Tag Archives: human

Bisphosphonates Showed the Smallest Increase In Fracture Rate Over 10 Years

Abstract

Ten-year fracture risk in the assessment of osteoporosis management efficacy in postmenopausal women: a pilot study.

The aim of the reported longitudinal, retrospective pilot study was to establish changes in 10-year fracture risk in postmenopausal women with respect to applied fracture management.
A group of 191 postmenopausal women with a mean age of 68.76± 6.72 years was divided into subgroups. The subgroups were made up of untreated patients (n = 41), patients treated with vitamin D plus calcium (n = 46), and patients treated with bisphosphonates, vitamin D and calcium (n = 104). Repeated densitometric measurements and clinical data were taken into consideration (both baseline and follow-up). Ten-year fracture risk was established, using FRAX(TM) and Garvan nomograms. The mean follow-up period was 2.01±1.87 years.
Generally, the mean fracture probability increased in the studied women over the observation period. Patients on bisphosphonate therapy demonstrated the smallest increase in fracture probability. The probability rate for either any fractures or hip fractures decreased when the T-score increased. A diminished number of falls non-significantly decreased the probability for hip fractures and any fractures.
Ten-year fracture risk increased irrespective of applied management, while a decreased risk was observed only in women with improved bone status.

Pluskiewicz W, Drozdzowska B, Adamczyk P
Climacteric Feb 2013
PMID: 22335356

Genistein + EPA + DHA + Vitamin D + K1 Increases Bone Density in Postmenopausal Women

Abstract

Effect of a combination of genistein, polyunsaturated fatty acids and vitamins D3 and K1 on bone mineral density in postmenopausal women: a randomized, placebo-controlled, double-blind pilot study.

Many postmenopausal women desire non-pharmaceutical alternatives to hormone therapy for protection against osteoporosis. Soybean isoflavones, especially genistein, are being studied for this purpose. This study examined the effects of synthetic genistein in combination with other potential bone-protective dietary molecules on bone mineral density (BMD) in early postmenopausal women.
In this 6-month double-blind pilot study, 70 subjects were randomized to receive daily either calcium only or the geniVida™ bone blend (GBB), which consisted of genistein (30 mg/days), vitamin D3 (800 IU/days), vitamin K1 (150 μg/days) and polyunsaturated fatty acids (1 g polyunsaturated fatty acids as ethyl ester: eicosapentaenoic acid/docosahexaenoic acid ratio = ~2/1). Markers of bone resorption and formation and BMD at the femoral neck, lumbar spine, Ward’s triangle, trochanter and intertrochanter, total hip and whole body were assessed.
Subjects supplemented with the GBB (n = 30) maintained femoral neck BMD, whereas in the placebo group (n = 28), BMD significantly decreased (p = 0.007). There was also a significant difference (p < 0.05) in BMD between the groups at Ward’s triangle in favor of the GBB group. Bone-specific alkaline phosphatase and N-telopeptide significantly increased in the GBB group in comparison with those in baseline and in the placebo group. The GBB was well tolerated, and there were no significant differences in adverse events between groups.
The GBB may help to prevent osteoporosis and reduce fracture risk, at least at the hip, in postmenopausal women. Larger and longer-term clinical trials are warranted.

Lappe J, Kunz I, Bendik I, Prudence K…
Eur J Nutr Feb 2013
PMID: 22302614 | Free Full Text

Vitamin D Level Influences Bone Density in Saudi Men and Women

Abstract

Influence of vitamin D levels on bone mineral density and osteoporosis.

The effects of vitamin D on bone mass remain to be understood. This study was conducted with the objective of evaluating the influence of 25-hydroxyvitamin D (25OHD) levels on bone mineral density (BMD) among Saudi nationals.
Cross-sectional study carried out at university hospital from 1 February 2008 to 31 May 2008.
Healthy Saudi men and women in the peak bone mass (PBM) age group and those aged ≥ 50 years were recruited from the outpatient department of King Fahd University Hospital, Al Khobar, Saudi Arabia, between February 1, 2008, and May 31, 2008. Patient age and sex were documented, and body mass index was calculated. Hematological, biochemical, and serum 25OHD tests were performed. BMD was determined by dual-energy x-ray absorptiometry of the upper femur and lumbar spine. Patients were divided into three groups, based on their 25OHD level.
Data from 400 patients were analyzed. Among individuals with a normal 25OHD level, 50% of women and 7% of men in the PBM age group and 26.4% of women and 49.2% of men aged ≥ 50 years had low bone mass. In patients with 25OHD insufficiency, 84.2% of women and 88.9% of men in the PBM age group and 83.3% of women and 80% of men aged ≥ 50 years had low bone mass. Results for patients with 25OHD deficiency revealed that none of the men and women in the PBM age group or ≥ 50 years old had normal BMD. Significant positive correlations between 25OHD level and BMD and significant negative correlations with parathyroid hormone were shown in most of the groups.
This study showed that the vitamin D level significantly influences BMD reading among Saudi individuals. Evaluation and treatment of hypovitaminosis D should be considered during management of low bone mass.

Sadat-Ali M, Al Elq AH, Al-Turki HA, Al-Mulhim FA…
Ann Saudi Med
PMID: 22048506 | Free Full Text

Gamma-Tocotrienol Inhibits Osteoclasts In Vitro

Abstract

Direct inhibition of osteoclast formation and activity by the vitamin E isomer gamma-tocotrienol.

Vitamin E homologues, specifically tocotrienols, have been shown to have favorable effects on bone. They possess properties that are indicative of anti-resorptive activity, suggesting the potential for vitamin E in preventing bone loss. To investigate the anti-resorptive activity of the various vitamin E homologues, we cultured human osteoclasts from blood-derived CD14+ cells on collagen, dentin, and calcium phosphate substrates, with some samples supplemented with vitamin E homologues in their cell culture medium. These were compared to the clinically used bisphosphonate, pamidronate. Compounds were either added at the start of culture to study effects on osteoclast formation, or at the start of osteoclastic resorption to determine their effects on activity. The alpha- and gamma-tocotrienol isomers inhibited osteoclast formation without consequent reduction in total cell number. Only gamma-tocotrienol inhibited osteoclast activity without toxicity. Gamma-tocotrienol was the most potent inhibitor of both osteoclast formation and activity and requires further investigation into its anti-resorptive effects on bone.

Brooks R, Kalia P, Ireland DC, Beeton C…
Int J Vitam Nutr Res Nov 2011
PMID: 22673919

Icariin Stimulates Proliferation and Differentiation of Human Osteoblasts In Vitro

Abstract

Icariine stimulates proliferation and differentiation of human osteoblasts by increasing production of bone morphogenetic protein 2.

Icariine is a flavonoid isolated from a traditional Chinese medicine Epimedium pubescens and is the main active compound of it. Recently, Epimedium pubescens was found to have a therapeutic effect on osteoporosis. But the mechanism is unclear. The aim of the study was to research the effect of Icariine on the proliferation and differentiation of human osteoblasts.
Human osteoblasts were obtained by inducing human marrow mesenchymal stem cells (hMSCs) directionally and were cultured in the presence of various concentrations of Icariine. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) test was used to observe the effect of Icariine on cell proliferation. The activity of alkaline phosphatase (ALP) and the amount of calcified nodules were assayed to observe the effect on cell differentiation. The expression of bone morphogenetic protein 2 (BMP-2) mRNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR).
Icariine (20 microg/ml) increased significantly the proliferation of human osteoblasts. And, Icariine (10 microg/ml and 20 microg/ml) increased the activity of ALP and the amount of calcified nodules of human osteoblasts significantly (P < 0.05). BMP-2 mRNA synthesis was elevated significantly in response to Icariine (20 microg/ml).
Icariine has a direct stimulatory effect on the proliferation and differentiation of cultured human osteoblast cells in vitro, which may be mediated by increasing production of BMP-2 in osteoblasts.

Yin XX, Chen ZQ, Liu ZJ, Ma QJ…
Chin. Med. J. Feb 2007
PMID: 17355822 | Free Full Text

Horny Goat Weed Phytoestrogens Maintain Bone Density Over 2 Years in Women

Abstract

Epimedium-derived phytoestrogen flavonoids exert beneficial effect on preventing bone loss in late postmenopausal women: a 24-month randomized, double-blind and placebo-controlled trial.

Epimedium brevicornum maxim, a nonleguminous medicinal plant, has been found to be rich in phytoestrogen flavonoids. Results from a 24-month randomized double-blind placebo-controlled clinical trial showed that Epimedium-derived phytoestrogen flavonoids were able to exert beneficial effects on preventing bone loss in late postmenopausal women, without resulting in a detectable hyperplasia effect on the endometrium.
We performed a 24-mo randomized double-blind placebo-controlled clinical trial for evaluating the effect of the Epimedium-derived phytoestrogen flavonoids (EPFs) on BMD, bone turnover biochemical markers, serum estradiol, and endometrial thickness in postmenopausal women.
One hundred healthy late postmenopausal women, with a natural menopausal history within 10 approximately 18 yr and with a BMD T-score at the lumbar spine between -2 and -2.5 SD, were randomized into EPF treatment group (n = 50; a daily dose of 60 mg Icariin, 15 mg Daidzein, and 3 mg Genistein) or placebo control group (n = 50). All participants received 300 mg element calcium daily. BMD, bone turnover biochemical markers, serum estradiol, and endometrial thickness were measured at baseline and 12 and 24 mo after intervention.
Eighty-five participants completed the trial. The patterns of BMD changes were significantly different between the EPF treatment group and placebo control group by repeated-measures ANOVA (p = 0.045 for interaction between time and group at femoral neck; p = 0.006 for interaction between time and group at lumbar spine). BMD was found with a decreased tendency in the placebo control group at 12 (femoral neck: -1.4%, p = 0.104; lumbar spine: -1.7%, p = 0.019) and 24 mo (femoral neck: -1.8%, p = 0.048; lumbar spine: -2.4%, p = 0.002), whereas EPF treatment maintained BMD at 12 (femoral neck: 1.1%, p = 0.285; lumbar spine:1.0%, p = 0.158) and 24 mo (femoral neck: 1.6%, p = 0.148; lumbar spine: 1.3%, p = 0.091). The difference in lumbar spine between the two groups was significant at both 12 (p = 0.044) and 24 mo (p = 0.006), whereas the difference in the femoral neck was marginal at 12 mo (p = 0.061) and significant at 24 mo (p = 0.008). Levels of bone biochemical markers did not change in the placebo control group. In contrast, EPF intervention significantly decreased levels of deoxypyrdinoline at 12 (-43%, p = 0.000) and 24 mo (-39%, p = 0.000), except for osteocalcin at 12 (5.6%, p = 0.530) and 24 mo (10.7%, p = 0.267). A significant difference in deoxypyrdinoline between the two groups was found at both 12 (p = 0.000) and 24 mo (p = 0.001). Furthermore, neither serum estradiol nor endometrial thickness was found to be changed in either groups during the clinical trial.
EPFs exert a beneficial effect on preventing bone loss in late postmenopausal women without resulting in a detectable hyperplasia effect on the endometrium.

Zhang G, Qin L, Shi Y
J. Bone Miner. Res. Jul 2007
PMID: 17419678

NAD+ Involved in Stimulation and Maintenance of Osteoblasts In Vitro

Abstract

Extracellular NAD+: a novel autocrine/paracrine signal in osteoblast physiology.

Intercellular communication allows co-ordination of cell metabolism and sensitivity to extracellular stimuli. In bone cells, paracrine stimulation and cell-to-cell coupling through gap junctions induce the formation of complex intercellular networks, which favours the intercellular exchange of nutrients and second messengers, ultimately controlling the process of bone remodelling. The importance of local factors in bone remodelling is known since many years. Bone cells secrete and respond to a variety signals, among which include prostaglandins, cytokines, growth factors, and ATP. We here report evidence that extracellular NAD(+) is a novel extracellular signal stimulating osteoblast differentiation. We found that HOBIT human osteoblastic cells, which are known to express ADP-ribosyl cyclase/CD38 activity, respond to micromolar concentrations of extracellular NAD(+) with oscillatory increases of the cytosolic Ca(2+) concentration. The initial Ca(2+) response was followed by a time-dependent inhibition of cell growth, the appearance of an epithelial morphology, and by an increase of alkaline phosphatase and osteocalcin expression. Under resting condition HOBIT cells release NAD(+) in the extracellular medium and the release is significantly potentiated by mechanical stimulation. Taken together these results point to NAD(+) as a novel autocrine/paracrine factor involved in stimulation and maintenance of the osteoblast differentiated phenotype.

Romanello M, Bicego M, Pirulli D, Crovella S…
Biochem. Biophys. Res. Commun. Dec 2002
PMID: 12445818

Review: Vitamin K2 (MK-4) Monotherapy Modestly Increases Bone Density and Reduces Fractures in Eight Studies

Abstract

Vitamin k2 therapy for postmenopausal osteoporosis.

Vitamin K may play an important role in the prevention of fractures in postmenopausal women with osteoporosis. Menatetrenone is the brand name of a synthetic vitamin K2 that is chemically identical to menaquinone-4. The present review study aimed to clarify the effect of menatetrenone on the skeleton in postmenopausal women with osteoporosis, by reviewing the results of randomized controlled trials (RCTs) in the literature. RCTs that investigated the effect of menatetrenone on bone mineral density (BMD), measured by dual-energy X-ray absorptiometry and fracture incidence in postmenopausal women with osteoporosis, were identified by a PubMed search for literature published in English. Eight studies met the criteria for RCTs. Small RCTs showed that menatetrenone monotherapy decreased serum undercarboxylated osteocalcin (ucOC) concentrations, modestly increased lumbar spine BMD, and reduced the incidence of fractures (mainly vertebral fracture), and that combined alendronate and menatetrenone therapy enhanced the decrease in serum ucOC concentrations and further increased femoral neck BMD. This review of the literature revealed positive evidence for the effects of menatetrenone monotherapy on fracture incidence in postmenopausal women with osteoporosis. Further studies are required to clarify the efficacy of menatetrenone in combination with bisphosphonates against fractures in postmenopausal women with osteoporosis.

Iwamoto J
Nutrients 2014
PMID: 24841104 | Free Full Text

One interesting passage from the full text talks about the unpublished dose range study from Japan:

Orimo, H., et al. “Clinical evaluation of soft capsule menatetrenone (Ea-0167) in the treatment of osteoporosis: late phase II dose study.” J New Remedies Clinics 41 (1992): 1249-79.

A dose-finding study of menatetrenone in Japan [7] administered daily doses of 15, 45, 90, and 135 mg and revealed that 45 mg was the minimum effective dose for improving bone mass parameters evaluated by microdensitometry and/or single photon absorptiometry in postmenopausal women with osteoporosis. This optimal dose (45 mg/day) for the treatment of osteoporosis is about 150–180 times greater than the recommended daily dietary intake of vitamin K (250–300 μg) [8]. No toxic effects of menatetrenone (45 mg/day) have been reported [7]. High-dose vitamin K is needed to prevent fractures in postmenopausal women with osteoporosis [9]. However, the effect of menatetrenone on the skeleton remains a matter of controversy [10–17], and the role of menatetrenone in the treatment of osteoporosis therefore needs to be clarified.

Skipping Breakfast Associated with Lower Bone Density in Young Women

Abstract

Relationship between skipping breakfast and bone mineral density in young Japanese women.

It is well known that insufficient nutrient intake leads to poor bone status. To find a simple evaluation method for prevention of nutrition intake disorder, a cross-sectional study with 275 healthy Japanese female students aged 19-25 was conducted.
Anthropometric parameters, bone mineral density (BMD) at lumbar and total hip, bone metabolic markers and physical activity were measured in study participants and the frequency of skipping meals (breakfast, lunch, supper), and absolute values for nutrient intakes were assessed using a Diet History Questionnaire.
The frequency of skipping breakfast significantly correlate to total energy intake (ρ= -0.276, p<0.001). BMI, total intake of energy, intake of protein, intake of phosphate, and energy expenditure positively correlated significantly to BMD at lumbar and total hip (p<0.05) using simple linear regression. BMI (regression coefficient (b))=0.088, p<0.001), bone alkaline phosphatase (b= -0.050, p=0.012), total energy expenditure (b=0.019, p<0.001), and frequency of skipping breakfast (b= -0.018, p=0.048) were independent risk factors for lower total hip BMD by multiple regression analysis. The total hip BMD in participants who skipped breakfast three or more times was significantly lower than in those who did not skip breakfast (p=0.007).
In conclusion, managing the frequency of skipping breakfast and reducing it to <3 times per week may be beneficial for the maintenance of bone health in younger women.

Kuroda T, Onoe Y, Yoshikata R, Ohta H
Asia Pac J Clin Nutr 2013
PMID: 24231019 | Free Full Text

Breakfast and Exercise in High School Increases Bone Density in Men

Abstract

Consuming breakfast and exercising longer during high school increases bone mineral density in young adult men.

We examined the bone mineral densities (BMDs) of young adult men and analyzed the factors associated with BMD differences. Between 1993 and 2002, all male freshmen in the Wakayama Medical University, Japan were recruited into the present study, which included a self-administrated questionnaire survey, anthropometric measurements, and BMD measurements of the spine and hip. Of a total of 387 freshmen, 382 (98.7 %; mean age, 20.3 years; age range, 18-29 years) completed the study. The mean BMDs of the spine (L2-4) and femoral neck (FN) were 1.21 (standard deviation, 0.13) g/cm(2) and 1.12 (0.14) g/cm(2), respectively. The L2-4 BMDs were not associated with age, while FN BMDs were significantly inversely associated with age. The BMDs at L2-4 and FN were significantly associated with body mass index (BMI). After adjustment for age and BMI, multivariate regression analysis indicated that BMDs at L2-4 and FN were associated with current longer exercise duration (L2-4, p = 0.024; FN, p = 0.001), those at L2-4 with milk intake (p = 0.024), and those at FN with consuming breakfast (p = 0.004). Similarly, habits of consuming breakfast and exercising longer (on a weekly basis) during high school were linked with significantly higher L2-4 and FN BMDs. High-impact activities during high school significantly influenced the later BMDs. In conclusion, to maximize peak bone mass, consuming breakfast and completing a longer duration of stronger exercise in the late high school years for at least 10 h per week is recommended.

Ishimoto Y, Yoshida M, Nagata K, Yamada H…
J. Bone Miner. Metab. May 2013
PMID: 23263782