attacks in studies.”

The current findings contrast with previous suggestions of cardiovascular benefit from calcium supplementation. One study found that calcium increases the HDL:LDL cholesterol ratio by almost 20% (Am. J. Med. 2002;112:343-7).

In addition, a one-third decrease in deaths from cardiovascular events was observed among women who had the greatest intake of calcium from either diet or supplements in the Iowa Women's Health Study (Am. J. Epidemiol. 1999;149:151-61).

Following completion of a 5-year osteoporosis study (Am. J. Med. 2006;1119:777-85), Dr. Mark J. Bolland and his associates at the University of Auckland (New Zealand) reassessed their data to compare cardiovascular events. Women were randomized to 1 g/day of elemental calcium (Citracal) or placebo. All of the 1,471 participants were postmenopausal for at least 5 years and older than age 55 years at baseline, and 10% of those were older than age 80 at baseline.

Death, sudden death, myocardial infarction, angina, other chest pain, stroke, and transient ischemic attacks events were recorded every 6 months. In all, 336 women stopped taking the calcium and 296 stopped taking the placebo before the study end.

A total of 21 of the 732 women in the calcium group experienced 24 myocardial infarctions, a statistically significant difference vs. 10 of the 739 in the placebo group who had 10 such events. A composite end point of sudden death, myocardial infarction, angina, or chest pain was also higher in the calcium group (155 events among 87 women) vs. the placebo group (135 events among 93 women).

No significant differences were found in angina, chest pain, transient ischemic attack, stroke, or sudden death events between groups. There were 34 deaths in the calcium group and 29 in the placebo, a nonsignificant difference.

Dr. Redberg was not surprised by the elevated MI risk. She said research by Dr. Linda Demer, vice chair of medicine at the University of California, Los Angeles, has indicated increased cardiovascular risk associated with calcium.

“It's called the calcium paradox. Women lose calcium from their bones as they get older and it ends up in their arteries and the lining of their vessel walls, leading to accelerated atherosclerosis,” Dr. Redberg said. “This study is a confirmation of that hypothesis, that calcium can end up in the walls of your arteries.” Dr. Redberg is also a professor of medicine at the University of California, San Francisco.

The mean age was 74 years and participants were white, a possible limitation for generalizing results to other ages or racial groups, the authors said.

However, Dr. Redberg said that the inclusion of older women in the study is a strength because they are the most likely to be prescribed calcium supplements. It is very unusual for studies to include people older than age 80, she added.

'It is an important finding because so many women are prescribed calcium supplements.' DR. REDBERG

FORT LAUDERDALE, FLA. — Prediction of which patients with osteoarthritis will progress has been challenging for clinicians. However, there is promise—researchers identified serum and urinary markers independently associated with 5-year radiographic progression of knee osteoarthritis in a study presented at the World Congress on Osteoarthritis.

Combined use of serum type II collagen helical peptide (Helix-II) and urinary crosslinked C-telopeptide (uCTX-II) might predict disease outcome in these patients, Dr. Patrick Garnero said. Helix-II and CTX-II are type II collagen fragments believed to reflect different osteoarthritis breakdown events from the triple helix and the telopeptide regions of knee cartilage.

Dr. Garnero and his associates previously demonstrated that high urinary levels of these markers were associated with highly destructive hip osteoarthritis (Ann. Rheum. Dis. 2006;65:1639-44). However, urinary markers have limitations, including wide variations in urine dilution and some difficulty obtaining precise sampling among elderly patients.

“Based on this, we launched a study to investigate a new serum-based assay,” said Dr. Garnero, a researcher at Synarc Inc. in Lyon, France.

They compared standing anterior-posterior knee x-rays and Helix-II and CTX-II levels among 83 patients with knee osteoarthritis at baseline and at 2, 3, and 5 years. At baseline, mean age was 62 years and 54% were women. In terms of disease severity, the majority (77%) of patients had a baseline Kellgren-Lawrence (KL) score of 3. The remaining patients scored as follows: KL 0, 13%; KL 1, 5%; KL 2, 4%; and KL 4, 1%.

Joint space was measured on radiographs at the narrowest point. Progression was defined as a reduction in tibiofemoral joint space of 2 mm or a need for total knee replacement during follow-up. A total of 24 patients progressed and 59 did not.

“At baseline and 5 years, both markers were higher in patients with progressive disease. It was not significant at baseline, but the average over 5 years was significant,” Dr. Garnero said at the meeting, sponsored by the Osteoarthritis Research Society International.

For example, after adjustment for age, gender, and body mass index, each standard deviation increase in serum Helix-II was associated with a relative risk of 1.69 for progression. Patients with the highest quartile of serum Helix-II levels and a uCTX-II level above the median had a risk of radiologic progression 8 times higher (RR, 7.79).

“The combined measurement of serum helix-II and uCTX-II may be useful to predict disease outcome in knee osteoarthritis,” Dr. Garnero said.

FORT LAUDERDALE, FLA. — Prediction of which patients with osteoarthritis will progress has been challenging for clinicians. However, there is promise—researchers identified serum and urinary markers independently associated with 5-year radiographic progression of knee osteoarthritis in a study presented at the World Congress on Osteoarthritis.

Combined use of serum type II collagen helical peptide (Helix-II) and urinary crosslinked C-telopeptide (uCTX-II) might predict disease outcome in these patients, Dr. Patrick Garnero said. Helix-II and CTX-II are type II collagen fragments believed to reflect different osteoarthritis breakdown events from the triple helix and the telopeptide regions of knee cartilage.

Dr. Garnero and his associates previously demonstrated that high urinary levels of these markers were associated with highly destructive hip osteoarthritis (Ann. Rheum. Dis. 2006;65:1639-44). However, urinary markers have limitations, including wide variations in urine dilution and some difficulty obtaining precise sampling among elderly patients.

“Based on this, we launched a study to investigate a new serum-based assay,” said Dr. Garnero, a researcher at Synarc Inc. in Lyon, France.

They compared standing anterior-posterior knee x-rays and Helix-II and CTX-II levels among 83 patients with knee osteoarthritis at baseline and at 2, 3, and 5 years. At baseline, mean age was 62 years and 54% were women. In terms of disease severity, the majority (77%) of patients had a baseline Kellgren-Lawrence (KL) score of 3. The remaining patients scored as follows: KL 0, 13%; KL 1, 5%; KL 2, 4%; and KL 4, 1%.

Joint space was measured on radiographs at the narrowest point. Progression was defined as a reduction in tibiofemoral joint space of 2 mm or a need for total knee replacement during follow-up. A total of 24 patients progressed and 59 did not.

“At baseline and 5 years, both markers were higher in patients with progressive disease. It was not significant at baseline, but the average over 5 years was significant,” Dr. Garnero said at the meeting, sponsored by the Osteoarthritis Research Society International.

For example, after adjustment for age, gender, and body mass index, each standard deviation increase in serum Helix-II was associated with a relative risk of 1.69 for progression. Patients with the highest quartile of serum Helix-II levels and a uCTX-II level above the median had a risk of radiologic progression 8 times higher (RR, 7.79).

“The combined measurement of serum helix-II and uCTX-II may be useful to predict disease outcome in knee osteoarthritis,” Dr. Garnero said.

FORT LAUDERDALE, FLA. — Prediction of which patients with osteoarthritis will progress has been challenging for clinicians. However, there is promise—researchers identified serum and urinary markers independently associated with 5-year radiographic progression of knee osteoarthritis in a study presented at the World Congress on Osteoarthritis.

Combined use of serum type II collagen helical peptide (Helix-II) and urinary crosslinked C-telopeptide (uCTX-II) might predict disease outcome in these patients, Dr. Patrick Garnero said. Helix-II and CTX-II are type II collagen fragments believed to reflect different osteoarthritis breakdown events from the triple helix and the telopeptide regions of knee cartilage.

Dr. Garnero and his associates previously demonstrated that high urinary levels of these markers were associated with highly destructive hip osteoarthritis (Ann. Rheum. Dis. 2006;65:1639-44). However, urinary markers have limitations, including wide variations in urine dilution and some difficulty obtaining precise sampling among elderly patients.

“Based on this, we launched a study to investigate a new serum-based assay,” said Dr. Garnero, a researcher at Synarc Inc. in Lyon, France.

They compared standing anterior-posterior knee x-rays and Helix-II and CTX-II levels among 83 patients with knee osteoarthritis at baseline and at 2, 3, and 5 years. At baseline, mean age was 62 years and 54% were women. In terms of disease severity, the majority (77%) of patients had a baseline Kellgren-Lawrence (KL) score of 3. The remaining patients scored as follows: KL 0, 13%; KL 1, 5%; KL 2, 4%; and KL 4, 1%.

Joint space was measured on radiographs at the narrowest point. Progression was defined as a reduction in tibiofemoral joint space of 2 mm or a need for total knee replacement during follow-up. A total of 24 patients progressed and 59 did not.

“At baseline and 5 years, both markers were higher in patients with progressive disease. It was not significant at baseline, but the average over 5 years was significant,” Dr. Garnero said at the meeting, sponsored by the Osteoarthritis Research Society International.

For example, after adjustment for age, gender, and body mass index, each standard deviation increase in serum Helix-II was associated with a relative risk of 1.69 for progression. Patients with the highest quartile of serum Helix-II levels and a uCTX-II level above the median had a risk of radiologic progression 8 times higher (RR, 7.79).

“The combined measurement of serum helix-II and uCTX-II may be useful to predict disease outcome in knee osteoarthritis,” Dr. Garnero said.

FORT LAUDERDALE, FLA. — Symmetrical bilateral progression of knee osteoarthritis was a surprising result of a genetic study of hand osteoarthritis patients and their relatives.

“The most surprising [finding] was that progression occurred in a similar manner on both sides. This indicates to me that there is probably a strong genetic factor for progression,” Dr. Virginia Byers Kraus said in an interview during a poster session at the World Congress on Osteoarthritis, Osteoarthritis Research Society International.

Dr. Byers Kraus and associates studied 1,333 hand osteoarthritis patients for a median of 3.8 years. Participants whose osteoarthritis progressed in the medial compartment of one knee were significantly more likely to progress in the medial compartment of the other. The same held true for lateral compartment progressions.

“If you see these individuals [with hand OA], if they have an affected knee, the other is likely to be affected with osteoarthritis and they are likely to progress in parallel,” said Dr. Byers Kraus, an internist in the division of rheumatology, Duke University Medical Center, Durham, N.C. “It's a probable prognostic factor for patients.”

The cohort came from the Genetics of Generalized Osteoarthritis (GOGO) study. A total of 79% were women and the mean age was 69 years. Researchers scored baseline and follow-up radiographs for changes in Kellgren-Lawrence grade, minimal joint space, presence of osteophytes, and joint space narrowing of the medial and lateral knee compartments. They also assessed at least two affected siblings with three-joint bilateral bony enlargements in their hands to assess any genetic correlations.

“We found in a cohort with hand osteoarthritis they were more likely to have osteoarthritis [in other joints] if family members have hand osteoarthritis,” Dr. Byers Kraus said. “When you have a patient with hand osteoarthritis and relatives with hand osteoarthritis, there is an increased likelihood of bilateral knee osteoarthritis.”

The results may also have research implications. In studies of OA patients who don't progress, it's hard to assess the efficacy of a treatment. “This was responsible for the failure of a major trial on Actonel,” said Dr. Byers Kraus. “Age, female gender, obesity—outside of these, we are not good at identifying definite progressors.”

FORT LAUDERDALE, FLA. — Symmetrical bilateral progression of knee osteoarthritis was a surprising result of a genetic study of hand osteoarthritis patients and their relatives.

“The most surprising [finding] was that progression occurred in a similar manner on both sides. This indicates to me that there is probably a strong genetic factor for progression,” Dr. Virginia Byers Kraus said in an interview during a poster session at the World Congress on Osteoarthritis, Osteoarthritis Research Society International.

Dr. Byers Kraus and associates studied 1,333 hand osteoarthritis patients for a median of 3.8 years. Participants whose osteoarthritis progressed in the medial compartment of one knee were significantly more likely to progress in the medial compartment of the other. The same held true for lateral compartment progressions.

“If you see these individuals [with hand OA], if they have an affected knee, the other is likely to be affected with osteoarthritis and they are likely to progress in parallel,” said Dr. Byers Kraus, an internist in the division of rheumatology, Duke University Medical Center, Durham, N.C. “It's a probable prognostic factor for patients.”

The cohort came from the Genetics of Generalized Osteoarthritis (GOGO) study. A total of 79% were women and the mean age was 69 years. Researchers scored baseline and follow-up radiographs for changes in Kellgren-Lawrence grade, minimal joint space, presence of osteophytes, and joint space narrowing of the medial and lateral knee compartments. They also assessed at least two affected siblings with three-joint bilateral bony enlargements in their hands to assess any genetic correlations.

“We found in a cohort with hand osteoarthritis they were more likely to have osteoarthritis [in other joints] if family members have hand osteoarthritis,” Dr. Byers Kraus said. “When you have a patient with hand osteoarthritis and relatives with hand osteoarthritis, there is an increased likelihood of bilateral knee osteoarthritis.”

The results may also have research implications. In studies of OA patients who don't progress, it's hard to assess the efficacy of a treatment. “This was responsible for the failure of a major trial on Actonel,” said Dr. Byers Kraus. “Age, female gender, obesity—outside of these, we are not good at identifying definite progressors.”

FORT LAUDERDALE, FLA. — Symmetrical bilateral progression of knee osteoarthritis was a surprising result of a genetic study of hand osteoarthritis patients and their relatives.

“The most surprising [finding] was that progression occurred in a similar manner on both sides. This indicates to me that there is probably a strong genetic factor for progression,” Dr. Virginia Byers Kraus said in an interview during a poster session at the World Congress on Osteoarthritis, Osteoarthritis Research Society International.

Dr. Byers Kraus and associates studied 1,333 hand osteoarthritis patients for a median of 3.8 years. Participants whose osteoarthritis progressed in the medial compartment of one knee were significantly more likely to progress in the medial compartment of the other. The same held true for lateral compartment progressions.

“If you see these individuals [with hand OA], if they have an affected knee, the other is likely to be affected with osteoarthritis and they are likely to progress in parallel,” said Dr. Byers Kraus, an internist in the division of rheumatology, Duke University Medical Center, Durham, N.C. “It's a probable prognostic factor for patients.”

The cohort came from the Genetics of Generalized Osteoarthritis (GOGO) study. A total of 79% were women and the mean age was 69 years. Researchers scored baseline and follow-up radiographs for changes in Kellgren-Lawrence grade, minimal joint space, presence of osteophytes, and joint space narrowing of the medial and lateral knee compartments. They also assessed at least two affected siblings with three-joint bilateral bony enlargements in their hands to assess any genetic correlations.

“We found in a cohort with hand osteoarthritis they were more likely to have osteoarthritis [in other joints] if family members have hand osteoarthritis,” Dr. Byers Kraus said. “When you have a patient with hand osteoarthritis and relatives with hand osteoarthritis, there is an increased likelihood of bilateral knee osteoarthritis.”

The results may also have research implications. In studies of OA patients who don't progress, it's hard to assess the efficacy of a treatment. “This was responsible for the failure of a major trial on Actonel,” said Dr. Byers Kraus. “Age, female gender, obesity—outside of these, we are not good at identifying definite progressors.”

FORT LAUDERDALE, FLA. — People with symptomatic osteoarthritis can be differentiated from those with only radiographic evidence of disease using a combination of biomarkers, according to a study presented at the World Congress on Osteoarthritis.

Olga V. Nemirovsky, Ph.D., a researcher at Pfizer Inc. in St. Louis, and her associates, compared a large number of biomarkers of joint matrix protein degradation and synthesis and biomarkers of inflammation using urine, serum, and plasma samples from 83 participants.

Their aim was to identify biomarkers that would indicate any initial efficacy of disease-modifying osteoarthritis drugs for future clinical trials.

Participants included 22 people with symptomatic osteoarthritis; 30 people with only radiographic evidence of disease in their hip and/or knee joints; 19 with only radiographic evidence in their hand and/or spine joints; and 12 controls with no symptoms or radiographic signs of disease.

“We tried to assess each biomarker separately. Then we evaluated combinations of two biomarkers, and then applied multivariate analyses to all biomarkers,” said Dr. Nemirovsky.

Five markers contributed the most to the distinction between symptomatic patients and the others: plasma procollagen type III N-terminal propeptides (PIIINP), prostaglandin PGE2, 15-hydroxyeicosatetraenoic acid (15-HETE), collagen type II neoepitope (TIINE), and procollagen type II N-terminal propeptide (NPII). Although analysis of individual markers revealed significant differences, a combination of markers proved superior to any single assay.

Patients with symptomatic osteoarthritis had significantly higher levels of urinary C-terminal telopeptides of type II collagen (CTX-II), TIINE and collagen type III neoepitope (TIIINE) levels, osteopontin, plasma procollagen type I (PINP), prostaglandin PGE2, 15-HETE, and 3-nitrotyrosine (3-NT) compared with other groups, Dr. Nemirovsky said at the meeting, which was sponsored by the Osteoarthritis Research Society International.

On the other hand, the researchers found significantly lower levels of plasma NPII and urinary aggrecan neoepitope (Agg) in the symptomatic group.

Levels of Agg were higher for the group with radiographic disease in the hip/knee compared with the no-radiographic-evidence group or the symptomatic patients. The researchers used a model to distinguish the patients with radiographic evidence of hip/knee osteoarthritis from the radiographic hand/spine and no-radiographic-evidence groups.

The markers that contributed most to this distinction were Agg, TIINE, PIIINP, PGE2, and 15-HETE.

FORT LAUDERDALE, FLA. — People with symptomatic osteoarthritis can be differentiated from those with only radiographic evidence of disease using a combination of biomarkers, according to a study presented at the World Congress on Osteoarthritis.

Olga V. Nemirovsky, Ph.D., a researcher at Pfizer Inc. in St. Louis, and her associates, compared a large number of biomarkers of joint matrix protein degradation and synthesis and biomarkers of inflammation using urine, serum, and plasma samples from 83 participants.

Their aim was to identify biomarkers that would indicate any initial efficacy of disease-modifying osteoarthritis drugs for future clinical trials.

Participants included 22 people with symptomatic osteoarthritis; 30 people with only radiographic evidence of disease in their hip and/or knee joints; 19 with only radiographic evidence in their hand and/or spine joints; and 12 controls with no symptoms or radiographic signs of disease.

“We tried to assess each biomarker separately. Then we evaluated combinations of two biomarkers, and then applied multivariate analyses to all biomarkers,” said Dr. Nemirovsky.

Five markers contributed the most to the distinction between symptomatic patients and the others: plasma procollagen type III N-terminal propeptides (PIIINP), prostaglandin PGE2, 15-hydroxyeicosatetraenoic acid (15-HETE), collagen type II neoepitope (TIINE), and procollagen type II N-terminal propeptide (NPII). Although analysis of individual markers revealed significant differences, a combination of markers proved superior to any single assay.

Patients with symptomatic osteoarthritis had significantly higher levels of urinary C-terminal telopeptides of type II collagen (CTX-II), TIINE and collagen type III neoepitope (TIIINE) levels, osteopontin, plasma procollagen type I (PINP), prostaglandin PGE2, 15-HETE, and 3-nitrotyrosine (3-NT) compared with other groups, Dr. Nemirovsky said at the meeting, which was sponsored by the Osteoarthritis Research Society International.

On the other hand, the researchers found significantly lower levels of plasma NPII and urinary aggrecan neoepitope (Agg) in the symptomatic group.

Levels of Agg were higher for the group with radiographic disease in the hip/knee compared with the no-radiographic-evidence group or the symptomatic patients. The researchers used a model to distinguish the patients with radiographic evidence of hip/knee osteoarthritis from the radiographic hand/spine and no-radiographic-evidence groups.

The markers that contributed most to this distinction were Agg, TIINE, PIIINP, PGE2, and 15-HETE.

FORT LAUDERDALE, FLA. — People with symptomatic osteoarthritis can be differentiated from those with only radiographic evidence of disease using a combination of biomarkers, according to a study presented at the World Congress on Osteoarthritis.

Olga V. Nemirovsky, Ph.D., a researcher at Pfizer Inc. in St. Louis, and her associates, compared a large number of biomarkers of joint matrix protein degradation and synthesis and biomarkers of inflammation using urine, serum, and plasma samples from 83 participants.

Their aim was to identify biomarkers that would indicate any initial efficacy of disease-modifying osteoarthritis drugs for future clinical trials.

Participants included 22 people with symptomatic osteoarthritis; 30 people with only radiographic evidence of disease in their hip and/or knee joints; 19 with only radiographic evidence in their hand and/or spine joints; and 12 controls with no symptoms or radiographic signs of disease.

“We tried to assess each biomarker separately. Then we evaluated combinations of two biomarkers, and then applied multivariate analyses to all biomarkers,” said Dr. Nemirovsky.

Five markers contributed the most to the distinction between symptomatic patients and the others: plasma procollagen type III N-terminal propeptides (PIIINP), prostaglandin PGE2, 15-hydroxyeicosatetraenoic acid (15-HETE), collagen type II neoepitope (TIINE), and procollagen type II N-terminal propeptide (NPII). Although analysis of individual markers revealed significant differences, a combination of markers proved superior to any single assay.

Patients with symptomatic osteoarthritis had significantly higher levels of urinary C-terminal telopeptides of type II collagen (CTX-II), TIINE and collagen type III neoepitope (TIIINE) levels, osteopontin, plasma procollagen type I (PINP), prostaglandin PGE2, 15-HETE, and 3-nitrotyrosine (3-NT) compared with other groups, Dr. Nemirovsky said at the meeting, which was sponsored by the Osteoarthritis Research Society International.

On the other hand, the researchers found significantly lower levels of plasma NPII and urinary aggrecan neoepitope (Agg) in the symptomatic group.

Levels of Agg were higher for the group with radiographic disease in the hip/knee compared with the no-radiographic-evidence group or the symptomatic patients. The researchers used a model to distinguish the patients with radiographic evidence of hip/knee osteoarthritis from the radiographic hand/spine and no-radiographic-evidence groups.

The markers that contributed most to this distinction were Agg, TIINE, PIIINP, PGE2, and 15-HETE.

FORT LAUDERDALE, FLA. — Early screening of synovial fluid volume changes using magnetic resonance imaging could identify patients at risk for progressive knee osteoarthritis, according to interim findings of an ongoing study.

Synovial fluid volume decrease on MRI correlated with both osteophyte formation and joint space narrowing, whereas loss of cartilage volume did not predict progressive disease, Dr. Svetlana Krasnokutsky said during her presentation at the World Congress on Osteoarthritis.

Dr. Krasnokutsky and her associates are conducting a 2-year longitudinal biomarker study of 58 patients with knee osteoarthritis. She presented interim cross-sectional findings at the meeting, which was sponsored by the Osteoarthritis Research Society International.

At baseline, participants' mean age was 62 years, mean body mass index was 28 kg/m

Semiflexed, anterior-posterior radiographs of the knees at baseline will be repeated at 24 months. Also, 3T MRI with gadolinium will be performed at baseline and 24 months to measure cartilage, synovium, and bone marrow volumes. “X-rays are insensitive to a substantial portion of cartilage loss that can be seen on MRI,” said Dr. Krasnokutsky of New York University, New York.

The interim analysis indicates that total cartilage volume does not correlate with the Kellgren-Lawrence (KL) score. “We expected to see a decrease in cartilage volumes in the femur and tibia as the KL score increased, but we did not.” In addition, total cartilage volume did not correlate with KL score, joint space width, or osteophyte score.

In contrast, increasing synovial volume correlated with severity of knee osteoarthritis by KL score. “Synovitis is a biomarker of advancing disease and is a parallel feature of the failing joint,” Dr. Krasnokutsky said. Synovial volume correlated modestly with bone marrow lesion volume. However, it did not correlate to the Western Ontario and McMaster Universities osteoarthritis index pain score.

FORT LAUDERDALE, FLA. — Early screening of synovial fluid volume changes using magnetic resonance imaging could identify patients at risk for progressive knee osteoarthritis, according to interim findings of an ongoing study.

Synovial fluid volume decrease on MRI correlated with both osteophyte formation and joint space narrowing, whereas loss of cartilage volume did not predict progressive disease, Dr. Svetlana Krasnokutsky said during her presentation at the World Congress on Osteoarthritis.

Dr. Krasnokutsky and her associates are conducting a 2-year longitudinal biomarker study of 58 patients with knee osteoarthritis. She presented interim cross-sectional findings at the meeting, which was sponsored by the Osteoarthritis Research Society International.

At baseline, participants' mean age was 62 years, mean body mass index was 28 kg/m

Semiflexed, anterior-posterior radiographs of the knees at baseline will be repeated at 24 months. Also, 3T MRI with gadolinium will be performed at baseline and 24 months to measure cartilage, synovium, and bone marrow volumes. “X-rays are insensitive to a substantial portion of cartilage loss that can be seen on MRI,” said Dr. Krasnokutsky of New York University, New York.

The interim analysis indicates that total cartilage volume does not correlate with the Kellgren-Lawrence (KL) score. “We expected to see a decrease in cartilage volumes in the femur and tibia as the KL score increased, but we did not.” In addition, total cartilage volume did not correlate with KL score, joint space width, or osteophyte score.

In contrast, increasing synovial volume correlated with severity of knee osteoarthritis by KL score. “Synovitis is a biomarker of advancing disease and is a parallel feature of the failing joint,” Dr. Krasnokutsky said. Synovial volume correlated modestly with bone marrow lesion volume. However, it did not correlate to the Western Ontario and McMaster Universities osteoarthritis index pain score.

FORT LAUDERDALE, FLA. — Early screening of synovial fluid volume changes using magnetic resonance imaging could identify patients at risk for progressive knee osteoarthritis, according to interim findings of an ongoing study.

Synovial fluid volume decrease on MRI correlated with both osteophyte formation and joint space narrowing, whereas loss of cartilage volume did not predict progressive disease, Dr. Svetlana Krasnokutsky said during her presentation at the World Congress on Osteoarthritis.

Dr. Krasnokutsky and her associates are conducting a 2-year longitudinal biomarker study of 58 patients with knee osteoarthritis. She presented interim cross-sectional findings at the meeting, which was sponsored by the Osteoarthritis Research Society International.

At baseline, participants' mean age was 62 years, mean body mass index was 28 kg/m

Semiflexed, anterior-posterior radiographs of the knees at baseline will be repeated at 24 months. Also, 3T MRI with gadolinium will be performed at baseline and 24 months to measure cartilage, synovium, and bone marrow volumes. “X-rays are insensitive to a substantial portion of cartilage loss that can be seen on MRI,” said Dr. Krasnokutsky of New York University, New York.

The interim analysis indicates that total cartilage volume does not correlate with the Kellgren-Lawrence (KL) score. “We expected to see a decrease in cartilage volumes in the femur and tibia as the KL score increased, but we did not.” In addition, total cartilage volume did not correlate with KL score, joint space width, or osteophyte score.

In contrast, increasing synovial volume correlated with severity of knee osteoarthritis by KL score. “Synovitis is a biomarker of advancing disease and is a parallel feature of the failing joint,” Dr. Krasnokutsky said. Synovial volume correlated modestly with bone marrow lesion volume. However, it did not correlate to the Western Ontario and McMaster Universities osteoarthritis index pain score.

MIAMI – Intervene to prevent marijuana use in children as young as 8 years, a National Institute on Drug Abuse researcher suggested at the annual conference of the American Society for Addiction Medicine.

“Addiction is a developmental disease–it starts in adolescence and childhood with tobacco, THC [tetrahydrocannabinol], and alcohol,” said Jag H. Khalsa, Ph.D.

Physicians first can help children and their parents overcome the common misperception that marijuana carries much lower health risks, compared with other substances, Dr. Khalsa said.

“Young people think this drug is innocuous and does not do much harm. Drug use goes up with this perception and down with the perception that it is dangerous.”

Almost 20% of high school seniors smoke marijuana. Overall, 15 million Americans 12 years and older have used marijuana at least once in their lifetime, and there are 2-3 million new users each year, Dr. Khalsa said. He is chief of the medical consequences branch, division of pharmacotherapies and medical consequences of drug abuse, National Institute on Drug Abuse, Bethesda, Md. “Marijuana continues to remain the third most commonly used drug mentioned in the ER–so the consequences are significant,” Dr. Khalsa said.

Among the most important adverse effects of marijuana use are the cognitive effects: impairment in cognition, short-term memory loss, and executive dysfunction. These deficits can be dose-related and can persist up to 15 days, according to a NIDA-funded study (Neurology 2002;59:1337-43). College students who abused marijuana demonstrated impairment in cognitive function and ability to remember simple tasks at baseline. Effects were still observed after 7 days and 15 days of abstinence. However, deficits were no longer seen at day 28. “This suggests people recovered from the chronic effects of marijuana.” A more sophisticated follow-up study will use PET MRI to assess residual effects, Dr. Khalsa said.

Chronic marijuana use also may be associated with major depression, attention-deficit/hyperactivity disorder, and aggressive behaviors in drug-dependent adolescents.

Acute increases in heart rate, increased blood pressure, and cardiac output alterations are among the cardiovascular effects. Endocrine effects in humans include lower testosterone levels, decreased luteinizing hormone levels, infertility, and gynecomastia. “There are inconsistent reports, however, in the literature” regarding endocrine alterations, Dr. Khalsa said.

The immune effects are significant, he said.

THC suppresses macrophages, natural killer cells, and T lymphocytes, mediated through CB2 receptors on leukocytes. “Suppression of antitumor activity makes a person more susceptible to cancer,” he said. “Squamous cell carcinomas have been reported in the mouths of marijuana users.”

Marijuana smoke contains approximately 50% more carcinogenic compounds than tobacco smoke. However, “sometimes it is difficult to tease out effects between the people who smoke both tobacco and marijuana over the long term,” Dr. Khalsa said.

THC also can cause modest short-term bronchodilation. In addition, regular marijuana smoking leads to chronic cough and increased sputum production, he said.

For more information on the clinical effects of marijuana and research developments, visit www.nida.nih.gov

In Utero Exposure May Have Lasting Effects

Marijuana exposure in utero might spur neurologic changes associated with long-term memory impairment, Dr. Khalsa said.

For example, functional MRI (fMRI) demonstrated that young adults who had been exposed to marijuana prenatally had altered neural activity during visuospatial working memory tasks (Neurotoxicol. Teratol. 2006;28:286-95).

Researchers assessed 31 participants aged 18-22 years, including 16 exposed prenatally to marijuana and 15 others with no such exposure. They controlled for current drug use. The participants performed a visuospatial task while neural activity was imaged with fMRI.

As the amount of prenatal marijuana exposure increased, imaging showed significantly more neural activity in the left inferior and middle frontal gyri, left parahippocampal gyrus, left middle occipital gyrus, and left cerebellum. At the same time, the imaging demonstrated significantly less activity in right inferior and middle frontal gyri. The authors wrote that they “interpret the results to suggest that prenatal marijuana exposure alters neural functioning during visuospatial working memory processing in young adulthood.”

MIAMI – Intervene to prevent marijuana use in children as young as 8 years, a National Institute on Drug Abuse researcher suggested at the annual conference of the American Society for Addiction Medicine.

“Addiction is a developmental disease–it starts in adolescence and childhood with tobacco, THC [tetrahydrocannabinol], and alcohol,” said Jag H. Khalsa, Ph.D.

Physicians first can help children and their parents overcome the common misperception that marijuana carries much lower health risks, compared with other substances, Dr. Khalsa said.

“Young people think this drug is innocuous and does not do much harm. Drug use goes up with this perception and down with the perception that it is dangerous.”

Almost 20% of high school seniors smoke marijuana. Overall, 15 million Americans 12 years and older have used marijuana at least once in their lifetime, and there are 2-3 million new users each year, Dr. Khalsa said. He is chief of the medical consequences branch, division of pharmacotherapies and medical consequences of drug abuse, National Institute on Drug Abuse, Bethesda, Md. “Marijuana continues to remain the third most commonly used drug mentioned in the ER–so the consequences are significant,” Dr. Khalsa said.

Among the most important adverse effects of marijuana use are the cognitive effects: impairment in cognition, short-term memory loss, and executive dysfunction. These deficits can be dose-related and can persist up to 15 days, according to a NIDA-funded study (Neurology 2002;59:1337-43). College students who abused marijuana demonstrated impairment in cognitive function and ability to remember simple tasks at baseline. Effects were still observed after 7 days and 15 days of abstinence. However, deficits were no longer seen at day 28. “This suggests people recovered from the chronic effects of marijuana.” A more sophisticated follow-up study will use PET MRI to assess residual effects, Dr. Khalsa said.

Chronic marijuana use also may be associated with major depression, attention-deficit/hyperactivity disorder, and aggressive behaviors in drug-dependent adolescents.

Acute increases in heart rate, increased blood pressure, and cardiac output alterations are among the cardiovascular effects. Endocrine effects in humans include lower testosterone levels, decreased luteinizing hormone levels, infertility, and gynecomastia. “There are inconsistent reports, however, in the literature” regarding endocrine alterations, Dr. Khalsa said.

The immune effects are significant, he said.

THC suppresses macrophages, natural killer cells, and T lymphocytes, mediated through CB2 receptors on leukocytes. “Suppression of antitumor activity makes a person more susceptible to cancer,” he said. “Squamous cell carcinomas have been reported in the mouths of marijuana users.”

Marijuana smoke contains approximately 50% more carcinogenic compounds than tobacco smoke. However, “sometimes it is difficult to tease out effects between the people who smoke both tobacco and marijuana over the long term,” Dr. Khalsa said.

THC also can cause modest short-term bronchodilation. In addition, regular marijuana smoking leads to chronic cough and increased sputum production, he said.

For more information on the clinical effects of marijuana and research developments, visit www.nida.nih.gov

In Utero Exposure May Have Lasting Effects

Marijuana exposure in utero might spur neurologic changes associated with long-term memory impairment, Dr. Khalsa said.

For example, functional MRI (fMRI) demonstrated that young adults who had been exposed to marijuana prenatally had altered neural activity during visuospatial working memory tasks (Neurotoxicol. Teratol. 2006;28:286-95).

Researchers assessed 31 participants aged 18-22 years, including 16 exposed prenatally to marijuana and 15 others with no such exposure. They controlled for current drug use. The participants performed a visuospatial task while neural activity was imaged with fMRI.

As the amount of prenatal marijuana exposure increased, imaging showed significantly more neural activity in the left inferior and middle frontal gyri, left parahippocampal gyrus, left middle occipital gyrus, and left cerebellum. At the same time, the imaging demonstrated significantly less activity in right inferior and middle frontal gyri. The authors wrote that they “interpret the results to suggest that prenatal marijuana exposure alters neural functioning during visuospatial working memory processing in young adulthood.”

MIAMI – Intervene to prevent marijuana use in children as young as 8 years, a National Institute on Drug Abuse researcher suggested at the annual conference of the American Society for Addiction Medicine.

“Addiction is a developmental disease–it starts in adolescence and childhood with tobacco, THC [tetrahydrocannabinol], and alcohol,” said Jag H. Khalsa, Ph.D.

Physicians first can help children and their parents overcome the common misperception that marijuana carries much lower health risks, compared with other substances, Dr. Khalsa said.

“Young people think this drug is innocuous and does not do much harm. Drug use goes up with this perception and down with the perception that it is dangerous.”

Almost 20% of high school seniors smoke marijuana. Overall, 15 million Americans 12 years and older have used marijuana at least once in their lifetime, and there are 2-3 million new users each year, Dr. Khalsa said. He is chief of the medical consequences branch, division of pharmacotherapies and medical consequences of drug abuse, National Institute on Drug Abuse, Bethesda, Md. “Marijuana continues to remain the third most commonly used drug mentioned in the ER–so the consequences are significant,” Dr. Khalsa said.

Among the most important adverse effects of marijuana use are the cognitive effects: impairment in cognition, short-term memory loss, and executive dysfunction. These deficits can be dose-related and can persist up to 15 days, according to a NIDA-funded study (Neurology 2002;59:1337-43). College students who abused marijuana demonstrated impairment in cognitive function and ability to remember simple tasks at baseline. Effects were still observed after 7 days and 15 days of abstinence. However, deficits were no longer seen at day 28. “This suggests people recovered from the chronic effects of marijuana.” A more sophisticated follow-up study will use PET MRI to assess residual effects, Dr. Khalsa said.

Chronic marijuana use also may be associated with major depression, attention-deficit/hyperactivity disorder, and aggressive behaviors in drug-dependent adolescents.

Acute increases in heart rate, increased blood pressure, and cardiac output alterations are among the cardiovascular effects. Endocrine effects in humans include lower testosterone levels, decreased luteinizing hormone levels, infertility, and gynecomastia. “There are inconsistent reports, however, in the literature” regarding endocrine alterations, Dr. Khalsa said.

The immune effects are significant, he said.

THC suppresses macrophages, natural killer cells, and T lymphocytes, mediated through CB2 receptors on leukocytes. “Suppression of antitumor activity makes a person more susceptible to cancer,” he said. “Squamous cell carcinomas have been reported in the mouths of marijuana users.”

Marijuana smoke contains approximately 50% more carcinogenic compounds than tobacco smoke. However, “sometimes it is difficult to tease out effects between the people who smoke both tobacco and marijuana over the long term,” Dr. Khalsa said.

THC also can cause modest short-term bronchodilation. In addition, regular marijuana smoking leads to chronic cough and increased sputum production, he said.

For more information on the clinical effects of marijuana and research developments, visit www.nida.nih.gov

In Utero Exposure May Have Lasting Effects

Marijuana exposure in utero might spur neurologic changes associated with long-term memory impairment, Dr. Khalsa said.

For example, functional MRI (fMRI) demonstrated that young adults who had been exposed to marijuana prenatally had altered neural activity during visuospatial working memory tasks (Neurotoxicol. Teratol. 2006;28:286-95).

Researchers assessed 31 participants aged 18-22 years, including 16 exposed prenatally to marijuana and 15 others with no such exposure. They controlled for current drug use. The participants performed a visuospatial task while neural activity was imaged with fMRI.

As the amount of prenatal marijuana exposure increased, imaging showed significantly more neural activity in the left inferior and middle frontal gyri, left parahippocampal gyrus, left middle occipital gyrus, and left cerebellum. At the same time, the imaging demonstrated significantly less activity in right inferior and middle frontal gyri. The authors wrote that they “interpret the results to suggest that prenatal marijuana exposure alters neural functioning during visuospatial working memory processing in young adulthood.”

Inclusion of ultrasonography of the leg did not alter 3-month thromboembolic events in a large group of patients with suspected pulmonary embolism, compared with those assessed with a D-dimer test and multislice CT only, according to a randomized, multicenter study.

“We believe that our findings can be applied to a broad population with suspected pulmonary embolism, and that [the findings] lend support to the hypothesis that a negative MSCT [multislice CT] or ELISA [enzyme-linked immunosorbent assay] D-dimer measurement safely excludes pulmonary embolism in patients with a low or intermediate clinical probability of pulmonary embolism,” Dr. Marc Righini, an internist in the division of angiography and hemostasis at Geneva University Hospital, and his associates wrote.

They assessed 1,819 consecutive outpatients with a suspected pulmonary embolism who presented to the emergency department at one of six medical centers in Europe from January 2005 to August 2006. The prevalence of pulmonary embolism was 20.6%. Men made up about 45% of the study population, mean age was 59 years, and about 18% had a history of venous thromboembolism.

After exclusions, 855 patients were randomized to undergo double testing with a serum D-dimer assay and MSCT imaging. Another 838 patients had a triple assessment with serum D-dimer, venous compression ultrasonography of the leg, and MSCT.

The primary outcome was the risk of venous thromboembolism events at 3 months in patients who, because of the diagnostic tests' results, were not treated for pulmonary embolism. The thromboembolic risk at follow-up was 0.3% in the double-testing group (2 patients of 673 with complete follow-up) and 0.3% in the triple-testing group (2 patients of 686), thus indicating noninferiority of the double-testing strategy.

“Our results show that ultrasound is no longer required as a safety net for the identification of clots that might have been missed by MSCT,” the authors wrote (Lancet 2008;371:1343–52).

The dual strategy was 24% less expensive than the triple-testing protocol, according to a comparison of mean diagnostic test cost per patient. “Therefore, our data do not support the routine use of ultrasound,” they wrote. They added that ultrasound would allow avoidance of MSCT in only 1 of every 11 patients.

Inclusion of ultrasonography of the leg did not alter 3-month thromboembolic events in a large group of patients with suspected pulmonary embolism, compared with those assessed with a D-dimer test and multislice CT only, according to a randomized, multicenter study.

“We believe that our findings can be applied to a broad population with suspected pulmonary embolism, and that [the findings] lend support to the hypothesis that a negative MSCT [multislice CT] or ELISA [enzyme-linked immunosorbent assay] D-dimer measurement safely excludes pulmonary embolism in patients with a low or intermediate clinical probability of pulmonary embolism,” Dr. Marc Righini, an internist in the division of angiography and hemostasis at Geneva University Hospital, and his associates wrote.

They assessed 1,819 consecutive outpatients with a suspected pulmonary embolism who presented to the emergency department at one of six medical centers in Europe from January 2005 to August 2006. The prevalence of pulmonary embolism was 20.6%. Men made up about 45% of the study population, mean age was 59 years, and about 18% had a history of venous thromboembolism.

After exclusions, 855 patients were randomized to undergo double testing with a serum D-dimer assay and MSCT imaging. Another 838 patients had a triple assessment with serum D-dimer, venous compression ultrasonography of the leg, and MSCT.

The primary outcome was the risk of venous thromboembolism events at 3 months in patients who, because of the diagnostic tests' results, were not treated for pulmonary embolism. The thromboembolic risk at follow-up was 0.3% in the double-testing group (2 patients of 673 with complete follow-up) and 0.3% in the triple-testing group (2 patients of 686), thus indicating noninferiority of the double-testing strategy.

“Our results show that ultrasound is no longer required as a safety net for the identification of clots that might have been missed by MSCT,” the authors wrote (Lancet 2008;371:1343–52).

The dual strategy was 24% less expensive than the triple-testing protocol, according to a comparison of mean diagnostic test cost per patient. “Therefore, our data do not support the routine use of ultrasound,” they wrote. They added that ultrasound would allow avoidance of MSCT in only 1 of every 11 patients.

Inclusion of ultrasonography of the leg did not alter 3-month thromboembolic events in a large group of patients with suspected pulmonary embolism, compared with those assessed with a D-dimer test and multislice CT only, according to a randomized, multicenter study.

“We believe that our findings can be applied to a broad population with suspected pulmonary embolism, and that [the findings] lend support to the hypothesis that a negative MSCT [multislice CT] or ELISA [enzyme-linked immunosorbent assay] D-dimer measurement safely excludes pulmonary embolism in patients with a low or intermediate clinical probability of pulmonary embolism,” Dr. Marc Righini, an internist in the division of angiography and hemostasis at Geneva University Hospital, and his associates wrote.

They assessed 1,819 consecutive outpatients with a suspected pulmonary embolism who presented to the emergency department at one of six medical centers in Europe from January 2005 to August 2006. The prevalence of pulmonary embolism was 20.6%. Men made up about 45% of the study population, mean age was 59 years, and about 18% had a history of venous thromboembolism.

After exclusions, 855 patients were randomized to undergo double testing with a serum D-dimer assay and MSCT imaging. Another 838 patients had a triple assessment with serum D-dimer, venous compression ultrasonography of the leg, and MSCT.

The primary outcome was the risk of venous thromboembolism events at 3 months in patients who, because of the diagnostic tests' results, were not treated for pulmonary embolism. The thromboembolic risk at follow-up was 0.3% in the double-testing group (2 patients of 673 with complete follow-up) and 0.3% in the triple-testing group (2 patients of 686), thus indicating noninferiority of the double-testing strategy.

“Our results show that ultrasound is no longer required as a safety net for the identification of clots that might have been missed by MSCT,” the authors wrote (Lancet 2008;371:1343–52).

The dual strategy was 24% less expensive than the triple-testing protocol, according to a comparison of mean diagnostic test cost per patient. “Therefore, our data do not support the routine use of ultrasound,” they wrote. They added that ultrasound would allow avoidance of MSCT in only 1 of every 11 patients.

Calcium supplementation significantly increased the risk of a myocardial infarction among healthy, postmenopausal women, compared with those taking placebo, in a secondary analysis of an osteoporosis study.

Physicians should consider this increased cardiovascular risk against other clinical benefits of calcium supplementation in older women until confirmatory studies can be completed, the authors suggested.

“It is an important finding because so many women are prescribed calcium supplements,” Dr. Rita F. Redberg said in an interview. “I would not recommend calcium supplementation based on this finding. This raises enough concern. With any supplement, you have to show evidence of benefit without risk,” said Dr. Redberg, who was not involved in the study.

The HDL/LDL cholesterol ratios improved among the 732 women who took daily calcium supplementation, compared with the 739 participants who took placebo. This suggests that a different mechanism spurred the increase in myocardial infarction.

“This is an interesting point. It shows that just improving cholesterol does not reduce the risk of a heart attack,” said Dr. Redberg, director of women's cardiovascular services and professor of medicine at the University of California, San Francisco. “It was the same finding with estrogen: It lowered LDL, increased HDL, but did not reduce the number of heart attacks in studies.”

The current findings contrast with previous suggestions of cardiovascular benefit from calcium supplementation. One study found that calcium increases the HDL:LDL cholesterol ratio by almost 20% (Am. J. Med. 2002;112:343–7). In addition, a one-third decrease in deaths from cardiovascular events was observed among women who had the greatest intake of calcium from either diet or supplements in the Iowa Women's Health Study (Am. J. Epidemiol. 1999;149:151–61).

Following completion of a 5-year osteoporosis study (Am. J. Med. 2006;1119:777–85), Dr. Mark J. Bolland and his associates at the University of Auckland (New Zealand) reassessed their data to compare cardiovascular events. Women were randomized to 1 g/day of elemental calcium (Citracal) or placebo. All of the 1,471 participants were postmenopausal for at least 5 years and older than age 55 years at baseline, and 10% of those were older than age 80 at baseline.

Death, sudden death, myocardial infarction, angina, other chest pain, stroke, and transient ischemic attacks events were recorded every 6 months. In all, 336 women stopped taking the calcium and 296 stopped taking the placebo before the study end.

A total of 21 of the 732 women in the calcium group experienced 24 myocardial infarctions, a statistically significant difference compared with 10 of the 739 in the placebo group who had 10 such events. A composite end point of sudden death, myocardial infarction, angina, or chest pain was also higher in the calcium group (155 events among 87 women) compared with the placebo group (135 events among 93 women).

No significant differences were found in angina, chest pain, transient ischemic attack, stroke, or sudden death events between groups. There were 34 deaths in the calcium group and 29 in the placebo, a nonsignificant difference.

Dr. Redberg was not surprised by the elevated MI risk. She said research by Dr. Linda Demer, vice chair of medicine at the University of California, Los Angeles, has indicated increased cardiovascular risk associated with calcium. “It's called the calcium paradox. Women lose calcium from their bones as they get older and it ends up in their arteries and the lining of their vessel walls, leading to accelerated atherosclerosis. This study is a confirmation of that hypothesis.”

The mean age was 74 years and all participants were white, a possible limitation for generalizing results to other ages or racial groups, the authors said. However, Dr. Redberg said that the inclusion of older women in the study is a strength because they are the most likely to be prescribed calcium supplements. It is very unusual for studies to include people older than age 80, she added.

“What is effective for women for preventing osteoporosis?” Dr. Redberg said. “First we had estrogen, then vitamin D and calcium, and the bisphosphonates, but all have been shown to have significant side effects or risk. It may be safest to prescribe diet and weight-bearing exercises to prevent osteoporosis.”

Calcium supplementation significantly increased the risk of a myocardial infarction among healthy, postmenopausal women, compared with those taking placebo, in a secondary analysis of an osteoporosis study.

Physicians should consider this increased cardiovascular risk against other clinical benefits of calcium supplementation in older women until confirmatory studies can be completed, the authors suggested.

“It is an important finding because so many women are prescribed calcium supplements,” Dr. Rita F. Redberg said in an interview. “I would not recommend calcium supplementation based on this finding. This raises enough concern. With any supplement, you have to show evidence of benefit without risk,” said Dr. Redberg, who was not involved in the study.

The HDL/LDL cholesterol ratios improved among the 732 women who took daily calcium supplementation, compared with the 739 participants who took placebo. This suggests that a different mechanism spurred the increase in myocardial infarction.

“This is an interesting point. It shows that just improving cholesterol does not reduce the risk of a heart attack,” said Dr. Redberg, director of women's cardiovascular services and professor of medicine at the University of California, San Francisco. “It was the same finding with estrogen: It lowered LDL, increased HDL, but did not reduce the number of heart attacks in studies.”

The current findings contrast with previous suggestions of cardiovascular benefit from calcium supplementation. One study found that calcium increases the HDL:LDL cholesterol ratio by almost 20% (Am. J. Med. 2002;112:343–7). In addition, a one-third decrease in deaths from cardiovascular events was observed among women who had the greatest intake of calcium from either diet or supplements in the Iowa Women's Health Study (Am. J. Epidemiol. 1999;149:151–61).

Following completion of a 5-year osteoporosis study (Am. J. Med. 2006;1119:777–85), Dr. Mark J. Bolland and his associates at the University of Auckland (New Zealand) reassessed their data to compare cardiovascular events. Women were randomized to 1 g/day of elemental calcium (Citracal) or placebo. All of the 1,471 participants were postmenopausal for at least 5 years and older than age 55 years at baseline, and 10% of those were older than age 80 at baseline.

Death, sudden death, myocardial infarction, angina, other chest pain, stroke, and transient ischemic attacks events were recorded every 6 months. In all, 336 women stopped taking the calcium and 296 stopped taking the placebo before the study end.

A total of 21 of the 732 women in the calcium group experienced 24 myocardial infarctions, a statistically significant difference compared with 10 of the 739 in the placebo group who had 10 such events. A composite end point of sudden death, myocardial infarction, angina, or chest pain was also higher in the calcium group (155 events among 87 women) compared with the placebo group (135 events among 93 women).

No significant differences were found in angina, chest pain, transient ischemic attack, stroke, or sudden death events between groups. There were 34 deaths in the calcium group and 29 in the placebo, a nonsignificant difference.

Dr. Redberg was not surprised by the elevated MI risk. She said research by Dr. Linda Demer, vice chair of medicine at the University of California, Los Angeles, has indicated increased cardiovascular risk associated with calcium. “It's called the calcium paradox. Women lose calcium from their bones as they get older and it ends up in their arteries and the lining of their vessel walls, leading to accelerated atherosclerosis. This study is a confirmation of that hypothesis.”

The mean age was 74 years and all participants were white, a possible limitation for generalizing results to other ages or racial groups, the authors said. However, Dr. Redberg said that the inclusion of older women in the study is a strength because they are the most likely to be prescribed calcium supplements. It is very unusual for studies to include people older than age 80, she added.

“What is effective for women for preventing osteoporosis?” Dr. Redberg said. “First we had estrogen, then vitamin D and calcium, and the bisphosphonates, but all have been shown to have significant side effects or risk. It may be safest to prescribe diet and weight-bearing exercises to prevent osteoporosis.”

Calcium supplementation significantly increased the risk of a myocardial infarction among healthy, postmenopausal women, compared with those taking placebo, in a secondary analysis of an osteoporosis study.

Physicians should consider this increased cardiovascular risk against other clinical benefits of calcium supplementation in older women until confirmatory studies can be completed, the authors suggested.

“It is an important finding because so many women are prescribed calcium supplements,” Dr. Rita F. Redberg said in an interview. “I would not recommend calcium supplementation based on this finding. This raises enough concern. With any supplement, you have to show evidence of benefit without risk,” said Dr. Redberg, who was not involved in the study.

The HDL/LDL cholesterol ratios improved among the 732 women who took daily calcium supplementation, compared with the 739 participants who took placebo. This suggests that a different mechanism spurred the increase in myocardial infarction.

“This is an interesting point. It shows that just improving cholesterol does not reduce the risk of a heart attack,” said Dr. Redberg, director of women's cardiovascular services and professor of medicine at the University of California, San Francisco. “It was the same finding with estrogen: It lowered LDL, increased HDL, but did not reduce the number of heart attacks in studies.”

The current findings contrast with previous suggestions of cardiovascular benefit from calcium supplementation. One study found that calcium increases the HDL:LDL cholesterol ratio by almost 20% (Am. J. Med. 2002;112:343–7). In addition, a one-third decrease in deaths from cardiovascular events was observed among women who had the greatest intake of calcium from either diet or supplements in the Iowa Women's Health Study (Am. J. Epidemiol. 1999;149:151–61).

Following completion of a 5-year osteoporosis study (Am. J. Med. 2006;1119:777–85), Dr. Mark J. Bolland and his associates at the University of Auckland (New Zealand) reassessed their data to compare cardiovascular events. Women were randomized to 1 g/day of elemental calcium (Citracal) or placebo. All of the 1,471 participants were postmenopausal for at least 5 years and older than age 55 years at baseline, and 10% of those were older than age 80 at baseline.

Death, sudden death, myocardial infarction, angina, other chest pain, stroke, and transient ischemic attacks events were recorded every 6 months. In all, 336 women stopped taking the calcium and 296 stopped taking the placebo before the study end.

A total of 21 of the 732 women in the calcium group experienced 24 myocardial infarctions, a statistically significant difference compared with 10 of the 739 in the placebo group who had 10 such events. A composite end point of sudden death, myocardial infarction, angina, or chest pain was also higher in the calcium group (155 events among 87 women) compared with the placebo group (135 events among 93 women).

No significant differences were found in angina, chest pain, transient ischemic attack, stroke, or sudden death events between groups. There were 34 deaths in the calcium group and 29 in the placebo, a nonsignificant difference.

Dr. Redberg was not surprised by the elevated MI risk. She said research by Dr. Linda Demer, vice chair of medicine at the University of California, Los Angeles, has indicated increased cardiovascular risk associated with calcium. “It's called the calcium paradox. Women lose calcium from their bones as they get older and it ends up in their arteries and the lining of their vessel walls, leading to accelerated atherosclerosis. This study is a confirmation of that hypothesis.”

The mean age was 74 years and all participants were white, a possible limitation for generalizing results to other ages or racial groups, the authors said. However, Dr. Redberg said that the inclusion of older women in the study is a strength because they are the most likely to be prescribed calcium supplements. It is very unusual for studies to include people older than age 80, she added.

“What is effective for women for preventing osteoporosis?” Dr. Redberg said. “First we had estrogen, then vitamin D and calcium, and the bisphosphonates, but all have been shown to have significant side effects or risk. It may be safest to prescribe diet and weight-bearing exercises to prevent osteoporosis.”