Is There an Association Between Bone Microarchitecture and Fracture in Patients who were Treated for High-grade Osteosarcoma? A Controlled Study at Long-term Follow-up Using High-resolution Peripheral Quantitative CT.

BACKGROUND: Neoadjuvant chemotherapy in patients with primary osteosarcoma improves survival rates, but it also causes side effects in various organs including bone. Low bone mineral density (BMD) can occur owing partly to chemotherapy or limited mobility. This can cause a higher risk of fractures compared with those who do not receive such treatment. Changes in BMD alone cannot explain the propensity of fractures. Studying microarchitectural changes of bone might help to understand the effect. QUESTIONS/PURPOSES: (1) Do patients who were treated for osteosarcoma (more than 20 years previously) have low BMD? (2) Do these patients experience more fractures than controls who do not have osteosarcoma? (3) What differences in bone microarchitecture are present between patients treated for high-grade osteosarcoma and individuals who have never had osteosarcoma? METHODS: We contacted 48 patients who were treated for osteosarcoma and who participated in an earlier study. These patients underwent multimodal treatment including chemotherapy more than 20 years ago. Of the original patient group, 60% (29 of 48) were missing, leaving 40% (19 of 48) available for inclusion in this study; all 19 agreed to participate. There were nine men and 10 women with a mean age of 46 ± 4 years and a mean time from surgery to examination of 28 ± 3 years. BMD was measured by dual-energy x-ray absorptiometry, and any fracture history was assessed using a questionnaire. Additionally, high-resolution peripheral quantitative CT was performed to compare the groups in terms of microarchitectural changes, such as cortical and trabecular area, cortical and trabecular thickness, cortical porosity, and endocortical perimeter. Participants in the control group were selected from a cohort consisting of a population-based random sample of 499 healthy adult women and men. Osteoporosis or low BMD was not an exclusion criterion for entering this study; however, the patients in the control group were selected based on a normal BMD (that is, T score > -1.0 at both the spine and hip). Also, the participants were matched based on age and sex. Differences between patients and controls were assessed using the Wilcoxon rank sum test for continuous variables and a chi-square test for categorical variables. A multiple regression analysis was performed. Model assumptions were checked using histograms and quantile-quantile plots of residuals. RESULTS: Twelve of 19 patients who were treated for osteosarcoma had either osteopenia (eight patients) or osteoporosis (four patients). More patients with osteosarcoma reported sustaining fractures (11 of 19 patients) than did control patients (2 of 19 controls; p < 0.001). Among all microarchitectural parameters, only the endocortical perimeter was increased in patients compared with the control group (75 ± 15 mm versus 62 ± 18 mm; p = 0.04); we found no differences between the groups in terms of cortical and trabecular area, cortical and trabecular thickness, or cortical porosity. CONCLUSION: Although patients who were treated for osteosarcoma had osteopenic or osteoporotic BMD and a higher proportion of patients experienced fractures than did patients in the control group, we could not confirm differences in microarchitectural parameters using high-resolution peripheral quantitative CT. Therefore, it seems that bone geometry and microstructural parameters are not likely the cause of the increased proportion of fractures observed in our patients who were treated for osteosarcoma. Until we learn more about the bone changes associated with chemotherapy in patients with osteosarcoma, we recommend that patients undergo regular BMD testing, and we recommend that physicians consider osteoporosis treatment in patients with low BMD. These data might provide the impetus for future multicenter prospective studies examining the association between chemotherapy and bone microarchitecture. LEVEL OF EVIDENCE: Level III, therapeutic study.

[Adolf Lorenz and his mentor Eduard Albert]. / Adolf Lorenz und sein Mentor Eduard Albert.

At the end of the nineteenth century, the imperial capital of the k.k. Danube monarchy, Vienna, enabled the meeting of two important figures in medical history: the surgeon Eduard Albert (1841-1900) and his student Adolf Lorenz (1854-1946). Both men had comparable traits: they came from humble backgrounds, were exceptionally talented and longed for a career in the supreme medical discipline-surgery. Both achieved the highest goals in their disciplines but the spectrum of their interests was much broader. The life of both and their contacts to each other are reported here. In this respect the Memorial Book of House No. 528 by Eduard Albert in Senftenberg was also evaluated.

Adolf Lorenz and the Lolita Armour Case.

Almost 120 years ago, in 1902, the American multimillionaire J. Ogden Armour invited the Austrian orthopaedic surgeon Adolf Lorenz, professor at the University of Vienna, to treat his daughter Lolita. Lolita was born premature in 1896 and spent the first months of her life in an incubator. Later she was diagnosed with congenital dislocation of both hips. Lorenz had developed a "bloodless" treatment method and was invited by the Armour family to Chicago to "operate" on Lolita. Both hips had already been treated by an American orthopaedic surgeon before but without a satisfactory result. Lorenz should achieve a better one. The operation was performed in Chicago on 12 October 1902 and was accompanied by a very large media spectacle. This article is mainly based on contemporary newspaper reports.

[Adolf Lorenz und Tomás Garrigue Masaryk-an extraordinary encounter]. / Adolf Lorenz und Tomás Garrigue Masaryk ­ eine außergewöhnliche Begegnung.

Adolf Lorenz, the founder of orthopedics in Austria and father of the later Nobel laureate Konrad Lorenz, and the founder and first president of the Czechoslovak Republic, Tomás G. Masaryk, were in contact. In the seventies and eighties of the nineteenth century both studied at the University of Vienna: Masaryk, four years older, Philosophy and Lorenz Medicine. The first meetings took place in the dissecting room of the Anatomical Institute. Later both entered (scientific) careers and became well-known personalities. Almost 40 years after the first coincidental encounter, Lorenz remembered his former student, meanwhile president of the Czechoslovak Republic, and made contact with him. The correspondence kept in the Masaryk Institute in Prague will be presented here.

[Adolf Lorenz's decision to study medicine]. / Adolf Lorenz' Entscheidung zum Medizinstudium.

The childhood and adolescence years are decisive in life. It was the aim of this study to analyze the pubertal years of Adolf Lorenz, the founder of Austrian orthopedics who left his mark in all parts of the world, with respect to his choice of profession. As the son of poor people from the former frontier region of the Austro-Hungarian Monarchy with Poland, then known as Austrian-Silesia, he was provided with a scholarship in a boys' choir at a Carinthian monastery and then continued his studies at a college in Klagenfurt, capital of Carinthia. He spent the last year at college as a private teacher in Transylvania and passed his maturity examination as an extraordinary pupil. During this time he decided to study medicine. The people he then met and the events leading to this decision are illustrated in this article.

Do Patients After Chondrosarcoma Treatment Have Age-appropriate Bone Mineral Density in the Long Term?

BACKGROUND: In long-term survivors of osteosarcoma and Ewing sarcoma treated with the addition of radio- and chemotherapy, low bone mineral density (BMD) and fractures have been observed, presumably resulting from these adjuvants. Because patients with chondrosarcoma usually are not treated with conventional adjuvant treatment, observation of low BMD in patients with chondrosarcoma presumably would be the result of other mechanisms. However, BMD in patients with a history of chondrosarcoma has not been well characterized. QUESTIONS/PURPOSES: The aim of our study was to address the following questions: (1) Do long-term survivors of chondrosarcoma have normal BMD and, if not, which factors contribute to low BMD? (2) Is there a greater risk of fracture and does the Fracture Risk Assessment Tool (FRAX(®)) score reflect fracture likelihood? METHODS: All known patients with a history of chondrosarcoma treated at our institution before 2006 were identified. Of 127 patients believed to be alive at the time of this study, 30 agreed to participate in this study (11 females, 19 males; mean age at surgery, 39 ± 12 years; mean followup, 12 ± 5 years). With the data available, the 30 participants were not different from the 97 nonparticipants in terms of age, sex, BMI, tumor grade, tumor location (axial versus appendicular, lower extremity versus elsewhere), and use of any treatment known to influence osteopenia (chemotherapy, lower extremity surgery). BMD was measured and history of fractures was assessed using a questionnaire. The patients´ BMD measurements in this study were sex- and age-matched with a normative sex- and age-categorized reference population reported by Kudlacek et al. Associations were tested by univariate regressions and ANOVAs of all measures of BMD and eligible oncologic and demographic factors. RESULTS: Eighteen of 30 (60%) patients had a pathologic BMD according to the WHO dual-energy x-ray absorptiometry definition, 15 (50%) had osteopenia, and three (10%) had osteoporosis. T-scores in the study cohort were lower than reference values for the femur neck (mean difference, 0.64; 95% CI, 0.27-1.01; p < 0.0015), but not for the spine (mean difference, 0.39; 95% CI, -0.06 to 0.84; p = 0.09). Thirteen patients (45%) reported a history of fractures not distinguishing between low and high impact. The incidence of fractures was 2.8 greater than expected from a comparison with a published microcensus survey of the Austrian population. No effect of the FRAX(®) score on fracture risk could be identified (p = 0.057). CONCLUSIONS: Long-term survivors of chondrosarcoma appear to be at greater risk for having low BMD develop than the healthy population. Although these results are preliminary and based on a very small sampling of patients, if they can be confirmed in larger studies, BMD assessment by dual-energy x-ray absorptiometry might be considered as these patients are followed posttreatment by sarcoma care units. The reasons for low BMD still must be elucidated. LEVEL OF EVIDENCE: Level IV, prognostic study.

Do long term survivors of ewing family of tumors experience low bone mineral density and increased fracture risk?

BACKGROUND: Multimodal treatment regimens for Ewing's sarcoma have led to survival rates approaching 70% of patients with no metastases at diagnosis. However, these treatments have long-term side effects. Low bone mineral density (BMD) and risk of fractures can occur owing in part to chemotherapy and limited mobility from local control of the primary tumor. QUESTIONS/PURPOSES: We performed this study to answer the following questions: (1) Do long-term survivors of the Ewing family of tumors sustain low BMD? (2) Which factors are associated with BMD in these patients? (3) Do they experience fractures? (4) Are BMD and fractures associated with each other? METHODS: We queried our institutional registry to identify all known survivors of Ewing tumors who were treated before 2005. Of 100 such patients, 67 (67%) responded to a postal survey to participate in this study, and an additional 11 (11%) patients were excluded according to prespecified criteria. In the remaining 56 long-term survivors (27 females, 29 males; mean±SD age at followup, 32±10 years; mean followup, 15±7 years), BMD was measured by dual-energy x-ray absorptiometry and history of fractures was assessed using a questionnaire. Associations were tested using univariate and multivariate models by stepwise variable selection procedure, including Bonferroni correction. RESULTS: Thirty-one of 56 (56%) patients had a pathologic BMD. Seven (13%) had osteoporosis and 24 (43%) had osteopenia. Factors related to low BMD after Bonferroni correction were the length of time between surgery and followup and the BMI at followup. Twenty-one patients reported 29 fractures. With the numbers available, BMD levels were not associated with fractures. CONCLUSIONS: We could not confirm some potentially important predictors for fractures to be associated with clinical events of interest. However, the data are valuable as hypothesis-generating pilot data for future, multicenter prospective studies. If BMD changes cannot explain the propensity of fractures, there may be other bone characteristics like microarchitectural changes of bone to more accurately explain the effect. LEVEL OF EVIDENCE: Level IV, prognostic study. See the Instructions for Authors for a complete description of levels of evidence.

The 50 highest cited papers in hip and knee arthroplasty.

The 50 highest cited articles related to hip and knee arthroplasty were searched in Thomson ISI Web of Science®. The 50 highest cited articles had up to 2495 citations. The top 10 papers according to absolute number were cited 580 times at least. Most papers were published in the Journal of Bone and Joint Surgery American Volume (n = 22). Eight countries contributed to the list with most contributions from the United States (n = 30). The majority of papers were published since 1990 (n = 27). Studies focusing on the clinical outcome of hip arthroplasty dominate the literature in orthopedic arthroplasty in respect to absolute citations numbers. In the last decade however, papers on perioperative management have been published that show a high citation frequency.

Expression of gap junction proteins connexins 26, 30, and 43 in Dupuytren's disease.

BACKGROUND AND PURPOSE: Dupuytren's disease (DD) is a benign fibroproliferative process of the palmar aponeurosis showing similarities to wound healing. Communication of cells involved in wound healing is mediated by the composition of gap junction (GJ) proteins. We investigated the expression of 3 GJ proteins, connexins 26, 30, and 43 (Cx26, Cx30, and Cx43) in DD. PATIENTS AND METHODS: Fragments of Dupuytren's tissue from 31 patients (mean age 56 (30-76) years, 24 male) were analyzed immunohistochemically and compared to control tissue for expression of the GJ proteins Cx26, Cx30, and Cx43 and also alfa-smooth muscle actin (α-SMA). RESULTS: 14 of 31 samples could be attributed to the involutional phase (α-SMA positive) whereas 17 samples had to be considered cords in the residual phase (α-SMA negative). Expression of Cx26 and Cx43 was seen in 12 of the 14 samples from the involutional phase, and Cx30 was seen in 7 of these. Only 4 of the 17 samples from the residual phase showed any Cx, and there was none in the controls. INTERPRETATION: The high expression of GJ proteins Cx26, Cx30, and Cx43 in α-SMA positive myofibroblast-rich nodules, which are characteristic of the active involutional phase of DD, suggests that connexins could be a novel treatment target for the treatment of DD.

Guillaume Dupuytren: his life and surgical contributions.

Guillaume Dupuytren (1777-1835) was one of the most influential surgeons of the past. He described and popularized many conditions, including Dupuytren disease, which continues to carry his name. This article reviews Guillaume Dupuytren's life and his contributions in surgery.

Expression of VEGF, its receptors, and HIF-1α in Dupuytren's disease.

BACKGROUND AND PURPOSE: Dupuytren's disease (DD) is a benign fibroproliferative process that affects the palmar fascia. The pathology of DD shows similarities with wound healing and tumor growth; hypoxia and angiogenesis play important roles in both. We investigated the role of angiogenic proteins in DD. PATIENTS AND METHODS: The expression of vascular endothelial growth factor (VEGF), its receptors vascular endothelial growth factor receptor 1 (VEGFR1) and vascular endothelial growth factor receptor 2 (VEGFR2), hypoxia-inducible factor alfa (HIF-1α), and alfa-smooth muscle actin (α-SMA) were analyzed immunohistochemically in fragments of excised Dupuytren's tissue from 32 patients. We compared these values to values for expression in a control group. RESULTS: 15 of 32 samples could be attributed to the involutional phase (α-SMA positive), whereas 17 samples were considered to be cords at the residual phase (α-SMA negative). In the involutional phase, the HIF-1α and VEGFR2 expression was statistically significantly higher than in the residual phase and in the controls. INTERPRETATION: Both the VEGFR2 receptor and HIF-1α were expressed in α-SMA positive myofibroblast-rich nodules with characteristics of DD in the active involutional phase. Thus, hypoxia and (subsequently) angiogenesis may have a role in the pathophysiology of DD.

Evaluation of FRAX in patients with periprosthetic fractures following primary total hip and knee arthroplasty.

The fracture risk assessment tool (FRAX) is a tool which calculates an individual 10-year fracture risk based on epidemiological data in patients with a risk of osteporosis. The aim of this study was to evaluate the value of FRAX to estimate the risk of postoperative periprosthetic fractures (PPF) in patients following with total hip and knee arthroplasty. 167 patients (137 periprosthetic fractures in total hip arthroplasty and 30 periprosthetic fractures in total knee arthroplasty) were included in this study. Patients' data was retrieved retrospectively. In each patient the 10-year probability of a major osteoporotic fracture (MOF) and an osteoporotic hip fracture (HF) was calculated using FRAX. According to the NOGG guideline 57% of total hip arthroplasty (THA) patients and 43.3% of total knee arthroplasty (TKA) patients were in need of osteoporosis treatment, whereas only 8% and 7% received an adequate one respectively. 56% of the patients with PPF after THA and 57% of the patients with PPF after TKA reported about a previous fracture. Significant associations between the 10-year probability of a MOF and HF calculated by FRAX and PPF in THA and TKA were seen. The results of the present study show that FRAX might have the potential to estimate the PPF in patients following THA and TKA. FRAX should be calculated before and after THA or TKA in order to assess the risk and counsel patients. The data show a clear undertreatment of patients with PPF in respect to osteoporosis.

The most influential papers in unicompartmental knee arthroplasty.

PURPOSE: Unicompartmental knee arthroplasty (UKA) is a treatment option for anteromedial osteoarthritis of the knee. The number of UKA has been increasing constantly worldwide in recent decades. The aim of this study was to determine the most frequently cited scientific articles addressing this subject and to establish a ranking of the 50 most influential papers. METHODS: The 50 most cited articles related to UKA were searched in Web of Science® (Clarivate Analytics, Penn., USA) by the use of defined search terms. All types of scientific papers with reference to this topic were ranked according to the absolute number of citations and analyzed for the following characteristics: journal title, year of publication, number of citations, citation density, geographic origin, article type, and level of evidence. RESULTS: The 50 most cited articles had up to 453 citations. Most papers were published in the Journal of Bone and Joint Surgery (British volume). More than half of the articles were published in the 2000s and 2010s (n = 30). Ten countries contributed to the top 50 list, with most contributions from the UK (n = 17). Most articles could be attributed to the category of Clinical Science (n = 33), and most reported level IV studies. CONCLUSION: Most of the frequently cited articles in UKA are clinical studies that have a low level of evidence. Few basic scientific studies could be identified, which suggests that most product development is done by commercial companies.

Outcome parameters in orthogeriatric co­management - a mini-review.

Recognizing hip and other fragility fractures as an adverse event of chronic geriatric conditions led to the concept of orthogeriatric co-management (OGC). OGC today represents various forms of structural cooperation between orthopedic trauma surgeons and multiprofessional geriatric teams taking care of frail elderly patients. The models are country specific. Despite several published models there are still no clear recommendations on how this service should be best organized. The 12 outcome parameters published by the Experts' Roundtable in 2013 were recommended to be used for the further assessment of different OCG models. This literature review was prepared accordingly and showed the need for further studies to determine the best OGC model and to define a uniform set of outcome parameters for use in future clinical studies.

The most cited papers in osteoporosis and related research.

Osteoporosis is a systemic disease of the bone that affects millions of people and causes burden for both the affected individual and health systems and societies worldwide. Since the 1970s much research has been done in the field of osteoporosis. The number of citations of a paper reflects its influence and importance to the field. Thomson ISI Web of Science database was searched to retrieve a list of the fifty most cited articles related to osteoporosis and its research. The fifty most cited articles in absolute numbers in the field of osteoporosis were cited from 877 to 3056 times (mean 1141 ± 537). Most papers were published in the basic science category (n = 23). 395 authors contributed; a single paper had between one and 62 authors (mean: 10.02 ± 9.9 authors). 12 authors (3.04%) contributed between 7 and 4 papers; 340 authors (86.1%) were at least named once. Corresponding authors were from eight countries with most contributions from the United States (n = 34, 68%). The majority of papers were published in the 1990s (n = 29). The list of 50 most cited papers presents citation classics in the field of osteoporosis and related research.

Estrogen regulation of growth and alkaline phosphatase expression by cultured human bone marrow stromal cells.

Estrogen has been reported to regulate the growth and differentiation of cultured murine osteoprogenitor cells in bone marrow stroma. This study tested the ability of 17beta-estradiol (E2) to regulate growth and expression of alkaline phosphatase (ALP), an osteoblastic differentiation marker, in strains of normal human bone marrow stromal cells derived from different donors. In eight strains examined, E2 at 1 and 10 nM produced at most modest effectxs on growth and ALP activity. Growth inhibition, seen in 4 of the 8 strains, was more common than stimulation (2 of the 8 strains); the greatest observed E2 effect was an inhibition of ca. 50%. E2 altered ALP activity less dramatically than cell growth. Differences from control in total ALP per culture were seen in only two strains: one was a reduction, one an increase. Colony forming assays were used to determine if E2 changed the proportion of ALP-expressing cells in marrow stromal cell cultures. In contrast to growth experiments, ALP expression under colony forming conditions (200 cells per 35 mm-diameter well) was dependent on the type of serum supplementation used. Under permissive conditions using medium supplemented with 10% charcoal-treated fetal bovine serum, 10 nM E2 increased the number of ALP-positive colonies (cfu-ap) but not the total number of colonies formed (cfu-f). When cells cultured in the presence or absence of 10 nM E2 were replated at colony forming densities, significantly higher proportions of cfu-ap were found in 2 of 6 strains examined, while pretreatment with E2 affected the number of cfu-f in only 1 of the 6 strains. Similar results were obtained when colony formation was carried out in the presence of dexamethasone and ascorbate, although these agents themselves increased the formation of both cfu-f and cfu-ap. These results show that the direct effects of E2 on human marrow stromal cells are small and vary depending on the cell strain and on the experimental conditions; however, the E2 actions observed in this study were consistent with reports that E2 exerts direct actions on osteoblasts and osteoblast progenitor cells that favor rather than suppress their phenotypic expression.

Body image and self-esteem in lower-limb amputees.

BACKGROUND: Limb amputation is often an inevitable procedure in the advanced condition of various diseases and poses a dramatic impact on a patient's life. The aim of the present study is to analyze the impact of lower-limb amputations on aesthetic factors such as body image and self-esteem as well as quality of life (QoL). METHODS: 298 patients (149 uni- or bilateral lower-limb amputees and 149 controls) were included in this cross-sectional study in three centers. Demographic data was collected and patients received a 118-item questionnaire including the Multidimensional Body-Self Relations Questionnaire (MBSRQ), the Rosenberg Self-esteem (RSE) scale and the SF-36 Health Survey (QoL). ANOVA and student's t-test were used for statistical analysis. RESULTS: Unilateral lower-limb amputees showed a significant lower MBSRQ score of 3.07±0.54 compared with 3.41±0.34 in controls (p<0.001) and a lower score in the RSE compared to controls (21.63±4.72 vs. 21.46±5.86). However, differences were not statistically significant (p = 0.36). Patients with phantom pain sensation had a significantly reduced RSE (p = 0.01). The SF-36 health survey was significantly lower in patients with lower-limb amputation compared to controls (42.17±14.47 vs. 64.05±12.39) (p<0.001). CONCLUSION: This study showed that lower-limb amputations significantly influence patients' body image and QoL. Self-esteem seems to be an independent aspect, which is not affected by lower-limb amputation. However, self-esteem is influenced significantly by phantom pain sensation.