Tag: osteoporosis

Categories : Obstetrics & Gynaecology Skeletal SystemTags :

Stopping HRT Leads to a Period of Higher Fracture Risk for Most Women

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Photo by Mehmet Turgut Kirkgoz on Unsplash

A new study has found that the bone fracture protection women get from menopausal hormone therapy (MHT, also known as HRT) disappears within a year of stopping treatment.

In the new study, published in Lancet Healthy Longevity, experts from the School of Medicine at the University of Nottingham, also found that in most cases, stopping treatment is then followed by some years of elevated fracture risk compared to women who have never used MHT. Fracture risks then falls to be similar to, and then lower than women who have never used MHT.

The study was funded by the National Institute for Health and Care Research (NIHR) SPCR.

During menopause, all women experience a drop in hormone levels, particularly of oestrogen. This can cause a range of distressing mental and physical side effects, requiring use of MHT. However, oestrogen deficiency in women also leads to increased age-related bone weakening. Previous studies have confirmed a protective role of the oestrogen component in MHT treatments, and MHT is known to decrease fracture risk when it is being used.

However, MHT is also associated with increased risk of breast cancer and blood clots, so long-term MHT use is not recommended. For women using MHT to counteract increasing bone fragility, it is, therefore, important to know the strength and persistence of any protective effect after stopping treatment. Detailed information on this aspect from past studies has been unclear – covering only the first couple of years, and also being somewhat conflicting.

In this new study, experts used data for 6 000 000 women from around 2000 GP surgeries in the UK, which allowed them to follow-up of fracture risk levels for up to 25 years. The researchers identified all women with records of first fracture (cases) and matched each to a number of women of the same age and from the same practice, but without record of fracture (controls). They then compared the MHT use in cases before their fracture with the MHT use among their matched controls.

The findings of our study confirmed that women on MHT show a progressively reducing fracture risk compared with women not using MHT. More importantly, we also observed a clear pattern of risk change after therapy was discontinued. For most women, the bone protective effect of MHT use disappears completely within about one year of treatment being stopped, then their fracture risk rises compared to never users, peaking after about three years, before declining to become again equivalent to never users – about 10 years after discontinuation – and then again continuing to decline relative to never users. So, even after stopping MHT, women should benefit from notably reduced fracture risk in their later decades.”

Dr Yana Vinogradova, from the Centre for Academic Primary Care in the School of Medicine, and lead author of the study

This observed risk pattern was the same for all menopausal hormonal treatments, but the level of excess risk depended on the treatment type and the length of past MHT use.

“Our comparative illustration of observed patterns of fracture risk for short and long use can help doctors and patients when discussing MHT treatment options, and to consider how fracture risk may change after stopping MHT use. Anticipating periods of increased risk might prompt doctors to check patients’ bone health at discontinuation, particularly for patients most at risk with other fracture risk factors such as smoking or inactivity.

“These novel findings may also usefully stimulate further clinical and biological research into these treatments,” adds Dr Vinogradova.

Source: University of Nottingham

Categories : IT in Healthcare Lab Tests and ImagingTags :

New AI–based Test Detects Early Signs of Osteoporosis from X-ray Images

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Investigators have developed an artificial intelligence-assisted diagnostic system that can estimate bone mineral density in both the lumbar spine and the femur of the upper leg, based on X-ray images. The advance is described in a study published in the Journal of Orthopaedic Research.

A total of 1454 X-ray images were analysed using the scientists’ system. Performance rates for the lumbar and femur of patients with bone density loss, or osteopenia, were 86.4% and 84.1%, respectively, in terms of sensitivity. The respective specificities were 80.4% and 76.3%. (Sensitivity reflected the ability of the test to correctly identify people with osteopenia, whereas specificity reflected its ability to correctly identify those without osteopenia). The test also had high sensitivity and specificity for categorising patients with and without osteoporosis.

“Bone mineral density measurement is essential for screening and diagnosing osteoporosis, but limited access to diagnostic equipment means that millions of people worldwide may remain undiagnosed,” said corresponding author Toru Moro, MD, PhD, of the University of Tokyo. “This AI system has the potential to transform routine clinical X-rays into a powerful tool for opportunistic screening, enabling earlier, broader, and more efficient detection of osteoporosis.”

Source: Wiley

Categories : Metabolic DisordersTags :

Drug may Counteract the Muscle Loss and Osteoporosis after Rapid Weight Loss

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Photo by I Yunmai on Unsplash

Weight loss medication has taken the world by storm and helped many overweight people. But for some, significant weight loss also comes with a loss of muscle mass and can lead to an increased risk of osteoporosis.

New research now suggests that the monoclonal antibody drug bimagrumab may be able to alleviate some of this risk, says PhD student Frederik Duch Bromer and postdoc Andreas Lodberg from the Department of Biomedicine at Aarhus University, who are behind the study published in the Journal of Cachexia, Sarcopenia and Muscle.

“We are the first to study how certain drugs affect bones, and the results show that bimagrumab can increase the amount of bone tissue while building muscle mass, and this could be very important for the many people currently taking weight loss medication.”

Bimagrumab was originally developed to treat muscle loss and dysfunction, but since then, it has beome apparent that it also has a fat “burning” component to it. So, if approved, it could be part of a second-generation weight loss drug on the market.

Therefore, it’s relevant to research how this particular patient group reacts to the drug,” says Andreas Lodberg.

“An estimated two billion people will be categorised as overweight by 2035, so it’s also important that we research the drugs that come on the market for this particular patient group in order to better understand their long-term impact on the body.”

Osteoporosis can prove costly for patients and society

Patients on weight loss medication often have a history of weight fluctuation, which can contribute to the development of osteoporosis. Brittle bones increase the risk of serious fractures, and this is costly for both patients and society.

Therefore, the research results could be good news for patients on weight loss medication. And according to Frederik Duch Bromer, the study shows that bimagrumab not only counteracts the breakdown of bone and muscle tissue, it actually promotes the build-up of both.

“Bimagrumab slightly increases the calcium content in bones and promotes the formation of new bone in what we call the shell (cortex) of the long bones. We also saw a significant build-up of bone tissue in the area around the femoral head, which is typically where many older people incur fractures.”

According to Frederik Duch Bromer, the results also showed that bimagrumab has no effect on the blood. Similar drugs have previously been shown to increase red blood cell production, increasing the risk of blood clots.

The study is based on mice with both osteoporosis and reduced muscle mass, and the drug is now being tested in several phase 2 clinical trials. Andreas Lodberg emphasises that more research is needed.

“Our study shows that bimagrumab has a positive effect in many areas, but we also have indications that the drug may have other side effects, and we’ll now investigate this further to get a clearer picture of the implications of using the drug for patients.”

Andreas Lodberg and Frederik Duch Bromer hope to be able to continue with further research to investigate both the positive results and possible side effects.

Source: Aarhus University

Categories : Skeletal SystemTags :

Study of Osteoblast-blocking Protein could Help Future Osteoporosis Treatment

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Osteoporosis. Credit: Scientific Animations CC4.0

Scientists have identified a protein that blocks the activity of bone-forming cells (osteoblasts) by stopping them from maturing during the journey to sites of bone formation, finds a new study published in Communications Biology.

A team of researchers led by Dr Amy Naylor and Professor Roy Bicknell along with their team including Dr Georgiana Neag from the University of Birmingham have found that protein CLEC14A, which is found on endothelial cells in bone, block the function of bone development cells called osteoblasts.

During bone development, the endothelial cell’s job is to transport immature osteoblasts to sites where new bone is needed. However, when the protein CLEC14A is also present on the outside of the endothelial cell, osteoblasts are prevented from maturing to the point where they can form bone tissue.

This additional understanding of how blood vessel cells control bone-forming osteoblasts under normal, healthy conditions provide an avenue to develop treatments for patients who have insufficient bone formation

Dr Amy Naylor

In this study, osteoblast cells were taken from transgenic mice that either have been bred to produce CLEC14A or not. The osteoblasts were subsequently used in vitro in an induction solution, and the team found that cells taken from the protein-free mice reached maturation after 4 days while those in the presence of CLEC14A matured 8 days later. Furthermore, the CLEC14A-free samples saw a significant increase in mineralised bone tissue at day 18 in the study.

Dr Amy Naylor, Associate Professor in the School of Infection, Inflammation and Immunology at the University of Birmingham said:

“In the last decade, a specific type of blood vessel cell was identified within bones. This blood vessel is called ‘type-H’ and is responsible for guiding bone-forming osteoblasts to the places where bone growth is needed. Now we have discovered that a protein called CLEC14A can be found on the surface of type-H blood vessel cells.

“In the experiments we performed, when CLEC14A protein is present the osteoblasts that were sharing a ride on the endothelial cells produce less bone. Conversely, when the protein is removed, they produce more bone.

“This additional understanding of how blood vessel cells control bone-forming osteoblasts under normal, healthy conditions provide an avenue to develop treatments for patients who have insufficient bone formation, for example in patients with fractures that do not heal, osteoporosis or with chronic inflammatory diseases.”

Source: University of Birmingham

Categories : Skeletal SystemTags :

Radiology’s Role in Monitoring the Silent Disease – Osteoporosis

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Images of a hip and lumbar spine, where bone density is typically measured.

Osteoporosis is often called a ‘silent disease,’ because it progresses, without symptoms, until a fracture occurs most commonly in your hips, spine and wrists.  However, a bone density scan can alert doctors to the disease before a patient has experienced any symptoms.

Radiology imaging techniques play a crucial role in the early diagnosis, management and monitoring of low bone density. The rapid evolution of high-quality imaging techniques, using reduced radiation doses, has positioned radiology ideally for this role.

What is osteoporosis

A healthy bone viewed under a microscope, looks like honeycomb. Osteoporosis, put simply, is when the ‘holes and spaces’ in the honeycomb increase in size, causing the bones to lose density or mass and develop abnormal tissue structure. This is caused by the body losing too much bone or making too little bone because of a lack of calcium, vitamin D and not doing any weight-bearing exercises or both. This can lead to a decrease in bone strength which, in turn, can increase the risk of broken or fractured bones.

There are degrees of bone density loss which are determined by radiologists doing a DEXA scan.

‘The standard method of determining your bone density,’ says Dr Hein Els, director at SCP Radiology, ‘is a DEXA scan (dual-energy X-ray absorptiometry). This involves using two X-ray beams, at different energy levels. to measure the bone mineral density. It has a high accuracy for overall bone density and is commonly found in clinics and hospitals.’ 

The scan uses a low radiation exposure making it safer for routine screening and follow-up.

‘The amount of radiation is minimal,’ says Dr Els, ‘it’s equivalent to 1 or 2 days of background radiation at sea level.’ 

Osteoporosis vs osteopenia

Osteoporosis and osteopenia are both conditions measured on a DEXA scan and characterised by decreased bone density. While they are related, they differ in severity and implications for bone health.

The fracture risk is higher in osteoporosis due to more significant bone fragility.

Understanding and managing both conditions are crucial for maintaining bone health and preventing fractures.

Measuring bone density

‘We measure your bone mass density by comparing it to that of a healthy, young adult. The result will tell us how much lower (or higher) your bone mass score,’ explains Dr Els. ‘Software is also used to calculate a predicted 10-year fracture risk for a major osteoporotic fracture and a hip fracture. The result is a T-score which you will be given by your doctor.’

Who is at greater risk

The vast majority of patients referred for a DEXA scan are women.  However, men over the age of 50 are also at risk, though not to the same degree as women.  The aim is to prevent fractures later in life by maintaining healthy bone mineral density, which means it is beneficial to know your bone mineral density. Fractures in the elderly population are a significant cause of morbidity and mortality.

Apart from diagnosing osteoporosis and osteopenia and assessing fracture risk, DEXA scans are helpful in the following ways:

  • Monitoring bone density changes over time: For individuals diagnosed with osteoporosis or those undergoing treatment for bone loss, DEXA scans are used to monitor changes in bone density. This helps in evaluating the effectiveness of treatment
  • Postmenopausal women: Are at a higher risk of developing osteoporosis due to decreased oestrogen levels. DEXA scans are recommended for postmenopausal women, especially those with additional risk factors
  • Men over 50 can also be at risk of osteoporosis
  • A family history of osteoporosis or fractures can increase an individual’s risk. DEXA scans can help assess bone density in those with a genetic predisposition
  • Individuals with a low body mass index (BMI) are at a higher risk for osteoporosis and may benefit from bone density testing
  • Smokers and heavy alcohol users are risk factors for osteoporosis
  • Patients with fragility fractures: Individuals who have experienced fractures from minor falls or injuries may undergo DEXA scans to determine if osteoporosis is the underlying cause

How do you treat low bone mass density?

This can be done through medication such as bisphosphonates, hormone-related therapy and other bone-building medications or through lifestyle changes. This includes an adequate intake of calcium and vitamin D, regular weight-bearing exercise, quitting smoking and limiting alcohol.

The DEXA scan is the safest, most reliable method of determining your bone loss and whether your bones are normal or if you are osteopenic or osteoporotic – the precursor to osteoporosis or full-blown osteoporosis. Regular medical check-ups and proactive lifestyle changes can significantly mitigate the risks associated with these conditions.

‘There is no need to be harbouring this silent disease,’ says Dr Els, ‘when radiography is available to test for these and can put you on a path to wellness.’  

Categories : Skeletal SystemTags :

New Study Reveals Promising Drug Target for Osteoporosis Treatment

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Photo by Mehmet Turgut Kirkgoz on Unsplash

In a recent study published in Journal of Cellular Physiology, researchers from Tokyo University of Science discovered a new target for the treatment of osteoporosis, which is responsible for 8.9 million fractures globally each year. They focused on improving a common bone-strengthening drug, teriparatide, which has a tendency to also increase bone resorption. By targeting a newly identified gene, they were able to suppress teriparatide’s bone resorption effect.

Induction of parathyroid hormone (PTH) signalling using the synthetic PTH-derived peptide – teriparatide, has demonstrated strong bone-promoting effects in patients with osteoporosis. These effects are mediated by osteogenesis, the process of bone formation involving the differentiation and maturation of bone-forming cells called osteoblasts. However, PTH induction is also associated with the differentiation of macrophages into osteoclasts, which resorb bone. Although, bone remodelling by osteoblasts and osteoclasts is crucial for maintaining skeletal health, PTH-induced osteoclast differentiation can decrease treatment efficacy in patients with osteoporosis. However, precise molecular mechanisms underlying the dual action of PTH signaling in bone remodelling are not well understood.

To bridge this gap, Professor Tadayoshi Hayata and Ms Chisato Sampei, from Tokyo University of Science, along with their colleagues, conducted a series of experiments to identify druggable target genes downstream of PTH signalling in osteoblasts. Explaining the rationale behind their study , corresponding author, Prof. Hayata says, “In Japan, it is estimated that 12.8 million people, or one in ten people, suffer from osteoporosis, which can significantly deteriorate their quality of life. Teriparatide is classified as a drug that promotes bone formation, but it also promotes bone resorption, which may limit bone formation. However, the full scope of its pharmacological action remains unknown.”

The researchers treated cultured mouse osteoblast cells and mice with teriparatide. They then assessed gene expression changes induced by PTH in both the cultured cells and bone cells isolated from the femurs of the treated animals, using advanced RNA-sequencing analysis. Among several upregulated genes, they identified a novel PTH-induced gene – ‘Gprc5a’, encoding an orphan G protein-coupled receptor, which has been previously explored as a therapeutic target. However, its precise role in osteoblast differentiation had not been fully understood.

PTH induction has been known to activate the cyclic adenosine monophosphate (cAMP) and protein kinase C (PKC) signaling pathways. Interestingly, the team found that in addition to PTH induction, activation of cAMP and PKC also resulted in overexpression of Gprc5a, albeit to a lesser extent, underscoring the potential involvement of other molecular pathways. Notably, upregulation of Gprc5a was suppressed upon inhibition of transcription, but, remained unaffected upon suppressing protein synthesis, suggesting that Gprc5a could be transcribed early on in response to PTH signaling and serves as a direct target gene.

Furthermore, the researchers examined the effect of Gprc5a downregulation on osteoblast proliferation and differentiation. Notably, while PTH induction alone did not affect cell proliferation, Gprc5a knockdown resulted in an increase in the expression of cell-cycle-related genes and osteoblast differentiation markers. These findings suggest that Gprc5a suppresses osteoblast proliferation and differentiation.

Diving deeper into the molecular mechanisms underlying the effects of Gprc5a, in PTH-induced osteogenesis, the researchers identified Activin receptor-like kinase 3 (ALK3) – a bone morphogenetic protein (BMP) signalling pathway receptor, as an interacting partner of Gprc5a. In line with their speculation, overexpression of Gprc5a indeed, led to suppression of BMP signalling via receptors including ALK3.

Overall, these findings reveal that Gprc5a – a novel inducible target gene of PTH, negatively regulates osteoblast proliferation and differentiation, by partially suppressing BMP signaling. Gprc5a can thus, be pursued as a novel therapeutic target while devising treatments against osteoporosis. The study sheds light on the complex process of bone remodeling and explains the bone-promoting and bone-resorbing effects of PTH signaling.

“Our study shows Gprc5a may function as a negative feedback factor for the bone formation promoting effect of teriparatide. Suppressing Gprc5a function may, therefore, increase the effectiveness of teriparatide in non-responding patients. In the future, we hope that our research will lead to improved quality of life and healthy longevity for people suffering from osteoporosis,” concludes Prof Hayata.

Source: Tokyo University of Science

Categories : Skeletal SystemTags :

Poor Sleep When Young may Drive Osteoporosis in Later Life

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Photo by Andrea Piacquadio

Adequate sleep can help prevent osteoporosis, according to a growing body of research. As part of the University of Colorado Department of Medicine’s annual Research Day, held on April 23, faculty member Christine Swanson, MD, MCR, described her clinical research on how sleep interacts with osteoporosis.

“Osteoporosis can occur for many reasons such as hormonal changes, aging, and lifestyle factors,” said Swanson, an associate professor in the Division of Endocrinology, Metabolism, and Diabetes. “But some patients I see don’t have an explanation for their osteoporosis.

“Therefore, it’s important to look for novel risk factors and consider what else changes across the lifespan like bone does – sleep is one of those,” she added.

How bone density and sleep change over time

In people’s early- to mid-20s, they reach what is called peak bone mineral density, which is higher for men than it is for women, Swanson said. This peak is one of the main determinants of fracture risk later in life.

Bone density mostly plateaus for a couple of decades. Then, when women enter the menopausal transition, they experience accelerated bone loss. Men also experience bone density decline as they age.

Sleep patterns also evolve over time. As people get older, their total sleep time decreases, and their sleep composition changes. For instance, sleep latency, which is the time it takes to fall asleep, increases with age. On the other hand, slow wave sleep, which is deep restorative sleep, decreases as we age.

“And it’s not just sleep duration and composition that change. Circadian phase preference also changes across the lifespan in both men and women,” Swanson said, referring to people’s preference for when they go to sleep and when they wake up.

How is sleep linked to bone health?

Genes that control our internal clock are present in all of our bone cells, Swanson said.

“When these cells resorb and form bone, they release certain substances into the blood that let us estimate how much bone turnover is going on at a given time,” she said.

These markers of bone resorption and formation follow a daily rhythm. The amplitude of this rhythm is larger for markers of bone resorption than it is for markers of bone formation, she said.

“This rhythmicity is likely important for normal bone metabolism and suggests that sleep and circadian disturbance could directly affect bone health,” she said.

Researching the connection between sleep and bone health

To further understand this relationship, Swanson and colleagues researched how markers of bone turnover responded to cumulative sleep restriction and circadian disruption.

For this study, participants lived in a completely controlled inpatient environment. The participants did not know what time it was, and they were put on a 28-hour schedule instead of a 24-hour day.

“This circadian disruption is designed to simulate the stresses endured during rotating night shift work and is roughly equivalent to flying four time zones west every day for three weeks,” she said. “The protocol also caused participants to get less sleep.”

The research team measured bone turnover markers at the beginning and end of this intervention and found significant detrimental changes in bone turnover in both men and women in response to the sleep and circadian disruption. The detrimental changes included declines in markers of bone formation that were significantly greater in younger individuals in both sexes compared to the older individuals.

In addition, young women showed significant increases in the bone resorption marker.

If a person is forming less bone while still resorbing the same amount – or even more – then, over time, that could lead to bone loss, osteoporosis, and increased fracture risk, Swanson said.

“And sex and age may play an important role, with younger women potentially being the most susceptible to the detrimental impact of poor sleep on bone health,” she said.

Research in this area is ongoing, she added.

Source: University of Colorado Anschutz Medical Campus

Categories : Ageing Skeletal SystemTags :

Walking Fitness can Predict Fracture Risk in Older Adults

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Photo by Teona Swift on Unsplash

The ability to walk one kilometre comfortably can help predict fracture risk, according to researchers at the Garvan Institute of Medical Research. The findings, published in JAMA Network Open, suggest that simply asking a patient about walking limitation could allow clinicians to identify those in need of further bone health screening and prescribe interventions that could prevent fractures from occurring.

“We’ve discovered that trouble walking even short distances appears closely tied to higher fracture risk over the following five years,” says lead author of the study, Professor Jacqueline Center, Head of Garvan’s Clinical Studies and Epidemiology Lab.

“Just a few simple questions about how far someone can walk could give doctors an early warning sign to check bone health.”

The researchers examined data on nearly 267 000 adults aged 45 and older from the Sax Institute’s 45 and Up Study, a major ongoing research initiative that has been tracking health outcomes in adults in the Australian state of New South Wales for more than 15 years.

Participants were asked if health issues limited their ability to walk various distances, with answer options of ‘not at all,’ ‘a little,’ or ‘a lot’. The group was then followed for five years to track fracture outcomes.

The researchers found that one in five adults reported some walking limitation at the beginning of the study.

Those with more difficulty walking were significantly more likely to experience a fracture during follow-up. For example, women who said they were limited ‘a lot’ in walking one kilometre had a 60% higher fracture risk than women with no limitation.

For men, the increased risk was over 100%.

“We saw a clear ‘dose-response’ pattern, where greater walking limitation meant higher fracture risk. This suggests a direct relationship between low walking ability and weaker bones,” says first author of the study Dr Dana Bliuc, Senior Research Officer at Garvan.

Approximately 60% of all fractures in the study were attributable to some level of walking limitation.

The link remained strong even after accounting for other factors like age, falls, prior fractures, and weight, and the findings were consistent across different fracture sites like hips, vertebrae, arms, and legs.

“In this generally healthy community-based population, we still found one in five people had trouble walking a kilometre,” says Professor Center.

“We think this simple assessment could help identify many more at-risk individuals who may benefit from bone density screening or preventative treatment.”

Osteoporosis medications, lifestyle changes, and other interventions are available to improve bone strength and avoid first or repeat fractures.

However, screening rates currently remain low, meaning many miss out on fracture risk assessments.

Finding easy but accurate ways to detect at-risk people is an important target for research.

“Fracture risk assessment generally relies on a bone density test, which many people have not had when seeing their doctor,” says Professor Center.

“Asking about walking ability takes just seconds and could be a free, non-invasive way to tell if someone needs their bones checked.”

The researchers stress that walking limitation may have many causes beyond weak bones, from heart disease to arthritis.

However, a difficulty in walking even short distances appears closely tied to fracture risk independently.

“We hope these findings will encourage clinicians to consider walking ability as a red flag for possible bone health issues. For patients, if you can’t walk a full kilometre comfortably, it may be wise to ask your doctor about getting your bones checked,” says Dr Bliuc.

Source: Garvan Institute of Medical Research

Categories : Skeletal SystemTags :

Topical Corticosteroids Linked to Osteoporosis Risk

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Source: Pixabay

New research indicates that higher doses of topical corticosteroids, commonly used to treat inflammatory skin conditions, are linked with elevated risks of osteoporosis and bone fractures associated with osteoporosis. The findings are published in the Journal of the European Academy of Dermatology and Venereology.

Drawing on the Taiwan National Health Insurance Research Database, the study’s investigators selected 129 682 osteoporosis cases and 34 999 major osteoporotic fracture (MOF) cases and matched them with 518 728 and 139 996 controls (without osteoporosis or MOF) by sex and age.

The team found clear dose–response relationships between long-term use of topical corticosteroids and osteoporosis and MOF, as well as differences in sex and age.

All topical corticosteroids prescriptions were converted to prednisolone equivalents (mg) according to their anti-inflammatory potency. Effects were not clear in exposure periods of six or 12 months, but effects were seen when analysis was extended to the longer term (three to five years). Compared with no doses, low, medium, and high cumulative of doses topical corticosteroids were associated with 1.22-, 1.26-, and 1.34-times higher odds of developing osteoporosis over five years. These respective doses were linked with 1.12-, 1.19-, and 1.29-times higher odds of experiencing MOF. Women had higher risks of osteoporosis and MOF than men. Also, younger people (under the age of 50 years) had a higher risk of osteoporosis compared with other age groups.

“This study emphasises that using topical corticosteroids to treat inflammatory skin conditions should be done very carefully and clinicians should be aware of these potential side effects,” said corresponding author Chia-Yu Chu, MD PhD, of National Taiwan University Hospital and National Taiwan University College of Medicine.

Source: Wiley

Categories : Skeletal SystemTags :

AI Finds that an Antimalarial Drug might Treat Osteoporosis Too

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Photo by Ekamelev on Unsplash

Using a deep learning algorithm, which is a kind of artificial intelligence (AI), researchers reporting have found that dihydroartemisinin (DHA), an antimalarial drug and derivative of a traditional Chinese medicine, could treat osteoporosis as well. Publishing their findings in ACS Central Science, the team showed that in mice, DHA effectively reversed osteoporosis-related bone loss.

In healthy people, there is a balance between the osteoblasts that build new bone and osteoclasts that break it down. Current treatments for osteoporosis primarily focus on slowing the activity of the ‘wrecking crew’ of osteoclasts. But osteoblasts, or more specifically, their precursors known as bone marrow mesenchymal stem cells (BMMSCs), could be the basis for a different approach. During osteoporosis, these multipotent cells tend to turn into fat-creating cells instead, but they could be reprogrammed to help treat the disease. Previously, Zhengwei Xie and colleagues developed a deep learning algorithm that could predict how effectively certain small-molecule drugs reversed changes to gene expression associated with the disease. This time, joined by Yan Liu and Weiran Li, they wanted to use the algorithm to find a new treatment strategy for osteoporosis that focused on BMMSCs.

The team ran their program on a profile of differently expressed genes in newborn and adult mice. One of the top-ranked compounds identified was DHA, a derivative of artemisinin and a key component of malaria treatments. Administering DHA extract for six weeks to mice with induced osteoporosis significantly reduced bone loss in their femurs and nearly completely preserved bone structure. To improve delivery, the team designed a more robust system using injected, DHA-loaded nanoparticles. Bones of mice with osteoporosis that received the treatment were similar to those of the control group, and the treatment showed no evidence of toxicity. In further tests, the team determined that DHA interacted with BMMSCs to maintain their stemness and ultimately produce more osteoblasts. The researchers say that this work demonstrates that DHA is a promising therapeutic agent for osteoporosis.

Source: American Chemical Society