Navigation Links
Revealing a novel mode of action for an osteoporosis drug
Date:8/29/2014

Raloxifene is a U.S. Food and Drug Administration (FDA)-approved treatment for decreasing fracture risk in osteoporosis. While raloxifene is as effective at reducing fracture risk as other current treatments, this works only partially by suppressing bone loss. With the use of wide- and small-angle x-ray scattering (WAXS and SAXS, respectively), researchers carried out experiments at the U.S. Department of Energy's (DOE's) Advanced Photon Source (APS) at Argonne National Laboratory that revealed an additional mechanism underlying raloxifene action, providing an explanation for how this drug can achieve equivalent clinical benefit.

These data, together with complementary techniques, help define a novel mechanism by which raloxifene increases inherent bone toughness.

In osteoporosis, decreased bone density increases the risk of fracture. All current drugs for treatment of this disease act upon living cells within the bone matrix to either decrease bone resorption, a process by which the mineral components of bone are broken down and released into the bloodstream, or to increase net bone formation during remodeling, a process by which bone is also broken down but then reforms bone. In either case, treatment results in an overall increase in bone density, and therefore a reduction in fracture risk.

While raloxifene is known to mildly suppress bone loss, "It has always been somewhat paradoxical that raloxifene suppresses bone loss less than other osteoporosis therapies, yet reduces fracture risk to about the same level," said David B. Burr of Indiana University School of Medicine and lead author of the Bone article on this research.

To uncover the density-independent mechanism by which raloxifene (marketed as Evista by Eli Lilly and Company) increases bone toughness, researchers in this study from the Indiana University School of Medicine; Purdue University; Indiana UniversityPurdue University at Indianapolis; the University of California, San Diego; Northwestern University; and Argonne National Laboratory assessed the effect of the drug on devitalized bone cleared of living cells that normally mediate resorption and remodeling.

In these bone samples, raloxifene prolonged the loading that the bone could bear before fracturing, indicating that the drug was acting upon the physical properties of the bone itself. Using ultra-short-echo-time nuclear magnetic resonance, researchers found that raloxifene-mediated water retention within the bone matrix is associated with the observed increase in toughness.

In order to elucidate the mechanism underlying this association, researchers collected WAXS and SAXS diffraction patterns of carbonated hydroxyapatite crystals (cAp), the mineral component of bone that had been subjected to four-point bending. These data, collected at the X-ray Science Division 1-ID x-ray beamline at the Argonne APS, a Department of Energy user facility, allowed the researchers to measure mechanical strains on cAp crystals at a resolution of 1μm and showed that raloxifene increased the amount of physical deformation, or strain, that occurred at the collagen-mineral interface before fracture.

This increased strain between cAp and collagen reduces stresses and may be caused by water-mediated slipping between these components at their interface, increasing the amount of energy the bone can absorb prior to fracture.

"The x-ray diffraction data," Burr said, "allowed us to explain the mechanism by which increases in bound water would improve the fracture properties of bone."

According to Burr, this work uncovers an entirely novel mechanism of action for raloxifene and "paves the way for a new class of drugs to treat osteoporosis, therapies that do not act by altering cellular activity or bone remodeling, but act by directly changing the physical properties of the bone matrix constituents."


'/>"/>

Contact: Tona Kunz
tkunz@anl.gov
630-252-5560
DOE/Argonne National Laboratory
Source:Eurekalert

Related medicine news :

1. The Tennessee Car Accident Lawyers at Michael D. Ponce & Associates Alert Public of CDC Survey Revealing Majority of High School Seniors Admitting to Texting Behind Wheel
2. DotComSecrets’ Russell Brunson Is Revealing Online Money Making Secrets in Free Webinars for Students
3. Seeing is believing: Biologists and physicists produce revealing images of cell organization, behavior
4. Parents: Revealing Your Past Smoking, Pot Use May Not Help Your Kids
5. Bel Marra Health Reports on a New Study Revealing Why Men Struggle to Figure Out Women
6. Bel Marra Health Reports on a New Study Revealing a Natural Remedy for Hypertension, Insomnia, and Aging
7. Bel Marra Health Reports on a New Study Revealing Health Benefits From Walking Barefoot
8. Statement from the Sensory Processing Disorder Foundation Endorsing New Breakthrough Study Revealing Biological Basis for Sensory Processing Disorders in Kids
9. The Secret to Revealing and Enhancing Younger-Looking Skin from Sublime Beauty
10. Bel Marra Health Reports on Recent Research Revealing Water May be Contaminated with Prescription Drugs
11. Bel Marra Health Reports on Recent Research Revealing A Gene To Restore Hearing Loss
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:9/11/2019)... JERSEY CITY, N.J. (PRWEB) , ... September 11, ... ... enterprise content management, will exhibit at the 2019 AHIMA Health Data and Information ... are encouraged to stop by booth #505 to learn more about GRM’s ...
(Date:9/11/2019)... ... September 11, 2019 , ... Executives at health systems and hospitals ... the healthcare industry over the past several years has been intense. For professionals and ... of healthcare in America will depend largely on how these executives respond. Will they ...
(Date:9/11/2019)... ... September 10, 2019 , ... Episcopal Relief & ... vulnerable communities impacted by Hurricane Dorian. , In partnership with the Episcopal ... of Georgia, and the Episcopal Farmworker Ministry, Episcopal Relief & Development is giving ...
(Date:9/9/2019)... ... September 09, 2019 , ... Cardinal Park Family Dental Care is proud ... The practice offers family dentistry , laser gum disease treatment, full mouth reconstruction, ... 20th year that Cardinal Park Family Dental Care has provided state-of-the-art, comprehensive dental care ...
(Date:9/8/2019)... ... September 08, 2019 , ... Crowdfunders suffering from stress, ... on Kickstarter (over 13-times its campaign goal) for DEZZIO's GoRelax – ... and reducing tension. , “We created GoRelax after realizing that acupressure mats are ...
Breaking Medicine News(10 mins):
(Date:9/11/2019)... , ... September 11, 2019 , ... ... to attempts by professionals to change a person’s gender identity from transgender to ... attempts. The study was authored by researchers at The Fenway Institute, Massachusetts General ...
(Date:9/11/2019)... ... September 11, 2019 , ... U.S. Oral Surgery Management ... serves premier oral and maxillofacial surgeons – is pleased to announce a new ... with three locations in the Atlanta area. It is USOSM’s second partnership in ...
(Date:9/11/2019)... , ... September 11, 2019 , ... ... today announced Orion Pharma, a globally operating Finnish pharmaceutical company, has licensed Genedata ... system, and other medical indications. , “As part of our strategy to ...
Breaking Medicine Technology: