An existing osteoporosis drug is the first ever found to prevent cartilage loss from osteoarthritis following injury to a joint, and may also regenerate some cartilage that has been lost to osteoarthritis, according to an early study presented at the annual meeting of the American Society for Bone and Mineral Research in Denver. While the study was in mice, the model closely mimics human osteoarthritis that develops following knee injuries, according to the study authors.
Cartilage can become damaged by many kinds of injury and by mechanical stresses that come with age. Over time, damaged cartilage deteriorates to cause osteoarthritis (OA), with its attendant joint inflammation and pain. Currently available drugs like steroids or non-steroidal anti-inflammatory agents (e.g. Advil, Aleve) reduce pain but do not address the loss of cartilage behind the osteoarthritis, which is projected to afflict more than 50 million Americans by 2020.
Cartilage forms the sponge-like, shock-absorbing layers that keep the impact of running and jumping and lifting from grinding bones against each other in joints. The cell type at the heart of osteoarthritis is the chondrocyte, the cartilage-producing cell responsible for maintaining the integrity of joint cartilage.
Outside of joints, chondrocytes undergo a normal maturation process that helps to form bone as part of fracture healing and bone growth in children. Disease processes and injury, however, cause chondrocytes in joint surface cartilage to become like those that help to heal bone elsewhere, but in a place where bone is not supposed to form. This mistaken maturation contributes to the gradual destruction of the joint seen in osteoarthritis.
Parathyroid hormone (PTH), known as teriparatide in drug form, has emerged as a major player in the maintenance and healing of bone, and the race is on to design new applications for it. Past studies have established that PTH prevents chondrocytes from undergoing maturation, and stimulates their proliferation, preserving larger pools of cartilage cells in the joint. Signaling molecules like PTH have their effect in the body by interacting with specifically shaped proteins on the cell surfaces called receptors. PTH docks into its receptors, like a ship coming into port, which changes the shape of the dock such that biochemical signals are sent.
The authors of the current study observed that chondrocytes within injured and degenerating cartilage have more PTH type 1 receptors on their surfaces. This makes them especially sensitive to the PTH signal that prevents harmful chondrocyte maturation into bone in the joint cartilage. Thus, PTH therapy should increase the cartilage supply exactly where cartilage loss is causing disease.
"Right now physicians have no way to bring back cartilage in patients who have lost it to osteoarthritis," said Randy Rosier, M.D., Ph.D., professor within the Department of Orthopaedics and Rehabilitation at the University of Rochester Medical Center. "Our current results, at least in mice, show that we can inhibit cartilage degeneration and improve the volume of cartilage in diseased joints. It's remarkable enough that this compound delays the loss of cartilage, but these results show it also may be able to restore, at least to some extent, cartilage in already degraded joint surfaces."
Researchers examined the impact of a daily dose of Forteo®/teriparatide, manufactured by Eli Lilly, and a generic version of teriparatide made by Sigma on the progress of OA following injury in study mice.
Experiments established a five-fold increase in PTH type 1 receptor expression in the articular cartilage of mice with injury-related osteoarthritis when compared to healthy cartilage. Injury triggers genetic mechanisms in an attempt to begin repairs, a repair response that may be responsible for the increase in PTH receptor in the joint. This in turn makes damaged cartilage particularly responsive to PTH.
In the current study, one group of mice with cartilage and ligament injuries was randomized to receive either saline as a control, Forteo® or generic PTH daily for 12 weeks. A second group of mice with joint injuries did not receive treatment until 8 weeks after injury. The delay was an attempt to determine the effect of treatment once the osteoarthritic process was already underway and some cartilage lost, a scenario that more closely mimics clinical reality. Patients do not visit their physician after an injury asking the doctor to prevent the onset of osteoarthritis 10 years in the future, Rosier said. They come in when an old injury and time have combined to degrade cartilage to the point where function is lost and pain felt.
Studies revealed that after 12 weeks of Forteo®- or generic PTH treatment, there was approximately 27 percent more joint cartilage compared to saline-treated mice. Strikingly, delayed teriparatide treatment was even more effective in improving the amount of cartilage, with up to 35 percent more cartilage in Forteo®- and PTH-treated groups than in the saline group, suggesting an ability to regenerate at least some of the lost cartilage.
With a new use patent application in place, the team will next seek to confirm the durability of the effect in further animal studies, and prepare to seek funding from the National Institutes of Health to begin pilot clinical studies of PTH treatment of osteoarthritis in humans, possibly in the later half of 2010.
Along with Rosier, the study was led by Erik Sampson, Todd O'Brien, Di Chen, Susan Bukata, J. Edward Puzas, Regis O'Keefe and Michael Zuscik within the Department of Orthopaedics and by Hani Awad in the Department of Biomedical Engineering at the University of Rochester Medical Center. The study was funded by the National Institutes of Health.
"These pre-clinical findings provide strong proof-of-concept support for the potential use of teriparatide to slow joint cartilage degeneration in OA patients, and perhaps even reverse it," Rosier said. "In the near future, we hope this serves as the foundation of new treatments that restore function to long injured joints, perhaps staving off joint replacement surgeries for some years."
Source:
Greg Williams
University of Rochester Medical Center
View drug information on Forteo.
четверг, 29 сентября 2011 г.
понедельник, 26 сентября 2011 г.
Laziness Increases Back Pain Risk
Officeworkers who rarely exercise are at increased risk of back injuries, according to UQ researchers working on a European Space Agency study.
The researchers participated in the Agency's Berlin Bed-Rest Study, monitoring 20 healthy, young men who spent 56 days lying in bed.
Lead researcher Dr Daniel Belavy said prolonged inactivity shrunk the deep muscles that protected the mens' backs.
He said that in some cases it took six months to recover but even then the muscles did not return to their normal size.
Dr Belavy said surface muscles closer to the skin, stomach and back became overactive, a condition which persisted for up to a year after returning to normal activity levels.
"If you sit around too much long-term, such as a desk job with no sport in your spare time, the muscles can slowly change in a bad way, giving you a bigger risk of hurting your back," Dr Belavy said.
He said short-term inactivity such as sitting at a desk for a couple of hours was not a major risk.
But a long-term habit of driving to work, working a desk job, going home watching TV and then going to bed would increase the chances of back problems.
Targeting inactivity could also be used in intervention and rehabilitation programs to decrease low back pain and future health care costs.
"I make sure my workspace is well set up so that I can sit with good posture and concentrate on sitting well," he said.
"This with regular attention to posture and regular 'earth-like' exercise such as walking and jogging can help to keep all the muscles fit and functioning."
UQ's Dr Julie Hides, Dr Stephen Wilson, and retired Associate Professor Carolyn Richardson also worked on the project.
The research has been published in Spine, an international journal for the study of the spine and also in the international Journal of Applied Physiology.
Dr Belavy gained his PhD under a joint study program between UQ's School of Information Technology and Electrical Engineering and the School of Health and Rehabilitation Sciences.
He has also been made the study coordinator of the upcoming 2nd Berlin Bed-Rest Study which starts in September.
Twenty-four subjects will spend 60 days in bed with their heads tilted six degrees down to simulate the body's fluid shift that occurs in microgravity of space.
The aim is to study muscle control changes and the effects of vibration exercise.
He will be based at the Centre of Muscle and Bone Research in the CharitГ© University Medicine Berlin.
University of Queensland, Brisbane, Australia
uq.au
The researchers participated in the Agency's Berlin Bed-Rest Study, monitoring 20 healthy, young men who spent 56 days lying in bed.
Lead researcher Dr Daniel Belavy said prolonged inactivity shrunk the deep muscles that protected the mens' backs.
He said that in some cases it took six months to recover but even then the muscles did not return to their normal size.
Dr Belavy said surface muscles closer to the skin, stomach and back became overactive, a condition which persisted for up to a year after returning to normal activity levels.
"If you sit around too much long-term, such as a desk job with no sport in your spare time, the muscles can slowly change in a bad way, giving you a bigger risk of hurting your back," Dr Belavy said.
He said short-term inactivity such as sitting at a desk for a couple of hours was not a major risk.
But a long-term habit of driving to work, working a desk job, going home watching TV and then going to bed would increase the chances of back problems.
Targeting inactivity could also be used in intervention and rehabilitation programs to decrease low back pain and future health care costs.
"I make sure my workspace is well set up so that I can sit with good posture and concentrate on sitting well," he said.
"This with regular attention to posture and regular 'earth-like' exercise such as walking and jogging can help to keep all the muscles fit and functioning."
UQ's Dr Julie Hides, Dr Stephen Wilson, and retired Associate Professor Carolyn Richardson also worked on the project.
The research has been published in Spine, an international journal for the study of the spine and also in the international Journal of Applied Physiology.
Dr Belavy gained his PhD under a joint study program between UQ's School of Information Technology and Electrical Engineering and the School of Health and Rehabilitation Sciences.
He has also been made the study coordinator of the upcoming 2nd Berlin Bed-Rest Study which starts in September.
Twenty-four subjects will spend 60 days in bed with their heads tilted six degrees down to simulate the body's fluid shift that occurs in microgravity of space.
The aim is to study muscle control changes and the effects of vibration exercise.
He will be based at the Centre of Muscle and Bone Research in the CharitГ© University Medicine Berlin.
University of Queensland, Brisbane, Australia
uq.au
пятница, 23 сентября 2011 г.
Recent Increase In Multiple Myeloma Survival Attributed To Novel Therapies
Multiple myeloma is one of the most common and devastating bone marrow cancers in the U.S., but survival rates have risen dramatically over the past decade. Recent analyses suggest that this trend may be attributed to new types of drugs and aggressive therapeutic interventions such as stem cell transplantation, according to the results of two studies prepublished online in Blood, the official journal of the American Society of Hematology.
Multiple myeloma (MM) is a neoplasm of plasma cells, a type of cell that resides in the bone marrow and produces antibody proteins. Survival rates for MM have traditionally been grim, with most patients dying within two to three years after diagnosis. However, within the last decade, a group of new therapies has been developed and approved for use in MM patients, including thalidomide (Thalidomid®), lenalidomide (Revlimid®), and bortezomib (Velcade®). Used alone or paired with traditional chemotherapy, these drugs have been shown to be highly effective in recently diagnosed and relapsed MM patients. Also, over the past decade high-dose chemotherapy and peripheral blood stem cell transplantation has been increasingly used for treatment of MM, especially in younger patients. Two recent studies analyzed outcomes in large populations of MM patients, comparing results with regard to diagnosis date, age, and gender.
Recent Major Improvement in Long-Term Survival of Younger Patients with Multiple Myeloma
In one study, a research team from the German Cancer Research Center and Weill Cornell Medical Center in New York analyzed trends in five- and 10-year survival of MM patients in the U.S. to understand how new therapies and innovative approaches have translated into better survival for patients. In this large epidemiologic study, 26,523 patients diagnosed with MM in the U.S. were studied from the 1990-1992 to 2002-2004 SEER (Surveillance, Epidemiology, and End Results) database.
The analyses found a definitive overall increase in the survival of MM patients over the past decade. In particular, five-year survival increased from 28.8 to 34.7 percent, and 10-year survival increased from 11.1 to 17.4 percent. Importantly, survival increased most dramatically in the youngest age group -- more than half (56.7 percent) of patients younger than 50 survived at least five years, and more than 40 percent (41.3 percent) survived at least 10 years. In real years, the average relative survival increased from four years after diagnosis in 1990-1992 to almost seven years after diagnosis in 2002-2004.
Patients age 50-59 also fared well, with approximately half (48.2 percent) surviving at least five years, and nearly a third (28.6 percent) surviving at least 10 years. However, only modest increases were seen in the age group 60-69, and virtually no improvement was seen in patients older than 70. Since about half of MM patients are diagnosed when they are 60 or older, the lack of improvement in the eldest groups is a critical finding of the research.
"The rise in survival among MM patients in this study may be attributed to improvements in stem cell protocols, supportive care, and therapies with better efficacy and lower toxicity," said Hermann Brenner, MD, of the Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, and lead author of the study. "However, the improvements among older patients in our analysis remained much more modest, suggesting a need to better understand the natural history and treatment options for multiple myeloma in this population."
Improved Survival in Multiple Myeloma and the Impact of Novel Therapies
A second study conducted by researchers at the Mayo Clinic evaluated outcomes for a large group of MM patients by comparing survival among two date-specific analyses -- one from time of diagnosis and one from time of relapse -- to better understand trends in survival over time. "We wanted to understand if the new therapies available to these patients would translate directly into improved survival," said lead author Shaji Kumar, MD, of the Mayo Clinic.
The first analysis studied 387 patient records to compare disease relapses before and after December 31, 2000, based on the availability of thalidomide and subsequent clinical trials of bortezomib and lenalidomide. The second analysis was conducted over a 36-year period (1971-2006) with a larger group of 2,981 patients with newly diagnosed MM. These patients were divided by date of diagnosis (before or after January 1, 1997) to understand the significance of the novel advances in MM therapies.
Study results illustrated a dramatic improvement in survival among patients diagnosed in recent years, both from the time of diagnosis and from relapse after stem cell transplantation. Among the patients in the relapse group, the researchers noted a significant improvement in overall survival for patients relapsing after 2000, compared with those relapsing before 2000 (24 vs. 12 months). Patients relapsing before 2000 were less likely to receive a prompt transplant and more likely to have relapsed disease at the time of transplant and to have had more treatment regimens prior to transplant, compared with the group who relapsed after 2000, but the improvement seen in the recent times was independent of these differences.
In the larger group of newly diagnosed MM patients, diagnosis within the last decade translated into a 50 percent improvement in overall survival (45 vs. 30 months). Though the team divided the groups into six-year intervals to understand trends throughout the 36 years, they found no significant changes in survival until the most recent six-year period. When the team examined the relative impact of age and gender, they found that patients younger than 65 benefited the most from the recent improvements and that female patients fared slightly better.
"These results demonstrate a clear improvement in survival among myeloma patients in the last decade, and while supportive care may have contributed to this trend, we believe that the introduction of novel drugs played a major role," said Dr. Kumar. "This study also highlights the need to target the older patient population for innovative approaches to improve outcomes, considering these patients are more frail and more likely to have co-morbidities that may limit their treatment options. This progress reflects the effort of myeloma researchers worldwide, making myeloma a model for other cancers to follow."
The American Society of Hematology (hematology/) is the world's largest professional society concerned with the causes and treatment of blood disorders. Its mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems, by promoting research, clinical care, education, training, and advocacy in hematology.
Blood, the official journal of the American Society of Hematology, is the most cited peer-reviewed publication in the field. Blood is issued to Society members and other subscribers twice per month, available in print and online at bloodjournal/.
Source: Laura Stark
American Society of Hematology
View drug information on Revlimid; Velcade.
Multiple myeloma (MM) is a neoplasm of plasma cells, a type of cell that resides in the bone marrow and produces antibody proteins. Survival rates for MM have traditionally been grim, with most patients dying within two to three years after diagnosis. However, within the last decade, a group of new therapies has been developed and approved for use in MM patients, including thalidomide (Thalidomid®), lenalidomide (Revlimid®), and bortezomib (Velcade®). Used alone or paired with traditional chemotherapy, these drugs have been shown to be highly effective in recently diagnosed and relapsed MM patients. Also, over the past decade high-dose chemotherapy and peripheral blood stem cell transplantation has been increasingly used for treatment of MM, especially in younger patients. Two recent studies analyzed outcomes in large populations of MM patients, comparing results with regard to diagnosis date, age, and gender.
Recent Major Improvement in Long-Term Survival of Younger Patients with Multiple Myeloma
In one study, a research team from the German Cancer Research Center and Weill Cornell Medical Center in New York analyzed trends in five- and 10-year survival of MM patients in the U.S. to understand how new therapies and innovative approaches have translated into better survival for patients. In this large epidemiologic study, 26,523 patients diagnosed with MM in the U.S. were studied from the 1990-1992 to 2002-2004 SEER (Surveillance, Epidemiology, and End Results) database.
The analyses found a definitive overall increase in the survival of MM patients over the past decade. In particular, five-year survival increased from 28.8 to 34.7 percent, and 10-year survival increased from 11.1 to 17.4 percent. Importantly, survival increased most dramatically in the youngest age group -- more than half (56.7 percent) of patients younger than 50 survived at least five years, and more than 40 percent (41.3 percent) survived at least 10 years. In real years, the average relative survival increased from four years after diagnosis in 1990-1992 to almost seven years after diagnosis in 2002-2004.
Patients age 50-59 also fared well, with approximately half (48.2 percent) surviving at least five years, and nearly a third (28.6 percent) surviving at least 10 years. However, only modest increases were seen in the age group 60-69, and virtually no improvement was seen in patients older than 70. Since about half of MM patients are diagnosed when they are 60 or older, the lack of improvement in the eldest groups is a critical finding of the research.
"The rise in survival among MM patients in this study may be attributed to improvements in stem cell protocols, supportive care, and therapies with better efficacy and lower toxicity," said Hermann Brenner, MD, of the Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, and lead author of the study. "However, the improvements among older patients in our analysis remained much more modest, suggesting a need to better understand the natural history and treatment options for multiple myeloma in this population."
Improved Survival in Multiple Myeloma and the Impact of Novel Therapies
A second study conducted by researchers at the Mayo Clinic evaluated outcomes for a large group of MM patients by comparing survival among two date-specific analyses -- one from time of diagnosis and one from time of relapse -- to better understand trends in survival over time. "We wanted to understand if the new therapies available to these patients would translate directly into improved survival," said lead author Shaji Kumar, MD, of the Mayo Clinic.
The first analysis studied 387 patient records to compare disease relapses before and after December 31, 2000, based on the availability of thalidomide and subsequent clinical trials of bortezomib and lenalidomide. The second analysis was conducted over a 36-year period (1971-2006) with a larger group of 2,981 patients with newly diagnosed MM. These patients were divided by date of diagnosis (before or after January 1, 1997) to understand the significance of the novel advances in MM therapies.
Study results illustrated a dramatic improvement in survival among patients diagnosed in recent years, both from the time of diagnosis and from relapse after stem cell transplantation. Among the patients in the relapse group, the researchers noted a significant improvement in overall survival for patients relapsing after 2000, compared with those relapsing before 2000 (24 vs. 12 months). Patients relapsing before 2000 were less likely to receive a prompt transplant and more likely to have relapsed disease at the time of transplant and to have had more treatment regimens prior to transplant, compared with the group who relapsed after 2000, but the improvement seen in the recent times was independent of these differences.
In the larger group of newly diagnosed MM patients, diagnosis within the last decade translated into a 50 percent improvement in overall survival (45 vs. 30 months). Though the team divided the groups into six-year intervals to understand trends throughout the 36 years, they found no significant changes in survival until the most recent six-year period. When the team examined the relative impact of age and gender, they found that patients younger than 65 benefited the most from the recent improvements and that female patients fared slightly better.
"These results demonstrate a clear improvement in survival among myeloma patients in the last decade, and while supportive care may have contributed to this trend, we believe that the introduction of novel drugs played a major role," said Dr. Kumar. "This study also highlights the need to target the older patient population for innovative approaches to improve outcomes, considering these patients are more frail and more likely to have co-morbidities that may limit their treatment options. This progress reflects the effort of myeloma researchers worldwide, making myeloma a model for other cancers to follow."
The American Society of Hematology (hematology/) is the world's largest professional society concerned with the causes and treatment of blood disorders. Its mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems, by promoting research, clinical care, education, training, and advocacy in hematology.
Blood, the official journal of the American Society of Hematology, is the most cited peer-reviewed publication in the field. Blood is issued to Society members and other subscribers twice per month, available in print and online at bloodjournal/.
Source: Laura Stark
American Society of Hematology
View drug information on Revlimid; Velcade.
вторник, 20 сентября 2011 г.
Congenital Abnormality Is The Focus Of University Of Hawaii At Manoa Research
Researchers at the University of Hawai'i at Manoa have developed innovative techniques that could have profound effects on congenital cervical vertebrae malformation research.
In the cover-featured research article of the November issue of Molecular Reproduction and Development, researchers looked into congenital cervical vertebrae malformation in humans that can cause neural problems and increase susceptibility to stillbirth in women. Research advancement on abnormal vertebrae development has been limited due to the lack of lab animals with taxonomic equivalency to humans (animal models), and restrictions on human subject research.
Leading the research effort was Dr. Jinzeng Yang, a molecular biologist in the College of Tropical Agriculture and Human Resources' Department of Human Nutrition, Food and Animal Sciences. Researchers from Yang's laboratory have developed a new mouse model that reveals how patterning and developmental proteins can influence cervical vertebrae formation.
The mouse model uses a gene suppression technique that induces skeletal formation. The mice and their offspring appear normal but have striking cervical vertebrae formation. Yang's new gene suppression technique offers benefits, in this case, over the mouse model generated by complete gene removal (knockout mice), which cause mice to die shortly after birth.
Yang's laboratory has been studying myostatin, a protein playing a dominant role in reducing muscle mass. By genetically blocking the function of myostatin by its partial DNA sequences, mice were developed with 40 percent more muscle mass. Yang's graduate student Zicong Li, the first author of the publication, hypothesized that this gene suppression strategy would also work to stimulate skeletal development by inhibiting growth differentiation factor 11 (GDF11), a similar protein to myostatin, and produce live animals. Previously, the mice with complete removal of the GDF11 gene or knockout mice died shortly after birth. In collaboration with Dr. Stefan Moisyadi's laboratory in the UH Institute of Biogenesis Research, they generated the transgenic mice by using a new single plasmid system of piggyBac transgene delivery, which offers greater transposition rates and precision.
The original research article is titled, "Transgenic Over-Expression of Growth Differentiation Factor 11 Propeptide in Skeleton Results in Transformation of the Seventh Cervical Vertebra into a Thoracic Vertebra."
Work was supported by grants from the U.S. Department of Agriculture and the National Institutes of Health.
Source:
Jinzeng Yang
University of Hawaii at Manoa
In the cover-featured research article of the November issue of Molecular Reproduction and Development, researchers looked into congenital cervical vertebrae malformation in humans that can cause neural problems and increase susceptibility to stillbirth in women. Research advancement on abnormal vertebrae development has been limited due to the lack of lab animals with taxonomic equivalency to humans (animal models), and restrictions on human subject research.
Leading the research effort was Dr. Jinzeng Yang, a molecular biologist in the College of Tropical Agriculture and Human Resources' Department of Human Nutrition, Food and Animal Sciences. Researchers from Yang's laboratory have developed a new mouse model that reveals how patterning and developmental proteins can influence cervical vertebrae formation.
The mouse model uses a gene suppression technique that induces skeletal formation. The mice and their offspring appear normal but have striking cervical vertebrae formation. Yang's new gene suppression technique offers benefits, in this case, over the mouse model generated by complete gene removal (knockout mice), which cause mice to die shortly after birth.
Yang's laboratory has been studying myostatin, a protein playing a dominant role in reducing muscle mass. By genetically blocking the function of myostatin by its partial DNA sequences, mice were developed with 40 percent more muscle mass. Yang's graduate student Zicong Li, the first author of the publication, hypothesized that this gene suppression strategy would also work to stimulate skeletal development by inhibiting growth differentiation factor 11 (GDF11), a similar protein to myostatin, and produce live animals. Previously, the mice with complete removal of the GDF11 gene or knockout mice died shortly after birth. In collaboration with Dr. Stefan Moisyadi's laboratory in the UH Institute of Biogenesis Research, they generated the transgenic mice by using a new single plasmid system of piggyBac transgene delivery, which offers greater transposition rates and precision.
The original research article is titled, "Transgenic Over-Expression of Growth Differentiation Factor 11 Propeptide in Skeleton Results in Transformation of the Seventh Cervical Vertebra into a Thoracic Vertebra."
Work was supported by grants from the U.S. Department of Agriculture and the National Institutes of Health.
Source:
Jinzeng Yang
University of Hawaii at Manoa
суббота, 17 сентября 2011 г.
FDA Orders Postmarket Surveillance Of Certain TMJ Implants
Today the U.S. Food and Drug Administration ordered three manufacturers of temporomandibular joint (TMJ) implants to conduct postmarket surveillance studies to determine the length of time before the implants are removed or replaced due to pain or other reasons.
The TMJ connects the lower jaw (mandible) to the temporal bone in the skull. A person may have an implant to replace the socket in the temporal bone or the rounded edge of the lower jaw that glides in the temporal bone socket because of an injury, arthritis, physical abnormality, or lost mobility.
The three manufacturers, TMJ Solutions, TMJ Medical, and Biomet Microfixation, make all of the currently approved TMJ devices marketed in the United States. The companies will have 30 days to submit a study plan which will need to be approved by the agency before any postmarket studies can begin.
TMJ implants also can be used to treat temporomandibular disorder (TMD) that has not responded to more conservative treatments such as limiting jaw movement, soft diet, jaw splint or adjustments, medicine to reduce pain, or physical therapy.
The FDA analyzed TMJ implant-related adverse event reports submitted between April 30, 2004 and Aug. 17, 2010. The analysis described a substantial number of patients who had implants replaced within three years or less after implantation because of extreme pain. This is considerably shorter than the expected minimum five-year life span of the device, based on premarket mechanical testing.
The FDA is not recommending any changes on use of the implants. The agency may revise its recommendations or issue other recommendations after reviewing additional clinical data from the studies. Patients who have or are considering a TMJ implant should consult with their health care professional.
TMJ implant manufacturers were required to collect postmarket data on their implants as part of the approval process. However, the data collected did not adequately address the timing or reasons for replacement, and the studies lost contact over the years with many of the enrolled patients.
The TMJ implant postmarket surveillance studies must address the following:
- Time between initial implant and removal/replacement
- Association between patient diagnosis and the timeframe between implant and removal/replacement
- For replacement implants, the time between implant and subsequent removal/replacement
- Reasons for removal/replacement of the implant
- Associations between patient demographic and clinical data and the need or removal/replacement
- Assessment of devices that have been removed from patients
As part of its review, the FDA will consider whether labeling changes, additional preclinical and clinical testing requirements, or other regulatory actions are necessary for these devices.
Source:
U.S. Food and Drug Administration
The TMJ connects the lower jaw (mandible) to the temporal bone in the skull. A person may have an implant to replace the socket in the temporal bone or the rounded edge of the lower jaw that glides in the temporal bone socket because of an injury, arthritis, physical abnormality, or lost mobility.
The three manufacturers, TMJ Solutions, TMJ Medical, and Biomet Microfixation, make all of the currently approved TMJ devices marketed in the United States. The companies will have 30 days to submit a study plan which will need to be approved by the agency before any postmarket studies can begin.
TMJ implants also can be used to treat temporomandibular disorder (TMD) that has not responded to more conservative treatments such as limiting jaw movement, soft diet, jaw splint or adjustments, medicine to reduce pain, or physical therapy.
The FDA analyzed TMJ implant-related adverse event reports submitted between April 30, 2004 and Aug. 17, 2010. The analysis described a substantial number of patients who had implants replaced within three years or less after implantation because of extreme pain. This is considerably shorter than the expected minimum five-year life span of the device, based on premarket mechanical testing.
The FDA is not recommending any changes on use of the implants. The agency may revise its recommendations or issue other recommendations after reviewing additional clinical data from the studies. Patients who have or are considering a TMJ implant should consult with their health care professional.
TMJ implant manufacturers were required to collect postmarket data on their implants as part of the approval process. However, the data collected did not adequately address the timing or reasons for replacement, and the studies lost contact over the years with many of the enrolled patients.
The TMJ implant postmarket surveillance studies must address the following:
- Time between initial implant and removal/replacement
- Association between patient diagnosis and the timeframe between implant and removal/replacement
- For replacement implants, the time between implant and subsequent removal/replacement
- Reasons for removal/replacement of the implant
- Associations between patient demographic and clinical data and the need or removal/replacement
- Assessment of devices that have been removed from patients
As part of its review, the FDA will consider whether labeling changes, additional preclinical and clinical testing requirements, or other regulatory actions are necessary for these devices.
Source:
U.S. Food and Drug Administration
среда, 14 сентября 2011 г.
Osteoporosis Prevalance In Older Australian Men Severely Underestimated
Despite a high prevalence of osteoporosis in elderly Australian men, awareness, diagnosis and treatment of the condition remain low, according to a study published in the Medical Journal of Australia.
Ms Kerrin Bleicher, a physiotherapist and PhD Student at the University of Sydney, and co-authors conducted a study to determine the proportion of older Australian men who meet the Pharmaceutical Benefits Scheme (PBS) criteria for osteoporosis treatment and are receiving effective treatment.
Of the 1705 men aged over 70 years who participated in the study, 25 per cent met one or more of the PBS criteria for osteoporosis treatment. Ninety per cent of the men who met the PBS criteria were unaware they had osteoporosis.
Ms Bleicher said that this lack of awareness may have resulted in substantial underestimation of osteoporosis prevalence in men in a recent report by the Australian Institute of Health and Welfare that relied on self-report of osteoporosis.
"Identifying men who will benefit from osteoporosis treatment and increasing the proportion of eligible men receiving appropriate treatment is a public health issue," Ms Bleicher said.
"Both non-pharmacological treatments and pharmacological treatments need to be implemented to reduce fracture rates.
"Currently it is projected that, because of the ageing population, hip fractures may double by 2026, and increase fourfold by 2051.
"An important step forward is to build public and general medical awareness that osteoporosis is common in older men and that minimal trauma fractures and vertebral deformities are indicators of increased risk of future fractures.
"Obtaining information about previous fractures, identifying vertebral deformities, and testing bone density, where appropriate, can identify men at higher risk of fracture who may benefit from interventions."
The Medical Journal of Australia is a publication of the Australian Medical Association.
The statements or opinions that are expressed in the MJA reflect the views of the authors and do not represent the official policy of the AMA unless that is so stated.
Source:
Medical Journal of Australia
Ms Kerrin Bleicher, a physiotherapist and PhD Student at the University of Sydney, and co-authors conducted a study to determine the proportion of older Australian men who meet the Pharmaceutical Benefits Scheme (PBS) criteria for osteoporosis treatment and are receiving effective treatment.
Of the 1705 men aged over 70 years who participated in the study, 25 per cent met one or more of the PBS criteria for osteoporosis treatment. Ninety per cent of the men who met the PBS criteria were unaware they had osteoporosis.
Ms Bleicher said that this lack of awareness may have resulted in substantial underestimation of osteoporosis prevalence in men in a recent report by the Australian Institute of Health and Welfare that relied on self-report of osteoporosis.
"Identifying men who will benefit from osteoporosis treatment and increasing the proportion of eligible men receiving appropriate treatment is a public health issue," Ms Bleicher said.
"Both non-pharmacological treatments and pharmacological treatments need to be implemented to reduce fracture rates.
"Currently it is projected that, because of the ageing population, hip fractures may double by 2026, and increase fourfold by 2051.
"An important step forward is to build public and general medical awareness that osteoporosis is common in older men and that minimal trauma fractures and vertebral deformities are indicators of increased risk of future fractures.
"Obtaining information about previous fractures, identifying vertebral deformities, and testing bone density, where appropriate, can identify men at higher risk of fracture who may benefit from interventions."
The Medical Journal of Australia is a publication of the Australian Medical Association.
The statements or opinions that are expressed in the MJA reflect the views of the authors and do not represent the official policy of the AMA unless that is so stated.
Source:
Medical Journal of Australia
воскресенье, 11 сентября 2011 г.
Orthopedic Oncologist Shares New Limb Sparing Surgical Techniques
James C. Wittig, M.D., chief of the division of skin and sarcoma cancer at the John Theurer Cancer Center at Hackensack University Medical Center presented eleven different educational videos on innovative approaches to orthopedic oncology at the American Academy of Orthopaedic Surgeons Conference. Dr. Wittig is known for inventing some of the most-used best practices in limb-sparing surgery. In 2009, he and his colleagues began filming their surgeries so that other surgeons across the globe could use their radically innovative techniques.
"We have spent years developing some of the best practices in limb-sparing surgery, and sharing this knowledge is going to benefit patients worldwide," said Dr. Wittig. "Conference attendees represent some of the finest minds in orthopedics today, so to be chosen to lead such a great number of presentations is an honor and speaks to the importance of limb sparing surgery and its significance to the field."
The videos range in content from radical resection and reconstruction of a distal femur tumor to a radical sacrectomy and reconstruction for a high-grade primary sarcoma of the sacrum. All of the educational videos describe various orthopedic oncology procedures pertaining to radical limb sparing surgery and reconstruction for bone and soft tissue tumors in different locations, representing state-of-the-art approaches to these surgeries.
"The physicians and staff of the John Theurer Cancer Center are focused on delivering extraordinary care," said Andrew Pecora M.D., F.A.C.P., C.P.E., chief innovations officer and professor and vice president of cancer services, John Theurer Cancer Center. "The multimedia presentations by Dr. Wittig and his team exemplify this approach from both a patient care and an educational perspective"
The conference was held in San Diego, California from February 15-19 featuring international experts in orthopedics as well as a keynote address from one of the greatest football coaches of all-time Lou Holtz. Limb sparing surgery and innovative approaches to orthopedic oncology have increasingly assumed a more prominent role within both cancer and orthopedic care. The work by Dr. Wittig and colleagues points to increasing options for patients with tumors in difficult locations of the body and how new approaches are improving patient care.
Titles and short descriptions of the video presentations Dr. Witting and colleagues present are listed below:
Osteosarcoma of Distal Femur: Radical Resection & Reconstruction with Distal Femur Tumor Prosthesis
Authors: James C. Wittig, Camilo E. Villalobos, Brett Hayden, Andrew Silverman, Benjamin Lerner, Martin M Malawer
This video describes limb-sparing resection of an Osteosarcoma involving the distal femur and knee joint. A modular segmental distal femur tumor prosthesis is utilized to reconstruct the knee joint. Emphasis is placed on meticulous neurovascular dissection and multiple muscle transfers to optimize function and minimize complications. The procedure described is a safe, reliable technique for limb sparing surgery for sarcomas of the distal femur.
Limb-Sparing Total Scapula & Proximal Humerus (Tikhoff-Linberg) Resection and Reconstruction
Authors: James C. Wittig, Camilo E. Villalobos, Brett Hayden, Andrew Silverman, Benjamin Lerner, Martin M Malawer
This video depicts a 60 year old male patient who was presented with a fungating squamous cell carcinoma involving the shoulder girdle. The radiologic studies demonstrated an extensive loss of soft tissue overlying the scapula, proximal humerus and distal clavicle. The patient underwent a limb sparing radical resection of the left scapula as well the proximal humerus including the deltoid, rotator cuff muscles, portions of the trapezius and the clavicle. A modular proximal humerus tumor prosthesis was used for reconstruction. It was stabilized to the clavicle and second rib with heavy Dacron tapes. Multiple muscle rotation flaps were used for coverage and to stabilize the prosthesis
Intraarticular Proximal Humerus Resection and Prosthetic Reconstruction for a Pathologic Fracture
Authors: James C. Wittig, Andrew Silverman. Camilo E.Villalobos, Brett Hayden, Benjamin Lerner
This is a patient with a pathologic fracture of his right humerus due to metastatic renal cell carcinoma. Dr. Wittig and his team performed an intraarticular resection of the right proximal humerus. A modular proximal humerus tumor prosthesis was utilized for reconstruction. Static and dynamic methods were utilized for stabilizing the prosthesis. Reconstruction of the glenohumeral ligaments with gore-tex aortic graft was performed to provide multidirectional stability. Multiple muscle transfers and rotational flaps were performed for dynamic stabilization as well as to power the shoulder girdle and cover the entire prosthesis with soft tissue. The goal of the reconstruction is to stabilize the shoulder girdle for optimal hand and elbow function without compromising rotation. Our patients have been pain-free and have shown good elbow and hand function.
Primary MFH of Proximal Tibia: Limb-Sparing Resection with Prosthetic and Soft Tissue Reconstruction
Authors: James C. Wittig, Camilo E. Villalobos, Brett Hayden, Andrew Silverman, Benjamin Lerner, Martin M Malawer
A limb-sparing resection of the proximal tibia is performed for a patient with a primary Malignant Fibrous Histiocytoma (MFH) of bone. A modular segmental proximal tibia endoprosthesis is used to reconstruct the bony defect and knee joint. Emphasis is placed on neurovascular dissection and reconstruction of the extensor mechanism with a medial gastrocnemius muscle flap.
Radical Resection of the Distal Humerus and Reconstruction with a Distal Humerus Tumor Prosthesis
Authors: James C. Wittig, Andrew Silverman, Brett Hayden, Camilo E. Villalobos, Benjamin Lerner
The distal humerus is a relatively rare site for developing a tumor. Limb sparing resection and reconstruction is challenging due to the close proximity of several critical neurovascular structures as well as the paucity of surrounding soft tissues. The video describes an anterior approach for resecting tumors involving the distal humerus and reconstruction with an endoprosthetic replacement. Limb-sparing resection for tumors involving the distal humerus through an anterior approach and reconstruction with a modular distal humerus tumor prosthesis and multiple muscle transfers is a safe and reliable method for treating tumors in this location.
Chondrosarcoma of the Proximal Femur: Limb-Sparing Resection and Prosthetic Reconstruction
Authors: James C. Wittig, Andrew Silverman, Camilo E. Villalobos, Brett Hayden, Benjamin Lerner
A limb-sparing resection of a Proximal Femur is performed for an 81 year old male patient with a Chondrosarcoma of the right proximal femur. Modular segmental proximal femur tumor prosthesis is utilized to reconstruct the proximal femur. Emphasis is placed on preservation of neurovascular structures and employment of major muscle rotations to optimize post-operative hip function and minimize infection. Proximal femur resection with endoprosthetic reconstruction is a complex surgical procedure. Preservation of the acetabulum and joint capsule, capsulorraphy, and reconstruction of the abductor mechanism are major determinants of joint stability. This reconstruction can also be used for a variety of nononcologic indications, as for major total hip revision surgeries and persistent infection.
Intermuscular Liposarcoma of the Posterior Thigh: Radical Resection and Sciatic Nerve Preservation
Authors: James C. Wittig, Brett Hayden, Andrew Silverman, Benjamin Lerner, Camilo E. Villalobos
This video demonstrates radical resection of an intermuscular myxoid liposarcoma of the posterior thigh in a 39 year old patient. The surgical procedure included radical resection of the intermuscular tumor as well as the use of multiple muscle rotation flaps for soft tissue closure. Strong emphasis in this video is placed on sciatic nerve dissection, mobilization, and preservation prior to tumor removal. This reconstruction technique is a safe and reliable method for treatment of soft tissue tumors in this location.
Radical Sacrectomy and Reconstruction for a High Grade Primary Sarcoma of the Sacrum
Authors: James C. Wittig, Benjamin Lerner, Andrew Silverman, Brett Hayden, Camilo E. Villalobos, Sheeraz Qureshi
This video details a radical subtotal sacrectomy and reconstruction for a high grade primary sarcoma. Sarcomas of the sacrum are extremely rare. Resection of sacral tumors is complex and risky, often requiring resection of multiple sacral nerve roots. These surgeries are associated with multiple complications. The patient, a 43 year old woman, presented with a sarcoma arising from the right side of her sacrum. The tumor had a large soft tissue component. Resection and reconstruction was undertaken through three separate approaches. This video details the steps of this complex surgical procedure.
Spinopelvic Fusion and Gluteus Maximus Muscle Rotation Following Radical Sacral Tumor Removal
Authors: James C. Wittig, Benjamin Lerner, Andrew Silverman, Brett Hayden, Camilo E. Villalobos, Sheeraz Qureshi
This video details a radical subtotal sacrectomy and reconstruction for a high grade primary sarcoma. Sarcomas of the sacrum are extremely rare. Resection of sacral tumors is risky, often requiring resection of multiple sacral nerve roots. These surgeries are associated with multiple complications. The patient, a 43 year old woman, presented with a sarcoma arising from the right side of her sacrum. The tumor had a large soft tissue component. Resection and reconstruction was undertaken through three separate approaches. The spine was fused to the iliac wings and the entire defect was covered with bilateral glutes maximus rotational flaps.
Revision Arthroplasty with a Total Femur Replacement for Multiply Failed Total Hip and Total Knee Replacement
Authors: Calin Moucha, Richard Greendyk, Benjamin Lerner, Andrew Silverman, Brett Hayden, Camilo E. Villalobos and James C. Wittig
The number of revision total knee replacement (TKR) surgeries done worldwide is increasing at a rapid pace. On rare occasions the failed TKR needs to be revised during the same surgery as an ipsilateral failed total hip replacement. In these instances the femoral bone stock is usually highly deficient and a total femoral replacement may be required. This video demonstrates a surgical technique that utilizes a total femoral replacement prosthesis for revision arthroplasty. After an extensive negative infection work-up a decision was made to undergo the procedure described. The video highlights the extensile exposure, resection of the femur, removal of a stemmed, well-fixed tibial component, and reconstruction using a total femoral prosthesis.
Massive Reconstruction of Femur with a Total Femur Replacement for Failed Arthroplasties
Authors: Calin Moucha, Richard Greendyk, Benjamin Lerner, Andrew, Brett Hayden, Camilo E. Villalobos and James C. Wittig
The number of patients who require revision surgery for a failed total hip arthroplasty is increasing at a rapid rate. While multiple reconstructive options are available in the majority of cases, on rare occasions the femoral bone stock is so deficient that standard revision implants cannot be securely fixed in the remaining bone. This video demonstrates a surgical technique that utilizes a total femoral replacement prosthesis for revision arthroplasty of a highly deficient femur. The type of implant and surgical technique used in this case should be included in the revision surgeons armamentarium for treating patients with these increasingly more common, difficult cases.
Source:
Amy Leahing
John Theurer Cancer Center
"We have spent years developing some of the best practices in limb-sparing surgery, and sharing this knowledge is going to benefit patients worldwide," said Dr. Wittig. "Conference attendees represent some of the finest minds in orthopedics today, so to be chosen to lead such a great number of presentations is an honor and speaks to the importance of limb sparing surgery and its significance to the field."
The videos range in content from radical resection and reconstruction of a distal femur tumor to a radical sacrectomy and reconstruction for a high-grade primary sarcoma of the sacrum. All of the educational videos describe various orthopedic oncology procedures pertaining to radical limb sparing surgery and reconstruction for bone and soft tissue tumors in different locations, representing state-of-the-art approaches to these surgeries.
"The physicians and staff of the John Theurer Cancer Center are focused on delivering extraordinary care," said Andrew Pecora M.D., F.A.C.P., C.P.E., chief innovations officer and professor and vice president of cancer services, John Theurer Cancer Center. "The multimedia presentations by Dr. Wittig and his team exemplify this approach from both a patient care and an educational perspective"
The conference was held in San Diego, California from February 15-19 featuring international experts in orthopedics as well as a keynote address from one of the greatest football coaches of all-time Lou Holtz. Limb sparing surgery and innovative approaches to orthopedic oncology have increasingly assumed a more prominent role within both cancer and orthopedic care. The work by Dr. Wittig and colleagues points to increasing options for patients with tumors in difficult locations of the body and how new approaches are improving patient care.
Titles and short descriptions of the video presentations Dr. Witting and colleagues present are listed below:
Osteosarcoma of Distal Femur: Radical Resection & Reconstruction with Distal Femur Tumor Prosthesis
Authors: James C. Wittig, Camilo E. Villalobos, Brett Hayden, Andrew Silverman, Benjamin Lerner, Martin M Malawer
This video describes limb-sparing resection of an Osteosarcoma involving the distal femur and knee joint. A modular segmental distal femur tumor prosthesis is utilized to reconstruct the knee joint. Emphasis is placed on meticulous neurovascular dissection and multiple muscle transfers to optimize function and minimize complications. The procedure described is a safe, reliable technique for limb sparing surgery for sarcomas of the distal femur.
Limb-Sparing Total Scapula & Proximal Humerus (Tikhoff-Linberg) Resection and Reconstruction
Authors: James C. Wittig, Camilo E. Villalobos, Brett Hayden, Andrew Silverman, Benjamin Lerner, Martin M Malawer
This video depicts a 60 year old male patient who was presented with a fungating squamous cell carcinoma involving the shoulder girdle. The radiologic studies demonstrated an extensive loss of soft tissue overlying the scapula, proximal humerus and distal clavicle. The patient underwent a limb sparing radical resection of the left scapula as well the proximal humerus including the deltoid, rotator cuff muscles, portions of the trapezius and the clavicle. A modular proximal humerus tumor prosthesis was used for reconstruction. It was stabilized to the clavicle and second rib with heavy Dacron tapes. Multiple muscle rotation flaps were used for coverage and to stabilize the prosthesis
Intraarticular Proximal Humerus Resection and Prosthetic Reconstruction for a Pathologic Fracture
Authors: James C. Wittig, Andrew Silverman. Camilo E.Villalobos, Brett Hayden, Benjamin Lerner
This is a patient with a pathologic fracture of his right humerus due to metastatic renal cell carcinoma. Dr. Wittig and his team performed an intraarticular resection of the right proximal humerus. A modular proximal humerus tumor prosthesis was utilized for reconstruction. Static and dynamic methods were utilized for stabilizing the prosthesis. Reconstruction of the glenohumeral ligaments with gore-tex aortic graft was performed to provide multidirectional stability. Multiple muscle transfers and rotational flaps were performed for dynamic stabilization as well as to power the shoulder girdle and cover the entire prosthesis with soft tissue. The goal of the reconstruction is to stabilize the shoulder girdle for optimal hand and elbow function without compromising rotation. Our patients have been pain-free and have shown good elbow and hand function.
Primary MFH of Proximal Tibia: Limb-Sparing Resection with Prosthetic and Soft Tissue Reconstruction
Authors: James C. Wittig, Camilo E. Villalobos, Brett Hayden, Andrew Silverman, Benjamin Lerner, Martin M Malawer
A limb-sparing resection of the proximal tibia is performed for a patient with a primary Malignant Fibrous Histiocytoma (MFH) of bone. A modular segmental proximal tibia endoprosthesis is used to reconstruct the bony defect and knee joint. Emphasis is placed on neurovascular dissection and reconstruction of the extensor mechanism with a medial gastrocnemius muscle flap.
Radical Resection of the Distal Humerus and Reconstruction with a Distal Humerus Tumor Prosthesis
Authors: James C. Wittig, Andrew Silverman, Brett Hayden, Camilo E. Villalobos, Benjamin Lerner
The distal humerus is a relatively rare site for developing a tumor. Limb sparing resection and reconstruction is challenging due to the close proximity of several critical neurovascular structures as well as the paucity of surrounding soft tissues. The video describes an anterior approach for resecting tumors involving the distal humerus and reconstruction with an endoprosthetic replacement. Limb-sparing resection for tumors involving the distal humerus through an anterior approach and reconstruction with a modular distal humerus tumor prosthesis and multiple muscle transfers is a safe and reliable method for treating tumors in this location.
Chondrosarcoma of the Proximal Femur: Limb-Sparing Resection and Prosthetic Reconstruction
Authors: James C. Wittig, Andrew Silverman, Camilo E. Villalobos, Brett Hayden, Benjamin Lerner
A limb-sparing resection of a Proximal Femur is performed for an 81 year old male patient with a Chondrosarcoma of the right proximal femur. Modular segmental proximal femur tumor prosthesis is utilized to reconstruct the proximal femur. Emphasis is placed on preservation of neurovascular structures and employment of major muscle rotations to optimize post-operative hip function and minimize infection. Proximal femur resection with endoprosthetic reconstruction is a complex surgical procedure. Preservation of the acetabulum and joint capsule, capsulorraphy, and reconstruction of the abductor mechanism are major determinants of joint stability. This reconstruction can also be used for a variety of nononcologic indications, as for major total hip revision surgeries and persistent infection.
Intermuscular Liposarcoma of the Posterior Thigh: Radical Resection and Sciatic Nerve Preservation
Authors: James C. Wittig, Brett Hayden, Andrew Silverman, Benjamin Lerner, Camilo E. Villalobos
This video demonstrates radical resection of an intermuscular myxoid liposarcoma of the posterior thigh in a 39 year old patient. The surgical procedure included radical resection of the intermuscular tumor as well as the use of multiple muscle rotation flaps for soft tissue closure. Strong emphasis in this video is placed on sciatic nerve dissection, mobilization, and preservation prior to tumor removal. This reconstruction technique is a safe and reliable method for treatment of soft tissue tumors in this location.
Radical Sacrectomy and Reconstruction for a High Grade Primary Sarcoma of the Sacrum
Authors: James C. Wittig, Benjamin Lerner, Andrew Silverman, Brett Hayden, Camilo E. Villalobos, Sheeraz Qureshi
This video details a radical subtotal sacrectomy and reconstruction for a high grade primary sarcoma. Sarcomas of the sacrum are extremely rare. Resection of sacral tumors is complex and risky, often requiring resection of multiple sacral nerve roots. These surgeries are associated with multiple complications. The patient, a 43 year old woman, presented with a sarcoma arising from the right side of her sacrum. The tumor had a large soft tissue component. Resection and reconstruction was undertaken through three separate approaches. This video details the steps of this complex surgical procedure.
Spinopelvic Fusion and Gluteus Maximus Muscle Rotation Following Radical Sacral Tumor Removal
Authors: James C. Wittig, Benjamin Lerner, Andrew Silverman, Brett Hayden, Camilo E. Villalobos, Sheeraz Qureshi
This video details a radical subtotal sacrectomy and reconstruction for a high grade primary sarcoma. Sarcomas of the sacrum are extremely rare. Resection of sacral tumors is risky, often requiring resection of multiple sacral nerve roots. These surgeries are associated with multiple complications. The patient, a 43 year old woman, presented with a sarcoma arising from the right side of her sacrum. The tumor had a large soft tissue component. Resection and reconstruction was undertaken through three separate approaches. The spine was fused to the iliac wings and the entire defect was covered with bilateral glutes maximus rotational flaps.
Revision Arthroplasty with a Total Femur Replacement for Multiply Failed Total Hip and Total Knee Replacement
Authors: Calin Moucha, Richard Greendyk, Benjamin Lerner, Andrew Silverman, Brett Hayden, Camilo E. Villalobos and James C. Wittig
The number of revision total knee replacement (TKR) surgeries done worldwide is increasing at a rapid pace. On rare occasions the failed TKR needs to be revised during the same surgery as an ipsilateral failed total hip replacement. In these instances the femoral bone stock is usually highly deficient and a total femoral replacement may be required. This video demonstrates a surgical technique that utilizes a total femoral replacement prosthesis for revision arthroplasty. After an extensive negative infection work-up a decision was made to undergo the procedure described. The video highlights the extensile exposure, resection of the femur, removal of a stemmed, well-fixed tibial component, and reconstruction using a total femoral prosthesis.
Massive Reconstruction of Femur with a Total Femur Replacement for Failed Arthroplasties
Authors: Calin Moucha, Richard Greendyk, Benjamin Lerner, Andrew, Brett Hayden, Camilo E. Villalobos and James C. Wittig
The number of patients who require revision surgery for a failed total hip arthroplasty is increasing at a rapid rate. While multiple reconstructive options are available in the majority of cases, on rare occasions the femoral bone stock is so deficient that standard revision implants cannot be securely fixed in the remaining bone. This video demonstrates a surgical technique that utilizes a total femoral replacement prosthesis for revision arthroplasty of a highly deficient femur. The type of implant and surgical technique used in this case should be included in the revision surgeons armamentarium for treating patients with these increasingly more common, difficult cases.
Source:
Amy Leahing
John Theurer Cancer Center
четверг, 8 сентября 2011 г.
Wyeth Presents Data From Five-Year Vertebral Fracture Prevention Study With Bazedoxifene
Wyeth Pharmaceuticals, a division of Wyeth (NYSE: WYE), announces findings from a placebo-controlled Phase 3 study of bazedoxifene 20 mg extended to five years, which indicated a significant reduction versus placebo in new vertebral fractures in postmenopausal women with osteoporosis. These and other data were presented at the American Society for Bone and Mineral Research (ASBMR) Annual Meeting in Denver, Colo. Bazedoxifene, a selective estrogen receptor modulator (SERM), is under clinical investigation for the prevention and treatment of postmenopausal osteoporosis.
"These new data are important in that they suggest the reduction in vertebral fracture risk with bazedoxifene seen at five years is comparable to that seen at three years," says Stuart Silverman, M.D., Clinical Professor of Medicine at the University of California, Los Angeles and Cedars-Sinai Medical Center, and the study's lead investigator.
About Study 301
The results being presented are from a two-year extension of a three-year Phase 3 trial, which enrolled 7,492 generally healthy postmenopausal women aged 55 to 85 years with osteoporosis. The primary endpoint of the three-year Phase 3 study was the incidence of new vertebral fractures. Eligible subjects were randomized to daily treatment with bazedoxifene 20 mg or 40 mg, raloxifene (RLX) 60 mg, or placebo. At the conclusion of the pivotal three-year study, a total of 4,216 subjects were enrolled in the extension to five years. Patients receiving bazedoxifene 20 mg continued on that dosage, while the RLX 60 mg treatment arm was discontinued (as prespecified in the protocol) after the three-year database was finalized, and subjects receiving bazedoxifene 40 mg were transitioned to bazedoxifene 20 mg after all subjects completed four years of treatment. At five years, the study showed that the incidence of new vertebral fractures was significantly reduced in the bazedoxifene 20 mg group (4.5%) and in the group transitioned from bazedoxifene 40 mg to 20 mg (3.9%) compared with placebo (6.8%). This corresponds to relative risk reductions of 35% (P=0.014) and 40% (P=0.005), respectively. The incidence of venous thromboembolic events in this Phase 3 clinical trial was higher in bazedoxifene-treated subjects when compared with placebo. This finding is consistent with what was seen at three years.
Additional New Bazedoxifene Data Presented at ASBMR
Assessment of the Effect of Bazedoxifene on Non-Vertebral Fracture Risk (McCloskey EV, et al)
Data were also presented from a post-hoc analysis performed using the Fracture Risk Assessment Tool (FRAX(R)), which was developed by the World Health Organization to calculate a woman's 10-year risk of experiencing an osteoporotic fracture. This post-hoc analysis indicated that the higher a woman's risk of a fracture, the greater the reduction in non-vertebral fractures when receiving bazedoxifene therapy based on her FRAX score.
Safety and Tolerability of Bazedoxifene in Postmenopausal Women with Osteoporosis: Results of a 5-Year, Randomized, Placebo-controlled Phase 3 Trial (de Villiers TJ, et al)
Bazedoxifene five-year safety and tolerability data in postmenopausal women with osteoporosis were also presented. The incidence of adverse events (AEs), serious AEs and discontinuations due to AEs was similar to that seen in the placebo group. The incidence of cardiac or cerebrovascular events, including myocardial infarction and stroke, in the bazedoxifene treatment groups was similar to that seen in the placebo group. Subjects treated with bazedoxifene had a higher incidence of deep venous thrombosis, hot flushes and leg cramps compared with placebo-treated subjects. The effect of bazedoxifene on the breast and endometrium was comparable to placebo.
Cost-effectiveness of Bazedoxifene in the US Incorporating the FRAX(R) Algorithm (Strom, et al)
Data from an analysis performed using a Marcov cohort model and published U.S. cost and epidemiological data evaluated the potential cost-effectiveness and intervention thresholds of bazedoxifene treatment (20 mg and 40 mg doses combined) compared to placebo. Cost-effective scenarios were projected for women with strong risk factors and with a T-score above the threshold for osteoporosis. When effect was modeled for non-vertebral fractures, the data suggested that potential cost effectiveness improved further in women from the age of 60 years with prior fracture and at the threshold of osteoporosis (T-score=-2.5 SD).
About Bazedoxifene
Wyeth is pursuing regulatory approval of bazedoxifene for the prevention and treatment of postmenopausal osteoporosis in the United States and other countries worldwide. In April 2009, the European Commission granted marketing authorization for CONBRIZA(TM) (bazedoxifene) for the treatment of postmenopausal osteoporosis in women at increased risk of fracture. Wyeth intends to introduce CONBRIZA in certain European markets following receipt of necessary reimbursement authorizations in those markets.
Bazedoxifene paired with conjugated estrogens (BZA/CE) is also being studied by Wyeth for the treatment of moderate-to-severe menopausal vasomotor symptoms such as hot flushes, night sweats and vulvar and vaginal atrophy, and for the prevention of postmenopausal osteoporosis.
About Osteoporosis
Osteoporosis affects an estimated 75 million people in the United States, Europe and Japan. In the United States, the condition is a major public health threat for an estimated 44 million Americans, or 55 percent of the people 50 years of age and older. Osteoporosis is characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility and an increased risk of fractures. Up to 20 percent of a woman's expected lifetime bone loss can occur in the years immediately following menopause. The treatment of postmenopausal osteoporosis could lead to significant improvement in the overall health for millions of women worldwide as well as reduce costs associated with postmenopausal osteoporosis-related fractures.
About Wyeth Pharmaceuticals
Wyeth Pharmaceuticals, a division of Wyeth, has leading products in the areas of women's health care, infectious disease, gastrointestinal health, central nervous system, inflammation, transplantation, hemophilia, oncology, vaccines and nutritional products.
Wyeth is one of the world's largest research-driven pharmaceutical and health care products companies. It is a leader in the discovery, development, manufacturing and marketing of pharmaceuticals, vaccines, biotechnology products, nutritionals and non-prescription medicines that improve the quality of life for people worldwide. The Company's major divisions include Wyeth Pharmaceuticals, Wyeth Consumer Healthcare and Fort Dodge Animal Health.
The statements in this press release that are not historical facts are forward-looking statements that are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. In particular, clinical trial data are subject to differing interpretations, and the views of regulatory agencies, medical and scientific experts and others may differ from ours. In addition, there can be no assurance that bazedoxifene will be commercially successful in the markets where approved or that bazedoxifene will be approved in the future in other formulations or indications and/or in other countries, including the United States. Other risks and uncertainties that could cause actual results to differ materially from those expressed or implied by forward looking statements include, among others, risks related to our proposed merger with Pfizer, including satisfaction of the conditions of the proposed merger on the proposed timeframe or at all, contractual restrictions on the conduct of our business included in the merger agreement, and the potential for loss of key personnel, disruption in key business activities or any impact on our relationships with third parties as a result of the announcement of the proposed merger; the inherent uncertainty of the timing and success of, and expense associated with, research, development, regulatory approval and commercialization of our products and pipeline products; government cost-containment initiatives; restrictions on third-party payments for our products; substantial competition in our industry, including from branded and generic products; emerging data on our products and pipeline products; the importance of strong performance from our principal products and our anticipated new product introductions; the highly regulated nature of our business; product liability, intellectual property and other litigation risks and environmental liabilities; the outcome of government investigations; uncertainty regarding our intellectual property rights and those of others; difficulties associated with, and regulatory compliance with respect to, manufacturing of our products; risks associated with our strategic relationships; global economic conditions; interest and currency exchange rate fluctuations and volatility in the credit and financial markets; changes in generally accepted accounting principles; trade buying patterns; the impact of legislation and regulatory compliance; risks and uncertainties associated with global operations and sales; and other risks and uncertainties, including those detailed from time to time in our periodic reports filed with the Securities and Exchange Commission, including our current reports on Form 8-K, quarterly reports on Form 10-Q and annual report on Form 10-K, particularly the discussion under the caption "Item 1A, Risk Factors" in our Annual Report on Form 10-K for the year ended December 31, 2008, which was filed with the Securities and Exchange Commission on February 27, 2009. The forward-looking statements in this press release are qualified by these risk factors. We assume no obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise.
Source: Wyeth Pharmaceuticals
"These new data are important in that they suggest the reduction in vertebral fracture risk with bazedoxifene seen at five years is comparable to that seen at three years," says Stuart Silverman, M.D., Clinical Professor of Medicine at the University of California, Los Angeles and Cedars-Sinai Medical Center, and the study's lead investigator.
About Study 301
The results being presented are from a two-year extension of a three-year Phase 3 trial, which enrolled 7,492 generally healthy postmenopausal women aged 55 to 85 years with osteoporosis. The primary endpoint of the three-year Phase 3 study was the incidence of new vertebral fractures. Eligible subjects were randomized to daily treatment with bazedoxifene 20 mg or 40 mg, raloxifene (RLX) 60 mg, or placebo. At the conclusion of the pivotal three-year study, a total of 4,216 subjects were enrolled in the extension to five years. Patients receiving bazedoxifene 20 mg continued on that dosage, while the RLX 60 mg treatment arm was discontinued (as prespecified in the protocol) after the three-year database was finalized, and subjects receiving bazedoxifene 40 mg were transitioned to bazedoxifene 20 mg after all subjects completed four years of treatment. At five years, the study showed that the incidence of new vertebral fractures was significantly reduced in the bazedoxifene 20 mg group (4.5%) and in the group transitioned from bazedoxifene 40 mg to 20 mg (3.9%) compared with placebo (6.8%). This corresponds to relative risk reductions of 35% (P=0.014) and 40% (P=0.005), respectively. The incidence of venous thromboembolic events in this Phase 3 clinical trial was higher in bazedoxifene-treated subjects when compared with placebo. This finding is consistent with what was seen at three years.
Additional New Bazedoxifene Data Presented at ASBMR
Assessment of the Effect of Bazedoxifene on Non-Vertebral Fracture Risk (McCloskey EV, et al)
Data were also presented from a post-hoc analysis performed using the Fracture Risk Assessment Tool (FRAX(R)), which was developed by the World Health Organization to calculate a woman's 10-year risk of experiencing an osteoporotic fracture. This post-hoc analysis indicated that the higher a woman's risk of a fracture, the greater the reduction in non-vertebral fractures when receiving bazedoxifene therapy based on her FRAX score.
Safety and Tolerability of Bazedoxifene in Postmenopausal Women with Osteoporosis: Results of a 5-Year, Randomized, Placebo-controlled Phase 3 Trial (de Villiers TJ, et al)
Bazedoxifene five-year safety and tolerability data in postmenopausal women with osteoporosis were also presented. The incidence of adverse events (AEs), serious AEs and discontinuations due to AEs was similar to that seen in the placebo group. The incidence of cardiac or cerebrovascular events, including myocardial infarction and stroke, in the bazedoxifene treatment groups was similar to that seen in the placebo group. Subjects treated with bazedoxifene had a higher incidence of deep venous thrombosis, hot flushes and leg cramps compared with placebo-treated subjects. The effect of bazedoxifene on the breast and endometrium was comparable to placebo.
Cost-effectiveness of Bazedoxifene in the US Incorporating the FRAX(R) Algorithm (Strom, et al)
Data from an analysis performed using a Marcov cohort model and published U.S. cost and epidemiological data evaluated the potential cost-effectiveness and intervention thresholds of bazedoxifene treatment (20 mg and 40 mg doses combined) compared to placebo. Cost-effective scenarios were projected for women with strong risk factors and with a T-score above the threshold for osteoporosis. When effect was modeled for non-vertebral fractures, the data suggested that potential cost effectiveness improved further in women from the age of 60 years with prior fracture and at the threshold of osteoporosis (T-score=-2.5 SD).
About Bazedoxifene
Wyeth is pursuing regulatory approval of bazedoxifene for the prevention and treatment of postmenopausal osteoporosis in the United States and other countries worldwide. In April 2009, the European Commission granted marketing authorization for CONBRIZA(TM) (bazedoxifene) for the treatment of postmenopausal osteoporosis in women at increased risk of fracture. Wyeth intends to introduce CONBRIZA in certain European markets following receipt of necessary reimbursement authorizations in those markets.
Bazedoxifene paired with conjugated estrogens (BZA/CE) is also being studied by Wyeth for the treatment of moderate-to-severe menopausal vasomotor symptoms such as hot flushes, night sweats and vulvar and vaginal atrophy, and for the prevention of postmenopausal osteoporosis.
About Osteoporosis
Osteoporosis affects an estimated 75 million people in the United States, Europe and Japan. In the United States, the condition is a major public health threat for an estimated 44 million Americans, or 55 percent of the people 50 years of age and older. Osteoporosis is characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility and an increased risk of fractures. Up to 20 percent of a woman's expected lifetime bone loss can occur in the years immediately following menopause. The treatment of postmenopausal osteoporosis could lead to significant improvement in the overall health for millions of women worldwide as well as reduce costs associated with postmenopausal osteoporosis-related fractures.
About Wyeth Pharmaceuticals
Wyeth Pharmaceuticals, a division of Wyeth, has leading products in the areas of women's health care, infectious disease, gastrointestinal health, central nervous system, inflammation, transplantation, hemophilia, oncology, vaccines and nutritional products.
Wyeth is one of the world's largest research-driven pharmaceutical and health care products companies. It is a leader in the discovery, development, manufacturing and marketing of pharmaceuticals, vaccines, biotechnology products, nutritionals and non-prescription medicines that improve the quality of life for people worldwide. The Company's major divisions include Wyeth Pharmaceuticals, Wyeth Consumer Healthcare and Fort Dodge Animal Health.
The statements in this press release that are not historical facts are forward-looking statements that are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. In particular, clinical trial data are subject to differing interpretations, and the views of regulatory agencies, medical and scientific experts and others may differ from ours. In addition, there can be no assurance that bazedoxifene will be commercially successful in the markets where approved or that bazedoxifene will be approved in the future in other formulations or indications and/or in other countries, including the United States. Other risks and uncertainties that could cause actual results to differ materially from those expressed or implied by forward looking statements include, among others, risks related to our proposed merger with Pfizer, including satisfaction of the conditions of the proposed merger on the proposed timeframe or at all, contractual restrictions on the conduct of our business included in the merger agreement, and the potential for loss of key personnel, disruption in key business activities or any impact on our relationships with third parties as a result of the announcement of the proposed merger; the inherent uncertainty of the timing and success of, and expense associated with, research, development, regulatory approval and commercialization of our products and pipeline products; government cost-containment initiatives; restrictions on third-party payments for our products; substantial competition in our industry, including from branded and generic products; emerging data on our products and pipeline products; the importance of strong performance from our principal products and our anticipated new product introductions; the highly regulated nature of our business; product liability, intellectual property and other litigation risks and environmental liabilities; the outcome of government investigations; uncertainty regarding our intellectual property rights and those of others; difficulties associated with, and regulatory compliance with respect to, manufacturing of our products; risks associated with our strategic relationships; global economic conditions; interest and currency exchange rate fluctuations and volatility in the credit and financial markets; changes in generally accepted accounting principles; trade buying patterns; the impact of legislation and regulatory compliance; risks and uncertainties associated with global operations and sales; and other risks and uncertainties, including those detailed from time to time in our periodic reports filed with the Securities and Exchange Commission, including our current reports on Form 8-K, quarterly reports on Form 10-Q and annual report on Form 10-K, particularly the discussion under the caption "Item 1A, Risk Factors" in our Annual Report on Form 10-K for the year ended December 31, 2008, which was filed with the Securities and Exchange Commission on February 27, 2009. The forward-looking statements in this press release are qualified by these risk factors. We assume no obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise.
Source: Wyeth Pharmaceuticals
понедельник, 5 сентября 2011 г.
Increasing Dose Intensity Of Chemotherapy In Osteosarcoma Offers No Benefit Study Finds
A dose-intensive regimen of the chemotherapy drugs cisplatin and doxorubicin offered no clinical benefit over standard doses of the chemotherapy drugs in patients with a bone cancer called osteosarcoma, according to results from a randomized trial in the January 17 issue of the Journal of the National Cancer Institute. Although the dose-intensive regimen killed tumor cells better than the standard regimen after surgery, survival rates were similar in both groups.
Some studies in cancers such as non-Hodgkin lymphoma and breast cancer have suggested that increasing the intensity of a chemotherapy regimen--that is, decreasing the number of days between chemotherapy treatments--may improve survival. Because chemotherapy drugs can be very toxic, doctors often have to add additional medications to such dose-intense regimens so the patient can tolerate them. For example, some chemotherapy drugs cause a patient's white blood cell count to drop, so doctors also give patients a drug called granulocyte colony-stimulating factor (G-CSF) to increase their production of white blood cells.
In the new study, Ian J. Lewis, M.D., of St. James University Hospital in Leeds, England, with colleagues at the Medical Research Council Clinical Trials Unit in London and the European Osteosarcoma Intergroup, tested whether a dose-intensive regimen consisting of standard drugs used to treat osteosarcoma would improve survival when given before surgery to remove the tumor. A total of 497 patients age 40 or younger with high-grade osteosarcoma that had not spread elsewhere in the body were randomly assigned to receive six cisplatinвЂ"doxorubicin treatments at 3-week intervals (standard regimen) or to receive the treatments at 2-week intervals (dose-intense regimen). The patients receiving the dose-intense regimen also received injections of G-CSF to help them better tolerate the chemotherapy.
The researchers observed favorable tumor responses--measured by tumor cell death--in 36 percent of patients receiving the standard treatment and in 50 percent of those receiving the dose-intense regimen. However, after an average of about 5 years, overall survival and progression-free survival were similar in both groups; for example, overall survival was 55 percent in the conventional-treatment group and 58 percent in the dose-intense group. Those who received the dose-intense regimen had a lower risk of leukopenia (low white cell count) and neutropenia (low neutrophil count) but a higher risk of thrombocytopenia (platelet deficiency) and mucositis (inflamed mucus membranes).
"[The dose-intense regimen] resulted in more tumors having good histologic response to preoperative chemotherapy, but this did not translate into a demonstratable patient benefit in overall survival or progression-free survival over [the conventional regimen]," the authors write. "This emphasis placed on histologic response as the key treatment-related predictive factor is thereby challenged."
Indeed, writes editorialist Stephen L. George, Ph.D., of Duke University Medical Center, "promising early results measured by response rates often do not translate into long-term benefits such as longer progression-free survival or overall survival." Part of the reason for this, he writes, is that large increases in response rates are needed to translate into measurable differences in survival. George reviews the conditions under which response rate is a useful endpoint, and notes that this osteosarcoma clinical trial doesn't meet those circumstances. "It is clear that response rate as an endpoint is most useful in early phase clinical trials, in which interest focuses more on assessing activity than proving clinical benefit, and as an important but secondary outcome in more definitive trials," he writes.
Contact:
* Article: Medical Research Council Press Office
* Editorial: Chris Difrancesco, News Office, Duke University Medical Center
Citation:
* Article: Lewis IJ, Nooij M, Whelan J, Sydes MR, Grimer R, Hogendorn PCW, et al. Improvement in Histologic Response, But Not Survival, in Osteosarcoma Patients Treated With Intensified Chemotherapy: A Randomized Phase III Trial of the European Osteosarcoma Intergroup (MRC BO06, EORTC 80931, ISRCTN86294690 ). J Natl Cancer Inst 2006; 99:112-129.
* Editorial: George SL. Response rate as an endpoint in clinical trials. J Natl Cancer Inst 2006; 99:98-99.
Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage. Visit the Journal online at jnci.oxfordjournals/.
Contact: Andrea Widener
Journal of the National Cancer Institute
Some studies in cancers such as non-Hodgkin lymphoma and breast cancer have suggested that increasing the intensity of a chemotherapy regimen--that is, decreasing the number of days between chemotherapy treatments--may improve survival. Because chemotherapy drugs can be very toxic, doctors often have to add additional medications to such dose-intense regimens so the patient can tolerate them. For example, some chemotherapy drugs cause a patient's white blood cell count to drop, so doctors also give patients a drug called granulocyte colony-stimulating factor (G-CSF) to increase their production of white blood cells.
In the new study, Ian J. Lewis, M.D., of St. James University Hospital in Leeds, England, with colleagues at the Medical Research Council Clinical Trials Unit in London and the European Osteosarcoma Intergroup, tested whether a dose-intensive regimen consisting of standard drugs used to treat osteosarcoma would improve survival when given before surgery to remove the tumor. A total of 497 patients age 40 or younger with high-grade osteosarcoma that had not spread elsewhere in the body were randomly assigned to receive six cisplatinвЂ"doxorubicin treatments at 3-week intervals (standard regimen) or to receive the treatments at 2-week intervals (dose-intense regimen). The patients receiving the dose-intense regimen also received injections of G-CSF to help them better tolerate the chemotherapy.
The researchers observed favorable tumor responses--measured by tumor cell death--in 36 percent of patients receiving the standard treatment and in 50 percent of those receiving the dose-intense regimen. However, after an average of about 5 years, overall survival and progression-free survival were similar in both groups; for example, overall survival was 55 percent in the conventional-treatment group and 58 percent in the dose-intense group. Those who received the dose-intense regimen had a lower risk of leukopenia (low white cell count) and neutropenia (low neutrophil count) but a higher risk of thrombocytopenia (platelet deficiency) and mucositis (inflamed mucus membranes).
"[The dose-intense regimen] resulted in more tumors having good histologic response to preoperative chemotherapy, but this did not translate into a demonstratable patient benefit in overall survival or progression-free survival over [the conventional regimen]," the authors write. "This emphasis placed on histologic response as the key treatment-related predictive factor is thereby challenged."
Indeed, writes editorialist Stephen L. George, Ph.D., of Duke University Medical Center, "promising early results measured by response rates often do not translate into long-term benefits such as longer progression-free survival or overall survival." Part of the reason for this, he writes, is that large increases in response rates are needed to translate into measurable differences in survival. George reviews the conditions under which response rate is a useful endpoint, and notes that this osteosarcoma clinical trial doesn't meet those circumstances. "It is clear that response rate as an endpoint is most useful in early phase clinical trials, in which interest focuses more on assessing activity than proving clinical benefit, and as an important but secondary outcome in more definitive trials," he writes.
Contact:
* Article: Medical Research Council Press Office
* Editorial: Chris Difrancesco, News Office, Duke University Medical Center
Citation:
* Article: Lewis IJ, Nooij M, Whelan J, Sydes MR, Grimer R, Hogendorn PCW, et al. Improvement in Histologic Response, But Not Survival, in Osteosarcoma Patients Treated With Intensified Chemotherapy: A Randomized Phase III Trial of the European Osteosarcoma Intergroup (MRC BO06, EORTC 80931, ISRCTN86294690 ). J Natl Cancer Inst 2006; 99:112-129.
* Editorial: George SL. Response rate as an endpoint in clinical trials. J Natl Cancer Inst 2006; 99:98-99.
Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage. Visit the Journal online at jnci.oxfordjournals/.
Contact: Andrea Widener
Journal of the National Cancer Institute
пятница, 2 сентября 2011 г.
Vitamin D Supplements Associated With Reduced Fracture Risk In Older Adults
Oral vitamin D supplements at a dose of at least 400 international units per day are associated with a reduced risk of bone fractures in older adults, according to results of a meta-analysis published in the March 23 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.
"The anti-fracture benefits of vitamin D have been questioned by several recent trials, leading to uncertainty among patients and physicians regarding recommendations for vitamin D supplementation," the authors write as background information in the article. "Factors that may obscure a benefit of vitamin D are low adherence to treatment, low dose of vitamin D or the use of less potent ergocalciferol (vitamin D2)."
Heike A. Bischoff-Ferrari, Dr.P.H., of the University of Zurich, University Hospital, Zurich, Switzerland, and colleagues performed a meta-analysis on 12 previously published clinical trials of oral vitamin D supplements among adults age 65 or older. These double-blind randomized controlled trials involved 42,279 participants (average age 78) and looked at non-vertebral (non-spinal) fractures, including eight trials of 40,886 participants specifically studying hip fractures.
When the results of the trials were pooled, vitamin D supplements decreased the risk of non-vertebral fractures by 14 percent and of hip fractures by 9 percent. The authors then pooled the results of only the nine trials in which participants received doses of more than 400 international units per day. At this dosage, vitamin D supplements reduced non-vertebral fractures by 20 percent and hip fractures by 18 percent. Doses of 400 international units per day or lower did not reduce the risk of either fracture type. A greater reduction in risk was also seen among trial participants whose blood levels of 25-hydroxyvitamin D (a commonly used measure of blood vitamin D levels) achieved a greater increase.
Among individuals taking high doses of vitamin D, additional calcium did not appear to have any further protective effect against fractures. "Physiologically, the calcium-sparing effect of vitamin D may explain why we did not see an additional benefit of calcium supplementation at a higher dose of vitamin D," the authors write.
"The greater fracture reduction with a higher received dose or higher achieved 25-hydroxyvitamin D levels for both any non-vertebral fractures and hip fractures suggests that higher doses of vitamin D should be explored in future research to optimize anti-fracture efficacy," they conclude. "Also, it is possible that greater benefits may be achieved with earlier initiation of vitamin D supplementation and longer duration of use. Our results do not support use of low-dose vitamin D with or without calcium in the prevention of fractures among older individuals."
Arch Intern Med. 2009;169[6]:551-561.
archinte.ama-assn
"The anti-fracture benefits of vitamin D have been questioned by several recent trials, leading to uncertainty among patients and physicians regarding recommendations for vitamin D supplementation," the authors write as background information in the article. "Factors that may obscure a benefit of vitamin D are low adherence to treatment, low dose of vitamin D or the use of less potent ergocalciferol (vitamin D2)."
Heike A. Bischoff-Ferrari, Dr.P.H., of the University of Zurich, University Hospital, Zurich, Switzerland, and colleagues performed a meta-analysis on 12 previously published clinical trials of oral vitamin D supplements among adults age 65 or older. These double-blind randomized controlled trials involved 42,279 participants (average age 78) and looked at non-vertebral (non-spinal) fractures, including eight trials of 40,886 participants specifically studying hip fractures.
When the results of the trials were pooled, vitamin D supplements decreased the risk of non-vertebral fractures by 14 percent and of hip fractures by 9 percent. The authors then pooled the results of only the nine trials in which participants received doses of more than 400 international units per day. At this dosage, vitamin D supplements reduced non-vertebral fractures by 20 percent and hip fractures by 18 percent. Doses of 400 international units per day or lower did not reduce the risk of either fracture type. A greater reduction in risk was also seen among trial participants whose blood levels of 25-hydroxyvitamin D (a commonly used measure of blood vitamin D levels) achieved a greater increase.
Among individuals taking high doses of vitamin D, additional calcium did not appear to have any further protective effect against fractures. "Physiologically, the calcium-sparing effect of vitamin D may explain why we did not see an additional benefit of calcium supplementation at a higher dose of vitamin D," the authors write.
"The greater fracture reduction with a higher received dose or higher achieved 25-hydroxyvitamin D levels for both any non-vertebral fractures and hip fractures suggests that higher doses of vitamin D should be explored in future research to optimize anti-fracture efficacy," they conclude. "Also, it is possible that greater benefits may be achieved with earlier initiation of vitamin D supplementation and longer duration of use. Our results do not support use of low-dose vitamin D with or without calcium in the prevention of fractures among older individuals."
Arch Intern Med. 2009;169[6]:551-561.
archinte.ama-assn
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