Thesis--Copenhagen. / Summary in Danish. Bibliography: p. [210]-222.

Thesis--Copenhagen. / Summary in Danish. Bibliography: p. [210]-222.

PURPOSE: The goal of this thesis research project is to evaluate and compare post-operative complications among patients, who underwent short and long segment Anterior Cervical Discectomy/Corpectomy and Fusion (ACDF/ACCF). METHODS: Retrospective cohort study design allowed for evaluation of series of variables (age, sex, diagnosis, general post-operative outcome, and complications) while comparing them between the short and long segment groups. RESULTS: Patients within both cohorts tended to experience similar complications, except pseudarthrosis and adjacent segment disease, which both were more prevalent in the long segment group. Diagnosis or short versus long segment length did not have an effect on the general post-operative outcome. One-level ACDF patients were younger than multilevel ACDF surgery patients. Dysphagia was more likely to occur in older patients, with the risk of dysphagia incidence increased by 7% with each year of patient’s age. CONCLUSIONS: Study indicated that longer segment ACDF/ACCF does not carry higher risk of complications incidence than short segment treatment. Further studies are advised to increase generalizability of these results.

Orientador: Bruno Livani / Texto em português e inglês / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-25T16:03:28Z (GMT). No. of bitstreams: 1 Bervian_MichelRoberto_M.pdf: 4068927 bytes, checksum: bf1a7a79c46ef107971e898469875605 (MD5) Previous issue date: 2014 / Resumo: Objetivo: Realizar exames de imagem pré-operatórios, verificar a vascularização do segmento proximal do escafoide no intraoperatório e estabelecer correlações diagnósticas destes com o exame anatomopatológico. Justificativa: O diagnóstico pré-operatório do estado vascular do segmento proximal do escafoide é importante para o planejamento e direcionamento da escolha da técnica cirúrgica a ser utilizada. Métodos: Estudo experimental, prospectivo, caracterizado por ensaio não controlado. Os pacientes foram avaliados em relação à necrose do segmento proximal do escafoide em exames pré-operatórios (radiografia, tomografia computadorizada e ressonância nuclear magnética) e, no intraoperatório, no qual a condição vascular do segmento proximal do escafoide foi avaliada após sua perfuração, que demonstrou a presença ou não de sangramento. A ausência de sangramento estabelece como condição um segmento de necrose avascular ou esclerótico. Foi colhido material do segmento proximal e enviado para exame anatomopatológico, e os achados foram classificados em quatro tipos principais: viabilidade óssea, grau intermediário com maior ou menor viabilidade óssea e necrose completa. Foi utilizado o teste de qui-quadrado para testar a associação entre os achados dos exames de imagem e exame intraoperatório quando comparados com o exame de anatomopatológico. Resultados: Foram avaliados 19 pacientes do gênero masculino com diagnóstico de pseudoartrose do escafoide. Os resultados demonstraram que existe associação significativa entre a alteração radiográfica e a necrose óssea p<0,05 (0,026). A tomografia não apresentou associação significativa com o diagnóstico anatomopatológico da necrose do osso escafoide p>0,05 (0,125). A ressonância nuclear magnética mostrou que o hipossinal marcado em T1 apresentou correlação significativa com o diagnóstico anatomopatológico de necrose no segmento proximal do escafoide em todos os pacientes p<0,05 (0,002). Em 90% dos ossos considerados escleróticos na avaliação intraoperatória a necrose foi confirmada pelo exame anatomopatológico, e a associação foi significativa p<0,05 (0,003). Conclusão: Na pseudoartrose do escafoide, imagens de ressonância nuclear magnética com hipossinal de baixa intensidade marcado em T1 e ausência de sangramento no intraoperatório são fortes indicativos de necroseOsteonecrose do segmento proximal / Abstract: Background: The purpose of this study was to correlate the preoperative imaging, vascularity of the proximal pole, and histology of the proximal pole bone of established scaphoid fracture nonunions. Methods: This was a prospective observational study. Patients were evaluated preoperatively for necrosis of the proximal scaphoid fragment by radiography, computed tomography (CT) and magnetic resonance imaging (MRI). Vascular status of the proximal scaphoid was determined intraoperatively, demonstrating the presence or absence of puncate bone bleeding. Samples were harvested from the proximal scaphoid fragment and sent for pathological examination. We determined the association between the imaging and intraoperative examination and histological findings. Results: We evaluated 19 male patients diagnosed with scaphoid nonunion. CT evaluation showed no correlation to scaphoid proximal fragment necrosis. MRI showed a marked low signal intensity on T1-weighted, and the diagnosis of necrosis in the proximal scaphoid fragment was confirmed by the histology in all patients. Intraoperative assessment showed that 90% of bones had absence of intraoperative puncate bone bleeding, which was confirmed as necrosis by microscopic examination. Correlation between preoperative imaging, intraoperative findings and pathology was found in 41% of cases, with 26% for bone necrosis and 15% for viable bone. Conclusions: In scaphoid nonunion MRI images with marked low signal intensity on T1-weighted and the absence of intraoperative puncate bone bleeding are strong indicatives of osteonecrosis of the proximal fragment / Mestrado / Fisiopatologia Cirúrgica / Mestre em Ciências

Orientador: Saulo Santesso Garrido / Coorientador: Gildásio de Cerqueira Daltro / Banca: Mário Castro Carreiro / Banca: Ademario Galvão Spínola / Resumo: Pseudoartrose é o termo usado para designar a não consolidação de uma fratura, quando o processo de reparação óssea, por algum motivo deixou de atuar. A falta da união das superfícies ósseas fraturadas decorre da presença de um tecido fibroso ou fibro-cartilaginoso entre as extremidades. Portanto, não há união dos fragmentos de uma fratura, levando à formação de uma pseudocápsula com sinóvia e líquido sinovial. Apesar do desenvolvimento de numerosas técnicas de reparação óssea na cirurgia traumatológica, ainda é bastante desafiador a busca da melhor terapêutica a ser utilizada para o tratamento dos grupos de fraturas que apresentam alterações no processo de consolidação e que culminam em pseudoartrose. Estima-se que cerca de 5 a 10% das fraturas de ossos longos evoluem para a disfunção no processo de consolidação, sendo mais comum na tíbia, fíbula e úmero. Novos métodos de tratamento baseados em biotecnologia têm despertado interesse em todo o mundo. Atualmente existe uma gama heterogênea de biomaterias que podem ser utilizados como facilitadores da consolidação óssea no tratamento das fraturas complexas. Estes biomaterias apesar de não representarem o tratamento principal, auxiliam na consolidação ou estimulação dos fenômenos que envolvem o reparo ósseo. Dentre eles, nos últimos anos diversos estudos têm demonstrado o potencial terapêutico do Plasma Rico em Plaquetas na regeneração de tecidos moles, cartilagem e ósseo. O plasma rico em plaquetas é um concentrado de plaquetas... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Pseudoarthrosis is the term used to designate non-consolidation of a fracture, when the bone repair process for some reason ceased to act. The lack of union of the fractured bone surfaces results from the presence of a fibrous or fibro-cartilaginous tissue between the extremities. Therefore, there is no union of the fragments of a fracture, leading to the formation of a pseudocapsule with synovium and synovial fluid. Despite the development of numerous bone repair techniques in trauma surgery, it is still quite challenging to seek the best therapy to be used for the treatment of fracture groups that present changes in the consolidation process and culminate in pseudoarthrosis. It is estimated that approximately 5 to 10% of the fractures of long bones evolve to the dysfunction in the consolidation process, being more common in the tibia, fibula and humerus. New biotechnology-based treatment methods have attracted interest all over the world. There is currently a heterogeneous range of biomaterials that can be used as facilitators of bone healing in the treatment of complex fractures. These biomaterias, although they do not represent the main treatment, help in the consolidation or stimulation of the phenomena that involve the bone repair. In recent years, several studies have demonstrated the therapeutic potential of Platelet Rich Plasma in the regeneration of soft tissues, cartilage and bone. Platelet-rich plasma is in autogenous platelet concentrate obtained by centrifugatio... (Complete abstract click electronic access below) / Mestre

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Métodos: Estratégia de busca: abrangeu CENTRAL, MEDLINE, EMBASE e LILACS. Não houve restrições de idioma ou meios de publicações. A última estratégia de busca foi realizada em julho de 2009. Critério de seleção: foram incluídos ensaios clínicos randomizados e quase-randomizados que avaliaram o tratamento de fratura aguda e pseudartrose do terço médio da clavícula em adultos e adolescentes. Os desfechos primários foram: dor, qualidade de vida/função do ombro e falha do tratamento. Coleta e análise dos dados: dois autores, independentemente, selecionaram os estudos elegíveis, avaliaram a qualidade metodológica e extraíram os dados. Calculou-se o risco relativo com 95% de intervalo de confiança para as variáveis dicotômicas; para variáveis contínuas, a diferença entre as médias foi calculada com 95% de intervalo de confiança. Quando possível, os estudos foram agrupados. Resultados: Intervenções não cirúrgicas: dois estudos compararam imobilização em oito versus tipoia. Ambos possuíam baixo poder estatístico e alto risco de viés. Houve maiores níveis de dor e desconforto durante o tratamento nos pacientes submetidos à imobilização em oito. Um terceiro estudo, com baixo risco de viés, mas baixo poder estatístico, avaliou o ultrassom terapêutico. Não houve diferenças significantes entre o ultrassom de baixa intensidade e placebo nos desfechos avaliados. Intervenções não cirúrgicas versus cirúrgicas: Quatro estudos, dois com moderado e dois com alto risco de viés foram incluídos. Dois estudos compararam fixação com placa versus tipoia, com resultados favoráveis ao tratamento cirúrgico ao avaliar falha do tratamento e qualidade de vida/função do ombro. Outros dois estudos compararam fixação intramedular versus tratamento não cirúrgico; a cirurgia foi superior para os desfechos dor e qualidade de vida/função do ombro. Intervenções cirúrgicas: quatro estudos com baixo poder estatístico, cada qual avaliando diferentes comparações, foram incluídos; três possuíam alto risco de viés. Um estudo comparou placa de compressão de baixo contato com placa de compressão dinâmica em pseudartrose da clavícula; os pacientes tratados com placa de baixo contato apresentaram evolução melhor para: função do ombro, consolidação, retorno ao trabalho e menor incidência de sintomas relacionados ao implante. Outro estudo comparou fixação intramedular com pinos de Knowles versus fixação com placa para o tratamento de fratura aguda e pseudartrose da clavícula; a fixação intramedular acarretou em menor consumo de analgésicos após a cirurgia, menor número de complicações associadas ao implante e menor tempo cirúrgico e de internação. Um terceiro estudo, com baixo risco de viés, concluiu que a técnica de fixação tridimensional com placa ocasionou menor incidência de retardo de consolidação em relação à fixação na face superior das fraturas agudas da clavícula. Um último estudo avaliou a fixação intramedular das fraturas agudas da clavícula comparando redução fechada versus redução aberta. Houve diferenças significativas em favor da redução fechada quando avaliados os desfechos primários. Conclusão: os ensaios clínicos disponíveis na literatura não apresentam qualidade metodológica adequada e/ou poder estatístico apropriado, portanto, não há evidência suficiente para determinar quais os mais apropriados métodos de tratamento para a fratura e pseudartrose do terço médio da clavícula. Há uma tendência de melhores resultados funcionais e radiográficos a favor das intervenções cirúrgicas quando comparadas às intervenções não cirúrgicas. / Objectives: To evaluate the effectiveness of different methods of treatment for acute fracture or non-union of the middle third of the clavicle in adults and adolescents. Methods: Search strategy: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, trial registries and reference lists of articles. No language or publication restrictions were applied. Selection criteria: Randomised and quasi-randomised controlled trials evaluating any intervention for treating fractures or non-union of the middle third of the clavicle were considered. The primary outcomes were pain, treatment failure and health-related quality of life or shoulder function. Data collection and analysis: Two authors independently selected eligible trials and three authors assessed methodological quality and cross-checked data extraction. Results: Conservative interventions: Three trials were included in this comparison. Two trials compared the figure-of-eight bandage with sling in a total of 234 participants. Both trials were underpowered and compromised by poor methodology. One trial found slightly higher pain levels in the bandage group at 15 days, and the other trial reported greater discomfort during bandage wear. There were no significant differences in functional or other outcomes reported for either trial. The third trial, which evaluated therapeutic ultrasound in 120 participants, was also underpowered but had a low risk of bias. The trial found no statistically significant difference between low-intensity pulsed ultrasound and placebo in the time to clinical fracture healing or in any of the other reported outcomes. Surgical versus conservative interventions: Four studies, two with moderate and two with high risk of bias were included. Two compared plate fixation versus sling; plate fixation showed better patient-based upper extremity outcome scores and less treatment failure. Other two trials comparing intramedullary fixation versus conservative interventions presented better upper limb function to the surgery treatment. Surgical interventions: Data from four small trials, each testing a different comparison, were included. Three trials had design features that carry a high risk of bias, limiting the strength of their findings. Low-contact dynamic compression plates appeared to be associated with significantly better upper-limb function throughout the year following surgery, earlier fracture union and return to work, and a reduced incidence of implant-associated symptoms when compared with a standard dynamic compression plate in 36 adults with symptomatic non-union of the middle third of the clavicle. One study (69 participants) compared the Knowles pin versus plate for treating middle third clavicle fractures or non-union. Knowles pins appeared to be associated with lower pain levels and use of post-operative analgesics, reduced incidence of implant-associated symptoms, and shorter operation time and hospital stay. One study (133 participants) found that a three-dimensional technique for fixation with a reconstruction plate was associated with a significantly lower incidence of symptomatic delayed union than a standard superior position surgical approach. One study (201 participants) assessed the intramedullary fixation for treating acute clavicle fractures comparing closed and opened reduction; there were statistical significant differences in favour of closed reduction with percutaneous fixation for the primary outcomes. Conclusion: There is limited evidence, from single trials only, regarding the effectiveness of different methods for treating fracture and non-union of the middle third of the clavicle. Further research is warranted. / TEDE / BV UNIFESP: Teses e dissertações

Die Sprunggelenksarthrodese ist bei therapieresistenter Schmerzsymptomatik einer Sprunggelenksarthrose, nicht beherrschbarer Entzündung im Bereich des Rückfußes, Talusnekrose, schmerzhafter Pseudarthrose nach Arthrodese der Sprunggelenke sowie kontrakter Deformität des Rückfußes mit Gangstörung und Hautkomplikation indiziert. Sie stellt immer noch einen komplizierten Eingriff mit einer hohen Komplikationsrate dar. Dazu trägt neben den häufigen Wundheilungsstörungen die Pseudarthrose bei. Das Risiko für die Entstehung einer solchen Pseudarthrose hängt von klinischen Faktoren wie der sprunggelenksnahen Osteopenie, der Dauermedikation von Kortikoiden sowie dem Nikotinabusus und von operativen Faktoren wie der Komplexität des Verfahrens und Stabilität der Methode ab. Beim parallelen Auftreten dieser Faktoren mit Beeinträchtigung des biologischen und mechanischen Standbeins der Osteoneogenese potenziert sich dieses Risiko. Eine Sonderstellung unter den Risikofaktoren nimmt die sprunggelenksnahe Osteopenie ein. Nach entsprechender Analyse kommt sie hier signifikant vor. Ihre Diagnose beruft sich auf der nicht zu vernachlässigenden Anamnese, der bereits verordneten Medikation, der aussagefähigen, jedoch nicht standardisierten Knochendichtemessung und der entscheidenden Röntgendiagnostik. In Zukunft sollte präoperativ die bereits standardisierte Röntgendiagnostik mit einer Knochendichtemessung kombiniert werden. Leider ist präoperativ das Risiko, an einer Pseudarthrose nach einer Sprunggelenksarthrodese zu leiden, nur abschätzbar und nicht quantifizierbar. Neben der objektiven Befundung mittels Röntgen kann die subjektive Einschätzung des Patienten bei der Beurteilung der Pseudarthrose hilfreich sein. Somit müssen falsch positive Röntgenbefunde bei klinisch stummer Pseudarthrose im Sinne einer fibrösen Ankylosierung eingestuft und keiner Operation zugeführt werden. Bei einer Pseudarthrose nach der Sprunggelenksarthrodese mit Angabe einer Unzufriedenheit, einem moderaten Schmerz bei leichter Belastung, einem regelmäßigen Analgetikagebrauch, einem VAS-Wert ab 5, einer beschwerdefreien Gehstrecke unter 100m mit Gebrauch von 2 UAGS ist nach Aufklärung des Patienten die Re-Arthrodese zu diskutieren. Es sollten dann die Compliance jedes Patienten verbessert (Abstellen des Nikotinabusus), die präoperative Therapie von Neben- (Osteopenie) und Grunderkrankung (Umsetzung der immunsupprimierenden Therapie) optimiert und das geeignete Vorgehen (z.B. Zweizeitigkeit bei Pantalar-Arthrodese (zuerst talocrural und dann talotarsal) bzw. Nutzung interne Kompressionsmethoden mit autologem Knochenspan bei Knochendefekt) gewählt werden. / In painful osteoarthrosis, arthritis and pseudarthrosis of the ankle joint, in osteonecrosis of the talus and in deformity of the foot with limp and complications of skin the arthrodesis of the hindfoot is indicated. This is a difficult operation with many comlications like infection and pseudarthrosis. The risk of a pseudarthrosis depends on clinical factors like osteopenie, corticoid medication, nicotin and operative factors like the stabilisation. These factors injure the biological and mechanic basis of osteoneogenesis. The osteopenie is a significant risk factor. The diagnosis of the osteopenie is based on the anamnesis, the medication, the measurement of the bonemass and the x-ray. In future there must be standard to combinated the measurement of bonemass and x-ray. The risk of pseudarthrosis is not to quantify. The x-ray and the pain characterize a pseudarthrosis. So a painless pseudarthrosis don´t have to operate. When a patient with a pseudarthrosis is dissatisfied, when the pain is moderate with a value in the visuel analog scale of pain higher as 5, when analgetic medication are regular used, a painless walking less than 100m, a necessary use of supports a new arthrodesis ist indicated. Now the compliance of patient, the therapie of diseases and the operation methodes are improved.

Abstract The stem cell is a primitive cell that is capable of dividing to reproduce itself and can give rise to a selection of differentiated progeny. Stem cells are thought to be involved in or even main factors in many diseases. In postnatal humans, mesenchymal tissues have the capacity to regenerate from stem cells called mesenchymal stem cells (MSC). It is currently thought that these cells will become the basis of therapy for many diseases. In the present study, a novel in vitro method was developed to examine human bone marrow derived MSC differentiation into osteoblast lineage, and to study the role of MSC in a variety of mesenchymal diseases. The ability of MSCs to differentiate into osteoblasts was investigated during aging. In addition, the interindividual variability in the osteogenesis of MSCs and in the osteoblastic response of MSC to estrogen and testosterone was studied. Furthermore, an ex vivo model using a human aortic valve microenvironment was developed to explore whether the extracellular matrix influences the osteoblastic differentiation of the MSC. Finally, the role of MSC in neurofibromatosis type 1 (NF1) related congenital pseudarthrosis of the tibia (CPT) was studied. It was found that after menopause the osteogenic potential of MSCs does not decrease. It was also found that estrogen receptor (ER) alpha genotype confers interindividual variability of response to estrogen and testosterone in MSC derived osteoblasts. In addition, it was found that the non-calcified valves with living valve cells inhibited osteogenesis of co-cultured MSCs, whereas the calcified and devitalised valves promoted differentiation towards an osteoblastic lineage. Finally, MSCs from NF1-related pseudarthrosis showed altered NF1 gene expression, poor osteoblastic differentiation and bone formation. In conclusion, MSC can be easily isolated from the bone marrow and MSC has the capacity to regenerate tissue even at later stages of life. These results could help explain the contradictory effects of 17β-estradiol (E2) on osteoblasts in vitro and might also provide new insights into understanding the differences in responses to hormone replacement therapy. It seems that adult stem cells from bone marrow undergo milieu-dependent differentiation to express phenotypes that are similar to cells in the local microenvironment. Finally, the NF1 gene was shown to have a role in bone development and remodelling.

Orientador: Maurício Etchebehere / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-16T21:07:49Z (GMT). No. of bitstreams: 1 Ribak_Samuel_D.pdf: 49523344 bytes, checksum: ed945eca0e5edfae363666a01c273fde (MD5) Previous issue date: 2010 / Resumo: Avaliaram-se os aspectos clínicos, funcionais e radiográficos de 86 pacientes portadores de pseudoartroses do escafoide. Comparam-se 46 pacientes submetidos à técnica de enxerto ósseo vascularizado dorsal do rádio distal, baseado na artéria suprarretinacular intercompartimental 1,2* (Grupo I), e 40 pacientes submetidos à cirurgia pela técnica de enxerto ósseo convencional não vascularizado da mesma região, rádio distal (Grupo II), objetivando definir o melhor procedimento quanto à consolidação e função. A amostra foi composta por 25 pseudoartroses no terço médio e 21 no polo proximal nos pacientes do Grupo I, e 22 no terço médio, duas no polo distal e 16 no polo proximal nos pacientes do Grupo II. No transoperatório, 30 escafoides foram considerados não vascularizados nos pacientes do Grupo I, e 20 nos pacientes do Grupo II. A estabilização do escafóide foi realizada por três fios de Kirschner e, no pós-operatório, todos os pacientes foram submetidos à imobilização com tala gessada antebraquiopalmar por quatro semanas. O tempo de seguimento médio pósoperatório foi de 24.4 meses (Grupo I), e de 21.7 meses (Grupo II). Conseguiu-se consolidação de 89.1% nos pacientes do Grupo I e tempo médio de consolidação de 9.7 semanas. Nos pacientes do Grupo II, houve consolidação em 72.5%, com tempo médio de 12 semanas. Os resultados funcionais do Grupo I foram satisfatórios em 72% dos pacientes e 57,5% no Grupo II. Concluímos que a técnica de enxerto ósseo vascularizado apresenta, quanto ao índice de consolidação e função, resultados superioresaos do procedimento não vascularizado, sendo mais eficiente quando a condição do polo proximal do escafoide é esclerótica / Abstract: The clinical, functional and radiographic aspects of 86 patients presenting with scaphoid nonunion were evaluated in this study. Forty-six patients undergoing the technique of vascularized bone graft from the dorsal distal radius, based on the 1, 2 intercompartmental supraretinacular artery (Group I), and 40 patients undergoing the technique of usual nonvascularized bone graft of the same area (distal radius) (Group II), are compared with the purpose of determining the best procedure concerning healing and function. Our sample comprised nonunions in 25 middle-third and 21 proximal-pole patients (Group I), and in 22 middlethird, 2 distal-pole, and 16 proximal-pole patients (Group II). Transoperatively, 30 scaphoids in Group I patients and 20 in Group II patients were considered sclerotic. Scaphoid stabilization was achieved with three K-wires and, postoperatively, and immobilization consisted of a short-arm cast for all patients for four weeks. The average postoperative follow-up time was 24.4 months for Group I, and 21.7 months for Group II. Healing was achieved in 89.1% of Group I patients, with an average healing time of 9.7 weeks. Within Group II, healing was achieved in 72.5% of patients, with an average healing time of 12 weeks. The functional results were satisfactory in 72% of Group I patients and 57.5% of Group II patients. We therefore conclude, from the healing and function indices, that the vascularized bone graft technique produces superior results than the nonvascularized bone graft procedure, being more efficient when the proximal pole of the scaphoid is sclerotic / Doutorado / Fisiopatologia Cirúrgica / Doutor em Ciências

Indiana University-Purdue University Indianapolis (IUPUI) / Skeletal manifestations including short stature, osteoporosis, kyphoscoliosis, and tibial dysplasia cumulatively affect approximately 70% of patients with neurofibromatosis type 1 (NF1). Tibial pseudarthrosis, the chronic non-union of a spontaneous fracture, is a debilitating skeletal malady affecting young children with NF1. These non-healing fractures respond poorly to treatment and often require amputation of the affected limb due to limited understanding of the causative mechanisms. To better understand the cellular and molecular pathogenesis of these osseous defects, we have established a new mouse model which recapitulates a spectrum of skeletal pathologies frequently observed in patients with NF1. Nf1flox/-;Col2.3Cre mice, harboring Nf1 nullizygous osteoblasts on a Nf1+/- background, exhibit multiple osseous defects which are closely reminiscent of those found in NF1 patients, including runting (short stature), bone mass deficits, spinal deformities, and tibial fracture non-union. Through adoptive bone marrow transfer studies, we have demonstrated that the Nf1 haploinsufficient hematopoietic system pivotally mediates the pathogenesis of bone loss and fracture non-union in Nf1flox/-;Col2.3Cre mice. By genetic ablation of a single Nf1 allele in early myeloid development, under the control of LysMCre, we have further delineated that Nf1 haploinsufficient myeloid progenitors and osteoclasts are the culprit lineages mediating accelerated bone loss. Interestingly, conditional Nf1 haploinsufficiency in mature osteoclasts, induced by CtskCre, was insufficient to trigger enhanced lytic activity. These data provide direct genetic evidence for Nf1’s temporal significance as a gatekeeper of the osteoclast progenitor pool in primitive myelopoiesis. On the molecular level, we found that transforming growth factor-beta1 (TGF-β1), a primary mediator in the spatiotemporal coupling of bone remodeling, is pathologically overexpressed by five- to six- fold in both NF1 patients and in mice. Nf1 deficient osteoblasts, the principal source of TGF-β1 in the bone matrix, overexpress TGF-β1 in a gene dosage dependent fashion. Moreover, p21Ras dependent hyperactivation of the Smad pathway accentuates responses to pathological TGF-β1 signals in Nf1 deficient bone cells. As a proof of concept, we demonstrate that pharmacologic TβRI kinase inhibition can rescue bone mass defects and prevent tibial fracture non-union in Nf1flox/-;Col2.3Cre mice, suggesting that targeting TGF-β1 signaling in myeloid lineages may provide therapeutic benefit for treating NF1 skeletal defects.