Elderly men with a history of distal radius fracture have significantly lower calcaneal bone density and free androgen index than age-matched controls.

BACKGROUND: Age related bone loss is widely accepted as related to decreased serum levels of circulating sex hormones. Epidemiological data also show distal radius fractures in men to be a sensitive marker of bone fragility. The aim of this study was to assess if men with a history of distal radius fracture have lower bone mass density (BMD), lower free androgen index (FAI), lower total testosterone (T) and lower bio-available testosterone (Bio-T) than healthy age-matched controls. PATIENTS AND METHODS: A case-control study is based on consecutive cases treated for low energy distal radius fracture at our department and age-matched controls. Thirty-nine men treated between 1997-2004 and 45 age-matched controls underwent calcaneal bone density measurements (t-score) and analyses of T, Bio-T and serum hormone binding globulin (SHBG). RESULTS: The fracture group had lower BMD (p < 0.01) and lower FAI (p = 0.01). Linear regression analysis showed a correlation between Bio-T and t-scores (p = 0.03). Using analysis of covariance, a significant difference with lower Bio-T in the fracture group was shown. CONCLUSION: Bio-T seems to correlate with BMD in elderly men and may serve as a marker for increased fracture risk in this patient group.

Acidic preparations of lysed platelets upregulate proliferative pathways in osteoblast-like cells as demonstrated by genome-wide microarray analysis.

Platelets contain numerous growth factors essential for wound and fracture healing. We investigated the gene expression in human osteoblast-like cells stimulated with lysed platelets prepared in acidic, neutral, or alkaline buffers. Lysed platelets prepared in buffers at pH 5.4, 7.4, and 7.9, were added after neutralization to hFOB 1.19 cells. Genome-wide microarray analysis was performed using the Affymetrix GeneChip 7G Scanner. Biometric, cluster, and pathway analyses were performed with GeneSpring GX. Biometric analyses demonstrated that 53 genes were differentially regulated (p ≤ 0.005, ≥2-fold increase). Pathway analysis revealed 10 significant pathways of which eight are common ones regulating bone formation and cancer growth. Eleven genes were selected for quantitative real-time polymerase chain reaction (PCR) based on the microarray analysis of the lysed platelets prepared in the pH 5.4 experiments. In conclusion, acidic preparations of lysed platelet concentrates release factors essential for cell proliferation and particularly cell metabolism under hypoxic conditions. The genetic response from these factors was dominated by genes associated with the same pathways observed in bone formation and cancer growth. Activation of TGF-ß in the acidic preparation could be a stimulatory key factor of cell proliferation. These results support the hypothesis that acidification of platelets modifies the stimulatory response of mesenchymal cells in vitro, which is analogous with the observed milieu of a low pH present in wound and fracture sites, as well as in growing tumors.

Preparation for becoming members of health care teams: findings from a 5-year evaluation of a student interprofessional training ward.

SETTING: An orthopaedic interprofessional training ward manned by students at a University Hospital. OBJECTIVE: To assess to what extent students from different undergraduate programmes evaluated the effects of a 2-week rotation at the ward on their professional roles and the value of teamwork within health care. METHOD: A questionnaire was filled in by 841 students by the end of a 2-week rotation at the ward over 5 years. Questions concerned students' estimate of how the rotation had strengthened their insight into their own future professional role, into other students' professional roles and into the value of teamwork within health care. Differences between the different student categories and possible associations between the different estimates were statistically analysed. RESULTS: Students from all programmes reported that the rotation at the student ward had dramatically strengthened their insight about their own future professional role as well as the roles of the other professions and the value of teamwork within health care. CONCLUSION: Health care is a complicated system based on cooperation and professionalism. We suggest that interprofessional training of students from all professions within health care should be a part of their education as a worthwhile preparation for their future professional work and to ensure high-quality health care.

The content of bone morphogenetic proteins in platelets varies greatly between different platelet donors.

Platelet derivates and platelet rich plasma have been used to stimulate bone formation and wound healing because of the rich content of potent growth factors. However, not all reports have been conclusive since some have not been able to demonstrate a positive effect. We investigated the interindividual variation of bone morphogenetic proteins (BMPs) in platelets from healthy donors, and the pH-dependent effect on the release of BMPs in preparations of lysed platelets in buffer (LPB). Platelet concentrates from 31 healthy donors were prepared in pH 4.3 and pH 7.4 buffers and investigated with respect to BMP-2, -4, -6, and -7. BMP-2 and BMP-4 were significantly more common in acidic LPBs in comparison with neutral preparations. We also observed a considerable variation among platelet donors with respect to the release of BMPs at pH 4.3 and 7.4. In conclusion, a considerable variation was found among platelet donors, which may be of importance considering the ambiguous results previously reported on osteoblast proliferation and differentiation.

Liposarcoma: outcome based on the Scandinavian Sarcoma Group register.

BACKGROUND: The aim was to study the clinicopathological characteristics, treatment, and outcome of liposarcoma in an unselected, population-based patient sample, and to establish whether treatment was according to the Scandinavian Sarcoma Group (SSG) treatment guidelines. METHODS: The SSG Pathology Board reviewed 319 liposarcoma cases reported between 1986 and 1998. After the review, 237 patients without metastasis were analyzed for local recurrence rate in relation to surgical margins, radiotherapy, occurrence of metastasis, and survival. RESULTS: Seventy-eight percent of the patients were primarily operated on at a sarcoma center, 45% with wide margins. All patients operated on outside the center had nonwide margins. Low-grade lesions constituted 67% of cases. Despite nonwide surgery, only 58% of high-grade lesions were treated with postoperative radiotherapy. The risk of local recurrence after nonwide surgery, without irradiation, was 47% for high-grade lesions. The estimated 10-year, local recurrence-free and metastasis-free survival in the low-grade group was 87% and 95%, respectively. In the high-grade group, it was 75% and 61%, respectively. Independent adverse prognostic factors for local recurrence were surgery outside a sarcoma center and histological type dedifferentiated liposarcoma. For metastases, they were old age, large tumor size, high grade, and histological type myxoid liposarcoma with a round cell component. Radiotherapy showed significant effect on local recurrence rate for the same grade and margin. CONCLUSIONS: Patients with liposarcoma should be treated at specialized centers. Postoperative radiotherapy decreases the local recurrence rate. To maintain quality and provide support for further trials, reporting to quality registers is crucial.

Acidic preparations of platelet concentrates release bone morphogenetic protein-2.

BACKGROUND AND PURPOSE: Growth factors released from platelets have potent effects on fracture and wound healing. The acidic tide of wound healing, i.e. the pH within wounds and fractures, changes from acidic pH to neutral and alkaline pH as the healing process progresses. We investigated the influence of pH on lysed platelet concentrates regarding the release of growth factors. MATERIAL AND METHODS: Platelet concentrates free of leukocyte components were lysed and incubated in buffers with pH between 4.3 and 8.6. Bone morphogenetic protein-2 (BMP-2), platelet-derived growth factor (PDGF), transforming growth factor-beta(TGF-beta), and vascular endothelial growth factor (VEGF) were measured by quantitative enzyme-linked immunosorbent assays. RESULTS: PDGF, TGF-beta, and VEGF were present in all platelet preparations but the levels varied in a pH-dependent fashion. BMP-2 was only detected in the most acidic preparation (pH 4.3), which is interesting since BMP-2 has been reported to be an endogenous mediator of fracture repair and to be responsible for the initiation of fracture healing. INTERPRETATION: Our findings indicate that platelets release substantial amounts of BMP-2 only under conditions of low pH, the milieu associated with the critical initial stage of fracture healing.

Simulation of patient specific cervical hip fracture surgery with a volume haptic interface.

The interest for surgery simulator systems with anatomical models generated from authentic patient data is growing as these systems evolve. With access to volumetric patient data, e.g., from a computer tomography scan, haptic and visual feedback can be created directly from this dataset. This opens the door for patient specific simulations. Hip fracture surgery is one area where simulator systems is useful to train new surgeons and plan operations. To simulate the drilling procedure in this type of surgery, a repositioning of the fractured bone into correct position is first needed. This requires a segmentation process in which the bone segments are identified and the position of the dislocated part is determined. The segmentation must be automatic to cope with the large amount of data from the computer tomography scan. This work presents the first steps in the development of a hip fracture surgery simulation with patient specific models. Visual and haptic feedback is generated from the computer tomography data by simulating fluoroscopic images and the drilling process. We also present an automatic segmentation method to identify the fractured bone and determine the dislocation. This segmentation method is based on nonrigid registration with the Morphon method.

Inflammatory response in 85 patients with loosened hip prostheses: a prospective study comparing inflammatory markers in patients with aseptic and septic prosthetic loosening.

BACKGROUND: The most common complications of prosthetic hip joints are aseptic mechanical failure and infection. Delayed low-grade infections are seen most often, and they are also most difficult to distinguish from aseptic mechanical failures. METHODS: We conducted a prospective study to compare inflammatory markers in patients diagnosed with aseptic or septic prosthetic loosening. The diagnostic criteria were based on the decisions of experienced orthopedic surgeons and microbiological analysis of periprosthetic tissue samples taken perioperatively. RESULTS: Coagulase-negative staphylococci were the commonest pathogens in the infected patients. Pre- or perioperative elevation of C-reactive protein and erythrocyte sedimentation rate were significantly greater in the infection group, as were white blood cell count and levels of cytokines in synovial fluid. The patterns of infiltration of inflammatory cells in periprosthetic tissue were also significantly different between the groups. INTERPRETATION: A combination of clinical judgment and multiple tissue samples constitutes a good platform for distinguishing between septic and aseptic loosening of prostheses. Moreover, the combined use of several laboratory and histopathological markers of inflammation, especially infiltration of polymorphonuclear cells, further helps the diagnosis.

Variation of pH in lysed platelet concentrates influence proliferation and alkaline phosphatase activity in human osteoblast-like cells.

Activated platelets release a multifaceted blend of growth factors that has stimulatory effects on mesenchymal cells, both in vitro and in vivo, which imply beneficial effects on wound repair and tissue regeneration. Previous studies on fibroblast cultures have revealed that more potent growth factors, with respect to cell proliferation, are released in acidic preparations of lysed platelet concentrates in comparison with neutral and alkaline preparations. The current study was intended to investigate the influence of pH on lysed platelet concentrates with respect to release of growth factors, cell proliferation and alkaline phosphatase (ALP) activity in human osteoblast-like cells (hFOB 1.19). Cell proliferation was assessed with the MTT kit, ALP activity by conventional enzymatic reaction kinetics and growth factors platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta) by enzyme-linked immunosorbent assays. Osteoblast-like cells were stimulated with lysed platelet concentrates preincubated at pH 4.4, 5.4, 7.4, and 7.6. A 3-13-fold increase of cell proliferation was found in comparison with controls and the most evident increase was observed with platelets activated at pH 5.4. The highest ALP activity was observed in preparations at pH 7.6. Platelets incubated in an acidic environment (pH 5.4) induced a higher proliferation compared with preincubation at neutral or alkaline pH and the level of PDGF was also found to be higher in acidic preincubations. The level of TGF-beta was, in contrast, lowest at pH 4.4. We suggest, based on these experimental findings, that acidic milieu influence platelets to release growth factors more potent to stimulate osteoblast proliferation than neutral and alkaline platelet preparations. Lysed platelet concentrates prepared at an alkaline pH might release additional components with stimulating effects resulting in other features than cell proliferation. This is the first report, to our knowledge, about a pH dependent stimulatory effect of lysed platelet concentrates on human osteoblast-like cell proliferation. Lysed platelet concentrates, preincubated in acidic or alkaline buffers, may benefit fracture healing, implant fixation and might also be advantageous in the treatment of wounds with platelet constituents; however, this has to be investigated in extended experimental and clinical settings.

Women with low-energy fracture should be investigated for osteoporosis.

INTRODUCTION: Treatment of osteoporosis is becoming more effective, but methods to identify patients who are most suitable for investigation and treatment are still being debated. Should any type of fracture have higher priority for investigation of osteoporosis than any other? Is the number of previous fractures useful information? MATERIAL AND METHODS: We investigated 303 consecutive women patients between 55 and 75 years of age who had a newly diagnosed low-energy fracture. They answered a questionnaire on previous fractures which also dealt with risk factors. Bone mineral density (BMD) was measured at the hip, lumbar spine, and forearm. RESULTS: The distribution of fracture location was: distal forearm 56%, proximal humerus 12%, vertebra 18%, and hip 13%, all with similar age. Half of the subjects had had at least one previous fracture before the index fracture, 19% had had two previous fractures, and 6% had had three or more previous fractures. Patients with vertebral or hip fracture had lower BMD and had had more previous fractures than patients with forearm or humerus fractures. There was an inverse correlation between number of fractures and BMD. Osteoporosis was present in one-third of patients with forearm fracture, in one-half of those with hip or humerus fracture, and in two-thirds of those with vertebral fracture. INTERPRETATION: Vertebral fractures were the strongest marker of low BMD and forearm fractures the weakest. The number of previous fractures is helpful information for finding the most osteoporotic patient in terms of severity. Investigation of osteoporosis therefore seems warranted in every woman between the ages of 55 and 75 with a recent low-energy fracture, with highest priority being given to those with vertebral, hip, or multiple fractures.

The total costs of a displaced femoral neck fracture: comparison of internal fixation and total hip replacement. A randomised study of 146 hips.

We randomised 143 patients--age 75 years or older--with displaced femoral neck fracture to either internal fixation or total hip replacement (THR) and compared the socio-economic consequences. In the internal fixation group, 34 of 78 hips underwent secondary surgery. In the THR group, 12 of 68 hips dislocated, the majority in mentally impaired patients. We calculated the total hospital costs for two years after operation. When secondary surgery was included, there was no difference in costs between the internal fixation and THR groups, or between the mentally impaired and lucid subgroups. The costs to the community were calculated comparing the baseline cost before surgery with the average cost per month during the first postoperative year. No difference was found between the treatment groups. The Harris hip scores were higher in the THR group, and pain was more common in the internal fixation group. In lucid patients, THR gives a better clinical result at the same cost.

Time- and pH-dependent release of PDGF and TGF-beta from platelets in vitro.

We studied the spontaneous and thrombin-induced activation of platelets and their release of platelet derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta) at different pH values. Platelet activation was assayed with antibodies against P-selectin and performed in serum-free media. The release of PDGF and TGF-beta was determined by ELISA after 15 min and 12h. There was no activation at pH 5.0, while a time-dependent release of growth factors occurred at neutral and alkaline pH. The results suggest that release o f growth factors is not only dependent on platelet activation but also on incubation time and pH. Although the used serum-free experimental situation is different from normal conditions for platelets in vivo, the findings of a late release of growth factors may, nevertheless, be relevant to wound healing.

Fibroblast proliferation due to exposure to a platelet concentrate in vitro is pH dependent.

The influence of platelet-rich plasma lysates on fibroblast proliferation was studied in culture. Cells were exposed to platelet lysates that had been preincubated at different pHs (5.0, 7.1, and 7.6). Proliferation was evaluated with the MTT assay and incorporation of [3H]thymidine into macromolecules, while type I collagen production was assayed by Western blotting. Enzyme-linked immunosorbent assays were used to determine platelet-derived growth factor and transforming growth factor-beta concentrations. Platelets preincubated in an acidic environment (pH 5.0) induced the highest degree of fibroblast proliferation, and the concentration of platelet-derived growth factor in the different treated lysates was the highest at that particular pH. The concentration of transforming growth factor-beta, however, was lower after incubation at pH 5.0 than at either pH 7.1 or 7.6. These findings may be relevant to normal wound healing in vivo and useful in the treatment of wounds and delayed healing processes.