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Treating Pediatric Vitiligo: Consensus Statement Provides Recommendations
TOPLINE:
METHODOLOGY:
- While half of all vitiligo cases manifest within the initial two decades of life, no guidelines specifically address the management of vitiligo in children, adolescents, and young adults with vitiligo.
- A protocol was established to formulate consensus recommendations addressing questions related to pediatric vitiligo.
- Overall, 50 articles on topical corticosteroids and/or topical calcineurin inhibitors, five on topical Janus kinase inhibitors, and two each on pseudocatalase and microdermabrasion were included.
- The participants recorded their agreement levels with the formulated statements, using a 5-point Likert scale.
TAKEAWAY:
- TCIs, TCSs, JAK inhibitors, and phototherapy, specifically narrowband ultraviolet (UV)-B light therapy, are mainstay treatments; the combination of UV-B light and topical therapy may enhance initial repigmentation.
- Long-term monitoring for skin cancers is advised, and short outdoor UV exposure is suggested for pediatric patients.
- TCIs, such as tacrolimus and pimecrolimus, are recommended as first-line therapy, particularly on the face, applied twice daily for ≥ 3 months; continued use for 6-12 additional months is recommended if repigmentation is observed.
- The choice of TCS class depends on the site and planned usage duration. Short-term use or overlap with TCIs is recommended because of the risk for atrophy with long-term TCS use. Class 5-6 agents are another option.
- For areas with thin skin, TCSs can be considered second-line treatments.
- Topical JAK inhibitors, specifically topical 1.5% ruxolitinib cream, are recommended for patients aged ≥ 12 years, as first- or second-line therapy. Limitation to 10% body surface area is recommended to minimize systemic absorption. Limited evidence exists for children aged < 12 years.
IN PRACTICE:
“Effective therapy requires a focus on long-term therapeutic interventions to maximize the local gain and retention of pigmentation with a trial period of twice-weekly application. Counseling should include discussion of the chronicity of vitiligo and the need for long-term care,” the authors wrote.
LIMITATIONS:
Some of the recommendations were opinion-based because of the scarcity of evidence-based literature.
SOURCE:
The consensus statement was published on March 13 in JAMA Dermatology.
DISCLOSURES:
This work was supported by grants from Vitiligo Research Foundation and Incyte Pharmaceuticals. The majority of authors disclosed financial relationships outside this work; several reported no disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- While half of all vitiligo cases manifest within the initial two decades of life, no guidelines specifically address the management of vitiligo in children, adolescents, and young adults with vitiligo.
- A protocol was established to formulate consensus recommendations addressing questions related to pediatric vitiligo.
- Overall, 50 articles on topical corticosteroids and/or topical calcineurin inhibitors, five on topical Janus kinase inhibitors, and two each on pseudocatalase and microdermabrasion were included.
- The participants recorded their agreement levels with the formulated statements, using a 5-point Likert scale.
TAKEAWAY:
- TCIs, TCSs, JAK inhibitors, and phototherapy, specifically narrowband ultraviolet (UV)-B light therapy, are mainstay treatments; the combination of UV-B light and topical therapy may enhance initial repigmentation.
- Long-term monitoring for skin cancers is advised, and short outdoor UV exposure is suggested for pediatric patients.
- TCIs, such as tacrolimus and pimecrolimus, are recommended as first-line therapy, particularly on the face, applied twice daily for ≥ 3 months; continued use for 6-12 additional months is recommended if repigmentation is observed.
- The choice of TCS class depends on the site and planned usage duration. Short-term use or overlap with TCIs is recommended because of the risk for atrophy with long-term TCS use. Class 5-6 agents are another option.
- For areas with thin skin, TCSs can be considered second-line treatments.
- Topical JAK inhibitors, specifically topical 1.5% ruxolitinib cream, are recommended for patients aged ≥ 12 years, as first- or second-line therapy. Limitation to 10% body surface area is recommended to minimize systemic absorption. Limited evidence exists for children aged < 12 years.
IN PRACTICE:
“Effective therapy requires a focus on long-term therapeutic interventions to maximize the local gain and retention of pigmentation with a trial period of twice-weekly application. Counseling should include discussion of the chronicity of vitiligo and the need for long-term care,” the authors wrote.
LIMITATIONS:
Some of the recommendations were opinion-based because of the scarcity of evidence-based literature.
SOURCE:
The consensus statement was published on March 13 in JAMA Dermatology.
DISCLOSURES:
This work was supported by grants from Vitiligo Research Foundation and Incyte Pharmaceuticals. The majority of authors disclosed financial relationships outside this work; several reported no disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- While half of all vitiligo cases manifest within the initial two decades of life, no guidelines specifically address the management of vitiligo in children, adolescents, and young adults with vitiligo.
- A protocol was established to formulate consensus recommendations addressing questions related to pediatric vitiligo.
- Overall, 50 articles on topical corticosteroids and/or topical calcineurin inhibitors, five on topical Janus kinase inhibitors, and two each on pseudocatalase and microdermabrasion were included.
- The participants recorded their agreement levels with the formulated statements, using a 5-point Likert scale.
TAKEAWAY:
- TCIs, TCSs, JAK inhibitors, and phototherapy, specifically narrowband ultraviolet (UV)-B light therapy, are mainstay treatments; the combination of UV-B light and topical therapy may enhance initial repigmentation.
- Long-term monitoring for skin cancers is advised, and short outdoor UV exposure is suggested for pediatric patients.
- TCIs, such as tacrolimus and pimecrolimus, are recommended as first-line therapy, particularly on the face, applied twice daily for ≥ 3 months; continued use for 6-12 additional months is recommended if repigmentation is observed.
- The choice of TCS class depends on the site and planned usage duration. Short-term use or overlap with TCIs is recommended because of the risk for atrophy with long-term TCS use. Class 5-6 agents are another option.
- For areas with thin skin, TCSs can be considered second-line treatments.
- Topical JAK inhibitors, specifically topical 1.5% ruxolitinib cream, are recommended for patients aged ≥ 12 years, as first- or second-line therapy. Limitation to 10% body surface area is recommended to minimize systemic absorption. Limited evidence exists for children aged < 12 years.
IN PRACTICE:
“Effective therapy requires a focus on long-term therapeutic interventions to maximize the local gain and retention of pigmentation with a trial period of twice-weekly application. Counseling should include discussion of the chronicity of vitiligo and the need for long-term care,” the authors wrote.
LIMITATIONS:
Some of the recommendations were opinion-based because of the scarcity of evidence-based literature.
SOURCE:
The consensus statement was published on March 13 in JAMA Dermatology.
DISCLOSURES:
This work was supported by grants from Vitiligo Research Foundation and Incyte Pharmaceuticals. The majority of authors disclosed financial relationships outside this work; several reported no disclosures.
A version of this article appeared on Medscape.com.
Medtronic’s Duet EDMS Catheter Tubing Under Class I Recall
If this happens, potential harm to patients may include infections, cerebrospinal fluid (CSF) leakage, overdrainage of CSF, and abnormality of the ventricles. Uncontrolled overdrainage of CSF could lead to neurological injury or death if the disconnection is undetected.
The Food and Drug Administration has identified this as a Class I recall — the most serious type — due to the risk for serious injury or death. To date, there have been 26 reported injuries and no deaths related to this issue.
The recall includes 45,176 devices distributed in the United States between May 3, 2021, and January 9, 2024, with model numbers 46913, 46914, 46915, 46916, and 46917.
The Duet EDMS is used for temporary CSF drainage or sampling in patients who have surgery for open descending thoracic aortic aneurysm (TAA) or descending thoraco-abdominal aortic aneurysm (TAAA) or patients who have TAA/TAAA repair surgery and develop symptoms such as paraplegia.
Medtronic has sent an urgent medical device recall letter to all affected customers asking them to identify, quarantine, and return any unused recalled products.
Customers are also advised to check all Duet EDMS components for damage and ensure that all connections are secure and leak-free.
If a patient is currently connected to an impacted Duet EDMS and a leak or disconnection is detected, the device should be changed to a new alternative device utilizing a sterile technique.
It is not recommended that a Duet system device that is connected to a patient and working as intended be removed or replaced.
Customers in the United States with questions about this recall should contact Medtronic at 1-800-874-5797.
A version of this article appeared on Medscape.com.
If this happens, potential harm to patients may include infections, cerebrospinal fluid (CSF) leakage, overdrainage of CSF, and abnormality of the ventricles. Uncontrolled overdrainage of CSF could lead to neurological injury or death if the disconnection is undetected.
The Food and Drug Administration has identified this as a Class I recall — the most serious type — due to the risk for serious injury or death. To date, there have been 26 reported injuries and no deaths related to this issue.
The recall includes 45,176 devices distributed in the United States between May 3, 2021, and January 9, 2024, with model numbers 46913, 46914, 46915, 46916, and 46917.
The Duet EDMS is used for temporary CSF drainage or sampling in patients who have surgery for open descending thoracic aortic aneurysm (TAA) or descending thoraco-abdominal aortic aneurysm (TAAA) or patients who have TAA/TAAA repair surgery and develop symptoms such as paraplegia.
Medtronic has sent an urgent medical device recall letter to all affected customers asking them to identify, quarantine, and return any unused recalled products.
Customers are also advised to check all Duet EDMS components for damage and ensure that all connections are secure and leak-free.
If a patient is currently connected to an impacted Duet EDMS and a leak or disconnection is detected, the device should be changed to a new alternative device utilizing a sterile technique.
It is not recommended that a Duet system device that is connected to a patient and working as intended be removed or replaced.
Customers in the United States with questions about this recall should contact Medtronic at 1-800-874-5797.
A version of this article appeared on Medscape.com.
If this happens, potential harm to patients may include infections, cerebrospinal fluid (CSF) leakage, overdrainage of CSF, and abnormality of the ventricles. Uncontrolled overdrainage of CSF could lead to neurological injury or death if the disconnection is undetected.
The Food and Drug Administration has identified this as a Class I recall — the most serious type — due to the risk for serious injury or death. To date, there have been 26 reported injuries and no deaths related to this issue.
The recall includes 45,176 devices distributed in the United States between May 3, 2021, and January 9, 2024, with model numbers 46913, 46914, 46915, 46916, and 46917.
The Duet EDMS is used for temporary CSF drainage or sampling in patients who have surgery for open descending thoracic aortic aneurysm (TAA) or descending thoraco-abdominal aortic aneurysm (TAAA) or patients who have TAA/TAAA repair surgery and develop symptoms such as paraplegia.
Medtronic has sent an urgent medical device recall letter to all affected customers asking them to identify, quarantine, and return any unused recalled products.
Customers are also advised to check all Duet EDMS components for damage and ensure that all connections are secure and leak-free.
If a patient is currently connected to an impacted Duet EDMS and a leak or disconnection is detected, the device should be changed to a new alternative device utilizing a sterile technique.
It is not recommended that a Duet system device that is connected to a patient and working as intended be removed or replaced.
Customers in the United States with questions about this recall should contact Medtronic at 1-800-874-5797.
A version of this article appeared on Medscape.com.
Vitamin D Supplements May Be a Double-Edged Sword
This transcript has been edited for clarity.
Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr F. Perry Wilson of the Yale School of Medicine.
Imagine, if you will, the great Cathedral of Our Lady of Correlation. You walk through the majestic oak doors depicting the link between ice cream sales and shark attacks, past the rose window depicting the cardiovascular benefits of red wine, and down the aisles frescoed in dramatic images showing how Facebook usage is associated with less life satisfaction. And then you reach the altar, the holy of holies where, emblazoned in shimmering pyrite, you see the patron saint of this church: vitamin D.
Yes, if you’ve watched this space, then you know that I have little truck with the wildly popular supplement. In all of clinical research, I believe that there is no molecule with stronger data for correlation and weaker data for causation.
Low serum vitamin D levels have been linked to higher risks for heart disease, cancer, falls, COVID, dementia, C diff, and others. And yet, when we do randomized trials of vitamin D supplementation — the thing that can prove that the low level was causally linked to the outcome of interest — we get negative results.
Trials aren’t perfect, of course, and we’ll talk in a moment about a big one that had some issues. But we are at a point where we need to either be vitamin D apologists, saying, “Forget what those lying RCTs tell you and buy this supplement” — an $800 million-a-year industry, by the way — or conclude that vitamin D levels are a convenient marker of various lifestyle factors that are associated with better outcomes: markers of exercise, getting outside, eating a varied diet.
Or perhaps vitamin D supplements have real effects. It’s just that the beneficial effects are matched by the harmful ones. Stay tuned.
The Women’s Health Initiative remains among the largest randomized trials of vitamin D and calcium supplementation ever conducted — and a major contributor to the negative outcomes of vitamin D trials.
But if you dig into the inclusion and exclusion criteria for this trial, you’ll find that individuals were allowed to continue taking vitamins and supplements while they were in the trial, regardless of their randomization status. In fact, the majority took supplements at baseline, and more took supplements over time.
That means, of course, that people in the placebo group, who were getting sugar pills instead of vitamin D and calcium, may have been taking vitamin D and calcium on the side. That would certainly bias the results of the trial toward the null, which is what the primary analyses showed. To wit, the original analysis of the Women’s Health Initiative trial showed no effect of randomization to vitamin D supplementation on improving cancer or cardiovascular outcomes.
But the Women’s Health Initiative trial started 30 years ago. Today, with the benefit of decades of follow-up, we can re-investigate — and perhaps re-litigate — those findings, courtesy of this study, “Long-Term Effect of Randomization to Calcium and Vitamin D Supplementation on Health in Older Women” appearing in Annals of Internal Medicine.
Dr Cynthia Thomson, of the Mel and Enid Zuckerman College of Public Health at the University of Arizona, and colleagues led this updated analysis focused on two findings that had been hinted at, but not statistically confirmed, in other vitamin D studies: a potential for the supplement to reduce the risk for cancer, and a potential for it to increase the risk for heart disease.
The randomized trial itself only lasted 7 years. What we are seeing in this analysis of 36,282 women is outcomes that happened at any time from randomization to the end of 2023 — around 20 years after the randomization to supplementation stopped. But, the researchers would argue, that’s probably okay. Cancer and heart disease take time to develop; we see lung cancer long after people stop smoking. So a history of consistent vitamin D supplementation may indeed be protective — or harmful.
Here are the top-line results. Those randomized to vitamin D and calcium supplementation had a 7% reduction in the rate of death from cancer, driven primarily by a reduction in colorectal cancer. This was statistically significant. Also statistically significant? Those randomized to supplementation had a 6% increase in the rate of death from cardiovascular disease. Put those findings together and what do you get? Stone-cold nothing, in terms of overall mortality.
Okay, you say, but what about all that supplementation that was happening outside of the context of the trial, biasing our results toward the null?
The researchers finally clue us in.
First of all, I’ll tell you that, yes, people who were supplementing outside of the trial had higher baseline vitamin D levels — a median of 54.5 nmol/L vs 32.8 nmol/L. This may be because they were supplementing with vitamin D, but it could also be because people who take supplements tend to do other healthy things — another correlation to add to the great cathedral.
To get a better view of the real effects of randomization, the authors restricted the analysis to just those who did not use outside supplements. If vitamin D supplements help, then these are the people they should help. This group had about a 11% reduction in the incidence of cancer — statistically significant — and a 7% reduction in cancer mortality that did not meet the bar for statistical significance.
There was no increase in cardiovascular disease among this group. But this small effect on cancer was nowhere near enough to significantly reduce the rate of all-cause mortality.
Among those using supplements, vitamin D supplementation didn’t really move the needle on any outcome.
I know what you’re thinking: How many of these women were vitamin D deficient when we got started? These results may simply be telling us that people who have normal vitamin D levels are fine to go without supplementation.
Nearly three fourths of women who were not taking supplements entered the trial with vitamin D levels below the 50 nmol/L cutoff that the authors suggest would qualify for deficiency. Around half of those who used supplements were deficient. And yet, frustratingly, I could not find data on the effect of randomization to supplementation stratified by baseline vitamin D level. I even reached out to Dr Thomson to ask about this. She replied, “We did not stratify on baseline values because the numbers are too small statistically to test this.” Sorry.
In the meantime, I can tell you that for your “average woman,” vitamin D supplementation likely has no effect on mortality. It might modestly reduce the risk for certain cancers while increasing the risk for heart disease (probably through coronary calcification). So, there might be some room for personalization here. Perhaps women with a strong family history of cancer or other risk factors would do better with supplements, and those with a high risk for heart disease would do worse. Seems like a strategy that could be tested in a clinical trial. But maybe we could ask the participants to give up their extracurricular supplement use before they enter the trial. F. Perry Wilson, MD, MSCE, has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and his book, How Medicine Works and When It Doesn’t, is available now.
This transcript has been edited for clarity.
Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr F. Perry Wilson of the Yale School of Medicine.
Imagine, if you will, the great Cathedral of Our Lady of Correlation. You walk through the majestic oak doors depicting the link between ice cream sales and shark attacks, past the rose window depicting the cardiovascular benefits of red wine, and down the aisles frescoed in dramatic images showing how Facebook usage is associated with less life satisfaction. And then you reach the altar, the holy of holies where, emblazoned in shimmering pyrite, you see the patron saint of this church: vitamin D.
Yes, if you’ve watched this space, then you know that I have little truck with the wildly popular supplement. In all of clinical research, I believe that there is no molecule with stronger data for correlation and weaker data for causation.
Low serum vitamin D levels have been linked to higher risks for heart disease, cancer, falls, COVID, dementia, C diff, and others. And yet, when we do randomized trials of vitamin D supplementation — the thing that can prove that the low level was causally linked to the outcome of interest — we get negative results.
Trials aren’t perfect, of course, and we’ll talk in a moment about a big one that had some issues. But we are at a point where we need to either be vitamin D apologists, saying, “Forget what those lying RCTs tell you and buy this supplement” — an $800 million-a-year industry, by the way — or conclude that vitamin D levels are a convenient marker of various lifestyle factors that are associated with better outcomes: markers of exercise, getting outside, eating a varied diet.
Or perhaps vitamin D supplements have real effects. It’s just that the beneficial effects are matched by the harmful ones. Stay tuned.
The Women’s Health Initiative remains among the largest randomized trials of vitamin D and calcium supplementation ever conducted — and a major contributor to the negative outcomes of vitamin D trials.
But if you dig into the inclusion and exclusion criteria for this trial, you’ll find that individuals were allowed to continue taking vitamins and supplements while they were in the trial, regardless of their randomization status. In fact, the majority took supplements at baseline, and more took supplements over time.
That means, of course, that people in the placebo group, who were getting sugar pills instead of vitamin D and calcium, may have been taking vitamin D and calcium on the side. That would certainly bias the results of the trial toward the null, which is what the primary analyses showed. To wit, the original analysis of the Women’s Health Initiative trial showed no effect of randomization to vitamin D supplementation on improving cancer or cardiovascular outcomes.
But the Women’s Health Initiative trial started 30 years ago. Today, with the benefit of decades of follow-up, we can re-investigate — and perhaps re-litigate — those findings, courtesy of this study, “Long-Term Effect of Randomization to Calcium and Vitamin D Supplementation on Health in Older Women” appearing in Annals of Internal Medicine.
Dr Cynthia Thomson, of the Mel and Enid Zuckerman College of Public Health at the University of Arizona, and colleagues led this updated analysis focused on two findings that had been hinted at, but not statistically confirmed, in other vitamin D studies: a potential for the supplement to reduce the risk for cancer, and a potential for it to increase the risk for heart disease.
The randomized trial itself only lasted 7 years. What we are seeing in this analysis of 36,282 women is outcomes that happened at any time from randomization to the end of 2023 — around 20 years after the randomization to supplementation stopped. But, the researchers would argue, that’s probably okay. Cancer and heart disease take time to develop; we see lung cancer long after people stop smoking. So a history of consistent vitamin D supplementation may indeed be protective — or harmful.
Here are the top-line results. Those randomized to vitamin D and calcium supplementation had a 7% reduction in the rate of death from cancer, driven primarily by a reduction in colorectal cancer. This was statistically significant. Also statistically significant? Those randomized to supplementation had a 6% increase in the rate of death from cardiovascular disease. Put those findings together and what do you get? Stone-cold nothing, in terms of overall mortality.
Okay, you say, but what about all that supplementation that was happening outside of the context of the trial, biasing our results toward the null?
The researchers finally clue us in.
First of all, I’ll tell you that, yes, people who were supplementing outside of the trial had higher baseline vitamin D levels — a median of 54.5 nmol/L vs 32.8 nmol/L. This may be because they were supplementing with vitamin D, but it could also be because people who take supplements tend to do other healthy things — another correlation to add to the great cathedral.
To get a better view of the real effects of randomization, the authors restricted the analysis to just those who did not use outside supplements. If vitamin D supplements help, then these are the people they should help. This group had about a 11% reduction in the incidence of cancer — statistically significant — and a 7% reduction in cancer mortality that did not meet the bar for statistical significance.
There was no increase in cardiovascular disease among this group. But this small effect on cancer was nowhere near enough to significantly reduce the rate of all-cause mortality.
Among those using supplements, vitamin D supplementation didn’t really move the needle on any outcome.
I know what you’re thinking: How many of these women were vitamin D deficient when we got started? These results may simply be telling us that people who have normal vitamin D levels are fine to go without supplementation.
Nearly three fourths of women who were not taking supplements entered the trial with vitamin D levels below the 50 nmol/L cutoff that the authors suggest would qualify for deficiency. Around half of those who used supplements were deficient. And yet, frustratingly, I could not find data on the effect of randomization to supplementation stratified by baseline vitamin D level. I even reached out to Dr Thomson to ask about this. She replied, “We did not stratify on baseline values because the numbers are too small statistically to test this.” Sorry.
In the meantime, I can tell you that for your “average woman,” vitamin D supplementation likely has no effect on mortality. It might modestly reduce the risk for certain cancers while increasing the risk for heart disease (probably through coronary calcification). So, there might be some room for personalization here. Perhaps women with a strong family history of cancer or other risk factors would do better with supplements, and those with a high risk for heart disease would do worse. Seems like a strategy that could be tested in a clinical trial. But maybe we could ask the participants to give up their extracurricular supplement use before they enter the trial. F. Perry Wilson, MD, MSCE, has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and his book, How Medicine Works and When It Doesn’t, is available now.
This transcript has been edited for clarity.
Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr F. Perry Wilson of the Yale School of Medicine.
Imagine, if you will, the great Cathedral of Our Lady of Correlation. You walk through the majestic oak doors depicting the link between ice cream sales and shark attacks, past the rose window depicting the cardiovascular benefits of red wine, and down the aisles frescoed in dramatic images showing how Facebook usage is associated with less life satisfaction. And then you reach the altar, the holy of holies where, emblazoned in shimmering pyrite, you see the patron saint of this church: vitamin D.
Yes, if you’ve watched this space, then you know that I have little truck with the wildly popular supplement. In all of clinical research, I believe that there is no molecule with stronger data for correlation and weaker data for causation.
Low serum vitamin D levels have been linked to higher risks for heart disease, cancer, falls, COVID, dementia, C diff, and others. And yet, when we do randomized trials of vitamin D supplementation — the thing that can prove that the low level was causally linked to the outcome of interest — we get negative results.
Trials aren’t perfect, of course, and we’ll talk in a moment about a big one that had some issues. But we are at a point where we need to either be vitamin D apologists, saying, “Forget what those lying RCTs tell you and buy this supplement” — an $800 million-a-year industry, by the way — or conclude that vitamin D levels are a convenient marker of various lifestyle factors that are associated with better outcomes: markers of exercise, getting outside, eating a varied diet.
Or perhaps vitamin D supplements have real effects. It’s just that the beneficial effects are matched by the harmful ones. Stay tuned.
The Women’s Health Initiative remains among the largest randomized trials of vitamin D and calcium supplementation ever conducted — and a major contributor to the negative outcomes of vitamin D trials.
But if you dig into the inclusion and exclusion criteria for this trial, you’ll find that individuals were allowed to continue taking vitamins and supplements while they were in the trial, regardless of their randomization status. In fact, the majority took supplements at baseline, and more took supplements over time.
That means, of course, that people in the placebo group, who were getting sugar pills instead of vitamin D and calcium, may have been taking vitamin D and calcium on the side. That would certainly bias the results of the trial toward the null, which is what the primary analyses showed. To wit, the original analysis of the Women’s Health Initiative trial showed no effect of randomization to vitamin D supplementation on improving cancer or cardiovascular outcomes.
But the Women’s Health Initiative trial started 30 years ago. Today, with the benefit of decades of follow-up, we can re-investigate — and perhaps re-litigate — those findings, courtesy of this study, “Long-Term Effect of Randomization to Calcium and Vitamin D Supplementation on Health in Older Women” appearing in Annals of Internal Medicine.
Dr Cynthia Thomson, of the Mel and Enid Zuckerman College of Public Health at the University of Arizona, and colleagues led this updated analysis focused on two findings that had been hinted at, but not statistically confirmed, in other vitamin D studies: a potential for the supplement to reduce the risk for cancer, and a potential for it to increase the risk for heart disease.
The randomized trial itself only lasted 7 years. What we are seeing in this analysis of 36,282 women is outcomes that happened at any time from randomization to the end of 2023 — around 20 years after the randomization to supplementation stopped. But, the researchers would argue, that’s probably okay. Cancer and heart disease take time to develop; we see lung cancer long after people stop smoking. So a history of consistent vitamin D supplementation may indeed be protective — or harmful.
Here are the top-line results. Those randomized to vitamin D and calcium supplementation had a 7% reduction in the rate of death from cancer, driven primarily by a reduction in colorectal cancer. This was statistically significant. Also statistically significant? Those randomized to supplementation had a 6% increase in the rate of death from cardiovascular disease. Put those findings together and what do you get? Stone-cold nothing, in terms of overall mortality.
Okay, you say, but what about all that supplementation that was happening outside of the context of the trial, biasing our results toward the null?
The researchers finally clue us in.
First of all, I’ll tell you that, yes, people who were supplementing outside of the trial had higher baseline vitamin D levels — a median of 54.5 nmol/L vs 32.8 nmol/L. This may be because they were supplementing with vitamin D, but it could also be because people who take supplements tend to do other healthy things — another correlation to add to the great cathedral.
To get a better view of the real effects of randomization, the authors restricted the analysis to just those who did not use outside supplements. If vitamin D supplements help, then these are the people they should help. This group had about a 11% reduction in the incidence of cancer — statistically significant — and a 7% reduction in cancer mortality that did not meet the bar for statistical significance.
There was no increase in cardiovascular disease among this group. But this small effect on cancer was nowhere near enough to significantly reduce the rate of all-cause mortality.
Among those using supplements, vitamin D supplementation didn’t really move the needle on any outcome.
I know what you’re thinking: How many of these women were vitamin D deficient when we got started? These results may simply be telling us that people who have normal vitamin D levels are fine to go without supplementation.
Nearly three fourths of women who were not taking supplements entered the trial with vitamin D levels below the 50 nmol/L cutoff that the authors suggest would qualify for deficiency. Around half of those who used supplements were deficient. And yet, frustratingly, I could not find data on the effect of randomization to supplementation stratified by baseline vitamin D level. I even reached out to Dr Thomson to ask about this. She replied, “We did not stratify on baseline values because the numbers are too small statistically to test this.” Sorry.
In the meantime, I can tell you that for your “average woman,” vitamin D supplementation likely has no effect on mortality. It might modestly reduce the risk for certain cancers while increasing the risk for heart disease (probably through coronary calcification). So, there might be some room for personalization here. Perhaps women with a strong family history of cancer or other risk factors would do better with supplements, and those with a high risk for heart disease would do worse. Seems like a strategy that could be tested in a clinical trial. But maybe we could ask the participants to give up their extracurricular supplement use before they enter the trial. F. Perry Wilson, MD, MSCE, has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and his book, How Medicine Works and When It Doesn’t, is available now.
Long-Term Calcium and Vitamin D: Cancer Deaths Down, CVD Deaths Up in Older Women?
Some doctors may be scratching their heads over a new analysis reporting that combined calcium and vitamin D (CaD) supplements appear to be associated with a slight 6% increase in cardiovascular (CVD) mortality, a slight 7% decrease in cancer risk, and no effect on osteoporotic fracture in postmenopausal women.
The study, in Annals of Internal Medicine, found no effect of supplementation on all-cause mortality.
The findings emerged from an analysis of more than 20 years’ follow-up data on a randomized trial in postmenopausal women conducted as part of the Women’s Health Initiative (WHI).
Cynthia A. Thomson, PhD, RD, first author and cancer prevention scientist at the Arizona Cancer Center and a professor of health promotion sciences at the University of Arizona in Tucson said the findings recommend individualized assessment of the need for supplements for older women as they consider them in hopes of preventing fractures.
“Evaluate your patients individually and understand that there are some who may benefit from supplementation, for example, in terms of reducing colorectal cancer mortality,” Dr. Thomson said in an interview. The approach should be nuanced. “If you check the adequacy of vitamin D and calcium in their diets, supplementation may not be needed.” She added that supplementation is best considered in the context of a woman’s overall health profile, including risk factors for fracture, heart disease, and cancer, especially colorectal cancer (CRC).
Study Details
The investigators conducted postintervention follow-up of the WHI’s 7-year multicenter randomized intervention trial of CaD vs placebo.
Since existing evidence of long-term health outcomes was limited, the trial, begun in 1999 and closed in 2005, enrolled 36,282 postmenopausal women (mean age 62) with no history of breast or colorectal cancer. They were randomly assigned 1:1 to supplementation with 1000 mg of calcium carbonate (400 mg elemental calcium) plus 400 IU of vitamin D3 daily or placebo, taken twice daily in half doses.
Study outcomes were incidence of CRC, total and invasive breast cancer; disease-specific and all-cause mortality; total CVD; and hip fracture measured through December 2020, with analyses stratified by personal supplement usage.
Cancer. CaD was associated with reduced incident total cancer, CRC, and invasive breast cancer — notably among participants not taking CaD before randomization. Cancer incidence estimates varied widely, the authors noted, when stratified by supplement use before randomization. Noting that CaD seemed to have more cancer-related impact in those without prior supplementation, the authors suggested supplementation may affect cancer biology primarily by augmenting nutrient insufficiency.
An estimated 7% reduction in cancer mortality was observed after a median cumulative follow-up of 22.3 years: 1817 vs 1943 deaths (hazard ratio, 0.93; 95% CI, 0.87-0.99).
CVD. An estimated 6% increase in CVD mortality was seen in the CaD group: 2621 vs 2420 deaths (HR, 1.06; 95% CI, 1.01-1.12). Pretrial supplement users were found to be at higher CVD risk.
Hip fracture. No effect on hip fracture risk was measured, but the authors cautioned that hip fracture and CVD outcomes were available only for a subset of participants, and the effects of calcium alone vs vitamin D alone vs the combination could not be disentangled.
In a small subgroup analysis, some CaD users were seen to respond in terms of bone mineral density but since only 4 of the study’s 40 sites collected such information, the study was underpowered to examine the effect. ”Many other studies, however, show a response to supplementation in women who already have bone mineral deficits,” Dr. Thomson said.
The Calcification Question
One of the possible mechanisms of harm is that high-dose calcium supplements can increase the rate of blood coagulation and promote vascular calcification, said Emma Laing, PhD, RD, director of dietetics at the University of Georgia in Athens and a spokesperson for the Chicago-based Academy of Nutrition and Dietetics.
“Other factors that should be considered when determining a patient’s CVD risk are race, genetic predisposition, medical and social history, response to stress, and lifestyle behaviors, as well as the length of time supplements have been consumed,” added Dr. Laing, who was not involved in the WHI analysis.
“We asked ourselves if CaD supplements might contribute to calcification of the coronary arteries, since some believe this to be the case, although the literature is mixed,” said Dr. Thomson.
“So we did a shorter ancillary study in a small sample of several hundred [women] to see if there was any increase in calcification” and no difference was seen on imaging across the two arms. “However, women who were already on supplements before entering the study seemed to be at higher CVD risk,” she said.
Added study coauthor JoAnn E. Manson, MD, DrPH, chief of the division of preventive medicine at Brigham and Women’s Hospital and professor of women’s health at Harvard Medical School, both in Boston: “With no increase or decrease in coronary artery calcium at the end of the trial, we don’t believe starting or continuing calcium/vitamin D supplements should require screening for coronary artery disease.”
Some randomized trials and systematic reviews, however, have observed an increased risk of CVD in healthy patients on calcium supplements, with one Korean meta-analysis reporting a 15% increase in CVD risk in healthy postmenopausal women taking calcium supplements. Another meta-analysis found a link between calcium supplements and a greater risk of various cardiovascular outcomes, especially myocardial infarction.
Vitamin D Supplementation
As for vitamin D only supplementation, an updated meta-analysis including more than 83,000 individuals showed that it confers no cardiovascular protection and is therefore not indicated for this purpose.
Practice Considerations
Offering an outsider’s perspective, Sarah G. Candler, MD, MPH, an internist in Houston specializing in primary care for older high-risk adults, said: “Unfortunately, this latest study continues the trend of creating more questions than answers. If the adverse outcome of CVD death is a result of supplementation, it is unclear if this is due to the vitamin D, the calcium, or both. And it is unclear if this is dose dependent, time dependent, or due to concurrent risk factors unique to certain populations.
“It is recommended that patients at risk of osteoporosis based on age, sex, medications, and lifestyle be screened for osteoporosis and treated accordingly, including supplementation with CaD,” Dr. Candler said. “It remains unclear whether supplementation with CaD in the absence of osteoporosis and osteopenia is net beneficial or harmful, and at this time I would not recommend it to my patients.”
Added Dr. Manson: “The very small increase seen in cardiovascular mortality wouldn’t be a reason to discontinue supplementation among women who have been advised by their healthcare providers to take these supplements for bone health or other purposes.
“Among those at usual risk of fracture, we recommend trying to obtain adequate calcium and vitamin D from food sources first and to use supplements only for the purpose of filling gaps in intake,” Dr. Manson continued. Overall, the findings support the national recommended dietary allowances for daily calcium intake of 1200 mg and daily vitamin D intake of 600-800 IU among postmenopausal women for maintenance of bone health, she said.
While a 2022 study found that vitamin D supplementation alone did not prevent fractures in healthy adults, other research has shown that a calcium/vitamin D combination is more likely to protect the skeleton.
“Patients at risk for fractures will probably benefit from calcium and/or vitamin D supplementation if they do not meet dietary intake requirements, have malabsorption syndromes, are taking medications that affect nutrient absorption, or if they are older and not regularly exposed to sunlight,” said Dr. Laing. “A combination of biochemical, imaging, functional, and dietary intake data can help determine if a supplement is warranted.”
She stressed that additional research is needed in more diverse populations before changing practice guidelines. “However, doctors should continue to weigh the risks and benefits of prescribing supplements for each patient.”
The WHI program is funded by the National Heart, Lung, and Blood Institute. Dr. Thomson disclosed no competing interests. Dr. Manson reported a relationship with Mars Edge. Multiple authors reported grant support from government funding agencies. The outside commentators had no relevant competing interests to disclose.
Some doctors may be scratching their heads over a new analysis reporting that combined calcium and vitamin D (CaD) supplements appear to be associated with a slight 6% increase in cardiovascular (CVD) mortality, a slight 7% decrease in cancer risk, and no effect on osteoporotic fracture in postmenopausal women.
The study, in Annals of Internal Medicine, found no effect of supplementation on all-cause mortality.
The findings emerged from an analysis of more than 20 years’ follow-up data on a randomized trial in postmenopausal women conducted as part of the Women’s Health Initiative (WHI).
Cynthia A. Thomson, PhD, RD, first author and cancer prevention scientist at the Arizona Cancer Center and a professor of health promotion sciences at the University of Arizona in Tucson said the findings recommend individualized assessment of the need for supplements for older women as they consider them in hopes of preventing fractures.
“Evaluate your patients individually and understand that there are some who may benefit from supplementation, for example, in terms of reducing colorectal cancer mortality,” Dr. Thomson said in an interview. The approach should be nuanced. “If you check the adequacy of vitamin D and calcium in their diets, supplementation may not be needed.” She added that supplementation is best considered in the context of a woman’s overall health profile, including risk factors for fracture, heart disease, and cancer, especially colorectal cancer (CRC).
Study Details
The investigators conducted postintervention follow-up of the WHI’s 7-year multicenter randomized intervention trial of CaD vs placebo.
Since existing evidence of long-term health outcomes was limited, the trial, begun in 1999 and closed in 2005, enrolled 36,282 postmenopausal women (mean age 62) with no history of breast or colorectal cancer. They were randomly assigned 1:1 to supplementation with 1000 mg of calcium carbonate (400 mg elemental calcium) plus 400 IU of vitamin D3 daily or placebo, taken twice daily in half doses.
Study outcomes were incidence of CRC, total and invasive breast cancer; disease-specific and all-cause mortality; total CVD; and hip fracture measured through December 2020, with analyses stratified by personal supplement usage.
Cancer. CaD was associated with reduced incident total cancer, CRC, and invasive breast cancer — notably among participants not taking CaD before randomization. Cancer incidence estimates varied widely, the authors noted, when stratified by supplement use before randomization. Noting that CaD seemed to have more cancer-related impact in those without prior supplementation, the authors suggested supplementation may affect cancer biology primarily by augmenting nutrient insufficiency.
An estimated 7% reduction in cancer mortality was observed after a median cumulative follow-up of 22.3 years: 1817 vs 1943 deaths (hazard ratio, 0.93; 95% CI, 0.87-0.99).
CVD. An estimated 6% increase in CVD mortality was seen in the CaD group: 2621 vs 2420 deaths (HR, 1.06; 95% CI, 1.01-1.12). Pretrial supplement users were found to be at higher CVD risk.
Hip fracture. No effect on hip fracture risk was measured, but the authors cautioned that hip fracture and CVD outcomes were available only for a subset of participants, and the effects of calcium alone vs vitamin D alone vs the combination could not be disentangled.
In a small subgroup analysis, some CaD users were seen to respond in terms of bone mineral density but since only 4 of the study’s 40 sites collected such information, the study was underpowered to examine the effect. ”Many other studies, however, show a response to supplementation in women who already have bone mineral deficits,” Dr. Thomson said.
The Calcification Question
One of the possible mechanisms of harm is that high-dose calcium supplements can increase the rate of blood coagulation and promote vascular calcification, said Emma Laing, PhD, RD, director of dietetics at the University of Georgia in Athens and a spokesperson for the Chicago-based Academy of Nutrition and Dietetics.
“Other factors that should be considered when determining a patient’s CVD risk are race, genetic predisposition, medical and social history, response to stress, and lifestyle behaviors, as well as the length of time supplements have been consumed,” added Dr. Laing, who was not involved in the WHI analysis.
“We asked ourselves if CaD supplements might contribute to calcification of the coronary arteries, since some believe this to be the case, although the literature is mixed,” said Dr. Thomson.
“So we did a shorter ancillary study in a small sample of several hundred [women] to see if there was any increase in calcification” and no difference was seen on imaging across the two arms. “However, women who were already on supplements before entering the study seemed to be at higher CVD risk,” she said.
Added study coauthor JoAnn E. Manson, MD, DrPH, chief of the division of preventive medicine at Brigham and Women’s Hospital and professor of women’s health at Harvard Medical School, both in Boston: “With no increase or decrease in coronary artery calcium at the end of the trial, we don’t believe starting or continuing calcium/vitamin D supplements should require screening for coronary artery disease.”
Some randomized trials and systematic reviews, however, have observed an increased risk of CVD in healthy patients on calcium supplements, with one Korean meta-analysis reporting a 15% increase in CVD risk in healthy postmenopausal women taking calcium supplements. Another meta-analysis found a link between calcium supplements and a greater risk of various cardiovascular outcomes, especially myocardial infarction.
Vitamin D Supplementation
As for vitamin D only supplementation, an updated meta-analysis including more than 83,000 individuals showed that it confers no cardiovascular protection and is therefore not indicated for this purpose.
Practice Considerations
Offering an outsider’s perspective, Sarah G. Candler, MD, MPH, an internist in Houston specializing in primary care for older high-risk adults, said: “Unfortunately, this latest study continues the trend of creating more questions than answers. If the adverse outcome of CVD death is a result of supplementation, it is unclear if this is due to the vitamin D, the calcium, or both. And it is unclear if this is dose dependent, time dependent, or due to concurrent risk factors unique to certain populations.
“It is recommended that patients at risk of osteoporosis based on age, sex, medications, and lifestyle be screened for osteoporosis and treated accordingly, including supplementation with CaD,” Dr. Candler said. “It remains unclear whether supplementation with CaD in the absence of osteoporosis and osteopenia is net beneficial or harmful, and at this time I would not recommend it to my patients.”
Added Dr. Manson: “The very small increase seen in cardiovascular mortality wouldn’t be a reason to discontinue supplementation among women who have been advised by their healthcare providers to take these supplements for bone health or other purposes.
“Among those at usual risk of fracture, we recommend trying to obtain adequate calcium and vitamin D from food sources first and to use supplements only for the purpose of filling gaps in intake,” Dr. Manson continued. Overall, the findings support the national recommended dietary allowances for daily calcium intake of 1200 mg and daily vitamin D intake of 600-800 IU among postmenopausal women for maintenance of bone health, she said.
While a 2022 study found that vitamin D supplementation alone did not prevent fractures in healthy adults, other research has shown that a calcium/vitamin D combination is more likely to protect the skeleton.
“Patients at risk for fractures will probably benefit from calcium and/or vitamin D supplementation if they do not meet dietary intake requirements, have malabsorption syndromes, are taking medications that affect nutrient absorption, or if they are older and not regularly exposed to sunlight,” said Dr. Laing. “A combination of biochemical, imaging, functional, and dietary intake data can help determine if a supplement is warranted.”
She stressed that additional research is needed in more diverse populations before changing practice guidelines. “However, doctors should continue to weigh the risks and benefits of prescribing supplements for each patient.”
The WHI program is funded by the National Heart, Lung, and Blood Institute. Dr. Thomson disclosed no competing interests. Dr. Manson reported a relationship with Mars Edge. Multiple authors reported grant support from government funding agencies. The outside commentators had no relevant competing interests to disclose.
Some doctors may be scratching their heads over a new analysis reporting that combined calcium and vitamin D (CaD) supplements appear to be associated with a slight 6% increase in cardiovascular (CVD) mortality, a slight 7% decrease in cancer risk, and no effect on osteoporotic fracture in postmenopausal women.
The study, in Annals of Internal Medicine, found no effect of supplementation on all-cause mortality.
The findings emerged from an analysis of more than 20 years’ follow-up data on a randomized trial in postmenopausal women conducted as part of the Women’s Health Initiative (WHI).
Cynthia A. Thomson, PhD, RD, first author and cancer prevention scientist at the Arizona Cancer Center and a professor of health promotion sciences at the University of Arizona in Tucson said the findings recommend individualized assessment of the need for supplements for older women as they consider them in hopes of preventing fractures.
“Evaluate your patients individually and understand that there are some who may benefit from supplementation, for example, in terms of reducing colorectal cancer mortality,” Dr. Thomson said in an interview. The approach should be nuanced. “If you check the adequacy of vitamin D and calcium in their diets, supplementation may not be needed.” She added that supplementation is best considered in the context of a woman’s overall health profile, including risk factors for fracture, heart disease, and cancer, especially colorectal cancer (CRC).
Study Details
The investigators conducted postintervention follow-up of the WHI’s 7-year multicenter randomized intervention trial of CaD vs placebo.
Since existing evidence of long-term health outcomes was limited, the trial, begun in 1999 and closed in 2005, enrolled 36,282 postmenopausal women (mean age 62) with no history of breast or colorectal cancer. They were randomly assigned 1:1 to supplementation with 1000 mg of calcium carbonate (400 mg elemental calcium) plus 400 IU of vitamin D3 daily or placebo, taken twice daily in half doses.
Study outcomes were incidence of CRC, total and invasive breast cancer; disease-specific and all-cause mortality; total CVD; and hip fracture measured through December 2020, with analyses stratified by personal supplement usage.
Cancer. CaD was associated with reduced incident total cancer, CRC, and invasive breast cancer — notably among participants not taking CaD before randomization. Cancer incidence estimates varied widely, the authors noted, when stratified by supplement use before randomization. Noting that CaD seemed to have more cancer-related impact in those without prior supplementation, the authors suggested supplementation may affect cancer biology primarily by augmenting nutrient insufficiency.
An estimated 7% reduction in cancer mortality was observed after a median cumulative follow-up of 22.3 years: 1817 vs 1943 deaths (hazard ratio, 0.93; 95% CI, 0.87-0.99).
CVD. An estimated 6% increase in CVD mortality was seen in the CaD group: 2621 vs 2420 deaths (HR, 1.06; 95% CI, 1.01-1.12). Pretrial supplement users were found to be at higher CVD risk.
Hip fracture. No effect on hip fracture risk was measured, but the authors cautioned that hip fracture and CVD outcomes were available only for a subset of participants, and the effects of calcium alone vs vitamin D alone vs the combination could not be disentangled.
In a small subgroup analysis, some CaD users were seen to respond in terms of bone mineral density but since only 4 of the study’s 40 sites collected such information, the study was underpowered to examine the effect. ”Many other studies, however, show a response to supplementation in women who already have bone mineral deficits,” Dr. Thomson said.
The Calcification Question
One of the possible mechanisms of harm is that high-dose calcium supplements can increase the rate of blood coagulation and promote vascular calcification, said Emma Laing, PhD, RD, director of dietetics at the University of Georgia in Athens and a spokesperson for the Chicago-based Academy of Nutrition and Dietetics.
“Other factors that should be considered when determining a patient’s CVD risk are race, genetic predisposition, medical and social history, response to stress, and lifestyle behaviors, as well as the length of time supplements have been consumed,” added Dr. Laing, who was not involved in the WHI analysis.
“We asked ourselves if CaD supplements might contribute to calcification of the coronary arteries, since some believe this to be the case, although the literature is mixed,” said Dr. Thomson.
“So we did a shorter ancillary study in a small sample of several hundred [women] to see if there was any increase in calcification” and no difference was seen on imaging across the two arms. “However, women who were already on supplements before entering the study seemed to be at higher CVD risk,” she said.
Added study coauthor JoAnn E. Manson, MD, DrPH, chief of the division of preventive medicine at Brigham and Women’s Hospital and professor of women’s health at Harvard Medical School, both in Boston: “With no increase or decrease in coronary artery calcium at the end of the trial, we don’t believe starting or continuing calcium/vitamin D supplements should require screening for coronary artery disease.”
Some randomized trials and systematic reviews, however, have observed an increased risk of CVD in healthy patients on calcium supplements, with one Korean meta-analysis reporting a 15% increase in CVD risk in healthy postmenopausal women taking calcium supplements. Another meta-analysis found a link between calcium supplements and a greater risk of various cardiovascular outcomes, especially myocardial infarction.
Vitamin D Supplementation
As for vitamin D only supplementation, an updated meta-analysis including more than 83,000 individuals showed that it confers no cardiovascular protection and is therefore not indicated for this purpose.
Practice Considerations
Offering an outsider’s perspective, Sarah G. Candler, MD, MPH, an internist in Houston specializing in primary care for older high-risk adults, said: “Unfortunately, this latest study continues the trend of creating more questions than answers. If the adverse outcome of CVD death is a result of supplementation, it is unclear if this is due to the vitamin D, the calcium, or both. And it is unclear if this is dose dependent, time dependent, or due to concurrent risk factors unique to certain populations.
“It is recommended that patients at risk of osteoporosis based on age, sex, medications, and lifestyle be screened for osteoporosis and treated accordingly, including supplementation with CaD,” Dr. Candler said. “It remains unclear whether supplementation with CaD in the absence of osteoporosis and osteopenia is net beneficial or harmful, and at this time I would not recommend it to my patients.”
Added Dr. Manson: “The very small increase seen in cardiovascular mortality wouldn’t be a reason to discontinue supplementation among women who have been advised by their healthcare providers to take these supplements for bone health or other purposes.
“Among those at usual risk of fracture, we recommend trying to obtain adequate calcium and vitamin D from food sources first and to use supplements only for the purpose of filling gaps in intake,” Dr. Manson continued. Overall, the findings support the national recommended dietary allowances for daily calcium intake of 1200 mg and daily vitamin D intake of 600-800 IU among postmenopausal women for maintenance of bone health, she said.
While a 2022 study found that vitamin D supplementation alone did not prevent fractures in healthy adults, other research has shown that a calcium/vitamin D combination is more likely to protect the skeleton.
“Patients at risk for fractures will probably benefit from calcium and/or vitamin D supplementation if they do not meet dietary intake requirements, have malabsorption syndromes, are taking medications that affect nutrient absorption, or if they are older and not regularly exposed to sunlight,” said Dr. Laing. “A combination of biochemical, imaging, functional, and dietary intake data can help determine if a supplement is warranted.”
She stressed that additional research is needed in more diverse populations before changing practice guidelines. “However, doctors should continue to weigh the risks and benefits of prescribing supplements for each patient.”
The WHI program is funded by the National Heart, Lung, and Blood Institute. Dr. Thomson disclosed no competing interests. Dr. Manson reported a relationship with Mars Edge. Multiple authors reported grant support from government funding agencies. The outside commentators had no relevant competing interests to disclose.
FROM ANNALS OF INTERNAL MEDICINE
Meta-analysis Identifies Unique Risk Factors of Triple-Negative Breast Cancer
Key clinical point: The risk factors for overall breast cancer (such as parity, menopausal hormone therapy use, and alcohol consumption) did not increase the risk for triple-negative breast cancer (TNBC), which had a distinct risk factor profile.
Major finding: Parity, menopausal hormone therapy use, alcohol consumption, smoking, and higher body mass index were not significantly associated with TNBC risk (all P > .05); instead, family history (odds ratio [OR] 1.55; P < .001), longer duration of oral contraceptive use (OR 1.29; P < .001), and higher breast density (OR 2.19; P < .001) were significantly associated with an increased risk for TNBC.
Study details: This meta-analysis evaluated the association between TNBC incidence and established BC risk factors using data from 33 studies.
Disclosures: This study was supported by grants from the American Cancer Society and Royal College of Surgeons in Ireland - Medical University of Bahrain (RCSI-MUB Bahrain). The authors declared no conflicts of interest.
Source: Kumar N, Ehsan S, Banerjee S, et al. The unique risk factor profile of triple negative breast cancer: A comprehensive meta-analysis. J Natl Cancer Inst. 2024 (Mar 5). Doi: 10.1093/jnci/djae056 Source
Key clinical point: The risk factors for overall breast cancer (such as parity, menopausal hormone therapy use, and alcohol consumption) did not increase the risk for triple-negative breast cancer (TNBC), which had a distinct risk factor profile.
Major finding: Parity, menopausal hormone therapy use, alcohol consumption, smoking, and higher body mass index were not significantly associated with TNBC risk (all P > .05); instead, family history (odds ratio [OR] 1.55; P < .001), longer duration of oral contraceptive use (OR 1.29; P < .001), and higher breast density (OR 2.19; P < .001) were significantly associated with an increased risk for TNBC.
Study details: This meta-analysis evaluated the association between TNBC incidence and established BC risk factors using data from 33 studies.
Disclosures: This study was supported by grants from the American Cancer Society and Royal College of Surgeons in Ireland - Medical University of Bahrain (RCSI-MUB Bahrain). The authors declared no conflicts of interest.
Source: Kumar N, Ehsan S, Banerjee S, et al. The unique risk factor profile of triple negative breast cancer: A comprehensive meta-analysis. J Natl Cancer Inst. 2024 (Mar 5). Doi: 10.1093/jnci/djae056 Source
Key clinical point: The risk factors for overall breast cancer (such as parity, menopausal hormone therapy use, and alcohol consumption) did not increase the risk for triple-negative breast cancer (TNBC), which had a distinct risk factor profile.
Major finding: Parity, menopausal hormone therapy use, alcohol consumption, smoking, and higher body mass index were not significantly associated with TNBC risk (all P > .05); instead, family history (odds ratio [OR] 1.55; P < .001), longer duration of oral contraceptive use (OR 1.29; P < .001), and higher breast density (OR 2.19; P < .001) were significantly associated with an increased risk for TNBC.
Study details: This meta-analysis evaluated the association between TNBC incidence and established BC risk factors using data from 33 studies.
Disclosures: This study was supported by grants from the American Cancer Society and Royal College of Surgeons in Ireland - Medical University of Bahrain (RCSI-MUB Bahrain). The authors declared no conflicts of interest.
Source: Kumar N, Ehsan S, Banerjee S, et al. The unique risk factor profile of triple negative breast cancer: A comprehensive meta-analysis. J Natl Cancer Inst. 2024 (Mar 5). Doi: 10.1093/jnci/djae056 Source
Pro-Vegetarian Diet May Lower Risk for Breast Cancer
Key clinical point: The pro-vegetarian dietary pattern (PDP) was associated with a significantly lower risk for breast cancer (BC) in women, particularly postmenopausal women.
Major finding: Compared with women who had low adherence to PDP (score ≤ 33), the risk for BC was significantly lower among women with moderate adherence to PDP (score 34-38; adjusted odds ratio [aOR] 0.42; P = .003) and in those with high adherence to PDP (score ≥ 39; aOR 0.49; P = .017), with outcomes being similar in the subgroup of postmenopausal women.
Study details: Findings are from a case-control study including women with BC (n = 134) and those without cancer (n = 265).
Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.
Source: Hosseini Y, Hadi Sichani P, Moslemi E, et al. Pro-vegetarian dietary pattern and risk of breast cancer: A case-control study. Breast Cancer Res Treat. 2024 (Feb 28). doi: 10.1007/s10549-024-07243-8 Source
Key clinical point: The pro-vegetarian dietary pattern (PDP) was associated with a significantly lower risk for breast cancer (BC) in women, particularly postmenopausal women.
Major finding: Compared with women who had low adherence to PDP (score ≤ 33), the risk for BC was significantly lower among women with moderate adherence to PDP (score 34-38; adjusted odds ratio [aOR] 0.42; P = .003) and in those with high adherence to PDP (score ≥ 39; aOR 0.49; P = .017), with outcomes being similar in the subgroup of postmenopausal women.
Study details: Findings are from a case-control study including women with BC (n = 134) and those without cancer (n = 265).
Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.
Source: Hosseini Y, Hadi Sichani P, Moslemi E, et al. Pro-vegetarian dietary pattern and risk of breast cancer: A case-control study. Breast Cancer Res Treat. 2024 (Feb 28). doi: 10.1007/s10549-024-07243-8 Source
Key clinical point: The pro-vegetarian dietary pattern (PDP) was associated with a significantly lower risk for breast cancer (BC) in women, particularly postmenopausal women.
Major finding: Compared with women who had low adherence to PDP (score ≤ 33), the risk for BC was significantly lower among women with moderate adherence to PDP (score 34-38; adjusted odds ratio [aOR] 0.42; P = .003) and in those with high adherence to PDP (score ≥ 39; aOR 0.49; P = .017), with outcomes being similar in the subgroup of postmenopausal women.
Study details: Findings are from a case-control study including women with BC (n = 134) and those without cancer (n = 265).
Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.
Source: Hosseini Y, Hadi Sichani P, Moslemi E, et al. Pro-vegetarian dietary pattern and risk of breast cancer: A case-control study. Breast Cancer Res Treat. 2024 (Feb 28). doi: 10.1007/s10549-024-07243-8 Source
Real-World Study Supports Everolimus + Exemestane as HR+/HER2− BC Treatment
Key clinical point: Everolimus + exemestane demonstrated good efficacy and had a manageable safety profile in postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) breast cancer (BC).
Major finding: Everolimus + exemestane led to a median progression-free survival (PFS) of 6.6 months (95% CI 6.3-7.0 months). PFS was more favorable among patients with a greater vs lower body mass index (≥25 vs 20 to <25 kg/m2; P < .0001); however, the survival outcomes were worse among patients with vs without visceral metastases (hazard ratio 1.417; P < .0001). Stomatitis (42.6%) and fatigue (19.8%) were the most frequent adverse events.
Study details: Findings are from a prospective, non-interventional study including 2074 postmenopausal women with HR+/HER2− advanced BC who received everolimus + exemestane.
Disclosures: This study was funded by Novartis Deutschland GmbH, Germany. Two authors declared being employees of or holding stocks in Novartis. Some authors declared receiving honoraria or personal fees or having other ties with Novartis and various other sources. Eight authors declared no conflicts of interest.
Source: Lüftner D, Schuetz F, Schneeweiss A, et al. Efficacy and safety of everolimus plus exemestane in patients with hormone receptor-positive, HER-2-negative advanced breast cancer: Results from the open-label, multicentre, non-interventional BRAWO study. Int J Cancer. 2024 (Mar 6). doi: 10.1002/ijc.34912 Source
Key clinical point: Everolimus + exemestane demonstrated good efficacy and had a manageable safety profile in postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) breast cancer (BC).
Major finding: Everolimus + exemestane led to a median progression-free survival (PFS) of 6.6 months (95% CI 6.3-7.0 months). PFS was more favorable among patients with a greater vs lower body mass index (≥25 vs 20 to <25 kg/m2; P < .0001); however, the survival outcomes were worse among patients with vs without visceral metastases (hazard ratio 1.417; P < .0001). Stomatitis (42.6%) and fatigue (19.8%) were the most frequent adverse events.
Study details: Findings are from a prospective, non-interventional study including 2074 postmenopausal women with HR+/HER2− advanced BC who received everolimus + exemestane.
Disclosures: This study was funded by Novartis Deutschland GmbH, Germany. Two authors declared being employees of or holding stocks in Novartis. Some authors declared receiving honoraria or personal fees or having other ties with Novartis and various other sources. Eight authors declared no conflicts of interest.
Source: Lüftner D, Schuetz F, Schneeweiss A, et al. Efficacy and safety of everolimus plus exemestane in patients with hormone receptor-positive, HER-2-negative advanced breast cancer: Results from the open-label, multicentre, non-interventional BRAWO study. Int J Cancer. 2024 (Mar 6). doi: 10.1002/ijc.34912 Source
Key clinical point: Everolimus + exemestane demonstrated good efficacy and had a manageable safety profile in postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) breast cancer (BC).
Major finding: Everolimus + exemestane led to a median progression-free survival (PFS) of 6.6 months (95% CI 6.3-7.0 months). PFS was more favorable among patients with a greater vs lower body mass index (≥25 vs 20 to <25 kg/m2; P < .0001); however, the survival outcomes were worse among patients with vs without visceral metastases (hazard ratio 1.417; P < .0001). Stomatitis (42.6%) and fatigue (19.8%) were the most frequent adverse events.
Study details: Findings are from a prospective, non-interventional study including 2074 postmenopausal women with HR+/HER2− advanced BC who received everolimus + exemestane.
Disclosures: This study was funded by Novartis Deutschland GmbH, Germany. Two authors declared being employees of or holding stocks in Novartis. Some authors declared receiving honoraria or personal fees or having other ties with Novartis and various other sources. Eight authors declared no conflicts of interest.
Source: Lüftner D, Schuetz F, Schneeweiss A, et al. Efficacy and safety of everolimus plus exemestane in patients with hormone receptor-positive, HER-2-negative advanced breast cancer: Results from the open-label, multicentre, non-interventional BRAWO study. Int J Cancer. 2024 (Mar 6). doi: 10.1002/ijc.34912 Source
Axillary Lymph Node Dissection Can Be Safely Skipped in Breast Cancer Patients Undergoing Mastectomy
Key clinical point: Sentinel lymph node biopsy (SLNB), a less invasive strategy, resulted in comparable survival and regional disease control as axillary lymph node dissection (ALND) in patients with sentinel node-positive early breast cancer (BC) who underwent total mastectomy (TM).
Major finding: There were no significant differences in 5-year ipsilateral locoregional recurrence-free survival (LRRFS; P = .21), 5-year distant metastasis-free survival (P = .96), and disease-free survival (P > .05) between the SLNB-alone and ALND groups. However, receipt vs no receipt of radiation therapy improved local disease control in the SLNB group (5-year LRRFS; 100.0% vs 92.9%; P = .02).
Study details: Findings are from a retrospective study including 643 patients with early BC with 1-3 metastatic sentinel lymph nodes who underwent total mastectomy, of which 237 and 406 patients underwent SLNB alone and completion ALND, respectively.
Disclosures: The open access funding for this study was enabled and organized by Seoul National University. The authors declared no conflicts of interest.
Source: Chun JW, Kang E, Kim H-K, et al. Oncological safety of skipping axillary lymph node dissection in patients with clinical N0, sentinel node-positive breast cancer undergoing total mastectomy. Ann Surg Oncol. 2024 (Feb 17). doi: 10.1245/s10434-024-15049-7 Source
Key clinical point: Sentinel lymph node biopsy (SLNB), a less invasive strategy, resulted in comparable survival and regional disease control as axillary lymph node dissection (ALND) in patients with sentinel node-positive early breast cancer (BC) who underwent total mastectomy (TM).
Major finding: There were no significant differences in 5-year ipsilateral locoregional recurrence-free survival (LRRFS; P = .21), 5-year distant metastasis-free survival (P = .96), and disease-free survival (P > .05) between the SLNB-alone and ALND groups. However, receipt vs no receipt of radiation therapy improved local disease control in the SLNB group (5-year LRRFS; 100.0% vs 92.9%; P = .02).
Study details: Findings are from a retrospective study including 643 patients with early BC with 1-3 metastatic sentinel lymph nodes who underwent total mastectomy, of which 237 and 406 patients underwent SLNB alone and completion ALND, respectively.
Disclosures: The open access funding for this study was enabled and organized by Seoul National University. The authors declared no conflicts of interest.
Source: Chun JW, Kang E, Kim H-K, et al. Oncological safety of skipping axillary lymph node dissection in patients with clinical N0, sentinel node-positive breast cancer undergoing total mastectomy. Ann Surg Oncol. 2024 (Feb 17). doi: 10.1245/s10434-024-15049-7 Source
Key clinical point: Sentinel lymph node biopsy (SLNB), a less invasive strategy, resulted in comparable survival and regional disease control as axillary lymph node dissection (ALND) in patients with sentinel node-positive early breast cancer (BC) who underwent total mastectomy (TM).
Major finding: There were no significant differences in 5-year ipsilateral locoregional recurrence-free survival (LRRFS; P = .21), 5-year distant metastasis-free survival (P = .96), and disease-free survival (P > .05) between the SLNB-alone and ALND groups. However, receipt vs no receipt of radiation therapy improved local disease control in the SLNB group (5-year LRRFS; 100.0% vs 92.9%; P = .02).
Study details: Findings are from a retrospective study including 643 patients with early BC with 1-3 metastatic sentinel lymph nodes who underwent total mastectomy, of which 237 and 406 patients underwent SLNB alone and completion ALND, respectively.
Disclosures: The open access funding for this study was enabled and organized by Seoul National University. The authors declared no conflicts of interest.
Source: Chun JW, Kang E, Kim H-K, et al. Oncological safety of skipping axillary lymph node dissection in patients with clinical N0, sentinel node-positive breast cancer undergoing total mastectomy. Ann Surg Oncol. 2024 (Feb 17). doi: 10.1245/s10434-024-15049-7 Source
Obesity and Family History of Cancer Raise Breast Cancer Risk
Key clinical point: The coexistence of obesity and family history of cancer significantly increased the risk for breast cancer (BC) in women, suggesting that weight management is important in women with a family history of cancer.
Major finding: The risk for BC was significantly higher in women with vs without a family history of BC (adjusted hazard ratio [aHR] 1.63; 95% CI 1.22-2.49). The risk was further elevated in women with a body mass index (BMI) ≥ 24 kg/m2 and a family history of cancer vs women with BMI < 24 kg/m2 and no family history of cancer (adjusted hazard ratio 2.06; 95% CI 1.39-3.06).
Study details: Findings are from a population-based prospective cohort study that included 15,055 women, of which 4210 women had a family history of cancer.
Disclosures: This study was supported by the Nature Science Foundation of Minhang district, Shanghai, China. The authors declared no conflicts of interest.
Source: Cao J, Li J, Zhang Z, et al. Interaction between body mass index and family history of cancer on the risk of female breast cancer. Sci Rep. 2024;14:4927 (Feb 28). doi: 10.1038/s41598-024-54762-x Source
Key clinical point: The coexistence of obesity and family history of cancer significantly increased the risk for breast cancer (BC) in women, suggesting that weight management is important in women with a family history of cancer.
Major finding: The risk for BC was significantly higher in women with vs without a family history of BC (adjusted hazard ratio [aHR] 1.63; 95% CI 1.22-2.49). The risk was further elevated in women with a body mass index (BMI) ≥ 24 kg/m2 and a family history of cancer vs women with BMI < 24 kg/m2 and no family history of cancer (adjusted hazard ratio 2.06; 95% CI 1.39-3.06).
Study details: Findings are from a population-based prospective cohort study that included 15,055 women, of which 4210 women had a family history of cancer.
Disclosures: This study was supported by the Nature Science Foundation of Minhang district, Shanghai, China. The authors declared no conflicts of interest.
Source: Cao J, Li J, Zhang Z, et al. Interaction between body mass index and family history of cancer on the risk of female breast cancer. Sci Rep. 2024;14:4927 (Feb 28). doi: 10.1038/s41598-024-54762-x Source
Key clinical point: The coexistence of obesity and family history of cancer significantly increased the risk for breast cancer (BC) in women, suggesting that weight management is important in women with a family history of cancer.
Major finding: The risk for BC was significantly higher in women with vs without a family history of BC (adjusted hazard ratio [aHR] 1.63; 95% CI 1.22-2.49). The risk was further elevated in women with a body mass index (BMI) ≥ 24 kg/m2 and a family history of cancer vs women with BMI < 24 kg/m2 and no family history of cancer (adjusted hazard ratio 2.06; 95% CI 1.39-3.06).
Study details: Findings are from a population-based prospective cohort study that included 15,055 women, of which 4210 women had a family history of cancer.
Disclosures: This study was supported by the Nature Science Foundation of Minhang district, Shanghai, China. The authors declared no conflicts of interest.
Source: Cao J, Li J, Zhang Z, et al. Interaction between body mass index and family history of cancer on the risk of female breast cancer. Sci Rep. 2024;14:4927 (Feb 28). doi: 10.1038/s41598-024-54762-x Source
Breast-Conserving Surgery Does Not Increase Locoregional Recurrence in TNBC
Key clinical point: Compared with mastectomy, breast-conserving surgery (BCS) led to comparable locoregional recurrence (LRR; the first relapse site) events along with improved survival outcomes in patients with early-stage node-negative triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy.
Major finding: BCS vs mastectomy following neoadjuvant chemotherapy did not increase LRR (P = .5209) and was significantly associated with improved disease-free survival (adjusted hazard ratio [aHR] 0.51; P < .001) and overall survival (aHR 0.43; P < .001). Absence of pathologic complete response was the only determinant for worsened LRR risk (HR 2.22; P = .001).
Study details: This retrospective analysis of eight prospective trials included 1074 neoadjuvant chemotherapy-treated patients with early-stage node-negative TNBC and available surgery data.
Disclosures: This study received financial support from Deutschen Forschungsgemeinschaft (DFG) within the funding program Open Access Publikationskosten. Three authors declared being employees of GBG Forschungs GmbH. Ninel authors declared receiving honoraria, grants, consulting fees, or personal fees or having other ties with various sources. The other authors had no conflicts to declare.
Source: Krug D, Vladimirova V, Untch M, et al. Breast-conserving surgery is not associated with increased local recurrence in patients with early-stage node-negative triple-negative breast cancer treated with neoadjuvant chemotherapy. Breast. 2024;74:103701 (Feb 24). doi: 10.1016/j.breast.2024.103701 Source
Key clinical point: Compared with mastectomy, breast-conserving surgery (BCS) led to comparable locoregional recurrence (LRR; the first relapse site) events along with improved survival outcomes in patients with early-stage node-negative triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy.
Major finding: BCS vs mastectomy following neoadjuvant chemotherapy did not increase LRR (P = .5209) and was significantly associated with improved disease-free survival (adjusted hazard ratio [aHR] 0.51; P < .001) and overall survival (aHR 0.43; P < .001). Absence of pathologic complete response was the only determinant for worsened LRR risk (HR 2.22; P = .001).
Study details: This retrospective analysis of eight prospective trials included 1074 neoadjuvant chemotherapy-treated patients with early-stage node-negative TNBC and available surgery data.
Disclosures: This study received financial support from Deutschen Forschungsgemeinschaft (DFG) within the funding program Open Access Publikationskosten. Three authors declared being employees of GBG Forschungs GmbH. Ninel authors declared receiving honoraria, grants, consulting fees, or personal fees or having other ties with various sources. The other authors had no conflicts to declare.
Source: Krug D, Vladimirova V, Untch M, et al. Breast-conserving surgery is not associated with increased local recurrence in patients with early-stage node-negative triple-negative breast cancer treated with neoadjuvant chemotherapy. Breast. 2024;74:103701 (Feb 24). doi: 10.1016/j.breast.2024.103701 Source
Key clinical point: Compared with mastectomy, breast-conserving surgery (BCS) led to comparable locoregional recurrence (LRR; the first relapse site) events along with improved survival outcomes in patients with early-stage node-negative triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy.
Major finding: BCS vs mastectomy following neoadjuvant chemotherapy did not increase LRR (P = .5209) and was significantly associated with improved disease-free survival (adjusted hazard ratio [aHR] 0.51; P < .001) and overall survival (aHR 0.43; P < .001). Absence of pathologic complete response was the only determinant for worsened LRR risk (HR 2.22; P = .001).
Study details: This retrospective analysis of eight prospective trials included 1074 neoadjuvant chemotherapy-treated patients with early-stage node-negative TNBC and available surgery data.
Disclosures: This study received financial support from Deutschen Forschungsgemeinschaft (DFG) within the funding program Open Access Publikationskosten. Three authors declared being employees of GBG Forschungs GmbH. Ninel authors declared receiving honoraria, grants, consulting fees, or personal fees or having other ties with various sources. The other authors had no conflicts to declare.
Source: Krug D, Vladimirova V, Untch M, et al. Breast-conserving surgery is not associated with increased local recurrence in patients with early-stage node-negative triple-negative breast cancer treated with neoadjuvant chemotherapy. Breast. 2024;74:103701 (Feb 24). doi: 10.1016/j.breast.2024.103701 Source