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PURPOSE: Growth deficiency is a cardinal feature of osteogenesis imperfecta (OI) types III and IV, caused by pathogenic variants in type I collagen. OI-specific longitudinal growth charts are needed for patient care. METHODS: We compiled longitudinal length, weight, head circumference, and body mass index (BMI) data from 100 children with types III and IV OI and known type I collagen pathogenic variants. Effects of gender, OI type, and pathogenic variant were examined using multilevel modeling. OI-specific centile curves were constructed using generalized additive model for location, scale, and shape (GAMLSS). RESULTS: OI type and gender, but not the specific mutated collagen gene, significantly affect stature, but only OI type affects weight. Head circumference was not significantly different by gender, type, or mutated gene. In both genders, length curves for types III and IV OI overlap and the type IV 95th centile curve overlaps the lower US Centers for Disease Control and Prevention (CDC) curves for the general population. A pubertal growth spurt is generally absent or blunted in types III/IV OI. The body mass index 50th and 95th centile curves are distinctly shifted above respective US CDC curves in both genders. CONCLUSIONS: OI type is a stronger contributing factor than gender for OI growth, while curves do not differ for COL1A1 versus COL1A2 pathogenic variants. Types III and IV OI-specific growth curves are presented.
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Tamanho Corporal/genética , Colágeno Tipo I/genética , Osteogênese Imperfeita/genética , Adolescente , Estatura , Índice de Massa Corporal , Pesos e Medidas Corporais , Criança , Desenvolvimento Infantil/fisiologia , Pré-Escolar , Colágeno Tipo I/metabolismo , Feminino , Humanos , Lactente , Estudos Longitudinais , MasculinoRESUMO
OBJECTIVEEnhanced recovery after surgery (ERAS) pathways are associated with improved outcomes, lower morbidity and complications, and higher patient satisfaction in multiple surgical subspecialties. Despite these gains, there are few data to guide the application of ERAS concepts to spine surgery. The authors report the development and implementation of the first ERAS pathway for patients undergoing anterior cervical discectomy and fusion (ACDF) and cervical disc arthroplasty (CDA).METHODSThis was a retrospective cohort study of prospectively collected data. The authors created a multidisciplinary pathway based on best available evidence for interventions that positively influence outcomes after anterior cervical spine surgery. Patients were followed prospectively up to postoperative day 90. Patient data were collected via electronic medical record review and included demographics, comorbidities, baseline and perioperative opioid use, postoperative complications, and length of hospital stay (LOS). ERAS process measures and compliance with pathway elements were also tracked.RESULTSThirty-three patients were cared for under the pathway (n = 25 ACDF; n = 8 CDA). The median LOS was 416 minutes (interquartile range [IQR] 210-1643 minutes). Eight patients required an extended stay-longer than 23 hours. Reasons for extended admission included pain (n = 4), dyspnea (n = 1), hypoxia (n = 1), hypertension (n = 1), and dysphagia (n = 1). The median LOS for the 8 patients who required extended monitoring prior to discharge was 1585 minutes (IQR 1423-1713 minutes). Overall pathway compliance with included process measures was 85.6%. The median number of ERAS process elements delivered to each patient was 18. There was no strong association between LOS and number of ERAS process elements provided (Pearson's r = -0.20). Twelve percent of the cohort was opioid tolerant on the day of surgery. There were no significant differences between total intraoperatively or postanesthesia care unit-administered opioid, or LOS, between opioid-tolerant and opioid-naïve patients. There were no complications requiring readmission.CONCLUSIONSAn ERAS pathway for anterior cervical spine surgery facilitates safe, prompt discharge. The ERAS pathway was associated with minimal complications, and no readmissions within 90 days of surgery. Pain and respiratory compromise were both linked with extended LOS in this cohort. Further prospective studies are needed to confirm the potential benefits of ERAS for anterior cervical spine surgery, including longer-term complications, cost, and functional outcomes.
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Vértebras Cervicais/cirurgia , Recuperação Pós-Cirúrgica Melhorada , Alta do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Coluna Vertebral/cirurgia , Adulto , Idoso , Analgésicos Opioides/uso terapêutico , Artroplastia , Estudos de Coortes , Discotomia/métodos , Feminino , Humanos , Degeneração do Disco Intervertebral/cirurgia , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/etiologia , Estudos Retrospectivos , Fusão VertebralRESUMO
PURPOSE: To determine if there was a difference between patients participating in research and those who did not regarding their satisfaction with the medical encounter and their physician. METHODS: We prospectively randomized 128 patients to either complete 20 minutes of questionnaires (participate in research) or not. After the visit, all patients rated their satisfaction with their visit and satisfaction with the doctor on an 11-point ordinal satisfaction scales, with 0 being not at all satisfied and 10 being completely satisfied. Average satisfaction scores were analyzed in relation to demographics, questionnaires, and involvement in research. RESULTS: There were no significant differences between patients that did and did not participate in research for satisfaction with the medical encounter or satisfaction with the treating physician. Satisfaction was not associated with marital status, work status, or diagnosis. There was a significant correlation between greater satisfaction and both less education and lower self-efficacy. There was no significant correlation between patient satisfaction and magnitude of disability, pain intensity, or health anxiety. CONCLUSIONS: This study demonstrated that patients' participation in research can coexist with patient satisfaction. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic I.
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Pesquisa Biomédica , Participação do Paciente , Satisfação do Paciente , Adulto , Avaliação da Deficiência , Humanos , Relações Médico-Paciente , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
Background: The absence of consensus for prophylaxis of venous thromboembolism (VTE) in spine surgery underscores the importance of identifying patients at risk. This study incorporated machine learning (ML) models to assess key risk factors of VTE in patients who underwent posterior spinal instrumented fusion. Methods: Data was collected from the IBM MarketScan Database [2009-2021] for patients ≥18 years old who underwent spinal posterior instrumentation (3-6 levels), excluding traumas, malignancies, and infections. VTE incidence (deep vein thrombosis and pulmonary embolism) was recorded 90-day post-surgery. Risk factors for VTE were investigated and compared through several ML models including logistic regression, linear support vector machine (LSVM), random forest, XGBoost, and neural networks. Results: Among the 141,697 patients who underwent spinal fusion with posterior instrumentation (3-6 levels), the overall 90-day VTE rate was 3.81%. The LSVM model demonstrated the best prediction with an area under the curve (AUC) of 0.68. The most important features for prediction of VTE included remote history of VTE, diagnosis of chronic hypercoagulability, metastatic cancer, hemiplegia, and chronic renal disease. Patients who did not have these five key risk factors had a 90-day VTE rate of 2.95%. Patients who had an increasing number of key risk factors had subsequently higher risks of postoperative VTE. Conclusions: The analysis of the data with different ML models identified 5 key variables that are most closely associated with VTE. Using these variables, we have developed a simple risk model with additive odds ratio ranging from 2.80 (1 risk factor) to 46.92 (4 risk factors) over 90 days after posterior spinal fusion surgery. These findings can help surgeons risk-stratify their patients for VTE risk, and potentially guide subsequent chemoprophylaxis.
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BACKGROUND CONTEXT: Racial disparities in spine surgery have been thoroughly documented in the inpatient (IP) setting. However, despite an increasing proportion of procedures being performed as same-day surgeries, whether similar differences have developed in the outpatient (OP) setting remains to be elucidated. PURPOSE: This study aimed to investigate racial differences in postoperative outcomes between Black and White patients following OP and IP lumbar and cervical spine surgery. STUDY DESIGN/SETTING: Retrospective cohort study. PATIENT SAMPLE: Patients who underwent IP or OP microdiscectomy, laminectomy, anterior cervical discectomy and fusion (ACDF), or cervical disc replacement (CDR) between 2017 and 2021. OUTCOME MEASURES: Thirty-day rates of serious and minor adverse events, readmission, reoperation, nonhome discharge, and mortality. METHODS: A retrospective review of patients who underwent IP or OP microdiscectomy, laminectomy, anterior cervical discectomy and fusion (ACDF), or cervical disc replacement (CDR) between 2017 and 2021 was conducted using the National Surgical Quality Improvement Program (NSQIP) database. Disparities between Black and White patients in (1) adverse event rates, (2) readmission rates, (3) reoperation rates, (4) nonhome discharge rates, (5) mortality rates, (6) operative times, and (7) hospital LOS between Black and White patients were measured and compared between IP and OP surgical settings. Multivariable logistic regression analyses were used to adjust for potential effects of baseline demographic and clinical differences. RESULTS: Of 81,696 total surgeries, 49,351 (60.4%) were performed as IP and 32,345 (39.6%) were performed as OP procedures. White patients accounted for a greater proportion of IP (88.2% vs 11.8%) and OP (92.7% vs 7.3%) procedures than Black patients. Following IP surgery, Black patients experienced greater odds of serious (OR 1.214, 95% CI 1.077-1.370, p=.002) and minor adverse events (OR 1.377, 95% CI 1.113-1.705, p=.003), readmission (OR 1.284, 95% CI 1.130-1.459, p<.001), reoperation (OR 1.194, 95% CI 1.013-1.407, p=.035), and nonhome discharge (OR 2.304, 95% CI 2.101-2.528, p<.001) after baseline adjustment. Disparities were less prominent in the OP setting, as Black patients exhibited greater odds of readmission (OR 1.341, 95% CI 1.036-1.735, p=.026) but were no more likely than White patients to experience adverse events, reoperation, individual complications, nonhome discharge, or death (p>.050 for all). CONCLUSIONS: Racial inequality in postoperative complications following spine surgery is evident, however disparities in complication rates are relatively less following OP compared to IP procedures. Further work may be beneficial in elucidating the causes of these differences to better understand and mitigate overall racial disparities within the inpatient setting. These decreased differences may also provide promising indication that progress towards reducing inequality is possible as spine care transitions to the OP setting.
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Desigualdades de Saúde , Complicações Pós-Operatórias , Fusão Vertebral , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Ambulatórios/estatística & dados numéricos , Negro ou Afro-Americano/estatística & dados numéricos , Vértebras Cervicais/cirurgia , Discotomia/efeitos adversos , Discotomia/estatística & dados numéricos , Laminectomia/efeitos adversos , Laminectomia/estatística & dados numéricos , Pacientes Ambulatoriais/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etnologia , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Fusão Vertebral/estatística & dados numéricos , Fusão Vertebral/efeitos adversos , Brancos/estatística & dados numéricosRESUMO
Background: Lumbar disc herniation (LDH) is a common condition that can be characterized with disabling pain. While most patients recover without surgery, some still require operative intervention. The epidemiology and trends of laminotomy for LDH have not been recently studied, and current practice patterns might be different from historical norms. This study aimed to investigate the trends of inpatient and outpatient laminotomies for LDH and compare complication rates between these two sites of service. Methods: A large, national database was utilized to identify patients > 8 years old who underwent a laminotomy for LDH between 2009 and 2019. Two cohorts were created based on site of surgery: inpatient versus outpatient. The outpatient cohort was defined as patients who had a length of stay less than 1 day without any associated hospitalization. Epidemiologic analyses for these cohorts were performed by demographics. Patients in both groups were then 1:1 propensity-score matched based on age, sex, insurance type, geographic region, and comorbidities. Ninety-day postoperative complications were compared between cohorts utilizing multivariate logistic regressions. Results: The average incidence of laminotomy for LDH was 13.0 per 10,000 persons-years. Although the national trend in incidence had not changed from 2009 to 2019, the proportion of outpatient laminotomies significantly increased in this time period (p=.02). Outpatient laminotomies were more common among younger and healthier patients. Patients with inpatient laminotomies had significantly higher rates of surgical site infections (odds ratio [OR] 1.61, p<.001), venous thromboembolism (VTE) (OR 1.96, p<.001), hematoma (OR 1.71, p<.001), urinary tract infections (OR 1.41, p<.001), and acute kidney injuries (OR 1.75, p=.001), even when controlling for selected confounders. Conclusions: Our study demonstrated an increasing trend in the performance of laminotomy for LDH toward the outpatient setting. Even when controlling for certain confounders, patients requiring inpatient procedures had higher rates of postoperative complications. This study highlights the importance of carefully evaluating the advantages and disadvantages of performing these procedures in an outpatient versus inpatient setting.
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At the cornerstone of the pelvis and spine, the sacrum may be fractured in patients of all ages. Sacral fractures range from high-energy injuries, with mortality rates of up to 18%, to low-energy insufficiency fractures. The intricate geometry of the sacrum, the breadth of morphotypes, and the presence of congenital anomalies all can complicate the treatment of these fractures. Agreement on the surgical indications for these injuries is limited. This narrative review aims to update orthopedic surgeons on the clinical evaluation and the non-surgical and surgical management of these fractures.
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STUDY DESIGN: Institutional review board-approved retrospective cohort study. OBJECTIVES: Failure to achieve alignment goals may result in accelerated adjacent segment degeneration and poorer outcomes. In "open" spine surgery, intraoperative tools can fine tune alignment; minimally invasive spine surgery techniques may not allow for this type of intraoperative adjustment. The aim of this study was to identify pre-operative radiographic parameters that accurately predict post-operative alignment after minimally invasive lumbar spine surgery. We hypothesized that pre-operative supine and extension sagittal alignment would predict post-operative standing alignment. METHODS: 50 consecutive patients underwent lateral or anterior lumbar interbody fusion with or without percutaneous posterior instrumentation by a single-surgeon. Sagittal alignment parameters were evaluated on pre-operative standing scoliosis radiographs, dynamic radiographs, supine CT scout, and 6-week post-operative standing radiographs. Demographic and perioperative data were analyzed. RESULTS: The mean age was 67.8 years. The mean BMI was 29.7. On average, 3 levels were instrumented (range, 2-6). Surgical time was 4.5 ± 1.8 hours. Following surgery, global lordosis increased from 44.7 ± 17° to 48.6 ± 16° (P = .001). However, there was no significant difference between the pre-operative supine (48.5 ± 15°), pre-operative extension (49.2 ± 18°), or 6-week post-operative standing radiographs (48.6 ± 16°). There were strong correlations between post-operative alignment and pre-operative supine (r = .825) and extension (r = .851) alignment. CONCLUSIONS: Our results suggest that pre-operative supine and extension radiographs could be a gold standard for minimally invasive lumbar spine surgery alignment correction as they predict post-operative alignment. The extension alignment was the strongest predictor of post-operative alignment.
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STUDY DESIGN: Retrospective analysis on prospectively collected data. OBJECTIVE: The purposes of this study were to (1) assess disparities in relative utilization of outpatient cervical spine surgery between White and Black patients from 2010 to 2019 and (2) to measure how these racial differences have evolved over time. SUMMARY OF BACKGROUND DATA: Although outpatient spine surgery has become increasingly popularized over the last decade, it remains unknown how racial disparities in surgical utilization have translated to the outpatient setting and whether restrictive patterns of access to outpatient cervical spine procedures may exist. METHODS: A retrospective cohort study from 2010 to 2019 was conducted using the National Surgical Quality Improvement Program database. Relative utilization of outpatient (same-day discharge) for anterior cervical discectomy and fusion (OP-ACDF) and cervical disk replacement (OP-CDR) were assessed and trended over time between races. Multivariable regressions were subsequently utilized to adjust for baseline patient factors and comorbidities. RESULTS: Overall, Black patients were significantly less likely to undergo OP-ACDF or OP-CDR surgery when compared with White patients ( P <0.03 for both OP-ACDF and OP-CDR). From 2010 to 2019, a persisting disparity over time was found in outpatient utilization for both ACDF and CDR ( e.g. White vs. Black OP-ACDF: 6.0% vs. 3.1% in 2010 compared with 16.7% vs. 8.5% in 2019). These results held in all adjusted analyses. CONCLUSIONS: To our knowledge, this is the first study reporting racial disparities in outpatient spine surgery and demonstrates an emerging disparity in outpatient cervical spine utilization among Black patients. These restrictive patterns of access to same-day outpatient hospital and surgery centers may contribute to broader disparities in the overall utilization of major spine procedures that have been previously reported. Renewed interventions are needed to both understand and address these emerging inequalities in outpatient care before they become more firmly established within our orthopedic and neurosurgery spine delivery systems.
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Pacientes Ambulatoriais , Fusão Vertebral , Humanos , Estudos Retrospectivos , Discotomia/métodos , Vértebras Cervicais/cirurgia , Alta do Paciente , Fusão Vertebral/métodosRESUMO
STUDY DESIGN: Institutional Review Board-approved prospective cohort study. OBJECTIVES: To establish a conversion between Neck Disability Index (NDI) and Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference (PI). SUMMARY OF BACKGROUND DATA: As the National Institutes of Health (NIH) PROMIS is a global outcome measure, it can be difficult to interpret the clinical implications in patients with cervical spine surgery. To determine how a disease-specific legacy instrument (NDI) correlates with PROMIS PI and define levels of substantial and minimal disability, we developed a formula to convert NDI scores to PROMIS PI. MATERIALS AND METHODS: Adult patients undergoing cervical spine surgery at a single institution from 2016 to 2018 were prospectively enrolled. Patients undergoing surgery for instability due to trauma were excluded. Preoperative questionnaires, demographic data, presenting complaint (radiculopathy, myelopathy, myeloradiculopathy), and procedural data were recorded. Patients were included if they had completed the NDI and PROMIS PI. Correlation and regression analyses were performed. RESULTS: One hundred ninety-six patients met inclusion criteria. The average age was 56.9±12.9 years. The mean NDI score was 68.6±38 and PROMIS PI was 60.9±7.3. The PROMIS PI was strongly correlated with the NDI ( r =0.76, P <0.001). Linear regression analysis revealed the following formula. CONCLUSIONS: We performed a regression analysis allowing for the conversion of PROMIS PI scores with NDI. In keeping with the previous studies, our analysis showed that PROMIS PI was most strongly correlated to NDI. A PROMIS PI score >66 was correlated to substantial disability (NDI=50), whereas a PROMIS PI score <59 was correlated to minimal relative impairment (NDI=28). These results provide important reference, as PROMIS reporting becomes more widespread in the literature.
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Radiculopatia , Doenças da Medula Espinal , Adulto , Humanos , Pessoa de Meia-Idade , Idoso , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos , Doenças da Medula Espinal/cirurgia , Radiculopatia/cirurgia , Vértebras Cervicais/cirurgiaRESUMO
The objective of this study was to examine the health-related quality of life (HRQOL) outcomes for surgically-treated atypical femur fractures (AFFs) compared to typical femoral diaphyseal fractures. Two large trauma center databases were retrospectively queried for surgically-treated femur fractures. Fractures were grouped into AFFs and compared to a control cohort. Controls for the AFF group included women with diaphyseal fractures without additional AFF characteristics. Patients were contacted for administration of the Short Form-36v2 Health Survey. Surveys were completed an average of 30.3 months (range, 6-138 months) and 25.5 months (range, 5-77 months) postoperatively for the AFF and non-AFF groups, respectively. All patients were female, with 46 patients in the AFF and 26 patients in the non-AFF group. The average age of the AFF group was 70.1 years compared with an average age of 67.4 years in the non-AFF group (p = 0.287). Over 90% (91.3%) of patients in the AFF group had a history of bisphosphonate use while 26.9% of patients in the non-AFF group had used bisphosphonates (p < 0.0001). Patients with AFF reported their postoperative physical and mental health to be no different than similarly aged patients with femoral diaphyseal fractures, as measured by the Short Form 36, version 2 (SF-36v2) Health Survey. These data suggest that mid-term patient-reported quality of life outcomes are similar among women who sustain an AFF compared to a cohort of more typical femoral diaphyseal fractures. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.
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BACKGROUND: Healthcare resources have been greatly limited by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic halting non-essential surgical cases without clear service expansion protocols. QUESTIONS/PURPOSES: We sought to compare the peri-operative outcomes of patients undergoing spine surgery during the SARS-CoV-2 pandemic to a matched cohort prior to the pandemic. METHODS: We identified a consecutive sample of 127 adult patients undergoing spine surgery between March 9, 2020, and April 10, 2020, corresponding with the state of emergency declared in New York and the latest possible time for 1-month surgical follow-up. The study group was matched one-to-one based on age, gender, and body mass index with eligible control patients who underwent similar spine procedures prior to the SARS-CoV-2 outbreak. Surgeries performed for infectious or oncologic indications were excluded. Intra- and post-operative complication rates, re-operations, hospital length of stay, re-admissions, post-operative visit format, development of post-operative fever and/or respiratory symptoms, and SAR-CoV2 testing. RESULTS: A total of 254 patients (127 SARS-CoV-2 pandemic, 127 matched controls) were included. One hundred fifty-eight were male (62%), and 96 were female (38%). The mean age in the pandemic group was 59.8 ± 13.4 years; that of the matched controls was 60.3 ± 12.3. All patients underwent general anesthesia and did not require re-intubation. There were no significant differences in 1-month post-operative complication rates (16.5% pandemic vs. 12.6% control). There was one death in the pandemic group. No patients tested positive for the virus. CONCLUSION: This study represents the first report of post-operative outcomes in a large group of spine surgical patients in an area heavily affected by the SARS-CoV-2 pandemic.
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[This corrects the article DOI: 10.1007/s11420-020-09765-5.].
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PURPOSE: Abdominal adiposity is associated with low BMD and decreased growth hormone (GH) secretion, an important regulator of bone homeostasis. The purpose of our study was to determine the effects of a short course of GH on markers of bone turnover and bone marrow fat in premenopausal women with abdominal adiposity. MATERIALS AND METHODS: In a 6-month, randomized, double-blind, placebo-controlled trial we studied 79 abdominally obese premenopausal women (21-45 y) who underwent daily sc injections of GH vs. placebo. Main outcome measures were body composition by DXA and CT, bone marrow fat by proton MR spectroscopy, P1NP, CTX, 25(OH)D, hsCRP, undercarboxylated osteocalcin (ucOC), preadipocyte factor 1 (Pref 1), apolipoprotein B (ApoB), and IGF-1. RESULTS: GH increased IGF-1, P1NP, 25(OH)D, ucOC, bone marrow fat and lean mass, and decreased abdominal fat, hsCRP, and ApoB compared with placebo (p<0.05). There was a trend toward an increase in CTX and Pref-1. Among all participants, a 6-month increase in IGF-1 correlated with 6-month increase in P1NP (p=0.0005), suggesting that subjects with the greatest increases in IGF-1 experienced the greatest increases in bone formation. A six-month decrease in abdominal fat, hsCRP, and ApoB inversely predicted 6-month change in P1NP, and 6-month increase in lean mass and 25(OH)D positively predicted 6-month change in P1NP (p≤0.05), suggesting that subjects with greatest decreases in abdominal fat, inflammation and ApoB, and the greatest increases in lean mass and 25(OH)D experienced the greatest increases in bone formation. A six-month increase in bone marrow fat correlated with 6-month increase in P1NP (trend), suggesting that subjects with the greatest increases in bone formation experienced the greatest increases in bone marrow fat. Forward stepwise regression analysis indicated that increase in lean mass and decrease in abdominal fat were positive predictors of P1NP. When IGF-1 was added to the model, it became the only predictor of P1NP. CONCLUSION: GH replacement in abdominally obese premenopausal women for 6 months increased bone turnover and bone marrow fat. Reductions in abdominal fat, and inflammation, and increases in IGF-1, lean mass and vitamin D were associated with increased bone formation. The increase in bone marrow fat may reflect changes in energy demand from increased bone turnover.
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Adiposidade/efeitos dos fármacos , Medula Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Hormônio do Crescimento/farmacologia , Obesidade/tratamento farmacológico , Obesidade/fisiopatologia , Pré-Menopausa , Adulto , Apolipoproteínas B/metabolismo , Biomarcadores/metabolismo , Composição Corporal/efeitos dos fármacos , Medula Óssea/fisiopatologia , Osso e Ossos/efeitos dos fármacos , Feminino , Hormônio do Crescimento/administração & dosagem , Hormônio do Crescimento/uso terapêutico , Humanos , Inflamação/patologia , Osteocalcina/metabolismo , Osteogênese/efeitos dos fármacos , Fragmentos de Peptídeos/metabolismo , Placebos , Pré-Menopausa/efeitos dos fármacos , Pró-Colágeno/metabolismo , Espectroscopia de Prótons por Ressonância Magnética , Análise de Regressão , Fatores de TempoRESUMO
The cell surface receptor low-density lipoprotein receptor-related protein 5 (LRP5) is a key regulator of bone mass and bone strength. Heterozygous missense mutations in LRP5 cause autosomal dominant high bone mass (HBM) in humans by reducing binding to LRP5 by endogenous inhibitors, such as sclerostin (SOST). Mice heterozygous for a knockin allele (Lrp5(p.A214V) ) that is orthologous to a human HBM-causing mutation have increased bone mass and strength. Osteogenesis imperfecta (OI) is a skeletal fragility disorder predominantly caused by mutations that affect type I collagen. We tested whether the LRP5 pathway can be used to improve bone properties in animal models of OI. First, we mated Lrp5(+/p.A214V) mice to Col1a2(+/p.G610C) mice, which model human type IV OI. We found that Col1a2(+/p.G610C) ;Lrp5(+/p.A214V) offspring had significantly increased bone mass and strength compared to Col1a2(+/p.G610C) ;Lrp5(+/+) littermates. The improved bone properties were not a result of altered mRNA expression of type I collagen or its chaperones, nor were they due to changes in mutant type I collagen secretion. Second, we treated Col1a2(+/p.G610C) mice with a monoclonal antibody that inhibits sclerostin activity (Scl-Ab). We found that antibody-treated mice had significantly increased bone mass and strength compared to vehicle-treated littermates. These findings indicate increasing bone formation, even without altering bone collagen composition, may benefit patients with OI.