Osteoporosis

Osteoporosis treatment with abaloparatide in postmenopausal women does not lead to increased cardiovascular risk, according to a post hoc analysis of the pivotal ACTIVE and ACTIVExtend trials.

iStock/Thinkstock

“Neither treatment with abaloparatide or teriparatide was associated with an increase in serious cardiac [adverse events],” wrote Felicia Cosman, MD, of Columbia University, New York, and coauthors. The study was published in the Journal of Clinical Endocrinology.

To assess the cardiovascular safety profile of abaloparatide, a synthetic analogue of parathyroid hormone–related peptide, the researchers analyzed data on heart rate, blood pressure and cardiovascular-related adverse events (AEs) from patients taking part in the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial and its ACTIVExtend extension study.

The 2,460 participants in the ACTIVE trial were postmenopausal women between the ages of 49 and 86 years with osteoporosis; they were given 80 mcg of daily subcutaneous abaloparatide, 20 mcg of open-label daily subcutaneous teriparatide, or placebo in roughly equal numbers for 18 months. After a 1-month treatment-free period, 1,133 eligible participants from either the abaloparatide or placebo groups were enrolled in ACTIVExtend and given 70 mg of open-label alendronate once a week for 24 months. Because heart rate was only assessed pre- and post dose in the ACTIVE trial, an additional pharmacology study of abaloparatide involving 55 healthy volunteers (32 men and 23 women) was undertaken. After a dose of either abaloparatide or placebo, heart rate was measured at 15, 30, and 45 minutes and 1, 1.5, 2, 2.5, 4, 6, 8, and 12 hours.

Overall, treatment-emergent AEs were higher in the abaloparatide (165, 20.1%) and teriparatide (106, 13%) groups, compared with placebo (74, 9%), as were AEs that led to discontinuation of the study and were potentially associated with changes in heart rate or BP (27 in abaloparatide, 11 in teriparatide, and 5 in placebo). However, the percentage of patients with serious cardiac AEs was similar across groups (1%, 1%, and 0.9%, respectively).

During the ACTIVE trial, major cardiac adverse events plus heart failure were more common in the placebo group (1.7%) than the abaloparatide (0.5%) or teriparatide (0.6%) groups. During ACTIVExtend, major cardiac adverse plus heart failure were similarly common in the abaloparatide/alendronate (1.6%) and the placebo/alendronate (1.6%) groups.

On day 1 of treatment during ACTIVE, the mean change in heart rate from pretreatment to an hour post treatment was 7.9 bpm, 5.3 bpm, and 1.2 bpm for abaloparatide, teriparatide, and placebo, respectively (P < .0001 for abaloparatide and teriparatide vs. placebo; P < .05 for abaloparatide vs. teriparatide).

Subsequent visits saw similar changes. The mean maximum heart rate at 1 hour post dose was 80.7 bpm for abaloparatide, 79.0 bpm for teriparatide, and 73.7 bpm for placebo (P < .0001 for abaloparatide and teriparatide vs. placebo; P < .01 for abaloparatide vs. teriparatide). In the study of healthy volunteers, HR peaked at 15 minutes after dosing and then declined, resolving within 2.5-4 hours.

From predose to 1 hour post dose, small but significant decreases were observed in mean supine systolic and diastolic BP across groups (–2.7/–3.6 mm Hg with abaloparatide, –2.0/–3.6 with teriparatide, –1.5/–2.3 with placebo). During the first year of ACTIVE, the mean maximal decrease in BP from predose to 1 hour post dose was slightly higher (1-2 mm Hg) in the abaloparatide and teriparatide groups, compared with the placebo group (P < .05).

The authors acknowledged their study’s limitations, including the analysis of major cardiac adverse plus heart failure in ACTIVE being limited because of a low number of events and the trial not being designed in that regard.

Abaloparatide was approved by the Food and Drug Administration in 2017 on the basis of results from the ACTIVE and ACTIVExtend trials showing significant reductions in new vertebral and nonvertebral fractures, compared with placebo.

The analysis was partially funded by Radius Health. Its authors acknowledged numerous potential conflicts of interest, including receiving grants and research support from various organizations and pharmaceutical companies.

SOURCE: Cosman F et al. J Clin Endocrinol Metab. 2020 Jul 13. doi: 10.1210/clinem/dgaa450.

Osteoporosis treatment with abaloparatide in postmenopausal women does not lead to increased cardiovascular risk, according to a post hoc analysis of the pivotal ACTIVE and ACTIVExtend trials.

iStock/Thinkstock

“Neither treatment with abaloparatide or teriparatide was associated with an increase in serious cardiac [adverse events],” wrote Felicia Cosman, MD, of Columbia University, New York, and coauthors. The study was published in the Journal of Clinical Endocrinology.

To assess the cardiovascular safety profile of abaloparatide, a synthetic analogue of parathyroid hormone–related peptide, the researchers analyzed data on heart rate, blood pressure and cardiovascular-related adverse events (AEs) from patients taking part in the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial and its ACTIVExtend extension study.

The 2,460 participants in the ACTIVE trial were postmenopausal women between the ages of 49 and 86 years with osteoporosis; they were given 80 mcg of daily subcutaneous abaloparatide, 20 mcg of open-label daily subcutaneous teriparatide, or placebo in roughly equal numbers for 18 months. After a 1-month treatment-free period, 1,133 eligible participants from either the abaloparatide or placebo groups were enrolled in ACTIVExtend and given 70 mg of open-label alendronate once a week for 24 months. Because heart rate was only assessed pre- and post dose in the ACTIVE trial, an additional pharmacology study of abaloparatide involving 55 healthy volunteers (32 men and 23 women) was undertaken. After a dose of either abaloparatide or placebo, heart rate was measured at 15, 30, and 45 minutes and 1, 1.5, 2, 2.5, 4, 6, 8, and 12 hours.

Overall, treatment-emergent AEs were higher in the abaloparatide (165, 20.1%) and teriparatide (106, 13%) groups, compared with placebo (74, 9%), as were AEs that led to discontinuation of the study and were potentially associated with changes in heart rate or BP (27 in abaloparatide, 11 in teriparatide, and 5 in placebo). However, the percentage of patients with serious cardiac AEs was similar across groups (1%, 1%, and 0.9%, respectively).

During the ACTIVE trial, major cardiac adverse events plus heart failure were more common in the placebo group (1.7%) than the abaloparatide (0.5%) or teriparatide (0.6%) groups. During ACTIVExtend, major cardiac adverse plus heart failure were similarly common in the abaloparatide/alendronate (1.6%) and the placebo/alendronate (1.6%) groups.

On day 1 of treatment during ACTIVE, the mean change in heart rate from pretreatment to an hour post treatment was 7.9 bpm, 5.3 bpm, and 1.2 bpm for abaloparatide, teriparatide, and placebo, respectively (P < .0001 for abaloparatide and teriparatide vs. placebo; P < .05 for abaloparatide vs. teriparatide).

Subsequent visits saw similar changes. The mean maximum heart rate at 1 hour post dose was 80.7 bpm for abaloparatide, 79.0 bpm for teriparatide, and 73.7 bpm for placebo (P < .0001 for abaloparatide and teriparatide vs. placebo; P < .01 for abaloparatide vs. teriparatide). In the study of healthy volunteers, HR peaked at 15 minutes after dosing and then declined, resolving within 2.5-4 hours.

From predose to 1 hour post dose, small but significant decreases were observed in mean supine systolic and diastolic BP across groups (–2.7/–3.6 mm Hg with abaloparatide, –2.0/–3.6 with teriparatide, –1.5/–2.3 with placebo). During the first year of ACTIVE, the mean maximal decrease in BP from predose to 1 hour post dose was slightly higher (1-2 mm Hg) in the abaloparatide and teriparatide groups, compared with the placebo group (P < .05).

The authors acknowledged their study’s limitations, including the analysis of major cardiac adverse plus heart failure in ACTIVE being limited because of a low number of events and the trial not being designed in that regard.

Abaloparatide was approved by the Food and Drug Administration in 2017 on the basis of results from the ACTIVE and ACTIVExtend trials showing significant reductions in new vertebral and nonvertebral fractures, compared with placebo.

The analysis was partially funded by Radius Health. Its authors acknowledged numerous potential conflicts of interest, including receiving grants and research support from various organizations and pharmaceutical companies.

SOURCE: Cosman F et al. J Clin Endocrinol Metab. 2020 Jul 13. doi: 10.1210/clinem/dgaa450.

Osteoporosis treatment with abaloparatide in postmenopausal women does not lead to increased cardiovascular risk, according to a post hoc analysis of the pivotal ACTIVE and ACTIVExtend trials.

iStock/Thinkstock

“Neither treatment with abaloparatide or teriparatide was associated with an increase in serious cardiac [adverse events],” wrote Felicia Cosman, MD, of Columbia University, New York, and coauthors. The study was published in the Journal of Clinical Endocrinology.

To assess the cardiovascular safety profile of abaloparatide, a synthetic analogue of parathyroid hormone–related peptide, the researchers analyzed data on heart rate, blood pressure and cardiovascular-related adverse events (AEs) from patients taking part in the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial and its ACTIVExtend extension study.

The 2,460 participants in the ACTIVE trial were postmenopausal women between the ages of 49 and 86 years with osteoporosis; they were given 80 mcg of daily subcutaneous abaloparatide, 20 mcg of open-label daily subcutaneous teriparatide, or placebo in roughly equal numbers for 18 months. After a 1-month treatment-free period, 1,133 eligible participants from either the abaloparatide or placebo groups were enrolled in ACTIVExtend and given 70 mg of open-label alendronate once a week for 24 months. Because heart rate was only assessed pre- and post dose in the ACTIVE trial, an additional pharmacology study of abaloparatide involving 55 healthy volunteers (32 men and 23 women) was undertaken. After a dose of either abaloparatide or placebo, heart rate was measured at 15, 30, and 45 minutes and 1, 1.5, 2, 2.5, 4, 6, 8, and 12 hours.

Overall, treatment-emergent AEs were higher in the abaloparatide (165, 20.1%) and teriparatide (106, 13%) groups, compared with placebo (74, 9%), as were AEs that led to discontinuation of the study and were potentially associated with changes in heart rate or BP (27 in abaloparatide, 11 in teriparatide, and 5 in placebo). However, the percentage of patients with serious cardiac AEs was similar across groups (1%, 1%, and 0.9%, respectively).

During the ACTIVE trial, major cardiac adverse events plus heart failure were more common in the placebo group (1.7%) than the abaloparatide (0.5%) or teriparatide (0.6%) groups. During ACTIVExtend, major cardiac adverse plus heart failure were similarly common in the abaloparatide/alendronate (1.6%) and the placebo/alendronate (1.6%) groups.

On day 1 of treatment during ACTIVE, the mean change in heart rate from pretreatment to an hour post treatment was 7.9 bpm, 5.3 bpm, and 1.2 bpm for abaloparatide, teriparatide, and placebo, respectively (P < .0001 for abaloparatide and teriparatide vs. placebo; P < .05 for abaloparatide vs. teriparatide).

Subsequent visits saw similar changes. The mean maximum heart rate at 1 hour post dose was 80.7 bpm for abaloparatide, 79.0 bpm for teriparatide, and 73.7 bpm for placebo (P < .0001 for abaloparatide and teriparatide vs. placebo; P < .01 for abaloparatide vs. teriparatide). In the study of healthy volunteers, HR peaked at 15 minutes after dosing and then declined, resolving within 2.5-4 hours.

From predose to 1 hour post dose, small but significant decreases were observed in mean supine systolic and diastolic BP across groups (–2.7/–3.6 mm Hg with abaloparatide, –2.0/–3.6 with teriparatide, –1.5/–2.3 with placebo). During the first year of ACTIVE, the mean maximal decrease in BP from predose to 1 hour post dose was slightly higher (1-2 mm Hg) in the abaloparatide and teriparatide groups, compared with the placebo group (P < .05).

The authors acknowledged their study’s limitations, including the analysis of major cardiac adverse plus heart failure in ACTIVE being limited because of a low number of events and the trial not being designed in that regard.

Abaloparatide was approved by the Food and Drug Administration in 2017 on the basis of results from the ACTIVE and ACTIVExtend trials showing significant reductions in new vertebral and nonvertebral fractures, compared with placebo.

The analysis was partially funded by Radius Health. Its authors acknowledged numerous potential conflicts of interest, including receiving grants and research support from various organizations and pharmaceutical companies.

SOURCE: Cosman F et al. J Clin Endocrinol Metab. 2020 Jul 13. doi: 10.1210/clinem/dgaa450.

As the Food and Drug Administration focuses on other issues, companies, both big and small, are looking to boost physician and consumer interest in their “medical foods” – products that fall somewhere between drugs and supplements and promise to mitigate symptoms, or even address underlying pathologies, of a range of diseases.

Manufacturers now market an array of medical foods, ranging from powders and capsules for Alzheimer disease to low-protein spaghetti for chronic kidney disease (CKD). The FDA has not been completely absent; it takes a narrow view of what medical conditions qualify for treatment with food products and has warned some manufacturers that their misbranded products are acting more like unapproved drugs.

By the FDA’s definition, medical food is limited to products that provide crucial therapy for patients with inborn errors of metabolism (IEM). An example is specialized baby formula for infants with phenylketonuria. Unlike supplements, medical foods are supposed to be used under the supervision of a physician. This has prompted some sales reps to turn up in the clinic, and most manufacturers have online approval forms for doctors to sign. Manufacturers, advisers, and regulators were interviewed for a closer look at this burgeoning industry.
 

The market

The global market for medical foods – about $18 billion in 2019 – is expected to grow steadily in the near future. It is drawing more interest, especially in Europe, where medical foods are more accepted by physicians and consumers, Meghan Donnelly, MS, RDN, said in an interview. She is a registered dietitian who conducts physician outreach in the United States for Flavis, a division of Dr. Schär. That company, based in northern Italy, started out targeting IEMs but now also sells gluten-free foods for celiac disease and low-protein foods for CKD.

It is still a niche market in the United States – and isn’t likely to ever approach the size of the supplement market, according to Marcus Charuvastra, the managing director of Targeted Medical Pharma, which markets Theramine capsules for pain management, among many other products. But it could still be a big win for a manufacturer if they get a small slice of a big market, such as for Alzheimer disease.
 

Defining medical food

According to an update of the Orphan Drug Act in 1988, a medical food is “a food which is formulated to be consumed or administered enterally under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation.” The FDA issued regulations to accompany that law in 1993 but has since only issued a guidance document that is not legally binding.

Medical foods are not drugs and they are not supplements (the latter are intended only for healthy people). The FDA doesn’t require formal approval of a medical food, but, by law, the ingredients must be generally recognized as safe, and manufacturers must follow good manufacturing practices. However, the agency has taken a narrow view of what conditions require medical foods.

Policing medical foods hasn’t been a priority for the FDA, which is why there has been a proliferation of products that don’t meet the FDA’s view of the statutory definition of medical foods, according to Miriam Guggenheim, a food and drug law attorney in Washington, D.C. The FDA usually takes enforcement action when it sees a risk to the public’s health.

The agency’s stance has led to confusion – among manufacturers, physicians, consumers, and even regulators – making the market a kind of Wild West, according to Paul Hyman, a Washington, D.C.–based attorney who has represented medical food companies.

George A. Burdock, PhD, an Orlando-based regulatory consultant who has worked with medical food makers, believes the FDA will be forced to expand their narrow definition. He foresees a reconsideration of many medical food products in light of an October 2019 White House executive order prohibiting federal agencies from issuing guidance in lieu of rules.
 

Manufacturers and the FDA differ

One example of a product about which regulators and manufacturers differ is Theramine, which is described as “specially designed to supply the nervous system with the fuel it needs to meet the altered metabolic requirements of chronic pain and inflammatory disorders.”

It is not considered a medical food by the FDA, and the company has had numerous discussions with the agency about their diverging views, according to Mr. Charuvastra. “We’ve had our warning letters and we’ve had our sit downs, and we just had an inspection.”

Targeted Medical Pharma continues to market its products as medical foods but steers away from making any claims that they are like drugs, he said.

Confusion about medical foods has been exposed in the California Workers’ Compensation System by Leslie Wilson, PhD, and colleagues at the University of California, San Francisco. They found that physicians regularly wrote medical food prescriptions for non–FDA-approved uses and that the system reimbursed the majority of the products at a cost of $15.5 million from 2011 to 2013. More than half of these prescriptions were for Theramine.

Dr. Wilson reported that, for most products, no evidence supported effectiveness, and they were frequently mislabeled – for all 36 that were studied, submissions for reimbursement were made using a National Drug Code, an impossibility because medical foods are not drugs, and 14 were labeled “Rx only.”
 

Big-name companies joining in

The FDA does not keep a list of approved medical foods or manufacturers. Both small businesses and big food companies like Danone, Nestlé, and Abbott are players. Most products are sold online.

In the United States, Danone’s Nutricia division sells formulas and low-protein foods for IEMs. They also sell Ketocal, a powder or ready-to-drink liquid that is pitched as a balanced medical food to simplify and optimize the ketogenic diet for children with intractable epilepsy. Yet the FDA does not include epilepsy among the conditions that medical foods can treat.

Nestlé sells traditional medical foods for IEMs and also markets a range of what it calls nutritional therapies for such conditions as irritable bowel syndrome and dysphagia.

Nestlé is a minority shareholder in Axona, a product originally developed by Accera (Cerecin as of 2018). Jacquelyn Campo, senior director of global communications at Nestlé Health Sciences, said that the company is not actively involved in the operations management of Cerecin. However, on its website, Nestlé touts Axona, which is only available in the United States, as a “medical food” that “is intended for the clinical dietary management of mild to moderate Alzheimer disease.” The Axona site claims that the main ingredient, caprylic triglyceride, is broken down into ketones that provide fuel to treat cerebral hypometabolism, a precursor to Alzheimer disease. In a 2009 study, daily dosing of a preliminary formulation was associated with improved cognitive performance compared with placebo in patients with mild to moderate Alzheimer disease.

In 2013, the FDA warned Accera that it was misbranding Axona as a medical food and that the therapeutic claims the company was making would make the product an unapproved drug. Ms. Campo said Nestlé is aware of the agency’s warning, but added, “to our knowledge, Cerecin provided answers to the issues raised by the FDA.”

With the goal of getting drug approval, Accera went on to test a tweaked formulation in a 400-patient randomized, placebo-controlled trial called NOURISH AD that ultimately failed. Nevertheless, Axona is still marketed as a medical food. It costs about $100 for a month’s supply.

Repeated requests for comment from Cerecin were not answered. Danielle Schor, an FDA spokesperson, said the agency will not discuss the status of individual products.
 

More disputes and insurance coverage

Mary Ann DeMarco, executive director of sales and marketing for the Scottsdale, Ariz.–based medical food maker Primus Pharmaceuticals, said the company believes its products fit within the FDA’s medical foods rubric.

These include Fosteum Plus capsules, which it markets “for the clinical dietary management of the metabolic processes of osteopenia and osteoporosis.” The capsules contain a combination of genistein, zinc, calcium, phosphate, vitamin K2, and vitamin D. As proof of effectiveness, the company cites clinical data on some of the ingredients – not the product itself.

Primus has run afoul of the FDA before when it similarly positioned another product, called Limbrel, as a medical food for osteoarthritis. From 2007 to 2017, the FDA received 194 adverse event reports associated with Limbrel, including reports of drug-induced liver injury, pancreatitis, and hypersensitivity pneumonitis. In December 2017, the agency urged Primus to recall Limbrel, a move that it said was “necessary to protect the public health and welfare.” Primus withdrew the product but laid out a defense of Limbrel on a devoted website.

The FDA would not comment any further, said Ms. Schor. Ms. DeMarco said that Primus is working with the FDA to bring Limbrel back to market.

A lack of insurance coverage – even for approved medical foods for IEMs – has frustrated advocates, parents, and manufacturers. They are putting their weight behind the Medical Nutrition Equity Act, which would mandate public and private payer coverage of medical foods for IEMs and digestive conditions such as Crohn disease. That 2019 House bill has 56 cosponsors; there is no Senate companion bill.

“If you can get reimbursement, it really makes the market,” for Primus and the other manufacturers, Mr. Hyman said.

Primus Pharmaceuticals has launched its own campaign, Cover My Medical Foods, to enlist consumers and others to the cause.
 

Partnering with advocates

Although its low-protein breads, pastas, and baking products are not considered medical foods by the FDA, Dr. Schär is marketing them as such in the United States. They are trying to make a mark in CKD, according to Ms. Donnelly. She added that Dr. Schär has been successful in Europe, where nutrition therapy is more integrated in the health care system.

In 2019, Flavis and the National Kidney Foundation joined forces to raise awareness of nutritional interventions and to build enthusiasm for the Flavis products. The partnership has now ended, mostly because Flavis could no longer afford it, according to Ms. Donnelly.

“Information on diet and nutrition is the most requested subject matter from the NKF,” said Anthony Gucciardo, senior vice president of strategic partnerships at the foundation. The partnership “has never been necessarily about promoting their products per se; it’s promoting a healthy diet and really a diet specific for CKD.”

The NKF developed cobranded materials on low-protein foods for physicians and a teaching tool they could use with patients. Consumers could access nutrition information and a discount on Flavis products on a dedicated webpage. The foundation didn’t describe the low-protein products as medical foods, said Mr. Gucciardo, even if Flavis promoted them as such.

In patients with CKD, dietary management can help prevent the progression to end-stage renal disease. Although Medicare covers medical nutrition therapy – in which patients receive personalized assessments and dietary advice – uptake is abysmally low, according to a 2018 study.

Dr. Burdock thinks low-protein foods for CKD do meet the FDA’s criteria for a medical food but that the agency might not necessarily agree with him. The FDA would not comment.
 

Physician beware

When it comes to medical foods, the FDA has often looked the other way because the ingredients may already have been proven safe and the danger to an individual or to the public’s health is relatively low, according to Dr. Burdock and Mr. Hyman.

However, if the agency “feels that a medical food will prevent people from seeking medical care or there is potential to defraud the public, it is justified in taking action against the company,” said Dr. Burdock.

According to Dr. Wilson, the pharmacist who reported on the inappropriate medical food prescriptions in the California system, the FDA could help by creating a list of approved medical foods. Physicians should take time to learn about the difference between medical foods and supplements, she said, adding that they should also not hesitate to “question the veracity of the claims for them.”

Ms. Guggenheim believed doctors need to know that, for the most part, these are not FDA-approved products. She emphasized the importance of evaluating the products and looking at the data of their impact on a disease or condition.

“Many of these companies strongly believe that the products work and help people, so clinicians need to be very data driven,” she said.

A version of this article originally appeared on Medscape.com.

As the Food and Drug Administration focuses on other issues, companies, both big and small, are looking to boost physician and consumer interest in their “medical foods” – products that fall somewhere between drugs and supplements and promise to mitigate symptoms, or even address underlying pathologies, of a range of diseases.

Manufacturers now market an array of medical foods, ranging from powders and capsules for Alzheimer disease to low-protein spaghetti for chronic kidney disease (CKD). The FDA has not been completely absent; it takes a narrow view of what medical conditions qualify for treatment with food products and has warned some manufacturers that their misbranded products are acting more like unapproved drugs.

By the FDA’s definition, medical food is limited to products that provide crucial therapy for patients with inborn errors of metabolism (IEM). An example is specialized baby formula for infants with phenylketonuria. Unlike supplements, medical foods are supposed to be used under the supervision of a physician. This has prompted some sales reps to turn up in the clinic, and most manufacturers have online approval forms for doctors to sign. Manufacturers, advisers, and regulators were interviewed for a closer look at this burgeoning industry.
 

The market

The global market for medical foods – about $18 billion in 2019 – is expected to grow steadily in the near future. It is drawing more interest, especially in Europe, where medical foods are more accepted by physicians and consumers, Meghan Donnelly, MS, RDN, said in an interview. She is a registered dietitian who conducts physician outreach in the United States for Flavis, a division of Dr. Schär. That company, based in northern Italy, started out targeting IEMs but now also sells gluten-free foods for celiac disease and low-protein foods for CKD.

It is still a niche market in the United States – and isn’t likely to ever approach the size of the supplement market, according to Marcus Charuvastra, the managing director of Targeted Medical Pharma, which markets Theramine capsules for pain management, among many other products. But it could still be a big win for a manufacturer if they get a small slice of a big market, such as for Alzheimer disease.
 

Defining medical food

According to an update of the Orphan Drug Act in 1988, a medical food is “a food which is formulated to be consumed or administered enterally under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation.” The FDA issued regulations to accompany that law in 1993 but has since only issued a guidance document that is not legally binding.

Medical foods are not drugs and they are not supplements (the latter are intended only for healthy people). The FDA doesn’t require formal approval of a medical food, but, by law, the ingredients must be generally recognized as safe, and manufacturers must follow good manufacturing practices. However, the agency has taken a narrow view of what conditions require medical foods.

Policing medical foods hasn’t been a priority for the FDA, which is why there has been a proliferation of products that don’t meet the FDA’s view of the statutory definition of medical foods, according to Miriam Guggenheim, a food and drug law attorney in Washington, D.C. The FDA usually takes enforcement action when it sees a risk to the public’s health.

The agency’s stance has led to confusion – among manufacturers, physicians, consumers, and even regulators – making the market a kind of Wild West, according to Paul Hyman, a Washington, D.C.–based attorney who has represented medical food companies.

George A. Burdock, PhD, an Orlando-based regulatory consultant who has worked with medical food makers, believes the FDA will be forced to expand their narrow definition. He foresees a reconsideration of many medical food products in light of an October 2019 White House executive order prohibiting federal agencies from issuing guidance in lieu of rules.
 

Manufacturers and the FDA differ

One example of a product about which regulators and manufacturers differ is Theramine, which is described as “specially designed to supply the nervous system with the fuel it needs to meet the altered metabolic requirements of chronic pain and inflammatory disorders.”

It is not considered a medical food by the FDA, and the company has had numerous discussions with the agency about their diverging views, according to Mr. Charuvastra. “We’ve had our warning letters and we’ve had our sit downs, and we just had an inspection.”

Targeted Medical Pharma continues to market its products as medical foods but steers away from making any claims that they are like drugs, he said.

Confusion about medical foods has been exposed in the California Workers’ Compensation System by Leslie Wilson, PhD, and colleagues at the University of California, San Francisco. They found that physicians regularly wrote medical food prescriptions for non–FDA-approved uses and that the system reimbursed the majority of the products at a cost of $15.5 million from 2011 to 2013. More than half of these prescriptions were for Theramine.

Dr. Wilson reported that, for most products, no evidence supported effectiveness, and they were frequently mislabeled – for all 36 that were studied, submissions for reimbursement were made using a National Drug Code, an impossibility because medical foods are not drugs, and 14 were labeled “Rx only.”
 

Big-name companies joining in

The FDA does not keep a list of approved medical foods or manufacturers. Both small businesses and big food companies like Danone, Nestlé, and Abbott are players. Most products are sold online.

In the United States, Danone’s Nutricia division sells formulas and low-protein foods for IEMs. They also sell Ketocal, a powder or ready-to-drink liquid that is pitched as a balanced medical food to simplify and optimize the ketogenic diet for children with intractable epilepsy. Yet the FDA does not include epilepsy among the conditions that medical foods can treat.

Nestlé sells traditional medical foods for IEMs and also markets a range of what it calls nutritional therapies for such conditions as irritable bowel syndrome and dysphagia.

Nestlé is a minority shareholder in Axona, a product originally developed by Accera (Cerecin as of 2018). Jacquelyn Campo, senior director of global communications at Nestlé Health Sciences, said that the company is not actively involved in the operations management of Cerecin. However, on its website, Nestlé touts Axona, which is only available in the United States, as a “medical food” that “is intended for the clinical dietary management of mild to moderate Alzheimer disease.” The Axona site claims that the main ingredient, caprylic triglyceride, is broken down into ketones that provide fuel to treat cerebral hypometabolism, a precursor to Alzheimer disease. In a 2009 study, daily dosing of a preliminary formulation was associated with improved cognitive performance compared with placebo in patients with mild to moderate Alzheimer disease.

In 2013, the FDA warned Accera that it was misbranding Axona as a medical food and that the therapeutic claims the company was making would make the product an unapproved drug. Ms. Campo said Nestlé is aware of the agency’s warning, but added, “to our knowledge, Cerecin provided answers to the issues raised by the FDA.”

With the goal of getting drug approval, Accera went on to test a tweaked formulation in a 400-patient randomized, placebo-controlled trial called NOURISH AD that ultimately failed. Nevertheless, Axona is still marketed as a medical food. It costs about $100 for a month’s supply.

Repeated requests for comment from Cerecin were not answered. Danielle Schor, an FDA spokesperson, said the agency will not discuss the status of individual products.
 

More disputes and insurance coverage

Mary Ann DeMarco, executive director of sales and marketing for the Scottsdale, Ariz.–based medical food maker Primus Pharmaceuticals, said the company believes its products fit within the FDA’s medical foods rubric.

These include Fosteum Plus capsules, which it markets “for the clinical dietary management of the metabolic processes of osteopenia and osteoporosis.” The capsules contain a combination of genistein, zinc, calcium, phosphate, vitamin K2, and vitamin D. As proof of effectiveness, the company cites clinical data on some of the ingredients – not the product itself.

Primus has run afoul of the FDA before when it similarly positioned another product, called Limbrel, as a medical food for osteoarthritis. From 2007 to 2017, the FDA received 194 adverse event reports associated with Limbrel, including reports of drug-induced liver injury, pancreatitis, and hypersensitivity pneumonitis. In December 2017, the agency urged Primus to recall Limbrel, a move that it said was “necessary to protect the public health and welfare.” Primus withdrew the product but laid out a defense of Limbrel on a devoted website.

The FDA would not comment any further, said Ms. Schor. Ms. DeMarco said that Primus is working with the FDA to bring Limbrel back to market.

A lack of insurance coverage – even for approved medical foods for IEMs – has frustrated advocates, parents, and manufacturers. They are putting their weight behind the Medical Nutrition Equity Act, which would mandate public and private payer coverage of medical foods for IEMs and digestive conditions such as Crohn disease. That 2019 House bill has 56 cosponsors; there is no Senate companion bill.

“If you can get reimbursement, it really makes the market,” for Primus and the other manufacturers, Mr. Hyman said.

Primus Pharmaceuticals has launched its own campaign, Cover My Medical Foods, to enlist consumers and others to the cause.
 

Partnering with advocates

Although its low-protein breads, pastas, and baking products are not considered medical foods by the FDA, Dr. Schär is marketing them as such in the United States. They are trying to make a mark in CKD, according to Ms. Donnelly. She added that Dr. Schär has been successful in Europe, where nutrition therapy is more integrated in the health care system.

In 2019, Flavis and the National Kidney Foundation joined forces to raise awareness of nutritional interventions and to build enthusiasm for the Flavis products. The partnership has now ended, mostly because Flavis could no longer afford it, according to Ms. Donnelly.

“Information on diet and nutrition is the most requested subject matter from the NKF,” said Anthony Gucciardo, senior vice president of strategic partnerships at the foundation. The partnership “has never been necessarily about promoting their products per se; it’s promoting a healthy diet and really a diet specific for CKD.”

The NKF developed cobranded materials on low-protein foods for physicians and a teaching tool they could use with patients. Consumers could access nutrition information and a discount on Flavis products on a dedicated webpage. The foundation didn’t describe the low-protein products as medical foods, said Mr. Gucciardo, even if Flavis promoted them as such.

In patients with CKD, dietary management can help prevent the progression to end-stage renal disease. Although Medicare covers medical nutrition therapy – in which patients receive personalized assessments and dietary advice – uptake is abysmally low, according to a 2018 study.

Dr. Burdock thinks low-protein foods for CKD do meet the FDA’s criteria for a medical food but that the agency might not necessarily agree with him. The FDA would not comment.
 

Physician beware

When it comes to medical foods, the FDA has often looked the other way because the ingredients may already have been proven safe and the danger to an individual or to the public’s health is relatively low, according to Dr. Burdock and Mr. Hyman.

However, if the agency “feels that a medical food will prevent people from seeking medical care or there is potential to defraud the public, it is justified in taking action against the company,” said Dr. Burdock.

According to Dr. Wilson, the pharmacist who reported on the inappropriate medical food prescriptions in the California system, the FDA could help by creating a list of approved medical foods. Physicians should take time to learn about the difference between medical foods and supplements, she said, adding that they should also not hesitate to “question the veracity of the claims for them.”

Ms. Guggenheim believed doctors need to know that, for the most part, these are not FDA-approved products. She emphasized the importance of evaluating the products and looking at the data of their impact on a disease or condition.

“Many of these companies strongly believe that the products work and help people, so clinicians need to be very data driven,” she said.

A version of this article originally appeared on Medscape.com.

As the Food and Drug Administration focuses on other issues, companies, both big and small, are looking to boost physician and consumer interest in their “medical foods” – products that fall somewhere between drugs and supplements and promise to mitigate symptoms, or even address underlying pathologies, of a range of diseases.

Manufacturers now market an array of medical foods, ranging from powders and capsules for Alzheimer disease to low-protein spaghetti for chronic kidney disease (CKD). The FDA has not been completely absent; it takes a narrow view of what medical conditions qualify for treatment with food products and has warned some manufacturers that their misbranded products are acting more like unapproved drugs.

By the FDA’s definition, medical food is limited to products that provide crucial therapy for patients with inborn errors of metabolism (IEM). An example is specialized baby formula for infants with phenylketonuria. Unlike supplements, medical foods are supposed to be used under the supervision of a physician. This has prompted some sales reps to turn up in the clinic, and most manufacturers have online approval forms for doctors to sign. Manufacturers, advisers, and regulators were interviewed for a closer look at this burgeoning industry.
 

The market

The global market for medical foods – about $18 billion in 2019 – is expected to grow steadily in the near future. It is drawing more interest, especially in Europe, where medical foods are more accepted by physicians and consumers, Meghan Donnelly, MS, RDN, said in an interview. She is a registered dietitian who conducts physician outreach in the United States for Flavis, a division of Dr. Schär. That company, based in northern Italy, started out targeting IEMs but now also sells gluten-free foods for celiac disease and low-protein foods for CKD.

It is still a niche market in the United States – and isn’t likely to ever approach the size of the supplement market, according to Marcus Charuvastra, the managing director of Targeted Medical Pharma, which markets Theramine capsules for pain management, among many other products. But it could still be a big win for a manufacturer if they get a small slice of a big market, such as for Alzheimer disease.
 

Defining medical food

According to an update of the Orphan Drug Act in 1988, a medical food is “a food which is formulated to be consumed or administered enterally under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation.” The FDA issued regulations to accompany that law in 1993 but has since only issued a guidance document that is not legally binding.

Medical foods are not drugs and they are not supplements (the latter are intended only for healthy people). The FDA doesn’t require formal approval of a medical food, but, by law, the ingredients must be generally recognized as safe, and manufacturers must follow good manufacturing practices. However, the agency has taken a narrow view of what conditions require medical foods.

Policing medical foods hasn’t been a priority for the FDA, which is why there has been a proliferation of products that don’t meet the FDA’s view of the statutory definition of medical foods, according to Miriam Guggenheim, a food and drug law attorney in Washington, D.C. The FDA usually takes enforcement action when it sees a risk to the public’s health.

The agency’s stance has led to confusion – among manufacturers, physicians, consumers, and even regulators – making the market a kind of Wild West, according to Paul Hyman, a Washington, D.C.–based attorney who has represented medical food companies.

George A. Burdock, PhD, an Orlando-based regulatory consultant who has worked with medical food makers, believes the FDA will be forced to expand their narrow definition. He foresees a reconsideration of many medical food products in light of an October 2019 White House executive order prohibiting federal agencies from issuing guidance in lieu of rules.
 

Manufacturers and the FDA differ

One example of a product about which regulators and manufacturers differ is Theramine, which is described as “specially designed to supply the nervous system with the fuel it needs to meet the altered metabolic requirements of chronic pain and inflammatory disorders.”

It is not considered a medical food by the FDA, and the company has had numerous discussions with the agency about their diverging views, according to Mr. Charuvastra. “We’ve had our warning letters and we’ve had our sit downs, and we just had an inspection.”

Targeted Medical Pharma continues to market its products as medical foods but steers away from making any claims that they are like drugs, he said.

Confusion about medical foods has been exposed in the California Workers’ Compensation System by Leslie Wilson, PhD, and colleagues at the University of California, San Francisco. They found that physicians regularly wrote medical food prescriptions for non–FDA-approved uses and that the system reimbursed the majority of the products at a cost of $15.5 million from 2011 to 2013. More than half of these prescriptions were for Theramine.

Dr. Wilson reported that, for most products, no evidence supported effectiveness, and they were frequently mislabeled – for all 36 that were studied, submissions for reimbursement were made using a National Drug Code, an impossibility because medical foods are not drugs, and 14 were labeled “Rx only.”
 

Big-name companies joining in

The FDA does not keep a list of approved medical foods or manufacturers. Both small businesses and big food companies like Danone, Nestlé, and Abbott are players. Most products are sold online.

In the United States, Danone’s Nutricia division sells formulas and low-protein foods for IEMs. They also sell Ketocal, a powder or ready-to-drink liquid that is pitched as a balanced medical food to simplify and optimize the ketogenic diet for children with intractable epilepsy. Yet the FDA does not include epilepsy among the conditions that medical foods can treat.

Nestlé sells traditional medical foods for IEMs and also markets a range of what it calls nutritional therapies for such conditions as irritable bowel syndrome and dysphagia.

Nestlé is a minority shareholder in Axona, a product originally developed by Accera (Cerecin as of 2018). Jacquelyn Campo, senior director of global communications at Nestlé Health Sciences, said that the company is not actively involved in the operations management of Cerecin. However, on its website, Nestlé touts Axona, which is only available in the United States, as a “medical food” that “is intended for the clinical dietary management of mild to moderate Alzheimer disease.” The Axona site claims that the main ingredient, caprylic triglyceride, is broken down into ketones that provide fuel to treat cerebral hypometabolism, a precursor to Alzheimer disease. In a 2009 study, daily dosing of a preliminary formulation was associated with improved cognitive performance compared with placebo in patients with mild to moderate Alzheimer disease.

In 2013, the FDA warned Accera that it was misbranding Axona as a medical food and that the therapeutic claims the company was making would make the product an unapproved drug. Ms. Campo said Nestlé is aware of the agency’s warning, but added, “to our knowledge, Cerecin provided answers to the issues raised by the FDA.”

With the goal of getting drug approval, Accera went on to test a tweaked formulation in a 400-patient randomized, placebo-controlled trial called NOURISH AD that ultimately failed. Nevertheless, Axona is still marketed as a medical food. It costs about $100 for a month’s supply.

Repeated requests for comment from Cerecin were not answered. Danielle Schor, an FDA spokesperson, said the agency will not discuss the status of individual products.
 

More disputes and insurance coverage

Mary Ann DeMarco, executive director of sales and marketing for the Scottsdale, Ariz.–based medical food maker Primus Pharmaceuticals, said the company believes its products fit within the FDA’s medical foods rubric.

These include Fosteum Plus capsules, which it markets “for the clinical dietary management of the metabolic processes of osteopenia and osteoporosis.” The capsules contain a combination of genistein, zinc, calcium, phosphate, vitamin K2, and vitamin D. As proof of effectiveness, the company cites clinical data on some of the ingredients – not the product itself.

Primus has run afoul of the FDA before when it similarly positioned another product, called Limbrel, as a medical food for osteoarthritis. From 2007 to 2017, the FDA received 194 adverse event reports associated with Limbrel, including reports of drug-induced liver injury, pancreatitis, and hypersensitivity pneumonitis. In December 2017, the agency urged Primus to recall Limbrel, a move that it said was “necessary to protect the public health and welfare.” Primus withdrew the product but laid out a defense of Limbrel on a devoted website.

The FDA would not comment any further, said Ms. Schor. Ms. DeMarco said that Primus is working with the FDA to bring Limbrel back to market.

A lack of insurance coverage – even for approved medical foods for IEMs – has frustrated advocates, parents, and manufacturers. They are putting their weight behind the Medical Nutrition Equity Act, which would mandate public and private payer coverage of medical foods for IEMs and digestive conditions such as Crohn disease. That 2019 House bill has 56 cosponsors; there is no Senate companion bill.

“If you can get reimbursement, it really makes the market,” for Primus and the other manufacturers, Mr. Hyman said.

Primus Pharmaceuticals has launched its own campaign, Cover My Medical Foods, to enlist consumers and others to the cause.
 

Partnering with advocates

Although its low-protein breads, pastas, and baking products are not considered medical foods by the FDA, Dr. Schär is marketing them as such in the United States. They are trying to make a mark in CKD, according to Ms. Donnelly. She added that Dr. Schär has been successful in Europe, where nutrition therapy is more integrated in the health care system.

In 2019, Flavis and the National Kidney Foundation joined forces to raise awareness of nutritional interventions and to build enthusiasm for the Flavis products. The partnership has now ended, mostly because Flavis could no longer afford it, according to Ms. Donnelly.

“Information on diet and nutrition is the most requested subject matter from the NKF,” said Anthony Gucciardo, senior vice president of strategic partnerships at the foundation. The partnership “has never been necessarily about promoting their products per se; it’s promoting a healthy diet and really a diet specific for CKD.”

The NKF developed cobranded materials on low-protein foods for physicians and a teaching tool they could use with patients. Consumers could access nutrition information and a discount on Flavis products on a dedicated webpage. The foundation didn’t describe the low-protein products as medical foods, said Mr. Gucciardo, even if Flavis promoted them as such.

In patients with CKD, dietary management can help prevent the progression to end-stage renal disease. Although Medicare covers medical nutrition therapy – in which patients receive personalized assessments and dietary advice – uptake is abysmally low, according to a 2018 study.

Dr. Burdock thinks low-protein foods for CKD do meet the FDA’s criteria for a medical food but that the agency might not necessarily agree with him. The FDA would not comment.
 

Physician beware

When it comes to medical foods, the FDA has often looked the other way because the ingredients may already have been proven safe and the danger to an individual or to the public’s health is relatively low, according to Dr. Burdock and Mr. Hyman.

However, if the agency “feels that a medical food will prevent people from seeking medical care or there is potential to defraud the public, it is justified in taking action against the company,” said Dr. Burdock.

According to Dr. Wilson, the pharmacist who reported on the inappropriate medical food prescriptions in the California system, the FDA could help by creating a list of approved medical foods. Physicians should take time to learn about the difference between medical foods and supplements, she said, adding that they should also not hesitate to “question the veracity of the claims for them.”

Ms. Guggenheim believed doctors need to know that, for the most part, these are not FDA-approved products. She emphasized the importance of evaluating the products and looking at the data of their impact on a disease or condition.

“Many of these companies strongly believe that the products work and help people, so clinicians need to be very data driven,” she said.

A version of this article originally appeared on Medscape.com.

An intervention designed to prevent serious fall injuries among older adults was less effective than researchers expected but did identify important ways for clinicians to help, including screening all older patients for fall risk and deprescribing certain medications when possible.

The study was conducted by Shalender Bhasin, MD, MBBS, from Brigham and Women’s Hospital and Harvard Medical School in Boston and colleagues on behalf of the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) trial investigators and was published online July 8 in The New England Journal of Medicine.

Patients are often unaware of their increased risk until they have fallen for the first time, and they often underestimate how many of their risk factors can be improved, Dr. Bhasin said in an interview.

“Fall injuries are a very important cause of injury-related deaths among older adults, and these are preventable. Yet they are so difficult; for 30 years the rates of fall injuries have not declined,” he said.

Using a pragmatic, cluster-randomized trial, the researchers studied the clinical effectiveness of a “patient-centered intervention that combined elements of practice redesign (reconfiguration of workflow to improve quality of care) and an evidence-based, multifactorial, individually tailored intervention implemented by specially trained nurses in primary care settings,” the authors explained.

Participants in the intervention group worked with trained nurses (fall care managers) to identify their risk factors and determine which risks they wanted to modify. Participants in the control group received their typical care and a pamphlet with information on falls and were encouraged to talk with their primary care physicians (who received the results on risk factor screening) about fall prevention. Those in the intervention group also received the pamphlet.

Fall care managers evaluated patients’ home environments and in some cases visited the patient’s home, Dr. Bhasin said.

The researchers enrolled community-dwelling adults aged 70 years or older who were at higher risk for fall injuries from 86 primary care practices across 10 U.S. health care systems. Half of the practices were randomly assigned to provide the intervention to their patients; the other half of the practices provided enhanced usual care.

The researchers defined patients with increased risk for fall injuries as those who had suffered a fall-related injury at least twice during the previous year or those whose difficulties with balance or walking made them fearful of falling. Serious fall injuries were defined as falls that cause a fracture (other than a thoracic or lumbar vertebral fracture), joint dislocation, a cut needing closure, or falls that resulted in hospital admission for a “head injury, sprain or strain, bruising or swelling, or other serious injury,” they explained.

Demographic and baseline characteristics were similar for both groups of patients (mean age, 80 years; 62.0% women); 38.9% had experienced a fall-related injury during the previous year, and 35.1% had suffered at least two falls during the previous year.

The researchers hypothesized that serious fall injuries would be 20% lower in the intervention group, compared with the control group, but that was not the case.

The findings showed no significant difference between the intervention group (4.9 events per 100 person-years of follow-up) and the control group (5.3 events per 100 person-years of follow-up) for the rate of first adjudicated serious fall injury (hazard ratio, 0.92; P = .25). Results were similar in a practice-level analysis and a sensitivity analysis adjusted for participant-level covariates.

However, there was a difference in rates of first participant-reported fall injury, which was a secondary endpoint, at 25.6 events per 100 person-years of follow-up among participants in the intervention group versus 28.6 events among those in the control group (HR, 0.90; P = .004).

There were no significant differences between the groups for rates of all adjudicated serious fall injuries and all patient-reported fall injuries. Bone fractures and injuries resulting in hospitalization were the most frequent types of adjudicated serious fall injuries.

Rates of serious adverse events resulting in hospitalization were similar for the intervention group and the control group (32.8 and 33.3 hospitalizations per 100 person-years of follow-up, respectively), as well as rates of death (3.3 deaths per 100 person-years of follow-up in both groups).
 

Simple steps can help

“The most important thing clinicians can do is a quick screen for fall injury risk,” Dr. Bhasin said in an interview. The screening tool he uses consists of three questions and can be completed in less than a minute. Clinicians should share that information with patients, he continued.

“Just recognizing that they are at risk for falls, patients are much more motivated to take action,” Dr. Bhasin added.

The top three risk factors identified among trial participants were trouble with strength, gait, or balance; osteoporosis or vitamin D deficiency; and impaired vision. “The use of certain medications, postural hypotension, problems with feet or footwear, and home safety hazards were less commonly identified, and the use of certain medications was the least commonly prioritized,” the authors wrote.

It is vital that clinicians help patients implement changes, Dr. Bhasin said. He noted that many patients encounter barriers that prevent them from taking action, including transportation or insurance problems and lack of access to exercise programs in the community.

Deprescribing medications such as sleep medications and benzodiazepines is also a key piece of the puzzle, he added. “They’re pretty huge risks, and yet it is so hard to get people off these medications.”

Future research will focus on how to improve the intervention’s effectiveness and also will test the strategy among those with cognitive impairments who have even higher risk for fall injuries, Dr. Bhasin said.
 

Falls remain common

A report published online July 9 in Morbidity and Mortality Weekly Report underscores the prevalence of fall-related injuries: In 2018, more than one quarter (27.5%) of adults 65 years or older said they had fallen at least once during the previous year (35.6 million falls), and 10.2% said they had experienced a fall-related injury (8.4 million fall-related injuries). The percentage of adults who reported a fall increased during 2012-2016, then decreased during 2016-2018.

Briana Moreland, MPH, from Synergy America and the Division of Injury Prevention at National Center for Injury Prevention and Control of the Centers for Disease Control and Prevention and colleagues wrote that older adults and health care providers can work together to reduce fall risk.

“CDC created the Stopping Elderly Accidents, Deaths and Injuries (STEADI) initiative, which offers tools and resources for health care providers to screen their older patients for fall risk, assess modifiable fall risk factors, and to intervene with evidence-based fall prevention interventions (https://www.cdc.gov/steadi). These include medication management, vision screening, home modifications, referral to physical therapists who can address problems with gait, strength, and balance, and referral to effective community-based fall prevention programs,” Ms. Moreland and colleagues explain.

Dr. Bhasin has received grants from the National Institute on Aging (NIA) and Patient-Centered Outcomes Research Institute (PCORI) during the conduct of the study. He has received grants, personal fees, and nonfinancial support from AbbVie; grants from Transition Therapeutics, Alivegen, and Metro International Biotechnology; and personal fees from OPKO outside the submitted work. A coauthor received grants from the NIA and PCORI during the conduct of the study and is co-owner of Lynx Health, and another Peduzzi received grants and other compensation from NIA-PCORI during the conduct of the study. Two other authors have disclosed no relevant financial relationships. The remaining authors report a variety of relevant financial relationships; a complete list is available on the journal’s website. The authors of the article in Morbidity and Mortality Weekly Report have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

An intervention designed to prevent serious fall injuries among older adults was less effective than researchers expected but did identify important ways for clinicians to help, including screening all older patients for fall risk and deprescribing certain medications when possible.

The study was conducted by Shalender Bhasin, MD, MBBS, from Brigham and Women’s Hospital and Harvard Medical School in Boston and colleagues on behalf of the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) trial investigators and was published online July 8 in The New England Journal of Medicine.

Patients are often unaware of their increased risk until they have fallen for the first time, and they often underestimate how many of their risk factors can be improved, Dr. Bhasin said in an interview.

“Fall injuries are a very important cause of injury-related deaths among older adults, and these are preventable. Yet they are so difficult; for 30 years the rates of fall injuries have not declined,” he said.

Using a pragmatic, cluster-randomized trial, the researchers studied the clinical effectiveness of a “patient-centered intervention that combined elements of practice redesign (reconfiguration of workflow to improve quality of care) and an evidence-based, multifactorial, individually tailored intervention implemented by specially trained nurses in primary care settings,” the authors explained.

Participants in the intervention group worked with trained nurses (fall care managers) to identify their risk factors and determine which risks they wanted to modify. Participants in the control group received their typical care and a pamphlet with information on falls and were encouraged to talk with their primary care physicians (who received the results on risk factor screening) about fall prevention. Those in the intervention group also received the pamphlet.

Fall care managers evaluated patients’ home environments and in some cases visited the patient’s home, Dr. Bhasin said.

The researchers enrolled community-dwelling adults aged 70 years or older who were at higher risk for fall injuries from 86 primary care practices across 10 U.S. health care systems. Half of the practices were randomly assigned to provide the intervention to their patients; the other half of the practices provided enhanced usual care.

The researchers defined patients with increased risk for fall injuries as those who had suffered a fall-related injury at least twice during the previous year or those whose difficulties with balance or walking made them fearful of falling. Serious fall injuries were defined as falls that cause a fracture (other than a thoracic or lumbar vertebral fracture), joint dislocation, a cut needing closure, or falls that resulted in hospital admission for a “head injury, sprain or strain, bruising or swelling, or other serious injury,” they explained.

Demographic and baseline characteristics were similar for both groups of patients (mean age, 80 years; 62.0% women); 38.9% had experienced a fall-related injury during the previous year, and 35.1% had suffered at least two falls during the previous year.

The researchers hypothesized that serious fall injuries would be 20% lower in the intervention group, compared with the control group, but that was not the case.

The findings showed no significant difference between the intervention group (4.9 events per 100 person-years of follow-up) and the control group (5.3 events per 100 person-years of follow-up) for the rate of first adjudicated serious fall injury (hazard ratio, 0.92; P = .25). Results were similar in a practice-level analysis and a sensitivity analysis adjusted for participant-level covariates.

However, there was a difference in rates of first participant-reported fall injury, which was a secondary endpoint, at 25.6 events per 100 person-years of follow-up among participants in the intervention group versus 28.6 events among those in the control group (HR, 0.90; P = .004).

There were no significant differences between the groups for rates of all adjudicated serious fall injuries and all patient-reported fall injuries. Bone fractures and injuries resulting in hospitalization were the most frequent types of adjudicated serious fall injuries.

Rates of serious adverse events resulting in hospitalization were similar for the intervention group and the control group (32.8 and 33.3 hospitalizations per 100 person-years of follow-up, respectively), as well as rates of death (3.3 deaths per 100 person-years of follow-up in both groups).
 

Simple steps can help

“The most important thing clinicians can do is a quick screen for fall injury risk,” Dr. Bhasin said in an interview. The screening tool he uses consists of three questions and can be completed in less than a minute. Clinicians should share that information with patients, he continued.

“Just recognizing that they are at risk for falls, patients are much more motivated to take action,” Dr. Bhasin added.

The top three risk factors identified among trial participants were trouble with strength, gait, or balance; osteoporosis or vitamin D deficiency; and impaired vision. “The use of certain medications, postural hypotension, problems with feet or footwear, and home safety hazards were less commonly identified, and the use of certain medications was the least commonly prioritized,” the authors wrote.

It is vital that clinicians help patients implement changes, Dr. Bhasin said. He noted that many patients encounter barriers that prevent them from taking action, including transportation or insurance problems and lack of access to exercise programs in the community.

Deprescribing medications such as sleep medications and benzodiazepines is also a key piece of the puzzle, he added. “They’re pretty huge risks, and yet it is so hard to get people off these medications.”

Future research will focus on how to improve the intervention’s effectiveness and also will test the strategy among those with cognitive impairments who have even higher risk for fall injuries, Dr. Bhasin said.
 

Falls remain common

A report published online July 9 in Morbidity and Mortality Weekly Report underscores the prevalence of fall-related injuries: In 2018, more than one quarter (27.5%) of adults 65 years or older said they had fallen at least once during the previous year (35.6 million falls), and 10.2% said they had experienced a fall-related injury (8.4 million fall-related injuries). The percentage of adults who reported a fall increased during 2012-2016, then decreased during 2016-2018.

Briana Moreland, MPH, from Synergy America and the Division of Injury Prevention at National Center for Injury Prevention and Control of the Centers for Disease Control and Prevention and colleagues wrote that older adults and health care providers can work together to reduce fall risk.

“CDC created the Stopping Elderly Accidents, Deaths and Injuries (STEADI) initiative, which offers tools and resources for health care providers to screen their older patients for fall risk, assess modifiable fall risk factors, and to intervene with evidence-based fall prevention interventions (https://www.cdc.gov/steadi). These include medication management, vision screening, home modifications, referral to physical therapists who can address problems with gait, strength, and balance, and referral to effective community-based fall prevention programs,” Ms. Moreland and colleagues explain.

Dr. Bhasin has received grants from the National Institute on Aging (NIA) and Patient-Centered Outcomes Research Institute (PCORI) during the conduct of the study. He has received grants, personal fees, and nonfinancial support from AbbVie; grants from Transition Therapeutics, Alivegen, and Metro International Biotechnology; and personal fees from OPKO outside the submitted work. A coauthor received grants from the NIA and PCORI during the conduct of the study and is co-owner of Lynx Health, and another Peduzzi received grants and other compensation from NIA-PCORI during the conduct of the study. Two other authors have disclosed no relevant financial relationships. The remaining authors report a variety of relevant financial relationships; a complete list is available on the journal’s website. The authors of the article in Morbidity and Mortality Weekly Report have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

An intervention designed to prevent serious fall injuries among older adults was less effective than researchers expected but did identify important ways for clinicians to help, including screening all older patients for fall risk and deprescribing certain medications when possible.

The study was conducted by Shalender Bhasin, MD, MBBS, from Brigham and Women’s Hospital and Harvard Medical School in Boston and colleagues on behalf of the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) trial investigators and was published online July 8 in The New England Journal of Medicine.

Patients are often unaware of their increased risk until they have fallen for the first time, and they often underestimate how many of their risk factors can be improved, Dr. Bhasin said in an interview.

“Fall injuries are a very important cause of injury-related deaths among older adults, and these are preventable. Yet they are so difficult; for 30 years the rates of fall injuries have not declined,” he said.

Using a pragmatic, cluster-randomized trial, the researchers studied the clinical effectiveness of a “patient-centered intervention that combined elements of practice redesign (reconfiguration of workflow to improve quality of care) and an evidence-based, multifactorial, individually tailored intervention implemented by specially trained nurses in primary care settings,” the authors explained.

Participants in the intervention group worked with trained nurses (fall care managers) to identify their risk factors and determine which risks they wanted to modify. Participants in the control group received their typical care and a pamphlet with information on falls and were encouraged to talk with their primary care physicians (who received the results on risk factor screening) about fall prevention. Those in the intervention group also received the pamphlet.

Fall care managers evaluated patients’ home environments and in some cases visited the patient’s home, Dr. Bhasin said.

The researchers enrolled community-dwelling adults aged 70 years or older who were at higher risk for fall injuries from 86 primary care practices across 10 U.S. health care systems. Half of the practices were randomly assigned to provide the intervention to their patients; the other half of the practices provided enhanced usual care.

The researchers defined patients with increased risk for fall injuries as those who had suffered a fall-related injury at least twice during the previous year or those whose difficulties with balance or walking made them fearful of falling. Serious fall injuries were defined as falls that cause a fracture (other than a thoracic or lumbar vertebral fracture), joint dislocation, a cut needing closure, or falls that resulted in hospital admission for a “head injury, sprain or strain, bruising or swelling, or other serious injury,” they explained.

Demographic and baseline characteristics were similar for both groups of patients (mean age, 80 years; 62.0% women); 38.9% had experienced a fall-related injury during the previous year, and 35.1% had suffered at least two falls during the previous year.

The researchers hypothesized that serious fall injuries would be 20% lower in the intervention group, compared with the control group, but that was not the case.

The findings showed no significant difference between the intervention group (4.9 events per 100 person-years of follow-up) and the control group (5.3 events per 100 person-years of follow-up) for the rate of first adjudicated serious fall injury (hazard ratio, 0.92; P = .25). Results were similar in a practice-level analysis and a sensitivity analysis adjusted for participant-level covariates.

However, there was a difference in rates of first participant-reported fall injury, which was a secondary endpoint, at 25.6 events per 100 person-years of follow-up among participants in the intervention group versus 28.6 events among those in the control group (HR, 0.90; P = .004).

There were no significant differences between the groups for rates of all adjudicated serious fall injuries and all patient-reported fall injuries. Bone fractures and injuries resulting in hospitalization were the most frequent types of adjudicated serious fall injuries.

Rates of serious adverse events resulting in hospitalization were similar for the intervention group and the control group (32.8 and 33.3 hospitalizations per 100 person-years of follow-up, respectively), as well as rates of death (3.3 deaths per 100 person-years of follow-up in both groups).
 

Simple steps can help

“The most important thing clinicians can do is a quick screen for fall injury risk,” Dr. Bhasin said in an interview. The screening tool he uses consists of three questions and can be completed in less than a minute. Clinicians should share that information with patients, he continued.

“Just recognizing that they are at risk for falls, patients are much more motivated to take action,” Dr. Bhasin added.

The top three risk factors identified among trial participants were trouble with strength, gait, or balance; osteoporosis or vitamin D deficiency; and impaired vision. “The use of certain medications, postural hypotension, problems with feet or footwear, and home safety hazards were less commonly identified, and the use of certain medications was the least commonly prioritized,” the authors wrote.

It is vital that clinicians help patients implement changes, Dr. Bhasin said. He noted that many patients encounter barriers that prevent them from taking action, including transportation or insurance problems and lack of access to exercise programs in the community.

Deprescribing medications such as sleep medications and benzodiazepines is also a key piece of the puzzle, he added. “They’re pretty huge risks, and yet it is so hard to get people off these medications.”

Future research will focus on how to improve the intervention’s effectiveness and also will test the strategy among those with cognitive impairments who have even higher risk for fall injuries, Dr. Bhasin said.
 

Falls remain common

A report published online July 9 in Morbidity and Mortality Weekly Report underscores the prevalence of fall-related injuries: In 2018, more than one quarter (27.5%) of adults 65 years or older said they had fallen at least once during the previous year (35.6 million falls), and 10.2% said they had experienced a fall-related injury (8.4 million fall-related injuries). The percentage of adults who reported a fall increased during 2012-2016, then decreased during 2016-2018.

Briana Moreland, MPH, from Synergy America and the Division of Injury Prevention at National Center for Injury Prevention and Control of the Centers for Disease Control and Prevention and colleagues wrote that older adults and health care providers can work together to reduce fall risk.

“CDC created the Stopping Elderly Accidents, Deaths and Injuries (STEADI) initiative, which offers tools and resources for health care providers to screen their older patients for fall risk, assess modifiable fall risk factors, and to intervene with evidence-based fall prevention interventions (https://www.cdc.gov/steadi). These include medication management, vision screening, home modifications, referral to physical therapists who can address problems with gait, strength, and balance, and referral to effective community-based fall prevention programs,” Ms. Moreland and colleagues explain.

Dr. Bhasin has received grants from the National Institute on Aging (NIA) and Patient-Centered Outcomes Research Institute (PCORI) during the conduct of the study. He has received grants, personal fees, and nonfinancial support from AbbVie; grants from Transition Therapeutics, Alivegen, and Metro International Biotechnology; and personal fees from OPKO outside the submitted work. A coauthor received grants from the NIA and PCORI during the conduct of the study and is co-owner of Lynx Health, and another Peduzzi received grants and other compensation from NIA-PCORI during the conduct of the study. Two other authors have disclosed no relevant financial relationships. The remaining authors report a variety of relevant financial relationships; a complete list is available on the journal’s website. The authors of the article in Morbidity and Mortality Weekly Report have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

A new study has determined a benefit of cardiac CT scans beyond assessing heart health: Evaluating fracture rate and potential osteoporosis through the bone mineral density (BMD) of thoracic vertebrae.

“Our results represent a step toward appraisal and recognition of the clinical utility of opportunistic BMD screening from cardiac CT,” wrote Josephine Therkildsen, MD, of Hospital Unit West in Herning, Denmark, and coauthors. The study was published July 14 in Radiology.

To determine if further analysis of cardiac CT could help determine BMD and its association with fracture rate, the investigators launched a prospective observational study of 1,487 Danish patients with potential coronary artery disease who underwent cardiac CT scans between September 2014 and March 2016. Their mean age was 57 years (standard deviation, 9; range, 40-80). Nearly all of the patients were white, and 52.5% (n = 781) were women.

All participants underwent a noncontrast-enhanced cardiac CT, from which volumetric BMD of three thoracic vertebrae was measured via commercially available semiautomatic software. Their mean BMD was 119 mg/cm³ (SD, 34) with no significant difference noted between male and female patients. Of the 1,487 participants, 695 were defined as having normal BMD (> 120 mg/cm³), 613 as having low BMD (80-120 mg/cm³), and 179 as having very low BMD (< 80 mg/cm³). Median follow-up was 3.1 years (interquartile range, 2.7-3.4).

Incident fracture occurred in 80 patients (5.4%), of whom 48 were women and 32 were men. Patients who suffered fractures were significantly older than patients with no fractures (mean 59 years vs. 57 years; P = .03). Of the 80 patients with fractures, 31 were osteoporosis related.

In an unadjusted analysis, participants with very low BMD had a greater rate of any fracture (hazard ratio [HR], 2.6; 95% confidence interval, 1.4-4.7; P = .002) and of osteoporosis-related fracture (HR, 8.1; 95% CI, 2.4-27.0; P = .001). After adjustment for age and sex, their rates remained significantly greater for any fracture (HR, 2.1; 95% CI, 1.1-4.2; P = .03) and for osteoporosis-related fracture (HR, 4.0; 95% CI, 1.1-15.0; P = .04).

“Opportunistic” use of scans benefits both physicians and patients

“The concept of using a CT scan that was done for a different purpose allows you to be opportunistic,” Ethel S. Siris, MD, the Madeline C. Stabile Professor of Clinical Medicine in the department of medicine at Columbia University and director of the Toni Stabile Osteoporosis Center of the Columbia University Medical Center, New York–Presbyterian Hospital, New York, said in an interview. “If you’re dealing with older patients, and if you have the software for your radiologist to use to reanalyze the CT scan and say something about the bone, it’s certainly a way of estimating who may be at risk of future fractures.

“From a practical point of view, it’s hard to imagine that it would ever replace conventional bone mineral density testing via DXA [dual-energy x-ray absorptiometry],” she added. “That said, osteoporosis is woefully underdiagnosed because people don’t get DXA tested. This study showed that, if you have access to the scan of the thoracic or even the lumbar spine and if you have the necessary software, you can make legitimate statements about the numbers being low or very low. What that would lead to, I would hope, is some internists to say, ‘This could be a predictor of fracture risk. We should put you on treatment.’ And then follow up with a conventional DXA test.

“Is that going to happen? I don’t know. But the bottom line of the study is: Anything that may enhance the physician’s drive to evaluate a patient for fracture risk is good.”
 

Whatever the reason for the scan, CT can help diagnose osteoporosis

This study reinforces that CT exams – of the chest, in particular – can serve a valuable dual purpose as osteoporosis screenings, Miriam A. Bredella, MD, professor of radiology at Harvard Medical School and vice chair of the department of radiology at Massachusetts General Hospital, Boston, wrote in an accompanying editorial.

“In the United States, more than 80 million CT examinations are performed each year, many of which could be used to screen for osteoporosis without additional costs or radiation exposure,” she wrote. And thanks to the findings of the study by Therkildsen et al., which relied on both established and new BMD thresholds, the link between thoracic spine BMD and fracture risk is clearer than ever.

“I hope this study will ignite interest in using chest CT examinations performed for other purposes, such as lung cancer screening, for opportunistic osteoporosis screening and prediction of fractures in vulnerable populations,” she added.

The authors acknowledged their study’s limitations, including a small number of fracture events overall and the inability to evaluate associations between BMD and fracture rate at specific locations. In addition, their cohort was largely made up of white participants with a certain coronary artery disease risk profile; because of ethnical differences in BMD measurements, their results “cannot be extrapolated to other ethnical groups.”

Several of the study’s authors reported potential conflicts of interest, including receiving grants and money for consultancies and board memberships from various councils, associations, and pharmaceutical companies. Dr. Bredella reported no conflicts of interest. Dr. Siris has no relevant disclosures.

SOURCE: Therkildsen J et al. Radiology. 2020 Jul 14. doi: 10.1148/radiol.2020192706.

A new study has determined a benefit of cardiac CT scans beyond assessing heart health: Evaluating fracture rate and potential osteoporosis through the bone mineral density (BMD) of thoracic vertebrae.

“Our results represent a step toward appraisal and recognition of the clinical utility of opportunistic BMD screening from cardiac CT,” wrote Josephine Therkildsen, MD, of Hospital Unit West in Herning, Denmark, and coauthors. The study was published July 14 in Radiology.

To determine if further analysis of cardiac CT could help determine BMD and its association with fracture rate, the investigators launched a prospective observational study of 1,487 Danish patients with potential coronary artery disease who underwent cardiac CT scans between September 2014 and March 2016. Their mean age was 57 years (standard deviation, 9; range, 40-80). Nearly all of the patients were white, and 52.5% (n = 781) were women.

All participants underwent a noncontrast-enhanced cardiac CT, from which volumetric BMD of three thoracic vertebrae was measured via commercially available semiautomatic software. Their mean BMD was 119 mg/cm³ (SD, 34) with no significant difference noted between male and female patients. Of the 1,487 participants, 695 were defined as having normal BMD (> 120 mg/cm³), 613 as having low BMD (80-120 mg/cm³), and 179 as having very low BMD (< 80 mg/cm³). Median follow-up was 3.1 years (interquartile range, 2.7-3.4).

Incident fracture occurred in 80 patients (5.4%), of whom 48 were women and 32 were men. Patients who suffered fractures were significantly older than patients with no fractures (mean 59 years vs. 57 years; P = .03). Of the 80 patients with fractures, 31 were osteoporosis related.

In an unadjusted analysis, participants with very low BMD had a greater rate of any fracture (hazard ratio [HR], 2.6; 95% confidence interval, 1.4-4.7; P = .002) and of osteoporosis-related fracture (HR, 8.1; 95% CI, 2.4-27.0; P = .001). After adjustment for age and sex, their rates remained significantly greater for any fracture (HR, 2.1; 95% CI, 1.1-4.2; P = .03) and for osteoporosis-related fracture (HR, 4.0; 95% CI, 1.1-15.0; P = .04).

“Opportunistic” use of scans benefits both physicians and patients

“The concept of using a CT scan that was done for a different purpose allows you to be opportunistic,” Ethel S. Siris, MD, the Madeline C. Stabile Professor of Clinical Medicine in the department of medicine at Columbia University and director of the Toni Stabile Osteoporosis Center of the Columbia University Medical Center, New York–Presbyterian Hospital, New York, said in an interview. “If you’re dealing with older patients, and if you have the software for your radiologist to use to reanalyze the CT scan and say something about the bone, it’s certainly a way of estimating who may be at risk of future fractures.

“From a practical point of view, it’s hard to imagine that it would ever replace conventional bone mineral density testing via DXA [dual-energy x-ray absorptiometry],” she added. “That said, osteoporosis is woefully underdiagnosed because people don’t get DXA tested. This study showed that, if you have access to the scan of the thoracic or even the lumbar spine and if you have the necessary software, you can make legitimate statements about the numbers being low or very low. What that would lead to, I would hope, is some internists to say, ‘This could be a predictor of fracture risk. We should put you on treatment.’ And then follow up with a conventional DXA test.

“Is that going to happen? I don’t know. But the bottom line of the study is: Anything that may enhance the physician’s drive to evaluate a patient for fracture risk is good.”
 

Whatever the reason for the scan, CT can help diagnose osteoporosis

This study reinforces that CT exams – of the chest, in particular – can serve a valuable dual purpose as osteoporosis screenings, Miriam A. Bredella, MD, professor of radiology at Harvard Medical School and vice chair of the department of radiology at Massachusetts General Hospital, Boston, wrote in an accompanying editorial.

“In the United States, more than 80 million CT examinations are performed each year, many of which could be used to screen for osteoporosis without additional costs or radiation exposure,” she wrote. And thanks to the findings of the study by Therkildsen et al., which relied on both established and new BMD thresholds, the link between thoracic spine BMD and fracture risk is clearer than ever.

“I hope this study will ignite interest in using chest CT examinations performed for other purposes, such as lung cancer screening, for opportunistic osteoporosis screening and prediction of fractures in vulnerable populations,” she added.

The authors acknowledged their study’s limitations, including a small number of fracture events overall and the inability to evaluate associations between BMD and fracture rate at specific locations. In addition, their cohort was largely made up of white participants with a certain coronary artery disease risk profile; because of ethnical differences in BMD measurements, their results “cannot be extrapolated to other ethnical groups.”

Several of the study’s authors reported potential conflicts of interest, including receiving grants and money for consultancies and board memberships from various councils, associations, and pharmaceutical companies. Dr. Bredella reported no conflicts of interest. Dr. Siris has no relevant disclosures.

SOURCE: Therkildsen J et al. Radiology. 2020 Jul 14. doi: 10.1148/radiol.2020192706.

A new study has determined a benefit of cardiac CT scans beyond assessing heart health: Evaluating fracture rate and potential osteoporosis through the bone mineral density (BMD) of thoracic vertebrae.

“Our results represent a step toward appraisal and recognition of the clinical utility of opportunistic BMD screening from cardiac CT,” wrote Josephine Therkildsen, MD, of Hospital Unit West in Herning, Denmark, and coauthors. The study was published July 14 in Radiology.

To determine if further analysis of cardiac CT could help determine BMD and its association with fracture rate, the investigators launched a prospective observational study of 1,487 Danish patients with potential coronary artery disease who underwent cardiac CT scans between September 2014 and March 2016. Their mean age was 57 years (standard deviation, 9; range, 40-80). Nearly all of the patients were white, and 52.5% (n = 781) were women.

All participants underwent a noncontrast-enhanced cardiac CT, from which volumetric BMD of three thoracic vertebrae was measured via commercially available semiautomatic software. Their mean BMD was 119 mg/cm³ (SD, 34) with no significant difference noted between male and female patients. Of the 1,487 participants, 695 were defined as having normal BMD (> 120 mg/cm³), 613 as having low BMD (80-120 mg/cm³), and 179 as having very low BMD (< 80 mg/cm³). Median follow-up was 3.1 years (interquartile range, 2.7-3.4).

Incident fracture occurred in 80 patients (5.4%), of whom 48 were women and 32 were men. Patients who suffered fractures were significantly older than patients with no fractures (mean 59 years vs. 57 years; P = .03). Of the 80 patients with fractures, 31 were osteoporosis related.

In an unadjusted analysis, participants with very low BMD had a greater rate of any fracture (hazard ratio [HR], 2.6; 95% confidence interval, 1.4-4.7; P = .002) and of osteoporosis-related fracture (HR, 8.1; 95% CI, 2.4-27.0; P = .001). After adjustment for age and sex, their rates remained significantly greater for any fracture (HR, 2.1; 95% CI, 1.1-4.2; P = .03) and for osteoporosis-related fracture (HR, 4.0; 95% CI, 1.1-15.0; P = .04).

“Opportunistic” use of scans benefits both physicians and patients

“The concept of using a CT scan that was done for a different purpose allows you to be opportunistic,” Ethel S. Siris, MD, the Madeline C. Stabile Professor of Clinical Medicine in the department of medicine at Columbia University and director of the Toni Stabile Osteoporosis Center of the Columbia University Medical Center, New York–Presbyterian Hospital, New York, said in an interview. “If you’re dealing with older patients, and if you have the software for your radiologist to use to reanalyze the CT scan and say something about the bone, it’s certainly a way of estimating who may be at risk of future fractures.

“From a practical point of view, it’s hard to imagine that it would ever replace conventional bone mineral density testing via DXA [dual-energy x-ray absorptiometry],” she added. “That said, osteoporosis is woefully underdiagnosed because people don’t get DXA tested. This study showed that, if you have access to the scan of the thoracic or even the lumbar spine and if you have the necessary software, you can make legitimate statements about the numbers being low or very low. What that would lead to, I would hope, is some internists to say, ‘This could be a predictor of fracture risk. We should put you on treatment.’ And then follow up with a conventional DXA test.

“Is that going to happen? I don’t know. But the bottom line of the study is: Anything that may enhance the physician’s drive to evaluate a patient for fracture risk is good.”
 

Whatever the reason for the scan, CT can help diagnose osteoporosis

This study reinforces that CT exams – of the chest, in particular – can serve a valuable dual purpose as osteoporosis screenings, Miriam A. Bredella, MD, professor of radiology at Harvard Medical School and vice chair of the department of radiology at Massachusetts General Hospital, Boston, wrote in an accompanying editorial.

“In the United States, more than 80 million CT examinations are performed each year, many of which could be used to screen for osteoporosis without additional costs or radiation exposure,” she wrote. And thanks to the findings of the study by Therkildsen et al., which relied on both established and new BMD thresholds, the link between thoracic spine BMD and fracture risk is clearer than ever.

“I hope this study will ignite interest in using chest CT examinations performed for other purposes, such as lung cancer screening, for opportunistic osteoporosis screening and prediction of fractures in vulnerable populations,” she added.

The authors acknowledged their study’s limitations, including a small number of fracture events overall and the inability to evaluate associations between BMD and fracture rate at specific locations. In addition, their cohort was largely made up of white participants with a certain coronary artery disease risk profile; because of ethnical differences in BMD measurements, their results “cannot be extrapolated to other ethnical groups.”

Several of the study’s authors reported potential conflicts of interest, including receiving grants and money for consultancies and board memberships from various councils, associations, and pharmaceutical companies. Dr. Bredella reported no conflicts of interest. Dr. Siris has no relevant disclosures.

SOURCE: Therkildsen J et al. Radiology. 2020 Jul 14. doi: 10.1148/radiol.2020192706.

Six medical societies from across the globe are emphasizing the importance of individuals obtaining the daily recommended dose of vitamin D, especially given the impact of the COVID-19 pandemic on outdoor time.

The statement, “Joint Guidance on Vitamin D in the Era of COVID-19,” is supported by the American Society for Bone and Mineral Research, the Endocrine Society, and the American Association of Clinical Endocrinologists, among others.

They felt the need to clarify the recommendations for clinicians. Central to the guidance is the recommendation to directly expose the skin to sunlight for 15-30 minutes per day, while taking care to avoid sunburn.

The statement noted that “vitamin D is very safe when taken at reasonable dosages and is important for musculoskeletal health. Levels are likely to decline as individuals reduce outside activity (sun exposure) during the pandemic.”

It added that “most older and younger adults can safely take 400-1000 IU daily to keep vitamin D levels within the optimal range as recommended by [the US] Institute of Medicine guidelines.”

The statement also noted that the scientific evidence clearly supports the benefits that vitamin D (in combination with calcium intake) plays in building a strong skeleton and preventing bone loss.

Other societies supporting the statement are the European Calcified Tissue Society, the National Osteoporosis Foundation, and the International Osteoporosis Foundation.

What role for vitamin D in COVID-19?

Over recent months, the role of vitamin D in relation to prevention of COVID-19 has been the subject of intense debate. Now, these societies have joined forces and endorsed evidence-based guidance to clarify the issue around obtaining the daily recommended dosage of vitamin D.

During the pandemic, orders to stay at home meant individuals were likely to spend less time outdoors and have less opportunity to draw their vitamin D directly from sunlight, which is its main source, other than a limited number of foods or as a dietary supplement, the societies explained.

However, they acknowledged that the role of vitamin D in COVID-19 remains unclear.

“The current data do not provide any evidence that vitamin D supplementation will help prevent or treat COVID-19 infection; however, our guidance does not preclude further study of the potential effects of vitamin D on COVID-19,” the joint statement said.

Research to date suggests that vitamin D may play a role in enhancing the immune response, and given prior work demonstrating a role for the activated form of vitamin D – 1,25(OH)2D – in immune responses, “further research into vitamin D supplementation in COVID-19 disease is warranted,” it added. “Trials to date have been observational and there have been no randomized, controlled trials from which firm conclusions about causal relationships can be drawn. Observational studies suggest associations between low vitamin D concentrations and higher rates of COVID-19 infection.”

Medscape Medical News previously reported on the existing observational data regarding vitamin D in COVID-19. A recent rapid evidence review by the National Institute for Health and Care Excellence failed to find any evidence that vitamin D supplementation reduces the risk or severity of COVID-19.

A version of this article originally appeared on Medscape.com.

Six medical societies from across the globe are emphasizing the importance of individuals obtaining the daily recommended dose of vitamin D, especially given the impact of the COVID-19 pandemic on outdoor time.

The statement, “Joint Guidance on Vitamin D in the Era of COVID-19,” is supported by the American Society for Bone and Mineral Research, the Endocrine Society, and the American Association of Clinical Endocrinologists, among others.

They felt the need to clarify the recommendations for clinicians. Central to the guidance is the recommendation to directly expose the skin to sunlight for 15-30 minutes per day, while taking care to avoid sunburn.

The statement noted that “vitamin D is very safe when taken at reasonable dosages and is important for musculoskeletal health. Levels are likely to decline as individuals reduce outside activity (sun exposure) during the pandemic.”

It added that “most older and younger adults can safely take 400-1000 IU daily to keep vitamin D levels within the optimal range as recommended by [the US] Institute of Medicine guidelines.”

The statement also noted that the scientific evidence clearly supports the benefits that vitamin D (in combination with calcium intake) plays in building a strong skeleton and preventing bone loss.

Other societies supporting the statement are the European Calcified Tissue Society, the National Osteoporosis Foundation, and the International Osteoporosis Foundation.

What role for vitamin D in COVID-19?

Over recent months, the role of vitamin D in relation to prevention of COVID-19 has been the subject of intense debate. Now, these societies have joined forces and endorsed evidence-based guidance to clarify the issue around obtaining the daily recommended dosage of vitamin D.

During the pandemic, orders to stay at home meant individuals were likely to spend less time outdoors and have less opportunity to draw their vitamin D directly from sunlight, which is its main source, other than a limited number of foods or as a dietary supplement, the societies explained.

However, they acknowledged that the role of vitamin D in COVID-19 remains unclear.

“The current data do not provide any evidence that vitamin D supplementation will help prevent or treat COVID-19 infection; however, our guidance does not preclude further study of the potential effects of vitamin D on COVID-19,” the joint statement said.

Research to date suggests that vitamin D may play a role in enhancing the immune response, and given prior work demonstrating a role for the activated form of vitamin D – 1,25(OH)2D – in immune responses, “further research into vitamin D supplementation in COVID-19 disease is warranted,” it added. “Trials to date have been observational and there have been no randomized, controlled trials from which firm conclusions about causal relationships can be drawn. Observational studies suggest associations between low vitamin D concentrations and higher rates of COVID-19 infection.”

Medscape Medical News previously reported on the existing observational data regarding vitamin D in COVID-19. A recent rapid evidence review by the National Institute for Health and Care Excellence failed to find any evidence that vitamin D supplementation reduces the risk or severity of COVID-19.

A version of this article originally appeared on Medscape.com.

Six medical societies from across the globe are emphasizing the importance of individuals obtaining the daily recommended dose of vitamin D, especially given the impact of the COVID-19 pandemic on outdoor time.

The statement, “Joint Guidance on Vitamin D in the Era of COVID-19,” is supported by the American Society for Bone and Mineral Research, the Endocrine Society, and the American Association of Clinical Endocrinologists, among others.

They felt the need to clarify the recommendations for clinicians. Central to the guidance is the recommendation to directly expose the skin to sunlight for 15-30 minutes per day, while taking care to avoid sunburn.

The statement noted that “vitamin D is very safe when taken at reasonable dosages and is important for musculoskeletal health. Levels are likely to decline as individuals reduce outside activity (sun exposure) during the pandemic.”

It added that “most older and younger adults can safely take 400-1000 IU daily to keep vitamin D levels within the optimal range as recommended by [the US] Institute of Medicine guidelines.”

The statement also noted that the scientific evidence clearly supports the benefits that vitamin D (in combination with calcium intake) plays in building a strong skeleton and preventing bone loss.

Other societies supporting the statement are the European Calcified Tissue Society, the National Osteoporosis Foundation, and the International Osteoporosis Foundation.

What role for vitamin D in COVID-19?

Over recent months, the role of vitamin D in relation to prevention of COVID-19 has been the subject of intense debate. Now, these societies have joined forces and endorsed evidence-based guidance to clarify the issue around obtaining the daily recommended dosage of vitamin D.

During the pandemic, orders to stay at home meant individuals were likely to spend less time outdoors and have less opportunity to draw their vitamin D directly from sunlight, which is its main source, other than a limited number of foods or as a dietary supplement, the societies explained.

However, they acknowledged that the role of vitamin D in COVID-19 remains unclear.

“The current data do not provide any evidence that vitamin D supplementation will help prevent or treat COVID-19 infection; however, our guidance does not preclude further study of the potential effects of vitamin D on COVID-19,” the joint statement said.

Research to date suggests that vitamin D may play a role in enhancing the immune response, and given prior work demonstrating a role for the activated form of vitamin D – 1,25(OH)2D – in immune responses, “further research into vitamin D supplementation in COVID-19 disease is warranted,” it added. “Trials to date have been observational and there have been no randomized, controlled trials from which firm conclusions about causal relationships can be drawn. Observational studies suggest associations between low vitamin D concentrations and higher rates of COVID-19 infection.”

Medscape Medical News previously reported on the existing observational data regarding vitamin D in COVID-19. A recent rapid evidence review by the National Institute for Health and Care Excellence failed to find any evidence that vitamin D supplementation reduces the risk or severity of COVID-19.

A version of this article originally appeared on Medscape.com.

Although the adverse effects of systemic glucocorticoids (GCs) are well known, their association with hypertension in rheumatoid arthritis (RA) has been unclear. Now, a large population-based study shows that the drugs are linked to a 17% overall increased risk for incident hypertension among patients with RA.

Further, when the researchers stratified participants by dose category, they found that doses higher than 7.5 mg were significantly associated with hypertension. Cumulative dosage was not tied to any clear pattern of risk.

The authors, led by Ruth E. Costello, a researcher at the Centre for Epidemiology Versus Arthritis in the Centre for Musculoskeletal Research at the University of Manchester (England) concluded that patients who are taking these drugs for the treatment of RA should be monitored for high blood pressure, which is an important but modifiable cardiovascular risk factor, and treated appropriately.

The results of Ms. Costello and colleagues’ study were published June 27 in Rheumatology.

“While fractures associated with these steroid drugs are well studied, hypertension is a side effect that seems to have been less well studied, and yet it is an important cardiovascular risk factor that can be managed,” Ms. Costello said in an interview.

To better understand the possible association, Ms. Costello and colleagues identified 17,760 patients who were newly diagnosed with RA between 1992 and 2019 and were included in the Clinical Practice Research Datalink, which represents about 7% of the U.K. population. None of the patients had hypertension at initial RA diagnosis. Slightly more than two-thirds were women (68.1%), and the mean age was 56.3 years.

Of those patients, 7,421 (41.8%) were prescribed GCs during postdiagnosis follow-up. Most patients (73%) were followed for at least 2 years.

Patients who used GCs were slightly older than never-users (mean age, 57.7 vs. 55.3 years), were predominantly women, had a history of smoking, and had more comorbidities.

The overall incidence rate (IR) of hypertension was 64.1 per 1,000 person-years (95% confidence interval, 62.5-65.7). There were 6,243 cases of incident hypertension over 97,547 person-years of follow-up.

Among those exposed to GCs, 1,321 patients developed hypertension, for an IR of 87.6 per 1,000 person-years. Among unexposed participants, the IR for hypertension was 59.7 per 1,000 person-years. In Cox proportional hazards modeling, GC use was associated with a 17% increased risk for hypertension (hazard ratio, 1.17; 95% CI, 1.10-1.24).

The researchers noted that 40% of GC users with hypertension were not prescribed an antihypertensive agent at any point during the study. “Whilst some may have been offered lifestyle advice, left untreated this has important implications in terms of addressing modifiable risk factors in an RA population already at increased risk of CV disease,” they wrote.

They noted that cardiovascular disease is a major driver of the elevated mortality risk seen among adults with RA compared with the general population and that recent treatment recommendations address management of cardiovascular risks in these patients.

“There are several routes by which GCs may promote cardiovascular disease, including hypertension, metabolic changes, diabetes, and weight gain. We don’t currently know the extent to which each of these individual mechanisms may be increasing cardiovascular disease,” said Ms. Costello.

“Glucocorticoids increase fluid retention and promote obesity and hypertension,” said Rajat S. Bhatt, MD, a rheumatologist at Prime Rheumatology and Memorial Hermann Katy Hospital in Richmond, Texas, who sees hypertension in GC users in his clinical practice. “So patients need to be monitored for these risk factors,” he said in an interview.

Although hypertension may be a significant factor in the increase in cardiovascular disease in the RA population, Dr. Bhatt said the major driver is likely the intrinsic inflammatory state caused by the disease itself. As to why the GC-hypertension connection has flown under the radar in RA, he added, “That specific link has been difficult to tease out since RA patients are often on multiple medications.”

In regard to the role of dosage, Dr. Bhatt said that hypertension risk increases with higher GC doses, as the U.K. study indicates, and usually subsides when patients stop using GCs.

“Whether the observed dose association is causal or influenced by the underlying disease severity, our results suggest we should be vigilant in patients on all doses of GC, especially higher doses,” Ms. Costello added.

In regard to using drugs that are less cardiotoxic than GCs, Dr. Bhatt said that there are clinical scenarios in which GC therapy is the best choice, so just switching to nonsteroidal drugs is no panacea. “All RA drugs have adverse side effects, and anyway, the goal of rheumatology treatment is always to get patients off corticosteroids as soon as possible,” he said.

Ms. Costello and colleagues noted that their results are consonant with earlier research, including a single-center, cross-sectional study in which less than 6 months’ use of prednisolone at a median dose of 7.5 mg was associated with hypertension. In a German registry study, among patients who received doses of less than 7.5 mg for less than 6 months, there were higher rates of self-reported elevations in blood pressure.

The findings are at odds, however, with a recent matched-cohort study, which also used data from the Clinical Practice Research Datalink. That study found no association between GC use and hypertension.

GCs have come under increasing scrutiny in regard to several diseases. A study published July 7 found that even short-term courses of a few days’ duration entail risks for serious adverse events.

Ms. Costello’s group says that an estimate of GC-related incident hypertension in RA should allow more informed treatment decisions and that their findings highlight the ongoing need to monitor for and address this risk.

The study was supported by the Centre for Epidemiology Versus Arthritis and by the National Institute for Health Research Manchester Biomedical Research Centre. Coauthor William G. Dixon, PhD, has received consultancy fees from Google and Bayer unrelated to this study. Dr. Bhatt has disclosed no relevant financial relationships.

SOURCE: Costello RE et al. Rheumatology. 2020 June 27. doi: 10.1093/rheumatology/keaa209.

A version of this article originally appeared on Medscape.com.

Although the adverse effects of systemic glucocorticoids (GCs) are well known, their association with hypertension in rheumatoid arthritis (RA) has been unclear. Now, a large population-based study shows that the drugs are linked to a 17% overall increased risk for incident hypertension among patients with RA.

Further, when the researchers stratified participants by dose category, they found that doses higher than 7.5 mg were significantly associated with hypertension. Cumulative dosage was not tied to any clear pattern of risk.

The authors, led by Ruth E. Costello, a researcher at the Centre for Epidemiology Versus Arthritis in the Centre for Musculoskeletal Research at the University of Manchester (England) concluded that patients who are taking these drugs for the treatment of RA should be monitored for high blood pressure, which is an important but modifiable cardiovascular risk factor, and treated appropriately.

The results of Ms. Costello and colleagues’ study were published June 27 in Rheumatology.

“While fractures associated with these steroid drugs are well studied, hypertension is a side effect that seems to have been less well studied, and yet it is an important cardiovascular risk factor that can be managed,” Ms. Costello said in an interview.

To better understand the possible association, Ms. Costello and colleagues identified 17,760 patients who were newly diagnosed with RA between 1992 and 2019 and were included in the Clinical Practice Research Datalink, which represents about 7% of the U.K. population. None of the patients had hypertension at initial RA diagnosis. Slightly more than two-thirds were women (68.1%), and the mean age was 56.3 years.

Of those patients, 7,421 (41.8%) were prescribed GCs during postdiagnosis follow-up. Most patients (73%) were followed for at least 2 years.

Patients who used GCs were slightly older than never-users (mean age, 57.7 vs. 55.3 years), were predominantly women, had a history of smoking, and had more comorbidities.

The overall incidence rate (IR) of hypertension was 64.1 per 1,000 person-years (95% confidence interval, 62.5-65.7). There were 6,243 cases of incident hypertension over 97,547 person-years of follow-up.

Among those exposed to GCs, 1,321 patients developed hypertension, for an IR of 87.6 per 1,000 person-years. Among unexposed participants, the IR for hypertension was 59.7 per 1,000 person-years. In Cox proportional hazards modeling, GC use was associated with a 17% increased risk for hypertension (hazard ratio, 1.17; 95% CI, 1.10-1.24).

The researchers noted that 40% of GC users with hypertension were not prescribed an antihypertensive agent at any point during the study. “Whilst some may have been offered lifestyle advice, left untreated this has important implications in terms of addressing modifiable risk factors in an RA population already at increased risk of CV disease,” they wrote.

They noted that cardiovascular disease is a major driver of the elevated mortality risk seen among adults with RA compared with the general population and that recent treatment recommendations address management of cardiovascular risks in these patients.

“There are several routes by which GCs may promote cardiovascular disease, including hypertension, metabolic changes, diabetes, and weight gain. We don’t currently know the extent to which each of these individual mechanisms may be increasing cardiovascular disease,” said Ms. Costello.

“Glucocorticoids increase fluid retention and promote obesity and hypertension,” said Rajat S. Bhatt, MD, a rheumatologist at Prime Rheumatology and Memorial Hermann Katy Hospital in Richmond, Texas, who sees hypertension in GC users in his clinical practice. “So patients need to be monitored for these risk factors,” he said in an interview.

Although hypertension may be a significant factor in the increase in cardiovascular disease in the RA population, Dr. Bhatt said the major driver is likely the intrinsic inflammatory state caused by the disease itself. As to why the GC-hypertension connection has flown under the radar in RA, he added, “That specific link has been difficult to tease out since RA patients are often on multiple medications.”

In regard to the role of dosage, Dr. Bhatt said that hypertension risk increases with higher GC doses, as the U.K. study indicates, and usually subsides when patients stop using GCs.

“Whether the observed dose association is causal or influenced by the underlying disease severity, our results suggest we should be vigilant in patients on all doses of GC, especially higher doses,” Ms. Costello added.

In regard to using drugs that are less cardiotoxic than GCs, Dr. Bhatt said that there are clinical scenarios in which GC therapy is the best choice, so just switching to nonsteroidal drugs is no panacea. “All RA drugs have adverse side effects, and anyway, the goal of rheumatology treatment is always to get patients off corticosteroids as soon as possible,” he said.

Ms. Costello and colleagues noted that their results are consonant with earlier research, including a single-center, cross-sectional study in which less than 6 months’ use of prednisolone at a median dose of 7.5 mg was associated with hypertension. In a German registry study, among patients who received doses of less than 7.5 mg for less than 6 months, there were higher rates of self-reported elevations in blood pressure.

The findings are at odds, however, with a recent matched-cohort study, which also used data from the Clinical Practice Research Datalink. That study found no association between GC use and hypertension.

GCs have come under increasing scrutiny in regard to several diseases. A study published July 7 found that even short-term courses of a few days’ duration entail risks for serious adverse events.

Ms. Costello’s group says that an estimate of GC-related incident hypertension in RA should allow more informed treatment decisions and that their findings highlight the ongoing need to monitor for and address this risk.

The study was supported by the Centre for Epidemiology Versus Arthritis and by the National Institute for Health Research Manchester Biomedical Research Centre. Coauthor William G. Dixon, PhD, has received consultancy fees from Google and Bayer unrelated to this study. Dr. Bhatt has disclosed no relevant financial relationships.

SOURCE: Costello RE et al. Rheumatology. 2020 June 27. doi: 10.1093/rheumatology/keaa209.

A version of this article originally appeared on Medscape.com.

Although the adverse effects of systemic glucocorticoids (GCs) are well known, their association with hypertension in rheumatoid arthritis (RA) has been unclear. Now, a large population-based study shows that the drugs are linked to a 17% overall increased risk for incident hypertension among patients with RA.

Further, when the researchers stratified participants by dose category, they found that doses higher than 7.5 mg were significantly associated with hypertension. Cumulative dosage was not tied to any clear pattern of risk.

The authors, led by Ruth E. Costello, a researcher at the Centre for Epidemiology Versus Arthritis in the Centre for Musculoskeletal Research at the University of Manchester (England) concluded that patients who are taking these drugs for the treatment of RA should be monitored for high blood pressure, which is an important but modifiable cardiovascular risk factor, and treated appropriately.

The results of Ms. Costello and colleagues’ study were published June 27 in Rheumatology.

“While fractures associated with these steroid drugs are well studied, hypertension is a side effect that seems to have been less well studied, and yet it is an important cardiovascular risk factor that can be managed,” Ms. Costello said in an interview.

To better understand the possible association, Ms. Costello and colleagues identified 17,760 patients who were newly diagnosed with RA between 1992 and 2019 and were included in the Clinical Practice Research Datalink, which represents about 7% of the U.K. population. None of the patients had hypertension at initial RA diagnosis. Slightly more than two-thirds were women (68.1%), and the mean age was 56.3 years.

Of those patients, 7,421 (41.8%) were prescribed GCs during postdiagnosis follow-up. Most patients (73%) were followed for at least 2 years.

Patients who used GCs were slightly older than never-users (mean age, 57.7 vs. 55.3 years), were predominantly women, had a history of smoking, and had more comorbidities.

The overall incidence rate (IR) of hypertension was 64.1 per 1,000 person-years (95% confidence interval, 62.5-65.7). There were 6,243 cases of incident hypertension over 97,547 person-years of follow-up.

Among those exposed to GCs, 1,321 patients developed hypertension, for an IR of 87.6 per 1,000 person-years. Among unexposed participants, the IR for hypertension was 59.7 per 1,000 person-years. In Cox proportional hazards modeling, GC use was associated with a 17% increased risk for hypertension (hazard ratio, 1.17; 95% CI, 1.10-1.24).

The researchers noted that 40% of GC users with hypertension were not prescribed an antihypertensive agent at any point during the study. “Whilst some may have been offered lifestyle advice, left untreated this has important implications in terms of addressing modifiable risk factors in an RA population already at increased risk of CV disease,” they wrote.

They noted that cardiovascular disease is a major driver of the elevated mortality risk seen among adults with RA compared with the general population and that recent treatment recommendations address management of cardiovascular risks in these patients.

“There are several routes by which GCs may promote cardiovascular disease, including hypertension, metabolic changes, diabetes, and weight gain. We don’t currently know the extent to which each of these individual mechanisms may be increasing cardiovascular disease,” said Ms. Costello.

“Glucocorticoids increase fluid retention and promote obesity and hypertension,” said Rajat S. Bhatt, MD, a rheumatologist at Prime Rheumatology and Memorial Hermann Katy Hospital in Richmond, Texas, who sees hypertension in GC users in his clinical practice. “So patients need to be monitored for these risk factors,” he said in an interview.

Although hypertension may be a significant factor in the increase in cardiovascular disease in the RA population, Dr. Bhatt said the major driver is likely the intrinsic inflammatory state caused by the disease itself. As to why the GC-hypertension connection has flown under the radar in RA, he added, “That specific link has been difficult to tease out since RA patients are often on multiple medications.”

In regard to the role of dosage, Dr. Bhatt said that hypertension risk increases with higher GC doses, as the U.K. study indicates, and usually subsides when patients stop using GCs.

“Whether the observed dose association is causal or influenced by the underlying disease severity, our results suggest we should be vigilant in patients on all doses of GC, especially higher doses,” Ms. Costello added.

In regard to using drugs that are less cardiotoxic than GCs, Dr. Bhatt said that there are clinical scenarios in which GC therapy is the best choice, so just switching to nonsteroidal drugs is no panacea. “All RA drugs have adverse side effects, and anyway, the goal of rheumatology treatment is always to get patients off corticosteroids as soon as possible,” he said.

Ms. Costello and colleagues noted that their results are consonant with earlier research, including a single-center, cross-sectional study in which less than 6 months’ use of prednisolone at a median dose of 7.5 mg was associated with hypertension. In a German registry study, among patients who received doses of less than 7.5 mg for less than 6 months, there were higher rates of self-reported elevations in blood pressure.

The findings are at odds, however, with a recent matched-cohort study, which also used data from the Clinical Practice Research Datalink. That study found no association between GC use and hypertension.

GCs have come under increasing scrutiny in regard to several diseases. A study published July 7 found that even short-term courses of a few days’ duration entail risks for serious adverse events.

Ms. Costello’s group says that an estimate of GC-related incident hypertension in RA should allow more informed treatment decisions and that their findings highlight the ongoing need to monitor for and address this risk.

The study was supported by the Centre for Epidemiology Versus Arthritis and by the National Institute for Health Research Manchester Biomedical Research Centre. Coauthor William G. Dixon, PhD, has received consultancy fees from Google and Bayer unrelated to this study. Dr. Bhatt has disclosed no relevant financial relationships.

SOURCE: Costello RE et al. Rheumatology. 2020 June 27. doi: 10.1093/rheumatology/keaa209.

A version of this article originally appeared on Medscape.com.

A single yearly dose of zoledronic acid had no impact on the progression of abdominal aortic calcification in postmenopausal women with osteoporosis, based on data from 502 women.

Although bisphosphonates have been shown to reduce the formation and progression of vascular calcification in animal studies, the impact on aortic calcification in humans has not been studied, wrote Guoqi Cai, PhD, of the University of Tasmania, Australia, and colleagues.

In a post hoc analysis published in Osteoporosis International, the researchers reviewed data from the HORIZON Pivotal Fracture trial of women with osteoporosis.

The study population included 234 postmenopausal women with osteoporosis who received an annual infusion of 5 mg zoledronic acid (ZA) and 268 who received a placebo. The mean age of the women was 72.5 years. Overall, abdominal aortic calcification (AAC) was present in 292 women (58%) at baseline, defined as an AAC score greater than 0, and AAC scores were similar between the intervention and placebo groups.

Over 3 years, AAC progressed similarly between the ZA and placebo groups (29% and 31%, respectively). Progression was defined as an increase in AAC score, which was measured by comparing spinal x-rays at baseline and after 3 years. In a subgroup analysis, progression of AAC was similar between the ZA and placebo groups with and without baseline AAC.

“The lack of effect on the progression of vascular calcification with zoledronic acid treatment in this study does not rule out a potential role of bisphosphonates in reducing cardiovascular mortality mediated through other mechanisms,” the researchers noted.

No correlation appeared between change in AAC score and change in bone mineral density at the total hip and femoral neck during the study period in any of the groups.

The study findings were limited by several factors including the post hoc analysis, potential lack of sensitivity of the AAC-8 scale in measuring small AAC changes, and homogenous study population, the researchers noted.

However, the study is the first to examine the impact of zoledronic acid on aortic calcification in humans, and was strengthened by the randomized design, the researchers said. Although other studies on the impact of bisphosphonates on vascular calcification have been inconsistent, the “finding that zoledronic acid was not protective against vascular calcification agrees with previous trials of nitrogen-containing bisphosphonates conducted in postmenopausal women with osteoporosis,” as well as chronic kidney disease patients and renal transplant patients, they said.

“Thus, our findings do not support the use of zoledronic acid for the treatment of vascular calcification,” they concluded.

The study was supported by Novartis. Dr. Cai had no financial conflicts to disclose.

[email protected]

SOURCE: Cai G. et al. Osteoporosis Int. 2020 May 2. doi: 10.1007/s00198-020-05430-z.

A single yearly dose of zoledronic acid had no impact on the progression of abdominal aortic calcification in postmenopausal women with osteoporosis, based on data from 502 women.

Although bisphosphonates have been shown to reduce the formation and progression of vascular calcification in animal studies, the impact on aortic calcification in humans has not been studied, wrote Guoqi Cai, PhD, of the University of Tasmania, Australia, and colleagues.

In a post hoc analysis published in Osteoporosis International, the researchers reviewed data from the HORIZON Pivotal Fracture trial of women with osteoporosis.

The study population included 234 postmenopausal women with osteoporosis who received an annual infusion of 5 mg zoledronic acid (ZA) and 268 who received a placebo. The mean age of the women was 72.5 years. Overall, abdominal aortic calcification (AAC) was present in 292 women (58%) at baseline, defined as an AAC score greater than 0, and AAC scores were similar between the intervention and placebo groups.

Over 3 years, AAC progressed similarly between the ZA and placebo groups (29% and 31%, respectively). Progression was defined as an increase in AAC score, which was measured by comparing spinal x-rays at baseline and after 3 years. In a subgroup analysis, progression of AAC was similar between the ZA and placebo groups with and without baseline AAC.

“The lack of effect on the progression of vascular calcification with zoledronic acid treatment in this study does not rule out a potential role of bisphosphonates in reducing cardiovascular mortality mediated through other mechanisms,” the researchers noted.

No correlation appeared between change in AAC score and change in bone mineral density at the total hip and femoral neck during the study period in any of the groups.

The study findings were limited by several factors including the post hoc analysis, potential lack of sensitivity of the AAC-8 scale in measuring small AAC changes, and homogenous study population, the researchers noted.

However, the study is the first to examine the impact of zoledronic acid on aortic calcification in humans, and was strengthened by the randomized design, the researchers said. Although other studies on the impact of bisphosphonates on vascular calcification have been inconsistent, the “finding that zoledronic acid was not protective against vascular calcification agrees with previous trials of nitrogen-containing bisphosphonates conducted in postmenopausal women with osteoporosis,” as well as chronic kidney disease patients and renal transplant patients, they said.

“Thus, our findings do not support the use of zoledronic acid for the treatment of vascular calcification,” they concluded.

The study was supported by Novartis. Dr. Cai had no financial conflicts to disclose.

[email protected]

SOURCE: Cai G. et al. Osteoporosis Int. 2020 May 2. doi: 10.1007/s00198-020-05430-z.

A single yearly dose of zoledronic acid had no impact on the progression of abdominal aortic calcification in postmenopausal women with osteoporosis, based on data from 502 women.

Although bisphosphonates have been shown to reduce the formation and progression of vascular calcification in animal studies, the impact on aortic calcification in humans has not been studied, wrote Guoqi Cai, PhD, of the University of Tasmania, Australia, and colleagues.

In a post hoc analysis published in Osteoporosis International, the researchers reviewed data from the HORIZON Pivotal Fracture trial of women with osteoporosis.

The study population included 234 postmenopausal women with osteoporosis who received an annual infusion of 5 mg zoledronic acid (ZA) and 268 who received a placebo. The mean age of the women was 72.5 years. Overall, abdominal aortic calcification (AAC) was present in 292 women (58%) at baseline, defined as an AAC score greater than 0, and AAC scores were similar between the intervention and placebo groups.

Over 3 years, AAC progressed similarly between the ZA and placebo groups (29% and 31%, respectively). Progression was defined as an increase in AAC score, which was measured by comparing spinal x-rays at baseline and after 3 years. In a subgroup analysis, progression of AAC was similar between the ZA and placebo groups with and without baseline AAC.

“The lack of effect on the progression of vascular calcification with zoledronic acid treatment in this study does not rule out a potential role of bisphosphonates in reducing cardiovascular mortality mediated through other mechanisms,” the researchers noted.

No correlation appeared between change in AAC score and change in bone mineral density at the total hip and femoral neck during the study period in any of the groups.

The study findings were limited by several factors including the post hoc analysis, potential lack of sensitivity of the AAC-8 scale in measuring small AAC changes, and homogenous study population, the researchers noted.

However, the study is the first to examine the impact of zoledronic acid on aortic calcification in humans, and was strengthened by the randomized design, the researchers said. Although other studies on the impact of bisphosphonates on vascular calcification have been inconsistent, the “finding that zoledronic acid was not protective against vascular calcification agrees with previous trials of nitrogen-containing bisphosphonates conducted in postmenopausal women with osteoporosis,” as well as chronic kidney disease patients and renal transplant patients, they said.

“Thus, our findings do not support the use of zoledronic acid for the treatment of vascular calcification,” they concluded.

The study was supported by Novartis. Dr. Cai had no financial conflicts to disclose.

[email protected]

SOURCE: Cai G. et al. Osteoporosis Int. 2020 May 2. doi: 10.1007/s00198-020-05430-z.

Older adults, particularly postmenopausal women, are often advised to pursue low-impact, low-intensity exercise as a way to preserve joint health, but that approach might actually contribute to a decline in bone mineral density, researchers report.

Concerns about falls and fracture risk have led many clinicians to advise against higher-impact activities, like jumping, but that is exactly the type of activity that improves bone density and physical function, said Belinda Beck, PhD, professor at the Griffith University School of Allied Health Sciences in Southport, Australia.

“There has always been a quandary in terms of pursuing research on this,” she said in an interview. “We know from animal studies that bone only responds to high-intensity activity, but we worry about advising that for people with low bone mass, so instead we give them medications.”

“But not everyone likes to go on meds, they’re not 100% effective, and they’re not free of side effects,” said Beck, who is also the owner and director of The Bone Clinic in Brisbane, Australia.

In 2014, to assess whether high-intensity resistance and impact training (HiRIT) was a safe and effective way to improve bone mass, Beck and her colleagues conducted the LIFTMOR study of 101 postmenopausal women. The researchers showed that bone mineral density in the lumbar spine and femoral neck regions and functional performance measures were significantly better in the 49 participants randomized to HiRIT for 8 months than in the 52 randomized to low-intensity training.

Three years after the completion of LIFTMOR, the researchers looked at bone mineral density in 23 women from the HiRIT group in their retrospective observational study, the results of which were presented at the virtual American College of Sports Medicine 2020 Annual Meeting.

Ongoing gains were significantly better for the seven participants who continued with HiRIT (at least 25% compliance) than for the 16 who did not when looking at both bone mineral density of the lumbar spine (8.63% vs. 2.18%; P = .042) and femoral neck (3.67% vs. 2.85%; P = 0.14).

However, the women who discontinued HiRIT after 8 months maintained the gains in bone mineral density that they had achieved 3 years earlier.

Functional outcomes in the women who continued HiRIT were better than those in the women who did not, but the differences were not significant.

“The takeaway here is that this type of exercise appears to be a highly effective therapy to reduce risk of osteoporotic fracture, since it improves bone mass,” Beck said.

Jump more, lose less bone density

Given the widespread reluctance to suggest HiRIT-type activity to those with low bone mass, this research is significant, said Vanessa Yingling, PhD, from the Department of Kinesiology at California State University, East Bay.

“Once women hit 60, they’re somehow regarded as frail, but that becomes a self-fulfilling prophecy when we take this kinder, gentler approach to exercise,” Yingling said in an interview. “Building bone density in older adults is important, but maintaining current bone density is just as crucial. Without high-impact activity, we are likely to see decelerating density at a faster rate.”

The other key to the recent research is the functional testing, Yingling added. In addition to bone density measures, high-intensity activity can improve mobility and muscle strength, as the study noted.

This type of activity can be done in shorter bursts, making these workouts more efficient, she explained. For example, a Tabata high-intensity interval training session usually takes about 10 minutes, warm-up and cool-down included.

“A HiRIT workout even once or twice a week would likely improve function, strength, and bone density maintenance,” Beck said. “The result of that would be better fall prevention and potentially less medication usage for BMD issues.”

Both men and women can benefit from a HiRIT workout, Beck and Yingling said. Initially, supervision by a knowledgeable trainer or physical therapist is ideal, they added.

This article first appeared on Medscape.com.

Older adults, particularly postmenopausal women, are often advised to pursue low-impact, low-intensity exercise as a way to preserve joint health, but that approach might actually contribute to a decline in bone mineral density, researchers report.

Concerns about falls and fracture risk have led many clinicians to advise against higher-impact activities, like jumping, but that is exactly the type of activity that improves bone density and physical function, said Belinda Beck, PhD, professor at the Griffith University School of Allied Health Sciences in Southport, Australia.

“There has always been a quandary in terms of pursuing research on this,” she said in an interview. “We know from animal studies that bone only responds to high-intensity activity, but we worry about advising that for people with low bone mass, so instead we give them medications.”

“But not everyone likes to go on meds, they’re not 100% effective, and they’re not free of side effects,” said Beck, who is also the owner and director of The Bone Clinic in Brisbane, Australia.

In 2014, to assess whether high-intensity resistance and impact training (HiRIT) was a safe and effective way to improve bone mass, Beck and her colleagues conducted the LIFTMOR study of 101 postmenopausal women. The researchers showed that bone mineral density in the lumbar spine and femoral neck regions and functional performance measures were significantly better in the 49 participants randomized to HiRIT for 8 months than in the 52 randomized to low-intensity training.

Three years after the completion of LIFTMOR, the researchers looked at bone mineral density in 23 women from the HiRIT group in their retrospective observational study, the results of which were presented at the virtual American College of Sports Medicine 2020 Annual Meeting.

Ongoing gains were significantly better for the seven participants who continued with HiRIT (at least 25% compliance) than for the 16 who did not when looking at both bone mineral density of the lumbar spine (8.63% vs. 2.18%; P = .042) and femoral neck (3.67% vs. 2.85%; P = 0.14).

However, the women who discontinued HiRIT after 8 months maintained the gains in bone mineral density that they had achieved 3 years earlier.

Functional outcomes in the women who continued HiRIT were better than those in the women who did not, but the differences were not significant.

“The takeaway here is that this type of exercise appears to be a highly effective therapy to reduce risk of osteoporotic fracture, since it improves bone mass,” Beck said.

Jump more, lose less bone density

Given the widespread reluctance to suggest HiRIT-type activity to those with low bone mass, this research is significant, said Vanessa Yingling, PhD, from the Department of Kinesiology at California State University, East Bay.

“Once women hit 60, they’re somehow regarded as frail, but that becomes a self-fulfilling prophecy when we take this kinder, gentler approach to exercise,” Yingling said in an interview. “Building bone density in older adults is important, but maintaining current bone density is just as crucial. Without high-impact activity, we are likely to see decelerating density at a faster rate.”

The other key to the recent research is the functional testing, Yingling added. In addition to bone density measures, high-intensity activity can improve mobility and muscle strength, as the study noted.

This type of activity can be done in shorter bursts, making these workouts more efficient, she explained. For example, a Tabata high-intensity interval training session usually takes about 10 minutes, warm-up and cool-down included.

“A HiRIT workout even once or twice a week would likely improve function, strength, and bone density maintenance,” Beck said. “The result of that would be better fall prevention and potentially less medication usage for BMD issues.”

Both men and women can benefit from a HiRIT workout, Beck and Yingling said. Initially, supervision by a knowledgeable trainer or physical therapist is ideal, they added.

This article first appeared on Medscape.com.

Older adults, particularly postmenopausal women, are often advised to pursue low-impact, low-intensity exercise as a way to preserve joint health, but that approach might actually contribute to a decline in bone mineral density, researchers report.

Concerns about falls and fracture risk have led many clinicians to advise against higher-impact activities, like jumping, but that is exactly the type of activity that improves bone density and physical function, said Belinda Beck, PhD, professor at the Griffith University School of Allied Health Sciences in Southport, Australia.

“There has always been a quandary in terms of pursuing research on this,” she said in an interview. “We know from animal studies that bone only responds to high-intensity activity, but we worry about advising that for people with low bone mass, so instead we give them medications.”

“But not everyone likes to go on meds, they’re not 100% effective, and they’re not free of side effects,” said Beck, who is also the owner and director of The Bone Clinic in Brisbane, Australia.

In 2014, to assess whether high-intensity resistance and impact training (HiRIT) was a safe and effective way to improve bone mass, Beck and her colleagues conducted the LIFTMOR study of 101 postmenopausal women. The researchers showed that bone mineral density in the lumbar spine and femoral neck regions and functional performance measures were significantly better in the 49 participants randomized to HiRIT for 8 months than in the 52 randomized to low-intensity training.

Three years after the completion of LIFTMOR, the researchers looked at bone mineral density in 23 women from the HiRIT group in their retrospective observational study, the results of which were presented at the virtual American College of Sports Medicine 2020 Annual Meeting.

Ongoing gains were significantly better for the seven participants who continued with HiRIT (at least 25% compliance) than for the 16 who did not when looking at both bone mineral density of the lumbar spine (8.63% vs. 2.18%; P = .042) and femoral neck (3.67% vs. 2.85%; P = 0.14).

However, the women who discontinued HiRIT after 8 months maintained the gains in bone mineral density that they had achieved 3 years earlier.

Functional outcomes in the women who continued HiRIT were better than those in the women who did not, but the differences were not significant.

“The takeaway here is that this type of exercise appears to be a highly effective therapy to reduce risk of osteoporotic fracture, since it improves bone mass,” Beck said.

Jump more, lose less bone density

Given the widespread reluctance to suggest HiRIT-type activity to those with low bone mass, this research is significant, said Vanessa Yingling, PhD, from the Department of Kinesiology at California State University, East Bay.

“Once women hit 60, they’re somehow regarded as frail, but that becomes a self-fulfilling prophecy when we take this kinder, gentler approach to exercise,” Yingling said in an interview. “Building bone density in older adults is important, but maintaining current bone density is just as crucial. Without high-impact activity, we are likely to see decelerating density at a faster rate.”

The other key to the recent research is the functional testing, Yingling added. In addition to bone density measures, high-intensity activity can improve mobility and muscle strength, as the study noted.

This type of activity can be done in shorter bursts, making these workouts more efficient, she explained. For example, a Tabata high-intensity interval training session usually takes about 10 minutes, warm-up and cool-down included.

“A HiRIT workout even once or twice a week would likely improve function, strength, and bone density maintenance,” Beck said. “The result of that would be better fall prevention and potentially less medication usage for BMD issues.”

Both men and women can benefit from a HiRIT workout, Beck and Yingling said. Initially, supervision by a knowledgeable trainer or physical therapist is ideal, they added.

This article first appeared on Medscape.com.

Dairy consumption does not improve bone mineral density (BMD) or reduce the risk of osteoporotic fracture in women starting menopause, a new analysis of the Study of Women’s Health Across the Nation (SWAN) indicates.

copyright/Jupiterimages/Getty Images

And this was regardless of baseline menopausal status, say Taylor Wallace, PhD, of George Mason University, Fairfax, Va., and colleagues in their article published online in Menopause.

“Our previous work indicated a potential premenopausal critical window in regard to the effectiveness of calcium supplements,” they noted.

Clifford Rosen, MD, professor of medicine, Tufts University, Boston, said in an interview that he believes the study reinforces earlier work that dairy intake in women aged 45-55 years does not affect the rate of bone loss or fractures.

“The SWAN study is longitudinal and with sufficient numbers to support their conclusion,” Dr. Rosen said.
 

SWAN study: White women consume the most dairy

As dairy is known to be one of the foremost sources of calcium, along with other bone beneficial nutrients, Dr. Wallace and colleagues decided to examine intake of this food type with long-term bone health using the SWAN data.

The SWAN bone substudy started in 1996 and involved 3,302 pre- or early perimenopausal women aged 42-53 years. The sample size for the annualized rate of BMD loss and fracture analysis involved 1955 women.

A modified food frequency questionnaire was used at baseline, at visit 5, and again at visit 9 to record daily dairy consumption, among many other food items.

“Women were classified into four dairy groups based on this cumulative average dairy intake,” Wallace and colleagues note. Intake was grouped into < 0.5 servings/day; 0.5 to < 1.5 servings/day; 1.5 to < 2.5 servings/day, and ≥ 2.5 servings/day.

“Non-Hispanic white individuals were more likely to consume higher amounts of dairy compared to African American, Chinese, and Japanese individuals,” the authors noted.

They found no significant differences for baseline age, body mass index, femoral neck and lumbar spine BMD, calcium supplement use, or fracture history by dairy intake group.

There were also no differences in the hazard ratios or relative risk of nontraumatic fractures by frequency of daily dairy intake.
 

Findings on dairy and bone are inconsistent

The authors caution that several factors should be taken into account when considering these new findings.

“First, dairy intake was low [overall] among SWAN participants, with 65% reporting consumption of < 1.5 servings/day,” they point out.

Dairy intake was also “particularly low” among racial groups other than whites, which may be due to higher rates of lactose intolerance among ethnic minorities, they speculate.

They previously reported that the use of calcium dietary supplements in SWAN was associated with a lower annualized rate of femoral neck BMD loss as well as BMD loss at the lumbar spine over 10 years of follow-up, mainly in women who were premenopausal at baseline.

But no associations were observed in the risk of bone fracture in any women in that analysis, regardless of menopausal status.

In this new analysis, there were no significant differences in calcium supplement use across the dairy intake groups.

Dr. Wallace and colleagues also noted that the relevance of dairy product intake for bone health has been in question as some observational studies have even “suggested consumption to be associated with an increased risk of fractures.”

The lead author of one of these studies, Karl Michaelsson, MD, PhD, of Uppsala (Sweden) University, said in an interview that his study had looked only at milk intake, and the lack of benefit on bone health from high milk consumption may not apply to all dairy products.

We “may need to look at different types of dairy products,” he said.

Summing up, Stephanie Faubion, MD, MBA, medical director of the North American Menopause Society, said the new SWAN findings do add to the evidence base, “albeit inconsistent ... suggesting a lack of benefit from dairy intake on BMD and fracture risk.”
 

Vitamin D data were not available; dairy may help in this respect

Dr. Rosen also noted that no information was available on vitamin D levels in patients involved in SWAN, which he believes is a limitation of the study.

Nevertheless, “it is important to recognize that elderly individuals who increase their dairy intake may have health benefits as recognized in the Nurses’ Health Study, possibly due to increased protein intake, higher vitamin D levels, or greater calcium intake,” he observed.

A randomized trial of enhanced dairy intake in long-term care residents is currently underway, which should provide answers for a much more vulnerable population than those in the SWAN cohort, Dr. Rosen concluded.

Dr. Wallace has reported serving on the scientific advisory board of the Vitamin Shoppe and has received research support from the National Dairy Council and scientific consulting fees from several food companies. Dr. Rosen has reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Dairy consumption does not improve bone mineral density (BMD) or reduce the risk of osteoporotic fracture in women starting menopause, a new analysis of the Study of Women’s Health Across the Nation (SWAN) indicates.

copyright/Jupiterimages/Getty Images

And this was regardless of baseline menopausal status, say Taylor Wallace, PhD, of George Mason University, Fairfax, Va., and colleagues in their article published online in Menopause.

“Our previous work indicated a potential premenopausal critical window in regard to the effectiveness of calcium supplements,” they noted.

Clifford Rosen, MD, professor of medicine, Tufts University, Boston, said in an interview that he believes the study reinforces earlier work that dairy intake in women aged 45-55 years does not affect the rate of bone loss or fractures.

“The SWAN study is longitudinal and with sufficient numbers to support their conclusion,” Dr. Rosen said.
 

SWAN study: White women consume the most dairy

As dairy is known to be one of the foremost sources of calcium, along with other bone beneficial nutrients, Dr. Wallace and colleagues decided to examine intake of this food type with long-term bone health using the SWAN data.

The SWAN bone substudy started in 1996 and involved 3,302 pre- or early perimenopausal women aged 42-53 years. The sample size for the annualized rate of BMD loss and fracture analysis involved 1955 women.

A modified food frequency questionnaire was used at baseline, at visit 5, and again at visit 9 to record daily dairy consumption, among many other food items.

“Women were classified into four dairy groups based on this cumulative average dairy intake,” Wallace and colleagues note. Intake was grouped into < 0.5 servings/day; 0.5 to < 1.5 servings/day; 1.5 to < 2.5 servings/day, and ≥ 2.5 servings/day.

“Non-Hispanic white individuals were more likely to consume higher amounts of dairy compared to African American, Chinese, and Japanese individuals,” the authors noted.

They found no significant differences for baseline age, body mass index, femoral neck and lumbar spine BMD, calcium supplement use, or fracture history by dairy intake group.

There were also no differences in the hazard ratios or relative risk of nontraumatic fractures by frequency of daily dairy intake.
 

Findings on dairy and bone are inconsistent

The authors caution that several factors should be taken into account when considering these new findings.

“First, dairy intake was low [overall] among SWAN participants, with 65% reporting consumption of < 1.5 servings/day,” they point out.

Dairy intake was also “particularly low” among racial groups other than whites, which may be due to higher rates of lactose intolerance among ethnic minorities, they speculate.

They previously reported that the use of calcium dietary supplements in SWAN was associated with a lower annualized rate of femoral neck BMD loss as well as BMD loss at the lumbar spine over 10 years of follow-up, mainly in women who were premenopausal at baseline.

But no associations were observed in the risk of bone fracture in any women in that analysis, regardless of menopausal status.

In this new analysis, there were no significant differences in calcium supplement use across the dairy intake groups.

Dr. Wallace and colleagues also noted that the relevance of dairy product intake for bone health has been in question as some observational studies have even “suggested consumption to be associated with an increased risk of fractures.”

The lead author of one of these studies, Karl Michaelsson, MD, PhD, of Uppsala (Sweden) University, said in an interview that his study had looked only at milk intake, and the lack of benefit on bone health from high milk consumption may not apply to all dairy products.

We “may need to look at different types of dairy products,” he said.

Summing up, Stephanie Faubion, MD, MBA, medical director of the North American Menopause Society, said the new SWAN findings do add to the evidence base, “albeit inconsistent ... suggesting a lack of benefit from dairy intake on BMD and fracture risk.”
 

Vitamin D data were not available; dairy may help in this respect

Dr. Rosen also noted that no information was available on vitamin D levels in patients involved in SWAN, which he believes is a limitation of the study.

Nevertheless, “it is important to recognize that elderly individuals who increase their dairy intake may have health benefits as recognized in the Nurses’ Health Study, possibly due to increased protein intake, higher vitamin D levels, or greater calcium intake,” he observed.

A randomized trial of enhanced dairy intake in long-term care residents is currently underway, which should provide answers for a much more vulnerable population than those in the SWAN cohort, Dr. Rosen concluded.

Dr. Wallace has reported serving on the scientific advisory board of the Vitamin Shoppe and has received research support from the National Dairy Council and scientific consulting fees from several food companies. Dr. Rosen has reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Dairy consumption does not improve bone mineral density (BMD) or reduce the risk of osteoporotic fracture in women starting menopause, a new analysis of the Study of Women’s Health Across the Nation (SWAN) indicates.

copyright/Jupiterimages/Getty Images

And this was regardless of baseline menopausal status, say Taylor Wallace, PhD, of George Mason University, Fairfax, Va., and colleagues in their article published online in Menopause.

“Our previous work indicated a potential premenopausal critical window in regard to the effectiveness of calcium supplements,” they noted.

Clifford Rosen, MD, professor of medicine, Tufts University, Boston, said in an interview that he believes the study reinforces earlier work that dairy intake in women aged 45-55 years does not affect the rate of bone loss or fractures.

“The SWAN study is longitudinal and with sufficient numbers to support their conclusion,” Dr. Rosen said.
 

SWAN study: White women consume the most dairy

As dairy is known to be one of the foremost sources of calcium, along with other bone beneficial nutrients, Dr. Wallace and colleagues decided to examine intake of this food type with long-term bone health using the SWAN data.

The SWAN bone substudy started in 1996 and involved 3,302 pre- or early perimenopausal women aged 42-53 years. The sample size for the annualized rate of BMD loss and fracture analysis involved 1955 women.

A modified food frequency questionnaire was used at baseline, at visit 5, and again at visit 9 to record daily dairy consumption, among many other food items.

“Women were classified into four dairy groups based on this cumulative average dairy intake,” Wallace and colleagues note. Intake was grouped into < 0.5 servings/day; 0.5 to < 1.5 servings/day; 1.5 to < 2.5 servings/day, and ≥ 2.5 servings/day.

“Non-Hispanic white individuals were more likely to consume higher amounts of dairy compared to African American, Chinese, and Japanese individuals,” the authors noted.

They found no significant differences for baseline age, body mass index, femoral neck and lumbar spine BMD, calcium supplement use, or fracture history by dairy intake group.

There were also no differences in the hazard ratios or relative risk of nontraumatic fractures by frequency of daily dairy intake.
 

Findings on dairy and bone are inconsistent

The authors caution that several factors should be taken into account when considering these new findings.

“First, dairy intake was low [overall] among SWAN participants, with 65% reporting consumption of < 1.5 servings/day,” they point out.

Dairy intake was also “particularly low” among racial groups other than whites, which may be due to higher rates of lactose intolerance among ethnic minorities, they speculate.

They previously reported that the use of calcium dietary supplements in SWAN was associated with a lower annualized rate of femoral neck BMD loss as well as BMD loss at the lumbar spine over 10 years of follow-up, mainly in women who were premenopausal at baseline.

But no associations were observed in the risk of bone fracture in any women in that analysis, regardless of menopausal status.

In this new analysis, there were no significant differences in calcium supplement use across the dairy intake groups.

Dr. Wallace and colleagues also noted that the relevance of dairy product intake for bone health has been in question as some observational studies have even “suggested consumption to be associated with an increased risk of fractures.”

The lead author of one of these studies, Karl Michaelsson, MD, PhD, of Uppsala (Sweden) University, said in an interview that his study had looked only at milk intake, and the lack of benefit on bone health from high milk consumption may not apply to all dairy products.

We “may need to look at different types of dairy products,” he said.

Summing up, Stephanie Faubion, MD, MBA, medical director of the North American Menopause Society, said the new SWAN findings do add to the evidence base, “albeit inconsistent ... suggesting a lack of benefit from dairy intake on BMD and fracture risk.”
 

Vitamin D data were not available; dairy may help in this respect

Dr. Rosen also noted that no information was available on vitamin D levels in patients involved in SWAN, which he believes is a limitation of the study.

Nevertheless, “it is important to recognize that elderly individuals who increase their dairy intake may have health benefits as recognized in the Nurses’ Health Study, possibly due to increased protein intake, higher vitamin D levels, or greater calcium intake,” he observed.

A randomized trial of enhanced dairy intake in long-term care residents is currently underway, which should provide answers for a much more vulnerable population than those in the SWAN cohort, Dr. Rosen concluded.

Dr. Wallace has reported serving on the scientific advisory board of the Vitamin Shoppe and has received research support from the National Dairy Council and scientific consulting fees from several food companies. Dr. Rosen has reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

In a national sample of U.S. women in their mid-40s to mid-50s, those with high serum levels of per- and polyfluoroalkyl substances (PFAS) were likely to enter menopause 2 years earlier than those with low levels of these chemicals.

That is, the median age of natural menopause was 52.8 years versus 50.8 years in women with high versus low serum levels of these chemicals in an analysis of data from more than 1,100 women in the Study of Women’s Health Across the Nation (SWAN) Multi-Pollutant Study, which excluded women with premature menopause (before age 40) or early menopause (before age 45).

“This study suggests that select PFAS serum concentrations are associated with earlier natural menopause, a risk factor for adverse health outcomes in later life,” Ning Ding, PhD, MPH, University of Michigan, Ann Arbor, and colleagues concluded in their article, published online June 3 in the Journal of Clinical Endocrinology & Metabolism.

“Even menopause a few years earlier than usual could have a significant impact on cardiovascular and bone health, quality of life, and overall health in general among women,” senior author Sung Kyun Park, ScD, MPH, from the same institution, added in a statement.

PFAS don’t break down in the body, build up with time

PFAS have been widely used in many consumer and industrial products such as nonstick cookware, stain-repellent carpets, waterproof rain gear, microwave popcorn bags, and firefighting foam, the authors explained.

These have been dubbed “forever chemicals” because they do not degrade. Household water for an estimated 110 million Americans (one in three) may be contaminated with these chemicals, according to an Endocrine Society press release.

“PFAS are everywhere. Once they enter the body, they don’t break down and [they] build up over time,” said Dr. Ding. “Because of their persistence in humans and potentially detrimental effects on ovarian function, it is important to raise awareness of this issue and reduce exposure to these chemicals.”

Environmental exposure and accelerated ovarian aging

Earlier menopause has been associated with an increased risk of cardiovascular disease, osteoporosis, and earlier cardiovascular and overall mortality, and environmental exposure may accelerate ovarian aging, the authors wrote.

PFAS, especially the most studied types – perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) – are plausible endocrine-disrupting chemicals, but findings so far have been inconsistent.

A study of people in Ohio exposed to contaminated water found that women with earlier natural menopause had higher serum PFOA and PFOS levels (J Clin Endocriniol Metab. 2011;96:1747-53).

But in research based on National Health and Nutrition Survey Examination data, higher PFOA, PFOS, or perfluorononanoic acid (PFNA) levels were not linked to earlier menopause, although higher levels of perfluorohexane sulfonic acid (PFHxS) were (Environ Health Perspect. 2014;122:145-50).

There may have been reverse causation, where postmenopausal women had higher PFAS levels because they were not excreting these chemicals in menstrual blood.

In a third study, PFOA exposure was not linked with age at menopause onset, but this was based on recall from 10 years earlier (Environ Res. 2016;146:323-30).

The current analysis examined data from 1,120 premenopausal women who were aged 45-56 years from 1999 to 2000.

The women were seen at five sites (Boston; Detroit; Los Angeles; Oakland, Calif.; and Pittsburgh) and were ethnically diverse (577 white, 235 black, 142 Chinese, and 166 Japanese).

Baseline serum PFAS levels were measured using high performance liquid chromatography-mass spectrometry. The women were followed up to 2017 and incident menopause (12 consecutive months with no menstruation) was determined from annual interviews.

Of the 1,120 women and 5,466 person-years of follow-up, 578 women had a known date of natural incident menopause and were included in the analysis. The remaining 542 women were excluded mainly because their date of final menstruation was unknown because of hormone therapy (451) or they had a hysterectomy, or did not enter menopause during the study.

Compared with women in the lowest tertile of PFOS levels, women in the highest tertile had a significant 26%-27% greater risk of incident menopause – after adjusting for age, body mass index, and prior hormone use, race/ethnicity, study site, education, physical activity, smoking status, and parity.

Higher PFOA and PFNA levels but not higher PFHxS levels were also associated with increased risk.

Compared with women with a low overall PFAS level, those with a high level had a 63% increased risk of incident menopause (hazard ratio, 1.63; 95% confidence interval, 1.08-2.45), equivalent to having menopause a median of 2 years earlier.

Although production and use of some types of PFAS in the United States are declining, Dr. Ding and colleagues wrote, exposure continues, along with associated potential hazards to human reproductive health.

“Due to PFAS widespread use and environmental persistence, their potential adverse effects remain a public health concern,” they concluded.

SWAN was supported by the National Institutes of Health, Department of Health & Human Services through the National Institute on Aging, National Institute of Nursing Research, NIH Office of Research on Women’s Health, and the SWAN repository. The current article was supported by the National Center for Research Resources and National Center for Advancing Translational Sciences, NIH, National Institute of Environmental Health Sciences, and Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health. The authors have reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

In a national sample of U.S. women in their mid-40s to mid-50s, those with high serum levels of per- and polyfluoroalkyl substances (PFAS) were likely to enter menopause 2 years earlier than those with low levels of these chemicals.

That is, the median age of natural menopause was 52.8 years versus 50.8 years in women with high versus low serum levels of these chemicals in an analysis of data from more than 1,100 women in the Study of Women’s Health Across the Nation (SWAN) Multi-Pollutant Study, which excluded women with premature menopause (before age 40) or early menopause (before age 45).

“This study suggests that select PFAS serum concentrations are associated with earlier natural menopause, a risk factor for adverse health outcomes in later life,” Ning Ding, PhD, MPH, University of Michigan, Ann Arbor, and colleagues concluded in their article, published online June 3 in the Journal of Clinical Endocrinology & Metabolism.

“Even menopause a few years earlier than usual could have a significant impact on cardiovascular and bone health, quality of life, and overall health in general among women,” senior author Sung Kyun Park, ScD, MPH, from the same institution, added in a statement.

PFAS don’t break down in the body, build up with time

PFAS have been widely used in many consumer and industrial products such as nonstick cookware, stain-repellent carpets, waterproof rain gear, microwave popcorn bags, and firefighting foam, the authors explained.

These have been dubbed “forever chemicals” because they do not degrade. Household water for an estimated 110 million Americans (one in three) may be contaminated with these chemicals, according to an Endocrine Society press release.

“PFAS are everywhere. Once they enter the body, they don’t break down and [they] build up over time,” said Dr. Ding. “Because of their persistence in humans and potentially detrimental effects on ovarian function, it is important to raise awareness of this issue and reduce exposure to these chemicals.”

Environmental exposure and accelerated ovarian aging

Earlier menopause has been associated with an increased risk of cardiovascular disease, osteoporosis, and earlier cardiovascular and overall mortality, and environmental exposure may accelerate ovarian aging, the authors wrote.

PFAS, especially the most studied types – perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) – are plausible endocrine-disrupting chemicals, but findings so far have been inconsistent.

A study of people in Ohio exposed to contaminated water found that women with earlier natural menopause had higher serum PFOA and PFOS levels (J Clin Endocriniol Metab. 2011;96:1747-53).

But in research based on National Health and Nutrition Survey Examination data, higher PFOA, PFOS, or perfluorononanoic acid (PFNA) levels were not linked to earlier menopause, although higher levels of perfluorohexane sulfonic acid (PFHxS) were (Environ Health Perspect. 2014;122:145-50).

There may have been reverse causation, where postmenopausal women had higher PFAS levels because they were not excreting these chemicals in menstrual blood.

In a third study, PFOA exposure was not linked with age at menopause onset, but this was based on recall from 10 years earlier (Environ Res. 2016;146:323-30).

The current analysis examined data from 1,120 premenopausal women who were aged 45-56 years from 1999 to 2000.

The women were seen at five sites (Boston; Detroit; Los Angeles; Oakland, Calif.; and Pittsburgh) and were ethnically diverse (577 white, 235 black, 142 Chinese, and 166 Japanese).

Baseline serum PFAS levels were measured using high performance liquid chromatography-mass spectrometry. The women were followed up to 2017 and incident menopause (12 consecutive months with no menstruation) was determined from annual interviews.

Of the 1,120 women and 5,466 person-years of follow-up, 578 women had a known date of natural incident menopause and were included in the analysis. The remaining 542 women were excluded mainly because their date of final menstruation was unknown because of hormone therapy (451) or they had a hysterectomy, or did not enter menopause during the study.

Compared with women in the lowest tertile of PFOS levels, women in the highest tertile had a significant 26%-27% greater risk of incident menopause – after adjusting for age, body mass index, and prior hormone use, race/ethnicity, study site, education, physical activity, smoking status, and parity.

Higher PFOA and PFNA levels but not higher PFHxS levels were also associated with increased risk.

Compared with women with a low overall PFAS level, those with a high level had a 63% increased risk of incident menopause (hazard ratio, 1.63; 95% confidence interval, 1.08-2.45), equivalent to having menopause a median of 2 years earlier.

Although production and use of some types of PFAS in the United States are declining, Dr. Ding and colleagues wrote, exposure continues, along with associated potential hazards to human reproductive health.

“Due to PFAS widespread use and environmental persistence, their potential adverse effects remain a public health concern,” they concluded.

SWAN was supported by the National Institutes of Health, Department of Health & Human Services through the National Institute on Aging, National Institute of Nursing Research, NIH Office of Research on Women’s Health, and the SWAN repository. The current article was supported by the National Center for Research Resources and National Center for Advancing Translational Sciences, NIH, National Institute of Environmental Health Sciences, and Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health. The authors have reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

In a national sample of U.S. women in their mid-40s to mid-50s, those with high serum levels of per- and polyfluoroalkyl substances (PFAS) were likely to enter menopause 2 years earlier than those with low levels of these chemicals.

That is, the median age of natural menopause was 52.8 years versus 50.8 years in women with high versus low serum levels of these chemicals in an analysis of data from more than 1,100 women in the Study of Women’s Health Across the Nation (SWAN) Multi-Pollutant Study, which excluded women with premature menopause (before age 40) or early menopause (before age 45).

“This study suggests that select PFAS serum concentrations are associated with earlier natural menopause, a risk factor for adverse health outcomes in later life,” Ning Ding, PhD, MPH, University of Michigan, Ann Arbor, and colleagues concluded in their article, published online June 3 in the Journal of Clinical Endocrinology & Metabolism.

“Even menopause a few years earlier than usual could have a significant impact on cardiovascular and bone health, quality of life, and overall health in general among women,” senior author Sung Kyun Park, ScD, MPH, from the same institution, added in a statement.

PFAS don’t break down in the body, build up with time

PFAS have been widely used in many consumer and industrial products such as nonstick cookware, stain-repellent carpets, waterproof rain gear, microwave popcorn bags, and firefighting foam, the authors explained.

These have been dubbed “forever chemicals” because they do not degrade. Household water for an estimated 110 million Americans (one in three) may be contaminated with these chemicals, according to an Endocrine Society press release.

“PFAS are everywhere. Once they enter the body, they don’t break down and [they] build up over time,” said Dr. Ding. “Because of their persistence in humans and potentially detrimental effects on ovarian function, it is important to raise awareness of this issue and reduce exposure to these chemicals.”

Environmental exposure and accelerated ovarian aging

Earlier menopause has been associated with an increased risk of cardiovascular disease, osteoporosis, and earlier cardiovascular and overall mortality, and environmental exposure may accelerate ovarian aging, the authors wrote.

PFAS, especially the most studied types – perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) – are plausible endocrine-disrupting chemicals, but findings so far have been inconsistent.

A study of people in Ohio exposed to contaminated water found that women with earlier natural menopause had higher serum PFOA and PFOS levels (J Clin Endocriniol Metab. 2011;96:1747-53).

But in research based on National Health and Nutrition Survey Examination data, higher PFOA, PFOS, or perfluorononanoic acid (PFNA) levels were not linked to earlier menopause, although higher levels of perfluorohexane sulfonic acid (PFHxS) were (Environ Health Perspect. 2014;122:145-50).

There may have been reverse causation, where postmenopausal women had higher PFAS levels because they were not excreting these chemicals in menstrual blood.

In a third study, PFOA exposure was not linked with age at menopause onset, but this was based on recall from 10 years earlier (Environ Res. 2016;146:323-30).

The current analysis examined data from 1,120 premenopausal women who were aged 45-56 years from 1999 to 2000.

The women were seen at five sites (Boston; Detroit; Los Angeles; Oakland, Calif.; and Pittsburgh) and were ethnically diverse (577 white, 235 black, 142 Chinese, and 166 Japanese).

Baseline serum PFAS levels were measured using high performance liquid chromatography-mass spectrometry. The women were followed up to 2017 and incident menopause (12 consecutive months with no menstruation) was determined from annual interviews.

Of the 1,120 women and 5,466 person-years of follow-up, 578 women had a known date of natural incident menopause and were included in the analysis. The remaining 542 women were excluded mainly because their date of final menstruation was unknown because of hormone therapy (451) or they had a hysterectomy, or did not enter menopause during the study.

Compared with women in the lowest tertile of PFOS levels, women in the highest tertile had a significant 26%-27% greater risk of incident menopause – after adjusting for age, body mass index, and prior hormone use, race/ethnicity, study site, education, physical activity, smoking status, and parity.

Higher PFOA and PFNA levels but not higher PFHxS levels were also associated with increased risk.

Compared with women with a low overall PFAS level, those with a high level had a 63% increased risk of incident menopause (hazard ratio, 1.63; 95% confidence interval, 1.08-2.45), equivalent to having menopause a median of 2 years earlier.

Although production and use of some types of PFAS in the United States are declining, Dr. Ding and colleagues wrote, exposure continues, along with associated potential hazards to human reproductive health.

“Due to PFAS widespread use and environmental persistence, their potential adverse effects remain a public health concern,” they concluded.

SWAN was supported by the National Institutes of Health, Department of Health & Human Services through the National Institute on Aging, National Institute of Nursing Research, NIH Office of Research on Women’s Health, and the SWAN repository. The current article was supported by the National Center for Research Resources and National Center for Advancing Translational Sciences, NIH, National Institute of Environmental Health Sciences, and Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health. The authors have reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.