Miriam E. Tucker

PHILADELPHIA — Two government-affiliated programs provide a way for physicians and other health care professionals to serve as volunteers in the event of a national, regional, or local emergency, Dr. Anand K. Parekh said at the annual meeting of the American College of Physicians.

The Medical Reserve Corps (www.medicalreservecorps.gov

The Emergency System for Advance Registration of Volunteer Health Professionals (www.hrsa.gov/esarvhp

Those who are interested in volunteering should contact their state public health departments, said Dr. Parekh, a medical officer in the U.S. Department of Health and Human Services' Office of Public Health Emergency Preparedness and special assistant to the science adviser to the secretary of HHS.

In general, the Medical Reserve Corps (MRC) is an option for those who want to become actively involved in volunteer services by receiving training in advance as part of a local unit. The Emergency System for Advance Registration of Volunteer Health Professionals (ESAR-VHP), on the other hand, functions more as a reserve unit: The state keeps your name on file and calls only if an emergency arises.

Both groups were involved in the response to Hurricane Katrina. In the communities directly hit, 6,000 MRC volunteers supported local relief efforts. Another 1,500 MRC volunteers from elsewhere expressed willingness to deploy to the affected areas, and 600 of them actually did so.

Along with the 13 established ESAR-VHP state systems, another 7 state systems were temporarily launched within 2 weeks after the hurricane hit. In all, more than 8,300 health professional volunteers assisted Katrina victims through ESAR-VHP, Dr. Parekh said.

Both of the programs are still evolving, and currently efforts are underway to standardize the credentialing procedures and to increase pre-event training opportunities.

As of now, only “federalized” volunteers who engage in a national emergency response receive liability protection. Some states and localities also provide such protection; however, it is not uniform throughout the country.

PHILADELPHIA — Two government-affiliated programs provide a way for physicians and other health care professionals to serve as volunteers in the event of a national, regional, or local emergency, Dr. Anand K. Parekh said at the annual meeting of the American College of Physicians.

The Medical Reserve Corps (www.medicalreservecorps.gov

The Emergency System for Advance Registration of Volunteer Health Professionals (www.hrsa.gov/esarvhp

Those who are interested in volunteering should contact their state public health departments, said Dr. Parekh, a medical officer in the U.S. Department of Health and Human Services' Office of Public Health Emergency Preparedness and special assistant to the science adviser to the secretary of HHS.

In general, the Medical Reserve Corps (MRC) is an option for those who want to become actively involved in volunteer services by receiving training in advance as part of a local unit. The Emergency System for Advance Registration of Volunteer Health Professionals (ESAR-VHP), on the other hand, functions more as a reserve unit: The state keeps your name on file and calls only if an emergency arises.

Both groups were involved in the response to Hurricane Katrina. In the communities directly hit, 6,000 MRC volunteers supported local relief efforts. Another 1,500 MRC volunteers from elsewhere expressed willingness to deploy to the affected areas, and 600 of them actually did so.

Along with the 13 established ESAR-VHP state systems, another 7 state systems were temporarily launched within 2 weeks after the hurricane hit. In all, more than 8,300 health professional volunteers assisted Katrina victims through ESAR-VHP, Dr. Parekh said.

Both of the programs are still evolving, and currently efforts are underway to standardize the credentialing procedures and to increase pre-event training opportunities.

As of now, only “federalized” volunteers who engage in a national emergency response receive liability protection. Some states and localities also provide such protection; however, it is not uniform throughout the country.

PHILADELPHIA — Two government-affiliated programs provide a way for physicians and other health care professionals to serve as volunteers in the event of a national, regional, or local emergency, Dr. Anand K. Parekh said at the annual meeting of the American College of Physicians.

The Medical Reserve Corps (www.medicalreservecorps.gov

The Emergency System for Advance Registration of Volunteer Health Professionals (www.hrsa.gov/esarvhp

Those who are interested in volunteering should contact their state public health departments, said Dr. Parekh, a medical officer in the U.S. Department of Health and Human Services' Office of Public Health Emergency Preparedness and special assistant to the science adviser to the secretary of HHS.

In general, the Medical Reserve Corps (MRC) is an option for those who want to become actively involved in volunteer services by receiving training in advance as part of a local unit. The Emergency System for Advance Registration of Volunteer Health Professionals (ESAR-VHP), on the other hand, functions more as a reserve unit: The state keeps your name on file and calls only if an emergency arises.

Both groups were involved in the response to Hurricane Katrina. In the communities directly hit, 6,000 MRC volunteers supported local relief efforts. Another 1,500 MRC volunteers from elsewhere expressed willingness to deploy to the affected areas, and 600 of them actually did so.

Along with the 13 established ESAR-VHP state systems, another 7 state systems were temporarily launched within 2 weeks after the hurricane hit. In all, more than 8,300 health professional volunteers assisted Katrina victims through ESAR-VHP, Dr. Parekh said.

Both of the programs are still evolving, and currently efforts are underway to standardize the credentialing procedures and to increase pre-event training opportunities.

As of now, only “federalized” volunteers who engage in a national emergency response receive liability protection. Some states and localities also provide such protection; however, it is not uniform throughout the country.

PHILADELPHIA — Two government-affiliated programs provide a way for physicians and other health care professionals to serve as volunteers in the event of a national, regional, or local emergency, Dr. Anand K. Parekh said at the annual meeting of the American College of Physicians.

The Medical Reserve Corps (www.medicalreservecorps.gov

The Emergency System for Advance Registration of Volunteer Health Professionals (www.hrsa.gov/esarvhp

The MRC is an option for those who want to become actively involved in volunteer services by receiving training in advance. The ESAR-VHP, on the other hand, functions more as a reserve unit.

PHILADELPHIA — Two government-affiliated programs provide a way for physicians and other health care professionals to serve as volunteers in the event of a national, regional, or local emergency, Dr. Anand K. Parekh said at the annual meeting of the American College of Physicians.

The Medical Reserve Corps (www.medicalreservecorps.gov

The Emergency System for Advance Registration of Volunteer Health Professionals (www.hrsa.gov/esarvhp

The MRC is an option for those who want to become actively involved in volunteer services by receiving training in advance. The ESAR-VHP, on the other hand, functions more as a reserve unit.

PHILADELPHIA — Two government-affiliated programs provide a way for physicians and other health care professionals to serve as volunteers in the event of a national, regional, or local emergency, Dr. Anand K. Parekh said at the annual meeting of the American College of Physicians.

The Medical Reserve Corps (www.medicalreservecorps.gov

The Emergency System for Advance Registration of Volunteer Health Professionals (www.hrsa.gov/esarvhp

The MRC is an option for those who want to become actively involved in volunteer services by receiving training in advance. The ESAR-VHP, on the other hand, functions more as a reserve unit.

Tuberculosis cases reached an all-time low in the United States in 2005, but progress toward elimination of the disease has slowed, according to the Centers for Disease Control and Prevention.

Moreover, the number of multidrug-resistant (MDR) TB cases increased 13.3% from 2003 to 2004, marking the largest 1-year increase in such cases since 1993. A greater proportion of foreign-born patients than U.S.-born patients had MDR TB, the CDC said (MMWR 2006;55:305–8).

In 2005, a total of 14,093 TB cases was reported in the United States, representing a decline of 3.8% from 2004 and the lowest recorded rate (4.8 per 100,000 population) since national reporting began in 1953. However, the decline has slowed from an average of 7.1% per year during 1993–2000 to 3.8% per year during 2001–2005.

In 2005, the TB rate in foreign-born persons in the United States was 8.7 times that of U.S.-born persons. Although the total foreign-born population in the United States has increased 61.6% since 1993, the number of TB cases reported in this population hasn't changed substantially, resulting in a 36.0% decline in the TB rate among foreign-born persons. More than half of the 7,656 foreign-born TB patients in 2005 were from Mexico, the Philippines, Vietnam, India, and China, the CDC said.

Race/ethnicity data showed that TB rates in 2005 were increased 19.6 times among Asian Americans, 8.3-fold among blacks, and 7.3 times among Hispanics, compared with whites. But rates declined in almost all racial and ethnic populations from 2003 to 2005, with the most decline among American Indians/Alaska Natives (14.4%) and Asian Americans (14.1%).

The number of MDR TB cases increased from 113 cases in 2003 to 128 in 2004, the most recent year for which complete drug-susceptibility data are available. In 2004, 0.6% of U.S.-born and 1.6% of foreign-born TB patients had MDR TB. Approximately half of the foreign-born patients with MDR TB in 2004 were from Mexico, the Philippines, and Vietnam, the CDC said.

Also reported in the same MMWR issue, the first-ever data from the CDC and the WHO on rates of TB resistant to both first- and second-line antibiotics indicate that “extensively drug-resistant” TB accounted for 2% of all the MDR strains worldwide during the 2000–2004 period (MMWR 2006;55:301–5).

Tuberculosis cases reached an all-time low in the United States in 2005, but progress toward elimination of the disease has slowed, according to the Centers for Disease Control and Prevention.

Moreover, the number of multidrug-resistant (MDR) TB cases increased 13.3% from 2003 to 2004, marking the largest 1-year increase in such cases since 1993. A greater proportion of foreign-born patients than U.S.-born patients had MDR TB, the CDC said (MMWR 2006;55:305–8).

In 2005, a total of 14,093 TB cases was reported in the United States, representing a decline of 3.8% from 2004 and the lowest recorded rate (4.8 per 100,000 population) since national reporting began in 1953. However, the decline has slowed from an average of 7.1% per year during 1993–2000 to 3.8% per year during 2001–2005.

In 2005, the TB rate in foreign-born persons in the United States was 8.7 times that of U.S.-born persons. Although the total foreign-born population in the United States has increased 61.6% since 1993, the number of TB cases reported in this population hasn't changed substantially, resulting in a 36.0% decline in the TB rate among foreign-born persons. More than half of the 7,656 foreign-born TB patients in 2005 were from Mexico, the Philippines, Vietnam, India, and China, the CDC said.

Race/ethnicity data showed that TB rates in 2005 were increased 19.6 times among Asian Americans, 8.3-fold among blacks, and 7.3 times among Hispanics, compared with whites. But rates declined in almost all racial and ethnic populations from 2003 to 2005, with the most decline among American Indians/Alaska Natives (14.4%) and Asian Americans (14.1%).

The number of MDR TB cases increased from 113 cases in 2003 to 128 in 2004, the most recent year for which complete drug-susceptibility data are available. In 2004, 0.6% of U.S.-born and 1.6% of foreign-born TB patients had MDR TB. Approximately half of the foreign-born patients with MDR TB in 2004 were from Mexico, the Philippines, and Vietnam, the CDC said.

Also reported in the same MMWR issue, the first-ever data from the CDC and the WHO on rates of TB resistant to both first- and second-line antibiotics indicate that “extensively drug-resistant” TB accounted for 2% of all the MDR strains worldwide during the 2000–2004 period (MMWR 2006;55:301–5).

Tuberculosis cases reached an all-time low in the United States in 2005, but progress toward elimination of the disease has slowed, according to the Centers for Disease Control and Prevention.

Moreover, the number of multidrug-resistant (MDR) TB cases increased 13.3% from 2003 to 2004, marking the largest 1-year increase in such cases since 1993. A greater proportion of foreign-born patients than U.S.-born patients had MDR TB, the CDC said (MMWR 2006;55:305–8).

In 2005, a total of 14,093 TB cases was reported in the United States, representing a decline of 3.8% from 2004 and the lowest recorded rate (4.8 per 100,000 population) since national reporting began in 1953. However, the decline has slowed from an average of 7.1% per year during 1993–2000 to 3.8% per year during 2001–2005.

In 2005, the TB rate in foreign-born persons in the United States was 8.7 times that of U.S.-born persons. Although the total foreign-born population in the United States has increased 61.6% since 1993, the number of TB cases reported in this population hasn't changed substantially, resulting in a 36.0% decline in the TB rate among foreign-born persons. More than half of the 7,656 foreign-born TB patients in 2005 were from Mexico, the Philippines, Vietnam, India, and China, the CDC said.

Race/ethnicity data showed that TB rates in 2005 were increased 19.6 times among Asian Americans, 8.3-fold among blacks, and 7.3 times among Hispanics, compared with whites. But rates declined in almost all racial and ethnic populations from 2003 to 2005, with the most decline among American Indians/Alaska Natives (14.4%) and Asian Americans (14.1%).

The number of MDR TB cases increased from 113 cases in 2003 to 128 in 2004, the most recent year for which complete drug-susceptibility data are available. In 2004, 0.6% of U.S.-born and 1.6% of foreign-born TB patients had MDR TB. Approximately half of the foreign-born patients with MDR TB in 2004 were from Mexico, the Philippines, and Vietnam, the CDC said.

Also reported in the same MMWR issue, the first-ever data from the CDC and the WHO on rates of TB resistant to both first- and second-line antibiotics indicate that “extensively drug-resistant” TB accounted for 2% of all the MDR strains worldwide during the 2000–2004 period (MMWR 2006;55:301–5).

FORT LAUDERDALE, FLA. — Bisphosphonate therapy has dramatically improved the lives of patients with Paget's disease, but it's important to keep in mind the caveats when prescribing them, Dr. Kenneth W. Lyles said at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

Trials have demonstrated that all bisphosphonates are capable of improving bone remodeling and reducing pain. Efficacy at normalizing serum alkaline phosphatase levels varies from 15% with etidronate to 53% with pamidronate to 73% with risedronate to 89% with zoledronic acid.

“We are developing drugs that really help control this disease and improve pain. … They're very good drugs, but they come with a set of considerations,” said Dr. Lyles, professor of medicine at Duke University, Durham, N.C.

Potential adverse events are uncommon but have been reported with one or more of the various bisphosphonates:

▸ Osteomalacia. There have been some recent reports of patients developing osteomalacia after receiving etidronate at doses of 5 mg/kg for longer than 6 months, which exceeds the label recommendations. This information is expected to be included in the 2006 updated etidronate package insert.

▸ Iritis. Rarely, iritis occurs with aminobisphosphonate therapy. If further treatment is necessary, patients can be switched to a nonaminobisphosphonate such as etidronate or tiludronate. “You need to look for it, and change agents if it develops,” Dr. Lyles said.

▸ Acute phase response. This transient flu-like syndrome consisting of fever, myalgia, and leukopenia has been reported within 24–96 hours after first treatment with a bisphosphonate in 5%–40% of patients. It is seen more often with the intravenously agents than the oral ones. Its mechanism isn't completely understood, although it appears to be associated with an excessive release of tumor necrosis factor and interleukin-6 in treatment-naive patients. Patients should be warned of the possibility, and treated with aspirin, ibuprofen, or acetaminophen if it occurs, he advised.

▸ Osteonecrosis of the jaw. A series of papers since 2003 have reported this complication with alendronate, pamidronate, and zoledronate therapy. Most cases have occurred in patients who undergo tooth extraction or other dental procedures while on bisphosphonates, although malignancy and renal impairment have also been identified as risk factors. In patients who must undergo dental procedures, it may be best to give higher doses of bisphosphonate and shorten the course.

▸ Hypocalcemia. Because aminobisphosphonates block bone resorption, they can lead to hypocalcemia followed by a secondary hyperparathyroid response to restore normocalcemia. Although hypocalcemia has been reported in less than 1% overall among treated patients, severe cases have occurred in patients with malignancy, hypoparathyroidism, and unrecognized vitamin D deficiency. Patients should be screened for vitamin D and parathyroid hormone prior to initiation of bisphosphonate therapy, and should be on calcium supplementation. “If you miss this, you can have substantial problems,” he said.

▸ Vitamin D deficiency. Vitamin D insufficiency and frank deficiency are seen increasingly among the elderly in general, and among patients with Paget's disease in particular. Indeed, one study of 104 subjects over age 98 years revealed that 95% had undetectable levels of serum 25-hydroxyvitamin D, and that 38 of them had sustained a total of 55 fractures (J. Clin. Endocrinol. Metab. 2003;88:5109–15). Vitamin D supplementation is advised for patients with Paget's disease of bone before, during, and after bisphosphonate treatment, he advised.

Dr. Lyles has financial ties to Procter & Gamble, Aventis, Amgen, Roche/GlaxoSmithKline, Merck & Co., and Novartis Pharmaceuticals. He holds a patent for the use of zoledronate in patients who have sustained hip fractures.

FORT LAUDERDALE, FLA. — Bisphosphonate therapy has dramatically improved the lives of patients with Paget's disease, but it's important to keep in mind the caveats when prescribing them, Dr. Kenneth W. Lyles said at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

Trials have demonstrated that all bisphosphonates are capable of improving bone remodeling and reducing pain. Efficacy at normalizing serum alkaline phosphatase levels varies from 15% with etidronate to 53% with pamidronate to 73% with risedronate to 89% with zoledronic acid.

“We are developing drugs that really help control this disease and improve pain. … They're very good drugs, but they come with a set of considerations,” said Dr. Lyles, professor of medicine at Duke University, Durham, N.C.

Potential adverse events are uncommon but have been reported with one or more of the various bisphosphonates:

▸ Osteomalacia. There have been some recent reports of patients developing osteomalacia after receiving etidronate at doses of 5 mg/kg for longer than 6 months, which exceeds the label recommendations. This information is expected to be included in the 2006 updated etidronate package insert.

▸ Iritis. Rarely, iritis occurs with aminobisphosphonate therapy. If further treatment is necessary, patients can be switched to a nonaminobisphosphonate such as etidronate or tiludronate. “You need to look for it, and change agents if it develops,” Dr. Lyles said.

▸ Acute phase response. This transient flu-like syndrome consisting of fever, myalgia, and leukopenia has been reported within 24–96 hours after first treatment with a bisphosphonate in 5%–40% of patients. It is seen more often with the intravenously agents than the oral ones. Its mechanism isn't completely understood, although it appears to be associated with an excessive release of tumor necrosis factor and interleukin-6 in treatment-naive patients. Patients should be warned of the possibility, and treated with aspirin, ibuprofen, or acetaminophen if it occurs, he advised.

▸ Osteonecrosis of the jaw. A series of papers since 2003 have reported this complication with alendronate, pamidronate, and zoledronate therapy. Most cases have occurred in patients who undergo tooth extraction or other dental procedures while on bisphosphonates, although malignancy and renal impairment have also been identified as risk factors. In patients who must undergo dental procedures, it may be best to give higher doses of bisphosphonate and shorten the course.

▸ Hypocalcemia. Because aminobisphosphonates block bone resorption, they can lead to hypocalcemia followed by a secondary hyperparathyroid response to restore normocalcemia. Although hypocalcemia has been reported in less than 1% overall among treated patients, severe cases have occurred in patients with malignancy, hypoparathyroidism, and unrecognized vitamin D deficiency. Patients should be screened for vitamin D and parathyroid hormone prior to initiation of bisphosphonate therapy, and should be on calcium supplementation. “If you miss this, you can have substantial problems,” he said.

▸ Vitamin D deficiency. Vitamin D insufficiency and frank deficiency are seen increasingly among the elderly in general, and among patients with Paget's disease in particular. Indeed, one study of 104 subjects over age 98 years revealed that 95% had undetectable levels of serum 25-hydroxyvitamin D, and that 38 of them had sustained a total of 55 fractures (J. Clin. Endocrinol. Metab. 2003;88:5109–15). Vitamin D supplementation is advised for patients with Paget's disease of bone before, during, and after bisphosphonate treatment, he advised.

Dr. Lyles has financial ties to Procter & Gamble, Aventis, Amgen, Roche/GlaxoSmithKline, Merck & Co., and Novartis Pharmaceuticals. He holds a patent for the use of zoledronate in patients who have sustained hip fractures.

FORT LAUDERDALE, FLA. — Bisphosphonate therapy has dramatically improved the lives of patients with Paget's disease, but it's important to keep in mind the caveats when prescribing them, Dr. Kenneth W. Lyles said at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

Trials have demonstrated that all bisphosphonates are capable of improving bone remodeling and reducing pain. Efficacy at normalizing serum alkaline phosphatase levels varies from 15% with etidronate to 53% with pamidronate to 73% with risedronate to 89% with zoledronic acid.

“We are developing drugs that really help control this disease and improve pain. … They're very good drugs, but they come with a set of considerations,” said Dr. Lyles, professor of medicine at Duke University, Durham, N.C.

Potential adverse events are uncommon but have been reported with one or more of the various bisphosphonates:

▸ Osteomalacia. There have been some recent reports of patients developing osteomalacia after receiving etidronate at doses of 5 mg/kg for longer than 6 months, which exceeds the label recommendations. This information is expected to be included in the 2006 updated etidronate package insert.

▸ Iritis. Rarely, iritis occurs with aminobisphosphonate therapy. If further treatment is necessary, patients can be switched to a nonaminobisphosphonate such as etidronate or tiludronate. “You need to look for it, and change agents if it develops,” Dr. Lyles said.

▸ Acute phase response. This transient flu-like syndrome consisting of fever, myalgia, and leukopenia has been reported within 24–96 hours after first treatment with a bisphosphonate in 5%–40% of patients. It is seen more often with the intravenously agents than the oral ones. Its mechanism isn't completely understood, although it appears to be associated with an excessive release of tumor necrosis factor and interleukin-6 in treatment-naive patients. Patients should be warned of the possibility, and treated with aspirin, ibuprofen, or acetaminophen if it occurs, he advised.

▸ Osteonecrosis of the jaw. A series of papers since 2003 have reported this complication with alendronate, pamidronate, and zoledronate therapy. Most cases have occurred in patients who undergo tooth extraction or other dental procedures while on bisphosphonates, although malignancy and renal impairment have also been identified as risk factors. In patients who must undergo dental procedures, it may be best to give higher doses of bisphosphonate and shorten the course.

▸ Hypocalcemia. Because aminobisphosphonates block bone resorption, they can lead to hypocalcemia followed by a secondary hyperparathyroid response to restore normocalcemia. Although hypocalcemia has been reported in less than 1% overall among treated patients, severe cases have occurred in patients with malignancy, hypoparathyroidism, and unrecognized vitamin D deficiency. Patients should be screened for vitamin D and parathyroid hormone prior to initiation of bisphosphonate therapy, and should be on calcium supplementation. “If you miss this, you can have substantial problems,” he said.

▸ Vitamin D deficiency. Vitamin D insufficiency and frank deficiency are seen increasingly among the elderly in general, and among patients with Paget's disease in particular. Indeed, one study of 104 subjects over age 98 years revealed that 95% had undetectable levels of serum 25-hydroxyvitamin D, and that 38 of them had sustained a total of 55 fractures (J. Clin. Endocrinol. Metab. 2003;88:5109–15). Vitamin D supplementation is advised for patients with Paget's disease of bone before, during, and after bisphosphonate treatment, he advised.

Dr. Lyles has financial ties to Procter & Gamble, Aventis, Amgen, Roche/GlaxoSmithKline, Merck & Co., and Novartis Pharmaceuticals. He holds a patent for the use of zoledronate in patients who have sustained hip fractures.

FORT LAUDERDALE, FLA. — Bisphosphonate therapy has dramatically improved the lives of patients with Paget's disease, but it's important to keep in mind the caveats when prescribing them, Dr. Kenneth W. Lyles said at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

Clinical trials have demonstrated that all bisphosphonates are capable of improving bone remodeling and reducing pain. Efficacy at normalizing serum alkaline phosphatase levels varies from 15% with etidronate to 53% with pamidronate to 73% with risedronate to 89% with zoledronic acid.

“We are developing drugs that really help control this disease and improve pain…. They're very good drugs, but they come with a set of considerations,” said Dr. Lyles, professor of medicine at Duke University, Durham, N.C.

Potential adverse events are uncommon but have been reported with one or more of the various bisphosphonates:

▸ Osteomalacia. There have been some recent reports of patients developing osteomalacia after receiving etidronate at doses of 5 mg/kg for longer than 6 months, which exceeds the label recommendations. This information is expected to be included in the 2006 updated etidronate package insert.

▸ Acute phase response. This transient flu-like syndrome consisting of fever, myalgia, and leukopenia has been reported within 24–96 hours after first treatment with a bisphosphonate in 5%–40% of patients. It is seen more often with the intravenous agents than the oral ones. Its mechanism isn't completely understood, although it appears to be associated with an excessive release of tumor necrosis factor and interleukin-6 in treatment-naive patients. Patients should be warned of the possibility, and treated with aspirin, ibuprofen, or acetaminophen if it occurs.

▸ Osteonecrosis of the jaw. A series of papers since 2003 have reported this complication with alendronate, pamidronate and zoledronate therapy. Most cases have occurred in patients who undergo tooth extraction or other dental procedures while on bisphosphonates, although malignancy and renal impairment have also been identified as risk factors. In patients who must undergo dental procedures, it may be best to give higher doses of bisphosphonate and shorten the course.

▸ Hypocalcemia. Because aminobisphosphonates rapidly block bone resorption, they can lead to hypocalcemia followed by a secondary hyperparathyroid response to restore normocalcemia. Although hypocalcemia has been reported in less than 1% overall of treated patients, severe cases have occurred in patients with malignancy, hypoparathyroidism, and unrecognized vitamin D deficiency. Patients should always be screened for vitamin D and parathyroid hormone prior to initiation of bisphosphonate therapy, and should be on calcium supplementation afterward. “If you miss this, you can have substantial problems,” Dr. Lyles noted.

▸ Vitamin D deficiency. Vitamin D insufficiency and frank deficiency are being observed increasingly among the elderly in general, and among patients with Paget's disease in particular. Indeed, one study of 104 subjects over age 98 years revealed that 95% had undetectable levels of serum 25-hydroxyvitamin D, and that 38 of them had sustained a total of 55 fractures (J. Clin. Endocrinol. Metab. 2003;88:5109–15). Vitamin D supplementation is advised for patients with Paget's disease of bone before, during, and after bisphosphonate treatment.

Dr. Lyles has financial ties to Proctor & Gamble, Aventis, Amgen, Roche/GlaxoSmithKline, Merck & Co., and Novartis Pharmaceuticals. He holds a patent for the use of zoledronate in patients who have sustained hip fractures.

FORT LAUDERDALE, FLA. — Bisphosphonate therapy has dramatically improved the lives of patients with Paget's disease, but it's important to keep in mind the caveats when prescribing them, Dr. Kenneth W. Lyles said at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

Clinical trials have demonstrated that all bisphosphonates are capable of improving bone remodeling and reducing pain. Efficacy at normalizing serum alkaline phosphatase levels varies from 15% with etidronate to 53% with pamidronate to 73% with risedronate to 89% with zoledronic acid.

“We are developing drugs that really help control this disease and improve pain…. They're very good drugs, but they come with a set of considerations,” said Dr. Lyles, professor of medicine at Duke University, Durham, N.C.

Potential adverse events are uncommon but have been reported with one or more of the various bisphosphonates:

▸ Osteomalacia. There have been some recent reports of patients developing osteomalacia after receiving etidronate at doses of 5 mg/kg for longer than 6 months, which exceeds the label recommendations. This information is expected to be included in the 2006 updated etidronate package insert.

▸ Acute phase response. This transient flu-like syndrome consisting of fever, myalgia, and leukopenia has been reported within 24–96 hours after first treatment with a bisphosphonate in 5%–40% of patients. It is seen more often with the intravenous agents than the oral ones. Its mechanism isn't completely understood, although it appears to be associated with an excessive release of tumor necrosis factor and interleukin-6 in treatment-naive patients. Patients should be warned of the possibility, and treated with aspirin, ibuprofen, or acetaminophen if it occurs.

▸ Osteonecrosis of the jaw. A series of papers since 2003 have reported this complication with alendronate, pamidronate and zoledronate therapy. Most cases have occurred in patients who undergo tooth extraction or other dental procedures while on bisphosphonates, although malignancy and renal impairment have also been identified as risk factors. In patients who must undergo dental procedures, it may be best to give higher doses of bisphosphonate and shorten the course.

▸ Hypocalcemia. Because aminobisphosphonates rapidly block bone resorption, they can lead to hypocalcemia followed by a secondary hyperparathyroid response to restore normocalcemia. Although hypocalcemia has been reported in less than 1% overall of treated patients, severe cases have occurred in patients with malignancy, hypoparathyroidism, and unrecognized vitamin D deficiency. Patients should always be screened for vitamin D and parathyroid hormone prior to initiation of bisphosphonate therapy, and should be on calcium supplementation afterward. “If you miss this, you can have substantial problems,” Dr. Lyles noted.

▸ Vitamin D deficiency. Vitamin D insufficiency and frank deficiency are being observed increasingly among the elderly in general, and among patients with Paget's disease in particular. Indeed, one study of 104 subjects over age 98 years revealed that 95% had undetectable levels of serum 25-hydroxyvitamin D, and that 38 of them had sustained a total of 55 fractures (J. Clin. Endocrinol. Metab. 2003;88:5109–15). Vitamin D supplementation is advised for patients with Paget's disease of bone before, during, and after bisphosphonate treatment.

Dr. Lyles has financial ties to Proctor & Gamble, Aventis, Amgen, Roche/GlaxoSmithKline, Merck & Co., and Novartis Pharmaceuticals. He holds a patent for the use of zoledronate in patients who have sustained hip fractures.

FORT LAUDERDALE, FLA. — Bisphosphonate therapy has dramatically improved the lives of patients with Paget's disease, but it's important to keep in mind the caveats when prescribing them, Dr. Kenneth W. Lyles said at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

Clinical trials have demonstrated that all bisphosphonates are capable of improving bone remodeling and reducing pain. Efficacy at normalizing serum alkaline phosphatase levels varies from 15% with etidronate to 53% with pamidronate to 73% with risedronate to 89% with zoledronic acid.

“We are developing drugs that really help control this disease and improve pain…. They're very good drugs, but they come with a set of considerations,” said Dr. Lyles, professor of medicine at Duke University, Durham, N.C.

Potential adverse events are uncommon but have been reported with one or more of the various bisphosphonates:

▸ Osteomalacia. There have been some recent reports of patients developing osteomalacia after receiving etidronate at doses of 5 mg/kg for longer than 6 months, which exceeds the label recommendations. This information is expected to be included in the 2006 updated etidronate package insert.

▸ Acute phase response. This transient flu-like syndrome consisting of fever, myalgia, and leukopenia has been reported within 24–96 hours after first treatment with a bisphosphonate in 5%–40% of patients. It is seen more often with the intravenous agents than the oral ones. Its mechanism isn't completely understood, although it appears to be associated with an excessive release of tumor necrosis factor and interleukin-6 in treatment-naive patients. Patients should be warned of the possibility, and treated with aspirin, ibuprofen, or acetaminophen if it occurs.

▸ Osteonecrosis of the jaw. A series of papers since 2003 have reported this complication with alendronate, pamidronate and zoledronate therapy. Most cases have occurred in patients who undergo tooth extraction or other dental procedures while on bisphosphonates, although malignancy and renal impairment have also been identified as risk factors. In patients who must undergo dental procedures, it may be best to give higher doses of bisphosphonate and shorten the course.

▸ Hypocalcemia. Because aminobisphosphonates rapidly block bone resorption, they can lead to hypocalcemia followed by a secondary hyperparathyroid response to restore normocalcemia. Although hypocalcemia has been reported in less than 1% overall of treated patients, severe cases have occurred in patients with malignancy, hypoparathyroidism, and unrecognized vitamin D deficiency. Patients should always be screened for vitamin D and parathyroid hormone prior to initiation of bisphosphonate therapy, and should be on calcium supplementation afterward. “If you miss this, you can have substantial problems,” Dr. Lyles noted.

▸ Vitamin D deficiency. Vitamin D insufficiency and frank deficiency are being observed increasingly among the elderly in general, and among patients with Paget's disease in particular. Indeed, one study of 104 subjects over age 98 years revealed that 95% had undetectable levels of serum 25-hydroxyvitamin D, and that 38 of them had sustained a total of 55 fractures (J. Clin. Endocrinol. Metab. 2003;88:5109–15). Vitamin D supplementation is advised for patients with Paget's disease of bone before, during, and after bisphosphonate treatment.

Dr. Lyles has financial ties to Proctor & Gamble, Aventis, Amgen, Roche/GlaxoSmithKline, Merck & Co., and Novartis Pharmaceuticals. He holds a patent for the use of zoledronate in patients who have sustained hip fractures.

FORT LAUDERDALE, FLA. — Although the majority of fibrous dysplasia lesions are established early in childhood, many patients don't experience pain until later in life, Dr. Michael T. Collins reported at a meeting sponsored by the Paget's Foundation for Paget's Disease of Bone and Related Disorders.

Since many patients with fibrous dysplasia (FD) don't present early enough for prevention of lesions, efforts should focus on therapies directed toward management or regression of existing lesions, and awareness and appropriate treatment of pain. Bisphosphonates are usually effective in relieving pain, said Dr. Collins, who heads the Skeletal Clinical Studies Unit at the National Institute of Dental and Craniofacial Research (NIDCR) of the National Institutes of Health, Bethesda, Md.

The new findings are among the latest to come from ongoing research conducted within the NIDCR's Skeletal Clinical Studies Program. Over the last 4 years, the group has published a series of papers on the clinical and metabolic aspects of FD, a rare congenital disorder of bone metabolism in which normal bone and bone marrow are replaced with abnormal fibroosseous tissue.

Elizabeth Hart, a medical student and trainee with the NIDCR program, presented a poster on her onset/disease progression study, which included 44 FD patients who were screened over 32 years and who had at least two 99mTc-methylene diphosphonate bone scans. The median number of scans was four; the median age at first scan was 10 years and the median follow-up 4 years.

The bone scans were scored for location and extent of FD lesions using a validated FD-scoring tool—also developed by the NIDCR group—that captures the extreme variability of FD's mosaic nature by incorporating the extent of disease in each of 11 skeletal segments (J. Bone Miner. Res. 2005;20:219–26).

More than 90% of skeletal lesions were established before age 15 years. Craniofacial lesions were established earliest, followed by long bone, and then axial lesions. New lesions were rarely established later in life (after age 25), Ms. Hart reported.

Paradoxically, even though children experience more new lesions and more fractures, they report less pain than do adults. That finding, presented in a second poster by Marilyn H. Kelly, R.N., and Beth Brillante, R.N., came from a population of 33 children aged 5–18 years and 43 adults aged 23–62 years.

Pain was reported by 65% of the group overall, but the proportion among children was just 45%, compared with 81% of the adults.

The lower extremities were the sites most likely to be painful (56% of children and 89% of adults), while the sites most commonly associated with FD were the head (94% of children and 86% of adults) and the lower extremities (97% of children and 86% of adults).

The spine, which was the only site at which there was a significant increase in FD involvement over time (45% of children vs. 71% of adults), was not a significant source of overall pain morbidity, Ms. Kelly and her NIDCR associates reported.

The mechanism of bone pain in FD and its increase in adulthood are unknown and warrant further investigation, they wrote.

A previous study led by Ms. Kelly revealed that mental, emotional, and psychological function among both adults and children with FD is often normal, despite diminished physical function (Bone 2005;37:388–94). “In the all-important areas of relationships, education, and career, patients with FD are normal,” Dr. Collins noted in his overview presentation.

In fact, the parents' emotional state is the one most dramatically affected by the diagnosis. “Parents of children with this disease suffer. … One of our goals is that by educating parents that their children's life expectancy is not affected, and that their ability to achieve social and emotional health is not affected, parental emotional pain can be eased,” he remarked.

Another earlier finding from the NIDCR program changed previous thinking about the clinical management of FD in whom the optic nerve becomes encased. Optic neuropathy is a major concern in FD, because the optic nerve passes through the skull base, which is affected in more than 90% of FD patients. As skull involvement increases over time, the optic nerve becomes encased in almost all patients.

The prevailing belief had been that it was necessary to prophylactically decompress the nerve in all patients to avoid progressive vision loss. However, the NIDCR group was able to show that in fact 91% of completely encased optic nerves were asymptomatic and that only 5% progressed to vision loss. Therefore, prophylactic nerve decompression was not indicated (N. Engl. J. Med. 2002;347:1670–6).

Other previous data suggest that growth hormone (GH) excess is common in patients with both FD and the related disorder, McCune-Albright syndrome, and when present is associated with more severe craniofacial abnormalities (J. Clin. Endocrinol. Metab. 2002;87:5104–12). “This [finding] is significant because GH excess is often treatable, but unfortunately the diagnosis is often overlooked in children prior to complications,” Dr. Collins said, adding that it is still uncertain whether early diagnosis in children and treatment with GH will prevent morbidity.

More information is available at www.fibrousdysplasia.com

Craniofacial bone with FD has a sclerotic appearance (top right). Long bones appear lytic (bottom right), compared with normal bone. Photos Courtesy Dr. Michael T. Collins

FORT LAUDERDALE, FLA. — Although the majority of fibrous dysplasia lesions are established early in childhood, many patients don't experience pain until later in life, Dr. Michael T. Collins reported at a meeting sponsored by the Paget's Foundation for Paget's Disease of Bone and Related Disorders.

Since many patients with fibrous dysplasia (FD) don't present early enough for prevention of lesions, efforts should focus on therapies directed toward management or regression of existing lesions, and awareness and appropriate treatment of pain. Bisphosphonates are usually effective in relieving pain, said Dr. Collins, who heads the Skeletal Clinical Studies Unit at the National Institute of Dental and Craniofacial Research (NIDCR) of the National Institutes of Health, Bethesda, Md.

The new findings are among the latest to come from ongoing research conducted within the NIDCR's Skeletal Clinical Studies Program. Over the last 4 years, the group has published a series of papers on the clinical and metabolic aspects of FD, a rare congenital disorder of bone metabolism in which normal bone and bone marrow are replaced with abnormal fibroosseous tissue.

Elizabeth Hart, a medical student and trainee with the NIDCR program, presented a poster on her onset/disease progression study, which included 44 FD patients who were screened over 32 years and who had at least two 99mTc-methylene diphosphonate bone scans. The median number of scans was four; the median age at first scan was 10 years and the median follow-up 4 years.

The bone scans were scored for location and extent of FD lesions using a validated FD-scoring tool—also developed by the NIDCR group—that captures the extreme variability of FD's mosaic nature by incorporating the extent of disease in each of 11 skeletal segments (J. Bone Miner. Res. 2005;20:219–26).

More than 90% of skeletal lesions were established before age 15 years. Craniofacial lesions were established earliest, followed by long bone, and then axial lesions. New lesions were rarely established later in life (after age 25), Ms. Hart reported.

Paradoxically, even though children experience more new lesions and more fractures, they report less pain than do adults. That finding, presented in a second poster by Marilyn H. Kelly, R.N., and Beth Brillante, R.N., came from a population of 33 children aged 5–18 years and 43 adults aged 23–62 years.

Pain was reported by 65% of the group overall, but the proportion among children was just 45%, compared with 81% of the adults.

The lower extremities were the sites most likely to be painful (56% of children and 89% of adults), while the sites most commonly associated with FD were the head (94% of children and 86% of adults) and the lower extremities (97% of children and 86% of adults).

The spine, which was the only site at which there was a significant increase in FD involvement over time (45% of children vs. 71% of adults), was not a significant source of overall pain morbidity, Ms. Kelly and her NIDCR associates reported.

The mechanism of bone pain in FD and its increase in adulthood are unknown and warrant further investigation, they wrote.

A previous study led by Ms. Kelly revealed that mental, emotional, and psychological function among both adults and children with FD is often normal, despite diminished physical function (Bone 2005;37:388–94). “In the all-important areas of relationships, education, and career, patients with FD are normal,” Dr. Collins noted in his overview presentation.

In fact, the parents' emotional state is the one most dramatically affected by the diagnosis. “Parents of children with this disease suffer. … One of our goals is that by educating parents that their children's life expectancy is not affected, and that their ability to achieve social and emotional health is not affected, parental emotional pain can be eased,” he remarked.

Another earlier finding from the NIDCR program changed previous thinking about the clinical management of FD in whom the optic nerve becomes encased. Optic neuropathy is a major concern in FD, because the optic nerve passes through the skull base, which is affected in more than 90% of FD patients. As skull involvement increases over time, the optic nerve becomes encased in almost all patients.

The prevailing belief had been that it was necessary to prophylactically decompress the nerve in all patients to avoid progressive vision loss. However, the NIDCR group was able to show that in fact 91% of completely encased optic nerves were asymptomatic and that only 5% progressed to vision loss. Therefore, prophylactic nerve decompression was not indicated (N. Engl. J. Med. 2002;347:1670–6).

Other previous data suggest that growth hormone (GH) excess is common in patients with both FD and the related disorder, McCune-Albright syndrome, and when present is associated with more severe craniofacial abnormalities (J. Clin. Endocrinol. Metab. 2002;87:5104–12). “This [finding] is significant because GH excess is often treatable, but unfortunately the diagnosis is often overlooked in children prior to complications,” Dr. Collins said, adding that it is still uncertain whether early diagnosis in children and treatment with GH will prevent morbidity.

More information is available at www.fibrousdysplasia.com

Craniofacial bone with FD has a sclerotic appearance (top right). Long bones appear lytic (bottom right), compared with normal bone. Photos Courtesy Dr. Michael T. Collins

FORT LAUDERDALE, FLA. — Although the majority of fibrous dysplasia lesions are established early in childhood, many patients don't experience pain until later in life, Dr. Michael T. Collins reported at a meeting sponsored by the Paget's Foundation for Paget's Disease of Bone and Related Disorders.

Since many patients with fibrous dysplasia (FD) don't present early enough for prevention of lesions, efforts should focus on therapies directed toward management or regression of existing lesions, and awareness and appropriate treatment of pain. Bisphosphonates are usually effective in relieving pain, said Dr. Collins, who heads the Skeletal Clinical Studies Unit at the National Institute of Dental and Craniofacial Research (NIDCR) of the National Institutes of Health, Bethesda, Md.

The new findings are among the latest to come from ongoing research conducted within the NIDCR's Skeletal Clinical Studies Program. Over the last 4 years, the group has published a series of papers on the clinical and metabolic aspects of FD, a rare congenital disorder of bone metabolism in which normal bone and bone marrow are replaced with abnormal fibroosseous tissue.

Elizabeth Hart, a medical student and trainee with the NIDCR program, presented a poster on her onset/disease progression study, which included 44 FD patients who were screened over 32 years and who had at least two 99mTc-methylene diphosphonate bone scans. The median number of scans was four; the median age at first scan was 10 years and the median follow-up 4 years.

The bone scans were scored for location and extent of FD lesions using a validated FD-scoring tool—also developed by the NIDCR group—that captures the extreme variability of FD's mosaic nature by incorporating the extent of disease in each of 11 skeletal segments (J. Bone Miner. Res. 2005;20:219–26).

More than 90% of skeletal lesions were established before age 15 years. Craniofacial lesions were established earliest, followed by long bone, and then axial lesions. New lesions were rarely established later in life (after age 25), Ms. Hart reported.

Paradoxically, even though children experience more new lesions and more fractures, they report less pain than do adults. That finding, presented in a second poster by Marilyn H. Kelly, R.N., and Beth Brillante, R.N., came from a population of 33 children aged 5–18 years and 43 adults aged 23–62 years.

Pain was reported by 65% of the group overall, but the proportion among children was just 45%, compared with 81% of the adults.

The lower extremities were the sites most likely to be painful (56% of children and 89% of adults), while the sites most commonly associated with FD were the head (94% of children and 86% of adults) and the lower extremities (97% of children and 86% of adults).

The spine, which was the only site at which there was a significant increase in FD involvement over time (45% of children vs. 71% of adults), was not a significant source of overall pain morbidity, Ms. Kelly and her NIDCR associates reported.

The mechanism of bone pain in FD and its increase in adulthood are unknown and warrant further investigation, they wrote.

A previous study led by Ms. Kelly revealed that mental, emotional, and psychological function among both adults and children with FD is often normal, despite diminished physical function (Bone 2005;37:388–94). “In the all-important areas of relationships, education, and career, patients with FD are normal,” Dr. Collins noted in his overview presentation.

In fact, the parents' emotional state is the one most dramatically affected by the diagnosis. “Parents of children with this disease suffer. … One of our goals is that by educating parents that their children's life expectancy is not affected, and that their ability to achieve social and emotional health is not affected, parental emotional pain can be eased,” he remarked.

Another earlier finding from the NIDCR program changed previous thinking about the clinical management of FD in whom the optic nerve becomes encased. Optic neuropathy is a major concern in FD, because the optic nerve passes through the skull base, which is affected in more than 90% of FD patients. As skull involvement increases over time, the optic nerve becomes encased in almost all patients.

The prevailing belief had been that it was necessary to prophylactically decompress the nerve in all patients to avoid progressive vision loss. However, the NIDCR group was able to show that in fact 91% of completely encased optic nerves were asymptomatic and that only 5% progressed to vision loss. Therefore, prophylactic nerve decompression was not indicated (N. Engl. J. Med. 2002;347:1670–6).

Other previous data suggest that growth hormone (GH) excess is common in patients with both FD and the related disorder, McCune-Albright syndrome, and when present is associated with more severe craniofacial abnormalities (J. Clin. Endocrinol. Metab. 2002;87:5104–12). “This [finding] is significant because GH excess is often treatable, but unfortunately the diagnosis is often overlooked in children prior to complications,” Dr. Collins said, adding that it is still uncertain whether early diagnosis in children and treatment with GH will prevent morbidity.

More information is available at www.fibrousdysplasia.com

Craniofacial bone with FD has a sclerotic appearance (top right). Long bones appear lytic (bottom right), compared with normal bone. Photos Courtesy Dr. Michael T. Collins

WASHINGTON — More hospitals are implementing standardized insulin infusion protocols, many of which emulate the Yale protocol, Dr. Philip A. Goldberg said at a consensus conference sponsored by the American Association of Clinical Endocrinologists, American College of Endocrinology, and the American Diabetes Association.

Dr. Goldberg, a postdoctoral fellow at Yale University, New Haven, Conn., said the protocol was introduced in 2001 after the publication of the landmark Leuven, Belgium study (N. Engl. J. Med. 2001;345:1359–67). Until then, the “state of the art” in the intensive care unit had been to tolerate blood glucose levels as long as they did not exceed 200 mg/dL and to rarely address plasma glucose elevations. Glucose levels were rarely checked in nondiabetic patients, and existing “sliding scale” insulin orders took into account only the current blood glucose. In contrast, the Yale protocol incorporated two other essential elements: The velocity of change (based on both the current and previous values) and the current infusion rate. “If you don't incorporate all three of those, your drip will not be successful,” he said.

In the first 69 insulin drips used in 52 medical ICU patients with a baseline mean glucose of 299 mg/dL, the median time to achieve target blood glucose levels of 100–139 mg/dL (now 90–119 mg/dL) was 9 hours, and the median drip duration was 61 hours. The protocol worked equally well in diabetic and nondiabetic patients, and was not influenced by the severity of illness.

The protocol was complex enough to achieve strict glycemic control in critically ill patients and practical enough to be implemented by busy ICU nurses without the need for continuous expert supervision (Diabetes Care 2004;27:461–7). Importantly, the protocol also was readily accepted by the nursing staff, with 73% rating it as “very easy” or “somewhat easy” to use.

“It's only complex the first two or three times you do it. Once you actually run an ICU nurse through this protocol a few times, it's not complex at all compared to the other things they're doing,” said Dr. Goldberg.

Since then, other institutions have created their own versions of the Yale protocol—some including computerized algorithms—with similar success rates. “Everybody's institution has different local climates and needs to adjust these things … It's nice to see that people are taking our drip, adapting it to their local environment, and having some success with it,” Dr. Goldberg noted.

And in 2004, the Yale group again updated its protocol following the publication of the first American Association of Clinical Endocrinologists' national guideline on inpatient diabetes and metabolic control (Endocr. Pract. 2004;10:77–82) and the American Diabetes Association's technical review (Diabetes Care 2004;27:553–91). The blood glucose targets were lowered to 90–119 mg/dL and the IV bolus was increased by about 40% to gain more rapid control.

In 54 consecutive cardiothoracic ICU patients, mean blood glucose levels were another 12–13 mg/dL lower on average with the new protocol and with no concomitant increases in hypoglycemia. Similarly, mean glucose level was 118 mg/dL among 47 consecutive medical ICU patients receiving 63 drips. With the old protocol, levels averaged 123 mg/dL. The new protocol halved to 4.5 hours the median time to reach a glucose level below 140 mg/dL (the old target).

These results would have been impossible without “buy in” from the nursing staff, Dr. Goldberg emphasized. “The ICU nurses are the ones who are doing this. You have to recognize that up front.”

A major barrier still to be overcome is the long-held fear of hypoglycemia. Many hospital personnel believe that levels of 150–200 mg/dL are “normal” and that anything below 100 mg/dL is cause for concern. “There is a 'culture of hyperglycemia,' with a fear of hypoglycemia, or even of low normal,” he said.

To address these concerns, inservice training at Yale consists of 35 minutes addressing the “why” of the protocol and just 10 minutes for the “how.” The trainers review the published data and reinforce the message that most hypoglycemic episodes are benign and treatable.

It's also important to acknowledge to the nursing staff that the infusions will cause them extra work, Dr. Goldberg said. Some of the impact can be minimized with efficient use of ancillary staff, additional glucose meters, and use of lines in place for other reasons to sample venous or arterial blood for glucose measures.

Continuous glucose monitoring systems—currently approved for use only in diabetic outpatients—might also prove useful in the ICU setting. In a preliminary study, the Yale group found good correlation between values obtained with Medtronic Minimed's CGMS system and capillary glucose levels in 22 medical ICU patients (Diabetes Technol. Ther. 2004;6:339–47).

WASHINGTON — More hospitals are implementing standardized insulin infusion protocols, many of which emulate the Yale protocol, Dr. Philip A. Goldberg said at a consensus conference sponsored by the American Association of Clinical Endocrinologists, American College of Endocrinology, and the American Diabetes Association.

Dr. Goldberg, a postdoctoral fellow at Yale University, New Haven, Conn., said the protocol was introduced in 2001 after the publication of the landmark Leuven, Belgium study (N. Engl. J. Med. 2001;345:1359–67). Until then, the “state of the art” in the intensive care unit had been to tolerate blood glucose levels as long as they did not exceed 200 mg/dL and to rarely address plasma glucose elevations. Glucose levels were rarely checked in nondiabetic patients, and existing “sliding scale” insulin orders took into account only the current blood glucose. In contrast, the Yale protocol incorporated two other essential elements: The velocity of change (based on both the current and previous values) and the current infusion rate. “If you don't incorporate all three of those, your drip will not be successful,” he said.

In the first 69 insulin drips used in 52 medical ICU patients with a baseline mean glucose of 299 mg/dL, the median time to achieve target blood glucose levels of 100–139 mg/dL (now 90–119 mg/dL) was 9 hours, and the median drip duration was 61 hours. The protocol worked equally well in diabetic and nondiabetic patients, and was not influenced by the severity of illness.

The protocol was complex enough to achieve strict glycemic control in critically ill patients and practical enough to be implemented by busy ICU nurses without the need for continuous expert supervision (Diabetes Care 2004;27:461–7). Importantly, the protocol also was readily accepted by the nursing staff, with 73% rating it as “very easy” or “somewhat easy” to use.

“It's only complex the first two or three times you do it. Once you actually run an ICU nurse through this protocol a few times, it's not complex at all compared to the other things they're doing,” said Dr. Goldberg.

Since then, other institutions have created their own versions of the Yale protocol—some including computerized algorithms—with similar success rates. “Everybody's institution has different local climates and needs to adjust these things … It's nice to see that people are taking our drip, adapting it to their local environment, and having some success with it,” Dr. Goldberg noted.

And in 2004, the Yale group again updated its protocol following the publication of the first American Association of Clinical Endocrinologists' national guideline on inpatient diabetes and metabolic control (Endocr. Pract. 2004;10:77–82) and the American Diabetes Association's technical review (Diabetes Care 2004;27:553–91). The blood glucose targets were lowered to 90–119 mg/dL and the IV bolus was increased by about 40% to gain more rapid control.

In 54 consecutive cardiothoracic ICU patients, mean blood glucose levels were another 12–13 mg/dL lower on average with the new protocol and with no concomitant increases in hypoglycemia. Similarly, mean glucose level was 118 mg/dL among 47 consecutive medical ICU patients receiving 63 drips. With the old protocol, levels averaged 123 mg/dL. The new protocol halved to 4.5 hours the median time to reach a glucose level below 140 mg/dL (the old target).

These results would have been impossible without “buy in” from the nursing staff, Dr. Goldberg emphasized. “The ICU nurses are the ones who are doing this. You have to recognize that up front.”

A major barrier still to be overcome is the long-held fear of hypoglycemia. Many hospital personnel believe that levels of 150–200 mg/dL are “normal” and that anything below 100 mg/dL is cause for concern. “There is a 'culture of hyperglycemia,' with a fear of hypoglycemia, or even of low normal,” he said.

To address these concerns, inservice training at Yale consists of 35 minutes addressing the “why” of the protocol and just 10 minutes for the “how.” The trainers review the published data and reinforce the message that most hypoglycemic episodes are benign and treatable.

It's also important to acknowledge to the nursing staff that the infusions will cause them extra work, Dr. Goldberg said. Some of the impact can be minimized with efficient use of ancillary staff, additional glucose meters, and use of lines in place for other reasons to sample venous or arterial blood for glucose measures.

Continuous glucose monitoring systems—currently approved for use only in diabetic outpatients—might also prove useful in the ICU setting. In a preliminary study, the Yale group found good correlation between values obtained with Medtronic Minimed's CGMS system and capillary glucose levels in 22 medical ICU patients (Diabetes Technol. Ther. 2004;6:339–47).

WASHINGTON — More hospitals are implementing standardized insulin infusion protocols, many of which emulate the Yale protocol, Dr. Philip A. Goldberg said at a consensus conference sponsored by the American Association of Clinical Endocrinologists, American College of Endocrinology, and the American Diabetes Association.

Dr. Goldberg, a postdoctoral fellow at Yale University, New Haven, Conn., said the protocol was introduced in 2001 after the publication of the landmark Leuven, Belgium study (N. Engl. J. Med. 2001;345:1359–67). Until then, the “state of the art” in the intensive care unit had been to tolerate blood glucose levels as long as they did not exceed 200 mg/dL and to rarely address plasma glucose elevations. Glucose levels were rarely checked in nondiabetic patients, and existing “sliding scale” insulin orders took into account only the current blood glucose. In contrast, the Yale protocol incorporated two other essential elements: The velocity of change (based on both the current and previous values) and the current infusion rate. “If you don't incorporate all three of those, your drip will not be successful,” he said.

In the first 69 insulin drips used in 52 medical ICU patients with a baseline mean glucose of 299 mg/dL, the median time to achieve target blood glucose levels of 100–139 mg/dL (now 90–119 mg/dL) was 9 hours, and the median drip duration was 61 hours. The protocol worked equally well in diabetic and nondiabetic patients, and was not influenced by the severity of illness.

The protocol was complex enough to achieve strict glycemic control in critically ill patients and practical enough to be implemented by busy ICU nurses without the need for continuous expert supervision (Diabetes Care 2004;27:461–7). Importantly, the protocol also was readily accepted by the nursing staff, with 73% rating it as “very easy” or “somewhat easy” to use.

“It's only complex the first two or three times you do it. Once you actually run an ICU nurse through this protocol a few times, it's not complex at all compared to the other things they're doing,” said Dr. Goldberg.

Since then, other institutions have created their own versions of the Yale protocol—some including computerized algorithms—with similar success rates. “Everybody's institution has different local climates and needs to adjust these things … It's nice to see that people are taking our drip, adapting it to their local environment, and having some success with it,” Dr. Goldberg noted.

And in 2004, the Yale group again updated its protocol following the publication of the first American Association of Clinical Endocrinologists' national guideline on inpatient diabetes and metabolic control (Endocr. Pract. 2004;10:77–82) and the American Diabetes Association's technical review (Diabetes Care 2004;27:553–91). The blood glucose targets were lowered to 90–119 mg/dL and the IV bolus was increased by about 40% to gain more rapid control.

In 54 consecutive cardiothoracic ICU patients, mean blood glucose levels were another 12–13 mg/dL lower on average with the new protocol and with no concomitant increases in hypoglycemia. Similarly, mean glucose level was 118 mg/dL among 47 consecutive medical ICU patients receiving 63 drips. With the old protocol, levels averaged 123 mg/dL. The new protocol halved to 4.5 hours the median time to reach a glucose level below 140 mg/dL (the old target).

These results would have been impossible without “buy in” from the nursing staff, Dr. Goldberg emphasized. “The ICU nurses are the ones who are doing this. You have to recognize that up front.”

A major barrier still to be overcome is the long-held fear of hypoglycemia. Many hospital personnel believe that levels of 150–200 mg/dL are “normal” and that anything below 100 mg/dL is cause for concern. “There is a 'culture of hyperglycemia,' with a fear of hypoglycemia, or even of low normal,” he said.

To address these concerns, inservice training at Yale consists of 35 minutes addressing the “why” of the protocol and just 10 minutes for the “how.” The trainers review the published data and reinforce the message that most hypoglycemic episodes are benign and treatable.

It's also important to acknowledge to the nursing staff that the infusions will cause them extra work, Dr. Goldberg said. Some of the impact can be minimized with efficient use of ancillary staff, additional glucose meters, and use of lines in place for other reasons to sample venous or arterial blood for glucose measures.

Continuous glucose monitoring systems—currently approved for use only in diabetic outpatients—might also prove useful in the ICU setting. In a preliminary study, the Yale group found good correlation between values obtained with Medtronic Minimed's CGMS system and capillary glucose levels in 22 medical ICU patients (Diabetes Technol. Ther. 2004;6:339–47).

FORT LAUDERDALE, FLA. — Serum cathepsin K levels could serve as a useful measure in the management of patients with Paget's disease of bone, Dr. Daniela Merlotti said at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

Cathepsin K, a cysteine protease enzyme, is the most abundantly synthesized protein of the resorbing osteoclast, and plays an important role in the degradation of the organic matrix of bone. Recent studies have suggested that the enzyme may serve as a marker for fracture prediction and bone mineral density (J. Lab. Clin. Med. 2005;146:13–7) and as a parameter for bone metabolism in patients with early rheumatoid arthritis (Arthritis Res. Ther. 2005;7:R65–70), noted Dr. Merlotti of the University of Siena, Italy.

Serum cathepsin K levels were assessed before and after bisphosphonate treatment in 60 patients with Paget's disease and in 50 age-matched controls without the disease. Serum total alkaline phosphatase (ALP), carboxyterminal cross-linked telopeptide of type I collagen (sCTX), and bone-specific ALP were also measured.

At baseline, serum cathepsin K levels were significantly higher in the Paget's disease patients, compared with the controls, and were higher in patients with polyostotic disease than in those with monostotic disease. Baseline cathepsin K correlated positively with sCTX and urinary calcium, but not with total or bone-specific ALP. Similar but weaker correlations were seen in the controls, Dr. Merlotti said.

Overall, intravenous bisphosphonate treatment reduced cathepsin K levels by 28% at 3 days, 34% at 30 days, 45% at 3 months, 29% at 6 months, and 32% at 1 year. At each time point, the reduction in cathepsin K was significantly greater among the 20 patients treated with zoledronate than in the 40 who received pamidronate. With pamidronate, serum cathepsin K levels increased between 3 and 6 months, while on zoledronate the levels decreased continuously.

For the group as a whole, serum ALP dropped by 33% at 30 days and 24% at 90 days, then increased slightly thereafter up to 1 year. However, when examined separately, ALP levels in the zoledronate group continued to drop, while they increased after 6 months with pamidronate. At 6 months, serum ALP had normalized in 88% of the zoledronate patients, compared with just 31% of the pamidronate group, Dr. Merlotti reported.

The evaluation of cathepsin K levels at 3 months predicted the response to bisphosphonate treatment: The Paget's disease patients in whom cathepsin K was decreasing at 3 months had an 18% reduction in total serum ALP levels at 6 months, while those in whom cathepsin K was rising at 3 months showed a 5% increase in total serum ALP at 6 months, she said.

ALP levels in the zoledronate group continued to drop after 6 months but increased with pamidronate. DR. MERLOTTI

FORT LAUDERDALE, FLA. — Serum cathepsin K levels could serve as a useful measure in the management of patients with Paget's disease of bone, Dr. Daniela Merlotti said at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

Cathepsin K, a cysteine protease enzyme, is the most abundantly synthesized protein of the resorbing osteoclast, and plays an important role in the degradation of the organic matrix of bone. Recent studies have suggested that the enzyme may serve as a marker for fracture prediction and bone mineral density (J. Lab. Clin. Med. 2005;146:13–7) and as a parameter for bone metabolism in patients with early rheumatoid arthritis (Arthritis Res. Ther. 2005;7:R65–70), noted Dr. Merlotti of the University of Siena, Italy.

Serum cathepsin K levels were assessed before and after bisphosphonate treatment in 60 patients with Paget's disease and in 50 age-matched controls without the disease. Serum total alkaline phosphatase (ALP), carboxyterminal cross-linked telopeptide of type I collagen (sCTX), and bone-specific ALP were also measured.

At baseline, serum cathepsin K levels were significantly higher in the Paget's disease patients, compared with the controls, and were higher in patients with polyostotic disease than in those with monostotic disease. Baseline cathepsin K correlated positively with sCTX and urinary calcium, but not with total or bone-specific ALP. Similar but weaker correlations were seen in the controls, Dr. Merlotti said.

Overall, intravenous bisphosphonate treatment reduced cathepsin K levels by 28% at 3 days, 34% at 30 days, 45% at 3 months, 29% at 6 months, and 32% at 1 year. At each time point, the reduction in cathepsin K was significantly greater among the 20 patients treated with zoledronate than in the 40 who received pamidronate. With pamidronate, serum cathepsin K levels increased between 3 and 6 months, while on zoledronate the levels decreased continuously.

For the group as a whole, serum ALP dropped by 33% at 30 days and 24% at 90 days, then increased slightly thereafter up to 1 year. However, when examined separately, ALP levels in the zoledronate group continued to drop, while they increased after 6 months with pamidronate. At 6 months, serum ALP had normalized in 88% of the zoledronate patients, compared with just 31% of the pamidronate group, Dr. Merlotti reported.

The evaluation of cathepsin K levels at 3 months predicted the response to bisphosphonate treatment: The Paget's disease patients in whom cathepsin K was decreasing at 3 months had an 18% reduction in total serum ALP levels at 6 months, while those in whom cathepsin K was rising at 3 months showed a 5% increase in total serum ALP at 6 months, she said.

ALP levels in the zoledronate group continued to drop after 6 months but increased with pamidronate. DR. MERLOTTI

FORT LAUDERDALE, FLA. — Serum cathepsin K levels could serve as a useful measure in the management of patients with Paget's disease of bone, Dr. Daniela Merlotti said at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

Cathepsin K, a cysteine protease enzyme, is the most abundantly synthesized protein of the resorbing osteoclast, and plays an important role in the degradation of the organic matrix of bone. Recent studies have suggested that the enzyme may serve as a marker for fracture prediction and bone mineral density (J. Lab. Clin. Med. 2005;146:13–7) and as a parameter for bone metabolism in patients with early rheumatoid arthritis (Arthritis Res. Ther. 2005;7:R65–70), noted Dr. Merlotti of the University of Siena, Italy.

Serum cathepsin K levels were assessed before and after bisphosphonate treatment in 60 patients with Paget's disease and in 50 age-matched controls without the disease. Serum total alkaline phosphatase (ALP), carboxyterminal cross-linked telopeptide of type I collagen (sCTX), and bone-specific ALP were also measured.

At baseline, serum cathepsin K levels were significantly higher in the Paget's disease patients, compared with the controls, and were higher in patients with polyostotic disease than in those with monostotic disease. Baseline cathepsin K correlated positively with sCTX and urinary calcium, but not with total or bone-specific ALP. Similar but weaker correlations were seen in the controls, Dr. Merlotti said.

Overall, intravenous bisphosphonate treatment reduced cathepsin K levels by 28% at 3 days, 34% at 30 days, 45% at 3 months, 29% at 6 months, and 32% at 1 year. At each time point, the reduction in cathepsin K was significantly greater among the 20 patients treated with zoledronate than in the 40 who received pamidronate. With pamidronate, serum cathepsin K levels increased between 3 and 6 months, while on zoledronate the levels decreased continuously.

For the group as a whole, serum ALP dropped by 33% at 30 days and 24% at 90 days, then increased slightly thereafter up to 1 year. However, when examined separately, ALP levels in the zoledronate group continued to drop, while they increased after 6 months with pamidronate. At 6 months, serum ALP had normalized in 88% of the zoledronate patients, compared with just 31% of the pamidronate group, Dr. Merlotti reported.

The evaluation of cathepsin K levels at 3 months predicted the response to bisphosphonate treatment: The Paget's disease patients in whom cathepsin K was decreasing at 3 months had an 18% reduction in total serum ALP levels at 6 months, while those in whom cathepsin K was rising at 3 months showed a 5% increase in total serum ALP at 6 months, she said.

ALP levels in the zoledronate group continued to drop after 6 months but increased with pamidronate. DR. MERLOTTI

FORT LAUDERDALE, FLA. — The use of 18F-fluoride positron emission tomography may be useful in the follow-up of patients with monostotic forms of Paget's disease, Dr. Jean-Pierre Devogelaer said at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

In Paget's disease of bone, biochemical markers are used to monitor treatment response. However, in patients with limited bone involvement, these global indices often remain in the normal range, said Dr. Devogelaer, professor of rheumatology at Catholic University of Louvain and Saint-Luc University Hospital, Brussels.

Positron emission tomography (PET) using 18F-fluoride as an imaging agent appears to be of value in measuring regional skeletal metabolism, and therefore may be helpful in determining whether bisphosphonate therapy should be stopped or prolonged depending on the local level of pagetic activity, he said.

Twelve patients with monostotic Paget's disease of bone underwent 1-hour dynamic 18F-fluoride PET scans at baseline and at 1, 6, and 12 months after bisphosphonate treatment (intravenous pamidronate in nine, oral risedronate in two, and oral tiludronate in one). Biochemical markers were measured at the same time points. The affected areas were pelvis in three patients, tibia in three, femur in two, and humerus, vertebral body, skull, and scapula in one patient each.

Changes in bone metabolism as measured by the PET scans were assessed in two ways: via dynamic plasma clearance of 18F-fluoride to bone mineral, which requires arterial blood sampling; and with a standardized uptake value, a semiquantitative index that averages the tracer uptake with respect to the injected dose and the body weight. Calculation of the standardized uptake value does not require arterial sampling and therefore is a far more convenient method for measuring pagetic activity in a clinical setting, Dr. Devogelaer added.

The two values correlated with each other at all time points. Both showed huge activity prior to treatment and significant drops thereafter, by about 30% at 1 month, 40% at 6 months, and nearly 50% at 1 year.

In contrast, the biochemical markers correlated with the PET scan results at baseline but not after treatment: Total alkaline phosphatase dropped by about 25% at 1 year, but remained within the normal range throughout the study. Fasting levels of urinary N-terminal cross-linking telopeptide of type I collagen (NTX) decreased significantly up to 6 months, but not thereafter. Bone-specific alkaline phosphatase dropped by about 30%–35% at 1 month, but remained significant only up to 6 months. Such changes in biochemical markers are not adequate for follow-up, he said.

An audience member noted that PET scans are expensive and not covered for Paget's disease in the United States. Dr. Devogelaer replied, “We hope that the cost will decrease. But we see that with the biological parameters, there is no correlation after treatment. To appreciate the activity of monostotic Paget's disease of bone, we need something else.”

FORT LAUDERDALE, FLA. — The use of 18F-fluoride positron emission tomography may be useful in the follow-up of patients with monostotic forms of Paget's disease, Dr. Jean-Pierre Devogelaer said at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

In Paget's disease of bone, biochemical markers are used to monitor treatment response. However, in patients with limited bone involvement, these global indices often remain in the normal range, said Dr. Devogelaer, professor of rheumatology at Catholic University of Louvain and Saint-Luc University Hospital, Brussels.

Positron emission tomography (PET) using 18F-fluoride as an imaging agent appears to be of value in measuring regional skeletal metabolism, and therefore may be helpful in determining whether bisphosphonate therapy should be stopped or prolonged depending on the local level of pagetic activity, he said.

Twelve patients with monostotic Paget's disease of bone underwent 1-hour dynamic 18F-fluoride PET scans at baseline and at 1, 6, and 12 months after bisphosphonate treatment (intravenous pamidronate in nine, oral risedronate in two, and oral tiludronate in one). Biochemical markers were measured at the same time points. The affected areas were pelvis in three patients, tibia in three, femur in two, and humerus, vertebral body, skull, and scapula in one patient each.

Changes in bone metabolism as measured by the PET scans were assessed in two ways: via dynamic plasma clearance of 18F-fluoride to bone mineral, which requires arterial blood sampling; and with a standardized uptake value, a semiquantitative index that averages the tracer uptake with respect to the injected dose and the body weight. Calculation of the standardized uptake value does not require arterial sampling and therefore is a far more convenient method for measuring pagetic activity in a clinical setting, Dr. Devogelaer added.

The two values correlated with each other at all time points. Both showed huge activity prior to treatment and significant drops thereafter, by about 30% at 1 month, 40% at 6 months, and nearly 50% at 1 year.

In contrast, the biochemical markers correlated with the PET scan results at baseline but not after treatment: Total alkaline phosphatase dropped by about 25% at 1 year, but remained within the normal range throughout the study. Fasting levels of urinary N-terminal cross-linking telopeptide of type I collagen (NTX) decreased significantly up to 6 months, but not thereafter. Bone-specific alkaline phosphatase dropped by about 30%–35% at 1 month, but remained significant only up to 6 months. Such changes in biochemical markers are not adequate for follow-up, he said.

An audience member noted that PET scans are expensive and not covered for Paget's disease in the United States. Dr. Devogelaer replied, “We hope that the cost will decrease. But we see that with the biological parameters, there is no correlation after treatment. To appreciate the activity of monostotic Paget's disease of bone, we need something else.”

FORT LAUDERDALE, FLA. — The use of 18F-fluoride positron emission tomography may be useful in the follow-up of patients with monostotic forms of Paget's disease, Dr. Jean-Pierre Devogelaer said at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

In Paget's disease of bone, biochemical markers are used to monitor treatment response. However, in patients with limited bone involvement, these global indices often remain in the normal range, said Dr. Devogelaer, professor of rheumatology at Catholic University of Louvain and Saint-Luc University Hospital, Brussels.

Positron emission tomography (PET) using 18F-fluoride as an imaging agent appears to be of value in measuring regional skeletal metabolism, and therefore may be helpful in determining whether bisphosphonate therapy should be stopped or prolonged depending on the local level of pagetic activity, he said.

Twelve patients with monostotic Paget's disease of bone underwent 1-hour dynamic 18F-fluoride PET scans at baseline and at 1, 6, and 12 months after bisphosphonate treatment (intravenous pamidronate in nine, oral risedronate in two, and oral tiludronate in one). Biochemical markers were measured at the same time points. The affected areas were pelvis in three patients, tibia in three, femur in two, and humerus, vertebral body, skull, and scapula in one patient each.

Changes in bone metabolism as measured by the PET scans were assessed in two ways: via dynamic plasma clearance of 18F-fluoride to bone mineral, which requires arterial blood sampling; and with a standardized uptake value, a semiquantitative index that averages the tracer uptake with respect to the injected dose and the body weight. Calculation of the standardized uptake value does not require arterial sampling and therefore is a far more convenient method for measuring pagetic activity in a clinical setting, Dr. Devogelaer added.

The two values correlated with each other at all time points. Both showed huge activity prior to treatment and significant drops thereafter, by about 30% at 1 month, 40% at 6 months, and nearly 50% at 1 year.

In contrast, the biochemical markers correlated with the PET scan results at baseline but not after treatment: Total alkaline phosphatase dropped by about 25% at 1 year, but remained within the normal range throughout the study. Fasting levels of urinary N-terminal cross-linking telopeptide of type I collagen (NTX) decreased significantly up to 6 months, but not thereafter. Bone-specific alkaline phosphatase dropped by about 30%–35% at 1 month, but remained significant only up to 6 months. Such changes in biochemical markers are not adequate for follow-up, he said.

An audience member noted that PET scans are expensive and not covered for Paget's disease in the United States. Dr. Devogelaer replied, “We hope that the cost will decrease. But we see that with the biological parameters, there is no correlation after treatment. To appreciate the activity of monostotic Paget's disease of bone, we need something else.”

FORT LAUDERDALE, FLA. — Serum cathepsin K levels could be used to measure treatment response in patients with Paget's disease of bone, Dr. Daniela Merlotti said at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

Cathepsin K, a cysteine protease enzyme, is the most abundantly synthesized protein of the resorbing osteoclast and plays a role in the degradation of organic matrix in the bone, noted Dr. Merlotti of the University of Siena, Italy.

At baseline, serum cathepsin K levels were significantly higher in 60 Paget's disease patients, compared with 50 age-matched controls, and were higher in patients with polyostotic disease than in those with monostotic disease. Baseline cathepsin K correlated positively with cross-linked telopeptide of type I collagen (sCTX) and urinary calcium, but not with total or bone-specific alkaline phosphatase (ALP).

Overall, intravenous bisphosphonate treatment reduced cathepsin K levels by 28% at 3 days, 34% at 30 days, 45% at 3 months, 29% at 6 months, and 32% at 1 year. For the group as a whole, serum ALP dropped by 33% at 30 days and 24% at 90 days, then increased slightly thereafter up to 1 year.

Cathepsin K levels at 3 months predicted treatment response: Patients whose cathepsin K was decreasing at 3 months had an 18% reduction in total serum ALP levels at 6 months. Those whose cathepsin K was rising at 3 months showed a 5% increase in total serum ALP at 6 months.

FORT LAUDERDALE, FLA. — Serum cathepsin K levels could be used to measure treatment response in patients with Paget's disease of bone, Dr. Daniela Merlotti said at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

Cathepsin K, a cysteine protease enzyme, is the most abundantly synthesized protein of the resorbing osteoclast and plays a role in the degradation of organic matrix in the bone, noted Dr. Merlotti of the University of Siena, Italy.

At baseline, serum cathepsin K levels were significantly higher in 60 Paget's disease patients, compared with 50 age-matched controls, and were higher in patients with polyostotic disease than in those with monostotic disease. Baseline cathepsin K correlated positively with cross-linked telopeptide of type I collagen (sCTX) and urinary calcium, but not with total or bone-specific alkaline phosphatase (ALP).

Overall, intravenous bisphosphonate treatment reduced cathepsin K levels by 28% at 3 days, 34% at 30 days, 45% at 3 months, 29% at 6 months, and 32% at 1 year. For the group as a whole, serum ALP dropped by 33% at 30 days and 24% at 90 days, then increased slightly thereafter up to 1 year.

Cathepsin K levels at 3 months predicted treatment response: Patients whose cathepsin K was decreasing at 3 months had an 18% reduction in total serum ALP levels at 6 months. Those whose cathepsin K was rising at 3 months showed a 5% increase in total serum ALP at 6 months.

FORT LAUDERDALE, FLA. — Serum cathepsin K levels could be used to measure treatment response in patients with Paget's disease of bone, Dr. Daniela Merlotti said at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

Cathepsin K, a cysteine protease enzyme, is the most abundantly synthesized protein of the resorbing osteoclast and plays a role in the degradation of organic matrix in the bone, noted Dr. Merlotti of the University of Siena, Italy.

At baseline, serum cathepsin K levels were significantly higher in 60 Paget's disease patients, compared with 50 age-matched controls, and were higher in patients with polyostotic disease than in those with monostotic disease. Baseline cathepsin K correlated positively with cross-linked telopeptide of type I collagen (sCTX) and urinary calcium, but not with total or bone-specific alkaline phosphatase (ALP).

Overall, intravenous bisphosphonate treatment reduced cathepsin K levels by 28% at 3 days, 34% at 30 days, 45% at 3 months, 29% at 6 months, and 32% at 1 year. For the group as a whole, serum ALP dropped by 33% at 30 days and 24% at 90 days, then increased slightly thereafter up to 1 year.

Cathepsin K levels at 3 months predicted treatment response: Patients whose cathepsin K was decreasing at 3 months had an 18% reduction in total serum ALP levels at 6 months. Those whose cathepsin K was rising at 3 months showed a 5% increase in total serum ALP at 6 months.