RESUMO
Neurofibromatosis type 1 is a genetic syndrome characterized by a wide variety of tumor and non-tumor manifestations. Bone-related issues, such as scoliosis, tibial dysplasia, and low bone mineral density, are a significant source of morbidity for this population with limited treatment options. Some of the challenges to developing such treatments include the lack of consensus regarding the optimal methods to assess bone health in neurofibromatosis type 1 and limited data regarding the natural history of these manifestations. In this review, the Functional Committee of the Response Evaluation in Neurofibromatosis and Schwannomatosis International Collaboration: (1) presents the available techniques for measuring overall bone health and metabolism in persons with neurofibromatosis type 1, (2) reviews data for use of each of these measures in the neurofibromatosis type 1 population, and (3) describes the strengths and limitations for each method as they might be used in clinical trials targeting neurofibromatosis type 1 bone manifestations. The Response Evaluation in Neurofibromatosis and Schwannomatosis International Collaboration supports the development of a prospective, longitudinal natural history study focusing on the bone-related manifestations and relevant biomarkers of neurofibromatosis type 1. In addition, we suggest that the neurofibromatosis type 1 research community consider adding the less burdensome measurements of bone health as exploratory endpoints in ongoing or planned clinical trials for other neurofibromatosis type 1 manifestations to expand knowledge in the field.
Assuntos
Neurilemoma , Neurofibromatoses , Neurofibromatose 1 , Neoplasias Cutâneas , Humanos , Neurofibromatose 1/complicações , Neurofibromatose 1/terapia , Densidade Óssea/fisiologia , Estudos Prospectivos , Neurofibromatoses/complicações , Neurofibromatoses/terapiaRESUMO
The ability of the fracture risk assessment tool (FRAX) to discriminate between women who do and do not experience major osteoporotic fractures (MOFs) is suboptimal. Adding common clinical risk factors may improve discrimination. We used data from the Women's Health Initiative, a prospective study of women aged 50 to 79 years at baseline (n = 99,413; n = 5722 in BMD subset) enrolled at 40 US clinical centers. The primary outcome was incident MOFs assessed annually during 10 years' follow-up. For prediction of incident MOF, we examined the area under the receiver operatic characteristic curve (AUC) and net reclassification index (NRI) of the FRAX model alone and FRAX plus additional risk factors (singly or together: type 2 diabetes mellitus, frequent falls [≥2 falls in the past year], vasomotor symptoms, self-reported physical function score [RAND 36-item Health Survey subscale), and lumbar spine BMD). For NRI calculations, high risk was defined as predicted MOF risk ≥20%. We also assessed calibration as observed MOF events/expected MOF events. The AUC value for FRAX without BMD information was 0.65 (95% CI, 0.65 to 0.66). Compared with the FRAX model (without BMD), the AUC value was not improved by the addition of vasomotor symptoms, diabetes, or frequent falls, but was minimally increased by adding physical function score (AUC 0.66, 95% CI, 0.66 to 0.67). FRAX was well-calibrated for MOF prediction. The NRI of FRAX + additional variables versus FRAX alone was 5.7% (p < 0.001) among MOF cases and -1.7% among noncases (p > 0.99). Additional variables (diabetes, frequent falls, vasomotor symptoms, physical function score, or lumbar spine BMD) did not yield meaningful improvements in NRI or discrimination of FRAX for MOFs. Future studies should assess whether tools other than FRAX provide superior discrimination for prediction of MOFs. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
RESUMO
We evaluated functional measures of neuromuscular integrity and bone's resistance to fracture as a combined tool in discriminating osteoporosis patients with and without fractures. Functional aspects of neuromuscular integrity were quantified with a noninvasive measure of static and dynamic functional postural stability (FPS), and fracture resistance was obtained with bone shock absorption in patients with osteoporosis aged 65-85 and compared our measures with dual-energy X-ray absorptiometry and Fracture Risk Assessment Tool (FRAX [World Health Organization Collaborating Center for Metabolic Bone Diseases, Sheffield, UK]) in women with osteoporosis, some with and some without vertebral fractures. Patients with vertebral fracture showed larger static FPS (postural sway excursion) in the mediolateral and anterior-posterior directions, suggesting poorer balance. Most of the variables of dynamic FPS showed significant differences between fracture and no-fracture groups (e.g., the fracture group took significantly longer during turning, implying poorer dynamic balance control). Also, compared with healthy control subjects, all 4 dynamic FPS responses for osteoporosis patients with and without fracture were significantly poorer, suggesting potential risk for falls. In summary, patients with osteoporosis who have vertebral fractures (compared with patients with similarly low bone mineral density and other nonfracture risk fractures) have not only lower bone shock absorption damping (ζ) but also increased postural imbalance.
Assuntos
Densidade Óssea , Junção Neuromuscular/fisiopatologia , Osteoporose , Fraturas por Osteoporose , Equilíbrio Postural , Fraturas da Coluna Vertebral , Absorciometria de Fóton/métodos , Acidentes por Quedas/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Osteoporose/diagnóstico , Osteoporose/fisiopatologia , Fraturas por Osteoporose/diagnóstico , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/fisiopatologia , Medição de Risco/métodos , Fatores de Risco , Fraturas da Coluna Vertebral/diagnóstico , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/fisiopatologia , Estados UnidosRESUMO
GLOW is an observational, longitudinal, practice-based cohort study of osteoporosis in 60,393 women aged ≥55 years in 10 countries on three continents. In this Review, we present insights from the first 3 years of the study. Despite cost analyses being frequently based on spine and hip fractures, we found that nonvertebral, nonhip fractures were around five times more common and doubled the use of health-care resources compared with hip and spine fractures combined. Fractures not at the four so-called major sites in FRAX(®) (upper arm, forearm, hip and clinical vertebral fractures) account for >40% of all fractures. The risk of fracture is increased by various comorbidities, such as Parkinson disease, multiple sclerosis and lung and heart disease. Obesity, although thought to be protective against all fractures, substantially increased the risk of fractures in the ankle or lower leg. Simple assessment by age plus fracture history has good predictive value for all fractures, but risk profiles differ for first and subsequent fractures. Fractures diminish quality of life as much or more than diabetes mellitus, arthritis and lung disease, yet women substantially underestimate their own fracture risk. Treatment rates in patients at high risk of fracture are below those recommended but might be too frequent in women at low risk. Comorbidities and the limits of current therapeutic regimens jeopardize the efficacy of drugs; new regimens should be explored for severe cases.
Assuntos
Osteoporose/complicações , Fraturas por Osteoporose , Acidentes por Quedas/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Fraturas do Quadril/epidemiologia , Hospitalização/tendências , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Obesidade/complicações , Osteoporose/economia , Osteoporose Pós-Menopausa/tratamento farmacológico , Fraturas por Osteoporose/epidemiologia , Prevalência , Qualidade de Vida , Risco , Fatores de Risco , Fraturas da Coluna Vertebral/epidemiologiaRESUMO
Concern about the risk of bone loss in astronauts as a result of prolonged exposure to microgravity prompted the National Aeronautics and Space Administration to convene a Bone Summit with a panel of experts at the Johnson Space Center to review the medical data and research evidence from astronauts who have had prolonged exposure to spaceflight. Data were reviewed from 35 astronauts who had served on spaceflight missions lasting between 120 and 180 days with attention focused on astronauts who (1) were repeat fliers on long-duration missions, (2) were users of an advanced resistive exercise device (ARED), (3) were scanned by quantitative computed tomography (QCT) at the hip, (4) had hip bone strength estimated by finite element modeling, or (5) had lost >10% of areal bone mineral density (aBMD) at the hip or lumbar spine as measured by dual-energy X-ray absorptiometry (DXA). Because of the limitations of DXA in describing the effects of spaceflight on bone strength, the panel recommended that the U.S. space program use QCT and finite element modeling to further study the unique effects of spaceflight (and recovery) on bone health in order to better inform clinical decisions.
Assuntos
Medicina Aeroespacial , Astronautas , Osso e Ossos/metabolismo , Ausência de Peso/efeitos adversos , Absorciometria de Fóton , Doenças Ósseas/etiologia , Doenças Ósseas/metabolismo , Doenças Ósseas/prevenção & controle , Osso e Ossos/diagnóstico por imagem , Feminino , Humanos , Masculino , Avaliação das Necessidades , Fatores de Tempo , Estados Unidos , United States National Aeronautics and Space AdministrationRESUMO
Osteoporosis is a serious health concern affecting millions of Americans, with many patients going undiagnosed and untreated. Fractures due to osteoporosis and fracture-related complications are the most clinically relevant and costly consequences of this disorder. The Fracture Risk Assessment Tool (FRAX®), released by the World Health Organization (WHO) in February 2008, is a major achievement in helping determine which patients may be candidates for pharmacological therapy for osteoporosis. This Web-based algorithm, which has been incorporated into some dual x-ray absorptiometry (DXA) reporting software, calculates the 10-year probability of major osteoporotic fracture (clinical vertebral, hip, forearm, or humerus) and the 10-year probability of hip fracture in men and women based on easily obtained clinical risk factors and bone mineral density (BMD) of the femoral neck (optional). The National Osteoporosis Foundation updated its U.S. guidelines in February 2008 to incorporate FRAX and recommends that all postmenopausal women and men aged ≥50 years with a hip or vertebral fracture, a T-score ≤-2.5 at the femoral neck or spine (excluding secondary causes), or low bone mass (T-score between -1.0 and -2.5) and a 10-year probability of hip fracture ≥3% or of major osteoporosis-related fracture ≥20% (based on FRAX) should be considered candidates for drug therapy. Despite its demonstrated clinical utility, FRAX has limitations and should not be used in all situations. Acceptance and clinical use of FRAX may help identify men and women at increased risk for osteoporotic fracture, but implementing the tool into clinical practice may be a challenge for busy physicians.
Assuntos
Algoritmos , Fraturas Ósseas/etiologia , Osteoporose/complicações , Medição de Risco/métodos , Idoso , Densidade Óssea , Feminino , Fraturas Ósseas/epidemiologia , Humanos , Internet , Masculino , Pessoa de Meia-Idade , Osteoporose/tratamento farmacológico , Osteoporose Pós-Menopausa/complicações , Pós-Menopausa , Guias de Prática Clínica como Assunto , Fatores de Risco , Organização Mundial da SaúdeAssuntos
Absorciometria de Fóton , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/etiologia , Fraturas Ósseas/prevenção & controle , Osteoporose/complicações , Osteoporose/diagnóstico por imagem , Osteoporose/prevenção & controle , Medição de Risco , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Feminino , Fraturas Ósseas/epidemiologia , Humanos , Incidência , Masculino , Osteoporose/epidemiologia , Fatores de Risco , Organização Mundial da SaúdeRESUMO
Osteoporosis is a major public health problem. Oral bisphosphonates are effective for reducing the risk of osteoporotic fractures and are an important treatment option for patients at risk for this condition. Osteonecrosis of the jaw (ONJ) is uncommon among cancer patients who are receiving high-dose intravenous bisphosphonates and rarely is seen among patients who are taking oral bisphosphonates for osteoporosis. Dentists play an important role in discussing the implications of the overall dental and medical treatment plans with both patients and physicians. The low risk of ONJ with oral bisphosphonates should be balanced against the benefits of osteoporosis therapy.
Assuntos
Difosfonatos/efeitos adversos , Doenças Maxilomandibulares/induzido quimicamente , Osteonecrose/induzido quimicamente , Osteoporose/tratamento farmacológico , Administração Oral , Efeitos Psicossociais da Doença , Análise Custo-Benefício , Difosfonatos/uso terapêutico , Humanos , Fatores de RiscoRESUMO
BACKGROUND: Non-vertebral (NV) fractures are responsible for a great amount of morbidity, mortality and cost attributable to osteoporosis. OBJECTIVES: To identify risk factors for NV fractures in postmenopausal women with osteoporosis, and to design an assessment tool for prediction of these fractures. METHODS: 2546 postmenopausal women with osteoporosis included in the placebo groups of three risedronate controlled trials were included (mean age 72 years, mean femoral T-score -2.5; 60% and 53% of patients with prevalent vertebral and NV fractures, respectively). Over 3 years, 222 NV fractures were observed. Baseline data on 14 risk factors were included in a logistic regression analysis. RESULTS: 6 risk factors were associated with NV fracture risk: prevalent NV fracture (p = 0.004), number of prevalent vertebral fractures (p<0.001), femoral T-score (p = 0.031), serum level of 25-hydroxyvitamin D (p<0.001), age (p = 0.012) and height (p = 0.037). An NV risk index was developed by converting the multivariate logistic equation into an additive score. In the group of women with a score > or =2.1, the incidence of NV fracture was 13.2% (95% CI 11.1 to 15.3), 1.5 times higher than that of the general population. CONCLUSIONS: The NV risk index is a convenient tool for selection of patients with osteoporosis with a high risk for NV fractures, and may help to choose from available treatments those with a proven efficacy for reduction of NV fracture risk.
Assuntos
Fraturas Ósseas/etiologia , Osteoporose Pós-Menopausa/complicações , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estatura , Calcifediol/sangue , Feminino , Fraturas do Colo Femoral/etiologia , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Medição de Risco/métodos , Fatores de Risco , Fraturas da Coluna Vertebral/etiologiaRESUMO
OBJECTIVE: Recent randomized clinical trials have shown that risedronate reduces the risk of nonvertebral fractures and clinical vertebral fractures within 6 months of initiating treatment. The objective of the current study was to determine whether this early antifracture effect could be demonstrated in nonvertebral fractures for risedronate and other osteoporosis therapies in an observational administrative claims database. METHODS: A proprietary administrative claims database was used to identify managed care members who received a new prescription for risedronate, alendronate, or nasal calcitonin from July 1, 2000, to December 31, 2001. Patient records were analyzed for the incidence of nonvertebral fractures (clavicle, humerus, wrist, pelvis, hip, and leg) in the first 6 and 12 months following initiation of treatment. A Cox proportional hazards regression model was used to estimate relative risk (RR) of fracture at 6 and 12 months. RESULTS: In the 6-month analysis, 774 patients (11%) received calcitonin, 5,307 (75%) received alendronate, and 1,000 (14%) received risedronate. Twelve-month data were available for a subset (71%) of patients (656 calcitonin [13%], 3,716 alendronate [74%], and 652 risedronate [13%]). Most were women (93%); mean age was similar for alendronate and risedronate, and nasal calcitonin patients were about 3 years older, on average. Risedronate and alendronate patients were more likely to have used estrogen, while nasal calcitonin patients were more likely to have been hospitalized and had higher use of concomitant medications and more physician visits. Relative risks were adjusted for these differences. Risedronate and alendronate patients were similar with respect to these indicators of general health status. In the 6-month analysis, nonvertebral fractures were observed in 2.2% of patients receiving nasal calcitonin, 1.4% of patients receiving alendronate, and 0.6% of patients receiving risedronate. The adjusted RR reduction was 69% for risedronate versus calcitonin (RR = 0.31; 95% CI, 0.12 to 0.81; P = 0.02), 54% for risedronate versus alendronate (RR = 0.46; 95% CI, 0.20 to 1.06; P = 0.07), and 26% for alendronate versus calcitonin (RR = 0.74; 95% CI, 0.43 to 1.27; P = 0.28). In the 12-month analysis, nonvertebral fracture rates were 2.9% for nasal calcitonin, 2.4% for alendronate, and 0.9% for risedronate patients. The adjusted RR reduction was 75% for risedronate versus calcitonin (RR = 0.25; 95% CI, 0.10 to 0.64; P<0.01), 59% for risedronate versus alendronate (RR = 0.41; 95% CI, 0.18 to 0.94; P = 0.04), and 25% for alendronate versus calcitonin (RR = 0.75; 95% CI, 0.45 to 1.25; P = 0.27). CONCLUSIONS: This analysis of medical and pharmacy claims contained in an administrative database confirms the early fracture reduction with risedronate that was shown in randomized clinical trials. Risedronate was more effective than calcitonin in reducing the risk of nonvertebral fractures within the first 6 months of treatment. Risedronate was more effective than either calcitonin or alendronate in reducing the risk of nonvertebral fractures within 12 months of treatment.
Assuntos
Alendronato/uso terapêutico , Calcitonina/uso terapêutico , Ácido Etidrônico/análogos & derivados , Ácido Etidrônico/uso terapêutico , Revisão da Utilização de Seguros , Programas de Assistência Gerenciada/organização & administração , Osteoporose/tratamento farmacológico , Fraturas da Coluna Vertebral/prevenção & controle , Idoso , Alendronato/administração & dosagem , Calcitonina/administração & dosagem , Estudos de Coortes , Ácido Etidrônico/administração & dosagem , Feminino , Humanos , Masculino , Estudos Retrospectivos , Ácido RisedrônicoRESUMO
BACKGROUND: Pyridinoline (PYD) and deoxypyridinoline (DPD) are two of the most extensively characterized biochemical bone markers, but the interpretation of results is hampered by biologic and other preanalytical variability. We reviewed factors contributing to preanalytical variation of pyridinium cross-links in urine. METHODS: We searched four databases for English-language reports on PYD and/or DPD in urine. Searches were restricted to humans, except for studies of stability, when the search was expanded to other species. The 599 identified articles were supplemented with references from those articles and with articles known to the authors. RESULTS: The mean reported within-day variability was 71% for PYD (range, 57-78%) and 67% for DPD (range, 53-75%). The mean interday variability was 16% for both DPD and PYD (range for PYD, 12-21%; range for DPD, 5-24%). The mean intersubject variabilities across studies were 26% for PYD (range, 12-63%) and 34% for DPD (range, 8-98%) for healthy premenopausal women and 36% (range, 22-61%) and 40%, (range, 27-54%) for postmenopausal women, respectively. Specimen instability and errors in creatinine measurements were additional sources of variability. CONCLUSIONS: Intra- and intersubject variability can be reduced by collecting specimens at a specific time of the day and by maintaining similar patient status at each specimen collection regarding factors such as medications and dietary supplements.