Category: Skeletal System

Categories : Skeletal SystemTags :

Patients with Osteoarthritis are Often Prescribed NSAIDs Despite Contraindications

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Photo by Towfiqu barbhuiya

A new study published in the journal Osteoarthritis and Cartilage has found that people with newly diagnosed osteoarthritis (OA) of the knee or hip with contraindications to or precautions for NSAIDs still continue to be prescribed these drugs. Additionally they had higher use of opioids and slightly lower physical therapy (PT) use within the first year of OA diagnosis, both of which are not consistent with treatment guidelines for OA.

“We found individuals with contraindications to NSAIDs were still commonly prescribed them, placing them at risk for NSAID-related adverse events,” explains corresponding author Tuhina Neogi, MD, PhD, the Alan S. Cohen Professor of Rheumatology and professor of medicine at the school. “Additionally, they were not more likely to receive safer alternatives like PT despite its widespread recommendation as first-line intervention.”

The researchers used population-based register data to identify adults residing in Sweden (between 2004-13) without a previous knee or hip OA diagnosis. Among this group, between 2014-18, they identified people with knee or hip OA diagnosis and presence of contraindications to or precautions for oral NSAIDs at the time of OA diagnosis. They then estimated the risk of: 1) regular oral NSAID use; 2) regular opioid use; 3) PT during the first year after diagnosis among those with versus without contraindications or precautions.

Despite having contraindications to NSAIDs, 21% of those in the study were regular users of NSAIDs within the first year of their OA diagnosis. Similarly, 21% of those with precautions for using NSAIDs were also regular users. They also found a higher proportion of persons with contraindications were regular users of opioids than those without a contraindication or precaution, while a slightly lower proportion received PT.

Neogi stresses that more options for effective and safe management of OA symptoms are urgently needed, and greater work is required in narrowing and ultimately closing the evidence-knowledge-practice gap.

Source: Boston University

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 : Neurology Skeletal SystemTags :

A Single Gene Variant that Gave Rise to Humans’ Unique Skull Base

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Source: CC0

One of the unique features that Homo sapiens have compared with other closely related hominin species and primates is the shape of the base of the skull, which enabled larger brains to evolve. Now, in a study recently published in the American Journal of Human Genetics, a team from Tokyo Medical and Dental University (TMDU), the University of Helsinki, and the University of Barcelona has analysed a genomic variant responsible for this unique human skull base morphology.

Most of the genomic changes that occurred during human evolution did not occur directly to genes themselves, but in regions responsible for controlling and regulating the expression of genes. Variants in these same regions are often involved in genetic conditions, causing aberrant gene expression throughout development. Identifying and characterising such genomic changes is therefore crucial for understanding human development and disease.

The development of the basicranial region, the base of the skull where it joins the vertebra, was key in the evolution of Homo sapiens, as we developed a highly flexed skull base that allowed our increased brain size. Therefore, variants that affect the development of this region are likely to have been highly significant in our evolution.

First, the team searched for variants in just a single letter of the DNA code, called single nucleotide polymorphisms (SNPs), that caused different regulation of genes in the basicranial region in Homo sapiens compared with other extinct hominins. One of these SNPs stood out, located in a gene called TBX1.

They then used cell lines to show that the SNP, called “rs41298798,” is located in a region that regulates the expression levels of the TBX1 gene, and that the “ancestral” form of the SNP, found in extinct hominins, is associated with lower TBX1 expression, while the form found in Homo sapiens gives us higher levels of TBX1.

“We then employed a mouse model with lower TBX1 expression,” explains lead author Noriko Funato, “which resulted in distinct alterations to the morphology at the base of the skull and premature hardening of a cartilage joint where the bones fuse together, restricting the growth ability of the skull.” The changes in the Tbx1-knockout mice were reminiscent of the known basicranial morphology of Neanderthals.

These morphological changes are also reflected in human genetic conditions associated with lower TBX1 gene dosage, such as DiGeorge syndrome and velocardiofacial syndrome, further indicating the significance of this genetic variant in the evolution of our unique skull base morphology.

The identification of this genomic variant sheds light on human evolution, as well as providing insight into common genetic conditions associated with lower expression of the TBX1 gene, paving the way for greater understanding and management of these conditions.

Source: Tokyo Medical and Dental University

Categories : IT in Healthcare Skeletal SystemTags :

AI Helps Clinicians to Assess and Treat Leg Fractures

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Photo by Tima Miroshnichenko on Pexels

By using artificial intelligence (AI) techniques to process gait analyses and medical records data of patients with leg fractures, researchers have uncovered insights on patients and aspects of their recovery.

The study, which is published in the Journal of Orthopaedic Research, uncovered a significant association between the rates of hospital readmission after fracture surgery and the presence of underlying medical conditions. Correlations were also found between underlying medical conditions and orthopaedic complications, although these links were not significant.

It was also apparent that gait analyses in the early postinjury phase offer valuable insights into the injury’s impact on locomotion and recovery. For clinical professionals, these patterns were key to optimising rehabilitation strategies.

“Our findings demonstrate the profound impact that integrating machine learning and gait analysis into orthopaedic practice can have, not only in improving the accuracy of post-injury complication predictions but also in tailoring rehabilitation strategies to individual patient needs,” said corresponding author Mostafa Rezapour, PhD, of Wake Forest University School of Medicine. “This approach represents a pivotal shift towards more personalised, predictive, and ultimately more effective orthopaedic care.”

Dr. Rezapour added that the study underscores the critical importance of adopting a holistic view that encompasses not just the mechanical aspects of injury recovery but also the broader spectrum of patient health. “This is a step forward in our quest to optimize rehabilitation strategies, reduce recovery times, and improve overall quality of life for patients with lower extremity fractures,” he said.

Source: Wiley

Categories : Metabolic Disorders Skeletal SystemTags :

Type 2 Diabetes Alters the Behaviour of Discs in the Vertebral Column

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Type 2 diabetes alters the behaviour of discs in the vertebral column, making them stiffer, and also causes the discs to change shape earlier than normal. As a result, the disc’s ability to withstand pressure is compromised. This is one of the findings of a new rodent-based study published in PNAS Nexus.

Low back pain is a major cause of disability, often associated with intervertebral disc degeneration. People with type 2 diabetes face a higher risk of low back pain and disc-related issues. Yet the precise mechanisms of disc degeneration remain unclear.

Investigating the biomechanical properties of the intervertebral disc is crucial for understanding the disease and developing effective strategies for managing low back pain.

“These findings provide novel insight into the potential mechanisms underlying diabetes-related disc tissue damage and may inform the development of preventative and therapeutic strategies for this debilitating condition,” the research team wrote. The team consisted of engineers and physicians from the University of California San Diego, UC Davis, UCSF and the University of Utah.

The study emphasises that nanoscale deformation mechanisms of collagen fibrils accommodate compressive loading of the intervertebral disc.

In the context of type 2 diabetes, these mechanisms are compromised, resulting in collagen embrittlement.

These findings provide novel insight into the potential mechanisms underlying diabetes-related disc tissue damage and may inform the development of preventative and therapeutic strategies for this debilitating condition.

Researchers employed synchrotron small-angle x-ray scattering (SAXS), an experimental technique that looks at collagen fibril deformation and orientation at the nanoscale.

They wanted to explore how alterations in collagen behaviour contribute to changes in the disc’s ability to withstand compression.

They compared discs from healthy rats to those from rats with type 2 diabetes (UC Davis rat model). The healthy rats showed that collagen fibrils rotate and stretch when discs are compressed, allowing the disc to dissipate energy effectively.

“In diabetic rats, the way vertebral discs dissipate energy under compression is significantly impaired: diabetes reduces the rotation and stretching of collagen fibrils, indicating a compromised ability to handle pressure,” the researchers write.

Further analysis showed that the discs from diabetic rats exhibited a stiffening of collagen fibrils, with a higher concentration of non-enzymatic cross-links.

This increase in collagen cross-linking, induced by hyperglycaemia, limited plastic deformations via fibrillar sliding.

These findings highlight that fibril reorientation, straightening, stretching, and sliding are crucial mechanisms facilitating whole-disc compression.

Type 2 diabetes disrupts these efficient deformation mechanisms, leading to altered whole-disc biomechanics and a more brittle (low-energy) behaviour.

Source: University of California – San Diego

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