Purpose: To determine whether reduced serum levels of AHSG and elevated levels of BMP-2, 4, 7 are associated with post-arthroplasty HO. Patients: Thirty arthroplasty patients were included, 15 with evidence of peri-articular HO and 15 without (NHO). Methods: Blood samples were collected from all patients ≥ 8 weeks after arthroplasty. Analytes were measured using ELISAs. Mann-Whitney U tests were performed to compare serum analyte concentrations between HO and NHO groups, and between arthroplasty patients and healthy humans. Results: There is no difference in serum concentrations of AHSG, BMP-2, 4, 7 between HO and NHO patients. Arthroplasty patients showed significantly higher BMP-2 and BMP-4 and lower AHSG serum levels compared to healthy humans (p < 0.01). Conclusion: Baseline BMP-2, 4, 7 and AHSG serum levels are not markers of acquired HO. However, elevated baseline levels of BMP- 2, 4 and reduced levels of AHSG appear to be markers of severe inflammatory arthritis.

Purpose: To determine whether reduced serum levels of AHSG and elevated levels of BMP-2, 4, 7 are associated with post-arthroplasty HO. Patients: Thirty arthroplasty patients were included, 15 with evidence of peri-articular HO and 15 without (NHO). Methods: Blood samples were collected from all patients ≥ 8 weeks after arthroplasty. Analytes were measured using ELISAs. Mann-Whitney U tests were performed to compare serum analyte concentrations between HO and NHO groups, and between arthroplasty patients and healthy humans. Results: There is no difference in serum concentrations of AHSG, BMP-2, 4, 7 between HO and NHO patients. Arthroplasty patients showed significantly higher BMP-2 and BMP-4 and lower AHSG serum levels compared to healthy humans (p < 0.01). Conclusion: Baseline BMP-2, 4, 7 and AHSG serum levels are not markers of acquired HO. However, elevated baseline levels of BMP- 2, 4 and reduced levels of AHSG appear to be markers of severe inflammatory arthritis.

O objetivo deste trabalho foi estudar o efeito da radioterapia na profilaxia da ossificação heterotópica (OH) em pacientes com lesão medular traumática. Foram estudados 19 pacientes (15 homens e quatro mulheres), média de idade de 30,4 ± 10,8 anos (19 a 58 anos), com lesão medular traumática. A causa mais freqüente da lesão medular foi acidente de trânsito (42,1%), seguida por queda (26,3%), ferimento por projétil de arma de fogo (21%), mergulho (5,3%) e queda de objeto sobre as costas (5,3%). Dez pacientes eram tetraplégicos (52,6%) e nove (47,4%) eram paraplégicos. Apresentavam lesão medular completa (Frankel A) 14 pacientes (73,7%) e cinco pacientes (25,3%) tinham lesão incompleta (Frankel B). Todos os pacientes incluídos no estudo realizaram cintilografia óssea inicial até um mês após o traumatismo raquimedular e apresentaram diagnóstico negativo para OH. Os pacientes foram divididos em dois grupos: nove pacientes receberam radioterapia em dose única de 8 Gy nos quadris (Grupo Estudo) e 10 pacientes compuseram o Grupo Controle. Após seis meses de seguimento clínico e radiológico, um paciente do Grupo Estudo (11%) e cinco pacientes do Grupo Controle (50%) apresentaram OH. A distribuição da freqüência do desenvolvimento da OH nos dois grupos não mostrou diferença estatística significante, apesar da menor incidência de OH no grupo submetido à radioterapia (Grupo Estudo). Concluiu-se que, com o número de pacientes estudados, não foi possível comprovar a eficácia da radioterapia na prevenção da ossificação heterotópica, ainda que haja uma forte tendência para a correlação estatística / The goal of this study was to evaluate the effect of radiotherapy on the prophylaxis of heterotopic ossification (HO) after spinal cord injury (SCI). Nineteen SCI patients were studied (15 men and four women). The mean age was 30.4 ± 10.8 years (range 19 to 58 years). The most frequent causes of lesion were traffic accident (42.1%), fall (26.3%), shot gun (21%), diving (5.3%) and objects falling on the vertebral column (5.3%). Ten patients were tetraplegics (52.6%) and nine were paraplegics. Fourteen patients (73.7%) had complete lesion (Frankel A) and five had incomplete lesion (Frankel B). All patients realized initial scintigraphy until one month after SCI and showed negative results for HO. The patients were randomized in two groups: nine patients received single dose irradiation with 8 Gy on the hips (Study Group) and 10 patients were the Control Group. After six months of clinical and radiological follow up, one patient of the Study Group (11%) and five patients of Control Group (50%) showed HO. The frequency distribution of the development of HO in both groups showed no significant statistical difference, although there was lower incidence of HO in the radiotherapy group. We concluded that, with the number of patients studied, it was no possible to prove the efficacy of radiotherapy to prevent HO, although had a strong tendency for the statistical correlation

1 PURPOSE OF THE STUDY Heterotopic ossification is frequent and well known complication after primary total hip arthroplasty. Prophylaxis is crucial, ohterwise when ossification is matured, the only treatment option is surgical removal during revision hip surgery. Prophylaxis options are pre, peri- and postoperative modalities. Effectiveness of the profylaxis step sis the aim of this disertation. The goal of Study 1 was to prove the positive side effect of tranexamic acid application to reduce the heterotopic ossification ratio after elective total hip replacement. The goal of Study 2 was to prove the reduction in HO ratio with experimental modification of anterolateral approach with electrosurgery. The goal of Study 3 was to detect the knowledge among czech orthopaedic surgeons in ossification issues and compare the results of questionnaire with german results. 2 MATERIAL AND METHODS Study 1 Cohort of 401 total hip replacements were assessed prospectivelly. Stratification of particular degrees in Brooker scale, sex, laterality and fixation type were evaluated. The average follow up was 6,10 year (40m to 113m). Hips from 2012 are referential and hips from 2016 are administered to tranexamic acid procotol. Other secondary prophylactic modalities (farmacoprophylaxy or radiotherapy), tertiary...

Abstract Heterotopic ossification is a pathological condition in which bone forms outside the skeletal system. It can also occur in skin, which is the case in some genetic disorders. In multiple miliary osteoma cutis (MMOC), tiny bone fragments develop in the dermis and nearby subcutaneous tissue of the face and upper chest region during middle age. The etiology of the disease is poorly understood. The origin of the osteoma-forming cells is not known and also unknown are the signaling factors that direct the skin cells towards an osteogenic lineage. The purpose of this study was to investigate MMOC and the pathogenesis of ectopic bone formation by combining patient study and cell biology methods. The results from an extensive review of the literature and five new cases revealed MMOC as a distinct disease entity, where heterotopic bone formation is intramembranous. No correlation was found between MMOC and acne scars, hormonal disturbances or GNAS gene mutations. In cell culture studies mouse and human dermal fibroblasts and mouse dermal papilla (DP) cells were found to differentiate into osteoblast-like matrix mineralizing cells. The bone morphogenetic protein 4 (BMP-4) homodimer and BMP-2/7 heterodimer had significant effects on the osteogenic differentiation of the above mentioned cells. Interestingly, the BMPs enhanced the differentiation of mouse cells but reduced it in human cells. In mouse DP cells and human fibroblasts BMP-2/7 was more potent than BMP-4. The skin area affected by osteomas in patients was compared to their unaffected skin and also to the corresponding skin areas in controls with regard to osteogenic differentiation and gene expression studies. MMOC patients’ skin differs from controls both in osteoma and unaffected skin areas, which suggests MMOC is not only a local but also a systemic skin disease. The results confirm the previous findings that gene expression in skin is different in different parts of the body, which could explain why the osteomas develop in certain skin areas. The results of this study provide new information about MMOC and heterotopic ossification in skin and could be useful when developing treatments for MMOC. This study also presents new information about BMPs and their different effects in mouse and human cells, which may stimulate discussion about the generalization of mouse studies in humans and the clinical use of BMPs. / Tiivistelmä Virhesijaintinen luutuminen on patologinen tila, jossa luuta muodostuu luisen tukirangan ulkopuolelle. Tätä voi tapahtua myös ihossa, kuten käy tietyissä sairauksissa. Ihon lukuisat jyvämäiset osteoomat on tauti, jossa pieniä luujyväsiä ilmaantuu verinahkaan ja ihonalaiskudokseen keski-iässä. Taudin syytä, osteoomia muodostavien solujen alkuperää tai sitä, mitkä viestinvälittäjät saavat esiastesolut siirtymään luusolulinjalle, ei tiedetä. Tässä työssä tutkittiin ihon lukuisia jyvämäisiä osteoomia ja virhesijaintista luutumista yhdistämällä kliinisiä ja solubiologisia menetelmiä. Laajasta kirjallisuuteen perehtymisestä ja viidestä omasta potilaasta saadut tulokset osoittivat ihon lukuisten jyvämäisten osteoomien olevan oma erillinen tautinsa, jossa virhesijaintinen luutuminen tapahtuu suoran luutumisen mekanismilla. Tauti ei näytä olevan yhteydessä aknearpiin, hormonihäiriöihin tai GNAS-geenin mutaatioihin. Soluviljelykokeissa hiiren ja ihmisen verinahan fibroblastien ja hiiren karvatupen nystyn solujen havaittiin erilaistuvan osteoblastityyppisiksi soluväliainetta mineralisoiviksi soluiksi. Luun morfogeneettisillä proteiineilla (BMP) 4 ja 2/7 oli merkitsevä vaikutus yllä mainittujen solujen erilaistumisessa. Yllättävää kyllä, ne edistivät hiiren solujen, mutta vähensivät ihmisen solujen erilaistumista. Hiiren karvatupen soluille ja ihmisen fibroblasteille BMP-2/7 oli tehokkaampi kuin BMP-4. Potilaiden osteoma-aluetta verrattiin heidän terveeseen ihoalueeseensa samoin kuin vastaaviin ihoalueisiin kontrollihenkilöillä käyttäen menetelminä solujen erilaistamista luuta muodostavaan suuntaan sekä geenien ilmentymisen tutkimista. Potilaiden iho erosi kontrollien ihosta sekä osteooma-alueella että terveellä ihoalueella, mikä viittaa taudin olevan koko elimistöön vaikuttava. Tulokset vahvistavat aikaisempia löydöksiä siitä, että geenien ilmentyminen ihossa on erilaista eri puolilla kehoa. Tämä voisi selittää osteoomien esiintymisen vain tietyllä alueella. Tämän tutkimuksen tulokset antavat uutta tietoa ihon lukuisista jyvämäisistä osteoomista ja virhesijaintisesta luutumisesta ja saattavat olla hyödyksi kehitettäessä taudin hoitoa. Tutkimus antaa uutta tietoa luun morfogeneettisten proteiinien erilaisesta käyttäytymisestä hiirellä ja ihmisellä, mikä herättänee keskustelua hiirikokeiden yleistämisestä ihmiseen ja luun morfogeneettisten proteiinien kliinisestä käytöstä.