Constructive effect of exogenous melatonin against osteoporosis after ovariectomy in rats

OBJECTIVE: To analyze histomorphometric, densitometric and biochemical effects of melatonin on osteoporosis in ovariectomized rats. STUDY DESIGN: Wistar rats were divided into 6 groups. Group C: control; Group I: bilateral ovariectomy (OVX); Group II: OVX + vehicle; Group III: OVX + 10 mg/kg/day melatonin (MLT); Group IV: OVX + 30 mg/kg/day MLT; Group V: sham + 10 mg/kg/day MLT. Cortex, trabecula, osteoblast and osteoclast numbers were evaluated on vertebra and femur histomorphometrically. Hydroxyproline analysis was used to determine collagen content of femur and vertebrae. Bone mineral density and bone mineral content were measured. RESULTS: Trabecular thickness and trabecular area of vertebra and femur and cortical thickness of femur showed remarkable decrease after OVX, but increased after MLT treatment in the OVX+MLT groups. Following OVX, no statistically significant difference was found in number of osteoblasts or osteoclasts, trabecular number or levels of hydroxyproline after treatment with MLT. OVX caused significant decrease in bone mineral density, but treatment with MLT was unable to reverse this effect. CONCLUSION: MLT may trigger microscopic changes in bone, and time of application is critical for clinical recovery. It can be effective in helping treat postmenopausal osteoporosis. However, it is contraindicated in women who have normal-functioning ovaries.     

Jump exercise during remobilization restores integrity of the trabecular architecture after tail suspension in young rats.

Three-dimensional trabecular architecture was investigated in the femora of tail-suspended young growing rats, and the effects of jump exercise during remobilization were examined. Five-week-old male Wistar rats (n = 35) were randomly assigned to five body weight-matched groups: tail-suspended group (SUS; n = 7); sedentary control group for SUS (S(CON); n = 7); spontaneous recovery group after tail suspension (S+R(CON), n = 7); jump exercise group after tail suspension (S+R(JUM); n = 7); and age-matched control group for S+R(CON) and S+R(JUM) without tail suspension and exercise (S(CON)+R(CON); n = 7). Rats in SUS and S(CON) were killed immediately after tail suspension for 14 days. The jump exercise protocol consisted of 10 jumps/day, 5 days/wk, and jump height was 40 cm. Bone mineral density (BMD) of the femur and three-dimensional trabecular bone architecture at the distal femoral metaphysis were measured. Tail suspension induced a 13.6% decrease in total femoral BMD (P < 0.001) and marked deterioration of trabecular architecture. After 5 wk of free remobilization, femoral BMD, calf muscle weight, and body weight returned to age-matched control levels, but trabeculae remained thinner and less connected. On the other hand, S+R(JUM) rats showed significant increases in trabecular thickness, number, and connectivity compared with S+R(CON) rats (62.8, 31.6, and 24.7%, respectively; P < 0.05), and these parameters of trabecular architecture returned to the levels of S(CON)+R(CON). These results indicate that suspension-induced trabecular deterioration persists after remobilization, but jump exercise during remobilization can restore the integrity of trabecular architecture and bone mass in the femur in young growing rats.     

Differential effects of jump versus running exercise on trabecular architecture during remobilization after suspension-induced osteopenia in growing rats

High-impact exercise is considered to be very beneficial for bones. We investigated the ability of jump exercise to restore bone mass and structure after the deterioration induced by tail suspension in growing rats and made comparisons with treadmill running exercise. Five-week-old male Wistar rats (n = 28) were randomly assigned to four body weight-matched groups: a spontaneous recovery group after tail suspension (n = 7), a jump exercise group after tail suspension (n = 7), a treadmill running group after tail suspension (n = 7), and age-matched controls without tail suspension or exercise (n = 7). Treadmill running was performed at 25 m/min, 1 h/day, 5 days/wk. The jump exercise protocol consisted of 10 jumps/day, 5 days/wk, with a jump height of 40 cm. Bone mineral density (BMD) of the total right femur was measured by dual-energy X-ray absorptiometry. Three-dimensional trabecular bone architecture at the distal femoral metaphysis was evaluated using microcomputed tomography. After 5 wk of free remobilization, right femoral BMD, right hindlimb muscle weight, and body weight returned to age-matched control levels, but trabeculae remained thinner and less connected. Although both jump and running exercises during the remobilization period increased trabecular bone mass, jump exercise increased trabecular thickness, whereas running exercise increased trabecular number. These results indicate that restoration of trabecular bone architecture induced by jump exercise during remobilization is predominantly attributable to increased trabecular thickness, whereas running adds trabecular bone mass through increasing trabecular number, and suggest that jumping and running exercises have different mechanisms of action on structural characteristics of trabecular bone.     

Treatment with tacrolimus enhances alveolar bone formation and decreases osteoclast number in the maxillae: a histomorphometric and ultrastructural study in rats

Recent studies have suggested that tacrolimus monotherapy is a beneficial therapeutic alternative for the normalization of cyclosporin-induced bone loss in animal models and humans. The mechanism accounting for this action is unclear at present. In the present study, we attempted to determine the effect of tacrolimus monotherapy on alveolar bone using histological, histomorphometric and transmission electron microscopy (TEM). Groups of rats (n=10 each) were treated with either tacrolimus (1mg/kg/day, s.c.) or drug vehicle for 60 days. Fragments containing maxillary molars were processed for light microscopy to investigate the alveolar bone volume, trabecular separation, number of osteoclasts and osteoblasts, and transmission electron microscopy to investigate their ultrastructural basic phenotype. Treatment with tacrolimus monotherapy during 60 days may induce increases in alveolar bone volume (BV/TV,%; P<0.05) and a non-significant decrease in trabecular separation (Tb.Sp,mm; P>0.05), represented by a decrease in osteoclast number (N.Oc/BS; P<0.05) and maintenance of osteoblast number (N.Ob/BS; P>0.05). Osteoblasts were often observed as a continuous layer of active cells on the bone surface. Osteoclasts appeared to be detached from the resorbed bone surface, which was often filled by active osteoblasts and collagen-rich matrix. Moreover, osteoclasts in the treated group were frequently observed as inactive cells (without ruffled border, clear zone and detached from the bone surface). Within the limits of the present study, we conclude that tacrolimus leads to an increase in alveolar bone formation, which probably exerts action on osteoclasts. Tacrolimus could, therefore, play a crucial role in the control of both early osteoclast differentiations from precursors, as well as in functional activation.     

Comparative effects of alendronate and alfacalcidol on cancellous and cortical bone mass and bone mechanical properties in ovariectomized rats.

The purpose of the present study was to compare the effects of alendronate and alfacalcidol on cancellous and cortical bone mass and bone mechanical properties in ovariectomized rats. Twenty-six female Sprague-Dawley rats, 7 months of age, were randomized by the stratified weight method into four groups: the sham-operated control (Sham) group and the three ovariectomy (OVX) groups, namely, OVX + vehicle, OVX + alendronate (2.5 mg/kg, p.o., daily), and OVX + alfacalcidol (0.5 mug/kg, p.o., daily). At the end of the 8-week experimental period, bone histomorphometric analyses of cancellous bone at the proximal tibial metaphysis and cortical bone at the tibial diaphysis were performed, and the mechanical properties of the femoral distal metaphysis and femoral diaphysis were evaluated. OVX decreased cancellous bone volume per total tissue volume (BV/TV), and the maximum load of the femoral distal metaphysis, as a result of increases in serum osteocalcin (OC) levels, and also the number of osteoclasts (N.Oc), osteoclast surface (OcS) and bone formation rate (BFR) per bone surface (BS), and BFR/BV, without any effect on cortical area (Ct Ar), or maximum load of the femoral diaphysis. Alendronate prevented this decrease in cancellous BV/TV by suppressing increases in N.Oc/BS, OcS/BS, BFR/BS, and BFR/BV, without any apparent effect on Ct Ar, or maximum load of the femoral distal metaphysis and femoral diaphysis. On the other hand, alfacalcidol increased cancellous BV/TV, Ct Ar, and the maximum load of the femoral distal metaphysis and femoral diaphysis, by mildly decreasing trabecular BFR/BV, maintaining trabecular mineral apposition rate and osteoblast surface per BS, increasing periosteal and endocortical BFR/BS, and preventing an increase in endocortical eroded surface per BS. The present study clearly showed the differential skeletal effects of alendronate and alfacalcidol in ovariectomized rats. Alendronate prevented OVX-induced cancellous bone loss by suppressing bone turnover, while alfacalcidol improved cancellous and cortical bone mass and bone strength by suppressing bone resorption and maintaining or even increasing bone formation.     

A novel mathematical model of bone remodelling cycles for trabecular bone at the cellular level

After an initial phase of growth and development, bone undergoes a continuous cycle of repair, renewal and optimisation by a process called remodelling. This paper describes a novel mathematical model of the trabecular bone remodelling cycle. It is essentially formulated to simulate a remodelling event at a fixed position in the bone, integrating bone removal by osteoclasts and formation by osteoblasts. The model is developed to construct the variation in bone thickness at a particular point during the remodelling event, derived from standard bone histomorphometric analyses. The novelties of the approach are the adoption of a predator-prey model to describe the dynamic interaction between osteoclasts and osteoblasts, using a genetic algorithm-based solution; quantitative reconstruction of the bone remodelling cycle; and the introduction of a feedback mechanism in the bone formation activity to co-regulate bone thickness. The application of the model is first demonstrated by using experimental data recorded for normal (healthy) bone remodelling to predict the temporal variation in the number of osteoblasts and osteoclasts. The simulated histomorphometric data and remodelling cycle characteristics compare well with the specified input data. Sensitivity studies then reveal how variations in the model's parameters affect its output; it is hoped that these parameters can be linked to specific biochemical factors in the future. Two sample pathological conditions, hypothyroidism and primary hyperparathyroidism, are examined to demonstrate how the model could be applied more broadly, and, for the first time, the osteoblast and osteoclast populations are predicted for these conditions. Further data are required to fully validate the model's predictive capacity, but this work shows it has potential, especially in the modelling of pathological conditions and the optimisation of the treatment of those conditions.     

Ultrastructural changes in bones of the senescence-accelerated mouse (SAMP6): a murine model for senile osteoporosis

SAMP6, a substrain of senescence-accelerated mice, was developed as an animal model for senile osteoporosis. In the present study, we investigated the bone morphology, together with serum calcium and bone mineral density (BMD) in SAMP6 and age-matched normal mice SAMR1. We did not find any significant differences between SAMR1 and SAMP6 at 1 month of age with regard to the serum compositions and bone morphology. As compared with SAMR1, BMD, the femoral weight, femoral calcium and phosphorus levels were significantly reduced in SAMP6 at 2 and 5 months of age. The number of osteoblasts in trabecular bones was also significantly reduced. Swollen mitochondria and myelin-like structures were found in osteoblasts and osteocytes of SAMP6 mice at 2 and 5 months of age. There was a greater proportion of resting surface and less forming surface in the femoral endosteal surfaces of SAMP6 mice. The amount of trabecular bone in the lumbar vertebra and the distal metaphysis of the femur was reduced. The number of the mast cells in bone marrow of the tibia significantly increased in SAMP6 mice. These findings indicate that the lower bone mass in SAMP6 was due to the reduction in osteoblast formation and suggested that mast cells in bone marrows play a role in the pathogenesis of senile osteoporosis.     

Bone loss in the ovariectomized baboon Papio ursinus: densitometry, histomorphometry and biochemistry

To develop a non-human primate model of systemic bone loss after ovariectomy, 24 ovariectomized (OVX) and eight control (non-OVX) female baboons Papio ursinus were investigated over a period of 48 months using bone mineral density (BMD), iliac crest bone histomorphometry, bone turnover markers, and variables of calcium metabolism. Lumbar spine (L1-L4) BMD measured by dual energy X-ray absorptiometry (DXA) decreased in OVX animals in the first 12 months (-7.6%) and showed a slow trend towards recovery after 24 months. Controls showed a slow increase in spinal BMD over 4 years (+9.7%). Total hip BMD decreased slowly up to 48 months in all animals (OVX -12.6%versus controls -10%); this indicated that OVX had a limited effect on total hip BMD. Forearm BMD did not change. The significant decrease in trabecular bone volume (TBV) of the iliac crest from baseline to 12 months was followed by some recovery. Microarchitectural deterioration of trabecular bone in OVX animals was demonstrated by a decline in trabecular number and an increase in trabecular spacing. These changes were also evident on sections of whole vertebrae, proximal femora and iliac crests. Changes in iliac TBV reflected spinal but not hip BMD changes in the OVX animals. Static and dynamic histomorphometric variables indicated that bone turnover was increased for 36 months following OVX. Controls showed no changes in histomorphometric variables. Bone specific alkaline phosphatase (ALPs) in OVX animals remained elevated throughout the study; osteocalcin (OC) was significantly elevated only at 6 and 12 months, and deoxypyridinoline (Pyr-D) was elevated at 12 months but declined after 24 months. ALPs was thus more sensitive to the long-term effects of OVX than were OC or Pyr-D. Controls showed no changes in bone turnover markers. This study showed consistent deleterious changes in lumbar BMD, bone histomorphometry with microarchitectural deterioration together with altered biochemical markers of bone turnover in the first 12 months after OVX. Since these changes resemble those in post-menopausal women, the non-human primate Papio ursinus is suitable for the study of bone loss in post-menopausal women.     

益坤精胶囊对骨质疏松模型小鼠骨形态和血清中IL-6表达的影响

目的:观察益坤精胶囊对骨质疏松模型小鼠骨形态计量学指标及血清白介素-6(IL-6)的影响。方法:取60只C57雌性小鼠随机分为:模型组(等体积生理盐水)、雌激素组(尼尔雌醇,0.25 mg/kg)、益坤精胶囊高剂量组(1.44 g/kg)、中剂量组(0.72 g/kg)、低剂量组(0.36 g/kg)及假手术组(等体积生理盐水),各组灌胃均70 d。采用酶联免疫吸附测定(ELISA)法检测血清中IL-6浓度,BI-2000医学图像分析系统进行骨形态计量学指标检测,使用CT测量分析各组小鼠股骨远侧干骺端血管数量。结果:与假手术组比较,模型组骨小梁平均宽度、骨皮质平均厚度、骨小梁面积、成骨细胞数以及骨密度、骨血管数量均明显减小,而破骨细胞数、血清中IL-6的浓度明显上升(P0.05)。与模型组比较,雌激素组、益坤精胶囊高、中、低剂量组上述指标均明显改善(P0.05),且益坤精胶囊高剂量组与雌激素组疗效相当(P0.05)。结论:益坤精胶囊可明显改善骨质疏松模型小鼠的骨形态计量学指标,降低血清中IL-6水平,增加骨血管数量,且以1.44 g/kg益坤精胶囊灌胃效果最佳。     

Attenuation of bone mass and increase of osteoclast formation in decoy receptor 3 transgenic mice

Decoy receptor 3 (DcR3), a soluble receptor for FasL, LIGHT, and TL1A, induces osteoclast formation from monocyte, macrophage, and bone stromal marrow cells. However, the function of DcR3 on bone formation remains largely unknown. To understand the function of DcR3 in bone formation in vivo, transgenic mice overexpressing DcR3 were generated. Bone mineral density (BMD) and bone mineral content (BMC) of total body were significantly lower in DcR3 transgenic mice as compared with wild-type controls. The difference in BMD and BMC between DcR3 transgenic and control mice was confirmed by histomorphometric analysis, which showed a 35.7% decrease in trabecular bone volume in DcR3 transgenic mice in comparison with wild-type controls. The number of osteoclasts increased in DcR3 transgenic mice. In addition, local administration of DcR3 (30 microg/ml, 10 microl, once/day) into the metaphysis of the tibia via the implantation of a needle cannula significantly decreased the BMD, BMC, and bone volume of secondary spongiosa in tibia. Local injection of DcR3 also increased osteoclast numbers around trabecular bone in tibia. Furthermore, coadminstration of soluble tumor necrosis factor receptor inhibitor/Fc chimera (TNFRSF1A) but not osteoprotegerin inhibited the action of DcR3. In addition, in an assay of osteoclast activity on substrate plates, DcR3 significantly increased the resorption activity of mature osteoclasts. Treatment with higher concentrations of DcR3 slightly increased nodule formation and alkaline phosphatase activity of primary cultured osteoblasts. These results indicate that DcR3 may play an important role in osteoporosis or other bone diseases.     

IL-6, IL-1β及TNF-α与大鼠骨质疏松形成的关系

目的:研究白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)及肿瘤坏死因子-α(TNF-α)与大鼠骨质疏松形成的关系,为研究细胞因子与骨质疏松之间的相关作用机制提供参考。方法:选择2015年1月至2015年11月我院采购的90只雌性大鼠作为研究对象,按照数字随机法将大鼠分成观察组(n=45)以及对照组(n=45)。观察组制成骨质疏松模型,对照组不作处理,对比两组局部骨密度,成骨细胞,骨小梁以及破骨细胞在视野面积中的比例,骨组织相关细胞因子水平,分析IL-6、IL-1β以及TNF-α水平与大鼠骨质疏松的相关性。结果:观察组椎体骨密度(BD)和椎间盘BD以及小关节BD均明显低于对照组,差异均有统计学意义(P0.05);观察组骨小梁和成骨细胞在视野面积中的比例明显低于对照组,而破骨细胞在视野面积中的比例明显高于对照组,差异均有统计学意义(P0.05);观察组IL-6和IL-1β以及TNF-α均明显高于对照组,差异有统计学意义(P0.05)。IL-6、IL-1β以及TNF-α水平与大鼠椎体BD、椎间盘BD以及小关节BD均呈明显负相关。结论:去卵巢大鼠的细胞因子与其骨质疏松具有紧密联系,表现在IL-6、IL-1β以及TNF-α水平与大鼠椎体BD、椎间盘BD以及小关节BD均呈明显负相关。     

Targeted overexpression of G protein-coupled receptor kinase-2 in osteoblasts promotes bone loss

To investigate the role of G protein-coupled receptor kinases (GRKs) in regulating bone formation in vivo, we overexpressed the potent G protein-coupled receptor (GPCR) regulator GRK2 in osteoblasts, using the osteocalcin gene-2 promoter to target expression to osteoblastic cells. Using the parathyroid hormone (PTH) receptor as a model system, we found that overexpression of GRK2 in osteoblasts attenuated PTH-induced cAMP generation by mouse calvaria ex vivo. This decrease in GPCR responsiveness was associated with a reduction in bone mineral density (BMD) in transgenic (TG) mice compared with non-TG littermate controls. The decrease in BMD was most prominent in trabecular-rich lumbar spine and was not observed in cortical bone of the femoral shaft. Quantitative computed tomography indicated that the loss of trabecular bone was due to a decrease in trabecular thickness, with little change in trabecular number. Histomorphometric analyses confirmed the decrease in trabecular bone volume and demonstrated reduced bone remodeling, as evidenced by a decrease in osteoblast numbers and osteoblast-mediated bone formation. Osteoclastic activity also appeared to be reduced because urinary excretion of the osteoclastic activity marker deoxypyridinoline was decreased in TG mice compared with control animals. Consistent with reduced coupling of osteoblast-mediated bone formation to osteoclastic bone resorption, mRNA levels of both osteoprotegrin and receptor activator of NF-kappaB ligand were altered in calvaria of TG mice in a pattern that would promote a low rate of bone remodeling. Taken together, these data suggest that enhancing GRK2 activity and consequently reducing GPCR activity in osteoblasts produces a low bone-turnover state that reduces bone mass.     

骨质疏松兔松质骨微观结构和微观成分的时间序贯性变化

目的:研究去势手术建立骨质疏松兔模型中松质骨微观结构和微观成分的时间序贯性变化。方法:40只新西兰白兔随机分为假手术组(sham组,n=20)和骨质疏松组(OP组,n=20)。OP组兔子给予去势手术处理,sham组给予假手术处理。分别于术后的0周、4周、6周、8周,利用DXA测量腰椎骨密度(每组每个时间点选择5只动物)。之后处死动物,采集腰椎标本。利用Micro-CT、FTIR、腰椎轴向压缩试验得到松质骨的微观结构、微观成分(骨矿盐晶体和胶原)和宏观力学参数。利用t检验比较同一时间点两组之间的相关参数。结果:OP组BMD逐渐下降,松质骨微观结构逐渐疏松,微观组成属性逐渐改变,宏观力学强度均逐渐下降。FTIR在4周时即检测到OP组腰椎骨矿盐和胶原基质比(P=0.046)、骨矿盐结晶度(P=0.018)、胶原交联比(P=0.006)发生显著性改变,早于BMD和微观结构的变化。OP组腰椎宏观生物力学强度在第8周时达到最低点(P=0.001)。结论:去势手术后,腰椎松质骨骨矿盐晶体和胶原属性最早发生变化,松质骨微观成分和微观结构的改变是导致椎体强度明显改变的原因。FTIR技术可以较早的检测到骨质疏松发生过程中骨组织微观成分的改变。     

Physical activity in osteopenia treatment improved the mass of bones directly and indirectly submitted to mechanical impact

The effect of physical activity in the treatment of osteopenia induced by ovariectomy was studied in 34 two-month-old Wistar female rats. Animals were divided into three groups in which two were formed by ovariectomized (OVX) animals and the other one had sham-operated animals. Group 1, active OVX'd rats; group 2, sedentary OVX'd rats and group 3, sham-operated ones (control). After three months of daily physical activity in a motor-driven treadmill all rats were sacrificed. In order to perform a histomorphometric analysis, long bones, vertebrae, and nasal bone were selected at necropsy. Ovariectomized rats which exercised showed an increased trabecular bone volume, cortical thickness in the long bones and vertebrae and also an increased nasal bone thickness. Physical activity also increased the connection of osteocytes. It was concluded that physical activity in osteopenia treatment increases and restores the mass of bones directly and indirectly submitted to physical impact.     

The effect of restriction of dietary calcium on trabecular and cortical bone mineral density in the rats

This study aimed to investigate effects of restricted calcium intake on cortical and trabecular bone density in white rats. Low Ca diet was fed for six weeks, and bone density and bone metabolism parameters were assessed in blood. This study was carried out on 12 male white rats aged 12 weeks (Sprague-Dawley; SD). These rats were bred for 1 week and randomly assigned to the standard calcium diet group (SCa group, n = 6) and the low calcium diet group (LCa group; n = 6). The SCa group was given a modified AIN-93M mineral mix (with 0.5% Ca), which was made by adding calcium to a standard AIN93 diet, and the LCa Group was fed a modified AIN-93 Mineral mix (with 0.1% Ca). Femoral BMD and BMC were measured by DEXA in each rat. After trabecular bone was separated from cortical bone, volumetric bone mineral density (vBMD) was measured using pQCT. Serum Ca and P levels were measured as parameters of bone metabolism, and S-ALP, S-TrACP and-Dpd levels were also measured. The results revealed no significant differences in weight, growth rate, feed consumption and feed efficiency between the two groups before and after calcium-restricted diet (p > .05). No significant differences were also observed in bone length and bone mass between the two groups (p > .05). Although bilateral femoral BMDs were not significantly different between the two groups, bilateral femoral BMCs significantly decreased in the LCa group, compared with the SCa group (p = .023, p = .047). Bilateral cortical MDs were not significantly different between the two groups, either. However, trabecular BMD significantly decreased in the LCa group, compared with the SCa group (p = .041). U-Dpd and S-TrACP levels significantly declined in the LCa group, compared to the SCa group (p = .039, p = .010). There were no significant differences in serum Ca and P levels between the two groups (p > .05). However, a significant decrease in urinary Ca level (p = .001) and a significant increase in urinary P (p = .001) were observed in the LCa group, compared to the Sca group. These findings described that six-week low calcium diet led to decreased trabecular bone density, reduced urinary excretion of Ca and increased urinary excretion of P. As a result, Ca hemeostasis can be maintained.     

Fluoxetine treatment increases trabecular bone formation in mice

Mounting evidence exists for the operation of a functional serotonin (5-HT) system in osteoclasts and osteoblasts, which involves both receptor activation and 5-HT reuptake. In previous work we showed that the serotonin transporter (5-HTT) is expressed in osteoclasts and that its activity is required by for osteoclast differentiation in vitro. The purpose of the current study was to determine the effect of treatment with fluoxetine, a specific serotonin reuptake inhibitor, on bone metabolism in vivo. Systemic administration of fluoxetine to Swiss-Webster mice for 6 weeks resulted in increased trabecular BV and BV/TV in femurs and vertebrae as determined by micro-computed tomography (microCT). This correlated with an increase in trabecular number, connectivity, and decreased trabecular spacing. Fluoxetine treatment also resulted in increased volume in vertebral trabecular bone. However, fluoxetine-treated mice were not protected against bone loss after ovariectomy, suggesting that its anabolic effect requires the presence of estrogen. The effect of blocking the 5-HTT on bone loss following an LPS-mediated inflammatory challenge was also investigated. Subcutaneous injections of LPS over the calvariae of Swiss-Webster mice for 5 days resulted in increased numbers of osteoclasts and net bone loss, whereas new bone formation and a net gain in bone mass was seen when LPS was given together with fluoxetine. We conclude that fluoxetine treatment in vivo leads to increased bone mass under normal physiologic or inflammatory conditions, but does not prevent bone loss associated with estrogen deficiency. These data suggest that commonly used anti-depressive agents may affect bone mass.     

Response of cortical and cancellous bones to mild calcium deficiency in young growing female rats: a bone histomorphometry study.

The purpose of the present study was to clarify the differences in the alterations of cellular activities of osteoblasts and osteoclasts, mineralization, and bone mass in cortical and cancellous bones of young growing rats with mild calcium deficiency. Twenty female Sprague-Dawley rats, 6 weeks of age, were randomized by the stratified method into two groups with 10 rats in each group: 0.5% (normal) calcium diet group and 0.1% (low) calcium diet group. After 10 weeks of feeding, bone histomorphometric analysis was performed on cancellous bone of the proximal tibia as well as cortical bone of the tibial shaft. Calcium deficiency increased eroded surface (ES/bone surface [BS]) and the number of osteoclast (N.Oc/BS) with an increase in osteoblast surface (ObS/BS), but decreased bone formation rate (BFR/BS) in cancellous bone. However, cancellous bone volume was preserved, while cortical bone area was decreased as a result of decreased periosteal bone gain and enlargement of the marrow cavity. These results suggest that short-term mild calcium deficiency in young growing female rats increased bone resorption by increasing osteoclastic recruitment, and suppressed mineralization followed by increased osteoblastic recruitment in cancellous bone, but cancellous bone loss was counteracted through redistribution of calcium from cortical bone to cancellous bone.     

Cranberry juice improved antioxidant status without affecting bone quality in orchidectomized male rats

BACKGROUND: We reported that drinking citrus juice improves bone quality in orchidectomized senescent male rats. Because cranberry juice, like citrus, is rich in nutrients and phenolic compounds, beneficial effects of citrus juice might also be seen with cranberry juice. An experiment evaluated effect of drinking cranberry juice on bone quality in orchidectomized rats. METHODS: Thirty-two 1-year-old male rats were randomized to two groups: a sham-control group (n=8) and an orchidectomized group (n=24). The treatments for the 4 months duration of the study were SHAM, orchidectomy (ORX), ORX+drinking either 27% or 45% cranberry juice concentrate added to drinking water. At the termination of the study, the rats were euthanized, blood was collected for plasma antioxidant status and IGF-I. The femur, tibia and the 4th lumbar were evaluated for bone quality. Total calcium and magnesium concentration in the femurs were also evaluated. RESULTS: ORX did not affect red blood cell (RBC)-induced hemolysis despite lowering (p<0.05) plasma antioxidant capacity; reduced (p<0.05) plasma IGF-I, femoral density, femoral strength, time-induced femoral fracture, bone mineral content, bone mineral area; numerically (p=0.07) lowered 4th lumbar density; decreased (p<0.05) trabecular connectivity, trabecular number, femoral ash; increased (p<0.05) trabecular separation in comparison to the SHAM group. Drinking cranberry juice increased (p<0.05) plasma antioxidant status, protected RBC against hemolysis, but had no positive effect on bone quality or bone mineral status. CONCLUSIONS: Cranberry juice increases plasma antioxidant status without affecting bone quality.     

Cortical Bone Morphological and Trabecular Bone Microarchitectural Changes in the Mandible and Femoral Neck of Ovariectomized Rats

ObjectiveThis study used microcomputed tomography (micro-CT) to evaluate the effects of ovariectomy on the trabecular bone microarchitecture and cortical bone morphology in the femoral neck and mandible of female rats.ResultsRegarding the trabecular bone microarchitectural parameters, the BV/TV of the trabecular bone microarchitecture in the femoral necks of the control group (61.199±11.288%, median ± interquartile range) was significantly greater than that of the ovariectomized group (40.329±5.153%). Similarly, the BV/TV of the trabecular bone microarchitecture in the mandibles of the control group (51.704±6.253%) was significantly greater than that of the ovariectomized group (38.486±9.111%). Furthermore, the TbSp of the femoral necks in the ovariectomized group (0.185±0.066 mm) was significantly greater than that in the control group (0.130±0.026mm). Similarly, the TbSp of the mandibles in the ovariectomized group (0.322±0.047mm) was significantly greater than that in the control group (0.285±0.041mm). However, the TbTh and TbN trends for the mandibles and femoral necks were inconsistent between the control and ovariectomized groups. Regarding the cortical bone morphology parameters, the TtAr of the femoral necks in the ovariectomized group was significantly smaller than that in the control group. There was no significant difference in the TtAr, CtAr, or CtTh of the femoral necks between the control and ovariectomized groups, and no significant difference in the CtTh of the mandibles between the control and ovariectomized groups. Moreover, the BV/TV and TbSp of the mandibles were highly correlated with those of the femurs (r_s = 0.874 and r_s = 0.755 for BV/TV and TbSp, respectively). Nevertheless, the TbTh, TbN, and CtTh of the mandibles were not correlated with those of the femoral necks.ConclusionAfter the rats were ovariectomized, osteoporosis of the trabecular bone microarchitecture occurred in their femurs and mandibles; however, ovariectomy did not influence the cortical bone morphology. In addition, the parametric values of the trabecular bone microarchitecture in the femoral necks were highly correlated with those of the trabecular bone microarchitecture in the mandibles.