Tag Archives: animal

Magnesium Suppresses Bone Resorption Rats Fed a High-Phosphorus Diet

Abstract

Dietary magnesium supplementation suppresses bone resorption via inhibition of parathyroid hormone secretion in rats fed a high-phosphorus diet.

This study examined the effects of dietary magnesium (Mg) supplementation on bone turnover and serum parathyroid hormone (PTH) levels in rats fed a high-phosphorus (P) diet. Male rats were randomized by weight into three groups, and fed a control diet (control), a high-P diet (HP) or a high-P and high-Mg diet (HPHMg) for 14 days. Serum osteocalcin levels were significantly higher in the HP and HPHMg groups than in the control group. Serum CTx levels were significantly higher in the HP and HPHMg groups than in the control group, while the levels in the HPHMg group were significantly lower than in the HP group. Serum PTH levels were significantly higher in the HP group than in the control and HPHMg groups. Dietary Mg supplementation had a significant influence on serum PTH levels in the HP and HPHMg groups. These results suggest that dietary Mg supplementation suppresses the high bone resorption induced by a high-P diet via inhibition of PTH secretion. Moreover, our results suggest that dietary Mg supplementation may be beneficial for the prevention of bone loss with high-P diet administration.

Matsuzaki H, Fuchigami M, Miwa M
Magnes Res Sep 2010
PMID: 20810356 | Free Full Text

Review: Vitamin A Increases Fracture Risk at 2x Recommended Intake

Abstract

Vitamin A intake and osteoporosis: a clinical review.

If osteoporosis is linked with vitamin A (Vit A) A consumption, millions of people could be affected. A MEDLINE search was performed with keywords retinol, beta-carotene, and osteoporosis. Of 20 clinical studies, 3 were randomized controlled trials (RCTs), 14 were observational studies, and 3 were case reports. Most (8) observational studies were cross-sectional. Oral retinoyl palmitate (RP) in high doses induces fractures and radiographic osteoporosis in animals. Retinol intake from diet or supplements is negatively associated with lumbar, femoral neck, and trochanter bone mineral density (BMD). There is a graded increase in relative risk of hip fracture with increasing retinol intake, attributable primarily to retinol (either from diet or supplements) but not beta-carotene intake. Higher serum retinol levels are associated with higher risk of any fracture and with higher risk of hip fracture, whereas there is no evidence of harm associated with beta-carotene intake. The few RCTs involve serum markers of bone metabolism, not bone density or fracture outcomes. Observational studies are generally consistent in finding harm from either dietary or supplemental retinol intake on BMD and hip fracture risk. Total Vit A intake is more important than source in determining harm. Adverse effects may occur at a level of retinol intake that is only about twice the current recommendation for adult females.
It is not yet possible to set a specific level of retinol intake above which bone health is compromised. Pending further investigation, Vit A supplements should not be used with the express goal of improving bone health.

Crandall C
J Womens Health (Larchmt) Oct 2004
PMID: 15671709

The recommended dietary allowance (RDA) for Vitamin as preformed Vitamin A (Retinol Activity Equivalents) is 700 mcg (or 2,333 IU). This article suggests that twice that, or 4666 IU, increases fracture risk.

Korean Black Raspberry Increases Osteoblasts and Apoptosis of Osteoclasts in Ovariectomized Rats

Abstract

Bone-protecting effect of Rubus coreanus by dual regulation of osteoblasts and osteoclasts.

Bone loss occurs with increasing age and/or as a secondary occurrence to chronic metabolic disease. Certain nutritional and pharmacological, as well as nonpharmacologic interventions such as weight-bearing exercise and muscle strengthening help prevent bone loss. We examined the effect of the methanol extract from the fruit of Rubus coreanus (RCM) on postmenopausal osteoporosis.
Ovariectomized rats were assigned to sham (negative control), vehicle control, positive control, safflower seed 200 mg/kg, RCM 100 mg/kg (RCM 100), RCM 200 mg/kg (RCM 200), and RCM 400 mg/kg (RCM 400) groups for 10 weeks after the operation. Serum biochemistry, histochemistry, immunohistochemistry, and other related biomarkers of bone metabolism were investigated.
We observed that RCM could prevent bone loss by increasing the femur trabecular bone area in a dose-dependent manner in ovariectomized rats. The mineral composition of RCM contains many more valuable elements, especially potassium, magnesium, and vitamins D and B2, than safflower seed. The effect of RCM increased not only osteoblast differentiation but also osteoclast apoptosis. In addition, the extract of RCM contained in quercetin suggests that the extract of RCM resulted in improved aging-related bone loss through an antioxidant effect.
The present data provide the first direct in vivo evidence that RCM has a bone-protecting effect caused by estrogen deficiency, without undesirable side effects on the uterus and other solid organs. The beneficial effect of RCM may be mediated, at least in part, by dual regulation of the enhancement of osteoblast function and induction of osteoclast apoptosis.

Do SH, Lee JW, Jeong WI, Chung JY…
Menopause
PMID: 18709701

Eldecalcitol > Alfacalcidol in Ovariectomized Rats

Abstract

Effects of combined treatment with eldecalcitol and alendronate on bone mass, mechanical properties, and bone histomorphometry in ovariectomized rats: a comparison with alfacalcidol and alendronate.

Eldecalcitol (ELD), a 2β-hydroxypropyloxy derivative of 1α,25 (OH) 2D3, inhibits bone resorption more potently than alfacalcidol (ALF) while maintaining osteoblastic function in an ovariectomized (OVX) osteoporosis rat model. Alendronate (ALN), which is the most common bisphosphonate used for the treatment of osteoporosis, increases the bone mineral density (BMD) by suppressing bone resorption. In this study, we investigated the effects of combination treatments with ELD and ALN or with ALF and ALN on bone mass and strength in OVX rats. Seventy female rats, 32 weeks old, were assigned to seven groups: (1) a sham-operated control group; (2) an OVX-control group; (3) an ELD group; (4) an ALF group; (5) an ALN group; (6) an ELD+ALN group; and (7) an ALF+ALN group. OVX rats were orally treated with ELD (0.015 μg/kg), ALF (0.0375 μg/kg), or ALN (0.2mg/kg) daily for 12 weeks. In both the lumbar spine and the femur, ELD and ALF monotherapy significantly increased the BMD, and ELD+ALN and ALF+ALN significantly increased the BMD, compared with ALN monotherapy, as an additive effect. In particular, ELD+ALN resulted in a significantly higher BMD than ALF+ALN in the femur. On mechanical testing of the lumbar spine, ELD and ALF monotherapy significantly increased the ultimate load, and ELD+ALN and ALF+ALN significantly increased the ultimate load compared with ALN monotherapy. In the femur, ELD, ELD+ALN, and ALF+ALN treatment significantly increased the ultimate load, compared with the OVX-control group, and ELD+ALN resulted in a significantly higher ultimate load than ALN monotherapy. A histomorphometric analysis showed that ELD monotherapy and ELD+ALN combination therapy had a potent inhibitory effect on bone resorption parameters (osteoclast surface and eroded surface), while maintaining bone formation parameters (osteoblast surface and osteoid surface). By contrast, ALF and ALF+ALN significantly lowered the histological parameters of both bone resorption and formation. These results suggested that ELD or ALF used in combination with ALN has therapeutic advantages over ALN monotherapy, with ELD+ALN combination treatment producing an especially beneficial anti-osteoporotic effect by inhibiting osteoclastic bone resorption and maintaining osteoblastic function, compared with ALF+ALN combination treatment.

Sugimoto M, Futaki N, Harada M, Kaku S
Bone Jan 2013
PMID: 23041510

Vitamin K2 and/or Raloxifene Improves Bone in Ovariectomized Rats

Abstract

Raloxifene and vitamin K2 combine to improve the femoral neck strength of ovariectomized rats.

We evaluated the skeletal effects of two osteoporosis therapies in an ovariectomized rat model, raloxifene and vitamin K2, as well as the vitamin K2 plus raloxifene (K + Ral) combination. In two studies, 6-month-old rats were ovariectomized, except for sham-ovariectomy controls (Sham), and dosed orally with vehicle, 30 mg/kg vitamin K2, 1 mg/kg raloxifene, or the combination of K + Ral for 6 weeks following surgery. Vitamin K2 had no effect on serum estrogen, low-density lipoprotein cholesterol (LDL-C), or urinary deoxypyridinoline levels, but slightly increased osteocalcin levels compared to Ovx. Raloxifene lowered total cholesterol, LDL-C, osteocalcin, and urinary deoxypyridinoline levels to below Ovx levels, while having no effect on estrogen levels. Raloxifene, but not vitamin K2, prevented ovariectomy-induced loss of bone in the distal femoral metaphysis and proximal tibial metaphysis, as did the K + Ral combination. Raloxifene, but not vitamin K2, partially prevented, loss of vertebral bone mineral density (BMD), whereas K + Ral had BMD greater than that of Ovx. Vitamin K2 increased bone formation rate to above Ovx, whereas raloxifene and K + Ral reduced bone formation rate to Sham levels. Vitamin K2 had no effect on eroded surface compared to Ovx, while raloxifene and K + Ral reduced eroded surface to Sham levels. Groups were not different in the BMD of femoral midshaft; however vitamin K2 was observed to increase periosteal mineralizing surface of the tibial shaft to above Ovx, while raloxifene reduced periosteal mineralizing surface toward Sham levels. Femoral neck strength was not different between groups, indicating no significant beneficial effect of either raloxifene or vitamin K2 at this site. However, K + Ral had reproducibly greater femoral neck strength than Ovx or Sham. Raloxifene, but not vitamin K2, partially prevented loss of lumbar vertebra strength; but K + Ral was not different from Sham or Ovx. Therefore, raloxifene and vitamin K2 had complementary effects on bone resorption and formation activities, respectively, resulting in a reproducible, significant improvement of femoral neck strength. These rat data suggest interesting therapeutic possibilities that may require clinical verification.

Iwamoto J, Yeh JK, Schmidt A, Rowley E…
Calcif. Tissue Int. Aug 2005
PMID: 16059775

Curcumin + Alendronate Synergy in Ovariectomized Rats

Abstract

A synergistic bone sparing effect of curcumin and alendronate in ovariectomized rat.

The purpose of this study was to evaluate the therapeutic effects of combination therapy with curcumin and alendronate on bone remodeling after ovariectomy in rats.
Eighty female Sprague-Dawley rats underwent either a sham operation (the sham group) or bilateral ovariectomy (OVX). The ovariectomized animals were randomly distributed amongst four groups: untreated OVX group, curcumin-administered group, alendronate-administered group, and the combination therapy group. At 8 and 12 weeks after surgery, rats from each of the groups were euthanized. Serum biochemical markers of bone turnover, including osteocalcin and alkaline phosphatase (ALP), and the telopeptide fragment of type I collagen C-terminus (CTX) were analyzed. Bone histomorphometric parameters of the 4th lumbar vertebrae were determined by micro-computed tomography (CT). In addition, mechanical strength was determined by a three-point bending test.
Serum biochemical markers of bone turnover in the experiment groups (curcumin administered group, alendronate administered group, and the combination therapy group) were significantly lower than in the untreated OVX group (p < 0.05). The combination therapy group had lower ALP and CTX-1 concentrations at 12 weeks, which were statistically significant compared with the curcumin only and the alendronate only group (p < 0.05). The combination therapy group had a significant increase in BMD at 8 weeks and Cr.BMD at 12 weeks compared with the curcumin-only group (p = 0.005 and p = 0.013, respectively). The three point bending test showed that the 4th lumbar vertebrae of the combination therapy group had a significantly greater maximal load value compared to that of the curcumin only and the alendronate only group (p < 0.05).
The present study demonstrated that combination therapy with a high dose of curcumin and a standard dose of alendronate has therapeutic advantages over curcumin or alendronate monotherapy, in terms of the synergistic antiresorptive effect on bone remodeling, and improving bone mechanical strength.

Cho DC, Kim KT, Jeon Y, Sung JK
Acta Neurochir (Wien) Dec 2012
PMID: 23053289

High-Dose Curcumin Increases Bone Strength and Density in Ovariectomized Rats

Abstract

Therapeutic advantages of treatment of high-dose curcumin in the ovariectomized rat.

Although curcumin has a protective effect on bone remodeling, appropriate therapeutic concentrations of curcumin are not well known as therapeutic drugs for osteoporosis. The purpose of this study was to compare the bone sparing effect of treatment of low-dose and high-dose curcumin after ovariectomy in rats.
Forty female Sprague-Dawley rats underwent either a sham operation (the sham group) or bilateral ovariectomy (OVX). The ovariectomized animals were randomly distributed among three groups; untreated OVX group, low-dose (10 mg/kg) curcumin administered group, and high-dose (50 mg/kg) curcumin group. At 4 and 8 weeks after surgery, serum biochemical markers of bone turnover were analyzed. Bone histomorphometric parameters of the 4th lumbar vertebrae were determined by micro-computed tomography (CT). In addition, mechanical strength was determined by a three-point bending test.
High-dose curcumin group showed significantly lower osteocalcin, alkaline phosphatase, and the telopeptide fragment of type I collagen C-terminus concentration at 4 and 8 weeks compared with the untreated OVX group as well as low-dose curcumin group. In the analyses of micro-CT scans of 4th lumbar vertebrae, the high-dose curcumin treated group showed a significant increase in bone mineral densities (p=0.028) and cortical bone mineral densities (p=0.036) compared with the low-dose curcumin treated group. Only high-dose curcumin treated group had a significant increase of mechanical strength compared with the untreated OVX group (p=0.015).
The present study results demonstrat that a high-dose curcumin has therapeutic advantages over a low-dose curcumin of an antiresorptive effect on bone remodeling and improving bone mechanical strength.

Cho DC, Jung HS, Kim KT, Jeon Y…
J Korean Neurosurg Soc Dec 2013
PMID: 24527187 | Free Full Text

Curcumin Decreases Bone Density in Rats

Abstract

Effects of curcumin on the skeletal system in rats.

There is increasing interest in the discovery of natural compounds that could favorably affect the skeletal system. Curcumin is a constituent of turmeric, a plant which has been used for centuries as a dietary spice and a traditional Indian medicine. Curcumin has been reported to affect differentiation, activity and the lifespan of osteoblasts and osteoclasts in vitro. The aim of the present study was to investigate the effects of curcumin on the skeletal system of rats in vivo. Curcumin (10 mg/kg, po daily) was administered for four weeks to normal (non-ovariectomized) and bilaterally ovariectomized (estrogen-deficient) three-month-old female Wistar Cmd:(WI)WU rats. Ovariectomy was performed seven days before the start of curcumin administration. Bone mass, mineral and calcium content, macrometric and histomorphometric parameters, as well as the mechanical properties of the bone, were examined. Serum total cholesterol and estradiol levels were also determined. In rats with normal estrogen levels, curcumin decreased serum estradiol level and slightly increased cancellous bone formation, along with decreased mineralization. Estrogen deficiency induced osteoporotic changes in the skeletal system of the ovariectomized control rats. In ovariectomized rats, curcumin decreased body mass gain and serum total cholesterol level, slightly improved some bone histomorphometric parameters impaired by estrogen deficiency, but did not improve bone mineralization or mechanical properties. In conclusion, the results of the present in vivo study in rats did not support the hypothesis that curcumin, at doses that are readily achievable through dietary intake, could be useful for the prevention or treatment of osteoporosis.

Folwarczna J, Zych M, Trzeciak HI
Pharmacol Rep
PMID: 21098873 | Free Full Text

Curcumin Prevents Bone Loss in Ovariectomized Rats

Abstract

Curcumin protects against ovariectomy-induced bone loss and decreases osteoclastogenesis.

Curcumin has anti-oxidative activity. In view of the increasing evidence for a biochemical link between increased oxidative stress and reduced bone density we hypothesized that curcumin might increase bone density by elevating antioxidant activity in some target cell type. We measured bone density by Micro-CT, enzyme expression levels by quantitative PCR or enzyme activity, and osteoclast (OC) formation by tartrate-resistant acid phosphatase staining. The bone mineral density of the femurs of curcumin-administered mice was significantly higher than that of vehicle-treated mice after ovariectomy (OVX) and this was accompanied by reduced amounts of serum collagen-type I fragments, which are markers of bone resorption. Curcumin suppressed OC formation by increasing receptor activator of nuclear factor-κB ligand (RANKL)-induced glutathione peroxidase-1, and reversed the stimulatory effect of homocysteine, a known H(2) O(2) generator, on OC formation by restoring Gpx activity. Curcumin generated an aberrant RANKL signal characterized by reduced expression of nuclear factor of activated T cells 2 (NFAT2) and attenuated activation of mitogen-activated protein kinases (ERK, JNK, and p38). Curcumin thus inhibited OVX-induced bone loss, at least in part by reducing osteoclastogenesis as a result of increased antioxidant activity and impaired RANKL signaling. These findings suggest that bone loss associated with estrogen deficiency could be attenuated by curcumin administration.

Kim WK, Ke K, Sul OJ, Kim HJ…
J. Cell. Biochem. Nov 2011
PMID: 21732406

The ovariectomized, mature rat model of postmenopausal osteoporosis: an assessment of the bone sparing effects of curcumin.

Abstract

The ovariectomized, mature rat model of postmenopausal osteoporosis: an assessment of the bone sparing effects of curcumin.

Identification of natural health products that might benefit skeletal health could reduce the negative impact of osteoporotic bone fractures upon society. The objectives of this study were to evaluate an animal model of postmenopausal osteoporosis and to search for evidence that curcumin reduces bone mineral losses in a dose-dependent manner when endogenous estrogen levels are reduced. Bone mineral density was measured at the spine, femur and whole body before and at 2, 4 and 6 months after ovariectomy in each of 40 mature rats. Serum osteocalcin and C-telopeptide were measured as indicators of bone formation and resorption rates. Femoral compressive strength was measured at 6 months. Ovariectomy alone resulted in loss of mineral from the spine (p<0.005) and an increase in osteocalcin levels (p<0.05). At the same time, there was an increase in energy to fracture (p<0.01) due to an increased bone size. When ovariectomized animals were given etidronate there was no loss of mineral from the spine, the size of the femur increased (p<0.005), C-telopeptide levels were reduced (p<0.001) and femoral compressive strength increased (p<0.025). Administration of curcumin to ovariectomized animals resulted in changes that were intermediate between those produced by etidronate and by ovariectomy alone. The increase in femur size produced by the highest dose of curcumin was statistically significant (p< 0.01) and curcumin administration resulted in a significant, dose dependent, increase in energy to fracture. Curcumin produces beneficial changes in bone turnover and increases in bone strength using the ovariectomized mature rat model of postmenopausal osteoporosis.

French DL, Muir JM, Webber CE
Phytomedicine Dec 2008
PMID: 18693096