Bone histology of prehistoric inhabitants of the Canary Islands: comparison between El Hierro and Gran Canaria.

The trabecular bone mass (TBM) of the proximal epiphyses of right tibiae belonging to 273 prehispanic inhabitants of Gran Canaria (60. 81% males and 35.53% females) were assessed by histomorphometrical analysis of undecalcified samples and compared with that of 41 samples from El Hierro (52.63% males and 47.37% females). Among the prehispanic population of Gran Canaria 19.05% showed TBM values below 13.5% and 30.40% below 15%, although individual variability was high (range 6.71-35.4%). In sharp contrast with these results, only one case (2.44%) from El Hierro showed a TBM value below 15%, whereas mean TBM (23.50;+/- 5.60%) was significantly higher than that of the population of Gran Canaria (17.88 +/- 5.20%). The high prevalence of osteoporosis on Gran Canaria may reflect protein-calorie malnutrition. Prehistorically Gran Canaria exhibited a relatively high population density (30-40/km(2)) and a strong reliance on agriculture, in contrast with a lower population density (4/km(2)) on the island El Hierro, where the population consumed mainly marine products.     

Noninvasive estimation of bone mass in ancient vertebrae

Histomorphometry is useful in the assessment of trabecular bone mass (TBM), and thus, in the estimation of the prevalence and intensity of osteopenia in ancient population groups. However, it is a destructive method. It is therefore necessary to explore the accuracy of nondestructive approaches, such as radiography, bone mineral density (BMD) assessed by double-energy X-ray absorptiometry (DEXA), bone density (BD), or optical density (OD) in the diagnosis of osteopenia. We selected 51 vertebrae out of a total sample composed of 333 T12, L1, and L2 vertebrae belonging to adult pre-Hispanic inhabitants from El Hierro. These vertebrae underwent histomorphometrical analysis, a fine-grained film radiography with assessment of trabecular pattern following standard methods, OD, DEXA-assessed BMD, and BD. The presence of biconcave vertebrae and wedge-shaped vertebrae was also assessed by measuring anterior height (a), posterior height (p), and height at the middle point of the vertebral body (m), and further calculating the indices 2m/(a + p) ("spine score") and a/p. Significant correlations were observed between TBM and BMD (r=0.43), TBM and BD (r=0.49), TBM and OD (r=0.52), BMD and OD (r=0.51), and BMD and BD (r=0.36), but not between TBM and the indices 2m/(a + p) and a/p. In the stepwise multiple correlation analysis between TBM and BMD, BD, and OD, OD entered into first place and BD into second place, whereas BMD became displaced; the multiple correlation coefficient was 0.63, with a standard error of 3.78. A BMD greater than 0.60 g/cm2, or a bone density greater than 0.60 g/cm3, excluded osteopenia (TBM <15%) with a specificity greater than 90%, whereas a BMD value less than 0.35 g/cm2, a BD less than 0.35 g/cm3, or optical density >1.6 excluded a normal bone mass (TBM >20%) with a specificity greater than 90%. Based on radiographic criteria on the total sample, we also conclude that the overall prevalence of vertebral fractures in the adult pre-Hispanic population of El Hierro of any age is 7.5%.     

Ancient skeletal remains of the Canary Islands: bone histology and chemical analysis.

Prehispanic burials from the Canary Islands are often well preserved. Many of the bodies are mummified, most of them were not interred, but deposited in caves. Bone histological and trace element analysis of 117 skeletons of the prehispanic period of the Canary Islands was performed. In some of the islands we have found a high prevalence of osteoporosis, whereas in others, histomorphometrically assessed trabecular bone mass (TBM) (in undecalcified iliac crest specimens) was in the normal range. Bone trace elements analysis have shown high bone S(r), Mg and Mn, and low Fe, Zn and Cu in those skeletons with a more reduced TBM. These facts speak for a relative protein-calorie malnutrition and a consumption of a mainly vegetarian diet. This is especially marked in the skeletons from Gran Canaria.     

A comparison of the anabolic effects of rat and bovine parathyroid hormone (1-34) in ovariectomized rats

The current study was designed to compare the skeletal effects of comparable doses of rat parathyroid hormone 1-34 (rPTH) and bovine parathyroid hormone 1-34 (bPTH) in ovariectomized (OVX) rats. Female Sprague-Dawley rats were OVX or sham-operated at 6 months of age and maintained untreated for 28 days after surgery. Baseline control and OVX rats were sacrificed at the beginning of treatment. Beginning 28 days post-OVX, the remaining rats were subcutaneously injected daily with rPTH or bPTH at 0, 5, 25, or 50 microg/kg/d for 28 days. Bone area, bone mineral content (BMC), and bone mineral density (BMD) of the distal femoral metaphyses were determined ex vivo using dual energy X-ray absorptiometry. Quantitative bone histomorphometry was performed on undecalcified longitudinal sections of the proximal tibia from each rat. Baseline OVX rats exhibited osteopenia as demonstrated by their significantly reduced femoral BMD and proximal tibia cancellous bone volume compared with those of baseline sham controls. Both rPTH and bPTH restored bone in OVX rats by markedly stimulating bone formation in a dose-dependent manner. However, a difference in potency between the two forms of PTH was evident. The percentage increases of BMC, BMD, cancellous bone volume, trabecular thickness, mineralizing surface, and bone formation rate in the OVX rats treated with bPTH at 5 microg/kg/d were the same as or above those treated with rPTH at the 25 microg/kg/d dose level. A relative potency analysis showed that bPTH was approximately 4- to 6-fold relatively more potent than rPTH in increasing distal femoral BMD as well as cancellous bone volume, mineralizing surface, and bone formation rate of proximal tibial metaphyses at comparable dose levels and a given time. These results may serve as a reference for in vivo study design when rPTH or bPTH are to be the agents for studies on bone anabolism.     

Gender-related changes in three-dimensional microstructure of trabecular bone at the human proximal tibia with aging

Despite increasing interest in age- and gender-related bone alterations, data on trabecular microstructure at the proximal tibia are scarce. The aim of this study was to identify trabecular microstructural change at the human proximal tibia with age and gender, using micro-computed tomography (micro-CT) and scanning electron microscopy (SEM). Fifty-six proximal tibias from 28 Japanese men and women (57-98 years of age) were used in this study. The subjects were chosen to give an even age and gender distribution. Both women and men were divided into three age groups, middle (57-68 years), old (72-82 years) and elderly (87-98 years) groups. The trabecular bone specimens from the medial compartment of the proximal tibial metaphysis were examined. Trabecular bone mineral density (BMD), bone volume fraction (BV/TV) and trabecular thickness (Tb.Th) decreased between the middle-aged and elderly groups similarly in women and men. However, trabecular number (Tb.N) decreased by 13% between the middle-aged and elderly groups in women and nearly double that in men. As compared with women, men had higher BV/TV and lower trabecular separation (Tb.Sp) in the old age and elderly groups, and higher Tb.N and connectivity density (Conn.D) in the elderly group. Increased trabecular resorbing surfaces, perforated or disconnected trabeculae and microcallus formations were observed with age. These findings indicate that both BMD and BV/TV decreased at the proximal tibia with age similarly for women and men, but significant differences between women and men were observed for some microstructural parameters. These findings illustrate potential mechanisms underlying osteoporotic proximal tibial fracture.     

Effects of spirulina, a blue-green alga, on bone metabolism in ovariectomized rats and hindlimb-unloaded mice

The safety and effectiveness were examined of the spirulina alga on bone metabolism in ovariectomized estrogen-deficient rats and hindlimb-unloaded mice. The dosage range was from an amount equal to that recommended in so-called health foods for humans (0.08 g/kg BW/day) to a 100-fold higher dose. The bone mineral density (BMD) of the whole femur and tibia of ovariectomized rats in the any spirulina-treated groups was not significantly different from that of the ovariectomized group, although BMD of the distal femur and proximal tibia was significantly lower in the spirulina-treated groups than in the ovariectomized group after a 6 week-experimental period. BMD of the femur and tibia was not affected by treatment with any dose of spirulina in hindlimb-unloaded mice. These results suggest that the intake of spirulina decreased BMD in the trabecular bone of rodents under estrogen-deficient conditions.     

Protective actions of green tea polyphenols and alfacalcidol on bone microstructure in female rats with chronic inflammation

This study investigated the effects of green tea polyphenols (GTP) and alfacalcidol on bone microstructure and strength along with possible mechanisms in rats with chronic inflammation. A 12-week study using a 2 (no GTP vs. 0.5%, w/v GTP in drinking water)×2 (no alfacalcidol vs. 0.05 μg/kg alfacalcidol orally, 5×/week) factorial design was employed in lipopolysaccharide (LPS)-administered female rats. A group receiving placebo administration was used to compare with a group receiving LPS administration only to evaluate the effect of LPS. Changes in tibial and femoral microarchitecture and strength of femur were evaluated. Difference in expression of tumor necrosis factor-α (TNF-α) in proximal tibia using immunohistochemistry was examined. Compared to the placebo group, the LPS-administered-only group had significantly lower femoral mass, trabecular volume, thickness and number in proximal tibia and femur, and lower periosteal bone formation rate in tibial shafts but had significantly higher trabecular separation and osteoclast number in proximal tibia and eroded surface in endocortical tibial shafts. Both GTP and alfacalcidol reversed these LPS-induced detrimental changes in femur, proximal tibia and endocortical tibial shaft. Both GTP and alfacalcidol also significantly improved femoral strength, while significantly suppressed TNF-α expression in proximal tibia. There were significant interactions in femoral mass and strength, trabecular separation, osteoclast number and TNF-α expression in proximal tibia. A combination of both showed to sustain bone microarchitecture and strength. We conclude that a protective impact of GTP and alfacalcidol in bone microarchitecture during chronic inflammation may be due to a suppression of TNF-α.     

Bone mineral density, osteopenia, and osteoporosis in the rhesus macaques of Cayo Santiago

This cross-sectional study investigates metabolic bone disease and the relationship between age and bone mineral density (BMD) in males and females of a large, well-documented skeletal population of free-ranging rhesus monkeys (Macaca mulatta), from the Caribbean Primate Research Center Museum collection from Cayo Santiago, Puerto Rico. The sample consists of 254 individuals aged 1.0-20+ years. The data consist of measurements of bone mineral content and bone mineral density, obtained from dual-energy X-ray absorptiometry (DEXA), of the last lumbar vertebra from each monkey. The pattern of BMD differs between male and female rhesus macaques. Females exhibit an initial increase in BMD with age, with peak bone density occurring around age 9.5 years, and remaining constant until 17.2 years, after which there is a steady decline in BMD. Males acquire bone mass at a faster rate, and attain a higher peak BMD at an earlier age than do females, at around 7 years of age, and BMD remains relatively constant between ages 7-18.5 years. After age 7 there is no apparent effect of age on BMD in the males of this sample; males older than 18.5 years were excluded due to the presence of vertebral osteophytosis, which interferes with DEXA. The combined frequency of osteopenia and osteoporosis in this population is 12.4%. BMD values of monkeys with vertebral wedge fractures are generally higher than those of virtually all of the nonfractured osteopenic/osteoporotic individuals, thus supporting the view that BMD as measured by DEXA is a useful but imperfect predictor of fracture risk, and that low BMD may not always precede fractures in vertebral bones. Other factors such as bone quality (i.e., trabecular connectivity) should also be considered. The skeletal integrity of a vertebra may be compromised by the loss of key trabeculae, resulting in structural failure, but the spine may still show a BMD value within normal limits, or within the range of osteopenia.     

Greater efficacy of alfacalcidol in the red than in the yellow marrow skeletal sites in adult female rats

The present study compared the bone anabolic effects of graded doses of alfacalcidol in proximal femurs (hematopoietic, red marrow skeletal site) and distal tibiae (fatty, yellow marrow skeletal site). One group of 8.5-month-old female Sprague-Dawley rats were killed at baseline and 4 groups were treated 5 days on/2 days off/week for 12 weeks with 0, 0.025, 0.05 and 0.1 microg alfacalcidol/kg by oral gavage. The proximal femur, bone site with hematopoietic marrow, as well as the distal tibia bone site with fatty marrow, were processed undecalcified for quantitative bone histomorphometry. In the red marrow site of the proximal femoral metaphysis (PFM), 0.1 microg alfacalcidol/kg induced increased cancellous bone mass, improved architecture (decreased trabecular separation, increased connectivity), and stimulated local bone formation of bone 'boutons' (localized bone formation) on trabecular surfaces. There was an imbalance in bone resorption and formation, in which the magnitude of depressed bone resorption greater than depressed bone formation resulted in a positive bone balance. In addition, bone 'bouton' formation contributed to an increase in bone mass. In contrast, the yellow marrow site of the distal tibial metaphysis (DTM), the 0.1 microg alfacalcidol/kg dose induced a non-significant increased cancellous bone mass. The treatment decreased bone resorption equal to the magnitude of decreased bone formation. No bone 'bouton' formation was observed. These findings indicate that the highest dose of 0.1 microg alfacalcidol/kg for 12 weeks increased bone mass (anabolic effect) at the skeletal site with hematopoietic marrow of the proximal femoral metaphysis, but the increased bone mass was greatly attenuated at the fatty marrow site of the distal tibial metaphysis. In addition, the magnitude of the bone gain induced by alfacalcidol treatment in red marrow cancellous bone sites of the proximal femoral metaphysis was half that of the lumbar vertebral body. The latter data were from a previous report from the same animal and protocol. These findings indicated that alfacalcidol as an osteoporosis therapy is less efficacious as a positive bone balance agent that increased trabecular bone mass in a non-vertebral skeletal site where bone marrow is less hematopoietic.     

Bone Mass and Bone Quality Are Altered by Hypoactivity in the Chicken

Disuse induces a rapid bone loss in adults; sedentarity is now recognized as a risk factor for osteoporosis. Hypoactivity or confinement also decrease bone mass in adults but their effects are largely unknown and only few animal models have been described. We have used 10 chickens of the rapidly growing strain 857K bred in a large enclosure (FREE group); 10 others were confined in small cages with little space to move around (HYPO group). They were sacrificed at 53 days and femurs and tibias were evaluated by texture analysis, dual energy X-ray densitometry, microcomputed tomography (microCT) and histomorphometry. Hypoactivity had no effect on the length and diameter of the bones. Bone mineral density (BMD), microCT (trabecular bone volume and trabecular microarchitecture) and texture analysis were always found significantly reduced in the animals of the HYPO group. BMD was reduced at both femur and tibia diaphysises; BMD of the metaphysis was significantly reduced in the femur but not in the tibia. An increase in osteoid volume and surfaces was noted in the HYPO group. However, there was no alteration of the mineral phase as the osteoid thickness did not differ from control animals. Bone loss was much more pronounced at the lower femur metaphysis than at the upper metaphysis of the tibia. At the tibia, only microarchitectural changes of trabecular bone could be evidenced. The confined chicken represents a new method for the study of hypodynamia since these animals do not have surgical lesions.     

The Carabelli trait in human prehistoric populations of the Canary Islands

The incidence of the different degrees of expression of Carabelli's trait in the deciduous and permanent dentitions was obtained on 651 skulls of three human prehistoric aboriginal samples from Gran Canaria (n = 329), Tenerife (n = 297) and La Gomera (n = 25) Islands. In the Gran Canaria sample, the total trait frequency for the permanent first molar was slightly greater in males, who also showed a higher degree of expression than females. However, in this sample, as well as in the Tenerife sample, the differences between the two sexes were not statistically significant. A high concordance regarding the presence and grade of expression of the trait was found between right and left sides, as well as between the deciduous and permanent dentitions. Marked differences were observed with respect to the incidence of the diverse degrees of expression of the trait between the Gran Canaria and Tenerife populations, whose cultural and anthropological differences are well established. The findings suggest that Carabelli's trait could be useful in establishing phylogenetic relationships between closely related populations.     

Intrauterine growth restriction affects bone mineral density of the mandible and the condyle in growing rats

Objectives:To investigate in growing rats the effect of intrauterine growth restriction (IUGR) on the bone mineral density of the mandible and tibia, as well as the quality of the mandibular and condylar bone.Methods:Twelve male rats were born IUGR by mothers sustaining 50% food restriction during pregnancy. Twelve control male rats were born by mothers fed ad libitum. Dual-energy X-ray absorptiometry (DEXA) of the tibia, proximal tibial metaphysis and the mandible, biochemical markers, histology and histomorphometrical analysis on the mandibular and subchondral bone of the condyle were performed.Results:IUGR significantly affected bone mineral density (BMD) of both tibial and mandibular bones. IUGR rats had significantly lower osteocalcin values (p=0.021) and phosphorus (p=0.028), but not 25-OH vitamin D (p=0.352). Bone area percentage in the mandible was significantly lower (51.21±5.54) in IUGR compared to controls (66.00±15.49), and for subchondral bone of the condyle for IUGR (47.01±6.82) compared to controls (68.27±13.37). IUGR had a significant reduction in the fibrous layer, but not the proliferating layer, with the hypertrophic layer significantly increased.Conclusion:Maternal restricted nutrition during gestation can affect BMD of the mandible and the tibia of the offspring animals.     

Patterns in ontogeny of human trabecular bone from SunWatch Village in the Prehistoric Ohio Valley: general features of microarchitectural change

Although adult skeletal morphological variation is best understood within the framework of age-related processes, relatively little research has been directed towards the structure of and variation in trabecular bone during ontogeny. We report here new quantitative and structural data on trabecular bone microarchitecture in the proximal tibia during growth and development, as demonstrated in a subadult archaeological skeletal sample from the Late Prehistoric Ohio Valley. These data characterize the temporal sequence and variation in trabecular bone structure and structural parameters during ontogeny as related to the acquisition of normal functional activities and changing body mass. The skeletal sample from the Fort Ancient Period site of SunWatch Village is composed of 33 subadult and three young adult proximal tibiae. Nondestructive microCT scanning of the proximal metaphyseal and epiphyseal tibia captures the microarchitectural trabecular structure, allowing quantitative structural analyses measuring bone volume fraction, degree of anisotropy, trabecular thickness, and trabecular number. The microCT resolution effects on structural parameters were analyzed. Bone volume fraction and degree of anisotropy are highest at birth, decreasing to low values at 1 year of age, and then gradually increasing to the adult range around 6-8 years of age. Trabecular number is highest at birth and lowest at skeletal maturity; trabecular thickness is lowest at birth and highest at skeletal maturity. The results of this study highlight the dynamic sequential relationships between growth/development, general functional activities, and trabecular distribution and architecture, providing a reference for comparative studies.     

Harris lines in the prehispanic population of Gran Canaria (Canary Islands)

Harris lines were assessed in 194 right tibiae of prehispanic inhabitants of Gran Canaria, belonging to 52 adult females and 123 adult males. No Harris lines were detected in 45 (23%) of the adult individuals (13 females (25%) and 26 males (21%), these differences being not statistically significant. Female tibiae showed a slightly lower mean number of Harris lines at the distal end than male ones (1,692±1.681 in females vs 1.91±1.825 in males). Ages at which Harris lines were formed showed two peaks, a major one at the age of 1 year, and another between 15 and 16 years in males and between 11–12 and 14–15 years in females. Harris lines were more frequently observed at the distal than at the proximal end of the bone. The relative low number of lines detected in our population when compared with the high prevalence of osteoporosis among the adult population of this island is striking.     

Disproportional skeletal growth and markedly decreased bone mineral content in growth hormone receptor -/- mice

Growth hormone (GH) is important for skeletal growth as well as for a normal bone metabolism in adults. The skeletal growth and adult bone metabolism was studied in mice with an inactivated growth hormone receptor (GHR) gene. The lengths of femur, tibia, and crown-rump were, as expected, decreased in GHR-/- mice. Unexpectedly, GHR-/- mice displayed disproportional skeletal growth reflected by decreased femur/crown-rump and femur/tibia ratios. GHR-/- mice demonstrated decreased width of the growth plates in the long bones and disturbed ossification of the proximal tibial epiphysis. Furthermore, the area bone mineral density (BMD) as well as the bone mineral content (BMC)/body weight were markedly decreased in GHR-/- mice. The decrease in BMC in GHR-/- mice was not due to decreased trabecular volumetric BMD but to a decreased cross-sectional cortical bone area In conclusion, GHR-/- mice demonstrate disproportional skeletal growth and markedly decreased bone mineral content.     

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.     

A review of musculoskeletal adaptations in individuals following major lower-limb amputation

Structural musculoskeletal adaptations following amputation, such as bone mineral density (BMD) or muscle architecture, are often overlooked despite their established contributions to gait rehabilitation and the development of adverse secondary physical conditions. The purpose of this review is to provide a summary of the existing literature investigating musculoskeletal adaptations in individuals with major lower-limb amputations to inform clinical practice and provide directions for future research. Google Scholar, PubMed, and Scopus were searched for original peer-reviewed studies that included individuals with transtibial or transfemoral amputations. Summary data of twenty-seven articles indicated reduced BMD and increased muscle atrophy in amputees compared to controls, and in the amputated limb compared to intact and control limbs. Specifically, BMD was reduced in T-scores and Z-scores, femoral neck, and proximal tibia. Muscle atrophy was evidenced by decreased thigh cross-sectional area, decreased quadriceps thickness, and increased amounts of thigh fat. Overall, amputees have impaired musculoskeletal health. Future studies should include dysvascular etiologies to address their effects on musculoskeletal health and functional mobility. Moreover, clinicians can use these findings to screen increased risks of adverse sequelae such as fractures, osteopenia/porosis, and muscular atrophy, as well as target specific rehabilitation exercises to reduce these risks.     

运动与17β-雌二醇对去卵巢大鼠血清17β-雌二醇和后肢骨骨密度的影响

目的：观察跑台运动和17β-雌二醇（E2）对去卵巢大鼠血清E2水平和后肢骨骨密度（BMD）的影响。方法：按体重将120只成年雌性SD大鼠随机分为假手术、假手术运动、去卵巢、去卵巢运动、雌激素、雌激素加运动6个组。假手术运动、去卵巢运动和雌激素加运动组每周进行5次60min、18m／min的平坡跑台运动训练,雌激素和雌激素加运动组每周按体重颈部皮下注射3次E2,每次50μg／kg体重。分别在运动和给药正式处理7和14周时,用放射免疫法检测血清E2水平;用双能X线骨密度仪检测右侧胫骨和股骨BMD的变化。结果：运动和给药正式处理7周时,去卵巢组胫骨近端、股骨近端和远端BMD以及血清E2水平均显著低于假手术组;去卵巢运动加E2组股骨近端和远端BMD显著高于去卵巢组,E2组和去卵巢运动加E2组大鼠血清E2水平显著高于去卵巢组。运动和给药正式处理14周时,去卵巢组大鼠胫骨近端、股骨近端和远端BMD以及血清E2水平均显著低于假手术组,假手术运动组股骨近端BMD显著高于假手术组;去卵巢运动组、E2组和去卵巢运动加E2组大鼠血清E2水平显著高于去卵巢组,去卵巢运动组股骨远端BMD显著高于去卵巢组,E2组和去卵巢运动加E2组胫骨近端、股骨近端和远端BMD均显著高于去卵巢组;去卵巢运动组大鼠胫骨近端BMD和血清E2水平显著低于去卵巢运动加E2组,E2组胫骨近端BMD显著高于去卵巢运动加E2组。结论：E2和较高中等强度跑台运动对去卵巢大鼠股骨和胫骨松质骨骨量减缓的效应是独立的。     

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.