Researchers identify a treatment for a rare bone loss disorder that might also lead to help for aging brittle bones
A possible ‘first-line’ treatment for a rare bone loss disease has been identified by a research team led by Tohoku University in Japan. The research findings, published in the journal Molecular Cell, could also provide insight into treating age-related osteoporosis.
Hajdu-Cheney syndrome is a rare genetic disease that leads to severe osteoporosis and developmental defects, including the reabsorption of bones in the hands and feet. The disease is associated with mutations in a particular gene, called NOTCH2, which codes for proteins involved with bone maintenance. The NOTCH2 proteins usually help balance destruction and construction essential for bone maintenance and repair. Mutations associated with Hajdu-Cheney syndrome upset that balance, but the exact mechanisms causing bone resorption have not been well understood.
Now, through a series of detailed tests, molecular biologist Hiroyuki Inuzuka and his colleagues have worked out the specific molecular pathway that results in Hajdu-Cheney syndrome.
They found that this particular NOTCH2 mutation does not maintain normal NOTCH2 protein abundance, with the help of another protein, called FBW7. To discover this, the researchers knocked out the gene for Fbw7 in the bones of mice. Without the gene and resulting protein, the mice had severe osteoporosis, much like people with Hajdu-Cheney syndrome — indicating that FBW7 is the primary regulator of this system.
They further determined that in humans with Hajdu-Cheney syndrome, the FBW7 protein was unable to bind to NOTCH2 proteins because the binding spot is missing in osteoclasts. This mutation allows the osteoclasts to over-operate, breaking down too much bone tissue.
The researchers were able to reverse bone loss in the knock-out mice with the elevated NOTCH2 by giving them a medication that blocks osteoclast formation. They tried several different treatments, including a chemical compound called DAPT that was particularly effective. DAPT has been shown to help with osteoarthritis by inhibiting function of NOTCH proteins in other studies. Using DAPT as well as Zoledronic acid, a common medication for osteoporosis, “may become a first-line treatment for Hadju-Cheney syndrome,” the researchers conclude in their study.
“By clearly identifying the relationship between FBW7 and NOTCH2 proteins, we have identified potential therapeutic targets for patients with rare bone diseases as well as much more widespread age-related osteoporosis,” said Inuzuka.
Learn more: Reversing severe bone loss
The Latest on: Bone loss
via Google News
The Latest on: Bone loss
- If You’re Looking for a Bone-Building Workout, an MD Recommends Making This Surprising Tweak to Your Walkson May 18, 2022 at 8:01 am
Experts at Harvard Medical School have found that the slow movements involved in the Chinese martial art of tai chi can improve balance, reducing the risk of falls, and may even protect against ...
- Len Rome’s Local Health: Osteoporosis and bone healthon May 17, 2022 at 5:48 am
Broken bones are not only painful, but also in adults over 50, and more commonly in women, they can be a sign of a serious disease: osteoporosis.
- The #1 Best Vegetable to Prevent Bone Loss, Says Scienceon May 7, 2022 at 5:21 am
Your bones are fascinating and always changing. But unfortunately, they do begin to get weaker with age. And what many people don't realize is that this begins to happen as early as in your 30s, which ...
- Bone Loss in Premenopausal Women on Long-term Suppressive Therapy With Thyroid Hormoneon May 4, 2022 at 5:01 pm
One year later, after the second BMD measurement, no statistically significant loss of bone mass occurred in any region of the skeleton in any of the patients. However, a review of the individual ...
- Cancer-Treatment-Induced Bone Loss, Part 1on May 2, 2022 at 5:00 pm
Evidence also suggests that preventive CTIBL therapy may halt bone loss.  These patients should therefore be considered for CTIBL treatment and, perhaps, prophylaxis therapy if multiple risk ...
- Pricier, Questionable Bone Density Scan Growing in Useon April 28, 2022 at 11:17 am
He agreed with Clarke, however, that the QCT exaggerates bone mineral density loss in the spine if the T-score is used. If it is, more patients will be diagnosed incorrectly with osteoporosis with ...
- Everything you wanted to know, and do, about osteoporosison April 27, 2022 at 3:26 am
When: Since there are no real symptoms associated with the early stages of bone loss, it can be difficult to know when to seek medical attention for osteoporosis. It is a disease that takes years ...
- Exercise for Osteoporosison April 22, 2022 at 10:31 pm
This is especially important if you know you have bone loss or osteoporosis. - Weight-bearing exercise does not have to be high impact. Running, jogging and jumping may put stress on your spine.
- Your Cancer Answers: What are you doing to keep your bones strong and healthy?on April 22, 2022 at 11:06 am
This dose reduces bone loss and fracture rate in those with adequate calcium intake. Exercise can help to maintain your bone density, strengthen your muscles, improve your balance, and reduce the ...
via Bing News