Category: Skeletal System

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Nanorobots Transform Stem Cells into Bone Cells with a Little Push

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New method for the targeted production of specific cells

Figure 1
Schematic overview of the experimental workflow. MSCs (blue) were singly encapsulated using a microfluidic approach within calcium-crosslinked, RGD-functionalized alginate microgels (pink), followed by a secondary APA and calcium coating to enhance stability. Encapsulated cells were cultured for 21 days and subjected to cyclic hydrostatic pressure in regular cell culture media without any growth factors. Source: İyisan et al., Small Science, 2025.

For the first time, researchers at the Technical University of Munich (TUM) have succeeded in using nanorobots to stimulate stem cells with such precision that they are reliably transformed into bone cells. To achieve this, the robots exert external pressure on specific points in the cell wall. The new method offers opportunities for faster treatments in the future.

Prof Berna Özkale Edelmann’s nanorobots consist of tiny gold rods and plastic chains. Several million of them are contained in a gel cushion measuring just 60 micrometres, together with a few human stem cells. Powered and controlled by laser light, the robots, which look like tiny balls, mechanically stimulate the cells by exerting pressure. “We heat the gel locally and use our system to precisely determine the forces with which the nanorobots press on the cell – thereby stimulating it,” explains the professor of nano- and microrobotics at TUM. This mechanical stimulation triggers biochemical processes in the cell. Ion channels change their properties, and proteins are activated, including one that is particularly important for bone formation.

The research is described in Advanced Materials and Small Science.

Heart and cartilage cells: finding the correct stress pattern

If stimulation is carried out at the right rhythm and with the right (low) force, a stem cell can be reliably triggered to develop into a bone cell within three days. This process can be completed within three weeks. “The corresponding stress pattern can also be found for cartilage and heart cells,” asserts Berna Özkale Edelman. “It’s almost like at the gym: we train the cells for a particular area of application. Now we just have to find out which stress pattern suits each cell type,” says the head of the Microbiotic Bioengineering Lab at TUM.

Mechanical forces pave the way for transformation into bone cells

The research team produces bone cells using mesenchymal stem cells. These cells are considered to be the body’s ‘repair cells’. They are approximately 10 to 20 micrometres in size and are generally capable of developing into bone, cartilage or muscle cells, for example. The challenge: The transformation into differentiated cells is complex and has been difficult to control until now. “We have developed a technology that allows forces to be applied to the cell very precisely in a three-dimensional environment,” says TUM scientist Özkale Edelmann. “This represents an unprecedented advance in the field.” The researchers believe that this method can even be used to produce cartilage and heart cells from human stem cells.

Automation is the next step

For treatments, doctors will ultimately need far more differentiated cells – around one million. “That’s why the next step is to automate our production process so that we can produce more cells more quickly,” says Prof Özkale Edelmann.

Source: Technical University Munich

Categories : Lab Tests and Imaging Skeletal SystemTags :

When a Limp Isn’t Just a Sprain in Adolescents

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A timely X-ray can save young hips

Frog leg lateral view of the hips. Widening of the growth plate (physis) with blurring and irregularity of the femoral neck (metaphysis). Inferior offset of the head in relation to the neck (early slip).

Slipped Capital Femoral Epiphysis (SCFE) is the most common adolescent hip disorder. It occurs when the ball at the top of the thigh bone (femoral head) slips off the neck of the bone through the growth plate (physis). A bit like an ice cream sliding off a cone… Dr Ryno du Plessis, a renowned orthopaedic and joint replacement surgeon in the Western Cape, talks about what it is and why it is often misdiagnosed.

SCFE usually happens during growth spurts in children aged 9 to 16 years and is more common in boys and in children with obesity, endocrine disorders, or other risk factors.

Why is this problem often missed?

AP view of the hips. ‘Melting ice cream sign’: Femoral head (epiphysis) slipping off the femoral neck (metaphysis) though the growth plate (physis) like an ice cream melting from the cone.

Despite its frequency, SCFE is routinely misdiagnosed or diagnosed late – unfortunately, sometimes months after symptoms start. Studies show that over 50% of SCFE cases are not diagnosed at the first medical visit.

Here’s why:

  • Pain felt in the knee or thigh: Physicians often focus on the wrong joint and the hip is never X-rayed
  • Labeled as a groin strain: Adolescents in sports may be diagnosed with muscle strains or ‘growing pains’
  • Symptoms develop gradually: Children may limp without severe pain, leading to delayed concern
  • Physiotherapy prescribed early: Instead of imaging – patients are referred to physio – delaying diagnosis
  • Lack of hip-specific X-rays: It requires a frog-leg lateral X-ray.

Why does delay matter?

The longer the slip is left untreated, the more serious the outcome. Every week or month of delay increases the severity of the deformity, often silently.

Late diagnosis risks:

  • More severe deformity
  • Loss of bloody supply to the femoral head. This is known as avascular necrosis and can lead to pain, limited movement and eventually, hip collapse and osteoarthritis
  • Early-onset hip arthritis
  • Complex surgery

Children diagnosed early often need just one screw to stabilise the hip. Those who are diagnosed late may face major reconstructive surgery, longer recovery, and reduced hip function for life.

Red flags for parents, teachers and coaches

If you notice any of the following signs in a child or teen – especially those who are overweight – take it seriously and ask for a hip X-ray:

  • Limping for more than a week
  • Complaints of pain in the knee, thigh, groin, or buttock
  • Walking with the foot turned outwards
  • Stiffness or loss of motion in the hip
  • Sudden inability to walk or stand after a minor stumble (may indicate an unstable SCFE)

Radiology – diagnostic challenges

Dr Jaco Greyling, a radiologist from SCP Radiology, says SCFE diagnoses can be delayed due to several factors, including

  • Hip X-rays not ordered by the initial healthcare provider (eg, GP or physiotherapist)
  • Only a single anterior-posterior pelvis projection is performed, whereas a frog-leg lateral view must also be specifically requested by the referring physician. Radiologists should ensure the child returns for this view if it was not initially ordered
  • Findings in the pre-slip phase are subtle and may be missed, even by experienced radiologists

He says, ’the recommended imaging is an anterior-posterior pelvic view which shows malalignment and widening of the growth plate and a frog-leg lateral view, the most sensitive for detecting early or subtle slips.’

‘Key radiological signs,’ says Dr Greyling are:

  • Widening of the growth plate
  • Loss of height of the femoral head
  • Loss of alignment of the anatomical lines that intersect with the femoral head
  • ‘Melting ice cream sign’ slipping off the femoral neck at the growth plate (epiphysis).

Follow-up recommendations:

Dr Greyling suggests repeat imaging within two weeks if symptoms persist, and an early referral to a paediatric orthopaedic surgeon and an MRI for patients with risk factors and ongoing pain.

Who’s at risk?

  • Children aged 9-16 years
  • Boys are at greater risk than girls
  • BMI in the overweight/obese range
  • Family history of hip disorders
  • Endocrine disorders: Hypothyroidism, growth hormone treatment, kidney disease

Treatment

Early SCFE is usually treated with in-situ fixation using one or two screws. The goal is to stabilise the rounded end of a long bone to prevent further slippage.

In cases where both hips are at risk (especially in young or overweight patients), pinning of the opposite hip as well is sometimes recommended to prevent it from occurring.

Severe or late cases have a high risk of AVN, which is the death of bone tissue caused by a disruption in its blood supply, leading to pain, stiffness, and potential bone collapse or joint destruction over time and permanent disability.

The take-home message

SCFE is treatable and preventable if recognised early.

If a child has an unexplained limp, especially with thigh or knee pain, don’t assume it’s just a strain. Ask the doctor directly: “Could this be SCFE? Should we get hip X-rays done?”

One simple question. One X-ray. It could save a child’s hip.


Categories : Skeletal SystemTags :

‘Glue Gun’ Can 3D Print Bone Grafts Directly onto Fractures

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Graphical abstract. Credit: Device / Jeon et al. CC BY-SA

Scientists have developed a tool made from a modified glue gun that can 3D print bone grafts directly onto fractures and defects during surgery. The tool, described September 5th in the Cell Press journal Device, has been tested in rabbits to quickly create complex bone implants without the need for prefabricating in advance. What’s more, the team optimised the 3D-printed grafts for high structural flexibility, release of anti-inflammatory antibiotics, and promotion of natural bone regrowth at the grafting site.

Historically, bone implants have been made of metal, donor bone, or even more recently 3D-printed material. However, in cases involving irregular bone breaks, these implants must be designed and produced prior to surgery to allow for appropriate fitting.

“Our proposed technology offers a distinct approach by developing an in situ printing system that enables a real-time fabrication and application of a scaffold directly at the surgical site,” says Jung Seung Lee, co-author and associate professor of biomedical engineering at Sungkyunkwan University. “This allows for highly accurate anatomical matching even in irregular or complex defects without the need for preoperative preparation such as imaging, modelling, and trimming processes.”

The material fed into the glue gun is a filament comprised of two major components: a feature of natural bone known to promote healing called hydroxyapatite (HA) and a biocompatible thermoplastic called polycaprolactone (PCL). PCL can liquify in temperatures as low as 60°C, which when applied with a heat-modified glue gun, is cool enough to prevent tissue damage during surgical application while being able to conform to the jagged grooves of fractured bone. By adjusting the proportion of HA to PCL within the filament, the team can customise the hardness and strength of the grafts to fit different anatomical needs.

“Because the device is compact and manually operated, the surgeon can adjust the printing direction, angle, and depth during the procedure in real time,” says Lee. “Also, we demonstrated that this process could be completed in a matter of minutes. This highlights a significant advantage in terms of reducing operative time and improving procedural efficiency under real surgical conditions.”

Since infection is a common concern with surgical implants, the researchers incorporated vancomycin and gentamicin, two anti-bacterial compounds, into the filament. In both petri dish culture and liquid medium, the filament scaffold successfully inhibited the growth of E. coli and S. aureas, two common bacteria prone to cause infection post-surgery. Due to physical properties of HA and PCL within the filament, the drugs are released slowly and are able to diffuse directly onto the surgical site over several weeks.

“This localised delivery approach offers meaningful clinical advantages over systemic antibiotic administration by potentially reducing side effects and limiting the development of antibiotic resistance, while still effectively protecting against postoperative infection,” says Lee.

As a proof of concept, the device was tested on severe femoral bone fractures in rabbits. Within 12 weeks after surgery, the team found no signs of infection or necrosis and greater bone regeneration outcomes when compared to rabbits grafted with bone cement – a sealing compound commonly used for treating bone defects.

“The scaffold was designed not only to integrate biologically with surrounding bone tissue but also to gradually degrade over time and be replaced by newly formed bone,” says Lee. “The results showed that the printing group exhibited superior outcomes in key structural parameters such as bone surface area, cortical thickness, and polar moment of inertia, suggesting more effective bone healing and integration.”

Next, the team is setting their sights on optimising the anti-bacterial potential of the scaffold even further and preparing the procedure for human trials.

Source: EurekAlert!

Categories : Regenerative Medicine Skeletal SystemTags :

Repurposed Multiple Sclerosis Drug Could Help Bones Heal Faster

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Photo by Tima Miroshnichenko on Pexels

Researchers at the University of Arizona College of Medicine – Tucson found evidence that a drug that improves the ability to walk in people with multiple sclerosis can also make bone fractures heal faster.

The findings help further the understanding of specific factors involved in the bone healing process, and potentially open avenues for new therapeutic approaches.

“Broken bones are typically slow to heal in many people, and they can impact lives for months and in different ways. People lose time at work and daily activities at home with family and friends are impacted,” said senior author John Elfar, MD, professor, surgeon and chair of the Department of Orthopaedic Surgery at the U of A College of Medicine – Tucson. “This drug has the potential to change that.” 

Elfar partnered with Prem Kumar Govindappa, PhD, DVM, an assistant professor in the department, on the preclinical study that showed treatment with the drug 4-aminopyridine, or 4-AP, resulted in leg fractures healing faster and stronger than without the drug. The paper was published in The Journal of Bone and Joint Surgery.

“Mice with bone fractures healed quicker and were stronger after they healed after treatment with 4-AP,” said Elfar said, who is a member of the university’s BIO5 Institute. “We saw more bone mass and less intermediate cartilage, meaning there was accelerated bone healing.” 

The drug is approved for use in chronic neurological conditions, where it helps with walking by improving how signals from the brain and spinal cord reach limbs.

The team also saw improvements in bone mass and the ability to bear weight after treatment with 4-AP. Collagen deposition and bone mineralization, both of which are necessary for bone healing, also received a boost. Collagen forms the structural foundation of bones. In bone mineralization, minerals like calcium and phosphate join the newly forming bone matrix, strengthening and hardening the bone.

“We found that every fine-tuned measure of the strength of bone was better after administering 4-AP to mice,” Elfar said. “We also found more BMP2 protein in bone-forming cells at the fracture site, which again told us we found something that could accelerate the process.”

Examining human bone cells exposed to 4-AP in a dish, the scientists saw increased production of bone morphogenetic protein, or BMP2, a bone-building substance used clinically to help with some kinds of bone repair. BMP2 prompted the production of stem cells that become cells called osteoblasts, which are essential to form new bone.

The research team also measured 4-AP’s effects on human bone narrow mesenchymal stem cells and human osteoblast cells in the lab. 4-AP increased the conversion of the stem cells into osteoblasts and the latter’s ability to migrate and grow, which are essential to the healing process.

Elfar said that 4-AP’s role in driving BMP2 gene and protein activity is key to its bone healing effects, and using 4-AP to prompt BMP2 production in the body could be especially important.

“BMP2 is a hormone the body makes to accelerate bone healing,” Elfar said. 

BMP2 is known to modulate bone healing and is approved for use in certain medical procedures, including spinal fusion and sinus reconstruction surgery. An artificial version that has orthopedic medicine uses can have side effects, though, including bone resorption and cervical spine swelling. Finding a way to channel naturally produced BMP2 could improve bone healing while avoiding such problems.

The scientists previously showed that 4-AP could prevent bone and muscle loss in a mouse model of nerve damage. Similarly, they saw indications of 4-AP’s healing effects for wound, nerve and limb injuries. 

The researchers plan to eventually test 4-AP’s potential use in healing bones in a clinical trial. They also want to better understand the drug’s effects on BMP2 production, and more broadly, on the biology of healing bone.

Source: University of Arizona

Categories : Skeletal System Surgeries & ProceduresTags :

Minimally Invasive Procedure Relieves Painful Symptoms of Knee Osteoarthritis

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Photo by Towfiqu barbhuiya

A procedure that can be performed under mild sedation in less than two hours by an interventional radiologist relieves chronic knee pain caused by osteoarthritis, an NYU Langone Health study shows.

As they gradually break down, knee joints in people with osteoarthritis are known to become inflamed, which triggers the growth of small blood vessels (angiogenesis) and increased blood flow to joints. The study procedure, called genicular artery embolisation, kept this abnormal blood flow from ferrying in immune cells that cause the inflammation and related pain. 

For the new study, the researchers delivered chemical beads (biocompatible hydrogels) through an image-guided plastic tube to block blood flow in any of a half dozen arteries feeding the synovium lining in the knee. More than 60% of the 25 men and women who had the procedure at its facilities in Manhattan experienced significant improvements one year later.

Results of the study appear online in the Journal of Vascular Interventional Radiology.

“Our study shows that genicular artery embolisation is a safe and effective, minimally invasive treatment for those with moderate to severe symptomatic knee pain tied to osteoarthritis,” said study co-investigator and interventional radiologist Ryan M. Hickey, MD. “This work also provides evidence that genicular artery embolisation is offering more than just pain relief and could be modifying the disease process itself.”

“This procedure is particularly suited to those patients who are either not yet ready for knee replacement surgery or for whom surgery is not an option because of age or other risk factors, such as obesity, uncontrolled diabetes or heart disease, or smoking,” added Dr Hickey.

He says there is urgent need for alternative, less-invasive treatments for osteoarthritis. An estimated 24 million cases of osteoarthritis in a knee are diagnosed each year in the United States, a number he expects only to grow with the aging population.

Among the study’s other key results: significant, one-year postsurgical declines (on average 12%) in blood levels of vascular endothelial growth factor (VEGF), a protein that is needed to stimulate the formation of new blood vessels. Past research has also linked VEGF to other structural changes in the knee from osteoarthritis. Another protein biomarker, interleukin 1 receptor agonist (IL-1Ra), showed a similar decrease (15%). IL-1Ra is known for its role in countering inflammation. Tests of a half dozen other immune molecules involved in inflammation were inconclusive.

“Our research suggests that declines in vascular endothelial growth factor could serve as a valuable biomarker or chemical trace for determining success with genicular artery embolisation, offering a much-needed objective benchmark by which to measure its effectiveness,” said study principal investigator and lead author Bedros Taslakian, MD, MA.

“Our study findings also indicate that genicular artery embolisation may, if further larger clinical trials prove successful, slow down the progression of osteoarthritis by observing significant decreases in signalling proteins, specifically vascular endothelial growth factor and interleukin 1 receptor agonist, one year after the procedure,” said Dr Taslakian.

The improvements seen in the 25 patients in the current study were captured by standard patient survey scores for knee pain, stiffness, and the ability to bend, stand up, or walk up and down stairs freely. While subjective surveys are useful in monitoring disease progression, Dr Hickey says, independent blood tests like the NGF measure are more accurate and convenient for patients for tracking small declines or improvements over time.

The NYU Langone team has plans to further investigate precisely how embolisation alleviates inflammation and leads to pain relief.

Dr Hickey also says that more research is needed to establish how long the procedure’s benefits last and which osteoarthritis patients are most likely to benefit.

All study volunteers were diagnosed with moderate to severe osteoarthritis in the knee that had been unresponsive to first-line therapy. This includes knee injections of corticosteroids to reduce inflammation; fluid aspiration (arthrocentesis) to remove excess fluid from the joint; and injections of platelet-rich plasma to repair damaged tissue, as well as physiotherapy. Study participant ages ranged from 50 years old to 78 years old, with all having their embolisation procedures performed between January 2021 and January 2023.

As part of the procedure, interventional radiologists accessed each patient’s arteries through a small incision in the thigh, using video X-ray to guide the catheter to the precise knee artery selected earlier for embolisation. Study participants were then monitored during routine checkups for at least one year and across two dozen measures of pain, knee stiffness, and their ability to move about. Patients needed to achieve a four-point difference on a scale of 20 points to establish a clinically significant reduction in pain. Side effects from the procedure, the researchers say, were minimal and limited to dark skin blemishes on the knee and mild pain near the incision site.

Source: NYU Langone Health

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 : Skeletal SystemTags :

Simple Therapies Beat High-tech Ones for Knee Arthritis

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Knee braces, water therapy, and exercise are the most beneficial non-drug therapies, per meta-analysis of more than 100 clinical trials involving nearly 10 000 people

Photo by Towfiqu barbhuiya

Knee braces, water therapy and exercise are the most promising non-drug therapies for treating knee osteoarthritis, according to a new meta-analysis publishing June 18, 2025 in the open-access journal PLOS One by Yuan Luo of the First People’s Hospital of Neijiang, China.

Knee osteoarthritis (KOA) is a common and often debilitating condition that affects millions of older adults, causing pain and stiffening of the knee joint. Treatment often includes anti-inflammatory drugs, which are linked to gastrointestinal and cardiovascular adverse events.

In the new study, researchers examined the current evidence on non-drug therapies for treating KOA. They looked at data from 139 clinical trials involving nearly 10 000 people to compare 12 different non-drug treatments. These included laser therapy, electrical stimulation, braces, insoles, kinesiology tape, water-based therapy, exercise, and ultrasound. By combining results from all these studies into a powerful network meta-analysis, the team could rank the therapies based on how well they worked.

Knee braces came out on top across most categories, including reducing pain, improving function, and relieving stiffness. Hydrotherapy—exercises or treatments performed in warm water—was particularly effective at easing pain and general exercise was also consistently effective, improving both pain and physical function. High-intensity laser therapy and shock wave therapy showed some benefits, while ultrasound consistently scored the lowest in effectiveness.

The authors caution that differences in study design, small sample sizes, and variability in treatment duration between the 139 included studies may limit the precision of the rankings. However, they conclude that physical therapy has promising effects on KOA, offering potential treatments without the risks of anti-inflammatory drugs. Future studies should examine the clinical efficacy of combined therapies, as well as their cost-effectiveness.

The authors add: “Knee braces, hydrotherapy, and exercise are the most effective non-drug therapies for knee osteoarthritis. They reduce pain and improve mobility without the gastrointestinal or cardiovascular risks linked to common pain medications. Patients and clinicians should prioritize these evidence-based options.”

“Our analysis of nearly 10 000 patients reveals that simple, accessible therapies like knee bracing and water-based exercise outperform high-tech options like ultrasound. This could reshape clinical guidelines to focus on safer, lower-cost interventions.”

Provided by PLOS

Categories : Cancer Skeletal SystemTags :

Space-age Lessons Could Protect Childhood Cancer Survivors’ Bone Health

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Corresponding author Kiri Ness, PT, PhD, FAPTA, St. Jude Department of Epidemiology and Cancer Control, working with a patient.

Space has inspired and delighted people for centuries. The much-anticipated advent of crewed spaceflight taught invaluable lessons, even for the most unexpected groups back on terra firma. In the 1960s, astronauts returned from microgravity with decreased bone density. This decrease revealed that bones must undergo constant stress to grow and maintain themselves.

Survivors of childhood cancer, while seemingly unrelated to astronauts in the weightlessness of space, are one group unexpectedly impacted by this revelation. These two distinct groups share a connection in the loss of bone density occurring during a significant life event. Children receiving cancer treatment are often sedentary due to their therapy. Their listlessness mimics microgravity’s effect on astronauts, while the treatment itself may also negatively impact their bone health.

Recent research spearheaded by first author Chelsea Goodenough, PhD, St. Jude Department of Epidemiology and Cancer Control, characterised bone mineral density loss in survivors of childhood cancer. Published in JAMA Network Open, her study looked at survivors five or more years after treatment using the St. Jude Lifetime Cohort Study (St. Jude LIFE). She found that survivors were more likely than age-matched peers to experience low bone mineral density. Low bone mineral density predicted a higher chance of lacking independence, including being unemployed or requiring a personal care attendant, highlighting the need to find ways to intervene to protect and promote survivors’ bone health.

“Glucocorticoids given during cancer therapy can act as a giant hammer to bone mineral density,” said corresponding author Kiri Ness, PT, PhD, FAPTA, St. Jude Department of Epidemiology and Cancer Control. “We found that this loss could have long-term consequences for survivors. We saw 30-year-olds that functionally looked like they were in their 70s and 80s, showing the need for early interventions after treatment.”  

Modifiable factors influence survivors’ bone mineral density

“The unique aspect of this study is that we calculated the extent to which different factors contributed to loss of bone density,” Ness said. “That gives us a starting place to design interventions.”

Bone loss decades after treatment could be related to therapy, something investigators can’t change after the fact, but potentially modifiable factors could also be contributing. The St. Jude researchers wanted to see if they could identify any modifiable factors that could point to protective interventions for further investigation.

“We found that about 33% of bone density loss was due to cranial radiation for those who received it,” Ness explained. “But about 25% of the deficit was related to hormone deficiencies, such as hypogonadism.” Hypogonadism is a common consequence of childhood cancer therapy. During treatment, the patient receives hormone-disrupting chemicals, sometimes resulting in an extended deficiency of testosterone or oestrogen and human growth hormone. These three hormones are known to have significant impacts on bone health. Since hormone replacement therapies already exist, the study has identified an area for potential pharmaceutical intervention to address hypogonadism to improve bone density among survivors of childhood cancer. 

Lifestyle changes can impact bone health

“Compared to hypogonadism, smoking and sedentary behaviour were responsible for a smaller but still significant decrease in bone density,” Ness said. “But we already have interventions for both; we just need to test them for their effect on bone mineral density.”

Sedentary behaviour is a common experience during treatment. “Understandably, kids don’t feel good during cancer therapy,” Ness explained. “So, they lay in bed.” Lying in bed acts like microgravity: The kids don’t put stress on their bones, resulting in bone loss. However, survivors can prevent this with physical activity. Exercise has already been shown to help protect cardiovascular health among survivors, so the research provides another potential motivation for exercise.

Ness, whose research focuses on lifestyle interventions to support survivors of childhood cancer, already promotes the positives of physical activity. Her insistence, bolstered by this study, has gained her a reputation among patients. “The kids on the floor call me the ‘exercise lady,’” Ness proudly acknowledged. “When they see me, they say, ‘Here she comes, the exercise lady is here.’”

Physical activity to improve bone health could be as simple as jumping or as elaborate as a dedicated heavy weight-lifting programme. The increased activity will likely promote bone maintenance and, hopefully, growth, a parallel to the exercise programme astronauts undergo upon returning from space to re-establish their bone mass.

While exercise is one way in which survivors can improve their bone health, the study also suggested that those who develop a smoking habit may have one more reason to quit. Survivors who smoked were more likely to have a moderate or severe bone mineral density deficit, along with a host of other problems.

“Smoking is just a bad idea for survivors,” Ness said. “Smoking causes a lot of ill effects, not just bone loss. So, we need to encourage young cancer survivors never to start and give cessation interventions to those that have.” Over 20% of survivors in the study currently smoked, indicating a significant opportunity for intervention.

Better understanding means more chances to help

By attributing the sources of bone mineral density loss, the St. Jude scientists have created a roadmap for exploring potential interventions. The ultimate goal is to give survivors of childhood cancer as much independence as possible to take control of their futures.

“I want survivors to know that if they have low bone mineral density, it’s not an insurmountable problem,” Ness said. “You can be proactive – by being physically active, avoiding smoking and making sure your physician understands your chronic health condition. That’s how you give yourself the best chance of having an independent life as an adult, chasing your dreams.” 

Maybe, one day, they could even become an astronaut.

Written by Alex Generous, PhD.

Source: St. Jude Children’s Research Hospital

Categories : Skeletal SystemTags :

Beyond Hormones: Researchers Define X and Y Chromosome Contributions to Height

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Photo by Monstera on Pexels

A Geisinger study provides new insight into height differences between adult men and women, demonstrating that Y chromosome genes contribute more to height than their X chromosome counterparts, independent of male sex determination. The results were published this week in the Proceedings of the National Academy of Sciences.

Typical females have two X chromosomes, while typical males have one X and one Y chromosome. The differences between the X and Y chromosomes cause hormonal differences between males and females, but these differences have been insufficient to explain the average 13cm height difference between the sexes.

“Because height shows a large and reproducible difference between sexes and is widely measured, it serves as a valuable model for investigating the genomic factors underlying sex differences,” said Matthew Oetjens, Ph.D., assistant professor in Geisinger’s Department of Developmental Medicine and one of the study leads.

The Geisinger research team sought to determine the effects of sex-related factors on human height by examining height in people with an abnormal number of X or Y chromosomes, a genetic condition known as sex chromosome aneuploidy.

The team analysed genetic and clinical data on nearly one million participants enrolled in Geisinger’s MyCode Community Health Initiative, the National Institutes of Health’s All of Us cohort and the UK Biobank. Of these participants, 1225 had a sex chromosome aneuploidy. By incorporating people with more or fewer than two sex chromosomes into a model of height, they found that exchanging an X for a Y chromosome increased height by 3.1cm, independent of other sex-related factors, including hormonal differences. This result suggests that an estimated 23% of the average difference in height between men and women is explained by increased expression of shared genes on the Y chromosome relative to the X chromosome.

“Beyond its implications for understanding human height, this study provides broader insights into how sex chromosome aneuploidy research can uncover the mechanisms behind observed sex differences in various medical conditions,” said Alexander Berry, PhD, bioinformatics scientist and study co-lead.

SHOX, a gene found on both the X and Y chromosomes, is a known contributor to human height, but because two copies are found in both men and women, it has not been considered a likely contributor to the sex difference in height. However, recent studies have shown that SHOX is partially silenced on the second X chromosome in individuals with two or more X chromosomes. The Geisinger study’s results are consistent with the hypothesis that reduced SHOX expression in females results in a net difference in height between the sexes.

Source: Geisinger Health System

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Obesity Found to be a Leading Cause of Knee Osteoarthritis

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New research from the University of Sydney reveals that obesity, having a knee injury and occupational risks such as shift work and lifting heavy loads are primary causes of knee osteoarthritis.

The study also found that following a mediterranean diet, drinking green tea and eating dark bread could reduce the risk of developing knee osteoarthritis.

Published in Osteoarthritis and Cartilage, the study was led by Associate Professor Christina Abdel Shaheed and Dr Vicky Duong.

Using data from 131 studies conducted between 1988 to 2024, the researchers examined over 150 risk factors in participants ranging from 20 to 80 years old to determine which were associated with an increased risk of developing knee osteoarthritis. 

“Our research found that while factors such as eating ultra-processed foods and being overweight increase the risk, addressing lifestyle factors – such as losing weight or adopting a better diet – could significantly improve people’s health,” Associate Professor Abdel Shaheed said.

Co-author Professor David Hunter, a researcher at the Kolling Institute and Professor of Medicine at the University of Sydney, said: “Women were twice as likely to develop the condition than men, and older age was only mildly associated with increased risk.”

Reducing the risk of knee osteoarthritis

Dr Duong, lead author and post-doctoral researcher at the Kolling Institute, said: “Eliminating obesity and knee injuries combined could potentially reduce the risk of developing knee osteoarthritis by 14 percent across the population.

“We urge governments and the healthcare sector to take this seriously and to implement policy reforms that address occupational risks, subsidise knee injury prevention programs, and promote healthy eating and physical activity to reduce obesity.”

Source: University of Sydney