Category: Skeletal System

Plant-derived Substance Shows Osteoprotective Properties

Researchers have found that a substance derived from Saussurea controversa, a member of the thistle family, may have significant potential in recovering lost bone mass.

Metabolic bone diseases such as osteoporosis are called the silent epidemic of the 21st century. A person may only become aware of their condition by sustaining a hip or spine fracture.

According to statistics, every third woman and every fifth man after 50 have osteoporosis. Thus, it is promising to search for and obtain substances and materials for implants that have osteoinductive properties and are capable of initiating the processes of transformation of stem cells into bone.

Certain trace elements, such as calcium and magnesium, influence the processes of bone regeneration and the maintenance of their normal structure. Organic molecules that can bind to them provide an improvement in the selectivity of their therapeutic action – the resulting complexes play a significant role in bone formation and development. From this point of view, salts of chelidonic acid have great potential, for example, from the Saussurea controversa known since ancient times for its healing properties.

Researchers from the Immanuel Kant Baltic Federal University, Siberian State Medical University, and Tomsk Polytechnic University had previously discovered that calcium chelidonate is a promising drug for bone volume restoration. 

In their latest work, they obtained this substance in a semisynthetic way: extracts from Saussurea controversa were the source of the chelidonic acid, to which an alkali solution and calcium chloride were added.

“The content of this substance differs in the samples of raw material and, most likely, its biosynthesis depends on the amount of calcium in the soil. For pharmaceutical purposes, it is advisable to use calcium chelidonate obtained by a semisynthetic method,” explained Elena Avdeeva, candidate of pharmaceutical sciences, researcher, Siberian State Medical University

An X-ray analysis confirmed that the substance has a structure identical to a natural compound. Researchers tested the effect of the substance in vitro and in vivo: it promoted the conversion of human stem cells derived from adipose tissue (hAMMSC) and mouse mesenchymal stromal cells into osteoblasts respectively. 

Calcium chelidonate is non-toxic and promotes bone regeneration: in vitro studies have shown that a dose of only 10mg/L increases the number of viable stem cells. Titanium implants coated with calcium phosphate and bearing autologous bone marrow were introduced into mice. The researchers found that calcium chelidonate stimulated the growth of new bone on the surface of the implant with daily administration of the drug for 35 days.

“The use of substances with osteoprotective properties, in particular, calcium chelidonate, is promising for the treatment of several diseases associated with bone defects or bone metabolism disorders. We are considering the development of a pharmaceutical form of the substance and its introduction into practical medicine,” concluded Larisa Litvinova, Doctor of Medicine, professor, head of the laboratory of immunology and cellular biotechnology at the IKBFU.

Source: News-Medical.Net

Journal information: Avdeeva, E., et al. (2021) Calcium Chelidonate: Semi-Synthesis, Crystallography, and Osteoinductive Activity In Vitro and In Vivo. Pharmaceuticals. doi.org/10.3390/ph14060579.

Bone Loss Linked to Cognitive Decline in Women

Photo by Miikka Luotio on Unsplash
Photo by Miikka Luotio on Unsplash

Researchers  have discovered a link between cognitive decline and accelerated bone loss, and found that cognitive decline over five years increased future fracture risk in women. There was a less strong association in men.

The 16-year study enrolling individuals aged 65 and over was led by the Garvan Institute of Medical Research and , and has uncovered a potential new approach to help identify older people who may be at risk of fracture.
“Bone loss and cognitive decline are major public health issues, but both are ‘silent diseases’ that can go undetected and untreated for long periods, often until the conditions are severely progressed,” says Professor Jacqueline Center, Head of the Clinical Studies and Epidemiology lab at Garvan, endocrinologist at St Vincent’s Hospital and senior author of the findings published in the Journal of Bone and Mineral Research.

“Our study has revealed a link between the two in women, which suggests that cognition should be monitored together with bone health, as a decline in one could mean a decline in the other. These findings may help refine best practice guidelines of how cognition and bone health are monitored in older age, to ensure appropriate treatment can be more effectively administered.”

A growing problem with an ageing population

Osteoporosis affects some 200 million people worldwide, and more than 35 million for dementia — numbers set to double over the next 20 years due to rising life expectancy.

“Cognitive decline and bone loss both result in increased disability, loss of independence and an increased risk of mortality. There is some evidence that older individuals with dementia have a higher risk of hip fractures, but whether the decline of both bone and cognitive health are linked over time has not been studied,” said first author Dr Dana Bliuc from the Garvan Institute.

“We set out to understand the long-term association, with our study the first to investigate both cognitive and bone health data over more than 15 years.”

Data was drawn from the Canadian Multicentre Osteoporosis Study (CaMos), which has monitored skeletal health in community-dwelling people since 1995. The researchers examined cognitive and bone health measurements of 1741 women and 620 men aged 65 years and older, who were free of cognitive decline symptoms at the study outset.

Cognition link to bone health

“After adjusting for all other variables, we observed a significant link between a decline in cognitive health and bone loss in women. This association was weaker and not statistically significant in men,” said Dr Bliuc.

“Interestingly, we also saw that cognitive decline over the first five years was associated with a 1.7-fold increase in future fracture risk in women in the subsequent 10 years. This was independent of the level of bone loss,” Dr Bliuc added.

“While this study could not identify a causal link – whether a decline in cognitive function leads to a decline in bone loss, or vice versa – it suggests that cognitive decline should be monitored along with bone health, as a decline in one may signal the need for increased vigilance in the other,” said Professor Center.

The researchers add that the link could potentially be mediated by a third factor, such as oestrogen deficiency, linked to bone loss and cognitive decline. This research also opens the door for additional studies into what the link between these two common conditions may be.

“What our study highlights is that cognitive health is potentially an important factor for providing more information to individuals and their health professionals on fracture risk, and ultimately improve health outcomes for our older population,” said Professor Center.

Source: Garvan Institute of Medical Research

Journal information: Bliuc, D., et al. (2021) Cognitive decline is associated with an accelerated rate of bone loss and increased fracture risk in women: a prospective study from the Canadian Multicentre Osteoporosis Study. Journal of Bone & Mineral Research. doi.org/10.1002/jbmr.4402.

New Insights into What Stimulates Bone Growth

Photo by Nino Liverani on Unsplash
Photo by Nino Liverani on Unsplash

Researchers have discovered some new insights into how bone mass is maintained and how physical load stimulates bone growth.

Researchers from the National Cerebral and Cardiovascular Center Research Institute in Japan have revealed that the expression of the peptide osteocrin (OSTN) is influenced by load – decreasing when load is reduced, and increasing when it is added. Their study was published in Cell Reports.

Bones and skeletal muscles are strengthened by loads produced in exercise, preventing bone and muscle atrophy, and maintaining bone and muscle strength is important for maintaining physical activity. The growth of long bones, such as the femur and tibia, is a very complex process controlled by genetic and environmental factors, such as exercise and gravity.

Understanding bone loss would help retain bone density and strength in people who are unable to exercise due to immobility, the elderly, as well as astronauts in spaceflight.

Study lead author Haruko Watanabe-Takano said, “Not much is known about how mechanical force initiates biochemical signals to control bone growth. We investigated how load is related to the metabolic balance adjustment of bone maintenance.”

Bone mass and strength is maintained by the balanced activities of two types of cells – the bone-genearting osteoblasts, and the bone-dissolving osteoclasts – and is thought to be made in response to load demand. Specifically, the team investigated the expression of OSTN, a peptide produced by osteoblasts, in mice. OSTN is critical to the regulation of bone growth, as well as physical endurance.

The researchers found that OSTN was very strongly expressed in bones such as the tibia, radius, and ulna, and in regions experiencing load. They determined that OSTN was secreted by the periosteal osteoblasts in these bones. The periosteum is a fibrous membrane that covers nearly every bone in the body, except for the joints of the long bones. This tissue has a major role in bone growth and bone repair and has an impact on the blood supply of bone as well as skeletal muscle. Despite its importance, it has received little attention in the literature and in some ways is not well understood.

“We also found that OSTN expression decreased when load was reduced, and was increased by load stimulation,” says Watanabe-Takano. “Moreover, when we genetically engineered mice lacking OSTN, we found that they had reduced bone mass compared with normal mice and lacked load-induced recovery of bone mass after prolonged load reduction. Thus, we concluded that OSTN makes bone in response to stimulation by load, promoting bone formation.”

The team found that to create this effect, OSTN increases levels of another peptide, called C natriuretic peptide, which in turn drives bone-forming osteoblasts to multiply, mature, and become functional.

The findings have implications for treatments for bed-ridden patients and others at risk of bone loss, such as the elderly. Further studies will explore issues such as how periosteal cells detect load stimulation.

Source: News-Medical.Net

Journal information: Watanabe-Takano, H., et al. (2021) Mechanical load regulates bone growth via periosteal Osteocrin. Cell Reports. doi.org/10.1016/j.celrep.2021.109380.

New Biomaterial Produced from Frog Skin and Fish Scales

Photo by Robert Zunikoff on Unsplash

Researchers at Nanyang Technological University, Singapore (NTU Singapore) have developed a new biomaterial made entirely from discarded bullfrog skin and fish scales that could help in bone repair.

The porous biomaterial, which contains the same compounds that are predominant in bones, acts as a scaffold for osteoblasts, or bone-forming cells, to adhere to and multiply, leading to new bone formation. Bone-forming cells successfully latched onto the biomaterial and started growing, and it was found to have a low inflammatory risk.

This kind of scaffold could help regenerate bone tissue lost to disease or injury, such as jaw defects from trauma or cancer surgery. It could also assist bone growth around surgical implants such as dental implants.

The current standard practice of using a patient’s own tissues means extra surgery is needed for bone extraction. The biomaterial used, frog skin and fish scales, are a significant waste stream produced by Singapore’s aquaculture industry and using them helps repurpose this waste.

‘Waste-to-resource’

“We took the ‘waste-to-resource’ approach in our study and turned discards into a high-value material with biomedical applications, closing the waste loop in the process,” said Dalton Tay, Assistant Professor, Nanyang Technological University. “Our lab studies showed that the biomaterial we have engineered could be a promising option that helps with bone repair. The potential for this biomaterial is very broad, ranging from repairing bone defects due to injury or ageing, to dental applications for aesthetics. Our research builds on NTU’s body of work in the area of sustainability and is in line with Singapore’s circular economy approach towards a zero-waste nation.”

To make the biomaterial, the team first extracted Type 1 tropocollagen (many molecules of which form collagen fibres) from the discarded skins of the American bullfrog and hydroxyapatite (a calcium-phosphate compound) from the scales of snakehead fish, commonly known as the Toman fish.

Collagen and hydroxyapatite (HA) are two predominant components found in bones, thus conferring on the biomaterial a structure, composition, and ability to promote cell attachment similar to bone, as well as toughness.

The scientists removed all impurities from the bullfrog skin, then blended it to form a thick collagenous paste that is diluted with water, from which collagen was extracted. “Using this approach, we were able to obtain the highest ever reported yield of collagen of approximately 70 per cent from frog skin, thus making this approach commercially viable,” said Asst Prof Tay, who is also from the NTU School of Biological Sciences (SBS).

HA was harvested from discarded fish scales through calcination – a purification process that requires high heat – to remove the organic matter, and then air-dried.

The biomaterial was synthesised by adding HA powder to the extracted collagen, then cast into a mould to make a 3D porous scaffold — a two-week process which the team believes can be shortened.

Testing the biomaterial

To assess the biological performance of the porous biomaterial scaffold for bone repair, the scientists seeded bone-forming cells onto the scaffold.

The cells proliferated, and after a week, the cells were uniformly distributed across the scaffold – an indicator that the scaffold could promote proper cellular activities and eventually lead to tissue formation. The scientists also found that the presence of HA in the biomaterial significantly enhanced bone formation.

The biomaterial was also tested for its tendency to cause an inflammatory response, which is common after a biomaterial is implanted in the body.

Using real-time polymerase chain reaction, the scientists found that the expression of pro-inflammatory genes in human immune cells exposed to the biomaterial stayed “relatively modest” compared to a control exposed to endotoxins, a compound known to stimulate immune response, said Asst Prof Tay.

For instance, the expression of the gene IL6 in the biomaterial group was negligible and at least 50 times lower than that of the endotoxins-exposed immune cells. This suggests that the risk of the NTU-developed biomaterial to trigger an excessive acute inflammatory response is low.

The team is now further evaluating the long-term safety and efficacy of the biomaterial as dental products. Further research would involve studying how the body responds to this biomaterial in the long term, as well its use in other applications such as skin wounds, along with further development of the waste-to-resource pipeline.

A preprint copy of the article is available as a PDF for download.

Source: Nanyang Technical University

Fat Cells Tapped for Spinal Fusion

Photo by cottonbro from Pexels

Researchers at Johns Hopkins Medicine have come up with a method that uses adipose cells, better known as fat, as a practical and plentiful source of stem cells for use in spinal fusion surgeries.

Spinal fusion ‘welds’ two or more vertebrae together so that they heal into a single, solid bone. Unfortunately, the surgery — using bone taken from other parts of the patient’s body — fails in up to a fifth of procedures. Stem cells, harvested from a patient’s marrow and allowed to mature into bone cells, can improve the outcome of spinal fusions. However, the aspiration method for getting stem cells out of the marrow carries an infection risk and often is painful.

In a study published in the journal Spine, researchers sought to try out adipose cells rather than bone marrow as a source for the stem cells.

Performing spinal fusion procedures in rats, the researchers found that freshly isolated stem cells from fat worked just as well as the more commonly used bone marrow stem cells. The researchers say this suggests the technique could be a candidate for human clinical trials.

“Bone marrow stem cells are isolated in human patients from the hip,” said Christina Holmes, PhD, a former Johns Hopkins Medicine postdoctoral fellow now at Florida State University. “But using a huge needle to take out bone marrow is a painful procedure, and we can only get a limited number of cells, so we’ve found an alternative source by using stem cells from fat.”

Alexander Perdomo-Pantoja, MD, a postdoctoral fellow at the Johns Hopkins University School of Medicine, said spinal fusion procedures are used to treat many different conditions.

“Spinal fusions are used for anything that causes spinal instability, which usually produces significant mechanical pain,” he says. “You see it frequently when we get older as the intervertebral discs, ligaments and muscles in the spine deteriorate. But these procedures can also be used to treat instability when it is caused by tumors, fractures, deformities or trauma.”

The researchers isolated stem cells from fat and bone marrow, and implanted them into rat spines. For the adipose-derived stem cells, the researchers used freshly isolated cells to see if they could speed up and simplify the procedure.

Stem cells are currently sourced either from bone marrow or fat and are often grown in a lab culture to mature them enough for spinal fusion. During culturing, there is a risk of contamination or transformation into unusable bone. Holmes said that freshly isolating cells avoids these problems, along with reducing labour and material costs.

While stem cells from fat are commonly used in cosmetic procedures, they are not often used in spinal fusions, she adds.

“We feel that fat cells are a logical alternative to bone marrow cells because most patients have an adequate supply of fat cells,” Tsaid imothy Witham, MD, director of the Johns Hopkins Neurosurgery Spinal Fusion Laboratory. ”Fat also is much more accessible during surgery and can be harvested with less stem cell death than bone marrow. Spinal fusion is a very common procedure, and we feel this approach could be applied across a wide cohort of spinal fusion patients.”

The researchers found significantly more bone formation and blood supply in the fresh adipose-derived stem cells compared with what they saw in previous studies with cultured cells from both fat and bone marrow.

The next step for Witham and his team is identifying which cells are the most advantageous for spinal fusions and then characterising them.

Source: John Hopkins University

Journal information: Alexander Perdomo-Pantoja et al. Comparison of Freshly Isolated Adipose Tissue-derived Stromal Vascular Fraction and Bone Marrow Cells in a Posterolateral Lumbar Spinal Fusion Model, Spine (2020). DOI: 10.1097/BRS.0000000000003709

Unique Genetic Profile of Bone Cells Mapped

X-ray of a wrist. Photo by Cara Shelton on Unsplash

Pioneering new research has charted the unique genetic profile of the skeleton’s ‘master regulator’ cells, known as osteocytes.

The study led by the Garvan Institute of Medical Research was published in Nature Communications. The study describes the genes that are switched on or off in osteocytes, a multifunctional type of bone cell that regulates how bone material is grown or broken down in order to maintain healthy skeletons.

“This new information provides a kind of genetic shortlist we can look to when diagnosing bone diseases that have a genetic component,” said the study’s first author Dr Scott Youlten, Research Officer in the Bone Biology Lab. “Identifying this unique genetic pattern will also help us find new therapies for bone disease and better understand the impacts of current therapies on the skeleton.”

Far from static, the skeleton is a highly dynamic structure that is constantly remodelled throughout a person’s life. Though osteocytes are the most common cell type in bone, they have been hard to study as they are embedded within the skeleton’s hard mineral structure.

Osteocytes form a network inside bones on a scale and complexity which mirrors the neurons in the brain (42 billion osteocytes with over 23 trillion connections between them), which monitors bone health and responds to ageing and damage by signalling other cells to either add more bone or break down old bone. Osteoporosis, rare genetic skeletal disorders and other bone diseases arise from an imbalance in these processes.

To understand what genes are involved in controlling bone build-up or breakdown, the researchers isolated bone samples from different skeletal sites of experimental models in order to measure the average gene activity in osteocytes. In so doing, they found an osteocyte ‘signature’ of 1239 genes that are switched on. Of these genes, 77% had no previously known role in the skeleton, and many were completely novel and unique to osteocytes.

“Many of the genes we saw enriched in osteocytes are also found in neurons, which is interesting given these cells share similar physical characteristics and may suggest they are more closely related than we previously thought,” explained Dr Youlten.

Comparing the osteocyte signature genes with human genetic association studies of osteoporosis could identify new genes that may be associated with susceptibility to this common skeleton disease. Additionally, a number of these osteocyte genes were also shown to be responsible for rare bone diseases.

“Mapping the osteocyte transcriptome could help clinicians and researchers more easily establish whether a rare bone disease has a genetic cause, by looking through the ‘shortlist’ of genes known to play an active role in controlling the skeleton,” said Dr Youlten.

Co-senior author Professor Peter Croucher, Deputy Director of the Garvan Institute and Head of the Bone Biology Lab, said that “the osteocyte transcriptome map gives researchers a picture of the whole landscape of genes that are switched on in osteocytes for the first time, rather than just a small glimpse”.

“The majority of genes that we’ve found to be active within osteocytes had no previously known role in bones. This discovery will help us understand what controls the skeleton, which genes are important in rare and common skeletal diseases and help us identify new treatments that can stop development of bone disease and also restore lost bone.”

Source: Medical Xpress

Journal information: Nature Communications (2021). DOI: 10.1038/s41467-021-22517-1

Osteoporosis Rates are Increasing in US Women

Osteoporosis is present in Almost one in five American women aged 50 and older, according to data from the National Health and Nutrition Examination Survey (NHANES), and the osteoporosis rates are increasing.

Neda Sarafrazi, PhD, of the National Center for Health Statistics (NCHS) in Hyattsville, Maryland, and colleagues reported the findings in an NCHS Data Brief.

Osteoporosis is defined as bone mineral density (BMD) value at least 2.5 standard deviations below young-adult average at the femoral neck or lumbar spine was present, and was measured in NHANES with dual x-ray absorption dosimetry.

In cross-sectional survey data from 2017-2018, 19.6% of women 50 and older had osteoporosis at the femoral neck, lumbar spine, or both. In men, the age-adjusted prevalence was only 4.4% of men 50 and older.

All in all, osteoporosis was present in 12.6% of all American adults 50 and older, which was defined as a bone mineral density (BMD) value at least 2.5 standard deviations below the average for young adults at the femoral neck or lumbar spine.

Osteoporosis, as to be expected, was far more common among older adults, affecting 17.7% of all men and women 65 and older, versus 8.4% of those ages 50-64. In women ages 65 and older, the prevalence was 27% and at ages 50-64 was 13.1%. In men, prevalence values were 5.7% in those 65 and older and 3.3% for those 50-64.

Sarafrazi’s team found that osteoporosis had become slightly more prevalent over the years. In 2007-2008, 9.4% of Americans 50 and older had osteoporosis. While rates remained steady throughout for men, a big uptick of 5 percentage points was seen for women.

“Monitoring the prevalence of osteoporosis and low bone mass may inform public health programs that focus on reducing or preventing osteoporosis and its consequences,” suggested Sarafrazi’s group. “Healthy People 2020 has a goal of 5.3% or less for the prevalence of osteoporosis at the femur neck for adults aged 50 and over.”

“In the United States, the prevalence of osteoporosis among adults aged 50 and over at the femur neck only was 6.3% and has not met the 2020 goal,” they stressed.

The data also revealed high rates of low bone mass, a precursor of osteoporosis, defined as BMD of 1 to 2.5 standard deviations below the average for young adults.

Among all adults ages 50 and older, 43.1% had low bone mass at the femoral neck, lumbar spine, or both. Among women, prevalence was 51.5% and among men 33.5% .

The overall rate reached 47.5% in those 65 and older. However, older age seemed to be less of a factor for women, with almost no difference between the 50-64 and 65-plus age groups.

However, the prevalence rates of low bone mass in both sexes held steady during the decade between 2007-2008 and 2017-2018.  

Source: MedPage Today

Journal information: Sarafrazi N, et al “Osteoporosis or low bone mass in older adults: United States, 2017–2018” NCHS Data Brief 2021; No 405.

20% of Healthy Children May Have Benign Bone Tumours

Around 20% of healthy children may possess benign tumours, according to a review of radiographs taken nearly a century ago.

Although it sounds alarming, non-ossifying fibromas and other common benign bone tumours in symptom-free children are not dangerous. Such bone tumours are often discovered on x-rays taken for other causes, such as a fracture. 

“Understandably, these tumours cause a lot of anxiety for patients and families as they await confirmation that the tumour is benign,” said Christopher Collier, MD, Indiana University School of Medicine, Indiana University. “They need reassurance and often ask how common these tumours are, when did they first appear, and whether they will resolve over time? We don’t have much evidence to date to address these questions.”

To address these questions, the researchers analysed annual x-rays taken of children’s bones as they grew, however such studies today are not feasible today due to ethical concerns over sensitivity of children to ionising radiation. Therefore, they drew on a unique collection of radiographs from the Brush Inquiry, a study in which a series of healthy, ‘normal’ children in Ohio, underwent annual radiographs from 1926 to 1942.

Dr Collier’s team analysed a total of 25 555 digitised radiographs of 262 children, followed from infancy to adolescence, finding a high prevalence of bone tumours. A total of 35 benign bone tumors were found in 33 children – an overall rate of 18.9 percent when considering that only the left side of the children was radiographed.

Over half of the tumours were non-ossifying fibromas, which are connective tissue masses that have not hardened into bone. Generally, these fibromas appeared around age five, and again around the time of skeletal maturation, possibly linked to growth spurts. Of 19 non-ossifying fibromas detected, seven disappeared over time. Others may have resolved some time after the annual radiographs stopped.

Rarer benign bone tumoors included enostoses, sometimes called ‘bone islands’; and osteochondromas or enchondromas (tumours in cartilage). In patients with these tumours, they persisted to the last available radiograph.

The findings are similar to the rates of benign bone tumours in healthy adults. Dr Collier noted: “Despite the inherent limitations of our historical study, it may provide the best available evidence regarding the natural history of asymptomatic benign childhood bone tumors.”

Source: News-Medical.Net

NASA Awards Grant for Bone Loss Research


The US space agency NASA has awarded a US$750 000 grant to conduct research into how bone weakening in the absence of mechanical loading, as in zero gravity, can be reduced.

Dr Meghan E McGee-Lawrence, biomedical engineer in the Department of Cellular Biology and Anatomy at the Medical College of Georgia, the recipient of the grant, will use the money to better understand how bone loss occurs in space from lack of gravity and also from disuse here on Earth.

“It’s a problem for the astronauts who are on the International Space Station for long periods of time, and it’s going to continue to be a problem for eventually trying to send astronauts to Mars,” Dr McGee-Lawrence said. It is also a problem in patients with spinal cord injuries, undergoing prolonged bedrest or physical inactivity.

“If we can find a way to make bone more sensitive to mechanical loading, then we would be able to increase bone mass with less effort. That is a long-term goal,” she says.

Her focus is the natural sensors of mechanical loading on the bone called osteocytes, and her lab found that tears, called plasma membrane disruptions, occur in osteocytes from mechanical loading, resulting in repair. They showed that these disruptions from loads happen in under a minute, and set off changes like letting in extra calcium, influencing osteoblast and osteoclast activity. If there are few tears from mechanical loading, osteoblasts are not needed and so osteoclasts will resorb some bone matrix. Even walking around has been shown to cause plasma membrane disruptions, something not possible for bedrest patients or astronauts in space.

With this in mind she posed the question, “can we do anything to reverse those processes. Can we do something to the osteocytes to make them either more likely to experience tears or more likely to repair those tears and then, accordingly, make it so there is less bone loss during disuse.”

Fewer tears seem to be not good, and she and her team want to further investigate what happens to the repair rate with disuse. They also want to know the best healing rate; slow for better osteocyte survival, or does osteocyte survival enable faster repair?

“The good news is we can dial it in either direction,” she says. However, they believe faster repair is not better because the calcium influx is linked to the cell’s response.

“Think of a membrane disruption as a doorway into the cell. If you slam the door too quickly, then there is not enough time for the cell to sense that tear and initiate the signaling to respond,” she explained.

She believes that proteins involved in repairing membrane tears, like PRKD1, are logical targets for genetic and pharmacological methods to either increase tears or speed up repair.

“The ultimate goal is can we come up with a way, whether it’s a drug therapy or a different type of regimen that can make these processes work better in astronauts and people on earth who are subjected to disuse as well,” she said.

Even with resistive exercises, astronauts lose bone mass in space. Bisphosphonates are only really effective with age-related bone loss and not loss from inactivity or lack of gravity. With the current most advanced exercise device on the International Space Station, astronauts come back to Earth fitter than when they left but still lose some bone mass. On a three-year voyage to Mars, many astronauts could return with osteoporosis. “That is really a problem. Not only are they losing bone actively while they are in space, at some point they have to come back to gravity… and then what happens?” she says. Recovering bone strength on Earth is a long and difficult process for astronauts. She and her research team are also finding that osteocytes are less likely to repair and survive tears after a long period of disuse.

There are effective therapies, like bisphosphonates, that can help age-related bone loss, but they have not been shown to be effective when disuse is the primary driver. “That is why we need to come up with better targets, more effective targets, to try to prevent disuse-induced bone loss,” she said. While it has long been clear that mechanical load also translates to stronger bones, just how remains a question, she says. She suspects the plasma membrane tears are key.

“We think the formation of these tears is important for how the bone cells know they are being exposed to that level of loading,” she said, with high-impact loading from running and jumping being particularly important. “Cells need a way to know what is going on outside their cell membrane. This is one way to do that.”

Source: News-Medical.Net

Plant-based Protein Increases Bone Turnover

A Finnish study has found that increasing the share of dietary protein from plant versus animal sources leads to increased bone turnover and possible fracture risk.

The 136 adult participants followed one of three diets for a period of three weeks. One of them was modelled on the typical Finnish diet where 70% of protein came from animal sources and the rest from cereals. The second had half the protein come from animal sources and the other half from plants, and the third had 70% of protein from plants and the rest from animal sources

Dairy milk, which is fortified with vitamin D in Finland, was substituted with unfortified plant-based milk, which may have been a confounding variable. There was a marked increase in bone formation and resorption markers, which in the long term could indicate bone loss. These findings are in line with the Oxford-EPIC study, which followed participants for 18 years and found a higher rate of fractures in vegetarians compared to those on an omnivorous diet.

“The results could be different if fluid dairy products had been replaced with plant-based drinks fortified with vitamin D and calcium,” said Docent Suvi Itkonen, Department of Food and Nutrition, Faculty of Agriculture and Forestry, University of Helsinki. “Then again, the average vitamin D intake was also below the recommended level in the group where subjects consumed the animal protein-rich diet, but not to the same extent as in the other groups.”

Source: News-Medical.Net

Journal information: Itkonen, S. T., et al. (2021) Partial Replacement of Animal Proteins with Plant Proteins for 12 Weeks Accelerates Bone Turnover Among Healthy Adults: A Randomized Clinical Trial. The Journal of Nutrition.doi.org/10.1093/jn/nxaa264.