Tag Archives: abstract

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

Risk Factors and Protective Factors for Falls

Abstract

Lifestyle predicts falls independent of physical risk factors.

Many falls occur among older adults with no traditional risk factors. We examined potential independent effects of lifestyle on fall risk. Not smoking and going outdoors frequently or infrequently were independently associated with more falls, indicating lifestyle-related behavioral and environmental risk factors are important causes of falls in older women.
Physical and lifestyle risk factors for falls and population attributable risks (PAR) were examined.
We conducted a 4-year prospective study of 8,378 community-dwelling women (mean age = 71 years, SD = 3) enrolled in the Study of Osteoporotic Fractures. Data on number of falls were self-reported every 4 months. Fall rates were calculated (# falls/woman-years). Poisson regression was used to estimate relative risks (RR).

Physical risk factors (p < or = 0.05 for all) included tall height (RR = 0.89 per 5 in.), dizziness (RR = 1.16), fear of falling (RR = 1.20), self-reported health decline (RR = 1.19), difficulty with Instrumental Activities of Daily Living (IADLs) (RR = 1.12, per item), fast usual-paced walking speed (RR = 1.18, per 2 SD), and use of antidepressants (RR = 1.20), benzodiazepines (RR = 1.11), or anticonvulsants (RR = 1.62).

Protective physical factors (p < or = 0.05 for all) included good visual acuity (RR = 0.87, per 2 SD) and good balance (RR = 0.85 vs. poor).

Lifestyle predicted fewer falls including current smoking (RR = 0.76), going outdoors at least twice weekly but not more than once a day (RR = 0.89 and vs. twice daily). High physical activity was associated with more falls but only among IADL impaired women. Five potentially modifiable physical risk factors had PAR > or = 5%.
Fall interventions addressing modifiable physical risk factors with PAR > or = 5% while considering environmental/behavioral risk factors are indicated.

Faulkner KA, Cauley JA, Studenski SA, Landsittel DP…
Osteoporos Int Dec 2009
PMID: 19319617 | Free Full Text

Review: Moderate Alcohol May Benefit Bone, but Abuse has Toxic Effect

Abstract

Bone and the ‘comforts of life’.

Coffee drinking, smoking and especially alcohol abuse are considered to be risk factors for fractures and osteoporosis. Caffeine causes acute increase in urinary calcium excretion, but epidemiological evidence for the effects of coffee consumption on the risk of fractures is contradictory. Many, (but not all) studies point to decreased bone mass or increased fracture risk in smokers. Alcohol abuse is associated with deleterious changes in bone structure detected by histomorphometry, and with a decrease in bone mineral density (BMD).

 These changes may also be produced by factors commonly associated with alcohol abuse, e.g. nutritional deficiencies, liver damage and hypogonadism. Alcohol, however, has clear-cut direct effects on bone and mineral metabolism. Acute alcohol intoxication causes transitory hypoparathyroidism with resultant hypocalcaemia and hypercalciuria. As assessed by serum osteocalcin levels, prolonged moderate drinking decreases the function of osteoblasts, the bone-forming cells. In addition, chronic alcoholics are characterized by low serum levels of vitamin D metabolites. Thus, alcohol seems to have a direct toxic effect on bone and mineral metabolism. In contrast, it has recently been reported that moderate alcohol consumption by postmenopausal women may have a beneficial effect on bone.

Laitinen K, Välimäki M
Ann. Med. Aug 1993
PMID: 8217108

Melatonin Induces Bone Sialoprotein In Vitro

Abstract

Melatonin regulates human bone sialoprotein gene transcription.

Melatonin is produced by the pineal gland and regulates various physiological processes including osteoblast differentiation and bone formation. Bone sialoprotein (BSP) is a mineralized connective tissue-specific protein expressed in the early stage of cementum and bone mineralization. To elucidate the effects of melatonin on human BSP gene expression, we utilized human Saos2 osteoblast-like cells. Melatonin (100 nM) increased the level of BSP mRNA at 3 h, and the level became maximal at 12 and 24 h. We then investigated the melatonin-induced transcriptional activity of luciferase constructs (between -84LUC and -868LUC) including different lengths of the human BSP gene promoter transfected into Saos2 cells. The effects of melatonin abrogated in constructs included 2-bp mutations in the two cAMP response elements (CRE1 and CRE2). The effects of melatonin were suppressed by protein kinase A, tyrosine kinase, ERK1/2 and phosphatidylinositol 3-kinase inhibitors. Gel mobility shift assays showed that melatonin increased the binding of nuclear proteins to CRE1 and CRE2, and antibodies against CRE binding protein 1 (CREB1), phospho-CREB1, c-Fos, c-Jun, JunD and Fra2 disrupted CRE1 and CRE2 protein complex formation. These data indicate that melatonin induces BSP transcription via the CRE1 and CRE2 elements in the human BSP gene promoter.

Matsumura H, Ogata Y
J Oral Sci 2014
PMID: 24739710 | Free Full Text

Melatonin Benefits Bones in Old Rats

Abstract

Melatonin dietary supplement as an anti-aging therapy for age-related bone loss.

Introduction: Previous studies have shown that melatonin, an antioxidant molecule secreted from the pineal gland, is a positive regulator of bone mass. However, melatonin potential effects on bone mass have never been investigated in old population yet. The aim of this study was to assess the effects of dietary melatonin supplementation on mass accrual and biomechanical properties of old rat femora. Methods: Twenty 22-months-old male Wistar rats were divided into 2 randomly assigned groups. The first group was treated for 10 weeks with melatonin, whereas the second group left untreated (control). Rat femurs were collected, and their phenotypes and biomechanical properties were investigated by micro-computed tomography, histomorphometry and 3-point-bending test. Statistical analyses were performed by Student’s two-tailed unpaired t-test. In all experiments, a value of p < 0.05 was considered significant. Results: Rats treated with melatonin had higher bone volume, bone trabecular number, trabecular thickness and cortical thickness in comparison to control group. Histomorphometric analyses confirmed the increase of bone volume in melatonin-treated rats. In agreement with these findings, melatonin-treated rats demonstrated with higher bone stiffness, flexural modulus and ultimate load compared to controls. Conclusion: These compelling results are the first evidence indicating that dietary melatonin supplementation is able to exert beneficial effects against age-related bone loss in old rats; improving the microstructure and biomechanical properties of aged bones.

Tresguerres IF, Tamimi F, Eimar H, Barralet J…
Rejuvenation Res Mar 2014
PMID: 24617902