Monthly Archives: May 2014

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

Review: Melatonin Induces Osteoblastogenesis and Inhibits Osteoclastogenesis

Abstract

Melatonin effects on bone: potential use for the prevention and treatment for osteopenia, osteoporosis, and periodontal disease and for use in bone-grafting procedures.

An important role for melatonin in bone formation and restructuring has emerged, and studies demonstrate the multiple mechanisms for these beneficial actions. Statistical analysis shows that even with existing osteoporotic therapies, bone-related disease, and mortality are on the rise, creating a huge financial burden for societies worldwide. These findings suggest that novel alternatives need to be developed to either prevent or reverse bone loss to combat osteoporosis-related fractures. The focus of this review describes melatonin’s role in bone physiology and discusses how disruption of melatonin rhythms by light exposure at night, shift work, and disease can adversely impact on bone. The signal transduction mechanisms underlying osteoblast and osteoclast differentiation and coupling with one another are discussed with a focus on how melatonin, through the regulation of RANKL and osteoprotegerin synthesis and release from osteoblasts, can induce osteoblastogenesis while inhibiting osteoclastogenesis. Also, melatonin’s free-radical scavenging and antioxidant properties of this indoleamine are discussed as yet an additional mechanism by which melatonin can maintain one’s bone health, especially oral health. The clinical use for melatonin in bone-grafting procedures, in reversing bone loss due to osteopenia and osteoporosis, and in managing periodontal disease is discussed.

Maria S, Witt-Enderby PA
J. Pineal Res. Dec 2013
PMID: 24372640

Hypothesis: Melatonin for Osteoporosis

Abstract

Is postmenopausal osteoporosis related to pineal gland functions?

There is currently considerable interest in the pathogenesis of postmenopausal osteoporosis, which is the most common metabolic bone disease. Osteoporosis affects approximately 20 million persons in the United States, 90% of whom are postmenopausal women. Although there is evidence that estrogen deficiency is an important contributory factor, the pathogenesis of osteoporosis is multifactorial and presently poorly understood. There is evidence that pineal melatonin is an anti-aging hormone and that the menopause is associated with a substantial decline in melatonin secretion and an increased rate of pineal calcification. Animal data indicate that pineal melatonin is involved in the regulation of calcium and phosphorus metabolism by stimulating the activity of the parathyroid glands and by inhibiting calcitonin release and inhibiting prostaglandin synthesis. Hence, the pineal gland may function as a “fine tuner” of calcium homeostasis. In the following communication, we propose that the fall of melatonin plasma levels during the early stage of menopause may be an important contributory factor in the development of postmenopausal osteoporosis. Consequently, plasma melatonin levels taken in the early menopause could be used as an indicator or perhaps as a marker for susceptibility to postmenopausal osteoporosis. Moreover, light therapy, administration of oral melatonin (2.5 mg at night) or agents which induce a sustained release of melatonin secretion such as 5-methoxypsoralen, could be useful agents in the prophylaxis and treatment of postmenopausal osteoporosis. Finally, since application of external artificial magnetic fields has been shown to synchronize melatonin secretion in experimental animals and humans, we propose that treatment with artificial magnetic fields may be beneficial for postmenopausal osteoporosis.

Sandyk R, Anastasiadis PG, Anninos PA, Tsagas N
Int. J. Neurosci. Feb 1992
PMID: 1305608

Zinc + Manganese + Copper + Calcium is More Effective Than Calcium

Abstract

Spinal bone loss in postmenopausal women supplemented with calcium and trace minerals.

The effects of calcium supplementation (as calcium citrate malate, 1000 mg elemental Ca/d) with and without the addition of zinc (15.0 mg/d), manganese (5.0 mg/d) and copper (2.5 mg/d) on spinal bone loss (L2-L4 vertebrae) was evaluated in healthy older postmenopausal women (n = 59, mean age 66 y) in a 2-y, double-blind, placebo-controlled trial. Changes (mean +/- SEM) in bone density were -3.53 +/- 1.24% (placebo), -1.89 +/- 1.40% (trace minerals only), -1.25 +/- 1.46% (calcium only) and 1.48 +/- 1.40% (calcium plus trace minerals). Bone loss relative to base-line value was significant (P = 0.0061) in the placebo group but not in the groups receiving trace minerals alone, calcium alone, or calcium plus trace minerals. The only significant group difference occurred between the placebo group and the group receiving calcium plus trace minerals (P = 0.0099). These data suggest that bone loss in calcium-supplemented, older postmenopausal women can be further arrested by concomitant increases in trace mineral intake.

Strause L, Saltman P, Smith KT, Bracker M…
J. Nutr. Jul 1994
PMID: 8027856 | Free Full Text

CR Suppresses Bone Formation and Increases Resorption in Obese Rats

Abstract

Energy-restricted diet benefits body composition but degrades bone integrity in middle-aged obese female rats.

This study investigates the effects of a restricted diet (RD) on body composition and musculoskeletal health along with endocrines and molecular mechanism in established mature obese rats. Twenty female rats were fed with a high-fat diet (HFD) ad libitum for 4 months and then assigned to either HFD or RD group for another 4 months. Another 10 rats were on a low-fat diet for 8 months. Outcome measures included body composition, bone mineral density, microarchitecrure, and strength; serum leptin, adiponectin, insulin-like growth factor I, and liver glutathione peroxidase activity; and protein expression and spleen tumor necrosis factor α messenger RNA expression. We hypothesized that mature obese rats on a 35% energy restriction diet for 4 months would improve body composition but degrade microstructural and mechanical properties of long bones, and such changes in musculoskeletal integrity are related to the modulation of obesity-related endocrines and proinflammation. Relative to HFD, RD benefited body composition (decreased body weight and %fat mass and increased %fat-free mass); decreased insulin-like growth factor I and leptin; elevated adiponectin, glutathione peroxidase activity and protein expression and tumor necrosis factor α messenger RNA expression; and suppressed bone formation and increased bone resorption, resulting in decreased trabecular and cortical bone volume, bone mineral density, and bone strength. Relative to low-fat diet, RD had a similar effect on body composition and serum markers but increased bone turnover rate and decreased bone mineral density and strength. Our data suggest that long-term RD has a negative impact on bone remodeling in obese female rats, probably through modification of endocrines and elevation of proinflammation.

Shen CL, Zhu W, Gao W, Wang S…
Nutr Res Aug 2013
PMID: 23890357

Chondroitin from Deer Antler may be Osteogenetic

Abstract

Characterization of chondroitin sulfate from deer tip antler and osteogenic properties.

Deer antler is a highly regenerative tissue that involves cellular differentiation, osteogenesis and ossification processes. Chondroitin sulfate is the major glycosaminoglycan contained in antler connective tissue and has been isolated from cartilaginous antler by 4 M GuHCl extraction, gradient ultracentrifugation and chromatography techniques. We examined the disaccharide composition by 2-AB labeling and anion exchange HPLC analysis of the three resultant fractions (high, medium and low density fractions). The high density fraction consists of A-unit and D-unit disaccharide in the ratio of 1:1, whereas, the CS disaccharide composition ratio of A- unit:C-unit:D-Unit:E-unit contained in medium and low density fractions are 3:4:3:1 and 2:2:2:1, respectively. The only intact CS oligosaccharides of the medium density fraction upregulated gene expression of bone-specific proteins of a human osteoblastic cell line (hFOB1.19). Thus, CS oligosaccharides from cartilaginous deer antler, with their oversulfated chondroitin sulfate composition, demonstrated the physiological properties and may be good candidates for osteogenetic agents in humans.

Pothacharoen P, Kodchakorn K, Kongtawelert P
Glycoconj. J. Oct 2011
PMID: 21894464

Chondroitin Suppresses Osteoclasts In Vitro

Abstract

Comparison of the ability of chondroitin sulfate derived from bovine, fish and pigs to suppress human osteoclast activity in vitro.

Chondroitin sulfate (CS) compounds are commonly used to manage OA symptoms. Recent literature has indicated that abnormal subchondral bone metabolism may have a role in the pathogenesis of OA. The aim of this study was to access the effects of chondroitin sulfate obtained from bovine, fish and porcine sources on human osteoclast formation and activity in vitro. Human osteoclasts were generated from blood mononuclear cells. Cells were cultured over 17 days with the addition of macrophage colony stimulating factor (M-CSF) and then stimulated with receptor activator of nuclear factor kappa B ligand from day 7. Cells were treated with the CS commencing from day 7 onwards. To assess effects on osteoclasts, tartrate resistant acid phosphatate (TRAP) expression and resorption of whale dentine assays were used. Bovine-derived CS consistently suppressed osteoclast activity at concentrations as low as 1 μg/ml. Fish and porcine CS was less consistent in their effects varying with different donor cells. All CS compounds had little effect on TRAP activity. mRNA analysis using real-time PCR of bovine CS treated cells indicated that the inhibition of activity was not due to inhibition of the late stage NFATc1 transcription factor (p > 0.05). These results are consistent with CS inhibition of mature osteoclast activity rather than the formation of mature osteoclasts. It would appear that there are differences in activity of the different CS compounds with bovine-derived CS being the most consistently effective inhibitor of osteoclast resorption, but the results need to be confirmed.

Cantley MD, Rainsford KD, Haynes DR
Inflammopharmacology Dec 2013
PMID: 23644893