Caroline Harrison

Background: Osteoporosis is the most common bone disease which is characterized by decreased bone density and abnormal microstructure, leading to an increased risk of fracture in affected individuals. Current treatments such as bisphosphonates are aimed at reducing future bone loss and slowing the progression of disease, leaving space to develop more targeted therapeutics that can increase bone density.¹ Osteoclasts and osteoblasts are the primary cell types responsible for the resorption and creation of bone, respectively. Tipping the balance between the activity of these two cell types towards bone mineralization and away from resorption represents a promising therapeutic avenue.² Curcumin, a compound found in turmeric, has been shown to increase osteoblast activity and decrease osteoclast migration through mechanisms that have been defined in recent years.³

Objective: In this review, I investigated the current mechanistic understanding of curcumin’s effects on osteoclasts and osteoblasts, as well as evaluate potential therapeutic efficacy via animal model trials and a randomized clinical trial.

Search methods: I completed a literature review using PubMed and Google Scholar, using the following search terms: osteoporosis, curcumin, ER stress, osteoclasts, osteoblasts, and mineralization.

Results: Curcumin successfully increases osteoblast activity by upregulating osteoblastic differentiation genes such as Runx2 in precursor cells via the Wnt/β- catenin signaling pathway.⁴ Runx2 then upregulates ATF6, an ER stress protein that leads to increased osteogenesis.³ Additionally, curcumin leads to a decrease in the the levels of osteoclast migratory cytokine CCL3, preventing initiation of bone demineralization.⁵ These mechanistic results were corroborated by an in vivo study of zebrafish that showed a 49% increase in the rate of mineralization in curcumin-exposed embryos, a 40% increase in scale thickness in curcumin-exposed juvenile fish, and significant remineralization after scale damage.⁶ These results are further supported by a double-blinded randomized clinical trial that showed superiority of combination curcumin-bisphosphonate therapy compared to bisphosphonate therapy alone. Post-menopausal women diagnosed with osteoporosis were given a control calcium treatment, a bisphosphonate alone, or a bisphosphonate with curcumin for a 6-month period. Compared to pretest values, patients given combination therapy had lower bone resorption markers and higher bone mineral density compared to the control and to the bisphosphonate monotherapy. Additionally, no subjects left the study due to ill effects of the medication, suggesting it was well tolerated.⁷

Conclusions: The results of this search indicate that curcumin represents a potentially useful addition to the current clinical treatment of osteoporosis. Further research is needed to fully understand the mechanism behind curcumin mediated CCL3 inhibition and fully elucidate the role curcumin plays in osteoclast activities. Despite this gap, curcumin has been shown to positively impact bone mineralization in animal models and a clinical trial. Additional testing is needed to create a clinical protocol for use of curcumin.

Works Cited:

1. Gopinath V. Osteoporosis. Med Clin North Am. 2023;107(2):213-225. doi:10.1016/j.mcna.2022.10.013
2. Aibar-Almazán A, Voltes-Martínez A, Castellote-Caballero Y, Afanador-Restrepo DF, Carcelén-Fraile MDC, López-Ruiz E. Current Status of the Diagnosis and Management of Osteoporosis. Int J Mol Sci. 2022;23(16):9465. doi:10.3390/ijms23169465
3. Son HE, Kim EJ, Jang WG. Curcumin induces osteoblast differentiation through mild-endoplasmic reticulum stress-mediated such as BMP2 on osteoblast cells. Life Sci. 2018;193:34-39. doi:10.1016/j.lfs.2017.12.008
4. Pengjam Y, Syazwani N, Inchai J, et al. High water-soluble curcuminoids-rich extract regulates osteogenic differentiation of MC3T3-E1 cells: Involvement of Wnt/β-catenin and BMP signaling pathway. Chin Herb Med. 2021;13(4):534-540. doi:10.1016/j.chmed.2021.01.003
5. Liang Z, Xue Y, Wang T, Xie Q, Lin J, Wang Y. Curcumin inhibits the migration of osteoclast precursors and osteoclastogenesis by repressing CCL3 production. BMC Complement Med Ther. 2020;20(1):234. doi:10.1186/s12906-020-03014-2
6. Carnovali M, Ramoni G, Banfi G, Mariotti M. Herbal Preparation (Bromelain, Papain, Curcuma, Black Pepper) Enhances Mineralization and Reduces Glucocorticoid-Induced Osteoporosis in Zebrafish. Antioxidants. 2021;10(12):1987. doi:10.3390/antiox10121987
7. Khanizadeh F, Rahmani A, Asadollahi K, Ahmadi MRH. Combination therapy of curcumin and alendronate modulates bone turnover markers and enhances bone mineral density in postmenopausal women with osteoporosis. Arch Endocrinol Metab. 2018;62(4):438-445. doi:10.20945/2359-3997000000060