Chinese Lizard’s Tail Prevents Bone Loss in Ovariectomized Rats

Abstract

Antiosteoporotic activity of Saururus chinensis extract in ovariectomized rats.

Recent studies suggest that phytoestrogens may exert a protective effect against osteoporosis. This study examined whether treatment with phytoestrogen extracts from Saururus chinensis (SC) exerted a preventive effect on estrogen-deficiency-induced osteoporosis. Six- to seven-month-old female Sprague-Dawley rats were randomly assigned into either a sham-operated group or one of three ovariectomy (OVX) subgroups: OVX treated with vehicle, OVX with alendronate, and OVX with SC extract (SC). Rats began receiving treatment 4 weeks before the OVX treatment and continued receiving treatment for an additional 10 weeks after OVX (for a combined total of 14 weeks). The results showed that the SC treatment prevented loss of femur bone mineral density after OVX, as determined by a significant decrease in the levels of serum bone turnover markers osteocalcin and alkaline phosphatase as well as urinary deoxypyridinoline. Micro-computed tomography analysis showed that the SC treatment significantly prevented decreases in bone volume/tissue volume, trabecular number and trabecular thickness, while also preventing an increase in trabecular separation. It was concluded that SC treatment could prevent OVX-induced loss of bone mass and deterioration in trabecular microarchitecture by suppressing bone turnover, thereby maintaining bone structural integrity. Further, no stimulation of proliferation of uterine tissue was noted. Therefore, it is suggested that treatment with S. chinensis extracts might be a potential alternative therapy for treating postmenopausal osteoporosis.

Sung MJ, Davaatseren M, Hur HJ, Kim HJ…
Phytother Res Aug 2012
PMID: 22821855

Huang Jing Prevents Osteoporosis in Ovariectomized Rats

Abstract

Protective effects of Polygonatum sibiricum polysaccharide on ovariectomy-induced bone loss in rats.

To assess the ability of traditional Chinese medicine Polygonatum sibiricum polysaccharide to prevent bone loss in the ovariectomized rat.
PSP was administered intragastrically to the rats. After 35 days, the total body bone mineral density (BMD) was assessed in all of the rats. All sections were processed for immunohistochemistry and hematoxylin-eosin staining (H.E.).
BMD was lower in the ovariectomized group (OVX, 0.163 g/cm(2)), the group that received a moderate dose of PSP on OVX animals (OVX+MP, 0.163 g/cm(2)) and the group that received a low dose of PSP on OVX animals (OVX+LP, 0.162 g/cm(2)) than in the sham-operated group (SHAM, 0.180 g/cm(2)), the OVX+E(2) group (OVX+E(2), 0.176 g/cm(2)) and the group that received a high dose of PSP on OVX animals (OVX+HP, 0.174 g/cm(2)) (P<0.05). Clear arrangements of bone trabeculae were observed in the OVX+E(2) and OVX+HP. The expression of bone morphogenetic proteins (BMP) and basic fibroblast growth factor (bFGF) in the OVX, OVX+MP and OVX+LP was down regulated compared to the SHAM, OVX+E(2) and OVX+HP (P<0.05). The rats in the OVX+E(2) and OVX+HP had lower levels of bone Gla protein (BGP), bone alkaline phosphatase (BALP), tartrate-resistant acid phosphatase (TRAP) and tumor necrosis factor α(TNF-α) expression than the rats in the OVX, OVX+MP and OVX+LP (P<0.05).
This experiment demonstrates that the administration of PSP to ovariectomized rats reverses bone loss and prevents osteoporosis.

Zeng GF, Zhang ZY, Lu L, Xiao DQ…
J Ethnopharmacol Jun 2011
PMID: 21550389

Pine Bark Decreases Bone Turnover in Ovariectomized Rats

Abstract

Protective effect of Pycnogenol® on ovariectomy-induced bone loss in rats.

Pycnogenol® (PYC) is a natural plant extract from the bark of Pinus pinaster and has potent antioxidant activities. The protective effect of PYC on bone loss was studied in multiparous ovariectomized (OVX) female rats. Pycnogenol® (30 or 15 mg/kg body weight/day) was administered orally to 8-month-old OVX rats for 3 months. At the end of the experiment, bone strength was measured by a three-point bending test and bone mineral density was estimated by peripheral quantitative computed tomography. Ovariectomy significantly decreased femur bone strength and bone density. Supplementation with PYC suppressed the bone loss induced by OVX. The OVX treatment significantly increased serum osteocalcin (OC) and C-terminal telopeptide of type I collagen (CTx). Supplementation with PYC reduced the serum OC and CTx in OVX rats to a level similar to that of the sham-operated group. The results indicated that orally administered PYC can decrease the bone turnover rate in OVX rats, resulting in positive effects on the biomechanical strength of bone and bone mineral density.

Mei L, Mochizuki M, Hasegawa N
Phytother Res Jan 2012
PMID: 21710590

Ecdysone Increases Trabecular Bone in Ovariectomized Rats

Abstract

Beneficial effects of beta-Ecdysone on the joint, epiphyseal cartilage tissue and trabecular bone in ovariectomized rats.

Ecdysteroids are steroids found in invertebrates and plants. In mammals they have protein anabolic effects. We have recently published antiosteoporotic effects of Tinospora cordifolia (TC) extract and the search for the possible active ingredients yielded the presence of beta-Ecdysone (Ecd). Therefore, we investigated the effects of pure Ecd in ovariectomized rats on morphological changes in joint, epiphyseal cartilage and trabecular tissue. Following ovariectomy rats were fed for 1 month with Ecd containing food at a dose of 52.8 mg/day/animal. Positive and negative control animals received 17-beta Estradiol (E(2), 132 microg/day/animal) and soy free (sf) food respectively. At sacrifice, specimens consisting of upper tibiae-lower femurs and knee joint were harvested and processed for histomorphometry. The parameters measured included thickness of the joint cartilage, thickness of the whole epiphyseal growth plate and its three zones. Furthermore, the percentage of trabecular bone in the metaphysis region of tibiae was quantified. Ecd and E(2) induced a significant increase in the thickness of joint cartilage. The whole epiphyseal growth plate and its proliferative and hypertrophic zones were also increased by Ecd whereas E(2) reduced their size. The percentage of trabecular area in the metaphysis of tibia was significantly increased in Ecd and E(2) treated animals. Results provide a plausible explanation for the antiosteoporotic effects of TC. Hence, TC as well as other Ecd producing plants or pure Ecd may be of value in the prevention and treatment of osteoporosis and osteoarthritis which is of increasing importance due to aging and obesity among individuals.

Kapur P, Wuttke W, Jarry H, Seidlova-Wuttke D
Phytomedicine Apr 2010
PMID: 20171072

Ecdysone has Bone Protective Effects in Ovariectomized Rats

Abstract

Beta-ecdysone has bone protective but no estrogenic effects in ovariectomized rats.

Estrogens exert beneficial effects in the bone. Their chronic use however bares several risks. Therefore intensive search for non-estrogenic, bone protective compounds is going on. We observed that an extract of Tinospora cordifolia has antiosteoporotic effects and identified 20-OH-Ecdysone (beta-Ecdysone=Ecd) as a possible candidate for this action. Ovariectomized (ovx) rats were treated orally over 3 months with no Ecd (control) or 18, 57 or 121 mg Ecd/day/animal. Estradiol-17beta benzoate (E2) 159 microg/day/animal) fed animals served as positive controls. Bone mineral density (BMD) of tibia was measured by quantitative computer tomography, serum Osteocalcin and CrossLaps were measured in a ligand binding assay. Utilizing an estrogen receptor (ER) containing cytosolic extract of porcine uteri the capability of Ecd to bind to ER was tested. Ecd did not bind to ER. BMD was reduced by more than 50% in the control. In the Ecd animals BMD was dose dependently higher. Serum CrossLaps was lower in the Ecd and E2 group while serum Osteocalcin levels were decreased in the E2 but increased in the Ecd fed animals. Ecd has an antiosteoporotic effect which does not involve activation of ER.

Seidlova-Wuttke D, Christel D, Kapur P, Nguyen BT…
Phytomedicine Sep 2010
PMID: 20554186

Beta Blocker Prevents Bone Loss in Pediatric Burn Patients

Abstract

Long-term propranolol use in severely burned pediatric patients: a randomized controlled study.

To determine the safety and efficacy of propranolol given for 1 year on cardiac function, resting energy expenditure, and body composition in a prospective, randomized, single-center, controlled study in pediatric patients with large burns.
Severe burns trigger a hypermetabolic response that persists for up to 2 years postburn. Propranolol given for 1 month postburn blunts this response. Whether propranolol administration for 1 year after injury provides a continued benefit is currently unclear.
One-hundred seventy-nine pediatric patients with more than 30% total body surface area burns were randomized to control (n = 89) or 4 mg/kg/d propranolol (n = 90) for 12 months postburn. Changes in resting energy expenditure, cardiac function, and body composition were measured acutely at 3, 6, 9, and 12 months postburn. Statistical analyses included techniques that adjusted for non-normality, repeated-measures, and regression analyses. P < 0.05 was considered significant.
Long-term propranolol treatment significantly reduced the percentage of the predicted heart rate and percentage of the predicted resting energy expenditure, decreased accumulation of central mass and central fat, prevented bone loss, and improved lean body mass accretion. There were very few adverse effects from the dose of propranolol used.
Propranolol treatment for 12 months after thermal injury, ameliorates the hyperdynamic, hypermetabolic, hypercatabolic, and osteopenic responses in pediatric patients. This study is registered at clinicaltrials.gov: NCT00675714.

Herndon DN, Rodriguez NA, Diaz EC, Hegde S…
Ann. Surg. Sep 2012
PMID: 22895351

Beta Blockers Reversed Bone Loss in Calorie Restricted Rats

Abstract

Blocking β-adrenergic signaling attenuates reductions in circulating leptin, cancellous bone mass, and marrow adiposity seen with dietary energy restriction.

We tested whether β-adrenergic blockade attenuates bone loss and increased marrow adiposity during energy restriction (ER) and whether such an effect is associated with changes in serum leptin and leptin expression in bone and marrow tissues. Female 4-mo-old Sprague-Dawley rats were assigned into four groups (n = 10 each): two groups of 40% ER treated with vehicle (ERVEH; saline) or β-blocker (ERBB; DL-propranolol; 250 μg · kg(-1) · h(-1)) during 12 wk, and two groups of ad libitum-fed controls treated with the same two agents (CONVEH, CONBB, respectively). Over 84 days, CONVEH and CONBB rats gained but ERVEH and ERBB rats lost body fat mass; lean mass did not change in any group. Reduction in serum leptin in ERVEH rats was mitigated in ERBB rats (-5.32 vs. -1.15 ng/ml, respectively). The decline in proximal tibia cancellous vBMD observed in ERVEH rats was attenuated in ERBB rats (-85.24 vs. -53.94 mg/cm(3), respectively). Adipocyte number in ERVEH rats was dramatically higher vs. CON rats at week 12, but this increment was abolished by β-blockade in ERBB animals. The number of osteoblastic cells and marrow adipocytes staining positively for leptin in ERVEH rats tended to be lower vs. that of both CON groups, but β-blockade appears to reverse this effect in ERBB rats. In summary, β-adrenergic blockade mitigated metaphyseal bone loss and bone marrow adiposity during energy restriction and attenuated reductions in serum leptin. These data suggest an important role for β-adrenoreceptor signaling pathway in the cancellous bone and marrow fat response to energy restriction.

Baek K, Bloomfield SA
J. Appl. Physiol. Dec 2012
PMID: 22995391

Beta Blockers Prevent Bone Loss from Inner Ear Lesions in Rats

Abstract

Bone remodeling is regulated by inner ear vestibular signals.

Bone remodeling allows the conservation of normal bone mass despite constant changes in internal and external environments. The adaptation of the skeleton to these various stimuli led credence to the notion that bone remodeling is a true homeostatic function, and as such is under the control of specific centers in the central nervous system (CNS). Hypothalamic and brainstem centers, as well as the sympathetic nervous system (SNS), have been identified as regulators of bone remodeling. However, the nature of the afferent CNS stimuli that may modulate CNS centers involved in the control of bone remodeling, with the exception of leptin, remains unclear. Based on the partial efficacy of exercise and mechanical stimulation regimens to prevent microgravity-induced bone loss and the known alterations in vestibular functions associated with space flights, we hypothesized that inner ear vestibular signals may contribute to the regulation of bone remodeling. Using an established model of bilateral vestibular lesions and microtomographic and histomorphometric bone analyses, we show here that induction of bilateral vestibular lesion in rats generates significant bone loss, which is restricted to weight-bearing bones and associated with a significant reduction in bone formation, as observed in rats under microgravity conditions. Importantly, this bone loss was not associated with reduced locomotor activity or metabolic abnormalities, was accompanied with molecular signs of increased sympathetic outflow, and could be prevented by the β-blocker propranolol. Collectively, these data suggest that the homeostatic process of bone remodeling has a vestibulo-sympathetic regulatory component and that vestibular system pathologies might be accompanied by bone fragility.

Vignaux G, Besnard S, Ndong J, Philoxène B…
J. Bone Miner. Res. Apr 2013
PMID: 23553797

Beta Blockers May be Anticatabolic in Rats

Abstract

[Operational mechanism modification of bone mechanostat in an animal model of nutritional stress: effect of propranolol].

Propranolol (P) treatment exerts a preventive effect against the detrimental consequences to bone status in mildly chronically food-restricted growing rats (NGR) by an increment in cortical bone and by improving its spatial distribution.
To study the effect of beta-blocker on operational mechanism of bone mechanostat in an animal model of nutritional stress,

weanling male Wistar rats were randomly assigned to four groups: control (C), C + P (CP), NGR and NGR + P (NGRP). C and CP rats were fed freely with the standard diet. NGR and NGRP rats received, for 4 weeks, 80% of the amount of food consumed by C and CP respectively, the previous day, corrected by body weight. Propranolol (7 mg/kg/day) was injected ip 5 days per week, for four weeks in CP and NGRP rats. C and NGR received saline injections at an identical dosage regimen. Body weight and length were determined during the experimental period. Dietary intake was registered daily. Animals were sacrificed after 4 weeks of food restriction. Immediately, cuadriceps, femur and tibiae from each animal were dissected and weighed, and histomorphometric and mechanical studies were performed. Serum a-CTX, osteocalcin, intact PTH, calcium and phosphorous were determined. Body protein (% prot) was measured in all groups.
Food restriction induced detrimental effects on body and femoral growth, load-bearing capacity (Wf), % prot and cuadriceps weight in NGR us. C (p < 0.01). beta-blocker did not modify anthropometric and bone morphometric parameters in NGRP and CP vs. NGR and C, respectively (p > 0.05). However, Wf NGRP vs. NGR was significantly higher (p < 0.01). alpha-CTX was significantly higher in NGR vs. C (p < 0.01). No significant differences were observed in alpha-CTX levels between CP, NGRP and C (p > 0.05). Serum osteocalcin, intact PTH, calcium and phospho- rous showed no significant difference between groups (p > 0.05).
These results suggest that modeling increase in bone mass and strength in NGRP rats could be due to an anticatabolic interaction of the beta-blocker propranolol on operational mechanism of bone mechanostat in an animal model of nutritional stress.

Pintos PM, Lezón CE, Bozzini C, Friedman SM…
Rev. Invest. Clin.
PMID: 23745443

Beta Blocker Lowers Fracture Risk in Men and Women

Abstract

Association between beta-blocker use and fracture risk: the Dubbo Osteoporosis Epidemiology Study.

In animal model, mice treated with beta-blockers (BB) had increased bone mass. In humans, high bone mass is associated with reduce fracture risk. The present study sought to test the hypothesis that BB use is associated with reduced fracture risk.
Data from 3488 participants (1285 men) aged 50 years and above in the Dubbo Osteoporosis Epidemiology Study (DOES) were analyzed. Baseline characteristics of participants were obtained at the initial visit which had taken place between 1989 and 1993. Bone mineral density (BMD) at the lumbar spine and femoral neck was measured by dual energy X-ray absorptiometry (GE-LUNAR Corp, Madison, WI). Two hundred and sixty two (20%) men and 411 (19%) women had been on BB, as ascertained by direct interview and verification with medication history. The incidence of fragility fractures was ascertained during the follow-up period (1989-2008).
In men, BB use was associated with higher BMD at the femoral neck (0.96 versus 0.92 g/cm², P < 0.01), higher lumbar spine (1.32 versus 1.25 g/cm², P < 0.01), and lower fracture risk than those not on BB (odds ratio [OR]: 0.49; 95% CI: 0.32-0.75). In women, BB users also had higher femoral neck BMD (0.83 versus 0.81 g/cm², P < 0.01), higher lumbar spine BMD (1.11 versus 1.06 g/cm², P < 0.01), and lower risk of fracture than non-users (OR 0.68, 95% CI: 0.53-0.87). The associations between BB use and fracture risk were independent of age, BMD, and clinical risk factors. Subgroup analysis suggested that the association was mainly found in selective BB, not in non-selective BB.
Beta-blockers use, particularly selective BB, was associated with reduced fracture risk in both men and women, and the association was independent of BMD.

Yang S, Nguyen ND, Center JR, Eisman JA…
Bone Mar 2011
PMID: 21047567