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Timing found to be critical when using combination drug therapy for osteoporosis
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The use of parathyroid hormone prior to treatment by an antiresorptive drug, like alendronate, could be effective in the battle against osteoporosis, according to research published in the November issue of Cell Stem Cell.
Previous attempts to combine approaches of parathyroid hormone (PTH) and antiresorptive drugs have been ineffective, but further research has uncovered a combination that could open new pathways in the treatment of osteoporosis.
“Our research shows that inhibition of TGF-beta 1 activation by alendronate leads to insufficient recruitment of skeletal stem cells to resorptive sites for the new bone formation during PTH-stimulated bone remodeling,” Xu Cao, PhD, a senior author of the study stated in a press release.
Taken together, the findings help explain why the order and timing of combination drug therapy may be critical in the successful treatment of osteoporosis and may help direct the design of future clinical trials.
An improved understanding
“In clinical trials where PTH and alendronate were administered concurrently, the bone building effects of PTH were impaired,” Cao stated in the release. “This suggests that bone resorption is necessary for PTH-induced bone formation, but the underlying mechanisms are obscure.”
Cao’s group had previously shown that transforming growth factor-beta 1 (TGF-beta 1) plays a key role in bone formation after bone resorption. For the current study, the investigators identified a subset of skeletal stem cells that were recruited to bone remodeling sites in response to bone resorption.
The authors demonstrated that TGF beta-1 is essential for the recruitment of skeletal stem cells during PTH-stimulated bone remodeling. Furthermore, they found that alendronate inhibited the release of TGF-beta 1 during bone resorption.
In the release, Cao added that “an improved understanding of the role that bone resorption plays in PTH-induced bone formation would provide a key mechanistic rationale for the development of strategies that maximize the use of both PTH and antiresorptive drugs in the treatment of osteoporosis.”
Reference:
Wu X, Pang L, Lei W, et al. Inhibition of sca-1-positive skeletal stem cell recruitment by alendronate blunts the anabolic effects of parathyroid hormone on bone remodeling. Cell Stem Cell. 2010;7(5):571-580.
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