Tag Archives: human

Sophorae Fructus Inhibit Osteoclasts Rat Bone Cells

Abstract

Isoflavones extracted from Sophorae fructus upregulate IGF-I and TGF-beta and inhibit osteoclastogenesis in rat bone marrow cells.

Isoflavones have been a central subject in research on the natural phytoestrogens found in Leguminosae. Their effects on bone formation and remodeling are important in that they can act like estrogen by binding on estrogen receptors on the target cell surface. We, therefore, believed that isoflavones may help in the treatment of patients with estrogen deficiency disease such as estrogen replacement therapy (ERT) for osteoporosis. As commonly known, osteoporosis is one of the hormonal deficiency diseases, especially in menopausal women. When estrogen is no longer produced in the body a remarkable bone remodeling process occurs, and the associated events are regulated by growth factors in the osteoblast lineage. In the present study, we investigated whether isoflavones (Isocal) extracted from Sophorae fructus affect the growth factors IGF-I and TGF-beta that have been known to be related with bone formation. In the study, we found that the active control (PIII) effectively enhanced the level of nitric oxide (NO) and growth factors, and thereby inhibited osteoclastogenesis. The most efficient concentration was 10(-8)% within five days, whereas the comparative control (soybean isoflavone) was not as effective even at a lower concentration. In conclusion, the products which contain enriched glucosidic isoflavone and nutrient supplements such as shark cartilage and calcium can be used for osteoporosis therapy by enhancing the production of IGF-I and TGF-beta. Furthermore, the NO produced through endothelial constitutive NO synthase (ecNOS) may play a role in inhibiting bone reabsorption.

Joo SS, Won TJ, Kang HC, Lee DI
Arch. Pharm. Res. Jan 2004
PMID: 14969347

Review: Phytochemicals for Bone Osteoporosis

Abstract

Regulatory mechanism of food factors in bone metabolism and prevention of osteoporosis.

Aging induces a decrease in bone mass, and osteoporosis with its accompanying decrease in bone mass is widely recognized as a major public health problem. Bone loss with increasing age may be due to decreased bone formation and increased bone resorption. Pharmacologic and nutritional factors may prevent bone loss with aging, although chemical compounds in food and plants which act on bone metabolism are poorly understood. We have found that isoflavones (including genistein and daidzein), which are contained in soybeans, have a stimulatory effect on osteoblastic bone formation and an inhibitory effect on osteoclastic bone resorption, thereby increasing bone mass. Menaquinone-7, an analogue of vitamin K(2) which is abundant in fermented soybeans, has been demonstrated to stimulate osteoblastic bone formation and to inhibit osteoclastic bone resorption. Of various carotenoids, beta-cryptoxanthin, which is abundant in Satsuma mandarin (Citrus unchiu MARC), has a stimulatory effect on osteoblastic bone formation and an inhibitory effect on osteoclastic bone resorption. The supplementation of these factors has a preventive effect on bone loss induced by ovariectomy in rats, which are an animal model of osteoporosis, and their intake has been shown to have a stimulatory effect on bone mass in humans. Factors with an anabolic effect on bone metabolism were found in extracts obtained from wasabi leafstalk (Wasabi japonica MATSUM), the marine alga Sargassum horneri, and bee pollen Cistus ladaniferus. Phytocomponent p-hydroxycinnamic acid was also found to have an anabolic effect on bone metabolism. Food chemical factors thus play a role in bone health and may be important in the prevention of bone loss with increasing age.

Yamaguchi M
Yakugaku Zasshi Nov 2006
PMID: 17077614 | Free Full Text

Virtual Reality Training Improves Balance in Older Adults

Abstract

Effects of balance training using a virtual-reality system in older fallers.

Poor balance is considered a challenging risk factor for falls in older adults. Therefore, innovative interventions for balance improvement in this population are greatly needed. The aim of this study was to evaluate the effect of a new virtual-reality system (the Balance Rehabilitation Unit [BRU]) on balance, falls, and fear of falling in a population of community-dwelling older subjects with a known history of falls. In this study, 60 community-dwelling older subjects were recruited after being diagnosed with poor balance at the Falls and Fractures Clinic, Nepean Hospital (Penrith, NSW, Australia). Subjects were randomly assigned to either the BRU-training or control groups. Both groups received the usual falls prevention care. The BRU-training group attended balance training (two sessions/week for 6 weeks) using an established protocol. Change in balance parameters was assessed in the BRU-training group at the end of their 6-week training program. Both groups were assessed 9 months after their initial assessment (month 0). Adherence to the BRU-training program was 97%. Balance parameters were significantly improved in the BRU-training group (P < 0.01). This effect was also associated with a significant reduction in falls and lower levels of fear of falling (P < 0.01). Some components of balance that were improved by BRU training showed a decline after 9 months post-training. In conclusion, BRU training is an effective and well-accepted intervention to improve balance, increase confidence, and prevent falls in the elderly.

Duque G, Boersma D, Loza-Diaz G, Hassan S…
Clin Interv Aging 2013
PMID: 23467506 | Free Full Text

Teriparatide Increases Bone Strength More Than Density

Abstract

Femoral strength in osteoporotic women treated with teriparatide or alendronate.

To gain insight into the clinical effect of teriparatide and alendronate on the hip, we performed non-linear finite element analysis of quantitative computed tomography (QCT) scans from 48 women who had participated in a randomized, double-blind clinical trial comparing the effects of 18-month treatment of teriparatide 20 μg/d or alendronate 10mg/d. The QCT scans, obtained at baseline, 6, and 18 months, were analyzed for volumetric bone mineral density (BMD) of trabecular bone, the peripheral bone (defined as all the cortical bone plus any endosteal trabecular bone within 3 mm of the periosteal surface), and the integral bone (both trabecular and peripheral), and for overall femoral strength in response to a simulated sideways fall. At 18 months, we found in the women treated with teriparatide that trabecular volumetric BMD increased versus baseline (+4.6%, p<0.001), peripheral volumetric BMD decreased (-1.1%, p<0.05), integral volumetric BMD (+1.0%, p=0.38) and femoral strength (+5.4%, p=0.06) did not change significantly, but the ratio of strength to integral volumetric BMD ratio increased (+4.0%, p=0.04). An increase in the ratio of strength to integral volumetric BMD indicates that overall femoral strength, compared to baseline, increased more than did integral density. For the women treated with alendronate, there were small (<1.0%) but non-significant changes compared to baseline in all these parameters. The only significant between-treatment difference was in the change in trabecular volumetric BMD (p<0.005); related, we also found that, for a given change in peripheral volumetric BMD, femoral strength increased more for teriparatide than for alendronate (p=0.02). We conclude that, despite different compartmental volumetric BMD responses for these two treatments, we could not detect any overall difference in change in femoral strength between the two treatments, although femoral strength increased more than integral volumetric BMD after treatment with teriparatide.

Keaveny TM, McClung MR, Wan X, Kopperdahl DL…
Bone Jan 2012
PMID: 22015818

Teriparatide Decreases Bone Density, but Not Strength

Abstract

Changes in trabecular and cortical bone microarchitecture at peripheral sites associated with 18 months of teriparatide therapy in postmenopausal women with osteoporosis.

We used high-resolution peripheral quantitative computed tomography (HR-pQCT) to monitor changes in bone microarchitecture and strength at the distal radius and tibia associated with 18 months of teriparatide therapy in postmenopausal women with osteoporosis. Despite treatment-associated declines in total and cortical BMD, trabecular thinning and reduced trabecular bone volume, bone strength did not change significantly from baseline.
Teriparatide is an established anabolic therapy for osteoporosis; however, treatment effects at the distal radius are unclear. Therefore, we aimed to monitor changes in bone microarchitecture and estimated strength at the distal radius and tibia in osteoporotic postmenopausal women.
We used high-resolution peripheral quantitative computed tomography (Scanco Medical, Switzerland) to perform a standard three-dimensional morphological analysis of the distal radius and tibia in 11 osteoporotic postmenopausal women (mean age, 68.7 ± 12.7 years) at baseline, 6, 12, and 18 months after initiation of 20 μg/day of teriparatide. Ten of the women received bisphosphonate therapy prior to starting on teriparatide. In addition to the standard analysis, we quantified cortical bone mineral density (BMD), porosity, and thickness using an automated segmentation procedure and estimated bone strength (ultimate stress) using finite element analysis.
After 18 months, we observed a decrease in total BMD (p = 0.03) at the distal radius and a decrease in cortical BMD at the distal radius (p = 0.05) and tibia (p = 0.01). The declines in cortical BMD were associated with trends for increased cortical porosity at both sites. At the distal radius, 18 months of teriparatide treatment was also associated with trabecular thinning (p = 0.009) and reduced trabecular bone volume ratio (p = 0.08). We observed similar trends at the distal tibia. Despite these changes in bone quality, bone strength was maintained over the 18-month follow-up.
The observed changes in cortical bone structure are consistent with the effects of parathyroid hormone on intracortical bone remodeling. Controlled trials involving larger sample sizes are required to confirm the effects of teriparatide therapy on trabecular and cortical microarchitecture in the peripheral skeleton.

Macdonald HM, Nishiyama KK, Hanley DA, Boyd SK
Osteoporos Int Jan 2011
PMID: 20458576 | Full Text

Although our sample size was small, our results are consistent with previous reports of declines in cortical BMD at the radius [8, 9, 18] and at the femoral neck [6] with teriparatide therapy. The decrease in cortical BMD in the present study was coupled with increased cortical porosity at both sites; however, cortical porosity was only statistically different from baseline at the distal tibia after 12 months. Despite a more porous cortex, FE analysis indicated that bone strength did not appear to be compro- mised with teriparatide treatment. This finding supports observations from animal models in which treatment with PTH activated intracortical remodeling and lead to in- creased intracortical porosity [19, 20], but did not compro- mise bone strength [20]. This was likely due to localization of the porosity near the endocortical surface where its influence on bone’s mechanical properties is minimal [20], although this spatial distribution needs to be confirmed in future HR-pQCT studies. In the present study, a slightly thicker cortical shell and enlarged cortical area may also have offset the higher cortical porosity at the distal tibia. Similar changes in cortical bone geometry were observed in rabbits [19] and monkeys [20] treated with PTH and were attributed to increased bone formation on the endocortical surface. In addition, postmenopausal women treated with teriparatide for a median of 18 months had significantly larger cortical area at the distal radius compared with untreated women as measured with pQCT, but no pretreatment com- parison was obtained [18]. Whether PTH has an anabolic effect on the periosteal surface remains unclear [19, 20]….

We acknowledge limitations of our study including the small sample size and the fact that all but one of the women had received prior therapy with bisphosphonates. The degree to which prior bisphosphonate therapy blunts the bone response to teriparatide remains unclear, as in some instances, it does not appear to do so [4, 23]. Since distal radius fractures are recognized indicators of osteoporosis [24], there is an obvious need for larger clinical trials that employ HR-pQCT to monitor and compare the treatment- related effects of teriparatide on bone microarchitecture and strength in treatment-naïve subjects and subjects with a history of bisphosphonate therapy.

Teriparatide Stimulates Bone Formation and Resorption, and Decreases Fracture Risk

Abstract

Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis.

Once-daily injections of parathyroid hormone or its amino-terminal fragments increase bone formation and bone mass without causing hypercalcemia, but their effects on fractures are unknown.
We randomly assigned 1637 postmenopausal women with prior vertebral fractures to receive 20 or 40 microg of parathyroid hormone (1-34) or placebo, administered subcutaneously by the women daily. We obtained vertebral radiographs at base line and at the end of the study (median duration of observation, 21 months) and performed serial measurements of bone mass by dual-energy x-ray absorptiometry.
New vertebral fractures occurred in 14 percent of the women in the placebo group and in 5 percent and 4 percent, respectively, of the women in the 20-microg and 40-microg parathyroid hormone groups; the respective relative risks of fracture in the 20-microg and 40-microg groups, as compared with the placebo group, were 0.35 and 0.31 (95 percent confidence intervals, 0.22 to 0.55 and 0.19 to 0.50). New nonvertebral fragility fractures occurred in 6 percent of the women in the placebo group and in 3 percent of those in each parathyroid hormone group (relative risk, 0.47 and 0.46, respectively [95 percent confidence intervals, 0.25 to 0.88 and 0.25 to 0.861). As compared with placebo, the 20-microg and 40-microg doses of parathyroid hormone increased bone mineral density by 9 and 13 more percentage points in the lumbar spine and by 3 and 6 more percentage points in the femoral neck; the 40-microg dose decreased bone mineral density at the shaft of the radius by 2 more percentage points. Both doses increased total-body bone mineral by 2 to 4 more percentage points than did placebo. Parathyroid hormone had only minor side effects (occasional nausea and headache).
Treatment of postmenopausal osteoporosis with parathyroid hormone (1-34) decreases the risk of vertebral and nonvertebral fractures; increases vertebral, femoral, and total-body bone mineral density; and is well tolerated. The 40-microg dose increased bone mineral density more than the 20-microg dose but had similar effects on the risk of fracture and was more likely to have side effects.

Neer RM, Arnaud CD, Zanchetta JR, Prince R…
N. Engl. J. Med. May 2001
PMID: 11346808 | Free Full Text

Parathyroid hormone stimulates bone formation and resorption and can increase or decrease bone mass, depending on the mode of administration. Continuous infusions and daily subcutaneous injections of parathyroid hormone stimulate bone formation similarly but have different effects on bone resorption and bone mass.1,2 Continuous infusions, which result in a persistent elevation of the serum parathyroid hormone concentration, lead to greater bone resorption than do daily injections, which cause only transient increases in the serum parathyroid hormone concentration.3

Fruit + Vegetables Fails to Improve Bone Over 16 Weeks

Abstract

Effect of increased fruit and vegetable consumption on bone turnover in older adults: a randomised controlled trial.

Evidence suggests that increased fruit and vegetable (FV) intake may be associated with improved bone health, but there is limited evidence from intervention trials to support this. This 16-week study showed that increased FV consumption (five or more portions per day) does not have any effect on the markers of bone health in older adults.
Observational evidence suggests that increased FV consumption may be associated with improved bone health. However, there is lack of evidence from intervention trials to support this. This study examined the effect of increased FV consumption on bone markers among healthy, free-living older adults.
A randomised controlled trial was undertaken. Eighty-three participants aged 65-85 years, habitually consuming less than or equal to two portions of FV per day, were randomised to continue their normal diet or to consume five or more portions of FV per day for 16 weeks. FV were delivered to all participants each week, free of charge. Compliance was assessed at baseline and at 6, 12 and 16 weeks by diet histories and biomarkers of micronutrient status. Fasting serum bone markers (osteocalcin (OC) and C-terminal telopeptide of type 1 collagen (CTX)) were measured using enzyme-linked immunosorbent assay.
Eighty-two participants completed the intervention. The five portions per day group showed a significantly greater change in daily FV consumption compared to the two portions per day group (p < 0.001), and this was reflected in significant increases in micronutrient status. No significant differences were evident in change in bone markers between the two portions per day group and the five portions per day group over the 16 weeks (geometric mean of week 16 to baseline ratio (95% confidence interval): OC-0.95 (0.89-1.02) and 1.04 (0.91-1.18), respectively, p = 0.25; CTX-1.06 (0.95-1.19) and 0.98 (0.90-1.06) respectively, p = 0.20).
Increased FV consumption had no effect on bone markers in older adults. Larger intervention studies of longer duration are warranted to establish whether long-term FV consumption can benefit bone health.

Neville CE, Young IS, Gilchrist SE, McKinley MC…
Osteoporos Int Jan 2014
PMID: 23716039

Cranberry Inhibits Osteoclasts In Vitro

Abstract

A-type cranberry proanthocyanidins inhibit the RANKL-dependent differentiation and function of human osteoclasts.

This study investigated the effect of A-type cranberry proanthocyanidins (AC-PACs) on osteoclast formation and bone resorption activity. The differentiation of human pre-osteoclastic cells was assessed by tartrate-resistant acid phosphatase (TRAP) staining, while the secretion of interleukin-8 (IL-8) and matrix metalloproteinases (MMPs) was measured by ELISA. Bone resorption activity was investigated by using a human bone plate coupled with an immunoassay that detected the release of collagen helical peptides. AC-PACs up to 100 µg/mL were atoxic for osteoclastic cells. TRAP staining evidenced a dose-dependent inhibition of osteoclastogenesis. More specifically, AC-PACs at 50 µg/mL caused a 95% inhibition of RANKL-dependent osteoclast differentiation. This concentration of AC-PACs also significantly increased the secretion of IL-8 (6-fold) and inhibited the secretion of both MMP-2 and MMP-9. Lastly, AC-PACs (10, 25, 50 and 100 µg/ml) affected bone degradation mediated by mature osteoclasts by significantly decreasing the release of collagen helical peptides. This study suggests that AC-PACs can interfere with osteoclastic cell maturation and physiology as well as prevent bone resorption. These compounds may be considered as therapeutic agents for the prevention and treatment of periodontitis.

Tanabe S, Santos J, La VD, Howell AB…
Molecules 2011
PMID: 21399573 | Free Full Text

Alcohol Reduces Bone Resorption Markers

Abstract

Moderate ingestion of alcohol is associated with acute ethanol-induced suppression of circulating CTX in a PTH-independent fashion.

The “J shape” curve linking the risk of poor bone health to alcohol intake is now well recognized from epidemiological studies. Ethanol and nonethanol components of alcoholic beverages could influence bone remodeling. However, in the absence of a solid underlying mechanism, the positive association between moderate alcoholic intake and BMD remains questionable because of confounding associated social factors. The objective of this work was to characterize the short-term effects of moderate alcohol consumption on circulating bone markers, especially those involved in bone resorption. Two sequential blood-sampling studies were undertaken in fasted healthy volunteers (age, 20-47 yr) over a 6-h period using beer of different alcohol levels (<0.05-4.6%), solutions of ethanol or orthosilicic acid (two major components of beer), and water +/- calcium chloride (positive and negative controls, respectively). Study 1 (24 subjects) assessed the effects of the different solutions, whereas study 2 (26 subjects) focused on ethanol/beer dose. Using all data in a “mixed effect model,” we identified the contributions of the individual components of beer, namely ethanol, energy, low-dose calcium, and high-dose orthosilicic acid, on acute bone resorption. Markers of bone formation were unchanged throughout the study for all solutions investigated. In contrast, the bone resorption marker, serum carboxy terminal telopeptide of type I collagen (CTX), was significantly reduced after ingestion of a 0.6 liters of ethanol solution (>2% ethanol; p <or= 0.01, RM-ANOVA), 0.6 liters of beer (<0.05-4.6% ethanol; p < 0.02), or a solution of calcium (180 mg calcium; p < 0.001), but only after calcium ingestion was the reduction in CTX preceded by a significant fall in serum PTH (p < 0.001). Orthosilicic acid had no acute effect. Similar reductions in CTX, from baseline, were measured in urine after ingestion of the test solutions; however, the biological variability in urine CTX was greater compared with serum CTX. Modeling indicated that the major, acute suppressive effects of moderate beer ingestion (0.6 liters) on CTX were caused by energy intake in the early phase (approximately 0-3 h) and a “nonenergy” ethanol component in the later phase (approximately 3 to >6 h). The early effect on bone resorption is well described after the intake of energy, mediated by glucagon-like peptide-2, but the late effect of moderate alcohol ingestion is novel, seems to be ethanol specific, and is mediated in a non-calcitonin- and a non-PTH-dependent fashion, thus providing a mechanism for the positive association between moderate alcohol ingestion and BMD.

Sripanyakorn S, Jugdaohsingh R, Mander A, Davidson SL…
J. Bone Miner. Res. Aug 2009
PMID: 19257829 | Free Full Text

Silicon as Orthosilicic Acid Decreases Osteoblast Survivability In Vitro

Abstract

Divergent effects of orthosilicic acid and dimethylsilanediol on cell survival and adhesion in human osteoblast-like cells.

Although dietary silicon (Si) is recognized to be an important factor for the growth and development of bone and connective tissue, its biochemical role has yet to be identified. The predominant Si-containing species in blood and other biofluids is orthosilicic acid, Si(OH)(4). Dimethylsilanediol, (CH(3))(2)Si(OH)(2), is an environmental contaminant that results from decomposition of silicone compounds used in personal hygiene, health care and industrial products. We examined the in vitro effects of both Si species on the survival (colony forming efficiency), proliferation (DNA content), differentiation (alkaline phosphatase activity) and adhesion (relative protein content) of the human osteoblast-like cell lines Saos-2 and hFOB 1.19. Orthosilicic acid yielded a small, dose-dependent decrease in Saos-2 cell survivability up to its 1,700 micromol/L solubility limit, by which point survival was 20% less than that of untreated cells. This negative association, although small, correlated with a reduction in the proliferation and adhesion of Saos-2 cells as well as of hFOB 1.19 and osteoclast-like GCT cells. By contrast, dimethylsilanediol treatment had no discernable influence on Saos-2 survivability at concentrations up to 50 micromol/L, and yet significantly enhanced cell survival at higher doses. Moreover, dimethylsilanediol did not affect proliferation or adhesion of any cell line. The findings show that orthosilicic acid and dimethylsilanediol affect osteoblast-like cells very differently, providing insight into the mechanism by which silicon influences bone health, although the specific site of Si activity remains unknown. There was no evidence to suggest that dimethylsilanediol is cytotoxic at environmental/physiological concentrations.

Duivenvoorden WC, Middleton A, Kinrade SD
J Trace Elem Med Biol 2008
PMID: 18755397