Change in knee osteoarthritis cartilage detected by delayed gadolinium enhanced magnetic resonance imaging following treatment with collagen hydrolysate: a pilot randomized controlled trial.

OBJECTIVE: To determine whether either of two magnetic resonance imaging approaches - delayed gadolinium enhanced magnetic resonance imaging of cartilage (dGEMRIC), or T2 mapping - can detect short-term changes in knee hyaline cartilage among individuals taking a formulation of collagen hydrolysate. DESIGN: Single center, prospective, randomized, placebo-controlled, double-blind, pilot trial of collagen hydrolysate for mild knee osteoarthritis (OA). Participants were allowed to continue the prior analgesic use. The primary outcome was change in dGEMRIC T1 relaxation time in the cartilage regions of interest at the 24-week timepoint. Secondary endpoints included the change in dGEMRIC T1 relaxation time between baseline and 48 weeks, the change in T2 relaxation time at 0, 24 and 48 weeks, the symptom and functional measures obtained at each of the visits, and overall analgesic use. RESULTS: Among a sample of 30 randomized subjects the dGEMRIC score increased in the medial and lateral tibial regions of interest (median increase of 29 and 41 ms respectively) in participants assigned to collagen hydrolysate but decreased (median decline 37 and 36 ms respectively) in the placebo arm with the changes between the two groups at 24 weeks reaching significance. No other significant changes between the two groups were seen in the other four regions, or in any of the T2 values or in the clinical outcomes. CONCLUSIONS: These preliminary results suggest that the dGEMRIC technique may be able to detect change in proteoglycan content in knee cartilage among individuals taking collagen hydrolysate after 24 weeks.

Association of estrogen and aromatase gene polymorphisms with systemic lupus erythematosus.

Experimental and animal studies suggested that estrogens play an important role in the development of systemic lupus erythematosus (SLE) through a variety of mechanisms involved in the regulation of the immune system. The objective of this study was to investigate the association between genetic variations in estrogen metabolic pathway genes, including estrogen receptor alpha (ESR1), estrogen receptor beta (ESR2), and aromatase (CYP19A1), and risk of SLE. We performed a genetic study of SLE among 46 medical record-confirmed female SLE cases and 102 female controls participating in an Internet-based case-control study of SLE. Polymorphisms analysed included: ESR1 PvuII, XbaI, and GT repeat; ESR2 RsaI, AluI, and CA repeat; and CYP19A1 RsaI, SfaN1, and TTTA repeat. We found significant association of the ESR1 PvuII (PP vs. pp, odds ratio (OR): 3.1, 95% confidence interval (CI): 1.1-9.3) and XbaI (XX vs. xx, adjusted OR: 3.4, 95% CI: 1.1-10.5) with SLE. Carrying the PPXX genotype conferred the highest risk (PPXX vs. ppxx, OR: 4.6, 95% CI: 1.3-15.9). We also found an association of SLE with the ESR2 CA repeat (SS vs. LL, OR: 2.8, 95% CI: 1.0-8.0). Our results support a role of estrogen in pathogenesis of SLE and suggested that genetic variants in the estrogen receptor genes might influence susceptibility.

Effects of oral glucosamine sulphate on serum glucose and insulin during an oral glucose tolerance test of subjects with osteoarthritis.

BACKGROUND: and objective: Glucosamine is suggested to affect glucose transport and insulin resistance. The effects of oral glucosamine on serum glucose and insulin levels at the initiation and throughout the duration of a 3-h oral glucose tolerance test were examined. METHODS: Sera from 16 patients with osteoarthritis, but with no other diagnosed medical condition who had fasted overnight, were obtained every 15-30 min during the 3 h of continued fasting and during the 3 h after ingestion of 75 g of glucose with or without ingestion of 1500 mg of glucosamine sulphate. Glucose was analysed by high-performance liquid chromatography using a Metrohm-Peak 817 Bioscan, and the area under the curve (AUC) for glucose was calculated. Insulin was measured by radioimmunoassay every 30 min for 2 h. RESULTS: Three participants who were found to have previously undiagnosed abnormalities of glucose tolerance demonstrated significant (p = 0.04) incremental elevations in glucose levels after ingestion of glucosamine sulphate. The other 13 participants also had mean incremental elevations that were not significant (p = 0.20). Glucosamine sulphate ingestion had no effect on insulin levels. CONCLUSION: The results suggest that glucosamine ingestion may affect glucose levels and consequent glucose uptake in patients who have untreated diabetes or glucose intolerance.

Sulphate and osteoarthritis: decrease of serum sulphate levels by an additional 3-h fast and a 3-h glucose tolerance test after an overnight fast.

BACKGROUND: Low sulphate levels in blood may contribute to osteoarthritis by decreasing cartilage chondroitin sulphation. OBJECTIVE: To measure serum levels of sulphate during 3 h of fasting or glucose ingestion after overnight fasts to determine how much sulphate lowering may occur during this period. METHODS: Sera from 14 patients with osteoarthritis who fasted overnight were obtained every 15-30 min during 3 h of continued fasting and during 3 h after ingestion of 75 g of glucose. Sulphate was assayed by high-performance liquid chromatography with a Metrohm-Peak 761 Compact IC and simultaneously assayed for glucose by high-performance liquid chromatography with a Metrohm-Peak 817 Bioscan. RESULTS: Continuation of overnight fasting for 3 h resulted in a near-linear 3-h decrease in levels for all 14 patients ranging from 3% to 20% with a mean drop of 9.3%, whereas the 3-h decrease after glucose ingestion ranged from 10% to 33% with a mean drop of 18.9%. CONCLUSION: A 3-h continuation of fasting caused a marked reduction in serum sulphate levels, whereas ingestion of 75 g of glucose in the absence of protein resulted in doubling the reduction. This suggests that fasting and ingestion of protein-free calories may produce periods of chondroitin undersulphation that could affect osteoarthritis.

Low levels of human serum glucosamine after ingestion of glucosamine sulphate relative to capability for peripheral effectiveness.

BACKGROUND: Oral glucosamine preparations are widely used as a treatment for osteoarthritis, purportedly functioning by a variety of mechanisms suggested by results of in vitro experiments, and generally using glucosamine concentrations well in excess of 100 micromol/l. OBJECTIVE: To use high performance liquid chromatography with a high sensitivity Metrohm-Peak instrument for pulsed amperometric measurement of human serum glucosamine; a detection limit of 0.5 micromol/l at 1:10 serum dilution allowed measurement of low levels of glucosamine in human serum, which previously has not been possible. METHODS: Eighteen subjects with osteoarthritis were given 1,500 mg of commercial glucosamine sulphate after an overnight fast, and serum was then obtained at baseline and every 15-30 minutes over 3 hours, and additionally, from two subjects at 5 and 8 hours. Urine samples were collected at baseline and 3 hours after ingestion from three subjects. RESULTS: Baseline glucosamine was below the detection limit of 0.5 mumol/l for all subjects, but after ingestion, glucosamine was detected in 17/18 subjects, beginning to rise at 30-45 minutes to a maximum at 90-180 minutes, with a range of 1.9-11.5 micromol/l (0.34-2 microg/ml). CONCLUSION: This maximum concentration of 11.5 micromol/l has previously been shown to contribute less than 2% of the galactosamine incorporated into chondroitin sulphate in incubations of glucosamine with cultured human chondrocytes, and is a much lower concentration than the glucosamine concentrations claimed by other investigators to have various significant in vitro effects. This raises questions about current biological rationales for glucosamine use that were based on in vitro effects of glucosamine at much higher concentrations.

Indole-3-carbinol in women with SLE: effect on estrogen metabolism and disease activity.

Estrogen metabolism in women with SLE is weighted towards 16alpha-hydroxyestrone, an estrogenic compound that might fuel disease activity. Indole-3-carbinol (I3C) is a nutritional compound that can shift estrogen metabolism towards less estrogenic metabolites. However, the effects of I3C in women with SLE have not been studied. Open-label 1-week metabolic study of 375 mg/day I3C was carried out in women with SLE, followed by a 3-month observational period for disease activity. The primary outcome measure was the change in ratio of urinary 2:16alpha hydroxyestrone levels. Secondary measures included the SLE Disease Activity Index. Seventeen clinically premenopausal women fulfilling ACR criteria for probable/definite SLE (mean age 37.9 y, range 20-49 y, mean disease duration 4.3 y, range 0.5-15) completed the 1-week metabolic study; 12 took I3C for 3 months. The mean 2:16alpha hydroxyestrone ratio increased by 1.84 to 3.15 (P = 0.0001). Mean SLEDAI scores were 10.0 (baseline); 6.25 (3 months); and 8.8 (3 months after withdrawal; P = NS). Women with SLE can manifest a metabolic response to I3C and might benefit from its antiestrogenic effects. We did not observe any striking effects on SLE disease activity during the 3-month observational period.