Bone‐Specific Metabolism of Dietary Polyphenols in Resorptive Bone Diseases

Scope Curcumin prevents bone loss in resorptive bone diseases and inhibits osteoclast formation, a key process driving bone loss. Curcumin circulates as an inactive glucuronide that can be deconjugated in situ by bone's high β‐glucuronidase (GUSB) content, forming the active aglycone. Because curcumin is a common remedy for musculoskeletal disease, effects of microenvironmental changes consequent to skeletal development or disease on bone curcumin metabolism are explored. Methods and results Across sexual/skeletal development or between sexes in C57BL/6 mice ingesting curcumin (500 mg kg −1 ), bone curcumin metabolism and GUSB enzyme activity are unchanged, except for >twofold higher ( p < 0.05) bone curcumin‐glucuronide substrate levels in immature (4–6‐week‐old) mice. In ovariectomized (OVX) or bone metastasis‐bearing female mice, bone substrate levels are also >twofold higher. Aglycone curcumin levels tend to increase proportional to substrate such that the majority of glucuronide distributing to bone is deconjugated, including OVX mice where GUSB decreases by 24% ( p < 0.01). GUSB also catalyzes deconjugation of resveratrol and quercetin glucuronides by bone, and a requirement for the aglycones for anti‐osteoclastogenic bioactivity, analogous to curcumin, is confirmed. Conclusion Dietary polyphenols circulating as glucuronides may require in situ deconjugation for bone‐protective effects, a process influenced by bone microenvironmental changes.