Kerri Wachter

Osteoarthritis and psoriatic arthritis do share some simple clinical characteristics. Both commonly affect the spine. More importantly, in the hand both osteoarthritis and psoriatic arthritis show a very strong tendency to afflict the distal interphalangeal joints.

“So when you look at it from a very simplistic, clinical perspective, there are strong similarities between psoriatic arthritis and osteoarthritis,” said Dr. Dennis McGonagle of the University of Leeds (England).

Dr. McGonagle, Dr. Ai Lyn Tan, and their colleagues have used high-resolution magnetic resonance imaging to look more closely at how psoriatic arthritis (PsA) and osteoarthritis (OA) affect the distal interphalangeal (DIP) joints (Arthritis Rheum. 2006;54:1328–33). This type of imaging involves conventional 1.5-T MRI scanners coupled with coils that are designed specially for hand imaging that give very high quality images.

Seeing patients with definite OA or PsA, “the most striking abnormalities that we saw were related to the ligaments and the adjacent attachments or entheses,” he said.

Ligament and tendon insertions were involved in patients with either disease; however, enhancement on scanning (evidence of inflammation) of these structures was greater in patients with PsA. In these patients, ligament origins/insertions and extensor tendon insertions appeared to be the epicenter of the inflammatory response with diffuse involvement of adjacent structures. While ligaments tended to be thickened and abnormal in patients with OA, even when the cartilage appeared normal, there was less postcontrast enhancement compared with patients in the PsA group.

The ligaments are sites of very high mechanical stress, particularly in small joints. Both OA and PsA “are localized to sites of very high mechanical stress and 'wear and tear.' A simplistic explanation is that this mechanical stress leads to joint degeneration in osteoarthritis but joint inflammation in psoriatic arthritis,” said Dr. McGonagle.

“Inflammation is well recognized in osteoarthritis but it's thought to be secondary to mechanical factors. Psoriatic arthritis is much more an inflammatory disease. What we speculate is that normal or low levels of microdamage and repair of joints—that damage is misinterpreted by the immune system as some sort of severe damage and then you get this autoimmune reaction.”

There is evidence that most normal people walk around all of the time with low-grade microdamage of the joints, based on studies of insertions and ligaments, carried out in conjunction with Dr. Mike Benjamin of Cardiff University, Wales.

However, in the psoriatic phenotype, the body may misinterpret that damage, resulting in an overexaggerated immune response. After age 50 years, the cumulative microdamage to the joints becomes more pronounced, resulting in the secondary and less severe inflammation that accompanies wear and tear. This would fit with known data that PsA is a disease of younger individuals, while OA is a disease of older individuals said Dr. McGonagle.

It's unclear why the immune system is inadvertently activated in patients with PsA or why cumulative microdamage results in OA in some older individuals but not all. However, the hypothesis that microdamage may trigger both PsA and OA provides fertile ground for research. It is especially relevant for an appreciation that inflammation in the joints may not be primarily the result of immune system malfunction but could be a result of some intrinsic problem with the joints' response to normal locomotion.

Joint space in the distal interphalangeal PsA joint (left) is well preserved versus the OA joint (right). Photos courtesy Dr. Dennis McGonagle/Dr. Ai Lyn Tan

Osteoarthritis and psoriatic arthritis do share some simple clinical characteristics. Both commonly affect the spine. More importantly, in the hand both osteoarthritis and psoriatic arthritis show a very strong tendency to afflict the distal interphalangeal joints.

“So when you look at it from a very simplistic, clinical perspective, there are strong similarities between psoriatic arthritis and osteoarthritis,” said Dr. Dennis McGonagle of the University of Leeds (England).

Dr. McGonagle, Dr. Ai Lyn Tan, and their colleagues have used high-resolution magnetic resonance imaging to look more closely at how psoriatic arthritis (PsA) and osteoarthritis (OA) affect the distal interphalangeal (DIP) joints (Arthritis Rheum. 2006;54:1328–33). This type of imaging involves conventional 1.5-T MRI scanners coupled with coils that are designed specially for hand imaging that give very high quality images.

Seeing patients with definite OA or PsA, “the most striking abnormalities that we saw were related to the ligaments and the adjacent attachments or entheses,” he said.

Ligament and tendon insertions were involved in patients with either disease; however, enhancement on scanning (evidence of inflammation) of these structures was greater in patients with PsA. In these patients, ligament origins/insertions and extensor tendon insertions appeared to be the epicenter of the inflammatory response with diffuse involvement of adjacent structures. While ligaments tended to be thickened and abnormal in patients with OA, even when the cartilage appeared normal, there was less postcontrast enhancement compared with patients in the PsA group.

The ligaments are sites of very high mechanical stress, particularly in small joints. Both OA and PsA “are localized to sites of very high mechanical stress and 'wear and tear.' A simplistic explanation is that this mechanical stress leads to joint degeneration in osteoarthritis but joint inflammation in psoriatic arthritis,” said Dr. McGonagle.

“Inflammation is well recognized in osteoarthritis but it's thought to be secondary to mechanical factors. Psoriatic arthritis is much more an inflammatory disease. What we speculate is that normal or low levels of microdamage and repair of joints—that damage is misinterpreted by the immune system as some sort of severe damage and then you get this autoimmune reaction.”

There is evidence that most normal people walk around all of the time with low-grade microdamage of the joints, based on studies of insertions and ligaments, carried out in conjunction with Dr. Mike Benjamin of Cardiff University, Wales.

However, in the psoriatic phenotype, the body may misinterpret that damage, resulting in an overexaggerated immune response. After age 50 years, the cumulative microdamage to the joints becomes more pronounced, resulting in the secondary and less severe inflammation that accompanies wear and tear. This would fit with known data that PsA is a disease of younger individuals, while OA is a disease of older individuals said Dr. McGonagle.

It's unclear why the immune system is inadvertently activated in patients with PsA or why cumulative microdamage results in OA in some older individuals but not all. However, the hypothesis that microdamage may trigger both PsA and OA provides fertile ground for research. It is especially relevant for an appreciation that inflammation in the joints may not be primarily the result of immune system malfunction but could be a result of some intrinsic problem with the joints' response to normal locomotion.

Joint space in the distal interphalangeal PsA joint (left) is well preserved versus the OA joint (right). Photos courtesy Dr. Dennis McGonagle/Dr. Ai Lyn Tan

Osteoarthritis and psoriatic arthritis do share some simple clinical characteristics. Both commonly affect the spine. More importantly, in the hand both osteoarthritis and psoriatic arthritis show a very strong tendency to afflict the distal interphalangeal joints.

“So when you look at it from a very simplistic, clinical perspective, there are strong similarities between psoriatic arthritis and osteoarthritis,” said Dr. Dennis McGonagle of the University of Leeds (England).

Dr. McGonagle, Dr. Ai Lyn Tan, and their colleagues have used high-resolution magnetic resonance imaging to look more closely at how psoriatic arthritis (PsA) and osteoarthritis (OA) affect the distal interphalangeal (DIP) joints (Arthritis Rheum. 2006;54:1328–33). This type of imaging involves conventional 1.5-T MRI scanners coupled with coils that are designed specially for hand imaging that give very high quality images.

Seeing patients with definite OA or PsA, “the most striking abnormalities that we saw were related to the ligaments and the adjacent attachments or entheses,” he said.

Ligament and tendon insertions were involved in patients with either disease; however, enhancement on scanning (evidence of inflammation) of these structures was greater in patients with PsA. In these patients, ligament origins/insertions and extensor tendon insertions appeared to be the epicenter of the inflammatory response with diffuse involvement of adjacent structures. While ligaments tended to be thickened and abnormal in patients with OA, even when the cartilage appeared normal, there was less postcontrast enhancement compared with patients in the PsA group.

The ligaments are sites of very high mechanical stress, particularly in small joints. Both OA and PsA “are localized to sites of very high mechanical stress and 'wear and tear.' A simplistic explanation is that this mechanical stress leads to joint degeneration in osteoarthritis but joint inflammation in psoriatic arthritis,” said Dr. McGonagle.

“Inflammation is well recognized in osteoarthritis but it's thought to be secondary to mechanical factors. Psoriatic arthritis is much more an inflammatory disease. What we speculate is that normal or low levels of microdamage and repair of joints—that damage is misinterpreted by the immune system as some sort of severe damage and then you get this autoimmune reaction.”

There is evidence that most normal people walk around all of the time with low-grade microdamage of the joints, based on studies of insertions and ligaments, carried out in conjunction with Dr. Mike Benjamin of Cardiff University, Wales.

However, in the psoriatic phenotype, the body may misinterpret that damage, resulting in an overexaggerated immune response. After age 50 years, the cumulative microdamage to the joints becomes more pronounced, resulting in the secondary and less severe inflammation that accompanies wear and tear. This would fit with known data that PsA is a disease of younger individuals, while OA is a disease of older individuals said Dr. McGonagle.

It's unclear why the immune system is inadvertently activated in patients with PsA or why cumulative microdamage results in OA in some older individuals but not all. However, the hypothesis that microdamage may trigger both PsA and OA provides fertile ground for research. It is especially relevant for an appreciation that inflammation in the joints may not be primarily the result of immune system malfunction but could be a result of some intrinsic problem with the joints' response to normal locomotion.

Joint space in the distal interphalangeal PsA joint (left) is well preserved versus the OA joint (right). Photos courtesy Dr. Dennis McGonagle/Dr. Ai Lyn Tan

WASHINGTON – Low-intensity isometric exercise appears to significantly ease the perception of pain in healthy young adults, suggesting that such maneuvers could be a pain management tool for older adults with chronic pain conditions but limited mobility, according to research presented at the annual meeting of the American Pain Society.

In the study, 22 college-age adults performed isometric contractions of the left elbow flexor muscle at an intensity equal to a quarter of their maximal voluntary contraction held until task failure. Following the exercises, the duration it took for patients to first feel experimental pain, or the pain threshold, increased by 50%, compared with baseline, reported Marie Hoeger Bement, Ph.D., professor of physical therapy at Marquette University in Milwaukee.

These findings could have important implications for patients with chronic pain conditions. “Isometric contractions are very easy to prescribe and individualize,” said Dr. Bement. These exercises are especially useful in patients with limited mobility or a fear of falling. “Almost anybody can do it.”

To measure the participants' baseline pain threshold, a weighted blade was placed for 2 minutes on the right index finger of the 11 men and 11 women. The students held a timer in their left hands and were instructed to trigger the timer when they first felt pain. The students also were asked to rate their pain on a 0–10 point scale every 20 seconds during the 2-minute test.

Each student participated in four sessions. For the first session, students performed three maximal voluntary contractions (2 seconds in duration). The next three sessions were randomized.

Patients could be asked to perform a contraction at 25% maximal voluntary contraction to failure (8 minutes on average), at 25% maximal voluntary contraction for 2 minutes, or at 80% maximal voluntary contraction to failure (40 seconds on average). A force transducer measured the force of the contractions. Intensity was based on a percentage of the maximal contraction.

During the session of three maximal voluntary contractions, there was a statistically significant increase in pain threshold over baseline, a finding that Dr. Bement said was “very surprising.” She added, “I'm amazed at what potential exercise has in managing some of chronic pain conditions.”

Pain ratings at 40, 60, and 80 seconds also were significantly decreased. The effect on pain rating appears to be short lived, however, as pain ratings returned to baseline levels by 2 minutes.

When students performed at 80% maximal voluntary contraction, there was no change in the pain threshold; however, there were improvements in pain ratings at 40 and 60 seconds. When students performed at 25% maximal voluntary contraction for 2 minutes, there were no changes in either the pain threshold or the pain ratings.

When students performed at 25% maximal voluntary contraction to failure, there was a roughly 50% increase in pain threshold over baseline. Likewise, pain ratings were decreased at all time points between 40 and 120 seconds.

During the low-intensity, long-duration session, women reported greater pain ratings than did men, both before and after contractions. Women also reported greater increases in pain than did men during the 2 minutes measured. “What's really exciting is that women have a tendency to report greater decreases in pain than men after that low-intensity, long-duration contraction.” So they're experiencing a greater analgesic effect than are men, Dr. Bement said.

To assess whether the sex difference in pain perception was because of hormonal fluctuations in the women, the researchers recruited 20 healthy, college-age women to perform the low-intensity, long-duration contraction (25% maximal voluntary contraction until failure). The women were tested during the midfollicular phase (5–8 days past menses) and the midluteal phase (6–8 days past ovulation). Ovulation was determined using an ovulation test kit.

Baseline pain threshold did not vary with hormone phase. The pain threshold increased with contraction for both menstrual phases, similar to the increases seen in the previous study. Likewise, phase made no difference in pain ratings. Similar to the first study, the women reported decreased pain from 40–100 seconds with exercise, regardless of phase.

WASHINGTON – Low-intensity isometric exercise appears to significantly ease the perception of pain in healthy young adults, suggesting that such maneuvers could be a pain management tool for older adults with chronic pain conditions but limited mobility, according to research presented at the annual meeting of the American Pain Society.

In the study, 22 college-age adults performed isometric contractions of the left elbow flexor muscle at an intensity equal to a quarter of their maximal voluntary contraction held until task failure. Following the exercises, the duration it took for patients to first feel experimental pain, or the pain threshold, increased by 50%, compared with baseline, reported Marie Hoeger Bement, Ph.D., professor of physical therapy at Marquette University in Milwaukee.

These findings could have important implications for patients with chronic pain conditions. “Isometric contractions are very easy to prescribe and individualize,” said Dr. Bement. These exercises are especially useful in patients with limited mobility or a fear of falling. “Almost anybody can do it.”

To measure the participants' baseline pain threshold, a weighted blade was placed for 2 minutes on the right index finger of the 11 men and 11 women. The students held a timer in their left hands and were instructed to trigger the timer when they first felt pain. The students also were asked to rate their pain on a 0–10 point scale every 20 seconds during the 2-minute test.

Each student participated in four sessions. For the first session, students performed three maximal voluntary contractions (2 seconds in duration). The next three sessions were randomized.

Patients could be asked to perform a contraction at 25% maximal voluntary contraction to failure (8 minutes on average), at 25% maximal voluntary contraction for 2 minutes, or at 80% maximal voluntary contraction to failure (40 seconds on average). A force transducer measured the force of the contractions. Intensity was based on a percentage of the maximal contraction.

During the session of three maximal voluntary contractions, there was a statistically significant increase in pain threshold over baseline, a finding that Dr. Bement said was “very surprising.” She added, “I'm amazed at what potential exercise has in managing some of chronic pain conditions.”

Pain ratings at 40, 60, and 80 seconds also were significantly decreased. The effect on pain rating appears to be short lived, however, as pain ratings returned to baseline levels by 2 minutes.

When students performed at 80% maximal voluntary contraction, there was no change in the pain threshold; however, there were improvements in pain ratings at 40 and 60 seconds. When students performed at 25% maximal voluntary contraction for 2 minutes, there were no changes in either the pain threshold or the pain ratings.

When students performed at 25% maximal voluntary contraction to failure, there was a roughly 50% increase in pain threshold over baseline. Likewise, pain ratings were decreased at all time points between 40 and 120 seconds.

During the low-intensity, long-duration session, women reported greater pain ratings than did men, both before and after contractions. Women also reported greater increases in pain than did men during the 2 minutes measured. “What's really exciting is that women have a tendency to report greater decreases in pain than men after that low-intensity, long-duration contraction.” So they're experiencing a greater analgesic effect than are men, Dr. Bement said.

To assess whether the sex difference in pain perception was because of hormonal fluctuations in the women, the researchers recruited 20 healthy, college-age women to perform the low-intensity, long-duration contraction (25% maximal voluntary contraction until failure). The women were tested during the midfollicular phase (5–8 days past menses) and the midluteal phase (6–8 days past ovulation). Ovulation was determined using an ovulation test kit.

Baseline pain threshold did not vary with hormone phase. The pain threshold increased with contraction for both menstrual phases, similar to the increases seen in the previous study. Likewise, phase made no difference in pain ratings. Similar to the first study, the women reported decreased pain from 40–100 seconds with exercise, regardless of phase.

WASHINGTON – Low-intensity isometric exercise appears to significantly ease the perception of pain in healthy young adults, suggesting that such maneuvers could be a pain management tool for older adults with chronic pain conditions but limited mobility, according to research presented at the annual meeting of the American Pain Society.

In the study, 22 college-age adults performed isometric contractions of the left elbow flexor muscle at an intensity equal to a quarter of their maximal voluntary contraction held until task failure. Following the exercises, the duration it took for patients to first feel experimental pain, or the pain threshold, increased by 50%, compared with baseline, reported Marie Hoeger Bement, Ph.D., professor of physical therapy at Marquette University in Milwaukee.

These findings could have important implications for patients with chronic pain conditions. “Isometric contractions are very easy to prescribe and individualize,” said Dr. Bement. These exercises are especially useful in patients with limited mobility or a fear of falling. “Almost anybody can do it.”

To measure the participants' baseline pain threshold, a weighted blade was placed for 2 minutes on the right index finger of the 11 men and 11 women. The students held a timer in their left hands and were instructed to trigger the timer when they first felt pain. The students also were asked to rate their pain on a 0–10 point scale every 20 seconds during the 2-minute test.

Each student participated in four sessions. For the first session, students performed three maximal voluntary contractions (2 seconds in duration). The next three sessions were randomized.

Patients could be asked to perform a contraction at 25% maximal voluntary contraction to failure (8 minutes on average), at 25% maximal voluntary contraction for 2 minutes, or at 80% maximal voluntary contraction to failure (40 seconds on average). A force transducer measured the force of the contractions. Intensity was based on a percentage of the maximal contraction.

During the session of three maximal voluntary contractions, there was a statistically significant increase in pain threshold over baseline, a finding that Dr. Bement said was “very surprising.” She added, “I'm amazed at what potential exercise has in managing some of chronic pain conditions.”

Pain ratings at 40, 60, and 80 seconds also were significantly decreased. The effect on pain rating appears to be short lived, however, as pain ratings returned to baseline levels by 2 minutes.

When students performed at 80% maximal voluntary contraction, there was no change in the pain threshold; however, there were improvements in pain ratings at 40 and 60 seconds. When students performed at 25% maximal voluntary contraction for 2 minutes, there were no changes in either the pain threshold or the pain ratings.

When students performed at 25% maximal voluntary contraction to failure, there was a roughly 50% increase in pain threshold over baseline. Likewise, pain ratings were decreased at all time points between 40 and 120 seconds.

During the low-intensity, long-duration session, women reported greater pain ratings than did men, both before and after contractions. Women also reported greater increases in pain than did men during the 2 minutes measured. “What's really exciting is that women have a tendency to report greater decreases in pain than men after that low-intensity, long-duration contraction.” So they're experiencing a greater analgesic effect than are men, Dr. Bement said.

To assess whether the sex difference in pain perception was because of hormonal fluctuations in the women, the researchers recruited 20 healthy, college-age women to perform the low-intensity, long-duration contraction (25% maximal voluntary contraction until failure). The women were tested during the midfollicular phase (5–8 days past menses) and the midluteal phase (6–8 days past ovulation). Ovulation was determined using an ovulation test kit.

Baseline pain threshold did not vary with hormone phase. The pain threshold increased with contraction for both menstrual phases, similar to the increases seen in the previous study. Likewise, phase made no difference in pain ratings. Similar to the first study, the women reported decreased pain from 40–100 seconds with exercise, regardless of phase.

BETHESDA, MD. – Physicians can help minimize the potential for abuse of opioid pain medications by considering the agents' delivery route, bioavailability, and pharmacokinetics, said Dr. Pamela P. Palmer, director of PainCARE (Center for Advanced Research and Education) at the University of California, San Francisco, at a meeting of the National Institute on Drug Abuse.

“One thing we don't ever want to do is inhibit good pain therapies because we're afraid of abuse and diversion,” said Dr. Palmer, who is also chief medical officer of AcelRx Pharmaceuticals Inc., which is developing delivery methods to limit opioid abuse.

Dr. Palmer recommends matching opioid half-life with the indication. “You want short-acting drugs for short-acting problems and long-acting drugs for long-acting problems,” she said.

The same goes for route of delivery: Match the route with indication. For example, transdermal patches may be less than ideal for acute situations but work well in the chronic setting.

When choosing the optimal route, avoid options with poor bioavailability. Low bioavailability means that higher doses are needed to get the required effect. This excess loading contributes to the amount of drug available for abuse and diversion. For example, the bioavailability of oral oxymorphone is 10%. Ten times the intravenous dose would be required to achieve the same response orally.

Extended-release formulations with low bioavailability pose a particular risk for diversion and abuse. For example, a drug that is 10% bioavailable would require 10 times the intravenous amount to achieve the same response. To use a short-acting compound for long-acting pain with twice-daily dosing, the amount of drug needed goes up again, meaning that a lot of drug is now available for diversion and abuse.

In contrast, methadone is rarely abused for practical reasons. The drug is 100% bioavailable. The same amount of drug is available regardless of how it's administered. In addition, methadone is long lasting, based on the nature of the molecule, so an extended-release formulation isn't necessary. If you're suspicious about a patient possibly diverting or abusing opioids, “this is a great drug to start with.”

Transdermal delivery of opioids involves a delay in onset of action–about 4 hours. For this reason, Dr. Palmer thinks these drugs are not the best options for breakthrough pain. In the setting of outpatient cancer breakthrough pain, it's important to have fast-, short-acting compounds. This avoids layering on excess opioids when breakthrough pain resolves after a short time.

There are a number of new and upcoming ways to avoid the potential for abuse. One problem is that opioid drugs can be crushed or rapidly extracted with alcohol. The SABER (sucrose acetate isobutyrate extended release) technology overcomes this problem because the viscous gel locks the drug into the matrix, despite attempts to crush or melt it, or extract it with alcohol.

Another option is to add antagonists, such as naloxone and naltrexone. Naloxone has a bioavailability of 3% when taken orally, so when a patient takes a drug like Suboxone (buprenorphine and naloxone in a 4:1 ratio) sublingually, “they're not having any inhibition of the mu-opioid receptor due to the naloxone.” But if they attempted to crush and inject the drug, there would be 100% bioavailability of naloxone, and it would inhibit the action of buprenorphine, said Dr. Palmer. The drug is made by Reckitt Benckiser Pharmaceuticals Inc.

A similar drug, Oxytrex (oxycodone and naltrexone), is being developed by Pain Therapeutics Inc. and currently is in phase III trials. “What they're finding in their studies is that there may be less euphoria and less physical withdrawal related to this compound, compared with just the native oxycodone,” said Dr. Palmer.

In 2006, the FDA approved Ionsys (fentanyl iontophoretic transdermal system). This patient-activated analgesic system is indicated for the short-term management of acute postoperative pain in adult patients requiring opioid analgesia during hospitalization. The system (made by Alza Corp.) delivers a preprogrammed, 40-mcg dose of fentanyl through the skin over a 10-minute period. The drug is 100% bioavailable, said. Dr. Palmer.

AcelRx is developing a sublingual sufentanil “nanotab”–six times smaller than a nitroglycerin pill–with 90% bioavailability. Abusers “could crush this if they wanted to, but it's along the order of methadone: They're not going to get any advantage by crushing it and shooting up,” said Dr. Palmer.

Another problem is the tracking of opioids. “I can track a pair of socks through FedEx or UPS from New Jersey to California, yet when I write an OxyContin prescription, I have absolutely no idea how it's used,” said Dr. Palmer. With the technology that's available to track those socks, why isn't there a better way to track the use of prescription opioids, she queried.

Currently, Purdue Pharma L.P. uses radio-frequency identification (RFID) tags on bottles of OxyContin. However, this technology tracks the drugs from the manufacturer to the pharmacy only and does not help a physician to monitor patient use.

AcelRx is planning to use computerized dispensers for nanotab products that will allow physicians to download a patient's dosing history. Such technology also could be helpful in assuring that patients aren't confused by dosing regimens.

ELSEVIER GLOBAL MEDICAL NEWS

BETHESDA, MD. – Physicians can help minimize the potential for abuse of opioid pain medications by considering the agents' delivery route, bioavailability, and pharmacokinetics, said Dr. Pamela P. Palmer, director of PainCARE (Center for Advanced Research and Education) at the University of California, San Francisco, at a meeting of the National Institute on Drug Abuse.

“One thing we don't ever want to do is inhibit good pain therapies because we're afraid of abuse and diversion,” said Dr. Palmer, who is also chief medical officer of AcelRx Pharmaceuticals Inc., which is developing delivery methods to limit opioid abuse.

Dr. Palmer recommends matching opioid half-life with the indication. “You want short-acting drugs for short-acting problems and long-acting drugs for long-acting problems,” she said.

The same goes for route of delivery: Match the route with indication. For example, transdermal patches may be less than ideal for acute situations but work well in the chronic setting.

When choosing the optimal route, avoid options with poor bioavailability. Low bioavailability means that higher doses are needed to get the required effect. This excess loading contributes to the amount of drug available for abuse and diversion. For example, the bioavailability of oral oxymorphone is 10%. Ten times the intravenous dose would be required to achieve the same response orally.

Extended-release formulations with low bioavailability pose a particular risk for diversion and abuse. For example, a drug that is 10% bioavailable would require 10 times the intravenous amount to achieve the same response. To use a short-acting compound for long-acting pain with twice-daily dosing, the amount of drug needed goes up again, meaning that a lot of drug is now available for diversion and abuse.

In contrast, methadone is rarely abused for practical reasons. The drug is 100% bioavailable. The same amount of drug is available regardless of how it's administered. In addition, methadone is long lasting, based on the nature of the molecule, so an extended-release formulation isn't necessary. If you're suspicious about a patient possibly diverting or abusing opioids, “this is a great drug to start with.”

Transdermal delivery of opioids involves a delay in onset of action–about 4 hours. For this reason, Dr. Palmer thinks these drugs are not the best options for breakthrough pain. In the setting of outpatient cancer breakthrough pain, it's important to have fast-, short-acting compounds. This avoids layering on excess opioids when breakthrough pain resolves after a short time.

There are a number of new and upcoming ways to avoid the potential for abuse. One problem is that opioid drugs can be crushed or rapidly extracted with alcohol. The SABER (sucrose acetate isobutyrate extended release) technology overcomes this problem because the viscous gel locks the drug into the matrix, despite attempts to crush or melt it, or extract it with alcohol.

Another option is to add antagonists, such as naloxone and naltrexone. Naloxone has a bioavailability of 3% when taken orally, so when a patient takes a drug like Suboxone (buprenorphine and naloxone in a 4:1 ratio) sublingually, “they're not having any inhibition of the mu-opioid receptor due to the naloxone.” But if they attempted to crush and inject the drug, there would be 100% bioavailability of naloxone, and it would inhibit the action of buprenorphine, said Dr. Palmer. The drug is made by Reckitt Benckiser Pharmaceuticals Inc.

A similar drug, Oxytrex (oxycodone and naltrexone), is being developed by Pain Therapeutics Inc. and currently is in phase III trials. “What they're finding in their studies is that there may be less euphoria and less physical withdrawal related to this compound, compared with just the native oxycodone,” said Dr. Palmer.

In 2006, the FDA approved Ionsys (fentanyl iontophoretic transdermal system). This patient-activated analgesic system is indicated for the short-term management of acute postoperative pain in adult patients requiring opioid analgesia during hospitalization. The system (made by Alza Corp.) delivers a preprogrammed, 40-mcg dose of fentanyl through the skin over a 10-minute period. The drug is 100% bioavailable, said. Dr. Palmer.

AcelRx is developing a sublingual sufentanil “nanotab”–six times smaller than a nitroglycerin pill–with 90% bioavailability. Abusers “could crush this if they wanted to, but it's along the order of methadone: They're not going to get any advantage by crushing it and shooting up,” said Dr. Palmer.

Another problem is the tracking of opioids. “I can track a pair of socks through FedEx or UPS from New Jersey to California, yet when I write an OxyContin prescription, I have absolutely no idea how it's used,” said Dr. Palmer. With the technology that's available to track those socks, why isn't there a better way to track the use of prescription opioids, she queried.

Currently, Purdue Pharma L.P. uses radio-frequency identification (RFID) tags on bottles of OxyContin. However, this technology tracks the drugs from the manufacturer to the pharmacy only and does not help a physician to monitor patient use.

AcelRx is planning to use computerized dispensers for nanotab products that will allow physicians to download a patient's dosing history. Such technology also could be helpful in assuring that patients aren't confused by dosing regimens.

ELSEVIER GLOBAL MEDICAL NEWS

BETHESDA, MD. – Physicians can help minimize the potential for abuse of opioid pain medications by considering the agents' delivery route, bioavailability, and pharmacokinetics, said Dr. Pamela P. Palmer, director of PainCARE (Center for Advanced Research and Education) at the University of California, San Francisco, at a meeting of the National Institute on Drug Abuse.

“One thing we don't ever want to do is inhibit good pain therapies because we're afraid of abuse and diversion,” said Dr. Palmer, who is also chief medical officer of AcelRx Pharmaceuticals Inc., which is developing delivery methods to limit opioid abuse.

Dr. Palmer recommends matching opioid half-life with the indication. “You want short-acting drugs for short-acting problems and long-acting drugs for long-acting problems,” she said.

The same goes for route of delivery: Match the route with indication. For example, transdermal patches may be less than ideal for acute situations but work well in the chronic setting.

When choosing the optimal route, avoid options with poor bioavailability. Low bioavailability means that higher doses are needed to get the required effect. This excess loading contributes to the amount of drug available for abuse and diversion. For example, the bioavailability of oral oxymorphone is 10%. Ten times the intravenous dose would be required to achieve the same response orally.

Extended-release formulations with low bioavailability pose a particular risk for diversion and abuse. For example, a drug that is 10% bioavailable would require 10 times the intravenous amount to achieve the same response. To use a short-acting compound for long-acting pain with twice-daily dosing, the amount of drug needed goes up again, meaning that a lot of drug is now available for diversion and abuse.

In contrast, methadone is rarely abused for practical reasons. The drug is 100% bioavailable. The same amount of drug is available regardless of how it's administered. In addition, methadone is long lasting, based on the nature of the molecule, so an extended-release formulation isn't necessary. If you're suspicious about a patient possibly diverting or abusing opioids, “this is a great drug to start with.”

Transdermal delivery of opioids involves a delay in onset of action–about 4 hours. For this reason, Dr. Palmer thinks these drugs are not the best options for breakthrough pain. In the setting of outpatient cancer breakthrough pain, it's important to have fast-, short-acting compounds. This avoids layering on excess opioids when breakthrough pain resolves after a short time.

There are a number of new and upcoming ways to avoid the potential for abuse. One problem is that opioid drugs can be crushed or rapidly extracted with alcohol. The SABER (sucrose acetate isobutyrate extended release) technology overcomes this problem because the viscous gel locks the drug into the matrix, despite attempts to crush or melt it, or extract it with alcohol.

Another option is to add antagonists, such as naloxone and naltrexone. Naloxone has a bioavailability of 3% when taken orally, so when a patient takes a drug like Suboxone (buprenorphine and naloxone in a 4:1 ratio) sublingually, “they're not having any inhibition of the mu-opioid receptor due to the naloxone.” But if they attempted to crush and inject the drug, there would be 100% bioavailability of naloxone, and it would inhibit the action of buprenorphine, said Dr. Palmer. The drug is made by Reckitt Benckiser Pharmaceuticals Inc.

A similar drug, Oxytrex (oxycodone and naltrexone), is being developed by Pain Therapeutics Inc. and currently is in phase III trials. “What they're finding in their studies is that there may be less euphoria and less physical withdrawal related to this compound, compared with just the native oxycodone,” said Dr. Palmer.

In 2006, the FDA approved Ionsys (fentanyl iontophoretic transdermal system). This patient-activated analgesic system is indicated for the short-term management of acute postoperative pain in adult patients requiring opioid analgesia during hospitalization. The system (made by Alza Corp.) delivers a preprogrammed, 40-mcg dose of fentanyl through the skin over a 10-minute period. The drug is 100% bioavailable, said. Dr. Palmer.

AcelRx is developing a sublingual sufentanil “nanotab”–six times smaller than a nitroglycerin pill–with 90% bioavailability. Abusers “could crush this if they wanted to, but it's along the order of methadone: They're not going to get any advantage by crushing it and shooting up,” said Dr. Palmer.

Another problem is the tracking of opioids. “I can track a pair of socks through FedEx or UPS from New Jersey to California, yet when I write an OxyContin prescription, I have absolutely no idea how it's used,” said Dr. Palmer. With the technology that's available to track those socks, why isn't there a better way to track the use of prescription opioids, she queried.

Currently, Purdue Pharma L.P. uses radio-frequency identification (RFID) tags on bottles of OxyContin. However, this technology tracks the drugs from the manufacturer to the pharmacy only and does not help a physician to monitor patient use.

AcelRx is planning to use computerized dispensers for nanotab products that will allow physicians to download a patient's dosing history. Such technology also could be helpful in assuring that patients aren't confused by dosing regimens.

ELSEVIER GLOBAL MEDICAL NEWS

BALTIMORE – The interaction of cerebrovascular disease and Alzheimer's disease pathology appears to significantly increase the risk of dementia, Dr. Richard O'Brien said at a meeting on Alzheimer's disease and related disorders sponsored by Johns Hopkins University.

“Having cerebrovascular disease on top of just a little Alzheimer's pathology pushes you over the edge into being demented,” said Dr. O'Brien, reporting on data from the Baltimore Longitudinal Study of Aging (BLSA).

The BLSA was initiated in 1958 with the aim of helping researchers learn what happens as people age and sort out changes caused by aging from those caused by disease or other causes. Current enrollment is 2,135 volunteers, and 219 deceased participants are included in the autopsy component. Participants are evaluated yearly.

As of the last analysis in December 2006, 175 brains with normal, stroke, and/or Alzheimer's disease (AD) pathology had been autopsied. The average age at death was 87 years (range 57–102 years), and the group was predominantly male (69%). The group was generally well educated with an average of 18 years of schooling. Overall, 104 had a Consortium to Establish a Registry for Alzheimer's Disease (CERAD) pathology score of 2 or greater, indicating AD pathology. A total of 77 had had at least one stroke.

In those with no stroke, AD pathology could be relatively severe (up to a CERAD score of 2) and still have a relatively low risk of dementia. However, when at least one stroke has occurred, the risk of dementia jumps substantially with only a small amount of AD pathology (CERAD 1). In the absence of AD pathology, it takes about three cortical strokes to induce dementia. When there is moderate AD pathology (CERAD 2), dementia is apparent after two strokes on average. It was possible for patients with moderate AD pathology to never progress to dementia, as long as they remained free of strokes, said Dr. O'Brien, a professor of neurology at Johns Hopkins University, Baltimore.

Stroke alone increased the risk of dementia in this cohort as well. Of those with evidence of stroke on autopsy, 37 had symptomatic strokes. These patients had a fourfold greater risk of dementia than did those with no evidence of stroke. The remaining 40 participants with evidence of stroke at autopsy were asymptomatic. These individuals also had an increased risk of dementia (odds ratio 3.2). “Having a stroke significantly increased your risk of being demented, whether or not that stroke was clinically symptomatic,” said Dr. O'Brien, who is also chair of neurology at Johns Hopkins Bayview Medical Center in Baltimore.

When it comes to the association between strokes and dementia risk, numbers and location matter. “The more strokes you have, the more likely you are to be demented.” The researchers found that only the strokes that occur in the cortex increase the risk of becoming demented,” Dr. O'Brien said. The chance of being demented with one stroke was about 50%, the chance with two strokes was about 80%, and the chance with three strokes was 100%. Strokes in the subcortical part of the brain were not significantly related to dementia.

Stroke size was not a factor in dementia risk. Large strokes tend to be symptomatic. However, in this group the presence of asymptomatic (and presumably small) strokes still conferred a greater risk of dementia. In addition, microstrokes–those occurring in the cortex and requiring a microscope to see–were as likely to increase the risk of becoming demented as a very large stroke in this cohort.

If an older person is cognitively normal before a stroke, the chance of becoming demented is the same as for the age-matched stroke-free population. However, for those who have some cognition problems prior to a stroke, the chance of becoming demented after a stroke is extraordinarily high–a 40-fold increased risk, he said. Dr. O'Brien disclosed that he has no potential conflicts of interest.

The left image shows plaques and tangles (CERAD 2). The right image shows a middle cerebral artery stroke on an autopsy specimen. Photos courtesy Dr. Richard O'Brien

BALTIMORE – The interaction of cerebrovascular disease and Alzheimer's disease pathology appears to significantly increase the risk of dementia, Dr. Richard O'Brien said at a meeting on Alzheimer's disease and related disorders sponsored by Johns Hopkins University.

“Having cerebrovascular disease on top of just a little Alzheimer's pathology pushes you over the edge into being demented,” said Dr. O'Brien, reporting on data from the Baltimore Longitudinal Study of Aging (BLSA).

The BLSA was initiated in 1958 with the aim of helping researchers learn what happens as people age and sort out changes caused by aging from those caused by disease or other causes. Current enrollment is 2,135 volunteers, and 219 deceased participants are included in the autopsy component. Participants are evaluated yearly.

As of the last analysis in December 2006, 175 brains with normal, stroke, and/or Alzheimer's disease (AD) pathology had been autopsied. The average age at death was 87 years (range 57–102 years), and the group was predominantly male (69%). The group was generally well educated with an average of 18 years of schooling. Overall, 104 had a Consortium to Establish a Registry for Alzheimer's Disease (CERAD) pathology score of 2 or greater, indicating AD pathology. A total of 77 had had at least one stroke.

In those with no stroke, AD pathology could be relatively severe (up to a CERAD score of 2) and still have a relatively low risk of dementia. However, when at least one stroke has occurred, the risk of dementia jumps substantially with only a small amount of AD pathology (CERAD 1). In the absence of AD pathology, it takes about three cortical strokes to induce dementia. When there is moderate AD pathology (CERAD 2), dementia is apparent after two strokes on average. It was possible for patients with moderate AD pathology to never progress to dementia, as long as they remained free of strokes, said Dr. O'Brien, a professor of neurology at Johns Hopkins University, Baltimore.

Stroke alone increased the risk of dementia in this cohort as well. Of those with evidence of stroke on autopsy, 37 had symptomatic strokes. These patients had a fourfold greater risk of dementia than did those with no evidence of stroke. The remaining 40 participants with evidence of stroke at autopsy were asymptomatic. These individuals also had an increased risk of dementia (odds ratio 3.2). “Having a stroke significantly increased your risk of being demented, whether or not that stroke was clinically symptomatic,” said Dr. O'Brien, who is also chair of neurology at Johns Hopkins Bayview Medical Center in Baltimore.

When it comes to the association between strokes and dementia risk, numbers and location matter. “The more strokes you have, the more likely you are to be demented.” The researchers found that only the strokes that occur in the cortex increase the risk of becoming demented,” Dr. O'Brien said. The chance of being demented with one stroke was about 50%, the chance with two strokes was about 80%, and the chance with three strokes was 100%. Strokes in the subcortical part of the brain were not significantly related to dementia.

Stroke size was not a factor in dementia risk. Large strokes tend to be symptomatic. However, in this group the presence of asymptomatic (and presumably small) strokes still conferred a greater risk of dementia. In addition, microstrokes–those occurring in the cortex and requiring a microscope to see–were as likely to increase the risk of becoming demented as a very large stroke in this cohort.

If an older person is cognitively normal before a stroke, the chance of becoming demented is the same as for the age-matched stroke-free population. However, for those who have some cognition problems prior to a stroke, the chance of becoming demented after a stroke is extraordinarily high–a 40-fold increased risk, he said. Dr. O'Brien disclosed that he has no potential conflicts of interest.

The left image shows plaques and tangles (CERAD 2). The right image shows a middle cerebral artery stroke on an autopsy specimen. Photos courtesy Dr. Richard O'Brien

BALTIMORE – The interaction of cerebrovascular disease and Alzheimer's disease pathology appears to significantly increase the risk of dementia, Dr. Richard O'Brien said at a meeting on Alzheimer's disease and related disorders sponsored by Johns Hopkins University.

“Having cerebrovascular disease on top of just a little Alzheimer's pathology pushes you over the edge into being demented,” said Dr. O'Brien, reporting on data from the Baltimore Longitudinal Study of Aging (BLSA).

The BLSA was initiated in 1958 with the aim of helping researchers learn what happens as people age and sort out changes caused by aging from those caused by disease or other causes. Current enrollment is 2,135 volunteers, and 219 deceased participants are included in the autopsy component. Participants are evaluated yearly.

As of the last analysis in December 2006, 175 brains with normal, stroke, and/or Alzheimer's disease (AD) pathology had been autopsied. The average age at death was 87 years (range 57–102 years), and the group was predominantly male (69%). The group was generally well educated with an average of 18 years of schooling. Overall, 104 had a Consortium to Establish a Registry for Alzheimer's Disease (CERAD) pathology score of 2 or greater, indicating AD pathology. A total of 77 had had at least one stroke.

In those with no stroke, AD pathology could be relatively severe (up to a CERAD score of 2) and still have a relatively low risk of dementia. However, when at least one stroke has occurred, the risk of dementia jumps substantially with only a small amount of AD pathology (CERAD 1). In the absence of AD pathology, it takes about three cortical strokes to induce dementia. When there is moderate AD pathology (CERAD 2), dementia is apparent after two strokes on average. It was possible for patients with moderate AD pathology to never progress to dementia, as long as they remained free of strokes, said Dr. O'Brien, a professor of neurology at Johns Hopkins University, Baltimore.

Stroke alone increased the risk of dementia in this cohort as well. Of those with evidence of stroke on autopsy, 37 had symptomatic strokes. These patients had a fourfold greater risk of dementia than did those with no evidence of stroke. The remaining 40 participants with evidence of stroke at autopsy were asymptomatic. These individuals also had an increased risk of dementia (odds ratio 3.2). “Having a stroke significantly increased your risk of being demented, whether or not that stroke was clinically symptomatic,” said Dr. O'Brien, who is also chair of neurology at Johns Hopkins Bayview Medical Center in Baltimore.

When it comes to the association between strokes and dementia risk, numbers and location matter. “The more strokes you have, the more likely you are to be demented.” The researchers found that only the strokes that occur in the cortex increase the risk of becoming demented,” Dr. O'Brien said. The chance of being demented with one stroke was about 50%, the chance with two strokes was about 80%, and the chance with three strokes was 100%. Strokes in the subcortical part of the brain were not significantly related to dementia.

Stroke size was not a factor in dementia risk. Large strokes tend to be symptomatic. However, in this group the presence of asymptomatic (and presumably small) strokes still conferred a greater risk of dementia. In addition, microstrokes–those occurring in the cortex and requiring a microscope to see–were as likely to increase the risk of becoming demented as a very large stroke in this cohort.

If an older person is cognitively normal before a stroke, the chance of becoming demented is the same as for the age-matched stroke-free population. However, for those who have some cognition problems prior to a stroke, the chance of becoming demented after a stroke is extraordinarily high–a 40-fold increased risk, he said. Dr. O'Brien disclosed that he has no potential conflicts of interest.

The left image shows plaques and tangles (CERAD 2). The right image shows a middle cerebral artery stroke on an autopsy specimen. Photos courtesy Dr. Richard O'Brien

WASHINGTON — Postmenopausal women with a prior fall or those 80 years or older have a significantly greater risk of a subsequent fall, according to data presented at an international symposium sponsored by the National Osteoporosis Foundation.

Specifically, investigators found that women with a prior fall had an odds ratio of 2.7 and those 80 years or older had a OR of 1.5 for a future fall, based on a analysis of potential risk factors among 66,134 women in the National Osteoporosis Risk Assessment (NORA) study, said Dr. Elizabeth Barrett-Connor, chief of epidemiology in the department of family and preventive medicine at the University of California at San Diego.

The NORA study enrolled over 200,000 community-dwelling, postmenopausal women between 1997 and 1999. Women had to be at least 50 years old without osteoporosis. They also could not have had a bone mineral density measurement in the previous year or be taking an osteoporosis drug. At baseline, BMD was measured at the heel, forearm, or finger. The women were followed up at 1, 3, and 6 years with surveys asking about fractures in the previous 12 months. At baseline, average age was 63 years. Most (91%) were white. The average T score was −0.78. In all, 38% reported at least one fall in the past year.

“History of a fall in the year before a query was a strong predictor for falls,” said Dr. Barrett-Connor.

Potential risk factors included age, body mass index, a self-rating of health as being poor/fair, functional limitations, smoking, alcohol use, early menopause, height loss, peripheral T score, history of fracture after age 45, maternal history of fracture and/or osteoporosis, first-degree relatives with a history of fracture, estrogen therapy, calcium supplementation, use of medications (oral corticosteroids, thyroid medication, osteoporosis-specific drugs), history of depression, osteoporosis self-knowledge, and self-report of a fall within the previous 12 months at the year 1 survey. They also included arthritis, coronary artery disease, hypertension, diabetes, kidney/liver disease, cancers, memory problems, stroke, hyperthyroidism, hypothyroidism, epilepsy, poor vision, and poor hearing.

History of depression and history of stroke increased fall risk by more than 40%. An additional nine factors were identified that significantly increased fall risk by 9%–23%. The number of baseline risk factors was linearly associated with a risk of falling.

The study has several limitations. First, participants were volunteers and may not be a representative sample. Second, falls were self-reported and limited to a 12-month recall. That likely means that falls were underreported. Longitudinal attrition resulted in a slightly younger and healthier analytic sample, which may mean falls were underestimated for the whole cohort. No data were collected on factors known to be tied to falls, such as prescription medications, environment, gait, balance, and strength. Lastly, the cause of falls was not known.

Dr. Barrett-Connor disclosed research support from several pharmaceutical companies. She consults for Merck & Co. Two collaborators are employees of Merck.

JULIE KELLER/ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — Postmenopausal women with a prior fall or those 80 years or older have a significantly greater risk of a subsequent fall, according to data presented at an international symposium sponsored by the National Osteoporosis Foundation.

Specifically, investigators found that women with a prior fall had an odds ratio of 2.7 and those 80 years or older had a OR of 1.5 for a future fall, based on a analysis of potential risk factors among 66,134 women in the National Osteoporosis Risk Assessment (NORA) study, said Dr. Elizabeth Barrett-Connor, chief of epidemiology in the department of family and preventive medicine at the University of California at San Diego.

The NORA study enrolled over 200,000 community-dwelling, postmenopausal women between 1997 and 1999. Women had to be at least 50 years old without osteoporosis. They also could not have had a bone mineral density measurement in the previous year or be taking an osteoporosis drug. At baseline, BMD was measured at the heel, forearm, or finger. The women were followed up at 1, 3, and 6 years with surveys asking about fractures in the previous 12 months. At baseline, average age was 63 years. Most (91%) were white. The average T score was −0.78. In all, 38% reported at least one fall in the past year.

“History of a fall in the year before a query was a strong predictor for falls,” said Dr. Barrett-Connor.

Potential risk factors included age, body mass index, a self-rating of health as being poor/fair, functional limitations, smoking, alcohol use, early menopause, height loss, peripheral T score, history of fracture after age 45, maternal history of fracture and/or osteoporosis, first-degree relatives with a history of fracture, estrogen therapy, calcium supplementation, use of medications (oral corticosteroids, thyroid medication, osteoporosis-specific drugs), history of depression, osteoporosis self-knowledge, and self-report of a fall within the previous 12 months at the year 1 survey. They also included arthritis, coronary artery disease, hypertension, diabetes, kidney/liver disease, cancers, memory problems, stroke, hyperthyroidism, hypothyroidism, epilepsy, poor vision, and poor hearing.

History of depression and history of stroke increased fall risk by more than 40%. An additional nine factors were identified that significantly increased fall risk by 9%–23%. The number of baseline risk factors was linearly associated with a risk of falling.

The study has several limitations. First, participants were volunteers and may not be a representative sample. Second, falls were self-reported and limited to a 12-month recall. That likely means that falls were underreported. Longitudinal attrition resulted in a slightly younger and healthier analytic sample, which may mean falls were underestimated for the whole cohort. No data were collected on factors known to be tied to falls, such as prescription medications, environment, gait, balance, and strength. Lastly, the cause of falls was not known.

Dr. Barrett-Connor disclosed research support from several pharmaceutical companies. She consults for Merck & Co. Two collaborators are employees of Merck.

JULIE KELLER/ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — Postmenopausal women with a prior fall or those 80 years or older have a significantly greater risk of a subsequent fall, according to data presented at an international symposium sponsored by the National Osteoporosis Foundation.

Specifically, investigators found that women with a prior fall had an odds ratio of 2.7 and those 80 years or older had a OR of 1.5 for a future fall, based on a analysis of potential risk factors among 66,134 women in the National Osteoporosis Risk Assessment (NORA) study, said Dr. Elizabeth Barrett-Connor, chief of epidemiology in the department of family and preventive medicine at the University of California at San Diego.

The NORA study enrolled over 200,000 community-dwelling, postmenopausal women between 1997 and 1999. Women had to be at least 50 years old without osteoporosis. They also could not have had a bone mineral density measurement in the previous year or be taking an osteoporosis drug. At baseline, BMD was measured at the heel, forearm, or finger. The women were followed up at 1, 3, and 6 years with surveys asking about fractures in the previous 12 months. At baseline, average age was 63 years. Most (91%) were white. The average T score was −0.78. In all, 38% reported at least one fall in the past year.

“History of a fall in the year before a query was a strong predictor for falls,” said Dr. Barrett-Connor.

Potential risk factors included age, body mass index, a self-rating of health as being poor/fair, functional limitations, smoking, alcohol use, early menopause, height loss, peripheral T score, history of fracture after age 45, maternal history of fracture and/or osteoporosis, first-degree relatives with a history of fracture, estrogen therapy, calcium supplementation, use of medications (oral corticosteroids, thyroid medication, osteoporosis-specific drugs), history of depression, osteoporosis self-knowledge, and self-report of a fall within the previous 12 months at the year 1 survey. They also included arthritis, coronary artery disease, hypertension, diabetes, kidney/liver disease, cancers, memory problems, stroke, hyperthyroidism, hypothyroidism, epilepsy, poor vision, and poor hearing.

History of depression and history of stroke increased fall risk by more than 40%. An additional nine factors were identified that significantly increased fall risk by 9%–23%. The number of baseline risk factors was linearly associated with a risk of falling.

The study has several limitations. First, participants were volunteers and may not be a representative sample. Second, falls were self-reported and limited to a 12-month recall. That likely means that falls were underreported. Longitudinal attrition resulted in a slightly younger and healthier analytic sample, which may mean falls were underestimated for the whole cohort. No data were collected on factors known to be tied to falls, such as prescription medications, environment, gait, balance, and strength. Lastly, the cause of falls was not known.

Dr. Barrett-Connor disclosed research support from several pharmaceutical companies. She consults for Merck & Co. Two collaborators are employees of Merck.

JULIE KELLER/ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — Teriparatide appeared effective in raising lumbar spine bone mineral density, and showed promise in reducing nonvertebral fractures in patients on glucocorticoid therapy with low bone mineral density or a prior fragility fracture, according to data presented at an international symposium sponsored by the National Osteoporosis Foundation.

“In patients with glucocorticoid-induced osteoporosis treated with teriparatide or alendronate for 18 months, teriparatide resulted in significantly greater increases in lumbar spine bone mineral density (BMD) compared with alendronate. Significantly fewer patients had new vertebral fractures with teriparatide, compared with the alendronate group,” said Margaret R. Warner, Ph.D., a researcher with Eli Lilly & Co., which funded this trial.

At 18 months, lumbar spine BMD rose 7.2% for patients treated with teriparatide and 3.4% for those treated with alendronate. Differences could be seen between the two groups as early as 6 months.

Teriparatide (Forteo), made by Eli Lilly, contains recombinant human parathyroid hormone (1–34). It is currently indicated for the treatment of postmenopausal women with osteoporosis who are at high risk for fracture and to increase bone mass in men with primary or hypogonadal osteoporosis who are at high risk for fracture. Teriparatide is the only osteoporosis drug shown to stimulate new bone growth.

Glucocorticoid therapy is the most common cause of secondary osteoporosis. Only risedronate (Actonel, by Procter & Gamble Pharmaceuticals) and alendronate (Fosamax, by Merck & Co.) are indicated for the prevention and treatment of glucocorticoid-induced osteoporosis in men and women receiving glucocorticoids in a daily dosage equal to 7.5 mg or more of prednisone with low BMD.

The trial included men and women at least 21 years old who had taken a minimum dose of 5 mg/day of prednisone (or its equivalent) for 3 months or longer prior to screening. All patients had total hip, femoral neck, or lumbar spine T scores of at most −2.0 or at most −1.0 with a prior fragility fracture. A total of 428 patients (80% women) were randomized to receive 20 mcg/day teriparatide injection and an oral placebo tablet or 10 mg/day oral alendronate and an injectable placebo. All received calcium and vitamin D supplements and were followed for 18 months.

The primary end point was the effect of teriparatide on lumbar spine BMD in patients with glucocorticoid-induced osteoporosis versus alendronate. The researchers also looked at the effect of teriparatide versus alendronate on total hip and femoral neck BMD, on markers of bone turnover, and on the incidence of vertebral and nonvertebral fractures. In addition, markers of bone turnover were analyzed in roughly half of each group. Adverse event data were collected throughout.

At baseline, both groups were fairly evenly matched in terms of gender, race, age, average prednisone dose, and average duration of prednisone use. Both groups were evenly matched in terms of average BMD at the total hip, femoral neck, and lumbar spine, and vertebral and nonvertebral fractures. Three-quarters of the patients in both groups had rheumatologic disease, with rheumatoid arthritis accounting for 69% of disease in the alendronate group and 61% in the teriparatide group.

Total hip BMD rose 3.6% for the teriparatide group, versus 2.2% for the alendronate group. Femoral neck BMD rose 3.7% for the teriparatide group, versus 2.1% for the alendronate group.

In terms of biomarkers of bone turnover, the study measured serum procollagen type 1 N-propeptide (P1NP)—a marker of bone formation—and serum C-terminal telopeptide of type 1 collagen (CTX)—a marker of bone resorption. “In the teriparatide group, there were increases in serum P1NP and CTX, whereas with the antiresorptive agent there were decreases in serum P1NP and CTX,” said Dr. Warner.

“The adverse event profiles were similar for the two treatment groups, in terms of overall adverse events and serious adverse events,” said Dr. Warner. In the teriparatide group there were 182 reported adverse events, with 45 considered serious. There were 170 adverse events in the alendronate group, with 39 considered serious.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — Teriparatide appeared effective in raising lumbar spine bone mineral density, and showed promise in reducing nonvertebral fractures in patients on glucocorticoid therapy with low bone mineral density or a prior fragility fracture, according to data presented at an international symposium sponsored by the National Osteoporosis Foundation.

“In patients with glucocorticoid-induced osteoporosis treated with teriparatide or alendronate for 18 months, teriparatide resulted in significantly greater increases in lumbar spine bone mineral density (BMD) compared with alendronate. Significantly fewer patients had new vertebral fractures with teriparatide, compared with the alendronate group,” said Margaret R. Warner, Ph.D., a researcher with Eli Lilly & Co., which funded this trial.

At 18 months, lumbar spine BMD rose 7.2% for patients treated with teriparatide and 3.4% for those treated with alendronate. Differences could be seen between the two groups as early as 6 months.

Teriparatide (Forteo), made by Eli Lilly, contains recombinant human parathyroid hormone (1–34). It is currently indicated for the treatment of postmenopausal women with osteoporosis who are at high risk for fracture and to increase bone mass in men with primary or hypogonadal osteoporosis who are at high risk for fracture. Teriparatide is the only osteoporosis drug shown to stimulate new bone growth.

Glucocorticoid therapy is the most common cause of secondary osteoporosis. Only risedronate (Actonel, by Procter & Gamble Pharmaceuticals) and alendronate (Fosamax, by Merck & Co.) are indicated for the prevention and treatment of glucocorticoid-induced osteoporosis in men and women receiving glucocorticoids in a daily dosage equal to 7.5 mg or more of prednisone with low BMD.

The trial included men and women at least 21 years old who had taken a minimum dose of 5 mg/day of prednisone (or its equivalent) for 3 months or longer prior to screening. All patients had total hip, femoral neck, or lumbar spine T scores of at most −2.0 or at most −1.0 with a prior fragility fracture. A total of 428 patients (80% women) were randomized to receive 20 mcg/day teriparatide injection and an oral placebo tablet or 10 mg/day oral alendronate and an injectable placebo. All received calcium and vitamin D supplements and were followed for 18 months.

The primary end point was the effect of teriparatide on lumbar spine BMD in patients with glucocorticoid-induced osteoporosis versus alendronate. The researchers also looked at the effect of teriparatide versus alendronate on total hip and femoral neck BMD, on markers of bone turnover, and on the incidence of vertebral and nonvertebral fractures. In addition, markers of bone turnover were analyzed in roughly half of each group. Adverse event data were collected throughout.

At baseline, both groups were fairly evenly matched in terms of gender, race, age, average prednisone dose, and average duration of prednisone use. Both groups were evenly matched in terms of average BMD at the total hip, femoral neck, and lumbar spine, and vertebral and nonvertebral fractures. Three-quarters of the patients in both groups had rheumatologic disease, with rheumatoid arthritis accounting for 69% of disease in the alendronate group and 61% in the teriparatide group.

Total hip BMD rose 3.6% for the teriparatide group, versus 2.2% for the alendronate group. Femoral neck BMD rose 3.7% for the teriparatide group, versus 2.1% for the alendronate group.

In terms of biomarkers of bone turnover, the study measured serum procollagen type 1 N-propeptide (P1NP)—a marker of bone formation—and serum C-terminal telopeptide of type 1 collagen (CTX)—a marker of bone resorption. “In the teriparatide group, there were increases in serum P1NP and CTX, whereas with the antiresorptive agent there were decreases in serum P1NP and CTX,” said Dr. Warner.

“The adverse event profiles were similar for the two treatment groups, in terms of overall adverse events and serious adverse events,” said Dr. Warner. In the teriparatide group there were 182 reported adverse events, with 45 considered serious. There were 170 adverse events in the alendronate group, with 39 considered serious.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — Teriparatide appeared effective in raising lumbar spine bone mineral density, and showed promise in reducing nonvertebral fractures in patients on glucocorticoid therapy with low bone mineral density or a prior fragility fracture, according to data presented at an international symposium sponsored by the National Osteoporosis Foundation.

“In patients with glucocorticoid-induced osteoporosis treated with teriparatide or alendronate for 18 months, teriparatide resulted in significantly greater increases in lumbar spine bone mineral density (BMD) compared with alendronate. Significantly fewer patients had new vertebral fractures with teriparatide, compared with the alendronate group,” said Margaret R. Warner, Ph.D., a researcher with Eli Lilly & Co., which funded this trial.

At 18 months, lumbar spine BMD rose 7.2% for patients treated with teriparatide and 3.4% for those treated with alendronate. Differences could be seen between the two groups as early as 6 months.

Teriparatide (Forteo), made by Eli Lilly, contains recombinant human parathyroid hormone (1–34). It is currently indicated for the treatment of postmenopausal women with osteoporosis who are at high risk for fracture and to increase bone mass in men with primary or hypogonadal osteoporosis who are at high risk for fracture. Teriparatide is the only osteoporosis drug shown to stimulate new bone growth.

Glucocorticoid therapy is the most common cause of secondary osteoporosis. Only risedronate (Actonel, by Procter & Gamble Pharmaceuticals) and alendronate (Fosamax, by Merck & Co.) are indicated for the prevention and treatment of glucocorticoid-induced osteoporosis in men and women receiving glucocorticoids in a daily dosage equal to 7.5 mg or more of prednisone with low BMD.

The trial included men and women at least 21 years old who had taken a minimum dose of 5 mg/day of prednisone (or its equivalent) for 3 months or longer prior to screening. All patients had total hip, femoral neck, or lumbar spine T scores of at most −2.0 or at most −1.0 with a prior fragility fracture. A total of 428 patients (80% women) were randomized to receive 20 mcg/day teriparatide injection and an oral placebo tablet or 10 mg/day oral alendronate and an injectable placebo. All received calcium and vitamin D supplements and were followed for 18 months.

The primary end point was the effect of teriparatide on lumbar spine BMD in patients with glucocorticoid-induced osteoporosis versus alendronate. The researchers also looked at the effect of teriparatide versus alendronate on total hip and femoral neck BMD, on markers of bone turnover, and on the incidence of vertebral and nonvertebral fractures. In addition, markers of bone turnover were analyzed in roughly half of each group. Adverse event data were collected throughout.

At baseline, both groups were fairly evenly matched in terms of gender, race, age, average prednisone dose, and average duration of prednisone use. Both groups were evenly matched in terms of average BMD at the total hip, femoral neck, and lumbar spine, and vertebral and nonvertebral fractures. Three-quarters of the patients in both groups had rheumatologic disease, with rheumatoid arthritis accounting for 69% of disease in the alendronate group and 61% in the teriparatide group.

Total hip BMD rose 3.6% for the teriparatide group, versus 2.2% for the alendronate group. Femoral neck BMD rose 3.7% for the teriparatide group, versus 2.1% for the alendronate group.

In terms of biomarkers of bone turnover, the study measured serum procollagen type 1 N-propeptide (P1NP)—a marker of bone formation—and serum C-terminal telopeptide of type 1 collagen (CTX)—a marker of bone resorption. “In the teriparatide group, there were increases in serum P1NP and CTX, whereas with the antiresorptive agent there were decreases in serum P1NP and CTX,” said Dr. Warner.

“The adverse event profiles were similar for the two treatment groups, in terms of overall adverse events and serious adverse events,” said Dr. Warner. In the teriparatide group there were 182 reported adverse events, with 45 considered serious. There were 170 adverse events in the alendronate group, with 39 considered serious.

ELSEVIER GLOBAL MEDICAL NEWS

BALTIMORE — The lack of diagnostic criteria has hamstrung neurologists in their attempt to diagnose involuntary emotional expression disorder, Dr. Sharon Handel said at a meeting on Alzheimer's disease and related disorders sponsored by Johns Hopkins University.

Even when they make the diagnosis with certainty, neurologists have little to offer by way of Food and Drug Administration-approved therapy, said Dr. Handel, of the department of psychiatry at Johns Hopkins University, Baltimore.

Part of the problem with identifying this condition has been the numerous names under which it is known, she noted. Involuntary emotional expression disorder (IEED) is also known as pseudobulbar affect and pathologic laughing or crying.

It's been estimated that more than 1 million people in the United States have IEED. The disorder has been associated with cerebrovascular accident, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, and traumatic brain injury.

The hallmark of IEED is episodes of crying or laughing that are unrelated to or out of proportion with the eliciting stimulus. There is a disconnection between emotional experience and expression.

Emotional outbursts in IEED are involuntary, episodic, and incongruent with baseline mood. The outbursts are intense, but are followed by a return to baseline.

Disorders of affect—which IEED appears to be—involve impairment of the moment-to-moment regulation of emotion. “There's a disconnection of the neural networks in this condition from the experienced emotion to the display of emotion,” said Dr. Handel.

The neural networks of emotion involve the frontal lobes, the limbic system, the brainstem, the cerebellum, and white-matter tracts. In particular, the prefrontal cortex integrates complex sensory and limbic information that determines the emotional valence of a stimulus and modulates motor and autonomic responses involved in emotional expression. It's not clear where the neural interruption occurs in IEED.

For now, the current diagnostic criteria include:

▸ Episodes of involuntary crying, laughing, or related displays.

▸ An origin in brain injury or disease.

▸ A change in the patient's emotional behavior from that prior to the disease or injury.

▸ Incongruent or exaggerated mood.

▸ A response that is excessive or unrelated to the stimulus.

▸ Significant distress or impairment.

The differential diagnosis should include epilepsy; facial dystonia or dyskinesias; vocal tics; axis I disorders (such as major depression or bipolar disorder); axis II disorders (such as borderline personality disorder); and substance abuse.

“These patients often have major depression, and while specific treatment is often the same, I think it's important to differentiate the two conditions,” said Dr. Handel.

The differential diagnosis should also include affective lability, essential crying, and witzelsucht (a tendency to inappropriate jokes). With affective lability, the subjective and objective dimensions of affect are not dissociated. Essential crying is a hereditary and lifelong tendency to cry easily. Witzelsucht is an addiction to trivial joking, which can take the form of both an inappropriate giddy affect and irritability or aggressiveness.

In terms of clinical course, IEED frequently remits spontaneously within 6 months. Others may have remission with treatment within 3 months. Resolution of IEED can be independent of the resolution of depression. However, in some cases the disorder is chronic and persistent without treatment.

Treatment of IEED is still evolving. At present, there is no FDA-approved treatment for IEED. “What are typically used—at least up to this point—are SSRIs. They tend to work quite quickly,” said Dr. Handel.

In fact, response can be seen in just a few days in some patients.

Dextromethorphan, in combination with quinidine, is being studied to treat patients with IEED. Dextromethorphan is a nonopioid antitussive, but it also has a number of other neuropharmacologic properties. It is a potent sigma₁ agonist (inhibiting the release of the excitatory neurotransmitter, glutamate) and is also an N-methyl-D-aspartic acid glutamate receptor antagonist.

Dextromethorphan undergoes significant first-pass metabolism by the cytochrome P450 isoenzyme CYP2D6. Quinidine is a potent inhibitor of this isoenzyme, thereby increasing and sustaining dextromethorphan levels.

BALTIMORE — The lack of diagnostic criteria has hamstrung neurologists in their attempt to diagnose involuntary emotional expression disorder, Dr. Sharon Handel said at a meeting on Alzheimer's disease and related disorders sponsored by Johns Hopkins University.

Even when they make the diagnosis with certainty, neurologists have little to offer by way of Food and Drug Administration-approved therapy, said Dr. Handel, of the department of psychiatry at Johns Hopkins University, Baltimore.

Part of the problem with identifying this condition has been the numerous names under which it is known, she noted. Involuntary emotional expression disorder (IEED) is also known as pseudobulbar affect and pathologic laughing or crying.

It's been estimated that more than 1 million people in the United States have IEED. The disorder has been associated with cerebrovascular accident, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, and traumatic brain injury.

The hallmark of IEED is episodes of crying or laughing that are unrelated to or out of proportion with the eliciting stimulus. There is a disconnection between emotional experience and expression.

Emotional outbursts in IEED are involuntary, episodic, and incongruent with baseline mood. The outbursts are intense, but are followed by a return to baseline.

Disorders of affect—which IEED appears to be—involve impairment of the moment-to-moment regulation of emotion. “There's a disconnection of the neural networks in this condition from the experienced emotion to the display of emotion,” said Dr. Handel.

The neural networks of emotion involve the frontal lobes, the limbic system, the brainstem, the cerebellum, and white-matter tracts. In particular, the prefrontal cortex integrates complex sensory and limbic information that determines the emotional valence of a stimulus and modulates motor and autonomic responses involved in emotional expression. It's not clear where the neural interruption occurs in IEED.

For now, the current diagnostic criteria include:

▸ Episodes of involuntary crying, laughing, or related displays.

▸ An origin in brain injury or disease.

▸ A change in the patient's emotional behavior from that prior to the disease or injury.

▸ Incongruent or exaggerated mood.

▸ A response that is excessive or unrelated to the stimulus.

▸ Significant distress or impairment.

The differential diagnosis should include epilepsy; facial dystonia or dyskinesias; vocal tics; axis I disorders (such as major depression or bipolar disorder); axis II disorders (such as borderline personality disorder); and substance abuse.

“These patients often have major depression, and while specific treatment is often the same, I think it's important to differentiate the two conditions,” said Dr. Handel.

The differential diagnosis should also include affective lability, essential crying, and witzelsucht (a tendency to inappropriate jokes). With affective lability, the subjective and objective dimensions of affect are not dissociated. Essential crying is a hereditary and lifelong tendency to cry easily. Witzelsucht is an addiction to trivial joking, which can take the form of both an inappropriate giddy affect and irritability or aggressiveness.

In terms of clinical course, IEED frequently remits spontaneously within 6 months. Others may have remission with treatment within 3 months. Resolution of IEED can be independent of the resolution of depression. However, in some cases the disorder is chronic and persistent without treatment.

Treatment of IEED is still evolving. At present, there is no FDA-approved treatment for IEED. “What are typically used—at least up to this point—are SSRIs. They tend to work quite quickly,” said Dr. Handel.

In fact, response can be seen in just a few days in some patients.

Dextromethorphan, in combination with quinidine, is being studied to treat patients with IEED. Dextromethorphan is a nonopioid antitussive, but it also has a number of other neuropharmacologic properties. It is a potent sigma₁ agonist (inhibiting the release of the excitatory neurotransmitter, glutamate) and is also an N-methyl-D-aspartic acid glutamate receptor antagonist.

Dextromethorphan undergoes significant first-pass metabolism by the cytochrome P450 isoenzyme CYP2D6. Quinidine is a potent inhibitor of this isoenzyme, thereby increasing and sustaining dextromethorphan levels.

BALTIMORE — The lack of diagnostic criteria has hamstrung neurologists in their attempt to diagnose involuntary emotional expression disorder, Dr. Sharon Handel said at a meeting on Alzheimer's disease and related disorders sponsored by Johns Hopkins University.

Even when they make the diagnosis with certainty, neurologists have little to offer by way of Food and Drug Administration-approved therapy, said Dr. Handel, of the department of psychiatry at Johns Hopkins University, Baltimore.

Part of the problem with identifying this condition has been the numerous names under which it is known, she noted. Involuntary emotional expression disorder (IEED) is also known as pseudobulbar affect and pathologic laughing or crying.

It's been estimated that more than 1 million people in the United States have IEED. The disorder has been associated with cerebrovascular accident, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, and traumatic brain injury.

The hallmark of IEED is episodes of crying or laughing that are unrelated to or out of proportion with the eliciting stimulus. There is a disconnection between emotional experience and expression.

Emotional outbursts in IEED are involuntary, episodic, and incongruent with baseline mood. The outbursts are intense, but are followed by a return to baseline.

Disorders of affect—which IEED appears to be—involve impairment of the moment-to-moment regulation of emotion. “There's a disconnection of the neural networks in this condition from the experienced emotion to the display of emotion,” said Dr. Handel.

The neural networks of emotion involve the frontal lobes, the limbic system, the brainstem, the cerebellum, and white-matter tracts. In particular, the prefrontal cortex integrates complex sensory and limbic information that determines the emotional valence of a stimulus and modulates motor and autonomic responses involved in emotional expression. It's not clear where the neural interruption occurs in IEED.

For now, the current diagnostic criteria include:

▸ Episodes of involuntary crying, laughing, or related displays.

▸ An origin in brain injury or disease.

▸ A change in the patient's emotional behavior from that prior to the disease or injury.

▸ Incongruent or exaggerated mood.

▸ A response that is excessive or unrelated to the stimulus.

▸ Significant distress or impairment.

The differential diagnosis should include epilepsy; facial dystonia or dyskinesias; vocal tics; axis I disorders (such as major depression or bipolar disorder); axis II disorders (such as borderline personality disorder); and substance abuse.

“These patients often have major depression, and while specific treatment is often the same, I think it's important to differentiate the two conditions,” said Dr. Handel.

The differential diagnosis should also include affective lability, essential crying, and witzelsucht (a tendency to inappropriate jokes). With affective lability, the subjective and objective dimensions of affect are not dissociated. Essential crying is a hereditary and lifelong tendency to cry easily. Witzelsucht is an addiction to trivial joking, which can take the form of both an inappropriate giddy affect and irritability or aggressiveness.

In terms of clinical course, IEED frequently remits spontaneously within 6 months. Others may have remission with treatment within 3 months. Resolution of IEED can be independent of the resolution of depression. However, in some cases the disorder is chronic and persistent without treatment.

Treatment of IEED is still evolving. At present, there is no FDA-approved treatment for IEED. “What are typically used—at least up to this point—are SSRIs. They tend to work quite quickly,” said Dr. Handel.

In fact, response can be seen in just a few days in some patients.

Dextromethorphan, in combination with quinidine, is being studied to treat patients with IEED. Dextromethorphan is a nonopioid antitussive, but it also has a number of other neuropharmacologic properties. It is a potent sigma₁ agonist (inhibiting the release of the excitatory neurotransmitter, glutamate) and is also an N-methyl-D-aspartic acid glutamate receptor antagonist.

Dextromethorphan undergoes significant first-pass metabolism by the cytochrome P450 isoenzyme CYP2D6. Quinidine is a potent inhibitor of this isoenzyme, thereby increasing and sustaining dextromethorphan levels.

SNOWMASS, COLO. — Unicompartmental knee and total knee arthroplasties provide good results in carefully selected patients, said Dr. Thomas S. Thornhill, chairman of orthopedic surgery at Brig-ham and Women's Hospital in Boston, at a symposium sponsored by the American College of Rheumatology.

UKA is indicated for degenerative arthritis in patients who are not good candidates for osteotomy or total knee replacement regardless of age. UKA might be the first option to consider in a younger patient because “it's much easier to convert a [UKA] to a total [knee arthroplasty] than a total to another total,” he said.

He estimates that the revision rate for UKAs at his facility is about 1% per year. Most problems are related to wear and progression of disease in the lateral compartment. UKA can be performed with a small incision, involves a shorter hospital stay, lower cost, and more rapid rehabilitation than does a total knee replacement.

In their defense, TKA procedures that are cruciate sparing have good to excellent results at 10–15 years. The major problems with failure of TKA still are related to wear, loosening, and infection. “I would submit to you that most of these failures can be attributed to technical issues and patient selection,” said Dr. Thornhill.

The most common cause of failure is instability. Surgeons think they need to put the knee in loosely so it will bend and flex better. Instead the looseness creates shearing when the knee moves, he said.

Dr. Thornhill disclosed that he receives royalties from DePuy Inc. He also has received research grants from DePuy Inc., Biomet Inc., and Smith & Nephew.

SNOWMASS, COLO. — Unicompartmental knee and total knee arthroplasties provide good results in carefully selected patients, said Dr. Thomas S. Thornhill, chairman of orthopedic surgery at Brig-ham and Women's Hospital in Boston, at a symposium sponsored by the American College of Rheumatology.

UKA is indicated for degenerative arthritis in patients who are not good candidates for osteotomy or total knee replacement regardless of age. UKA might be the first option to consider in a younger patient because “it's much easier to convert a [UKA] to a total [knee arthroplasty] than a total to another total,” he said.

He estimates that the revision rate for UKAs at his facility is about 1% per year. Most problems are related to wear and progression of disease in the lateral compartment. UKA can be performed with a small incision, involves a shorter hospital stay, lower cost, and more rapid rehabilitation than does a total knee replacement.

In their defense, TKA procedures that are cruciate sparing have good to excellent results at 10–15 years. The major problems with failure of TKA still are related to wear, loosening, and infection. “I would submit to you that most of these failures can be attributed to technical issues and patient selection,” said Dr. Thornhill.

The most common cause of failure is instability. Surgeons think they need to put the knee in loosely so it will bend and flex better. Instead the looseness creates shearing when the knee moves, he said.

Dr. Thornhill disclosed that he receives royalties from DePuy Inc. He also has received research grants from DePuy Inc., Biomet Inc., and Smith & Nephew.

SNOWMASS, COLO. — Unicompartmental knee and total knee arthroplasties provide good results in carefully selected patients, said Dr. Thomas S. Thornhill, chairman of orthopedic surgery at Brig-ham and Women's Hospital in Boston, at a symposium sponsored by the American College of Rheumatology.

UKA is indicated for degenerative arthritis in patients who are not good candidates for osteotomy or total knee replacement regardless of age. UKA might be the first option to consider in a younger patient because “it's much easier to convert a [UKA] to a total [knee arthroplasty] than a total to another total,” he said.

He estimates that the revision rate for UKAs at his facility is about 1% per year. Most problems are related to wear and progression of disease in the lateral compartment. UKA can be performed with a small incision, involves a shorter hospital stay, lower cost, and more rapid rehabilitation than does a total knee replacement.

In their defense, TKA procedures that are cruciate sparing have good to excellent results at 10–15 years. The major problems with failure of TKA still are related to wear, loosening, and infection. “I would submit to you that most of these failures can be attributed to technical issues and patient selection,” said Dr. Thornhill.

The most common cause of failure is instability. Surgeons think they need to put the knee in loosely so it will bend and flex better. Instead the looseness creates shearing when the knee moves, he said.

Dr. Thornhill disclosed that he receives royalties from DePuy Inc. He also has received research grants from DePuy Inc., Biomet Inc., and Smith & Nephew.

Cartilage loss and bone marrow lesions are shown on sagittal image of the knee.

Moderate effusion and medial and lateral patella osteophytes as seen on axial view.

Cartilage loss with macerated remnants of medial meniscus on coronal image.

Effusion, lateral patella osteophyte, and lateral patella displacement are seen. Dr. David J. Hunter

Patellae that are positioned centrally in the trochlear groove and are not malaligned are thought to be less susceptible to the development of osteoarthritis. Patellae that are chronically poorly aligned can place excess stress on the articular surfaces of the patellofemoral (PF) joints and possibly promote knee degeneration.

Most studies of patellar malalignment have used x-rays of the knee in the lateral plane and skyline view. Few studies have taken advantage of the increased resolution and three-dimensional visualization afforded by magnetic resonance imaging. One reason is that although MRIs of the knee in flexion are more useful in evaluating PF alignment, clinical MRI of the knee is most commonly acquired with the knee extended in the supine position.

Dr. David J. Hunter, a rheumatologist, and his colleagues at Boston University recently compared a number of measures of patellofemoral (PF) malalignment with radiographic indices of osteoarthritis (OA)–the presence of joint space narrowing and osteophytes—in patients with symptomatic and radiographic knee OA (Arthritis Res. Ther. 2007;9:R26).

Study participants were part of the Boston Osteoarthritis of the Knee Study, a cross-sectional larger natural history study of symptomatic knee OA.

“Admittedly, identifying cause from a cross-sectional study is a little bit of a leap, but our belief is that patellar malalignment actually predisposes to these changes,” Dr. Hunter said in an interview.

Not only did the researchers find significant associations between PF malalignment and radiographic features of OA, they demonstrated that indices of patellar alignment can be measured easily on standard knee MRI.

Participants suspected of knee OA underwent a series of x-rays. Those with a definite osteophyte on any view in the symptomatic knee were eligible for the study. The researchers evaluated 213 patients—126 men (average age 68 years) and 87 women (average age 65 years).

MRI studies were performed with a 1.5-T magnet, and a positioning device was used to ensure uniformity of the extended knee position. The imaging protocol included sagittal spin-echo proton density-weighted and T2-weighted images and coronal and axial spin-echo fat-suppressed proton density-weighted and T2-weighted images.

Use of MRI allowed the researchers to evaluate several indices of patellofemoral alignment. “For some of the measures that we wanted to take of patellofemoral alignment, we would not be able to get them from radiographic films alone,” said Dr. Hunter, an assistant professor of medicine at Boston University. “The resolution and the different planes that can be acquired on MRI do provide advantages over standard x-ray.”

The researchers measured patellar alignment in the sagittal and transverse (axial) planes. In the sagittal plane, they measured the patellar length ratio (PLR).

To do so, they used the slice with clearly recognizable patellar margins and in which patellar bone volume appeared to be maximal. PLR was calculated as the ratio of patellar length to patellar ligament length. Patellar length was measured from the upper to the lower point of the inner surface of the patella—excluding osteophytes. Patellar ligament length was measured from the lower inner point of the patella to the highest point of the tibial tuberosity.

In the transverse plane, the researchers measured the trochlear depth (trochlear sulcus angle) and two indices describing patellar position (lateral patellar tilt angle and bisect offset of the patella). Sulcus angle (SA) is an indicator of femoral trochlear dysplasia, which is associated with PF OA and patellar instability. To measure SA, the researchers used the axial slice that referred to the proximal one-third of the femoral trochlear curve.

SA is the angle between two lines: one radiating from the lowest point of the trochlear sulcus along the lateral bony margin and the other from the lowest point of the trochlear sulcus along the medial bony margin.

For measurements of patellar alignment, the researchers used the axial slice that refers to the middle of the patella. The LPTA, which is the angle between the posterior condylar line and a line through the lateral interior bony margin of the patella, shows the angle of patellar inclination, which indicates the tightness or laxity of the lateral stabilizing mechanism of the patella.

Bisect offset (BO) indicates the lateral displacement of the patella in relation to the deepest part of the femoral sulcus. For the BO of the patella, the researchers used a line perpendicular to the posterior condylar line that runs through the lowest point of the femoral sulcus and up through the patella.

They then measured the distance between this line and the lateral border of the patella (a). They also measured the distance between this line and the medial border of the patella (b). BO was calculated as the formula: 100a/(a + b).

Participants had weight-bearing skyline radiography, and the x-rays were read by a rheumatologist who used a four-point scale to grade the presence of osteophytes in the medial and lateral parts of the patella and femur and the joint space narrowing in the medial and lateral parts of the PF joint.

There was a statistically significant association between PLR and both osteophytes and joint space narrowing in the lateral compartment. With increasing PLR, there was an increased risk of lateral joint space narrowing. A similar trend was found between increasing PLR and increasing lateral patellar osteophytosis. There was no significant association between PLR and indices of radiographic PF OA in the medial PF compartment.

SA showed a statistically significant association with medial joint space narrowing and lateral and medial patellar osteophytosis—with increasing SA, there was increased risk of medial joint space narrowing. LPTA showed a statistically significant association with joint space narrowing and osteophytosis of the lateral PF compartment. A more laterally displaced patella was positively associated with increased lateral joint space narrowing and also with lateral patellar osteophytosis. In contrast, lateral patella displacement was negatively associated with medial joint space narrowing—increased medial displacement of the patella was associated with medial joint space narrowing.

The findings suggest that alignment of the patella may be an important factor influencing PF joint degeneration, due to the aberrant distribution of forces with activity. “I think that the important message for clinicians here is that to date, the majority of people really haven't considered problems of malalignment of the patellofemoral joint as important features in patellofemoral osteoarthritis. This study suggests that they're strongly associated,” said Dr. Hunter.

The fact that MRI was performed with the knee placed in a supine position likely means that the findings from this analysis are conservative for measures that could potentially change with weight bearing (LPTA and BO).

Cartilage loss and bone marrow lesions are shown on sagittal image of the knee.

Moderate effusion and medial and lateral patella osteophytes as seen on axial view.

Cartilage loss with macerated remnants of medial meniscus on coronal image.

Effusion, lateral patella osteophyte, and lateral patella displacement are seen. Dr. David J. Hunter

Patellae that are positioned centrally in the trochlear groove and are not malaligned are thought to be less susceptible to the development of osteoarthritis. Patellae that are chronically poorly aligned can place excess stress on the articular surfaces of the patellofemoral (PF) joints and possibly promote knee degeneration.

Most studies of patellar malalignment have used x-rays of the knee in the lateral plane and skyline view. Few studies have taken advantage of the increased resolution and three-dimensional visualization afforded by magnetic resonance imaging. One reason is that although MRIs of the knee in flexion are more useful in evaluating PF alignment, clinical MRI of the knee is most commonly acquired with the knee extended in the supine position.

Dr. David J. Hunter, a rheumatologist, and his colleagues at Boston University recently compared a number of measures of patellofemoral (PF) malalignment with radiographic indices of osteoarthritis (OA)–the presence of joint space narrowing and osteophytes—in patients with symptomatic and radiographic knee OA (Arthritis Res. Ther. 2007;9:R26).

Study participants were part of the Boston Osteoarthritis of the Knee Study, a cross-sectional larger natural history study of symptomatic knee OA.

“Admittedly, identifying cause from a cross-sectional study is a little bit of a leap, but our belief is that patellar malalignment actually predisposes to these changes,” Dr. Hunter said in an interview.

Not only did the researchers find significant associations between PF malalignment and radiographic features of OA, they demonstrated that indices of patellar alignment can be measured easily on standard knee MRI.

Participants suspected of knee OA underwent a series of x-rays. Those with a definite osteophyte on any view in the symptomatic knee were eligible for the study. The researchers evaluated 213 patients—126 men (average age 68 years) and 87 women (average age 65 years).

MRI studies were performed with a 1.5-T magnet, and a positioning device was used to ensure uniformity of the extended knee position. The imaging protocol included sagittal spin-echo proton density-weighted and T2-weighted images and coronal and axial spin-echo fat-suppressed proton density-weighted and T2-weighted images.

Use of MRI allowed the researchers to evaluate several indices of patellofemoral alignment. “For some of the measures that we wanted to take of patellofemoral alignment, we would not be able to get them from radiographic films alone,” said Dr. Hunter, an assistant professor of medicine at Boston University. “The resolution and the different planes that can be acquired on MRI do provide advantages over standard x-ray.”

The researchers measured patellar alignment in the sagittal and transverse (axial) planes. In the sagittal plane, they measured the patellar length ratio (PLR).

To do so, they used the slice with clearly recognizable patellar margins and in which patellar bone volume appeared to be maximal. PLR was calculated as the ratio of patellar length to patellar ligament length. Patellar length was measured from the upper to the lower point of the inner surface of the patella—excluding osteophytes. Patellar ligament length was measured from the lower inner point of the patella to the highest point of the tibial tuberosity.

In the transverse plane, the researchers measured the trochlear depth (trochlear sulcus angle) and two indices describing patellar position (lateral patellar tilt angle and bisect offset of the patella). Sulcus angle (SA) is an indicator of femoral trochlear dysplasia, which is associated with PF OA and patellar instability. To measure SA, the researchers used the axial slice that referred to the proximal one-third of the femoral trochlear curve.

SA is the angle between two lines: one radiating from the lowest point of the trochlear sulcus along the lateral bony margin and the other from the lowest point of the trochlear sulcus along the medial bony margin.

For measurements of patellar alignment, the researchers used the axial slice that refers to the middle of the patella. The LPTA, which is the angle between the posterior condylar line and a line through the lateral interior bony margin of the patella, shows the angle of patellar inclination, which indicates the tightness or laxity of the lateral stabilizing mechanism of the patella.

Bisect offset (BO) indicates the lateral displacement of the patella in relation to the deepest part of the femoral sulcus. For the BO of the patella, the researchers used a line perpendicular to the posterior condylar line that runs through the lowest point of the femoral sulcus and up through the patella.

They then measured the distance between this line and the lateral border of the patella (a). They also measured the distance between this line and the medial border of the patella (b). BO was calculated as the formula: 100a/(a + b).

Participants had weight-bearing skyline radiography, and the x-rays were read by a rheumatologist who used a four-point scale to grade the presence of osteophytes in the medial and lateral parts of the patella and femur and the joint space narrowing in the medial and lateral parts of the PF joint.

There was a statistically significant association between PLR and both osteophytes and joint space narrowing in the lateral compartment. With increasing PLR, there was an increased risk of lateral joint space narrowing. A similar trend was found between increasing PLR and increasing lateral patellar osteophytosis. There was no significant association between PLR and indices of radiographic PF OA in the medial PF compartment.

SA showed a statistically significant association with medial joint space narrowing and lateral and medial patellar osteophytosis—with increasing SA, there was increased risk of medial joint space narrowing. LPTA showed a statistically significant association with joint space narrowing and osteophytosis of the lateral PF compartment. A more laterally displaced patella was positively associated with increased lateral joint space narrowing and also with lateral patellar osteophytosis. In contrast, lateral patella displacement was negatively associated with medial joint space narrowing—increased medial displacement of the patella was associated with medial joint space narrowing.

The findings suggest that alignment of the patella may be an important factor influencing PF joint degeneration, due to the aberrant distribution of forces with activity. “I think that the important message for clinicians here is that to date, the majority of people really haven't considered problems of malalignment of the patellofemoral joint as important features in patellofemoral osteoarthritis. This study suggests that they're strongly associated,” said Dr. Hunter.

The fact that MRI was performed with the knee placed in a supine position likely means that the findings from this analysis are conservative for measures that could potentially change with weight bearing (LPTA and BO).

Cartilage loss and bone marrow lesions are shown on sagittal image of the knee.

Moderate effusion and medial and lateral patella osteophytes as seen on axial view.

Cartilage loss with macerated remnants of medial meniscus on coronal image.

Effusion, lateral patella osteophyte, and lateral patella displacement are seen. Dr. David J. Hunter

Patellae that are positioned centrally in the trochlear groove and are not malaligned are thought to be less susceptible to the development of osteoarthritis. Patellae that are chronically poorly aligned can place excess stress on the articular surfaces of the patellofemoral (PF) joints and possibly promote knee degeneration.

Most studies of patellar malalignment have used x-rays of the knee in the lateral plane and skyline view. Few studies have taken advantage of the increased resolution and three-dimensional visualization afforded by magnetic resonance imaging. One reason is that although MRIs of the knee in flexion are more useful in evaluating PF alignment, clinical MRI of the knee is most commonly acquired with the knee extended in the supine position.

Dr. David J. Hunter, a rheumatologist, and his colleagues at Boston University recently compared a number of measures of patellofemoral (PF) malalignment with radiographic indices of osteoarthritis (OA)–the presence of joint space narrowing and osteophytes—in patients with symptomatic and radiographic knee OA (Arthritis Res. Ther. 2007;9:R26).

Study participants were part of the Boston Osteoarthritis of the Knee Study, a cross-sectional larger natural history study of symptomatic knee OA.

“Admittedly, identifying cause from a cross-sectional study is a little bit of a leap, but our belief is that patellar malalignment actually predisposes to these changes,” Dr. Hunter said in an interview.

Not only did the researchers find significant associations between PF malalignment and radiographic features of OA, they demonstrated that indices of patellar alignment can be measured easily on standard knee MRI.

Participants suspected of knee OA underwent a series of x-rays. Those with a definite osteophyte on any view in the symptomatic knee were eligible for the study. The researchers evaluated 213 patients—126 men (average age 68 years) and 87 women (average age 65 years).

MRI studies were performed with a 1.5-T magnet, and a positioning device was used to ensure uniformity of the extended knee position. The imaging protocol included sagittal spin-echo proton density-weighted and T2-weighted images and coronal and axial spin-echo fat-suppressed proton density-weighted and T2-weighted images.

Use of MRI allowed the researchers to evaluate several indices of patellofemoral alignment. “For some of the measures that we wanted to take of patellofemoral alignment, we would not be able to get them from radiographic films alone,” said Dr. Hunter, an assistant professor of medicine at Boston University. “The resolution and the different planes that can be acquired on MRI do provide advantages over standard x-ray.”

The researchers measured patellar alignment in the sagittal and transverse (axial) planes. In the sagittal plane, they measured the patellar length ratio (PLR).

To do so, they used the slice with clearly recognizable patellar margins and in which patellar bone volume appeared to be maximal. PLR was calculated as the ratio of patellar length to patellar ligament length. Patellar length was measured from the upper to the lower point of the inner surface of the patella—excluding osteophytes. Patellar ligament length was measured from the lower inner point of the patella to the highest point of the tibial tuberosity.

In the transverse plane, the researchers measured the trochlear depth (trochlear sulcus angle) and two indices describing patellar position (lateral patellar tilt angle and bisect offset of the patella). Sulcus angle (SA) is an indicator of femoral trochlear dysplasia, which is associated with PF OA and patellar instability. To measure SA, the researchers used the axial slice that referred to the proximal one-third of the femoral trochlear curve.

SA is the angle between two lines: one radiating from the lowest point of the trochlear sulcus along the lateral bony margin and the other from the lowest point of the trochlear sulcus along the medial bony margin.

For measurements of patellar alignment, the researchers used the axial slice that refers to the middle of the patella. The LPTA, which is the angle between the posterior condylar line and a line through the lateral interior bony margin of the patella, shows the angle of patellar inclination, which indicates the tightness or laxity of the lateral stabilizing mechanism of the patella.

Bisect offset (BO) indicates the lateral displacement of the patella in relation to the deepest part of the femoral sulcus. For the BO of the patella, the researchers used a line perpendicular to the posterior condylar line that runs through the lowest point of the femoral sulcus and up through the patella.

They then measured the distance between this line and the lateral border of the patella (a). They also measured the distance between this line and the medial border of the patella (b). BO was calculated as the formula: 100a/(a + b).

Participants had weight-bearing skyline radiography, and the x-rays were read by a rheumatologist who used a four-point scale to grade the presence of osteophytes in the medial and lateral parts of the patella and femur and the joint space narrowing in the medial and lateral parts of the PF joint.

There was a statistically significant association between PLR and both osteophytes and joint space narrowing in the lateral compartment. With increasing PLR, there was an increased risk of lateral joint space narrowing. A similar trend was found between increasing PLR and increasing lateral patellar osteophytosis. There was no significant association between PLR and indices of radiographic PF OA in the medial PF compartment.

SA showed a statistically significant association with medial joint space narrowing and lateral and medial patellar osteophytosis—with increasing SA, there was increased risk of medial joint space narrowing. LPTA showed a statistically significant association with joint space narrowing and osteophytosis of the lateral PF compartment. A more laterally displaced patella was positively associated with increased lateral joint space narrowing and also with lateral patellar osteophytosis. In contrast, lateral patella displacement was negatively associated with medial joint space narrowing—increased medial displacement of the patella was associated with medial joint space narrowing.

The findings suggest that alignment of the patella may be an important factor influencing PF joint degeneration, due to the aberrant distribution of forces with activity. “I think that the important message for clinicians here is that to date, the majority of people really haven't considered problems of malalignment of the patellofemoral joint as important features in patellofemoral osteoarthritis. This study suggests that they're strongly associated,” said Dr. Hunter.

The fact that MRI was performed with the knee placed in a supine position likely means that the findings from this analysis are conservative for measures that could potentially change with weight bearing (LPTA and BO).

WASHINGTON — Postmenopausal women with a prior fall or those 80 years of age or older have a significantly greater risk of a subsequent fall, according to data presented at an international symposium sponsored by the National Osteoporosis Foundation.

Specifically, the investigators found that women with a prior fall had an odds ratio of 2.7 and those 80 years or older had a odds ratio of 1.5 for a future fall, based on a analysis of potential risk factors for falls among 66,134 women enrolled in the National Osteoporosis Risk Assessment (NORA) study, said Dr. Elizabeth Barrett-Connor, chief of epidemiology in the department of family and preventive medicine at the University of California at San Diego.

The NORA study enrolled over 200,000 community-dwelling, postmenopausal women between 1997 and 1999. Women had to be at least 50 years old without a diagnosis of osteoporosis. They could not have had a bone mineral density measurement in the previous year or be taking an osteoporosis-specific medication. At baseline, BMD was measured at the heel, forearm, or finger. The women were followed up at 1, 3, and 6 years with surveys asking if they'd had a fracture in the previous year.

The sample of women in this study responded to all of the surveys. At baseline, the average age was 63 years. Most (91%) were white. The average T score was −0.78. In all, 38% reported at least one fall in the past year.

The researchers included a long list of potential risk factors. These included age, body mass index, a self-rating of health as being poor/fair, functional limitations, smoking and alcohol use, early menopause, height loss, peripheral T score, personal history of fracture after age 45, maternal history of fracture and/or osteoporosis, first-degree relatives with a history of fracture, history of estrogen therapy, calcium supplementation, use of certain medications (oral corticosteroids, thyroid medication, an osteoporosis-specific drug), history of depression, osteoporosis self-knowledge, and self-report of a fall within the previous 12 months at the year 1 survey. They also included arthritis, coronary artery disease, hypertension, diabetes, kidney/liver disease, breast cancer, other cancers, memory problems, stroke, hyperthyroidism, hypothyroidism, epilepsy, poor vision, and poor hearing.

In addition, history of depression and of stroke increased the risk of falling by over 40%. An additional nine factors were identified that significantly increased fall risk by 9%–23%. The number of baseline risk factors was linearly associated with a risk of falling.

The NORA study has several limitations. First, participants were volunteers and may not be a representative sample. Second, falls were self-reported and limited to a 12-month recall period. The gaps between surveys likely mean falls were underreported. Longitudinal attrition resulted in a slightly younger and healthier analytic sample. No data were collected on factors known to be associated with falls, such as prescription medications, environment, gait, balance, and muscle strength. Lastly, the cause of falls was not known.

Dr. Barrett-Connor disclosed research support from several pharmaceutical companies and is a consultant for Merck & Co. Two of her collaborators are employees of Merck.

WASHINGTON — Postmenopausal women with a prior fall or those 80 years of age or older have a significantly greater risk of a subsequent fall, according to data presented at an international symposium sponsored by the National Osteoporosis Foundation.

Specifically, the investigators found that women with a prior fall had an odds ratio of 2.7 and those 80 years or older had a odds ratio of 1.5 for a future fall, based on a analysis of potential risk factors for falls among 66,134 women enrolled in the National Osteoporosis Risk Assessment (NORA) study, said Dr. Elizabeth Barrett-Connor, chief of epidemiology in the department of family and preventive medicine at the University of California at San Diego.

The NORA study enrolled over 200,000 community-dwelling, postmenopausal women between 1997 and 1999. Women had to be at least 50 years old without a diagnosis of osteoporosis. They could not have had a bone mineral density measurement in the previous year or be taking an osteoporosis-specific medication. At baseline, BMD was measured at the heel, forearm, or finger. The women were followed up at 1, 3, and 6 years with surveys asking if they'd had a fracture in the previous year.

The sample of women in this study responded to all of the surveys. At baseline, the average age was 63 years. Most (91%) were white. The average T score was −0.78. In all, 38% reported at least one fall in the past year.

The researchers included a long list of potential risk factors. These included age, body mass index, a self-rating of health as being poor/fair, functional limitations, smoking and alcohol use, early menopause, height loss, peripheral T score, personal history of fracture after age 45, maternal history of fracture and/or osteoporosis, first-degree relatives with a history of fracture, history of estrogen therapy, calcium supplementation, use of certain medications (oral corticosteroids, thyroid medication, an osteoporosis-specific drug), history of depression, osteoporosis self-knowledge, and self-report of a fall within the previous 12 months at the year 1 survey. They also included arthritis, coronary artery disease, hypertension, diabetes, kidney/liver disease, breast cancer, other cancers, memory problems, stroke, hyperthyroidism, hypothyroidism, epilepsy, poor vision, and poor hearing.

In addition, history of depression and of stroke increased the risk of falling by over 40%. An additional nine factors were identified that significantly increased fall risk by 9%–23%. The number of baseline risk factors was linearly associated with a risk of falling.

The NORA study has several limitations. First, participants were volunteers and may not be a representative sample. Second, falls were self-reported and limited to a 12-month recall period. The gaps between surveys likely mean falls were underreported. Longitudinal attrition resulted in a slightly younger and healthier analytic sample. No data were collected on factors known to be associated with falls, such as prescription medications, environment, gait, balance, and muscle strength. Lastly, the cause of falls was not known.

Dr. Barrett-Connor disclosed research support from several pharmaceutical companies and is a consultant for Merck & Co. Two of her collaborators are employees of Merck.

WASHINGTON — Postmenopausal women with a prior fall or those 80 years of age or older have a significantly greater risk of a subsequent fall, according to data presented at an international symposium sponsored by the National Osteoporosis Foundation.

Specifically, the investigators found that women with a prior fall had an odds ratio of 2.7 and those 80 years or older had a odds ratio of 1.5 for a future fall, based on a analysis of potential risk factors for falls among 66,134 women enrolled in the National Osteoporosis Risk Assessment (NORA) study, said Dr. Elizabeth Barrett-Connor, chief of epidemiology in the department of family and preventive medicine at the University of California at San Diego.

The NORA study enrolled over 200,000 community-dwelling, postmenopausal women between 1997 and 1999. Women had to be at least 50 years old without a diagnosis of osteoporosis. They could not have had a bone mineral density measurement in the previous year or be taking an osteoporosis-specific medication. At baseline, BMD was measured at the heel, forearm, or finger. The women were followed up at 1, 3, and 6 years with surveys asking if they'd had a fracture in the previous year.

The sample of women in this study responded to all of the surveys. At baseline, the average age was 63 years. Most (91%) were white. The average T score was −0.78. In all, 38% reported at least one fall in the past year.

The researchers included a long list of potential risk factors. These included age, body mass index, a self-rating of health as being poor/fair, functional limitations, smoking and alcohol use, early menopause, height loss, peripheral T score, personal history of fracture after age 45, maternal history of fracture and/or osteoporosis, first-degree relatives with a history of fracture, history of estrogen therapy, calcium supplementation, use of certain medications (oral corticosteroids, thyroid medication, an osteoporosis-specific drug), history of depression, osteoporosis self-knowledge, and self-report of a fall within the previous 12 months at the year 1 survey. They also included arthritis, coronary artery disease, hypertension, diabetes, kidney/liver disease, breast cancer, other cancers, memory problems, stroke, hyperthyroidism, hypothyroidism, epilepsy, poor vision, and poor hearing.

In addition, history of depression and of stroke increased the risk of falling by over 40%. An additional nine factors were identified that significantly increased fall risk by 9%–23%. The number of baseline risk factors was linearly associated with a risk of falling.

The NORA study has several limitations. First, participants were volunteers and may not be a representative sample. Second, falls were self-reported and limited to a 12-month recall period. The gaps between surveys likely mean falls were underreported. Longitudinal attrition resulted in a slightly younger and healthier analytic sample. No data were collected on factors known to be associated with falls, such as prescription medications, environment, gait, balance, and muscle strength. Lastly, the cause of falls was not known.

Dr. Barrett-Connor disclosed research support from several pharmaceutical companies and is a consultant for Merck & Co. Two of her collaborators are employees of Merck.