Monthly Archives: May 2014

Glucosamine has Negative Effect On Intervertebral Discs

Abstract

Glucosamine Supplementation Demonstrates a Negative Effect On Intervertebral Disc Matrix in an Animal Model of Disc Degeneration.

Study Design. Laboratory based controlled in vivo study Objective. To determine the in vivo effects of oral glucosamine sulfate on intervertebral disc degeneration. Summary of Background Data. Although glucosamine has demonstrated beneficial effect in articular cartilage, clinical benefit is uncertain. A CDC report from 2009 reported that many patients are using glucosamine supplementation for low back pain (LBP), without significant evidence to support its use. Because disc degeneration is a major contributor of LBP, we explored the effects of glucosamine on disc matrix homeostasis in an animal model of disc degeneration.Methods. Eighteen skeletally mature New Zealand White rabbits were divided into four groups: control, annular puncture, glucosamine, and annular puncture+glucosamine. Glucosamine treated rabbits received daily oral supplementation with 107mg/day (weight based equivalent to human 1500mg/day). Annular puncture surgery involved puncturing the annulus fibrosus (AF) of 3 lumbar discs with a 16G needle to induce degeneration. Serial MRIs were obtained at 0, 4, 8, 12, and 20 weeks. Discs were harvested at 20 weeks for determination of glycosaminoglycan(GAG) content, relative gene expression measured by RT-PCR, and histological analyses.
Results. The MRI index and NP area of injured discs of glucosamine treated animals with annular puncture was found to be lower than that of degenerated discs from rabbits not supplemented with glucosamine. Consistent with this, decreased glycosaminoglycan was demonstrated in glucosamine fed animals, as determined by both histological and GAG content. Gene expression was consistent with a detrimental effect on matrix.
Conclusions. These data demonstrate that the net effect on matrix in an animal model in vivo, as measured by gene expression, MRI, histology, and total proteoglycan is anti-anabolic. This raises concern over this commonly used supplement, and future research is needed to establish the clinical relevance of these findings.

Jacobs L, Vo N, Coehlo JP, Dong Q…
Spine Jan 2013
PMID: 23324939

Glucosamine no Effect on Bone Resorption or Formation Markers

Abstract

Evaluation of the effect of glucosamine administration on biomarkers of cartilage and bone metabolism in bicycle racers.

In the present study, the effect of glucosamine administration (1.5 or 3 g/day) on cartilage and bone metabolism was investigated in bicycle racers, using cartilage‑ and bone‑specific biomarkers, including C‑terminal cross‑linked telopeptides of type II collagen (CTX‑II), C‑terminal propeptides of type II procollagen (CPII), N‑terminal telopeptides of bone‑specific type I collagen (NTx) and bone alkaline phosphatase (BAP). The results indicate that CPII (a marker of type II collagen synthesis) was not substantially changed, however, CTX‑II (a marker of type II degradation) was reduced by glucosamine administration, particularly at a dose of 3 g/day. Consistent with these observations, the ratio of CTX‑II/CPII was reduced by glucosamine administration and the effect of glucosamine was dose‑dependent. By contrast, the levels of NTx (a bone resorption marker) and BAP (a bone formation marker) were not altered by glucosamine administration. A previous study by this group reported that glucosamine exerts a chondroprotective action in soccer players by preventing type II collagen degradation but maintaining type II collagen synthesis. Together these observations indicate that glucosamine may exert a chondroprotective action by preventing type II collagen degradation in athletes of various sports, including soccer players and bicycle racers.

Momomura R, Naito K, Igarashi M, Watari T…
Mol Med Rep Mar 2013
PMID: 23358550

Review: Glucosamine Might Increase Osteoblasts and Suppress Resorption

Abstract

Biological activities of glucosamine and its related substances.

Glucosamine (GlcN) has been widely used to treat osteoarthritis (OA) in humans. We revealed that among GlcN-derivatives (GlcN and N-acetyl-d-glucosamine) and uronic acids (d-glucuronic acid and d-galacturonic acid), only GlcN induces the production of hyaluronic acid (HA) by synovial cells and chondrocytes, and the production level is much higher (>10-fold) in synovial cells compared with chondrocytes. Moreover, GlcN increases the expression of HA-synthesizing enzymes (HAS) in synovial cells and chondrocytes. These observations indicate that GlcN likely exhibits the chondroprotective action on OA by modulating the expression of HAS and inducing the production of HA (a major component of glycosaminoglycans contained in the synovial fluid) especially by synovial cells. The pathological change of subchondral bone is implicated in the initiation and progression of cartilage damage in OA. Thus, we further determined the effect of GlcN on the bone metabolism (osteoblastic cell differentiation). The results indicated that GlcN increases the mineralization of mature osteoblasts and the expression of middle and late stage markers (osteopontin and osteocalcin, respectively) during osteoblastic differentiation, and reduces the expression of receptor activator of NF-κB ligand (RANKL), a differentiation and activation factor for osteoclasts. These observations likely suggest that GlcN has a potential to induce the osteoblastic cell differentiation and suppress the osteoclastic cell differentiation, thereby increasing bone matrix deposition and decreasing bone resorption to modulate bone metabolism in OA.

Nagaoka I, Igarashi M, Sakamoto K
Adv. Food Nutr. Res. 2012
PMID: 22361198

Glucosamine Inhibits Bone Resorption in Rats

Abstract

Bone resorption and remodeling in murine collagenase-induced osteoarthritis after administration of glucosamine.

Glucosamine is an amino-monosaccharide and precursor of glycosaminoglycans, major components of joint cartilage. Glucosamine has been clinically introduced for the treatment of osteoarthritis but the data about its protective role in disease are insufficient. The goal of this study was to investigate the effect of long term administration of glucosamine on bone resorption and remodeling.
The effect of glucosamine on bone resorption and remodeling was studied in a model of collagenase-induced osteoarthritis (CIOA). The levels of macrophage-inflammatory protein (MIP)-1α, protein regulated upon activation, normal T-cell expressed, and secreted (RANTES), soluble receptor activator of nuclear factor kappa-B ligand (RANKL), tumor necrosis factor (TNF)-α, and interleukin (IL)-6, 4 and 10 in synovial fluid were measured by enzyme-linked immunosorbent assay (ELISA). Cell populations in synovial extracts and the expression of RANKL, of receptors for TNF-α (TNF-αR) and interferon γ (IFN-γR) on clusters of differentiation (CD) three positive T cells were analyzed by flow cytometry. Transforming growth factor (TGF)-β3, bone morphogenetic protein (BMP)-2, phosphorylated protein mothers against decapentaplegic homolog 2 (pSMAD-2), RANKL and Dickkopf-1 protein (DKK-1) positive staining in CIOA joints were determined by immunohistochemistry.
The administration of glucosamine hydrochloride in CIOA mice inhibited loss of glycosaminoglycans (GAGs) and proteoglycans (PGs) in cartilage, bone erosion and osteophyte formation. It decreased the levels of soluble RANKL and IL-6 and induced IL-10 increase in the CIOA joint fluids. Glucosamine limited the number of CD11b positive Ly6G neutrophils and RANKL positive CD3 T cells in the joint extracts. It suppressed bone resorption via down-regulation of RANKL expression and affected bone remodeling in CIOA by decreasing BMP-2, TGF-β3 and pSMAD-2 expression and up-regulating DKK-1 joint levels.
Our data suggest that glucosamine hydrochloride inhibits bone resorption through down-regulation of RANKL expression in the joints, via reduction of the number of RANKL positive CD3 T cells and the level of sRANKL in the joints extracts. These effects of glucosamine appear to be critical for the progression of CIOA and result in limited bone remodeling of the joints.

Ivanovska N, Dimitrova P
Arthritis Res. Ther. 2011
PMID: 21410959 | Free Full Text

Glucosamine Accelerates Fracture Repair in Rats

Abstract

Glucosamine-sulfate on fracture healing.

The aim of this study is to determine whether glucosamine-sulfate has any effects on bone-healing.
A unilateral fracture was created in the tibia of sixty-one female rats. Rats were given no drug or 230 mg/kg glucosamine-sulfate daily. Fractures were analyzed during the first, second and fourth weeks after creation of fracture. Quantitative measurement for new bone formation and osteoblast lining were determined histologically. Semiquantitative score for fracture healing was used for histomorphometric analyses. Bridging bone formation was assessed radiographically.
New bone formation and osteoblast lining were significantly higher in glucosamine-treated group at week 1. Surrounding connective tissue was more cellular and vascular, and the newly formed bone trabecules were present in greater amounts in glucosamine-treated group, compared to control group at week 1 and 4. But radiologically, the control group had better scores than that of the glucosamine-treated group at week 4.
These data demonstrate that daily glucosamine-sulfate administration accelerates early phase of fracture repair in the rat tibia, with increased new bone formation and osteoblast lining histologically, but radiologic bone union is not favored on radiographs.

Uğraş A, Güzel E, Korkusuz P, Kaya I…
Ulus Travma Acil Cerrahi Derg Jan 2013
PMID: 23588972 | Free Full Text

Glucosamine No Effect on Three Bone Markers in Horses

Abstract

Serum concentrations of keratan sulfate, osteocalcin, and pyridinoline crosslinks after oral administration of glucosamine to standardbred horses during race training.

To determine the effects of orally administered glucosamine on concentrations of markers of bone and cartilage metabolism in Standardbred horses during race training.
Twenty 16- to 20-month-old Standardbreds beginning race training.
Horses were randomly assigned to 2 groups. One group received glucosamine hydrochloride (4 g, PO, q 12 h), and the second (control) group received glucose (4 g, PO, q 12 h). Serum samples were obtained prior to onset of the study (baseline) and at regular intervals for 48 weeks for determination of concentrations of keratan sulfate (KS), osteocalcin (OC), and pyridinoline crosslinks (PYD).
Osteocalcin concentrations changed significantly with time; mean serum concentrations were significantly higher than baseline values for samples obtained at 24 to 48 weeks after onset of the study. Although a significant effect of time was observed for mean concentration of KS, concentrations did not differ significantly from baseline values at any time during the study when groups were analyzed separately. However, pooled analysis revealed significant increases of mean serum KS concentration at weeks 24 and 30. Significant changes in serum PYD concentrations were not detected. Oral administration of glucosamine did not significantly affect serum concentrations of any of the markers.
Increased serum OC in clinically normal Standardbreds during race training may reflect bone formation that accompanies adaptive remodeling of the appendicular skeleton. For these experimental conditions, glucosamine did not appear to exert a detectable influence on serum concentrations of these 3 markers of connective tissue metabolism.

Caron JP, Peters TL, Hauptman JG, Eberhart SW…
Am. J. Vet. Res. Aug 2002
PMID: 12171162

Tualang Honey Improves Bone Structure in Ovariectomized Rats

Abstract

Protective effects of Tualang honey on bone structure in experimental postmenopausal rats.

The objective of this study was to evaluate the effects of Tualang honey on trabecular structure and compare these effects with those of calcium supplementation in ovariectomized rats.
Forty female, Sprague-Dawley rats were randomly divided into five groups (n =8): four controls and one test arm. The control arm comprised a baseline control, sham-operated control, ovariectomized control, and ovariectomized calcium-treated rats (receiving 1% calcium in drinking water ad libitum). The test arm was composed of ovariectomized, Tualang honey-treated rats (received 0.2 g/kg body weight of Tualang honey). Both the sham-operated control and ovariectomized control groups received vehicle treatment (deionized water), and the baseline control group was sacrificed without treatment.
All rats were orally gavaged daily for six weeks after day one post-surgery. The bone structural analysis of rats in the test arm group showed a significant increase in the bone volume per tissue volume (BV/TV), trabecular thickness (Tb.Th) and trabecular number (Tb.N) and a significant decrease in inter-trabecular space (Tb.Sp) compared with the ovariectomized control group. The trabecular thickness (Tb.Th) in the test arm group was significantly higher compared with the ovariectomized-calcium treated group, and the inter-trabecular space (Tb.Sp) in the test arm group was significantly narrower compared with the ovariectomized-calcium treated group.
In conclusion, ovariectomized rats that received Tualang honey showed more improvements in trabecular bone structure than the rats that received calcium.

Zaid SS, Sulaiman SA, Othman NH, Soelaiman IN…
Clinics (Sao Paulo) Jul 2012
PMID: 22892923 | Free Full Text

From “Review of the Medicinal Effects of Tualang Honey and a Comparison with Manuka Honey”

Tualang honey (TH) is a Malaysian multifloral jungle honey. In recent years, there has been a marked increase in the number of studies published in medical databases regarding its potential health benefits. The honey is produced by the rock bee (Apis dorsata), which builds hives on branches of tall Tualang trees located mainly in the north-western region of Peninsular Malaysia. This review collates the results of the various studies of TH that range from research on tissue culture to randomised control clinical trials. Findings thus far show that, TH has antimicrobial, anti-inflammatory, antioxidant, antimutagenic, antitumor, and antidiabetic properties, in addition to wound-healing attributes. Some of its properties are similar to the well-researched Manuka honey (New Zealand and/or Australian monofloral honey). Distinct differences include higher phenolics, flavonoids, and 5-(hydroxymethyl) furfural (HMF). Compared with Manuka honey, TH is also more effective against some gram-negative bacterial strains in burn wounds.

 

Vitamin D Serum Level Should be at Least 30 ng/ml, Says the American Geriatrics Society

Abstract

Recommendations Abstracted from the American Geriatrics Society Consensus Statement on Vitamin D for Prevention of Falls and Their Consequences.

The goal of this Consensus Statement is to help primary care practitioners achieve adequate vitamin D intake from all sources in their older patients, with the goal of reducing falls and fall-related injuries. The workgroup graded the quality of evidence and assigned an evidence level using established criteria. Based on the evidence for fall and fracture reduction in the clinical trials of older community-dwelling and institutionalized persons and metaanalyses, the workgroup concluded that a serum 25 hydroxyvitamin D (25(OH)D) concentration of 30 ng/mL (75 nmol/L) should be a minimum goal to achieve in older adults, particularly in frail adults, who are at higher risk of falls, injuries, and fractures. The workgroup concluded that the goal-to reduce fall injuries related to low vitamin D status-could be achieved safely and would not require practitioners to measure serum 25(OH)D concentrations in older adults in the absence of underlying conditions that increase the risk of hypercalcemia (e.g., advanced renal disease, certain malignancies, sarcoidosis).

J Am Geriatr Soc Dec 2013
PMID: 24350602

Glycation Suppresses Bone Formation

Abstract

Advanced glycation end products suppress osteoblastic differentiation of stromal cells by activating endoplasmic reticulum stress.

Advanced glycation end products (AGEs) are involved in bone quality deterioration in diabetes mellitus. We previously showed that AGE2 or AGE3 inhibited osteoblastic differentiation and mineralization of mouse stromal ST2 cells, and also induced apoptosis and decreased cell growth. Although quality management for synthesized proteins in endoplasmic reticulum (ER) is crucial for the maturation of osteoblasts, the effects of AGEs on ER stress in osteoblast lineage are unknown. We thus examined roles of ER stress in AGE2- or AGE3-induced suppression of osteoblastogenesis of ST2 cells. An ER stress inducer, thapsigargin (TG), induced osteoblastic differentiation of ST2 cells by increasing the levels of Osterix, type 1 collagen (Col1), alkaline phosphatase (ALP) and osteocalcin (OCN) mRNA. AGE2 or AGE3 suppressed the levels of ER stress sensors such as IRE1α, ATF6 and OASIS, while they increased the levels of PERK and its downstream molecules, ATF4. A reduction in PERK level by siRNA did not affect the AGEs-induced suppression of the levels of Osterix, Col1 and OCN mRNA. In conclusion, AGEs inhibited the osteoblastic differentiation of stromal cells by suppressing ER stress sensors and accumulating abnormal proteins in the cells. This process might accelerate AGEs-induced suppression of bone formation found in diabetes mellitus.

Tanaka K, Yamaguchi T, Kaji H, Kanazawa I…
Biochem. Biophys. Res. Commun. Aug 2013
PMID: 23933252

Arginine and Lysine Have Positive Effect on Osteoblasts In Vitro

Abstract

Human osteopenic bone-derived osteoblasts: essential amino acids treatment effects.

The development of in vitro cell culture methods has made it possible to study bone cell metabolism and growth and obtain a deeper insight into the pathophysiology of common orthopedic diseases such as osteoporosis. After analyzing the effect of two essential amino acids, L-arginine (Arg) and L-lysine (Lys), in previous in vitro and in vivo studies, the present authors investigated the administration of Arg and Lys in osteoblasts derived from human osteopenic bone. After isolation, osteoblasts were cultured in DMEM supplemented with either Arg (0.625 mg/ml/day, Arg Group) or Lys (0.587 mg/ml/day, Lys Group), or both of them (Arg-Lys Group), whereas the Control Group was sham-treated. After 7 days the following parameters were tested in all groups: MTT proliferation test, Alkaline Phosphatase (ALP), Nitric Oxide (NO), Calcium (Ca), Phosphorus (P), Osteocalcin (OC), C-Terminal Procollagen type I (PICP), Interleukin-6 (IL-6), Transforming Growth Factor-beta 1 (TGF-beta 1), Platelet Derived Growth Factor (PDGF) and Insulin-Like Growth Factor-I (IGF-I). Results were compared with those obtained from human healthy bone to verify the effect of the amino acids on osteoblasts derived from pathological tissue. In addition, a comparison was also made with the results obtained from rat osteopenic bone to assess reliability of the in vitro model. The current results support previous findings and indicate that Arg and Lys stimulation has a positive effect on osteoblast proliferation, activation and differentiation. Therefore, administration of these amino acids may be useful in clinical treatment and prevention of osteoporosis.

Torricelli P, Fini M, Giavaresi G, Giardino R
Artif Cells Blood Substit Immobil Biotechnol Feb 2003
PMID: 12602815