Submitted to: Anticancer Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: June 3, 2013
Publication Date: August 1, 2013
Citation: Yan, L., Yee, J.A., Cao, J.J. 2013. Curcumin reduces trabecular and cortical bone in naive and Lewis lung carcinoma-bearing mice. Anticancer Research. 33:3153-3162. Interpretive Summary: Curcumin is a phenolic compound derived from the Curcuma longa plant, commonly known as turmeric. Curcumin has been used traditionally in Ayurvedic medicine as it has therapeutic properties including being anti-inflammatory, anti-oxidant and anti-microbial. The present study investigated the effects of dietary supplementation of curcumin on bone micro-structural changes in tumor-bearing and non-tumor-bearing mice. Dietary supplementation with 2% or 4% curcumin reduced trabecular bone volume and cortical bone density in both tumor-bearing and tumor-free mice. This deterioration may be associated with a disruption of the coupling of bone formation and bone resorption by curcumin. Curcumin has attracted attention in cancer prevention research. Clinical trials have been completed or are on-going with patients with malignancies. As skeleton is a favored site of metastasis for many cancers, the present demonstration that curcumin can have deteriorating effects on bone suggests the possibility of a combined effect of cancer-induced bone destruction and curcumin-stimulated bone loss which could present a risk of using curcumin in cancer prevention. This possibility would suggest that bone assessments should be performed on the participants of curcumin intervention trials, particular those with advanced malignancies.
Technical Abstract: The present study investigated the effects of dietary supplementation with curcumin on bone microstructural changes in female C57BL/6 mice in the presence or absence of Lewis lung carcinoma. Morphometric analysis showed that in tumor-bearing mice curcumin at 2% and 4% dietary levels (w/w) significantly reduced the ratio of bone volume to total volume (BV/TV), connectivity density and trabecular number (Tb.N.) and increased the structure model index and trabecular separation in vertebral bodies; at the 4% level curcumin significantly reduced BV/TV and Tb.N. and at either level it significantly reduced trabecular thickness in distal femurs compared with the controls. Curcumin at the 4% level significantly reduced the ratio of cortical bone area to total area and cortical thickness in the mid-shaft of the femur compared with the controls. Similar changes in trabecular and cortical bone were observed with curcumin-fed groups in non-tumor-bearing mice. Curcumin feeding reduced plasma concentrations of osteocalcin and increased tartrate-resistant acid phosphate 5b in mice regardless of the presence of tumor, suggesting that curcumin disrupts the balance of bone remodeling. Our results demonstrate that curcumin has osteolytic effects characterized by reduced trabecular bone volume and cortical bone density. As skeleton is a favored site of metastasis for many cancers and curcumin is under investigation for its chemopreventive effects, the assessment of bone structural changes is warranted for curcumin cancer prevention studies to determine its effects on skeleton health.