Effect of pamidronate administration on bone in patients with acute spinal cord injury.
(1/12)
Eleven subjects participated in a prospective placebo-controlled trial to address the efficacy of pamidronate in reducing bone loss in persons with acute spinal cord injury (SCI). We administered pamidronate (treatment) or normal saline (placebo) intravenously at baseline (22 to 65 days after injury) and sequentially over 12 months, with follow-up at 18 and 24 months. Regional bone mineral density (BMD) was lost over time, regardless of group. In the treatment group compared with the placebo group, we noted a mild early reduction in loss of total leg BMD. Significant bone loss from baseline occurred earlier in the placebo group at the regional sites than in the treatment group. However, by the end of the treatment and follow-up phases, both groups demonstrated a similar percent bone loss from baseline. Despite an early reduction in bone loss, pamidronate failed to prevent major, long-term bone loss in persons with acute neurologically complete SCI. (+info)
Relationship of fat mass and serum estradiol with lower extremity bone in persons with chronic spinal cord injury.
(2/12)
In the spinal cord injury (SCI) population, a relationship between adiposity and leg bone has not been reported, nor one between serum estradiol and leg bone mass. A cross-sectional, comparative study of 10 male pairs of monozygotic twins discordant for SCI was performed. Relationships were determined among bone mineral density (BMD), bone mineral content (BMC), lean mass, fat mass, and serum sex steroids. In the twins with SCI, significant relationships were evident between leg BMD or BMC with total body percent fat (r2= 0.49, P < 0.05; r2= 0.45, P = 0.05), leg fat mass (r2 = 0.76, P < 0.0005; r2= 0.69, P = 0.005), and serum estradiol (r2= 0.40, P = 0.05; r2= 0.37, P = 0.05). By stepwise regression analysis, in the twins with SCI, leg fat mass was found to be the single most significant predictor of leg BMD or BMC (F = 12.01, r2= 0.76, P = 0.008; F = 50.87, r2= 0.86, P < 0.0001). In the able-bodied twins, leg lean mass correlated with leg BMD and BMC (r2= 0.58, P = 0.01; r2= 0.87, P = 0.0001). By use of within-pair differences, significant correlations were found for leg lean mass loss with leg BMD loss (r2= 0.56, P = 0.01) or leg BMC loss (r2= 0.64, P = 0.0005). In conclusion, in twins with SCI, significant correlations were observed between fat mass and leg BMD or BMC as well as between serum estradiol values and leg BMD. The magnitude of the leg muscle mass loss was correlated with the magnitude of bone loss. (+info)
Inhibition of p38 mitogen-activated protein kinase prevents inflammatory bone destruction.
(3/12)
Mitogen-activated protein kinase (MAPK) pathways are implicated in joint destruction in rheumatoid arthritis (RA) by modulating the production and functions of inflammatory cytokines. Although p38 MAPK (p38) participates in signaling cascades leading to osteolysis in arthritis, the mechanisms of its action in this process remain incompletely understood. Here, we found that the osteoclast (Ocl) precursors expressed p38alpha, but not p38beta, p38delta, and p38gamma isoforms. Treatment of these cells with receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) resulted in p38 activation. Importantly, Ocl development induced by RANKL or RANKL and tumor necrosis factor (TNF)-alpha was blocked with the novel p38 inhibitor 4-(3-(4-chlorophenyl)-5-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)pyrimidine (SC-409). To validate in vitro data, p38 role was further investigated in streptococcal cell wall (SCW)-induced arthritis in rats. We found that SCW-induced joint swelling and bone destruction were attenuated by SC-409. Mechanistically, the data show that SCW-stimulated DNA binding activity of the transcription factor myocyte-enhancing factor 2 C, which is downstream of p38, was inhibited by SC-409. In addition, SC-409 inhibited SCW-stimulated expression of numerous factors, including TNF-alpha, interleukin-1beta, and RANKL. Although c-Jun NH2-terminal kinase and NF-kappaB pathways were activated in vitro by RANKL and in vivo by SCW, SC-409 had no significant effect on these pathways. In conclusion, our data show that p38 modulates the production and signaling of cytokines, thus providing a mechanism of the bone-sparing effect of SC-409 in rat arthritis. These data present SC-409 as a novel potent p38 inhibitor and suggest that p38-based therapies may be beneficial in preventing bone loss associated with RA. (+info)
A complementary method for the detection of osteoblastic metastases on digitized radiographs.
(4/12)
PURPOSE: This study was conducted to evaluate the diagnostic usefulness of gray level parameters in order to distinguish healthy bone from osteoblastic metastases on digitized radiographs. MATERIALS AND METHODS: Skeletal radiographs of healthy bone (n = 144) and osteoblastic metastases (n = 35) were digitized using pixels 0.175 mm in size and 4,096 gray levels. We obtained an optimized healthy bone classification to compare with pathological bone: cortical, trabecular, and flat bone. The osteoblastic metastases (OM) were classified in nonflat and flat bone. These radiological images were analyzed by using a computerized method. The parameters (gray scale) calculated were: mean, standard deviation, and coefficient of variation (MGL, SDGL, and CVGL, respectively) based on gray level histogram analysis. Diagnostic utility was quantified by measurement of parameters on healthy and pathological bone, yielding quantification of area under the receiver operating characteristic (ROC) curve, AUC. RESULTS: All three image parameters showed high and significant values of AUC when comparing healthy trabecular bone and nonflat bone OM, showing MGL the best discriminatory ability (0.97). As for flat bones, MGL showed no ability to distinguish between healthy and flat bone OM (0.50). This could be achieved by using SDGL or CVGL, with both showing a similar diagnostic ability (0.85 and 0.83, respectively). CONCLUSION: Our results show that the use of gray level parameters quantify healthy bone and osteoblastic metastases zones on digitized radiographs. This may be helpful as a complementary method for differential diagnosis. Moreover, our method will allow us to study the evolution of osteoblastic metastases under medical treatment. (+info)
Zebrafish short fin mutations in connexin43 lead to aberrant gap junctional intercellular communication.
(5/12)
Mutations in the zebrafish connexin43 (cx43) gene cause the short fin phenotype, indicating that direct cell-cell communication contributes to bone length. Three independently generated cx43 alleles exhibit short segments of variable sizes, suggesting that gap junctional intercellular communication may regulate bone growth. Dye coupling assays showed that all alleles are capable of forming gap junction channels. However, ionic coupling assays revealed allele-specific differences in coupling efficiency and gating. For instance, oocyte pairs expressing the weakest allele exhibited much higher levels of coupling than either of the strong alleles. Therefore, measurable differences in Cx43 function may be correlated with the severity of defects in bone length. (+info)
A complete skeleton of a Late Triassic saurischian and the early evolution of dinosaurs.
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Osteosarcoma of limb bones: a clinical, radiological and histopathological diagnostic agreement at Black Lion Teaching Hospital, Ethiopia.
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OBJECTIVES: To measure the strength of agreement in clinical, radiological and histopathological diagnosis of osteosarcoma in a 5 year study period. SETTING: Addis Ababa University, Black-Lion ('Tikur Anbessa') Hospital-BLH, is the country's highest tertiary level referral and teaching hospital. The departments involved in this study (Radiology, Pathology and Orthopedics) receive referred patients from all over the country. METHODS: All bone tumor patients, presenting to the three departments at BLH between the study period, December, 2003 - March, 2008 were recruited for the study. 51 patients with radiological diagnosis of osteosarcoma of the extremities were identified and their clinical and histopathological diagnoses reviewed in detail. All patients had a clinical examination, plain radiographs and biopsies of the affected part of the extremity. Radiographs of selected difficult cases were discussed at joint orthopedic & radiologic sessions every week. The radiological and histopathological diagnoses made were categorized separately using WHO classification of bone tumors. Strength of agreement between radiological and histopathological diagnoses was measured using Cohen's Kappa test. RESULTS: Of the total of 216 bone tumor patients presented and biopsied in the five year period, fifty one (51) had osteosarcoma of extremity bones. Commonest age affected by osteosarcoma was 16 (7-55 years) and sex ratio was 1:1. Osteosarcoma was also the single most common clinical, radiological and histological diagnosis made. Considering all bone tumors presented together, the study indicated that radiological diagnosis was confirmed by similar histological diagnosis in 172 out 205 cases (84%) and the corresponding Cohen's Kappa value (0.82) showed excellent level of agreement between radiological and histological diagnoses of all bone tumors. The agreement between radiological and histopathological diagnoses of osteosarcoma of the limbs was 84.5%. CONCLUSION: There is an excellent agreement between clinical, radiological and histopathological diagnoses of bone tumors in general and osteosarcoma in particular. In setups where there is limited or no histopathological service, joint clinical and radiological decision could lead to a higher degree of accuracy in diagnosis of bone tumors, especially osteosarcoma. Radiological diagnosis of bone tumors at Black Lion Hospital, Addis Ababa is excellent. (+info)
Pediatric sports-related lower extremity fractures: hospital length of stay and charges: what is the role of the primary payer?
(8/12)
OBJECTIVE: The purposes of this study were (a) to evaluate the distribution by primary payer (public vs. private) of U.S. pediatric patients aged 5-18 years who were hospitalized with a sports-related lower extremity fracture and (b) to discern the adjusted mean hospital length of stay and mean charge per day by payer type. METHODS: Children who were aged 5 to 18 years and had diagnoses of lower extremity fracture and sports-related injury in the 2006 Healthcare Cost and Utilization Project Kids' Inpatient Database were included. Lower extremity fractures are defined as International Classification of Diseases, 9th Revision, Clinical Modification codes 820-829 under Section "Injury and Poisoning (800-999)," while sports-related external cause of injury codes (E-codes) are E886.0, E917.0, and E917.5. Differences in hospital length of stay and cost per day by payer type were assessed via adjusted least square mean analysis. RESULTS: The adjusted mean hospital length of stay was 20% higher for patients with a public payer (2.50 days) versus a private payer (2.08 days). The adjusted mean charge per day differed about 10% by payer type (public, US$7,900; private, US$8,794). CONCLUSIONS: Further research is required to identify factors that are associated with different length of stay and mean charge per day by payer type, and explore whether observed differences in hospital length of stay are the result of private payers enhancing patient care, thereby discharging patients in a more efficient manner. (+info)