Mice lacking SLIT3 are unable to heal skeletal fractures, as displayed in image.
A molecule promoting blood vessel growth in bone can create an environment suitable for bone-building formation, representing a potential target for new drugs to treat osteoporosis and fractures, according to new research by Weill Cornell Medicine scientists.
The findings, published May 21 in Nature Medicine, show that a substance, which is best known for spurring nerve growth, called SLIT3, both reversed the bone-weakening effects of osteoporosis and helped fractures heal when administered in mice. The multi-center research effort could fuel drug development efforts targeting the SLIT3 pathway in humans, enabling a new approach for blood vessel-directed therapy to treat bone loss, persistent fractures and fragile bones.
Existing drugs for osteoporosis work in one of two ways: Either they block the cells that destroy bone or they promote bone formation by cells called osteoblasts. “But only those promoting new bone formation will help you actually heal a bone fracture,” said co-senior study author Dr. Matthew Greenblatt, an assistant professor of pathology and laboratory medicine at Weill Cornell Medicine. “Our findings have potentially demonstrated a third category: drugs that target blood vessel formation within bone, prompting new bone to form.”
Osteoporosis, which causes bones to thin and become brittle, leads to nearly 9 million fractures worldwide each year, or one every three seconds, according to the International Osteoporosis Foundation. Women are disproportionately affected, and the risk increases with age. One in two women and one in five men will have an osteoporotic fracture during their lifetimes, and these fractures kill as many women each year as breast cancer.
“Osteoporosis and skeletal fractures due to osteoporosis are both common and deadly,” Dr. Greenblatt said.
To counteract that trend, Dr. Greenblatt has been investigating the cellular causes of osteoporosis in an effort to promote bone growth. Prior research using mice genetically engineered to lack an adaptor protein known as SHN3 showed that its absence conferred high bone mass. Building on that discovery, Dr. Greenblatt and his team decided to examine the resulting changes in bone blood vessels. “We used those mice as a means to find the signals coming from osteoblasts to control the specific type of blood vessels present in bone,” he said.
The researchers were surprised to find that osteoblasts secreted unchanged amounts of almost all known factors promoting blood vessel growth, but SLIT3 levels rose significantly. And when the mice were genetically altered to delete SLIT3, they exhibited low bone mass. “We next asked if we could use SLIT3 to treat mice with skeletal disease, especially osteoporosis and fracture healing,” Dr. Greenblatt said. “When we gave the rodents SLIT3, it reversed their osteoporosis and made their fractures heal faster and stronger.”
“To my knowledge, this is the first example that we can develop a drug to treat bone disease in mice not by targeting the bone-forming cells,” he said, “but instead by targeting special types of blood vessels that exist in bone.”
Further research is needed to determine the best way to deliver SLIT3 to the bone in humans. SLIT3-pathway drugs could also be used in combination with existing drugs to improve patient outcomes.
“Only a small fraction of patients who’ve had a hip fracture and really require medication to prevent additional fractures get the drugs they need. Many people aren’t aware of how debilitating and deadly these kinds of fractures are,” Dr. Greenblatt said. “Having a totally new category of bone drugs that work on different sets of cells could open up new opportunities for treatment.”
In addition to benefiting seniors with osteoporosis, Dr. Greenblatt hopes his research will also help patients with bone injuries that aren’t healing properly, such as those who’ve undergone orthopedic surgery or have fragile bones due to genetic diseases. “Some of those people’s fractures don’t heal because they can’t grow the right type of blood vessels at the site of the fracture,” he said. “That’s what we think SLIT3 will do: help with that growth and promote healing.”
Learn more: Molecule Promoting Blood Vessel Growth in Bone Represents New Target for Osteoporosis Drugs
The Latest on: Osteoporosis
via Google News
The Latest on: Osteoporosis
- Reference values for bone metabolism in a Japanese cohort survey randomly sampled from a basic elderly resident registryon April 9, 2021 at 2:43 am
Sixty-three people (15.3%) were diagnosed as osteoporosis. BMD decreased with age in the femoral neck and total hip. On the other hand, there was no characteristic change with age in the lumber spine.
- North America Osteoporosis Treatment Market to Reach USD 8.29 Billion by 2027on April 8, 2021 at 11:43 pm
The MarketWatch News Department was not involved in the creation of this content. Apr 09, 2021 (The Expresswire) -- The ”North America osteoporosis treatment“ market size is expected to gain momentum ...
- The Bone Density Solution Reviews - Is Shelly Manning’s Bone Density Solution Book Worth Buying? By Nuvectramedicalon April 8, 2021 at 10:07 pm
Of course, most of the women are suffering badly from Osteoporosis that makes faster bone fractures and creates the condition as worsen. If you consider doctors or experts, they will suggest using ...
- Canes and Crutches Market Is Projected to Expand at a CAGR of 4.0% from 2019 to 2027on April 8, 2021 at 10:46 am
Moreover, factors such as increase in the number of people with disabilities and rise in prevalence of arthritis & osteoporosis boost the growth of the global canes and crutches market. Europe ...
- New State-by-State Reports Reveal the Huge Human and Economic Toll of Osteoporosison April 2, 2021 at 6:13 am
April 2, 2021 /PRNewswire/ -- A new series of state-by-state reports released today by the National Osteoporosis Foundation (NOF) highlights substantial differences across the states in the number ...
- New State-by-State Reports Reveal the Huge Human and Economic Toll of Osteoporosison April 2, 2021 at 6:11 am
Tax Planning Personal Finance Save for College Save for Retirement Invest in Retirement Research Mutual Funds Stocks ETFs Bonds Best Investments ...
- New State-by-State Reports Reveal the Huge Human and Economic Toll of Osteoporosison April 2, 2021 at 6:00 am
A new series of state-by-state reports released today by the National Osteoporosis Foundation (NOF) highlights substantial differences ...
- Ask the GP: Osteoporosis treatment could be why thyroid test was inconclusiveon March 31, 2021 at 6:00 pm
In your longer letter, you mention that you had intravenous drug treatment for osteoporosis in July 2019, and again in 2020. This may well be a reason the blood test was inconclusive, as a number of ...
- Circ-ITCH sponges miR-214 to promote the osteogenic differentiation in osteoporosis via upregulating YAP1on March 31, 2021 at 5:00 pm
Osteoporosis is the most prevailing primary bone disease and a growing health care burden. The aim of this study was to clarify the functional roles and mechanisms of the circ-ITCH regulating ...
- Just How Many Older Folks Have Osteoporosis?on March 30, 2021 at 9:15 pm
About one in five American women 50 and older have osteoporosis, National Health and Nutrition Examination Survey (NHANES) data showed. In cross-sectional survey data from 2017-2018, 19.6% of this ...
via Bing News