Tag: osteoporosis

A ‘Fountain of Youth’ for Bone Marrow Stem Cells

Source: National Cancer Institute on Unsplash

Scientists have shown that reduced bone marrow stem cell function with ageing is due to changes in their epigenome, and they were able to reverse these changes in isolated stem cells by adding acetate. This ‘fountain of youth’ for the epigenome could become important for the treatment of diseases such as osteoporosis.

One responsible mechanism for age-related osteoporosis and fracture risk involves the impaired function of the bone-marrow stem cells, which are required for the maintenance of bone integrity. 

For a long time, researchers have looked at epigenetics as a cause of ageing. Epigenetics looks at changes that affect the activity of genes. One of these is changes in proteins called histones, which package and thus control access to DNA. In this study, the researchers investigated the epigenome of mesenchymal stem cells, which are found in bone marrow and can give rise to different types of cells such as cartilage, bone and fat cells.

“We wanted to know why these stem cells produce less material for the development and maintenance of bones as we age, causing more and more fat to accumulate in the bone marrow. To do this, we compared the epigenome of stem cells from young and old mice,” explained Andromachi Pouikli, first author of the study. “We could see that the epigenome changes significantly with age. Genes that are important for bone production are particularly affected.”

The researchers then sought to find out if it was possible to rejuvenate the epigenome of stem cells. To do this, they treated isolated stem cells from mouse bone marrow with a nutrient solution which contained sodium acetate. The cell converts the acetate into a building block that enzymes can attach to histones to increase access to genes, thereby boosting their activity. “This treatment impressively caused the epigenome to rejuvenate, improving stem cell activity and leading to higher production of bone cells,” Pouikli said.

To see if this change could also be responsible for increased fracture risk and osteoporosis with age, the researchers studied human mesenchymal stem cells from hip surgery patients. In elderly patients with osteoporosis, the same epigenetic changes seen with mice were also seen in these human cells.

“Sodium acetate is also available as a food additive, however, it is not advisable to use it in this form against osteoporosis, as our observed effect is very specific to certain cells,” cautioned study leader Peter Tessarz. “However, there are already first experiences with stem cell therapies for osteoporosis. Such a treatment with acetate could also work in such a case. However, we still need to investigate in more detail the effects on the whole organism in order to exclude possible risks and side effects.”

The results were published in the journal Nature Aging.

Source: Max Planck Society

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.

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.

Osteoporosis Drug Enhances Natural Bone Formation

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