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At least 1,153 records · Page 64Linked to original sources
PubMed2001

[Osteoporosis in all young daughters of a mother with multiple osteoporotic fractures. A case of familial osteoporosis].

We herein describe a family whose female members are all osteoporotic: a postmenopausal mother and her three premenopausal daughters. The mother aged 60 presented axial and peripheral fractures, and very low bone mineral density (BMD). She reported that her grandmother had suffered a hip fracture. The eldest daughter aged 30 suffered multiple vertebral fractures during pregnancy and lactation associated with very low BMD. In view of these observations, the other two daughters aged 29 and 27 years respectively were evaluated. BMD was found to be severely diminished according to densitometric values for osteoporosis established by WHO, but they had no history of bone fractures. Probably the strong genetic component in bone mass is responsible for the severely diminished BMD observed in all the women in this family, as well as the occurrence of bone fractures in two of them. To our knowledge, there are no similar reports in the literature. Our results evidence the importance of evaluating bone mass in the offspring of an individual presenting severe osteoporosis, in order to detect family members with low bone mass and at high risk of developing bone fractures.

Adult↗
PubMedDate not supplied

Somatotyping in the obese children and adolescents.

Age-related somatic variability studied by 15 anthropometric parameters was assessed in 278 subjects (138 boys and 140 girls) aged between 5 and 20 years. Of these, 30% had simple obesity, 10.0% obesity associated with hypothyroidism, 10.0% obesity with diabetes, 25% obesity with adrenocortical reaction, 23.5% functional adiposo-genital syndrome and 1.5% Cushing's syndrome. The peculiarities related to the somatic development as a whole, the degree of bone development, and adiposity are interpreted in the main clinical forms of obesity, on the basis of the morphogram.

Adolescent↗
PubMed1998

Collagenase and tissue plasminogen activator production in developing rat calvariae: normal progression despite fetal exposure to microgravity.

Exposure to zero gravity has been shown to cause a decrease in bone formation. This implicates osteoblasts as the gravity-sensing cell in bone. Osteoblasts also are known to produce neutral proteinases, including collagenase and tissue plasminogen activator (tPA), which are thought to be important in bone development and remodeling. The present study investigated the effects of zero gravity on development of calvariae and their expression of collagenase and tPA. After in utero exposure to zero gravity for 9 days on the NASA STS-70 space shuttle mission, the calvariae of rat pups were examined by immunohistochemistry for the presence and location of these two proteinases. The ages of the pups were from gestational day 20 (G20) to postnatal (PN) day 35. Both collagenase and tPA were found to be present at all ages examined, with the greatest amount of both proteinases present in the PN14 rats. At later ages, high amounts were maintained for tPA but collagenase decreased substantially between ages PN21 to PN35. The location of collagenase was found to be associated with bone-lining cells, osteoblasts, osteocytes, and in the matrix along cement lines. In contrast, tPA was associated with endothelial cells lining the blood vessels entering bone. The presence and developmental expression of these two proteinases appeared to be unaffected by the exposure to zero gravity. The calvarial thickness of the pups was also examined; again the exposure to zero gravity showed little to no effect on the growth of the calvariae. Notably, from G20 to PN14, calvarial thickness increased dramatically, reaching a plateau after this age. It was apparent that elevated collagenase expression correlated with rapid bone growth in the period from G20 to PN14. To conclude, collagenase and tPA are present during the development of rat calvariae. Despite being produced by the same cell in vitro, i.e., the osteoblast, they are located in distinctly different places in bone in vivo. Their presence, developmental expression, and quantity do not seem to be affected by a brief exposure to zero gravity in utero.

Aging↗
PubMed2001

Craniofacial morphology, dentition, and skeletal maturity in four siblings with Seckel syndrome.

OBJECTIVE: To describe the craniofacial morphology, dentition, and hand maturity in four siblings with Seckel syndrome. PATIENTS: Two boys and two girls, with Seckel syndrome. The children studied showed extreme growth retardation, severe microcephaly, bird-headed profile with receding chin, prominent nose, mental retardation, and extremely delayed skeletal maturation. The growth hormone axis and pituitary thyroid function was normal. METHODS: Skeletal and dental development were investigated from radiographic material, and a cephalometric analysis was performed from profile radiographs. RESULTS: The craniums were remarkably small with an extremely short anterior cranial base (-4.3 to -5.5 standard units) and maxillary length (-3.8 to -4.7 SU). Differences in the morphology of the sella turcica were observed in girls and boys. Tooth maturity progressed normally. Tooth agenesis and tooth malformations were observed. Taurodontic root morphology was observed only in the girls. The approximate skeletal maturity showed retardation from 4 years 3 months to 4 years 11 months. Malformations of the hand-wrist skeleton occurred in the epiphyseal ossification centers of the middle phalangeal bone in the second, third, and fourth finger and in the distal phalangeal bone in the fifth finger. The epiphyseal ossification centers were lacking in the middle and distal phalangeal bones of the fifth finger. CONCLUSION: The underlying gene defect in the affected children seemingly affects bone development and growth but not dental maturation and eruption.

Adolescent↗
PubMed2006

Transcriptional co-repressors of Runx2.

Runx2 is an essential transcription factor for skeletal mineralization because it stimulates osteoblast differentiation of mesenchymal stem cells, promotes chondrocyte hypertrophy, and contributes to endothelial cell migration and vascular invasion of developing bones. Runx2 is also expressed during mouse embryo development in nascent mammary gland epithelium. Recent evidence implicates deregulation of Runx2 as a contributing factor in breast cancer-induced osteolysis and invasion, as well as in ectopic vascular calcification. Like other Runt domain proteins, Runx2 is a context-dependent transcriptional activator and repressor of genes that regulate cellular proliferation and differentiation. Proteins that temporally and spatially associate with Runx2 dictate these opposing transcriptional activities. Recent studies have identified several co-repressor proteins that bind to Runx2 to regulate gene expression. These co-factors include histone deacetylases (HDACs), transducin-like enhancer of split (TLE) proteins, mSin3a, and yes-associated protein (YAP). These proteins do not bind DNA themselves and appear to act by preventing Runx2 from binding DNA, altering chromatin structure, and/or by possibly blocking co-activator complexes. The nuclear localization of several of these factors is regulated by extracellular signaling events. Understanding the mechanisms whereby co-repressor proteins affect Runx2 activity during normal cellular development and tumor progression will identify new therapeutic targets for skeletal disorders such as osteoporosis and for bone metastatic cancers.

Animals↗
PubMed1979

Developmental interactions between the adjacent parts of combined heterologous skeletogenous territories.

The right limb buds of chick embryos (H.-H.stages 22 to 26) were transversely divided at approximately the presumptive zeugopod mid-length, and (1) the distal parts exchanged between wing and hind-limb bud in apdv-reversed orientation (operation A), or (2) the severed distal part of the leg bud was reoriented in situ (operation B). Both the proximal and distal segments of the zeugopodal bones developing from the recombined portions of presumptive heterologous territories showed characteristic differences of size and shape in comparison to the corresponding parts of the skeletal pieces of the zeugopod of the intact, control limbs. These developmental changes are interpreted as being the consequence of reciprocal influences exerted by the adjacent parts of mesenchymal territories (or blastemata) that, under normal developmental conditions, are destined to give rise to different bones. Such influences may enhance or depress the growth potential of the skeletogenous populations affected, and, within each cell population, modify the geometry of the growth processes by which the various parts of each skeletal piece attain their typical shape.

Animals↗
PubMed1996

Effect of maternal ethanol consumption on maternal and fetal calcium metabolism.

Alcohol consumption can have deleterious effects on both adult and developing bone. The mechanism(s) by which alcohol affects bone, however, is unknown. This study investigated the possibility that alcohol affects bone by alterations in calcium (Ca) metabolism. Female rats were fed lab chow ad libitum (C, Control) or a liquid diet with (E, Ethanol) or without (PF, Pair-Fed) ethanol. After 2 weeks on their respective diets, the rats were bred and the experimental diets continued throughout gestation. Blood (dams only) and tissue were collected on day 21 of gestation. The Ca content of maternal bone showed a trend toward a decrease in E and PF compared with C dams. Ionic Ca (iCa) levels were decreased in the blood of the E compared with PF and C dams. Serum parathyroid hormone levels were elevated in the E compared with C dams, consistent with the low iCa levels. Serum levels of 1,25(OH)2D, however, were elevated only in the PF dams. Mean fetal body weight and fetal skeletal ossification were reduced in the E compared with PF and C groups, but no group differences were found in fetal Ca content. These results indicate that maternal ethanol consumption compromised the ability of the dam to regulate her blood iCa levels, possibly partly due to a failure to increase 1,25(OH)2D levels. The delays in skeletal development observed in the ethanol exposed fetuses, however, do not appear to result from impaired placental Ca transfer.

Animals↗
PubMed1989

Association of the C-propeptide of type II collagen with mineralization of embryonic chick long bone and sternal development.

Several proteins may play a role in bone formation. The C-propeptide of type II collagen is intimately associated with endochondral bone formation in bovine growth plate. We have used an antibody against this peptide to determine its immunofluorescent distribution in early stages of embryonic chick limb development with emphasis on first bone formation which occurs in the mid-diaphyseal region. The C-propeptide II is first evident by immunofluorescent localization at stage 27 (day 5-6) of embryonic tibia development with chondrocytes in the central mid-diaphysis. In subsequent stages, there is an increase in the number of chondrocytes in which it is localized in discrete vacuoles. Up to stage 30, immunofluorescence is observed intracellularly, after which it appears in the matrix. The released C-propeptide II appears to remain only transiently associated with the cartilage matrix and becomes concentrated in the calcifying periosteum, the region outside of the cartilage core where bone formation first occurs in a sequence of events comparable to intramembranous bone formation. These observations can be reproduced in cultures of stage 35 hypertrophic chondrocytes (core cells) and periosteum cells (collar cells). Core cells contain intensely stained intracellular vacuoles while collar cells are negative, although the collar cell osteogenic matrix concentrates exogenously added C-propeptide II. Double label immuno-staining shows that the C-propeptide II, unlike type II collagen and proteoglycan, which are secreted and incorporated into extracellular sites, is initially stored in intracellular vacuoles. The matrix localization of the C-propeptide II during the transition from cartilage to bone indicates a close association with the initiation of mineralization events of cartilage and bone and its specific origin in chondrocytes and not osteoblasts. These observations suggest that the C-propeptide II made by chondrocytes is associated with the formation of bone.

Animals↗
PubMedDate not supplied

Establishment and characterization of a new osteogenic cell line (MOS-J) from a spontaneous C57BL/6J mouse osteosarcoma.

In this paper we describe the establishment and characterization of a transplantable cell line derived from a spontaneously occurring chondroblastic osteosarcoma in a C57BL/6J mouse. The tumor line, MOS-J, forms solid tumors when injected intramuscularly into immunocompetent syngeneic hosts, mimicking endochondral bone development. These transplantable tumors have the capacity to destroy and invade existing bone and invade vessels in close proximity to the tumor. In culture, MOS-J cells form layers of pleomorphic cells with high mitotic activity. These cells have marked alkaline phosphatase activity and form calcified foci in vitro that stain with alizarin red. MOS-J cells also promote osteoclast development in vitro from normal bone marrow cells. These characteristics indicate the potential utility of the MOS-J osteosarcoma cell line as a model for studies of human osteosarcoma and bone biology.

Alkaline Phosphatase↗
PubMed1994

Skeletal growth of commercial poultry species.

There have been significant increases in growth and development of commercial broilers, turkeys, and ducks. The large decline in days to market and disproportional increases in breast yield have contributed to greater incidences of various skeletal anomalies. Across all three species, tibial dyschondroplasia is observed about half-way through the growing period (50%), but in each case the birds have achieved 40% or less of their final BW. Relative tibia development (length and width) is significantly slower in broilers compared with turkeys and ducks, which suggests a greater susceptibility to biomechanical problems, the end result of which is abnormal long bone development. There are relatively few studies that have addressed changes in the femur as well as the tibia. There are indications that mineralization rates and other aspects of femur development occur more slowly than what is observed for the tibia. In this regard, the femur may be the weak link with respect to long bone developmental abnormalities. Nutrient restriction during short periods of the growout has proven to be an effective way of decreasing leg abnormalities. In all cases, however, there are corresponding declines in BW at normal market ages and associated declines in absolute breast muscle development. In the future, however, these fractional losses in measures of carcass yield may still be economically advantageous compared with the cost of increased leg problems under field conditions.

Animals↗
PubMed1994

Isolation of bone from muscles prevents the development of experimental callus-like heterotopic bone. A study of the interaction of bone and muscle in new bone formation.

Heterotopic bone (HB) has previously been provoked in the compartment of the profundus part of the vastus intermedius muscle (VIP) by manipulation of the rabbit knee immobilized in extension. The authors isolated the femoral bone of adult rabbits with a permeable or an impermeable polymer membrane to investigate the interactions of bone, periosteum, and muscle in callus-like HB formation, using the HB model. Heterotopic bone developed beside but not over the membrane if isolation was carried out before the immobilization-manipulation period, regardless of the type of membrane used. In cases where the femoral bone was isolated from the muscle by insertion of the tubular membrane one to two weeks after the immobilization-manipulation had begun, there was HB formation over and beside the membrane. No HB developed under the membrane in any of the cases of femoral bone isolation. Thus direct and extensive contact between bone and muscle appears to be essential at the onset of formation of experimental HB. An intertissue exchange of soluble substances derived from bone or muscle, however, does not seem to play an essential role here. After the onset of HB formation, its further development will not be prevented by subsequent isolation of muscle and bone. The study elucidates the interaction between bone and adjacent muscles and the results may be valuable in further investigations on HB and fracture healing.

Animals↗
PubMed2004

Is there a favorable subset of patients with prostate cancer who develop oligometastases?

OBJECTIVE: To analyze, retrospectively, the patterns and behavior of metastatic lesions in prostate cancer patients treated with external beam radiotherapy and to investigate whether patients with < or =5 lesions had an improved outcome relative to patients with >5 lesions. METHODS AND MATERIALS: The treatment and outcome of 369 eligible patients with Stage T1-T3aN0-NXM0 prostate cancer were analyzed during a minimal 10-year follow-up period. All patients were treated with curative intent to a mean dose of 65 Gy. The full history of any metastatic disease was documented for each subject, including the initial site of involvement, any progression over time, and patient survival. RESULTS: The overall survival rate for the 369 patients was 75% at 5 years and 45% at 10 years. The overall survival rate of patients who never developed metastases was 90% and 81% at 5 and 10 years, respectively. However, among the 74 patients (20%) who developed metastases, the survival rate at both 5 and 10 years was significantly reduced (p <0.0001). The overall survival rate for patients who developed bone metastases was 58% and 27% at 5 and 10 years, respectively, and patients with bone metastases to the pelvis fared worse compared with those with vertebral metastases. With regard to the metastatic number, patients with < or =5 metastatic lesions had superior survival rates relative to those with >5 lesions (73% and 36% at 5 and 10 years vs. 45% and 18% at 5 and 10 years, respectively; p = 0.02). In addition, both the metastasis-free survival rate and the interval measured from the date of the initial diagnosis of prostate cancer to the development of bone metastasis were statistically superior for patients with < or =5 lesions compared with patients with >5 lesions (p = 0.01 and 0.02, respectively). However, the survival rate and the interval from the date of diagnosis of bone metastasis to the time of death for patients in both groups were not significantly different, statistically (p = 0.17 and 0.27, respectively). CONCLUSIONS: Patients with < or =5 metastatic sites had significantly better survival rates than patients with >5 lesions. Because existing sites of metastatic disease may be the primary sites of origin for additional metastases, our findings suggest that early detection and aggressive treatment of patients with a small number of metastatic lesions is worth testing as an approach to improving long-term survival.

Aged↗
PubMed1991

Expression of bone sialoprotein (BSP) in developing human tissues.

Bone sialoprotein (BSP) and its messenger RNA were localized in developing human skeletal and nonskeletal tissues by means of immunohistochemistry and in situ hybridization. Both protein and mRNA were found in mature, bone-forming cells but not in their immature precursors. In addition, osteoclasts displayed positive immunostaining and high densities of autoradiographic grains by in situ hybridization experiments. BSP was expressed in fetal epiphyseal cartilage cells, particularly in hypertrophic chondrocytes of growth plates. Though neither the protein nor the mRNA were identified in a variety of other connective and nonconnective tissues, an unexpected finding was the expression of BSP in the trophoblast cells of placenta. These findings show that BSP is primarily an osteoblast-derived component of the bone matrix expressed at late stages of differentiation. We have also found that osteoclasts produce BSP, possibly as a mediator of cell attachment to bone.

Animals↗
PubMed1996

Semaphorin III is needed for normal patterning and growth of nerves, bones and heart.

The expression patterns of the recently discovered family of semaphorin genes suggests that they have widespread roles in embryonic development. Some seem to guide neuronal growth cones, but otherwise their functions are unknown. Semaphorin III is a membrane-associated secreted protein with a developmentally dynamic pattern of expression, including particular domains of the nervous system, the borders of developing bones, and the heart. In vitro, semaphorin III causes growth-cone collapse, and repels cutaneous sensory axons from the ventral spinal cord. Mutants in the Drosophila gene semaII, which encodes a related semaphorin, die after eclosion, but no responsible abnormality is evident. We have generated mice mutant in the semaIII gene by homologous recombination. Here we show that in the mutants, some sensory axons project into inappropriate regions of the spinal cord where semaIII is normally expressed. The cerebral cortex of homozygous mutant mice shows a paucity of neuropil and abnormally oriented neuronal processes, especially of the large pyramidal neurons. Certain embryonic bones and cartilaginous structures develop abnormally, with vertebral fusions and partial rib duplications. The few mice that survive more than a few days postnatally manifest pronounced and selective hypertrophy of the right ventricle of the heart and dilation of the right atrium. Thus, semaphorin III might serve as a signal that restrains growth in several developing organs.

Animals↗
PubMed2000

Tibial quantitative ultrasound versus whole-body and lumbar spine DXA in a Dutch pediatric and adolescent population.

RATIONALE AND OBJECTIVES: To understand normal bone development, studies in healthy children and adolescents are important. To assess the applicability of tibial quantitative ultrasound measurements (QUS) in children, we performed a study that compared dual-energy x-ray absorptiometry (DXA) of the lumbar spine and whole body with tibial QUS. METHODS: For this study we recruited 146 Dutch children and adolescents, 58 boys (median age, 14.1 years; range, 7.6-23.4 years) and 88 girls (median age, 18.0 years; range, 7.6-23.5 years). Tanner stage, weight, and height were assessed for all participants. Bone mineral density (BMD; g x cm(-2)) of the whole body and lumbar spine (L2-L4) and bone mineral apparent density (BMAD) of the lumbar spine (g x cm(-3)) were assessed by using the Lunar DPXL. For tibial QUS, the Soundscan compact system was used. RESULTS: Both lumbar as well as whole-body BMD showed a strong, significant correlation with tibial QUS in boys and girls: rtotal body boys = 0.81, rtotal body girls = 0.77, rlumbar spine boys = 0.79, and rlumbar spine girls = 0.72. Lumbar spine BMAD also showed significant correlations with tibial QUS: rboys= 0.63 and rgirls = 0.63 (for all correlations, P < 0.001). CONCLUSIONS: Our study showing strong, significant correlations between DXA and tibial QUS measurements suggests that tibial QUS is a technique that may be applicable in children and adolescents.

Absorptiometry, Photon↗
PubMed2004

Human stanniocalcin-2 exhibits potent growth-suppressive properties in transgenic mice independently of growth hormone and IGFs.

Stanniocalcin (STC)-2 was discovered by its primary amino acid sequence identity to the hormone STC-1. The function of STC-2 has not been examined; thus we generated two lines of transgenic mice overexpressing human (h)STC-2 to gain insight into its potential functions through identification of overt phenotypes. Analysis of mouse Stc2 gene expression indicates that, unlike Stc1, it is not highly expressed during development but exhibits overlapping expression with Stc1 in adult mice, with heart and skeletal muscle exhibiting highest steady-state levels of Stc2 mRNA. Constitutive overexpression of hSTC-2 resulted in pre- and postnatal growth restriction as early as embryonic day 12.5, progressing such that mature hSTC-2-transgenic mice are approximately 45% smaller than wild-type littermates. hSTC-2 overexpression is sometimes lethal; we observed 26-34% neonatal morbidity without obvious dysmorphology. hSTC-2-induced growth retardation is associated with developmental delay, most notably cranial suture formation. Organ allometry studies show that hSTC-2-induced dwarfism is associated with testicular organomegaly and a significant reduction in skeletal muscle mass likely contributing to the dwarf phenotype. hSTC-2-transgenic mice are also hyperphagic, but this does not result in obesity. Serum Ca2+ and PO4 were unchanged in hSTC-2-transgenic mice, although STC-1 can regulate intra- and extracellular Ca2+ in mammals. Interestingly, severe growth retardation induced by hSTC-2 is not associated with a decrease in GH or IGF expression. Consequently, similar to STC-1, STC-2 can act as a potent growth inhibitor and reduce intramembranous and endochondral bone development and skeletal muscle growth, implying that these tissues are specific physiological targets of stanniocalcins.

Animals↗
PubMed1994

[Treatment of tumor osteopathy in cancer of the prostate].

Some 40% of patients with prostate cancer present with disseminated disease at the time of diagnosis and up to 80% of the total will develop bone dissemination during the disease. The aging of the population and the elevated incidence of prostate cancer (13% of malignancies in males) bring the figure of prostate cancer diagnosed in Europe to 85,000 new cases every year. To begin with, a comment on the overall aspects of bone metastasis from prostate cancer such as incidence, development mechanisms, distribution, prognosis and clinical outcome is made placing special emphasis on the grading and the evaluation of major therapeutical regimes for this kind of patients. Bone metastasis are the most frequent cause of pain due to cancer and are also the cause of immobilization, pathological fractures, bone marrow affectation, medullary compression and sometimes hypercalcemia. It is obvious that any comprehensible therapeutical approach must be multidisciplinary.

Bone Neoplasms↗