Turmeric is widely consumed as a spice, and mixtures of polyphenolic curcuminoids extracted in various degrees of purity from the rhizome of turmeric are available for use as dietary supplements (9
). As most medical research has focused on pure curcumin, our studies are unique in that they evaluate turmeric extracts more analogous to the composition of currently available dietary supplements (9
). Of the two turmeric extracts tested, the curcuminoid-enriched turmeric extract preserved BMD, as well as the microarchitectural structure and trabecular connectivity of bone in OVX rats. Key architectural parameters assessed by μCT that are known to be tightly correlated to mechanical strength and that suffer adversely with OVX, including bone volume fraction, trabecular number, connectivity density, and trabecular spacing (20
), were significantly improved (34–55%) by curcuminoid treatment. Thus, these improvements in the architectural parameters of trabecular structure in OVX animals may translate into a reduction in fracture risk, which is the fundamental aim of all treatments targeting osteoporosis. This preservation of mass and microarchitecture of bone by curcuminoid-enriched turmeric did not appear to be an estrogenic effect, as uterine atrophy and weight gain in OVX animals were unaffected by curcuminoid treatment, results that are also consistent with prior studies documenting an lack of curcuminoid binding to ER-alpha or ER-beta (22
). Although not directly tested here, since abrogation of NF-κB activation is thought to be a major biological effect of curcuminoids (11
), it remains possible that NF-κB may be the central target in the process of protecting OVX-induced bone loss. Turmeric may thus have utility as a non-estrogen receptor (ER) therapeutic in the prevention of osteoporosis, a postulate that deserves further mechanistic investigation.
While the results from this translational study are encouraging, clinical data supporting the use of curcuminoids for osteoporosis is completely lacking. Of interest, however, is one clinical study that examined an oral dose of an uncharacterized curcuminoid product (4 g/day) in patients with monoclonal gammopathy, a potential precursor of multiple myeloma (27
). This dose of curcuminoids significantly reduced urinary N-telopeptide type I collagen levels in patients, suggesting that curcuminoids may indeed act in humans as an anti-resorptive agent in diseases characterized by an elevation in bone turnover and generalized bone loss. Unfortunately, in our study the measurement of serum markers for bone turnover after two weeks and two months of OVX (d 14 and d 56, respectively), which were little altered in OVX animals, also did not reveal turmeric treatment effects that could have elucidated whether bone was being favorably altered by an increase in bone formation and/or inhibition of bone resorption. Examination of longitudinal BMD changes in curcuminoid-enriched turmeric treated OVX animals suggests that assay of bone turnover biomarkers after one month of treatment, when OVX-induced BMD loss appears to have stabilized, may have been more informative. Additional pre-clinical and clinical studies will be necessary to determine how curcuminoids act on both bone formation and resorption pathways in vivo
under normal and pathological states.
We chose the intraperitoneal route of administration for testing and comparison of the two turmeric extracts as a proof-of-concept approach in an effort to eliminate variables that could alter the oral bioavailability of components in these complex botanicals, such as differential absorption of curcuminoids in the two extracts due to matrix effects of the additional components present in the more complex turmeric extract or the metabolism of non-curcuminoid components by intestinal microflora (28
). As with bisphosphonates, oral bioavailability of curcumin is low (29
). As a result, considerable research efforts are focused on identifying specific formulations to enhance curcuminoid oral bioavailability (e.g. curcuminoid nanoparticles or the use of lipid-based formulation vehicles to enhance absorption; 28
). Thus, it is possible that currently available turmeric dietary supplements may not be the most ideal agents for osteoporosis prevention. Additionally, because essential oils in the turmeric rhizome have also recently been reported to enhance curcuminoid oral bioavailability (32
), currently available turmeric dietary supplements, which, like the extracts tested here, do not contain essential oils, may not be the most optimal formulations for dietary curcuminoid supplementation.
Utilizing distinct and chemically well-characterized turmeric extracts, opposing trends for bone protection in translational models of arthritis vs. osteoporosis have now been identified, as the curcuminoid-enriched turmeric extract was most efficacious in protecting bone in osteoporosis, while we have previously demonstrated that the chemically complex turmeric fraction was most effective in preventing bone loss in arthritis (9
). These divergent results illustrate the importance of direct testing of well-characterized botanical extracts in complex disease states (2
). Moreover, because extract doses were normalized to curcuminoid content in the studies reported here, these results suggest that the non-curcuminoid constituents of the complex turmeric extract may have accounted for differences seen between the two turmeric treatment groups in altering bone loss in OVX animals. Preliminary studies in our laboratories have found that the non-curcuminoid portion of the complex turmeric extract is primarily composed of polysaccharides. Traditionally, these carbohydrates are thought to have minimal bioactivity by themselves, however, new functional effects of polysaccharides are emerging, particularly when combined with other bioactive molecules (33
). This additional component of the complex extract may have had deleterious effects on bone that could not be compensated for by the curcuminoids, or the polysaccharides may have blunted or antagonized the beneficial effects of the curcuminoids on bone in the hypogonadal rat.
Another possibility for the variable efficacies of the two turmeric extracts tested is their differing ratios of the three major curcuminoids, which may be an important determinant of bone protection, as the purified extract contained a higher percentage of curcumin and a lower percentage of demethoxycurcumin and bis-demethoxycurcumin relative to the complex extract. Indeed, differential effects of the three major curcuminoids have been reported in a number of biological systems (31
). Since all turmeric dietary supplements are composed of a mixture of the three major curcuminoids (9
), this possibility would also have important implications from a consumer standpoint as turmeric supplement labels do not indicate the relative amounts of these 3 compounds present in the product (9
). Additionally, our laboratories have identified vast discrepancies between the labeled curcuminoid content and the curcuminoid content detected by HPLC in a random selection of commercially available turmeric dietary supplements (9
). Due to the importance of extract composition in bioefficacy, it is clear that the degree of specificity of labeling of turmeric supplements at present is not sufficient to direct usage, should specific turmeric extracts prove to be clinically useful upon further study.
As osteoporosis becomes a widespread health and financial burden to millions of aging Americans, the development of affordable bone-protective therapeutics for the prevention of metabolic bone disorders merits continued study. These results are encouraging, considering the current availability and affordability of turmeric-derived curcuminoid products. Continued characterization of turmeric dietary supplement composition followed by rigorous pre-clinical and clinical testing will be necessary to identify turmeric-derived bone-active constituents, and to optimize their bioefficacy in dietary form.