Nutraceuticals: do they represent a new era in the management of osteoarthritis? - a narrative review from the lessons taken with five products.

OBJECTIVES: The aim of this first global systematic review on selected nutraceuticals was to synthesize and evaluate scientific relevant data available in the literature. Evidences that can support health, physiological or functional benefit on osteoarthritis (OA) were gathered and the level of evidence relative to each of these ingredients was highlighted. METHODOLOGY: Relevant scientific data (positive or not) regarding OA were searched for five groups of compounds (avocado/soybean unsaponifiables (ASU), n-3 polyunsaturated fatty acids, collagen hydrosylates (CHs), vitamin D, polyphenols) within preclinical (in vitro and in vivo), epidemiological, and clinical studies. The following criteria were evaluated to assess the methodology quality of each study: (1) study question; (2) study population; (3) primary endpoint; (4) study design (randomization, control, blinding, duration of follow up); (5) data analysis and interpretation. A scientific consensus was determined for all studied nutraceuticals to evaluate their efficacy in OA. RESULTS: The studied compounds demonstrated different potencies in preclinical studies. Most of them have demonstrated anti-catabolic and anti-inflammatory effects by various inhibitory activities on different mediators. Vitamin D showed a pro-catabolic effect in vitro and the polyphenol, Genistein, had only anti-inflammatory potency. The evaluation of the clinical data showed that ASU was the only one of the studied ingredients to present a good evidence of efficacy, but the efficient formulation was considered as a drug in some countries. Pycnogenol showed moderate evidence of efficacy, and vitamin D and collagen hydrolysate demonstrated a suggestive evidence of efficacy, whereas curcumin, epigallocatechin-3-gallate (EGCG) and resveratrol had only preclinical evidence of efficacy due to the lack of clinical data. The literature gathered for n-3 PUFA, nobiletin and genistein was insufficient to conclude for their efficacy in OA. CONCLUSION: Additional data are needed for most of the studied nutraceuticals. Studies of good quality are needed to draw solid conclusions regarding their efficacy but nutraceuticals could represent good alternates for OA management. Their use should be driven by any recommendations.

Characterization of three types of calcium channel in the luminal membrane of the distal nephron.

We previously reported a dual kinetics of Ca2+ transport by the distal tubule luminal membrane of the kidney, suggesting the presence of several types of channels. To better characterize these channels, we examined the effects of specific inhibitors (i.e., diltiazem, an L-type channel; omega-conotoxin MVIIC, a P/Q-type channel; and mibefradil, a T-type channel antagonist) on 0.1 and 0.5 mM Ca2+ uptake by rabbit nephron luminal membranes. None of these inhibitors influenced Ca2+ uptake by the proximal tubule membranes. In contrast, in the absence of sodium (Na+), the three channel antagonists decreased Ca2+ transport by the distal membranes, and their action depended on the substrate concentrations: 50 microM diltiazem decreased 0.1 mM Ca2+ uptake from 0.65 +/- 0.07 to 0.48 +/- 0.06 pmol. microg-1.10 s-1 (P < 0.05) without influencing 0.5 mM Ca2+ transport, whereas 100 nM omega-conotoxin MVIIC decreased 0.5 mM Ca2+ uptake from 1.02 +/- 0.05 to 0.90 +/- 0.05 pmol. microg-1.10 s-1 (P < 0.02) and 1 microM mibefradil decreased it from 1.13 +/- 0.09 to 0.94 +/- 0.09 pmol. microg-1.10 s-1 (P < 0.05); the latter two inhibitors left 0.1 mM Ca2+ transport unchanged. Diltiazem decreased the Vmax of the high-affinity channels, whereas omega-conotoxin MVIIC and mibefradil influenced exclusively the Vmax of the low-affinity channels. These results not only confirm that the distal luminal membrane is the site of Ca2+ channels, but they suggest that these channels belong to the L, P/Q, and T types.

Effects of fibronectin on hydroxyapatite formation.

There is increasing evidence that noncollagenous matrix proteins initiate bone mineralization in vivo. Fibronectin, which is present during the early phases of mineralization, may contribute to this process in bone tissues. In this context, the mineralization potential of fibronectin was tested in an agarose gel precipitation system and a metastable calcium phosphate solution. The protein inhibited the precipitation of calcium phosphate crystals in solution but had no apparent effect in gel. Conversely, fibronectin stimulated crystal formation when apatite powder was used to seed crystal growth in gel. Although these results in vitro do not clearly indicate that fibronectin is involved in the mineralization process, they are consistent with in vivo events. Free fibronectin (e.g. in biological fluids) could inhibit crystal growth but might also activate the mineralization process when absorbed on apatite powder in a bone environment and areas of ectopic mineralization.

Apatite precipitation after incubation of biphasic calcium-phosphate ceramic in various solutions: influence of seed species and proteins.

The dissolution-precipitation process for calcium-phosphate ceramics in contact with biological fluid was studied by incubating blocks of biphasic calcium phosphate composed of hydroxyapatite (HA) and beta-tricalcium phosphate (beta-TCP) in different solutions: ionic simulated body fluid (SBF) without protein or SBF that contained various proteins and macromolecules separately (fibronectin, vitronectin, albumin, and poly-L-glutamic acid). Transmission electron microscopy studies revealed that apatite-precipitated microcrystals appeared around ceramic crystals as a result of secondary nucleation; microcrystals were in continuity with the lattice planes of the HA crystals but in a different direction from that of beta-TCP; the size of the precipitates was smaller when fibronectin, vitronectin, and poly-(L-glutamic acid) were present in SBF as compared to SBF without protein; and fibronectin and vitronectin initiated crystal nucleation in the void spaces between the ceramic crystals.