Amount Of Trabecular Bone Research Articles

Marrow adipose tissue accumulation and dysgenesis of the trabecular bone after anterior cruciate ligament transection and reconstruction in the rat proximal tibial epiphysis

The accumulation of marrow adipose tissue (MAT) is frequently associated with bone loss. Although anterior cruciate ligament (ACL) injury induces bone loss, MAT accumulation after ACL injury has not been evaluated. In addition, no information about changes in MAT after ACL reconstruction is available. In this study, we aimed to examine (1) the effects of ACL transection on the amounts of trabecular bone and MAT present, and (2) whether ACL reconstruction inhibits the changes in the trabecular bone and MAT that are induced by ACL transection. ACL transection alone or with immediate reconstruction was performed on the right knees of rats. Untreated left knees were used as controls. Histomorphological changes in the trabecular bone and MAT in the proximal tibial epiphysis were examined prior to surgery and at one, four, and 12 weeks postsurgery. The trabecular bone area on the untreated side increased in a time-dependent manner. However, after ACL transection, the trabecular bone area did not increase during the experimental period, indicating dysgenesis of the bone (bone loss). Dysgenesis of the trabecular bone after ACL transection was attenuated by ACL reconstruction. MAT accumulation due to adipocyte hyperplasia and hypertrophy had been induced by ACL transection by four weeks postsurgery. This ACL transection-induced MAT accumulation was not prevented by ACL reconstruction. Based on these results, we conclude that (1) dysgenesis of the bone in the proximal tibia following ACL transection is accompanied by MAT accumulation, and (2) ACL reconstruction attenuates dysgenesis of the trabecular bone but cannot prevent MAT accumulation.

Spine Metastases in Immunocompromised Mice after Intracardiac Injection of MDA-MB-231-SCP2 Breast Cancer Cells.

Simple SummaryBreast cancer cells typically metastasize to bone, where their interaction with bone remodeling cell types enhances metastatic outgrowth and osteolytic bone destruction. The respective knowledge is largely based on xenograft models, where human breast cancer cells are injected into immunocompromised mice. Importantly, however, whereas skeletal analyses in these animals are usually restricted to hindlimb bones, human skeletal metastases are far more frequent in the spine. Therefore, our study addressed the question, if breast cancer cells injected into immunocompromised mice would also metastasize to the spine, and if this process is influenced by the amount of trabecular bone. We injected an established breast cancer cell line into immunocompromised mice with or without a transgene causing severe osteoporosis. Importantly, we found more tumor cell clusters of different size in spine sections than in femora, but the presence of the transgene did not affect their spreading and metastatic outgrowth.Breast cancer cells frequently metastasize to bone, where their interaction with bone remodeling cell types enhances osteolytic bone destruction. Importantly, however, whereas skeletal analyses of xenograft models are usually restricted to hindlimb bones, human skeletal metastases are far more frequent in the spine, where trabecular bone mass is higher compared to femur or tibia. Here, we addressed whether breast cancer cells injected into immunocompromised mice metastasize to the spine and if this process is influenced by the amount of trabecular bone. We also took advantage of mice carrying the Col1a1-Krm2 transgene, which display severe osteoporosis. After crossing this transgene into the immunocompromised NSG background we injected MDA-MB-231-SCP2 breast cancer cells and analyzed their distribution three weeks thereafter. We identified more tumor cells and clusters of different size in spine sections than in femora, which allowed influences on bone remodeling cell types to be analyzed by comparing tumor-free to tumor-burdened areas. Unexpectedly, the Col1a1-Krm2 transgene did not affect spreading and metastatic outgrowth of MDA-MB-231-SCP2 cells, suggesting that bone tumor interactions are more relevant at later stages of metastatic progression.

Recovery of the maternal skeleton after lactation is impaired by advanced maternal age but not by reduced IGF availability in the mouse.

Lactation results in substantial maternal bone loss that is recovered following weaning. However, the mechanisms underlying this recovery, and in particular the role of insulin-like growth factor 1 (IGF-I), is not clear. Furthermore, there is little data regarding whether recovery is affected by advanced maternal age. Using micro-computed tomography, we studied bone recovery following lactation in mice at 2, 5 and 7 months of age. We also investigated the effects of reduced IGF-I availability using mice lacking PAPP-A2, a protease of insulin-like growth factor binding protein 5 (IGFBP-5). In 2 month old mice, lactation affected femoral trabecular and cortical bone, but only cortical bone showed recovery 3 weeks after weaning. This recovery was not affected by deletion of the Pappa2 gene. The amount of trabecular bone was reduced in 5 and 7 month old mice, and was not further reduced by lactation. However, the recovery of cortical bone was impaired at 5 and 7 months compared with at 2 months. Recovery of the maternal skeleton after lactation is impaired in moderately-aged mice compared with younger mice. Our results may be relevant to the long-term effects of breastfeeding on the maternal skeleton in humans, particularly given the increasing median maternal age at childbearing.

Hydrogen gas protects against ovariectomy-induced osteoporosis by inhibiting NF-κB activation.

Osteoporosis is a prevalent condition among postmenopausal women, and lacks satisfactory therapeutic options. Hydrogen (H2) has been shown to be effective in alleviating many diseases. This study aimed to investigate the effects of H2 on inhibiting osteoclastogenesis and bone loss in ovariectomized mice. Osteoclast differentiation from Raw264.7 cells was induced with receptor activator NF-κB ligand (RANKL) with or without 60% H2. The number and resorption activity of osteocalsts were assessed by tartrate-resistant acid phosphatase staining and pit formation assay, respectively. The expression of osteoclast markers and NF-κB phosphorylation were detected by western blot. NF-κB nuclear translocation was assessed by immunofluorescence. NF-κB transcriptional activity was analyzed by luciferase assay. Bone loss in mice was induced by ovariectomy (OVX). OVX mice were given either regular air or 60% H2. Bone structure was analyzed by micro-computed tomography and hematoxylin and eosin staining. Cytokine levels were measured by enzyme-linked immunosorbent assay. The data were analyzed with one-way or two-way ANOVA followed by Bonferroni post hoc tests. H2 did not have any measurable effect on the proliferation of Raw264.7 cells. The number of osteoclasts and size of resorption pits of RANKL+H2-treated cells were 3 to 4 times less than RANKL treated cells. The expression of osteoclast marker genes of RANKL+H2-treated cells was 30% to 60% lower than RANKL-treated cells (P < 0.05). H2 markedly inhibited RANKL-induced activation, nuclear translocation, and transcriptional activity of NF-κB (P < 0.05, RANKL+H2 vs RANKL). The amount and density of trabecular bone and bone mineral density of ovariectomized mice were significantly less than sham-operated mice (P < 0.05 OVX vs sham). The amount of trabecular bone and bone mineral density of OVX mice that inhaled H2 were more than 40% higher, whereas the levels of serum proinflammatory cytokine interleukin 1β, IL-6, and tumor necrosis factor-α were more than 50% lower than those of OVX mice (P < 0.05). These results demonstrated that H2 could be an effective therapeutic agent of postmenopausal osteoporosis.

Peri-implant stress correlates with bone and cement morphology: Micro-FE modeling of implanted cadaveric glenoids.

Aseptic loosening of cemented joint replacements is a complex biological and mechanical process, and remains a clinical concern especially in patients with poor bone quality. Utilizing high resolution finite element analysis of a series of implanted cadaver glenoids, the objective of this study was to quantify relationships between construct morphology and resulting mechanical stresses in cement and trabeculae. Eight glenoid cadavers were implanted with a cemented central peg implant. Specimens were imaged by micro-CT, and subject-specific finite element models were developed. Bone volume fraction, glenoid width, implant-cortex distance, cement volume, cement-cortex contact, and cement-bone interface area were measured. Axial loading was applied to the implant of each model and stress distributions were characterized. Correlation analysis was completed across all specimens for pairs of morphological and mechanical variables. The amount of trabecular bone with high stress was strongly negatively correlated with both cement volume and contact between the cement and cortex (r = -0.85 and -0.84, p < 0.05). Bone with high stress was also correlated with both glenoid width and implant-cortex distance. Contact between the cement and underlying cortex may dramatically reduce trabecular bone stresses surrounding the cement, and this contact depends on bone shape, cement amount, and implant positioning.

Effects of preexisting microdamage, collagen cross‐links, degree of mineralization, age, and architecture on compressive mechanical properties of elderly human vertebral trabecular bone

Previous studies have shown that the mechanical properties of trabecular bone are determined by bone volume fraction (BV/TV) and microarchitecture. The purpose of this study was to explore other possible determinants of the mechanical properties of vertebral trabecular bone, namely collagen cross-link content, microdamage, and mineralization. Trabecular bone cores were collected from human L2 vertebrae (n = 49) from recently deceased donors 54-95 years of age (21 men and 27 women). Two trabecular cores were obtained from each vertebra, one for preexisting microdamage and mineralization measurements, and one for BV/TV and quasi-static compression tests. Collagen cross-link content (PYD, DPD, and PEN) was measured on surrounding trabecular bone. Advancing age was associated with impaired mechanical properties, and with increased microdamage, even after adjustment by BV/TV. BV/TV was the strongest determinant of elastic modulus and ultimate strength (r² = 0.44 and 0.55, respectively). Microdamage, mineralization parameters, and collagen cross-link content were not associated with mechanical properties. These data indicate that the compressive strength of human vertebral trabecular bone is primarily determined by the amount of trabecular bone, and notably unaffected by normal variation in other factors, such as cross-link profile, microdamage and mineralization.

Grand challenges in bone endocrinology.

Grand challenges in bone endocrinology.

Carbamazepine and bone mineral metabolism.

The status of bone mineral metabolism was studied in 21 epileptic out-patients receiving carbamazepine as the sole anticonvulsant drug. Hypocalcaemia was found in 3, hypophosphataemia in one and elevated serum alkaline phosphatase in 4 of the cases. Serum 25-hydroxyvitamin D values were significantly lower in the patients than in the controls. No statistically significant difference was observed in bone mineral density between the patients and controls. Histomorphometric analysis of the iliac crest cancellous bone did not reveal any statistically significant difference in the amount of trabecular bone or osteoid between the patients and controls, but the patients had an increased amount of trabecular resorption surfaces. An increased amount of osteoid, suggesting histological osteomalacia, was found in 2 of the 18 biopsies. We conclude that epileptic out-patients receiving carbamazepine therapy have vitamin D deficiency and may develop osteomalacic changes in their skeleton.

Osteomalacia in institutionalized epileptic patients on long-term anticonvulsant therapy

The occurrence of anticonvulsant osteomalacia was studied in 31 epileptic inpatients, 16 women and 15 men. Disturbances in biochemical parameters indicating osteomalacia were frequent. Thirty two per cent of the patients were hypocalcemic, 55% had an increase in S-ALP and 26% in U-HOP, and dU-Ca was decrease in 55%. The S-25OHD3 concentrations were significantly lower in the patients compared with healthy controls. BMD was decreased in females but not in males compared wih the controls. Histomorphometric analysis revealed an increase in the amount of osteoid, but the amount of trabecular bone was no lower than in the controls. The amount of resorption surfaces was increased in the females, but not in the males. The patients who took less physical activity had a pronounced decrease in BMD. The conclusion drawn was that osteomalacia is a frequent complication of long-term anticonvulsant medication, especially among institutionalized patients.

Long-term tissue response to bioabsorbable poly- l-lactide and metallic screws: An experimental study

Late, clinically manifest, adverse inflammatory reactions have sometimes occurred after the use of slowly degrading bioabsorbable poly- l-lactide (PLLA) devices in clinical series of bone fixation. In this study, long-term tissue response to bioabsorbable fracture fixation screws made of poly- l-lactide and to similar metallic screws in cancellous bone was examined and compared with intact bone. The postoperative evaluation of the rabbit femora was performed by using plain radiography, microradiography, histology, histomorphometry, and oxytetracycline labeling studies. The follow-up times were 36 and 51 months in groups of 15 and 14 rabbits, respectively. A walling-off response by formation of trabecular bone which outlined the screw profile was observed in the PLLA and metallic groups both. Connective tissue between this bone front and the implant was seen only in the PLLA group. There was no difference in the thickness of the layer between the two follow-up groups. Between the surgically handled femora and the intact control bone, there was no statistically significant difference in the amount of trabecular bone. The osteoid formation activity in the tissue–implant interface showed no differences between the groups. However, active osteoblasts were visible only in the PLLA group. The amount of birefringent PLLA material diminished between the 36-month and the 51-month follow-up groups. Within the follow-up times of this study, both the PLLA screws and the metallic screws were rather inert. Also, long-term walling-off was a typical response to both PLLA and metallic screws in cancellous bone. PLLA screws did not evoke any osteostimulatory reaction over the long-term follow-up. The findings clearly demonstrated that the overall degradation process of PLLA was very slow and accompanied by fibrous tissue formation. Macrophage activity seemed to be related to the slow degradation process of PLLA and might be associated with the formation of connective tissue replacing the original implant. The results of this study showed no significant differences between the bioabsorbable PLLA screws and the metallic screws in biocompatibility, and no signs of inflammatory foreign-body reactions occurred during the follow-up.

Tissue restoration after resorption of polyglycolide and poly-laevo-lactic acid screws

Despite worldwide clinical use of bio-absorbable devices for internal fixation in orthopaedic surgery, the degradation behaviour and tissue replacement of these implants are not fully understood. In a long-term experimental study, we have determined the patterns of tissue restoration 36 and 54 months after implantation of polyglycolic acid and poly-laevo-lactic acid screws in the distal femur of the rabbit. After 36 months in the polyglycolic acid group the specimens showed no remaining polymer and loose connective tissue occupied 80% of the screw track. Tissue restoration remained poor at 54 months, the amounts of trabecular bone and haematopoietic elements being significantly lower than those in the intact control group. The amount of trabecular bone within the screw track at 54 months in the polyglycolic acid group was less than in the empty drill holes (p = 0.04). In the poly-laevo-lactic acid group, polymeric material was present in abundance after 54 months, occupying 60% of the cross-section of the core area of the screw track. When using absorbable internal fixation implants we should recognise that the degradation of the devices will probably not be accompanied by the restoration of normal trabecular bone.

Osteoporosis in Men

Hip fractures in men account for one third of all hip fractures and have a higher mortality than in women. The public health burden will increase as the increase in the numbers of elderly men in the community increases. In addition, the age-specific incidence of hip fractures may be increasing in some, but not all, countries. Vertebral fractures may be a public health problem as recent studies suggest that the prevalence in the community is 20-30%, similar to that reported in women. Forearm fractures should probably not be regarded as a public health problem. Peak bone mass is higher in men than women because men have bigger bones. Peak bone mineral density is the same. The amount of trabecular bone lost at the spine and iliac crest during ageing is similar in men and women. Cortical bone loss is less in men because endocortical resorption is less and periosteal formation is greater. Bone loss accelerates in elderly men because endocortical resorption and increasing cortical porosity increase the surface available for resorption. Bone fragility is less in men than women because: (a) the cross-sectional surface of the bone is larger; (b) trabecular bone loss is less as a percentage of the higher peak bone mass; (c) trabecular bone loss occurs by thinning rather than perforation; and (d) periosteal appositional growth compensates for endocortical resorption by maintaining the bending strength of bone. Reduced BMD in men with fractures may be due to reduced peak bone size and mass, and bone loss. Bone loss occurs by reduced bone formation. Whether men with fractures have increased bone fragility due to reduced periosteal appositional growth during ageing is unknown. The age-related decline in testosterone, adrenal androgens, growth hormone, and insulin-like growth factor 1 may contribute to reduced bone formation and bone loss. Men with vertebral fractures often have hypogonadism or illnesses with few clinical features that should be considered with a high index of suspicion (alcoholism, myeloma, malabsorption, primary hyperparathyroidism, haemochromatosis, Cushing's disease). Secondary hyperparathyroidism may contribute to bone loss by activating bone turnover and so increasing the number of bone remodelling units with impaired bone formation in each. There is no proven treatment for osteoporosis in men because there have been no trials using anti-fracture efficacy as an end point. Testosterone replacement should be considered in men with proven hypogonadism and vitamin D deficiency should be corrected if present. Calcium supplements and bisphosphonates are reasonable options given the lack of information.

Osteoporosis in MCHR1-deficient mice

It is well recognized that the hypothalamus is of central importance in the regulation of food intake and fat mass. Recent studies indicate that it also plays an important role in the regulation of bone mass. Melanin concentrating hormone (MCH) is highly expressed in the hypothalamus and has been implicated in regulation of energy homeostasis. We developed MCHR1 inactivated mice to evaluate the physiological role of this receptor. Interestingly, the MCHR1 −/− mice have osteoporosis, caused by a reduction in the cortical bone mass, while the amount of trabecular bone is unaffected. The reduction in cortical bone mass is due to decreased cortical thickness. Serum levels of c-telopeptide, a marker of bone resorption, are increased in MCHR1 −/− mice, indicating that the MCHR1 −/− mice have a high bone turnover osteoporosis. In conclusion, the MCHR1 −/− mice have osteoporosis, indicating that MCHR1-signalling is involved in a tonic stimulation of bone mass.

Prenatal exposure to IL-1beta results in disturbed skeletal growth in adult rat offspring.

Events occurring early in life or prenatally are able to play important roles in the pathogenesis of diseases in adult life. Different sorts of stress or hormonal influences, during particular periods of pregnancy, may result in persistent or transient changes in physiology. IL-1 is a multifunctional cytokine that is involved in bone metabolism. The aim of the present study was to investigate whether exposure to IL-1beta during fetal life has any effect on skeletal growth or bone mineral density in adult rat offspring. Pregnant rats were given intraperitoneal injections of IL-1beta, 1 microg/rat, or saline on days 8, 10, and 12 of gestation. Male IL-1-exposed offspring showed reduced height, areal bone mineral density, and bone mineral content at vertebra L5. Tibial length was reduced in both male and female offspring. Peripheral quantitative computed tomography analyses revealed reduced cortical bone mineral content caused by a decreased cortical cross-sectional area as a result of a decreased cortical thickness, whereas there was no reduction in the amount of trabecular bone in the tibia of male offspring. Our results demonstrate that prenatal exposure to IL-1 can induce specific programming of skeletal tissue. In conclusion, prenatal IL-1 exposure results in decreased skeletal growth and a reduced amount of cortical bone but unchanged trabecular bone mineral density in adult rat offspring.

Effects of liver-derived insulin-like growth factor I on bone metabolism in mice.

Insulin-like growth factor (IGF) I is an important regulator of both skeletal growth and adult bone metabolism. To better understand the relative importance of systemic IGF-I versus locally expressed IGF-I we have developed a transgenic mouse model with inducible specific IGF-I gene inactivation in the liver (LI-IGF-I-/-). These mice are growing normally up to 12 weeks of age but have a disturbed carbohydrate and lipid metabolism. In this study, the long-term effects of liver-specific IGF-I inactivation on skeletal growth and adult bone metabolism were investigated. The adult (week 8-55) axial skeletal growth was decreased by 24% in the LI-IGF-I-/- mice whereas no major reduction of the adult appendicular skeletal growth was seen. The cortical cross-sectional bone area, as measured in the middiaphyseal region of the long bones, was decreased in old LI-IGF-I-/- mice. This reduction in the amount of cortical bone was caused mainly by decreased periosteal circumference and was associated with a weaker bone determined by a decrease in ultimate load. In contrast, the amount of trabecular bone was not decreased in the LI-IGF-I-/- mice. DNA microarray analysis of 30-week-old LI-IGF-I-/- and control mice indicated that only four genes were regulated in bone whereas approximately 40 genes were regulated in the liver, supporting the hypothesis that liver-derived IGF-I is of minor importance for adult bone metabolism. In summary, liver-derived IGF-I exerts a small but significant effect on cortical periosteal bone growth and on adult axial skeletal growth while it is not required for the maintenance of the trabecular bone in adult mice.

Diagnosis and treatment of postmenopausal osteoporosis

T HE NATIONAL Osteoporosis Foundation 1 estimates that over 20 million postmenopausal white women have either osteoporosis or low bone density at the hip. Patients with hip fractures have an excess mortality of 10% to 20% within 1 year, and only one third of patients regain their premorbid level of independence. Although vertebral compression fractures are not associated with increased mortality, they can result in significant pain, limitation of activity, and in very severe cases, restrictive lung disease and changes in gastrointestinal (GI) function. Osteoporosis is a reduction in the mass of bone per unit volume, clinically known as bone mineral d6nsity (BMD). Any degree of skeletal fragility sufficient to increase the risk of fracture is considered osteoporosis. The reduction in bone mass results from failure to attain optimal peak bone mass a -(which occurs at age 30-35) and/or subsequent excess bone resorption compared with bone formation. After age 40 to 50, cortical bone is lost at a rate of 0.3% to 0.5% per year, with an acceleration to 5% to 7% per year in postmenopausal women. Cumulative bone mass loss can range from 20% to 30% in men to as much as 40% to 50% in some women. Postmenopausal women lose a disproportionate amount of trabecular bone and are at risk for vertebral and radial fracture; older men and women lose an excess of both cortical and trabecular bone and experience fractures of the femoral neck, proximal humerus, proximal tibia, and pelvis.

Osteoporosis changes the amount of vertebral trabecular bone at risk of fracture but not the vertebral load distribution.

A finite-element study to investigate the amount of trabecular bone at risk of fracture and the distribution of load between trabecular core and cortical shell, for healthy, osteopenic, and osteoporotic vertebrae. To determine differences between healthy, osteopenic, and osteoporotic vertebrae with regard to the risk of fracture and the load distribution. The literature contains no reports on the effects of osteopenia and osteoporosis on load distribution in vertebral bodies, nor any reports on the amount of trabecular bone at risk of fracture. Computed tomography data of vertebral bodies were used to construct patient-specific finite-element models. These models were then used in finite-element analyses to determine the physiologic stresses and strains in the vertebrae. For all three classes of vertebrae the contribution of the trabecular core to the total load transfer decreased from about 70% near the endplates to about 50% in the midtransverse region. The amount of trabecular bone that is at risk of fracture was about 1% for healthy vertebrae, about 3% for osteopenic vertebrae, and about 16% for osteoporotic vertebrae. Our finite-element models indicated that neither osteopenia nor osteoporosis had any effect on the contribution of the trabecular core to the total load placed on the vertebra. The trabecular core carried about half the load. Our finite-element models indicated that osteoporosis had a significant effect on the amount of trabecular bone at risk of fracture, which increased from about 1% in healthy vertebrae to about 16% for osteoporotic vertebrae.

Effect of Elcatonin on Osteoinduction by Recombinant Human Bone Morphogenetic Protein-2

To evaluate the effect of elcatonin on osteoinduction by recombinant human bone morphogenetic protein-2 (rhBMP-2), 5 μg of rhBMP-2 was implanted into intramuscular sites of rats. For 14 days after the implantation, elcatonin was administered intraperitoneally with total dosage of 80 U, 8 U, and 0.8 U, respectively. For the control group, only physiological saline was administered. At 21 days after implantation, the area of the oval shadow in the radiologic findings depended on the elcatonin dose and the amount of trabecular bone and the number of osteoblasts observed in the histologic findings depended on the dosage of elcatonin. The values of ALP activity and Ca content also showed an elcatonin dose dependency. These results suggested that elcatonin is effective in enhancing osteoinduction by rhBMP-2 within the dose range of this study, and that elcatonin has an anabolic effect on osteoblasts in addition to an antiresorptive effect.

Three-dimensional in vivo morphometry of trabecular bone in the OVX rat model of osteoporosis

This paper describes the application of synchrotron radiation microtomography to osteoporosis research. By taking advantage of the high intensity, collimation, and monochromaticity of synchrotron radiation, we have been able to image the three-dimensional trabecular bone structure in living rats, thus providing serial data on the earliest architectural changes that occur with estrogen loss. Results from these in vivo animal experiments demonstrate that one of the earliest manifestations of estrogen loss, in addition to a decrease in the amount of trabecular bone, is decreased connectivity. We demonstrate that estrogen replacement therapy, when initiated soon after significant changes have occurred, restores bone mass to baseline levels but does not recover the trabecular connectivity. Even without an associated recovery in trabecular connectivity, finite element calculations on the three-dimensional images suggest that estrogen recovers the original structural modulus of elasticity. We believe the recovery of the elastic properties is due to an increase in trabecular thickness above baseline values.

Effects of Neonatal Administration of Monosodium Glutamate on Bone in Rats.

It has been known that monosodium glutamate (MSG) treatment to neonatal rodents affects hypothalamic arcuate nucleus, the primary site of growth hormone releasing hormone, and consequently inhibits growth hormone release. However, there have been few reports on bone changes with aging after MSG treatment to neonatal rodents. Male and female neonatal F344 rats were subcutaneously given 4,000 mg/kg of MSG on days 0, 2, 4, 6, and 8 after birth, and the changes of the femurs were examined at 12 months of age. As a result, the bone length, diameters of the femur diaphysis and bone mineral density, especially the metaphysis region, were decreased by the treatment. Histologically, the amount of trabecular bone in the epiphysis and metaphysis regions also decreased in MSG-treated rats, together with an increase of adipose tissue in the bone marrow.