Breaking News
March 25, 2019 - Females on ketogenic diet fail to show metabolic benefits in animal model
March 25, 2019 - Modulating stiffness of blood-forming stem cells could facilitate mobilization procedures
March 25, 2019 - Gene editing regulations to be tightened
March 25, 2019 - CPAP treatment can result in weight loss in people with sleep apnea and obseity
March 25, 2019 - Breast Density Categorization Varies With Screening Modality
March 25, 2019 - Researchers explore link between metal exposure and Parkinson’s symptoms
March 25, 2019 - Later meal timing may contribute to weight gain
March 25, 2019 - Around one in hundred people has autism spectrum condition in China
March 25, 2019 - Research paves way for new standard of care to improve heart’s pump function
March 25, 2019 - Exposure to HIV virus, antiretroviral therapy before birth linked to obesity and asthma-like symptoms
March 25, 2019 - Transgender men preserve their fertility potential after one year of testosterone therapy
March 25, 2019 - Tighter Blood Pressure Control May Prevent Brain Lesions
March 25, 2019 - A reward now or later? Exploring impulsivity in Parkinson’s disease patients
March 25, 2019 - Financial incentives fail to increase completion rates of colorectal cancer screening tests mailed to patients
March 25, 2019 - New research program launched to highlight sexual harassment in academia
March 25, 2019 - Hemoglobin A1c blood test does not detect diabetes in most patients, shows study
March 25, 2019 - Wyss Technology licensed by Sherlock Biosciences to create affordable molecular diagnostics
March 25, 2019 - DWK Life Sciences launches KIMBLE GLS 80 Media Bottle and Multiport Cap System
March 25, 2019 - New study aims to reduce online sexual exploitation of children
March 25, 2019 - Want healthier eating habits? Start with a workout
March 25, 2019 - New approach to prescribing antibiotics could curb resistance
March 24, 2019 - Theravance Biopharma Announces First Patient Dosed in Phase 2b/3 Study of TD-1473 in Patients with Ulcerative Colitis
March 24, 2019 - Prenatal DHA prevents blood-pressure increase from obesity during childhood
March 24, 2019 - Combined immunosuppression may be effective, safe in treating older patients with Crohn’s disease
March 24, 2019 - GSK sells health drinks arm, buys US cancer treatment firm
March 24, 2019 - Bacteria and innate immune factors in birth canal, cervix may be key to predicting preterm births
March 24, 2019 - IgG antibodies play unexpected role in atherosclerosis
March 24, 2019 - Sounds and vibrations are quite similar for the brain, finds new study
March 24, 2019 - Practices for Reducing COPD Hospital Readmissions Explored
March 24, 2019 - Could an eye doctor diagnose Alzheimer’s before you have symptoms?
March 24, 2019 - Enzyme inhibitor stops inflammation and neurodevelopmental disorders in mouse models
March 24, 2019 - Walk, Dance, Clean: Even a Little Activity Helps You Live Longer
March 24, 2019 - Americans used less eye care in 2014 versus 2008
March 24, 2019 - Study finds link between depression in 20s linked to memory loss in 50s
March 24, 2019 - New tool helps physiotherapy students to master complex fine motor skills
March 24, 2019 - The AMR Centre secures £2.3m funding boost
March 24, 2019 - Study examines effects of taking ondansetron during first trimester of pregnancy
March 24, 2019 - Researchers identify a more effective treatment for cancer
March 24, 2019 - Open-source solution for multiparametric optical mapping of the heart’s electrical activity
March 24, 2019 - New nanotechnology approach shows promise in treating triple negative breast cancer
March 24, 2019 - Trevena Announces Publication of APOLLO-1 Results in The Journal of Pain Research Highlighting Oliceridine’s Potential for Management of Moderate-to-Severe Acute Pain
March 24, 2019 - Maternal deaths following C-section 50 times higher in Africa compared to high-income countries
March 24, 2019 - Apple watch could detect irregular heart beat says study
March 24, 2019 - Queen Mary University of London’s BCI boosts radionuclide imaging capabilities with MILabs VECTor technology
March 24, 2019 - Girls should be encouraged to gain more ball skills, shows study
March 24, 2019 - Acute doses of synthetic cannabinoid can impair critical thinking and memory
March 24, 2019 - Presence of bacteria in urine does not always point to infection, shows study
March 24, 2019 - Scientists identify a new role for nerve-supporting cells
March 24, 2019 - Hidden differences between pathology of CTE and Alzheimer’s disease discovered
March 24, 2019 - Knowing causative genes of osteoporosis may open door to more effective treatments
March 24, 2019 - Toilet-seat based cardiovascular monitoring system getting ready to begin commercialization
March 24, 2019 - New model for intensive care identifies factors that send ill patients to ICU
March 24, 2019 - Recommendations Issued for HSCT in Multiple Myeloma
March 24, 2019 - Deep brain stimulation provides sustained relief for severe depression
March 24, 2019 - “Statistical significance” may soon be a thing of past?
March 24, 2019 - Researchers track effects of epigenetic marks carried by sperm chromosomes
March 24, 2019 - AHA News: Family Adopts Three Children With Three Different Heart Conditions
March 24, 2019 - Research into opioid painkillers could provide clues for safer drug development
March 23, 2019 - Lung cancer survivor recounts her lifetime struggles
March 23, 2019 - Radial and femoral approach for PCI achieve similar results in terms of survival
March 23, 2019 - Study sheds light on the optimal timing of coronary angiography in NSTEMI patients
March 23, 2019 - Excess hormones could cause a condition that can lead to blindness in women, study finds
March 23, 2019 - Dramatic shifts in first-time opioid prescriptions bring hope, concern
March 23, 2019 - Antidepressant drugs may not work when neurons are out of shape
March 23, 2019 - TTUHSC El Paso to establish endowed chair in neurology through a major grant
March 23, 2019 - New device approved by FDA for treating patients with moderate-to-severe heart failure
March 23, 2019 - People with peripheral artery disease have lower Omega-3 Index, shows research
March 23, 2019 - Trigger warnings have minimal impact on how people respond to content, shows research
March 23, 2019 - Gilead Announces Data From Two Studies Supporting Further Development of GS-6207, a Novel, Investigational HIV-1 Capsid Inhibitor as a Component of Future Long-Acting HIV Therapies
March 23, 2019 - Selfish genetic elements amplify inflammation and age-related diseases
March 23, 2019 - Study provides new understanding of how the brain recovers from damage caused by stroke
March 23, 2019 - CRISPR/Cas libraries could revolutionize drug discovery
March 23, 2019 - Allergic reaction during pregnancy may alter sexual-development in offspring’s brain
March 23, 2019 - Seeing through a robot’s eyes helps those with profound motor impairments
March 23, 2019 - Recent research shows that ease of breastfeeding after C-section differs culturally
March 23, 2019 - Newly discovered parameters offer more control over efficient release of drugs
March 23, 2019 - ‘De-tabooing’ of abortion- Women would like more support from health care community
March 23, 2019 - Anti-TB drugs can increase susceptibility to Mtb reinfection
March 23, 2019 - New survey indicates need of attention to neglected tropical diseases
March 23, 2019 - Innovative in vitro method to develop easy-to-swallow medicine for children and older people
Study raises hopes for new approaches to treat osteoporosis

Study raises hopes for new approaches to treat osteoporosis

image_pdfDownload PDFimage_print

A handful of brain cells deep in the brain may play a surprising role in controlling women’s bone density, according to new research by UC San Francisco and UCLA scientists.

In a study published January 11, 2019 in Nature Communications, researchers showed that blocking a particular set of signals from these cells causes female (but not male) mice to build extraordinarily strong bones and maintain them into old age, raising hopes for new approaches to preventing or treating osteoporosis in older women.

“Our collaborators who study bone for a living said they’d never seen bone this strong,” said study senior author Holly Ingraham, PhD. “Our current understanding of how the body controls bone growth can’t explain this, which suggests we may have uncovered a completely new pathway that could be used to improve bone strength in older women and others with fragile bones.”

More than 200 million people worldwide suffer from osteoporosis, a weakening of the bones to the point where falls or even minor stresses like bending over or coughing can trigger fractures. In healthy individuals, bone tissue is constantly being recycled — old bone tissue is broken down and replaced by new bone. As we age, this cycle tilts in favor of bone loss, causing our bones to become increasingly porous and fragile.

Women are at particularly high risk of osteoporosis after menopause (nearly one in three post-menopausal women in the U.S. and Europe suffer from weakened bones) because of declining levels of the sex hormone estrogen, which normally promotes bone growth.

Estrogen plays many roles in the female body, particularly in the regulation of reproduction, but its function in the brain is still poorly understood. The Ingraham lab has long sought to understand how estrogen’s signaling in the brain impacts the female metabolism at different life stages, including how estrogen-sensitive neurons in a brain region called the hypothalamus balance energetic demands needed for survival or reproduction.

Their new study began when Stephanie Correa, PhD, then an Ingraham lab postdoctoral researcher and now an assistant professor at UCLA, found that genetically deleting the estrogen receptor protein in hypothalamic neurons caused mutant animals to gain a little weight, and also to become less active. Correa expected to find that the animals had put on extra fat or gained lean muscle, but these did not explain the difference. To find the source of the extra weight, she decided to use an extra-sensitive laboratory technique that could also reveal changes in bone density. To her surprise, she discovered that her heavy mice were truly just big-boned: the animals’ bone mass had increased by as much as 800 percent.

“I was immediately struck by the size of the effect. The two groups didn’t overlap at all, which I had never seen,” Correa said. “We knew right away it was a game changer and a new, exciting direction with potential applications for improving women’s health.”

The mutant animals’ extra-dense bones also proved to be super-strong. When collaborators such as UCSF’s Aaron Fields, PhD, an assistant professor in the Department of Orthopedic Surgery, tested the mechanical strength of these bones by crushing them, his equipment almost failed, Ingraham says.

After Correa moved to UCLA, Ingraham lab postdoctoral fellows Candice Herber, PhD, and William Krause, PhD, spearheaded a series of experiments that zeroed in on a specific population of just a few hundred estrogen-sensitive brain cells — located in a region of the hypothalamus called the arcuate nucleus — which appeared to be responsible for these dramatic increases in bone density. The authors hypothesized that estrogen must normally signal these neurons to shift energy away from bone growth, but that deleting the estrogen receptors had reversed that shift.

Notably, interfering with arcuate estrogen signaling in male mice appeared to have no effect. “Most neuroscientists limit studies to male mice, and few study estrogen, which may explain why this had never been seen before,” Ingraham said. “I’ve always been interested in how sex hormones make male and female brains different, and this is a really wonderful example of how dramatic those differences can be.”

Further experiments showed that Ingraham and Correa’s mutant animals maintained their enhanced bone density well into old age. Normal female mice begin to lose significant bone mass by 20 weeks of age, but mutant animals maintained elevated bone mass well into their second year of life, quite an old age by mouse standards.

Remarkably, Herber and Krause were even able to reverse existing bone degeneration in an experimental model of osteoporosis. In female mice that had already lost more than 70 percent of their bone density due to experimentally lowered blood estrogen, deletion of arcuate estrogen receptors caused bone density to rebound by 50 percent in a matter of weeks.

These results highlight the opposite roles played by estrogen in the blood, where it promotes bone stability, and in the hypothalamus, where it appears to restrain bone formation, Ingraham said. “We hypothesize that after puberty the estrogen system in the female brain actively shifts resources away from bone growth and towards things like reproduction, which could contribute to women’s higher risk of weakened bones as we age.”

The dramatic pattern of enhanced bone growth seen in the current study is unlike anything in the scientific literature, the researchers say, suggesting that Correa’s fortuitous discovery may have uncovered a totally novel biological pathway by which the brain regulates bone density. Ingraham and colleagues are now investigating exactly how this brain-bone communication happens, and whether drugs could be developed to boost bone strength in post-menopausal women without potentially dangerous effects of estrogen replacement therapy.

“This new pathway holds great promise because it allows the body to shift new bone formation into overdrive,” Correa said.

“I’m in the clouds about this result,” Ingraham added. “If our next experiments show that the brain releases a novel circulating factor that triggers enhanced bone growth, we might have a real chance of developing a drug that counteracts osteoporosis.”

Tagged with:

About author

Related Articles