Category: Skeletal System

Categories : Skeletal SystemTags :

Unique Genetic Profile of Bone Cells Mapped

On By ModernMedia
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

Categories : Skeletal SystemTags :

Osteoporosis Rates are Increasing in US Women

On By ModernMedia

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.

Categories : Paediatrics Skeletal SystemTags :

20% of Healthy Children May Have Benign Bone Tumours

On By ModernMedia

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

Categories : Skeletal SystemTags :

NASA Awards Grant for Bone Loss Research

On By ModernMedia


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

Categories : Diet and Nutrition Skeletal SystemTags :

Plant-based Protein Increases Bone Turnover

On By ModernMedia

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.

Categories : New Compounds and Treatments Skeletal SystemTags :

Osteoporosis Drug Enhances Natural Bone Formation

On By ModernMedia

A new osteoporosis drug, NaQuinate, that treats osteoporosis by enhancing its response to weight bearing, has completed its first human clinical trial. 

NaQuinate is a naphthoquinone carboxylic acid, and is found naturally as a Vitamin K metabolite. It has been shown in mouse models that NaQuinate responds synergistically to mechanical loading, building bone density. In a separate trial, the efficacy of NaQuinate is being evaluated against that of bisphosphonates without loading and anabolics with loading.

Haoma Medica’s Chief Medical Officer, Dr Cenk Oguz, said: ”We are delighted that the first-in-human study has completed its last dosing. There were no significant safety or tolerability concerns up to the highest doses tested which underlines our expectation that NaQuinate is safe and well tolerated.”
Haoma Medica’s CEO,  Dr Steve Deacon, said:”Our pre-clinical research has revealed an exciting feature of NaQuinate where it appears to have the capacity to work in harmony with the body’s natural response to weight bearing exercise to synergistically enhance bone formation when and where required – now that would be a ‘smart’ drug. Together with the safety data from this first-in-human study, this supports the potential that NaQuinate treatment could provide a safe, novel and smart therapeutic approach to bone disorders like osteoporosis and better maintain healthy skeletal aging.”

Source: PR NewsWire