Osteoblast-specific overexpression of human interleukin-7 rescues the bone mass phenotype of interleukin-7-deficient female mice

Interleukin-7 is a critical cytokine for lymphoid development and a direct inhibitor of in vitro osteoclastogenesis in murine bone marrow cultures. To explore the role of IL-7 in bone, we generated transgenic mouse lines bearing the 2.3-kb rat collagen 1α1 promoter driving the expression of human IL-7 specifically in osteoblasts. In addition, we crossed these mice with IL-7-deficient mice to determine if the alterations in lymphopoiesis, bone mass, and osteoclast formation observed in the IL-7 knockout (KO) mice could be rescued by osteoblast-specific overexpression of IL-7. Here, we show that mice overexpressing human IL-7 in the osteoblast lineage showed increased trabecular bone volume in vivo by μCT and decreased osteoclast formation in vitro. Furthermore, targeted overexpression of IL-7 in osteoblasts rescued the osteopenic bone phenotype and B-cell development of IL-7 KO mice but did not have an effect on T lymphopoiesis, which occurs in the periphery. The bone phenotypes in IL-7 KO mice and targeted IL-7-overexpressing mouse models were observed only in females. These results likely reflect both direct inhibitory effects of IL-7 on osteoclastogenesis in vivo and sex-specific differences in responses to IL-7.     

High-fat diet decreases cancellous bone mass but has no effect on cortical bone mass in the tibia in mice

Body mass has a positive effect on bone health. Whether mass derived from an obesity condition or excessive fat accumulation is beneficial to bone has not been established; neither have the mechanisms by which obesity affects bone metabolism. The aim of this study was to examine the effects of obesity on bone structure and osteoblastic expression of key markers involved in bone formation and resorption in a diet-induced obesity mouse model. Six-wk-old male C57BL/6 mice (n = 21) were assigned to two groups and fed either a control (10 kcal% energy as fat) or high-fat diet (HFD, 45 kcal% energy as fat) for 14 weeks. Bone marrow stromal/osteoblastic cells (BMSC) were cultured. Osteoprogenitor activity [alkaline phosphatase (ALP) positive colonies] and mineralization (calcium nodule formation) were determined. Gene expression was measured using quantitative real-time PCR. Bone structure of proximal and midshaft tibia was evaluated by micro-computed tomography. Mice fed the HFD were 31% heavier (P < 0.01) than those fed the control diet. There were more ALP positive colony forming units at d 14 and calcium nodules at d 28 of culture by BMSC from HFD mice than from control mice (P < 0.01). Receptor activator of NF-κB ligand (RANKL) mRNA levels and the ratio of RANKL to osteoprotegerin expression in HFD animals was higher (P < 0.01) than in control diet animals. Serum tartrate-resistant acid phosphatase levels were higher in HFD fed mice when compared to control diet fed mice (P < 0.05). There were no significant differences in tibial fat-free weight, length, and cortical parameters of midshaft between the two groups. Compared with control mice, tibial trabecular bone volume was reduced, and trabecular separation was increased in HFD mice. Trabecular number was lower (P < 0.05) and connectivity density tended to be less (P = 0.07) in HFD mice than in control mice. In conclusion, our data indicate that obesity induced by a high-fat diet decreases cancellous bone mass but has no effect on cortical bone mass in the tibia in mice.     

Material properties of femoral cancellous bone in axial loading

Summary In part I of this communication we reported on some time independent material properties of cancellous bone specimens from different regions of human femora. In part II we will report on our investigations of the time dependent behaviour, i.e. stress relaxation and creep. Cylindrical specimens were obtained from the head and condyles of pairs of cadaveric femora and subjected to axial loading. The data were evaluated statistically. The median_L values for relaxation of cancellous bone were greater in the femoral head than in the condyles, greater proximally than distally and greater medially than laterally in the condyles. The distribution of creep was found to be the reverse. The correlation analysis showed that a linear correlation between compressive stength, apparent density and the time dependent properties cannot be assumed.The time dependent properties reported here would appear to demonstrate the visco-elastic behaviour of cancellous bone.An experimental foundation and explanation is presented for the clinical practice of re-tightening cancellous bone screws one time only.

---

Zusammenfassung Materialeigenschaften der Spongiosa interessieren u.a. wegen der Verankerung der Prothesen überwiegend im spongiösen Bereich des Knochens. Im 2. Teil der Arbeit über Materialeigenschaften der Spongiosa wird das zeitabhängige Materialverhalten —Kriechen und Relaxation — von zylindrischen Proben der Femurspongiosa untersucht. Die statistischen Kennzahlen fur Kriechen, Relaxation, Bruchfestigkeit and scheinbare Dichte werden für verschiedene Bezirke des Femurkopfes and der Femurkondylen angegeben. Unterschiedliche Werte für Relaxation und Kriechen wurden für die Spongiosa des Kopfes und der Kondylen gefunden. Innerhalb der Kondylen wurde medial für die Relaxation ein größerer Mittelwert und für das Kriechen ein kleinerer Mittelwert ermittelt als lateral. Die berechneten Korrelationskoeffizienten nach Bravais und Pearsson lassen bei einem Signifikanzniveau von 1% keinen linearen Zusammenhang zwischen Kriechen bzw. Relaxation und Bruchfestigkeit bzw. scheinbarer Dichte vermuten.Die hier mitgeteilten zeitabhängigen Werte der Spongiosa zeigen das viscoelastische Verhalten dieses Materials. Zum Schluß wird experimentell belegt, warum z. B. nur ein einmaliges Nachziehen von Spongiosaschrauben sinnvoll erscheint.

     

Material properties of femoral cancellous bone in axial loading

Summary The time independent material behavior of cylindrical specimens obtained from the cancellous bone of 20 cadaveric human femora were determined. In this part of the publication, the nominal values for compressive strength, limits of elasticity (yield point), strain, elastic modulus and apparent density are being reported for the cancellous bone of the femoral head and condyle. The correlations between the various parameters are analysed. A positive linear correlation between the four parameters compressive stength, limit of elasticity, modulus of elasticity and apparent density could not be excluded. The material properties vary considerably both within one single bone and between individuals. Compressive strength, modulus of elasticity and apparent density found for cancellous bone of the femoral head are greater than those found in the condyles. Within the condyles, compressive strength, elastic modulus and apparent density increase from the proximal parts to the parts closer to the joint. The medial femoral condyle showed higher compressive strength than the lateral one. Relating each of the three other parameters to the apparent density of the individual specimen did not result in equalizing the data for the material properties. This indicates that the mechanical properties of cancellous bone are strongly related to the direction of loading.

---

Zusammenfassung Das zeitunabhängige Materialverhalten von Zylinderproben der Femurspongiosa wird beschrieben. Es werden statistische Kennzahlen für Bruchfestigkeit, Elastizitätsgrenze, Dehnung, E-Modul und scheinbare Dichte für die Spongiosa verschiedener Femurbezirke im Kopf- und Kondylenbereich angegeben. Weiter werden durch Korrelationsanalysen die Zusammenhänge zwischen den einzelnen Größen aufgezeigt. Danach ist bei einem Signifikanzniveau von 1% ein linearer positiver Zusammenhang zwischen den 4 Größen Bruchfestigkeit, Elastizitatsgrenze, E-Modul und scheinbare Dichte nicht auszuschließen. Die Materialkennzahlen variieren sowohl innerhalb eines Knochens als auch von Individuum zu Individuum schr stark. Die Bruchfestigkeit, der E-Modul und die scheinbare Dichte der Kopfspongiosa sind größer als die der Kondylen. Innerhalb der Kondylen nehmen die Bruchfestigkeit, E-Modul und scheinbare Dichte von cranial nach caudal zu, der tibiale Condylus femoris zeigt eine höhere Bruchfestigkeit als der fibulare. Durch Beziehen der einzelnen Meßwerte auf die scheinbare Dichte der entsprechenden Proben werden keine konstanten Werte für die Material kennzahIen der Spongiosa erreicht. Das deutet darauf hin, daß die Materialdaten der Spongiosa wesentlich von der Belastungsrichtung abhängen.

     

Caloric restriction leads to high marrow adiposity and low bone mass in growing mice

The effects of caloric restriction (CR) on the skeleton are well studied in adult rodents and include lower cortical bone mass but higher trabecular bone volume. Much less is known about how CR affects bone mass in young, rapidly growing animals. This is an important problem because low caloric intake during skeletal acquisition in humans, as in anorexia nervosa, is associated with low bone mass, increased fracture risk, and osteoporosis in adulthood. To explore this question, we tested the effect of caloric restriction on bone mass and microarchitecture during rapid skeletal growth in young mice. At 3 weeks of age, we weaned male C57Bl/6J mice onto 30% caloric restriction (10% kcal/fat) or normal diet (10% kcal/fat). Outcomes at 6 (n = 4/group) and 12 weeks of age (n = 8/group) included body mass, femur length, serum leptin and insulin‐like growth factor 1 (IGF‐1) values, whole‐body bone mineral density (WBBMD, g/cm²), cortical and trabecular bone architecture at the midshaft and distal femur, bone formation and cellularity, and marrow fat measurement. Compared with the normal diet, CR mice had 52% and 88% lower serum leptin and 33% and 39% lower serum IGF‐1 at 6 and 12 weeks of age (p < .05 for all). CR mice were smaller, with lower bone mineral density, trabecular, and cortical bone properties. Bone‐formation indices were lower, whereas bone‐resorption indices were higher (p < .01 for all) in CR versus normal diet mice. Despite having lower percent of body fat, bone marrow adiposity was elevated dramatically in CR versus normal diet mice (p < .05). Thus we conclude that caloric restriction in young, growing mice is associated with impaired skeletal acquisition, low leptin and IGF‐1 levels, and high marrow adiposity. These results support the hypothesis that caloric restriction during rapid skeletal growth is deleterious to cortical and trabecular bone mass and architecture, in contrast to potential skeletal benefits of CR in aging animals. © 2010 American Society for Bone and Mineral Research.     

Reduced femoral bone mass in both diet-induced and genetic hyperlipidemia mice

Growing evidence argues for a relationship between lipid and bone metabolisms with inconsistent conclusions. Sphingosine-1-phosphate (S1P) has been recognized as a suitable candidate for possible link between lipid metabolism and bone metabolism. This study was designed to investigate the effects of hyperlipidemia on bone metabolism using diet-induced and genetic-induced hyperlipidemia animal models and to explore whether S1P is involved. Wild-type mice and low-density lipoprotein receptor gene deficient (LDLR^−/−) mice at age of 8 weeks were placed on either control diet or high-fat diet (HFD) for 12 weeks. Bone structural parameters were determined using microCT. Cross-linked type I collagen (CTx) and S1P levels in plasma were measured by ELISA methods. Bone marrow cells from wild type and LDLR^−/− mice were induced to differentiate into osteoblasts, osteoclasts and adipocytes respectively. Gene expressions in distal femur metaphyses and cultured cells were studied by qRT-PCR. Moderate hypercholesterolemia was found in HFD-feeding mice; severe hypercholesterolemia and moderate hypertriglyceridemia were present in LDLR^−/− mice. Femoral trabecular bone mass was reduced in both diet-induced and genetic hyperlipidemia mice. Mice feeding on HFD showed higher CTx levels, and mice with hyperlipidemia had elevated S1P levels. Correlation analysis found a positive correlation between CTx and S1P levels. Lower Runx2 expression and higher TRAP expression were found in both diet-induced and genetic hyperlipidemia mice, indicating decreased osteoblastic functions and increased osteoclastic functions in these mice. Bone marrow cells from LDLR^−/− mice also showed increased adipogenesis and inhibited osteogenesis accompanied by enhanced PPARγ expression. In conclusion, our study found decreased bone mass in both diet-induced and genetic hyperlipidemia mice.     

Deletion of a single allele of the Dkk1 gene leads to an increase in bone formation and bone mass.

Wnt/beta-catenin signaling has been proven to play a central role in bone biology. Unexpectedly, the Wnt antagonist Dkk2 is required for terminal osteoblast differentiation and mineralized matrix formation. We show that Dkk1, unlike Dkk2, negatively regulates osteoblast differentiation and bone formation. INTRODUCTION: The Wnt co-receptor LRP5 is a critical regulator of bone mass. Dickkopf (Dkk) proteins act as natural Wnt antagonists by bridging LRP5/6 and Kremen, inducing the internalization of the complex. Wnt antagonists are thus expected to negatively regulation bone formation. However, Dkk2 deficiency results in increased bone, questioning the precise role of Dkks in bone metabolism. MATERIALS AND METHODS: In this study, we investigated specifically the role of Dkk1 in bone in vitro and in vivo. Using rat primary calvaria cells, we studied the effect of retroviral expression of Dkk1 on osteoblast differentiation. In addition, the effect of Dkk1 osteoblast was studied in MC3T3-E1 cells by means of recombinant protein. Finally, to address the role of Dkk1 in vivo, we analyzed the bone phenotype of Dkk1(+/-) animals. RESULTS: Retroviral expression of Dkk1 in rat primary calvaria cells resulted in a complete inhibition of osteoblast differentiation and formation of mineralized nodules, with a marked decrease in the expression of alkaline phosphatase. Dkk1 expression also increased adipocyte differentiation in these cell cultures. Recombinant murine Dkk1 (rmDkk1) inhibited spontaneous and induced osteoblast differentiation of MC3T3-E1 cells. To determine the role of Dkk1 in vivo and overcome the embryonic lethality of homozygous deletion, we studied the bone phenotype in heterozygous Dkk1-deficient mice. Structural, dynamic, and cellular analysis of bone remodeling in Dkk1(+/-) mice showed an increase in all bone formation parameters, with no change in bone resorption, leading to a marked increase in bone mass. Importantly, the number of osteoblasts, mineral apposition, and bone formation rate were all increased several fold. CONCLUSIONS: We conclude that Dkk1 protein is a potent negative regulator of osteoblasts in vitro and in vivo. Given that a heterozygous decrease in Dkk1 expression is sufficient to induce a significant increase in bone mass, antagonizing Dkk1 should result in a potent anabolic effect.     

Osteoblast-specific targeting of soluble colony-stimulating factor-1 increases cortical bone thickness in mice.

The soluble and membrane-bound forms of CSF-1 are synthesized by osteoblasts and stromal cells in the bone microenvironment. Transgenic mice, generated to selectively express sCSF-1 in bone, showed increased cortical thickness in the femoral diaphysis caused by new bone formation along the endosteal surface. The ability of sCSF-1 to enhance bone cell activity in vivo is potentially relevant for increasing cortical bone in a variety of disorders. INTRODUCTION: The soluble form of colony-stimulating factor-1 (sCSF-1) and the membrane-bound form of CSF-1 (mCSF-1) have been shown to support osteoclastogenesis in vitro; however, the effect of each peptide on bone remodeling in vivo is unclear. To determine the effect of sCSF-1, selectively expressed in bone, the skeletal phenotype of transgenic mice harboring the human sCSF-1 cDNA under the control of the osteocalcin promoter was assessed. METHODS: At 5 and 14 weeks, mice were analyzed for CSF-1 protein levels, weighed, and X-rayed, and femurs were removed for peripheral quantitative computed tomography, histology, and histomorphometry. RESULTS: High levels of human sCSF-1 were detected in bone extracts and, to a lesser extent, in plasma. Adult transgenic mice showed normal body weight and increased circulating monocytic cells. At 5 weeks, the femoral diaphysis was similar in CSF-1T and wt/wt littermates. However, by 14 weeks, the femoral diaphysis in CSF-1T mice showed increased cortical thickness and bone mineral density. In contrast to the diaphysis, the femoral metaphysis of CSF-1T mice showed normal cancellous bone comparable with wt/wt littermates at each time point. Histological sections demonstrated increased woven bone along the endosteal surface of the diaphysis and intracortical remodeling. Fluorochrome-labeling analysis confirmed endocortical bone formation in CSF-1T, with a 3.1-fold increase in the percentage of double-labeled surfaces and a 3.6-fold increase in the bone formation rate compared with wt/wt mice. Although remodeling resulted in a slightly porous cortex, sCSF-1 preferentially stimulated endocortical bone formation, leading to increased cortical thickness. CONCLUSIONS: These findings indicate that sCSF-1 is a key determinant of bone cell activity in the corticoendosteal envelope.     

Strain-dependent variations in the response of cancellous bone to ovariectomy in mice.

The goal of this study was to characterize the skeletal response to ovariectomy in mice (129P3, C57BL/6, and B6129PF2) commonly used in gene manipulation studies to evaluate their potential as preclinical models of postmenopausal osteoporosis. The magnitude of cancellous bone loss and cellular indices of increased bone turnover in response to ovariectomy varied with mouse type and skeletal site, but in general, were less pronounced and less consistent than in Sprague-Dawley rats, the established preclinical model for postmenopausal bone loss. INTRODUCTION: The ovariectomized (OVX) rat is the most widely used preclinical rodent model for postmenopausal osteoporosis. However, the underlying mechanisms of bone disorders, including osteoporosis, have been explored predominantly in the mouse. The purpose of this study was to evaluate mice (129P3 and C57BL/6 inbred strains and their F2 hybrid offspring, B6129PF2), commonly used for gene knockout and overexpression studies, for their potential as preclinical models of postmenopausal bone loss. MATERIALS AND METHODS: The mice were OVX or sham-operated at 4 months of age and killed at 1 or 3 months after surgery. Lumbar vertebrae and distal femora were subjected to histomorphometric assessment. RESULTS: Mice in the two strains and the F2 hybrids (will be referred to as strain for the remainder of the abstract) lost vertebral cancellous bone after OVX; bone volume (BV/TV) was 20% and 27% lower at 1 and 3 months after surgery, respectively. The decreased cancellous BV/TV was associated with an increase in osteoclast surface at 1 month after OVX in the 129P3 strain only. Osteoblast surface was increased by 20% with OVX at both 1 and 3 months after surgery, irrespective of mouse strain. However, bone formation rate was not altered by OVX in any of the mouse strains. In contrast to the lumbar vertebrae, cancellous bone loss in response to OVX differed in the distal femur among the three mouse strains. OVX had no significant effect on distal femur BV/TV in the B6129PF2 mouse strain. In the C57BL/6 strain, cancellous BV/TV was reduced by OVX at 1 month after surgery but not at 3 months after surgery, whereas distal femur BV/TV in 129P3 mice was reduced at 3 months after surgery. Osteoclast surface was not affected by OVX at either time-point in the C57BL/6 strain, but was increased by 116% at 1 month after surgery in the 129P3 strain. Osteoblast surface was increased with OVX at 1 month after surgery, irrespective of strain, whereas bone formation rate was not altered by OVX at either time-point in any of the strains. CONCLUSIONS: The magnitude of cancellous bone loss and cellular indices of increased bone turnover in response to OVX varied with mouse strain and skeletal site, but in general, were less pronounced and less consistent than in the Sprague-Dawley rat. Although mouse models will continue to provide insights into genetic influences on bone mass and turnover, caution should be exercised when using 129P3 and C57BL/6 mice, and their F2 hybrids, as models for postmenopausal bone loss and preclinical testing of potential therapies for osteoporosis.     

Subchondral cancellous bone in osteoarthrosis and rheumatoid arthritis of the femoral head

Summary Thirty-three femoral heads taken from patients undergoing total hip replacement for osteoarthrosis and rheumatoid arthritis have been examined in undecalcified, plastic-embedded sections, using a quantitative histological method. The characteristic change of trabecular remodelling in the subchondral cancellous bone of the femoral heads was that total osteoid surface in the medial osteoarthritis (medial O.A.) and rheumatoid arthritis (R.A.) was significantly less than in the proximal osteoarthrosis (proximal O.A.) (P<0.01). Resorption surface was slightly greater in R.A. than in proximal O.A. (P<0.05). Bone area in the deep area was not different in each group. In the superficial area it was significantly less in medial O.A. than in proximal O.A. (P<0.05). The average width of trabeculae was slightly less in medial O.A. and R.A. It is suggested that subchondral trabecular remodelling may be a basic pathological process of general importance in the evolution of these diseases.

---

Zusammenfassung 33 Hüftköpfe, die von Patienten mit Coxarthrose und rheumatoider Arthritis stammen und bei denen eine Totalendoprothese durchgeführt wurde, wurden in unkalzifizierten plastikeingebetteten Schnitten untersucht, wobei eine quantitative histologische Methode zur Anwendung kam.Die charakteristischen Veränderungen der trabikulären Struktur im subchondralen spongiösen Knochen der Hüftköpfe bestand darin, daß die gesamte Osteoidoberfläche bei den medialen Osteoarthrosen (Mediale O.A.) und rheumatoiden Arthritiden (R.A.) erheblich kleiner war als bei den proximalen Osteoarthrosen (proximale O.A.) (P<0.01). Die resorbierende Oberfläche war geringfügig größer bei den R.A. als bei den proximalen O.A. (P<0.05).Die Ausdehnung des Knochens in den tiefergelegenen Schichten war in allen Gruppen gleich. In der oberflächlichen Schicht war sie erheblich geringer. Bei den medialen O.A. und R.A. als bei den proximalen O.A. (P<0.05). Die durchschnittliche Breite der Trabikular war bei der medialen O.A. und R.A. geringfügig kleiner. Es besteht die Vermutung, daß subchondraler Umbau der Trabikular ein grundlegender pathologischer Prozeß von allgemeiner Bedeutung in der Entwicklung dieser Krankheitsbilder sein könnte.

     

Progressive increase in bone mass and development of odontomas in aging osteopetrotic c-src-deficient mice

The critical role of c-src in osteoclast-mediated bone resorption has been emphasized by gene deletion experiments in mice. However, the long-term effects of the lack of c-src and impaired osteoclast function on the skeleton remain unknown. To further study the physiological role of c-src and to circumvent the early death of src(-/-) mice, due to starvation in the absence of erupted teeth, we maintained mice on a liquid diet. At the age of 2 months the src(-/-) mice presented signs of airway obstruction and all mice died progressively between 2.5 and 6 months of age. Radiography demonstrated severe osteopetrosis of the whole skeleton. Histomorphometrical analysis of the src(-/-) mice confirmed a significant increase in bone mass with age, resulting in complete loss of bone marrow spaces in some bones and explaining the consistent hepatosplenomegaly, due to extraskeletal hematopoesis. Histopathological examination of the skull revealed the presence of odontomas in the region of the unerupted incisors, with a penetrance of 100% in the aging src(-/-) mice. Although odontomas are benign lesions, their progressive growth leads to the obliteration of the nasal airways, progressive suffocation, and death in src(-/-) mice. These results suggest that: (i) in the absence of bone resorption, bone formation continues and leads to progressive accentuation of the osteopetrotic phenotype in src(-/-) mice; (ii) osteoclastic function is required for regular eruption of the incisors and deficient bone resorption is associated with the development of odontomas; and (iii) src(-/-) mice die by suffocation due to airway obliteration as a result of progressive odontoma growth.     

松质骨螺钉治疗股骨后髁骨折

1993年 8月～ 1998年 10月 ,笔者共收治 11例股骨后髁骨折患者 ,均为单侧后髁骨折 (Ｈｏｆｆａ骨折 ) ,采用松质骨螺钉内固定 ,术后早期开始关节功能锻炼 ,取得了满意效果。1　病例资料本组男 9例 ,女 2例 ,年龄 2 0～ 6 4岁。车祸伤 8例 ,跌伤 3例。外侧 3例 ,内侧 8例 ;合并髌骨粉碎性骨折 1例。 11例骨折均有不同程度移位 ,受伤至手术时间 3～ 46ｈ。2　治疗方法采用膝前外侧或前内侧切口 ,显露股骨髁关节面 ,使骨折块解剖复位。选择适当长度松质骨螺钉 ,自骨折髁后内 (或外 )侧面关节外部分 ,偏后斜向前外 (或内 )方向拧入螺钉固定 ,使…     

Glucocorticoid excess during adolescence leads to a major persistent deficit in bone mass and an increase in central body fat.

Endogenous Cushing's syndrome (CS) in children causes growth retardation, decreased bone mass, and increased total body fat. No prospective controlled studies have been performed in children to determine the long-term sequelae of CS on peak bone mass and body composition. A 15-year-old girl with Cushing disease (CD), and her healthy identical co-twin, were followed for 6 years after the CD was cured. At the 6-year follow-up both twins had areal bone mineral density (BMD) and body composition determined by dual-energy X-ray absorptiometry (DXA) and three-dimensional quantitative computed tomography (3DQCT). Z scores for height, weight, and body mass index (BMI) were -2.3, -0.8 and 0.2, and 1.2, 0.2, and -0.6, in the twin with CD and her co-twin, respectively. In the twin with CD, areal BMD and bone mineral apparent density (BMAD) at different sites varied from 0.7 to 3 SD below her co-twin. Volumetric lumbar spine bone density Z score was -0.75 and 1.0, and total body, abdominal visceral, and subcutaneous fat (%) was 42, 10, and 41 versus 26, 4, and 17 in the twin with CD and her co-twin, respectively. The relationship between total body fat and L2-L4 BMAD was inverse in the twin with CD (p < 0.05), which by contrast in her co-twin was opposite and direct (p < 0.001). In the twin with CD, despite cure, there was a persistent deficit in bone mass and increase in total and visceral body fat. These observations suggest that hypercortisolism (exogenous or endogenous) during adolescence may have persistent adverse effects on bone and fat mass.     

Chemical composition of normal and osteoarthrotic cancellous bone of the femoral head

Summary Using EDTA extraction and collagenase digestion, cancellous bone from the femoral heads of ten normal and eight osteoarthrotic individuals was analyzed for its content of collagen, sialoprotein, proteoglycan, and carbohydrate. The EDTA extractability of the matrix proteins of the osteoarthrotic bone was significantly increased (P< 0.001), as was the soluble collagenase-resistant fraction (SCRF). EDTA residues, bone matrix size, the collagenase-resistant fraction (CRF), and the insoluble collagenase-resistant fraction (ICRF) of the osteoarthrotic cases were not different from those of the controls. The amounts of carbohydrate and proteoglycans were considerably elevated in the bone matrix of the osteoarthrotic bone (P<0.01 and P<0.001, respectively). In the EDTA extracts, sialoprotein and proteoglycan contents were found in significant higher amounts (P<0.05 and P<0.01, respectively) in the osteoarthrotic cases. In the SCRF, the hexose and sialic acid contents were higher in the osteoarthrotic bone (P<0.01), while in the ICRF all the analyses were significantly increased in the osteoarthrotic bone (P<0.001). The ratios of collagen to non-collagenaus components were lower in the osteoarthrotic than in normal bones. The quantitative and qualitative variations in cancellous bone proteins from the femoral head in osteoarthrosis found in this study suggest that alterations in subchondral bone play a role in the pathophysiology of cartilage degeneration in osteoarthrosis.

---

Zusammenfassung Mittels EDTA Extraktion und Kollagenase-Fermentierung wurde der Gehalt an Kollagen, Sialoprotein, Proteoglycan und Karbohydrat im Knochenmaterial der Hüftköpfe von 10 normalen und 8 osteoarthrotischen Personen analysiert. Die EDTA Extrahierbarkeit der Matrixproteine des osteoarthrotischen Knochens war signifikant gestiegen (P>0,001) ebenso wie der lösliche Kollagenase resistente Teil (LKRT). EDTA Reste, die Größe der Knochenmatrix, der Kollagenase resistente Teil (KRT) and der unlösliche Kollagenase resistente Teil (UKRT) der osteoarthrotischen Hüftköpfe unterschieden sich nicht von den Kontrollfällen. Die Mengen von Karbohydrat und Proteoglycan waren deutlich erhöht in der Knochenmatrix der osteoarthrotischen Knochen (P<0,01 bzw. P<0,001). In den EDTA Extrakten war der Gehalt an Sialoprotein und Proteoglycan bei den osteoarthrotischen Hüftköpfen deutlich höher (P< 0,05 bzw. P< 0,01). Im LKRT war der Gehalt an Hexose and sialischer Säure höher im osteoarthrotischen Knochen (P<0,01), während im UKRT alle Analysen deutlich h6her waren im osteoarthrotischen Knochen (P<0,001). Das Verhältnis von Kollagen zum kollagefreien Anteil war niedriger im osteoarthrotischen als im normalen Knochen. Quantitative and qualitative Veränderungen in Knochenproteinen des osteoarthrotischen Hüftkopfes, wie sie die vorliegende Studie ausweist, lassen vermuten, daß Veranderungen im subchondralen Knochen eine wichtige Rolle spielen in der Pathophysiologie der Degeneration des Gelenkknorpels bei Osteoarthrosis.

     

定量CT对股骨头松质骨骨密度的测量

目的探讨利用定量CT(quantitative computed tomography,QCT)中"3D Spine Exam Analysis"软件分析模块测量股骨头松质骨的骨密度的可重复性,以及患者双侧股骨头松质骨骨密度的差异性。方法回顾性研究330名(女性239人,男性91人)受试者的股骨头松质骨骨密度,对其中因各种原因仅可获得一侧髋关节图像的受试者149人进行可重复性研究;对其余的受试者181人进行双侧股骨头松质骨骨密度的差异性研究。利用QCT Pro软件中"3D Spine Exam Analysis"软件分析模块将股骨头划分为上、中、下3个层面:靠近股骨颈上部皮质、经股骨颈中心、靠近股骨颈下部皮质,并对各个层面进行测量。结果2名不同操作者测量同一股骨头的相同层面松质骨骨密度值的差异无统计学意义(P_上=0. 148 0. 05,P_中=0. 05,P_下=0. 0970. 05)。同一患者双侧股骨头相对应层面的松质骨骨密度之间具有良好相关性。在上层,两侧股骨头的松质骨骨密度之间的差异无统计学意义(P_上=0. 4450. 05);而在中层与下层,两侧股骨头的松质骨骨密度之间的差异有统计学意义(P_中=0. 0000. 05,P_下=0. 0000. 05)。结论利用QCT中"3D Spine Exam Analysis"软件分析模块进行股骨头松质骨的骨密度测量具有较好的可重复性。患者双侧股骨头不同层面松质骨的骨密度具有良好的相关性,并且左侧股骨头的中层与下层的松质骨骨密度显著大于右侧。     

Drilling and cancellous bone grafting for avascular necrosis of the femoral head

Objectives  

Maintenance of form and function and prevention of further deterioration of avascular necrosis of the femoral head through core decompression and cancellous bone grafting.     

Increased femoral neck cancellous bone and connectivity in coxarthrosis (hip osteoarthritis)

Patients with coxarthrosis (cOA) have a reduced incidence of intracapsular femoral neck fracture, suggesting that cOA offers protection. The distribution of bone in the femoral neck was compared in cases of coxarthrosis and postmortem controls to assess the possibility that disease-associated changes might contribute to reduced fragility. Whole cross-section femoral neck biopsies were obtained from 17 patients with cOA and 22 age- and sex-matched cadaveric controls. Densitometry was performed using peripheral quantitated computed tomography (pQCT) and histomorphometry on 10-microm plastic-embedded sections. Cortical bone mass was not different between cases and controls (P > 0.23), but cancellous bone mass was increased by 75% in cOA (P = 0.014) and histomorphometric cancellous bone area by 71% (P < 0.0001). This was principally the result of an increase of apparent density (mass/vol) of cancellous bone (+45%, P = 0.001). Whereas cortical porosity was increased in the cases (P < 0.0001), trabecular width was also increased overall in the cases by 52% (P < 0.001), as was cancellous connectivity measured by strut analysis (P < 0.01). Where osteophytic bone was present (n = 9) there was a positive relationship between the amount of osteophyte and the percentage of cancellous area (P < 0.05). Since cancellous bone buttresses and stiffens the cortex so reducing the risk of buckling, the increased cancellous bone mass and connectivity seen in cases of cOA probably explain, at least in part, the ability of patients with cOA to resist intracapsular fracture of the femoral neck during a fall.     

Changes of cancellous bone mass in rat mandibular condyle following ovariectomy.

Changes in cancellous bone of the rat mandibular condyle following estrogen deficiency were histomorphometrically examined with 120-day-old female Fischer rats. Sixty-four animals were either ovariectomized bilaterally (ovx) or subjected to sham surgery (sham), and eight from each group were killed at 7, 14, 30, and 60 days after surgery. Seven intact animals were killed on day 0. Before killing, tetracycline and calcein were administered to all animals. Following histological observation, bone histomorphometry of the mandibular condyle was done using a confocal laser scanning microscope and an image analyzer. The sampling site was divided into two regions for analysis: (1) a "subchondral region," formed by the region connected to cartilage; and (2) a "central region," formed by the region beneath the former. The changes in these two regions were analyzed separately. In the sham group's condyle, the bone volume of the subchondral and central regions increased with the passage of time, although the bone turnover became low. This bone gain could be due to the effects of growth and the mechanical stimulus by occlusal load. In the subchondral region of the ovx group's condyle, the bone volume decreased significantly at 7 days, but recovered to reach approximately the same value as the sham group from 14 days onward. In the central region of the ovx group's condyle, the bone volume was unchanged, but revealed a significantly lower value than that of the sham group at 60 days (p < 0.01). Thus, ovariectomy inhibited bone gain, which was observed in the sham group's condyle even though there was no bone loss. On the other hand, the trabecular separation in the ovx's condyle of both the subchondral and central regions increased considerably and small marrow cavities interconnected to form a large bone marrow. Therefore, the ovx rat mandibular condyles dynamically altered their structures under the effects of estrogen deficiency and occlusal loads. Consequently, estrogen deficiency induced transient subchondral bone loss and recovery, whereas, in the central region, it inhibited bone gain. This suggests that mechanical loading modulates the normal ovx-induced bone loss found in other parts of the skeleton.     

Phosphodiesterase inhibitors, pentoxifylline and rolipram, increase bone mass mainly by promoting bone formation in normal mice

The administration of either Pentoxifylline (PTX), a methylxanthine derivative and an inhibitor of cyclic AMP (c-AMP) phosphodiesterases (PDEs), or Rolipram, an inhibitor specific to type-4 PDE (PDE4) in normal mice, significantly increased both cortical and cancellous bone mass. Vertebrae and tibiae from mice treated with PTX or Rolipram were analyzed by means of bone densitometry and histomorphometry. The results revealed that both PTX and Rolipram increased bone mass in normal mice mainly through the acceleration of bone formation. These findings suggest that both PTX and Rolipram can enhance physiological bone formation and thereby increase bone mass in normal mice. The possibility that these agents may be of value for the treatment of osteoporosis is discussed.