Raloxifene, an FDA-approved treatment for decreasing fracture risk in patients with osteoporosis, has been found to have a novel mechanism of action that differs from other drugs used to treat the condition, according to new study results published in Bone.
All current osteoporosis treatments work by acting on living cells within the bone matrix to decrease bone resorption or increase bone formation during remodeling, both of which boost overall bone density and thereby lower fracture risk.
Raloxifene, however, only mildly suppresses bone loss despite achieving results similar to these other osteoporosis treatments, according to lead researcher David B. Burr of Indiana University School of Medicine.
Burr and colleagues evaluated raloxifene’s effect on devitalized bone cleared of living cells that mediate resorption and remodeling. The drug appeared to be acting on the physical properties of the bone itself, as it extended the loading that the bone could bear before fracturing.
Ultra-short-echo-time nuclear magnetic resonance indicated that raloxifene-mediated water retention within the bone matrix is linked to the increase in bone toughness.
The researchers collected wide- and small-angle x-ray scattering (WAXS and SAXS) diffraction patterns of carbonated hydroxyapatite crystals (cAp), which allowed measurement of mechanical strains on the cAp crystals at a resolution of 1 mcm and demonstrated that raloxifene increased the physical deformation that occurred at the collagen-mineral interface before fracture.
The researchers determined that the increased strain between cAp and collagen decreases stresses. They also found that water-mediated slipping between these components at their interface may be the cause, therefore increasing the amount of energy the bone can absorb before fracture.
This study “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,” Burr concluded.
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. Burr of Indiana University School of Medicine and lead author of the Bone article on this research.