breastfeeding – NIH Director's Blog (original) (raw)
Maternal Brain Hormone Key to Strengthening Bones Could Help Treat Osteoporosis, Bone Fractures
Posted on August 1st, 2024 by Dr. Monica M. Bertagnolli
Credit: Donny Bliss/NIH
More than 200 million people around the world have osteoporosis, a condition that weakens bones to the point that they break easily. Women are at especially high risk after menopause due to declining levels of the hormone estrogen, which helps keep bones strong. While osteoporosis rarely has noticeable symptoms, it can lead to serious injuries when otherwise minor slips and falls cause broken bones that in turn can lead to further fracture risk and fracture-related mortality. So, I’m pleased to share NIH-supported research suggesting a surprising candidate for strengthening bones: a maternal hormone produced in the brain.
The study in mice reported in Nature shows that this newly discovered hormone maintains and rebuilds bone strength in lactating females, even as estrogen levels dip and calcium is lost to the demands of milk production. 1 The findings suggest this hormone—or a drug that acts similarly—could be key to treating osteoporosis and preventing and healing broken bones.
The findings come from a team led by Holly Ingraham, University of California, San Francisco. The researchers knew from studies in mice and humans that a protein related to parathyroid hormone, which is made in the mammary glands, is the main driver for stripping calcium from maternal bones for milk production. As a result of this process, nursing mothers tend to lose a lot of bone. In humans, this bone loss is 10% on average, compared to nearly 30% in mice. Fortunately, these losses are reversed after lactation ends, suggesting to the researchers there must be some other bone-strengthening factor in play.
Previous work in Ingraham’s lab, also supported by NIH, offered other clues. The researchers found that in female mice, blocking a certain estrogen receptor in select neurons in a small area of the brain led to the development of bones that were exceptionally dense and strong. 2 This was an early hint that an unidentified hormone might have a role. The team’s search in this latest study led them to brain-derived communication network factor 3 (CCN3).
The new findings showed that, in lactating female mice, CCN3 is produced in the same brain area identified in the previous study. When the researchers prevented the brain from making CCN3, lactating female mice rapidly lost bone. The researchers also found that male and female young adult and older mice gained a considerable amount of bone mass and strength when their levels of circulating CCN3 were boosted over a two-week period. In fact, in some female mice that were very old or completely lacked estrogen, the hormone more than doubled their bone mass. Tests showed that the animals’ bones weren’t just denser, but also stronger.
Further studies conducted by co-author Thomas Ambrosi, University of California, Davis, revealed that bone stem cells were responsible for receiving signals and generating the new bone. When those cells were exposed to CCN3, they ramped up bone production even more. When the researchers applied a hydrogel patch containing CCN3 to the sites of bone breaks, this spurred the formation of new bone. As a result, the researchers saw rapid bone healing in older mice comparable to what would be expected in much younger mice.
In future studies, the researchers want to gain insight into the underlying mechanisms of CCN3. They also plan to explore the hormone’s potential for treating bone loss in people at increased risk, including postmenopausal women, breast cancer survivors taking estrogen blockers, and those with other conditions leading to unhealthy bone mass, such as genetic bone disorders, chronic kidney disease, or premature ovarian failure. They suggest that more immediate local uses for CCN3 include fracture repair, cartilage regeneration, and bone improvements for anchoring dental implants. It’s a great example of how finding an answer to a scientific puzzle—like how maternal bones stay strong during breastfeeding—can potentially lead to advances that help many more people.
References:
[1] Babey ME, et al. A maternal brain hormone that builds bone. Nature. DOI: 10.1038/s41586-024-07634-3 (2024).
[2] Herber CB, et al. Estrogen signaling in arcuate Kiss1 neurons suppresses a sex-dependent female circuit promoting dense strong bones. Nature Communications. DOI: 10.1038/s41467-018-08046-4 (2019).
NIH Support: National Institute of Diabetes and Digestive and Kidney Diseases, National Institute on Aging, National Institute of General Medical Sciences, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Posted In: Health, Science, Uncategorized
Tags: aging, basic research, Bone, bone fracture, breastfeeding, calcium, estrogen, hormone, maternal health, menopause, osteoporosis
Studies Confirm COVID-19 mRNA Vaccines Safe, Effective for Pregnant Women
Posted on June 1st, 2021 by Dr. Francis Collins
Credit: GettyImages/bogdankosanovic
Clinical trials have shown that COVID-19 vaccines are remarkably effective in protecting those age 12 and up against infection by the coronavirus SARS-CoV-2. The expectation was that they would work just as well to protect pregnant women. But because pregnant women were excluded from the initial clinical trials, hard data on their safety and efficacy in this important group has been limited.
So, I’m pleased to report results from two new studies showing that the two COVID-19 mRNA vaccines now available in the United States appear to be completely safe for pregnant women. The women had good responses to the vaccines, producing needed levels of neutralizing antibodies and immune cells known as memory T cells, which may offer more lasting protection. The research also indicates that the vaccines might offer protection to infants born to vaccinated mothers.
In one study, published in JAMA [1], an NIH-supported team led by Dan Barouch, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, wanted to learn whether vaccines would protect mother and baby. To find out, they enrolled 103 women, aged 18 to 45, who chose to get either the Pfizer/BioNTech or Moderna mRNA vaccines from December 2020 through March 2021.
The sample included 30 pregnant women,16 women who were breastfeeding, and 57 women who were neither pregnant nor breastfeeding. Pregnant women in the study got their first dose of vaccine during any trimester, although most got their shots in the second or third trimester. Overall, the vaccine was well tolerated, although some women in each group developed a transient fever after the second vaccine dose, a common side effect in all groups that have been studied.
After vaccination, women in all groups produced antibodies against SARS-CoV-2. Importantly, those antibodies neutralized SARS-CoV-2 variants of concern. The researchers also found those antibodies in infant cord blood and breast milk, suggesting that they were passed on to afford some protection to infants early in life.
The other NIH-supported study, published in the journal Obstetrics & Gynecology, was conducted by a team led by Jeffery Goldstein, Northwestern’s Feinberg School of Medicine, Chicago [2]. To explore any possible safety concerns for pregnant women, the team took a first look for any negative effects of vaccination on the placenta, the vital organ that sustains the fetus during gestation.
The researchers detected no signs that the vaccines led to any unexpected damage to the placenta in this study, which included 84 women who received COVID-19 mRNA vaccines during pregnancy, most in the third trimester. As in the other study, the team found that vaccinated pregnant women showed a robust response to the vaccine, producing needed levels of neutralizing antibodies.
Overall, both studies show that COVID-19 mRNA vaccines are safe and effective in pregnancy, with the potential to benefit both mother and baby. Pregnant women also are more likely than women who aren’t pregnant to become severely ill should they become infected with this devastating coronavirus [3]. While pregnant women are urged to consult with their obstetrician about vaccination, growing evidence suggests that the best way for women during pregnancy or while breastfeeding to protect themselves and their families against COVID-19 is to roll up their sleeves and get either one of the mRNA vaccines now authorized for emergency use.
References:
[1] Immunogenicity of COVID-19 mRNA vaccines in pregnant and lactating women. Collier AY, McMahan K, Yu J, Tostanoski LH, Aguayo R, Ansel J, Chandrashekar A, Patel S, Apraku Bondzie E, Sellers D, Barrett J, Sanborn O, Wan H, Chang A, Anioke T, Nkolola J, Bradshaw C, Jacob-Dolan C, Feldman J, Gebre M, Borducchi EN, Liu J, Schmidt AG, Suscovich T, Linde C, Alter G, Hacker MR, Barouch DH. JAMA. 2021 May 13.
[2] Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in pregnancy: Measures of immunity and placental histopathology. Shanes ED, Otero S, Mithal LB, Mupanomunda CA, Miller ES, Goldstein JA. Obstet Gynecol. 2021 May 11.
[3] COVID-19 vaccines while pregnant or breastfeeding. Centers for Disease Control and Prevention.
Links:
COVID-19 Research (NIH)
Barouch Laboratory (Beth Israel Deaconess Medical Center and Harvard Medical School, Boston)
Jeffery Goldstein (Northwestern University Feinberg School of Medicine, Chicago)
NIH Support: National Institute of Allergy and Infectious Diseases; National Cancer Institute, National Institute of Child Health and Human Development; National Center for Advancing Translational Sciences; National Institute of Biomedical Imaging and Bioengineering
Posted In: News
Tags: breast milk, breastfeeding, cord blood, COVID-19, COVID-19 vaccine, gynecology, infants, Moderna vaccine, mRNA vaccine, neutralizing antibodies, obstetrics, pandemic, Pfizer/BioNTech vaccine, placenta, pregnancy, pregnancy complications, SARS-CoV-19 variants, SARS-CoV-2, T cells, women's health