Comparative Effects of Turmeric Secondary Metabolites Across Resorptive Bone Diseases

<b>Background</b>: Turmeric (<i>Curcuma longa</i> L.) rhizomes, whose secondary metabolites include polyphenols and terpenoids, have been used medicinally for millennia. However, modern scientific inquiry has primarily focused on medicinal effects of turmeric's polyphenolic curcuminoids, including when evaluating turmeric use to maintain bone health. <b>Methods</b>: Disease-specific biological effects of turmeric's major secondary metabolites (polyphenols and/or terpenoids), with or without associated turmeric rhizome-derived polysaccharides, were determined in vivo using pre-clinical models of clinically relevant resorptive bone diseases induced by different mechanisms. These included inflammatory arthritis, cancer-driven osteolytic bone metastases, and hormone deficiency-driven post-menopausal osteoporosis. <b>Results</b>: In the arthritis model, the safety profile of curcuminoids alone was superior. However, curcuminoids and terpenoids each had anti-inflammatory effects and prevented bone resorption, with polysaccharide-containing curcuminoid extracts having greater effect than curcuminoids alone. In the human osteolytic breast cancer bone metastases model, curcuminoid extracts containing polysaccharides tended to yield greater effects in reducing bone osteolysis and tumor progression than curcuminoids alone or more complex extracts. In contrast, only purified curcuminoids prevented bone loss in a post-menopausal osteoporosis model, while polysaccharide-containing curcuminoid extracts were without effect. In vitro metabolite effects on disease-specific mechanistic pathways in synoviocytes, osteoclasts, or breast cancer cells were consistent with documented in vivo outcomes and included differential metabolite-specific effects. <b>Conclusions</b>: In summary, these findings suggest that turmeric's potential medicinal musculoskeletal effects are complex, pathway- and target-specific, and not limited to curcuminoids, with safety concerns potentially limiting certain uses.