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1.
Horm Res Paediatr ; : 1-9, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32224610

RESUMO

INTRODUCTION: Although growth hormone (GH) is essential for attainment of peak bone mass, bone health in prepubertal children with GH deficiency is not routinely evaluated. The objective of this study was to evaluate bone microarchitecture in GH-deficient (GHD) boys using high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: Fifteen control and fifteen GHD, GH naïve pre-pubertal boys were recruited for a case-control study at a major academic center. Subjects with panhypopituitarism, chromosomal pathology, chronic steroids, or stimulant use were excluded. Volumetric bone mineral density (vBMD; total, cortical, and trabecular), bone geometry (total, cortical and trabecular cross-sectional area, cortical perimeter), bone microarchitecture, and estimated bone strength of the distal radius and tibia were assessed by HR-pQCT. Areal BMD and body composition were assessed by DXA. Insulin-like growth factor 1 (IGF-1), osteocalcin, C telopeptide, and P1NP levels were measured. RESULTS: GHD subjects had a significantly smaller cortical perimeter of the distal radius compared to controls (p < 0.001), with the difference in cortical perimeter persisting after adjusting for height z score, age, lean mass, and 25-hydroxyvitamin D level (p < 0.05).No significant differences were found in vBMD. No significant differences were found in microarchitecture, estimated strength, areal BMD, body composition, or bone turnover markers. Analysis showed significant positive correlations between IGF-1 levels and cortical parameters. DISCUSSION/CONCLUSIONS: Prepubertal GHD boys had deficits in bone geometry not evident with DXA. Larger prospective/longitudinal HR-pQCT studies are needed to determine the extent of these deficits, the need for routine bone evaluation, and the timing of GH replacement for prevention or restoration of these deficits.

2.
AIDS ; 34(3): 351-361, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31725429

RESUMO

OBJECTIVE: We tested whether bone-related extracellular vesicle phenotypes changed after initiating antiretroviral therapy (ART) and determined whether changes in levels of extracellular vesicles correlated with changes in bone mineral density (BMD). DESIGN: Extracellular vesicle phenotypes were measured in blinded serum samples from 15 adults with HIV at baseline, 1, 3, 6 and 12 months after ART initiation. Not all samples were available at each time point so we averaged early (TP1, 1-3 months) and late (TP2, 6-12 months) time points. METHODS: Extracellular vesicles were stained for osteocalcin (OC), RANKL (CD254), RANK (CD265), M-CSF (macrophage colony stimulating factor), and CD34. Serum OC, procollagen type I N-terminal propeptide (P1NP), and C-terminal telopeptide of type 1 collagen (CTx) were also measured. RESULTS: BMD significantly decreased from baseline to 12 months. Levels of OC+EVs, serum OC, serum P1NP, and CTx were significantly higher at early and late time points compared with baseline. Increases in EVs expressing OC, RANKL, RANK, and CD34 from baseline to TP1 were associated with decreases in total hip BMD from baseline to 12 months. Change in serum OC, P1NP, and CTx from baseline to TP1 or TP2 did not correlate with change in BMD. CONCLUSION: Early changes in extracellular vesicles expressing markers of bone activity were associated with total hip bone loss 12 months after ART initiation. These data suggest that serum extracellular vesicles may serve as novel biomarkers of bone remodeling. Future studies are required to determine if extracellular vesicles contribute to the effects of ART on changes in bone turnover markers and BMD.

3.
Bone ; 132: 115211, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31870633

RESUMO

BACKGROUND: Postmenopausal women with isolated osteoporosis at the 1/3 radius (1/3RO) present a therapeutic dilemma. Little is known about whether these patients have generalized skeletal fragility, and whether this finding warrants treatment. The aim of this study was to investigate the biochemical and microarchitectural phenotype of women with 1/3RO compared to women with classic postmenopausal osteoporosis by DXA at the spine and hip (PMO), and controls without osteoporosis at any site. METHODS: This cross-sectional study enrolled 266 postmenopausal women, who were grouped according to densitometric pattern. Subjects had serum biochemistries, areal BMD (aBMD) measured by DXA, trabecular and cortical vBMD, microarchitecture, and stiffness by high resolution peripheral QCT (HR-pQCT, voxel size ~82 µm) of the distal radius and tibia. RESULTS: Mean age was 68 ± 7 years. DXA T-Scores reflected study design. By HR-pQCT, 1/3RO had abnormalities at both radius and tibia compared to controls: lower total, cortical and trabecular vBMD, cortical thickness and trabecular number, higher trabecular separation and heterogeneity, and lower whole bone stiffness. In contrast, the magnitude and pattern of abnormalities in vBMD, microarchitecture and stiffness in 1/3RO were similar to those in PMO; the difference compared to controls was similar among the two groups. Serum calcium, creatinine, parathyroid hormone, 25-hydroxyvitamin D, and 24-hour urine calcium did not differ. CONCLUSIONS: Although aBMD appeared relatively preserved at the spine and hip by DXA, women with 1/3RO had significant microarchitectural and biomechanical deficits comparable to those in women with typical PMO. Further study is required to guide treatment decisions in this population.

4.
J Biomech Eng ; 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31260520

RESUMO

High-resolution peripheral quantitative computed tomography (HRpQCT) is a promising imaging modality that provides in vivo three-dimensional assessment of bone microstructure by scanning fixed regions of the distal radius and tibia. However, how microstructural parameters and mechanical analysis based on these segment scans correlate to whole distal radius and tibia mechanics is not well-characterized. On 26 sets of cadaveric radius and tibia, HRpQCT scans were performed on the standard scan segment, a segment distal to the standard segment, and a segment proximal to the standard segment. Whole distal bone stiffness was determined through mechanical testing. Segment bone stiffness was estimated using linear finite element (FE) analysis based on segment scans. Standard morphological and Individual Trabecula Segmentation (ITS) analyses were used estimate microstructural properties. Significant variations in microstructural parameters were observed among segments at both sites. Correlation to whole distal bone stiffness was moderate for microstructural parameters at the standard segment, but correlation was significantly increased for FE-predicted segment bone stiffness based on standard segment scans. Similar correlation strengths were found between FE-predicted segment bone stiffness and whole distal bone stiffness. Additionally, microstructural parameters at the distal segment had higher correlation to whole distal bone stiffness than at standard or proximal segments. Our results suggest that FE-predicted segment stiffness is a better predictor of whole distal bone stiffness for clinical HRpQCT analysis, and that microstructural parameters at the distal segment is more highly correlated with whole distal bone stiffness than at the standard or proximal segments.

5.
J Bone Miner Res ; 34(9): 1552-1561, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31348548

RESUMO

Pregnancy and lactation-associated osteoporosis (PLO) is a rare, severe, early form of osteoporosis in which young women present with fractures, usually multiple vertebral fractures, during late pregnancy or lactation. In studies of idiopathic osteoporosis (IOP) in premenopausal women, we enrolled 78 women with low-trauma fractures and 40 healthy controls, all with normal menses and no secondary cause of bone loss. In 15 of the affected women, the PLO subgroup, fractures had occurred during late pregnancy or lactation. We hypothesized that clinical, bone structural, and metabolic characteristics would differ between women with PLO and those with (non-PLO) IOP and controls. All were evaluated > 12 months postpartum, when structural and remodeling characteristics would be expected to reflect baseline premenopausal status rather than transient postpartum changes. As previously reported, affected subjects (PLO and IOP) had BMD and microarchitectural deficiencies compared to controls. Women with PLO did not differ from those with IOP in terms of age, BMI, body fat, menarcheal age, parity, or age at first pregnancy. However, women with PLO had a more severe clinical presentation than those with IOP: more fractures (5.5 ± 3.3 versus 2.6 ± 2.1; p = 0.005); more vertebral fractures (80% versus 17%; p < 0.001); and higher prevalence of multiple fractures. BMD deficits were more profound and cortical width tended to be lower in PLO. PLO subjects also had significantly lower tissue-level mineral apposition rate and bone formation rates (0.005 ± 0.005 versus 0.011 ± 0.010 mm2 /mm/year; p = 0.006), as well as lower serum P1NP (33 ± 12 versus 44 ± 18 µg/L; p = 0.02) and CTX (257 ± 102 versus 355 ± 193 pg/mL; p = 0.01) than IOP. The finding that women with PLO have a low bone remodeling state assessed more than a year postpartum increases our understanding of the pathogenic mechanism of PLO. We conclude that women with PLO may have underlying osteoblast functional deficits which could affect their therapeutic response to osteoanabolic medications. © 2019 American Society for Bone and Mineral Research.

6.
J Bone Miner Res ; 34(9): 1549-1551, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31237962

RESUMO

The public health implications of osteoporosis are enormous but the disease remains underdiagnosed and undertreated. In October 2018, the National Institutes of Health (NIH) convened a Pathways to Prevention (P2P) Workshop entitled "Appropriate Use of Drug Therapies for Osteoporotic Fracture Prevention" designed to identify research gaps, suggest future research opportunities, and advance the field through an evidence-based assessment. By design, the P2P report focused on "gaps" in our knowledge base. Unfortunately, however, the report did not sufficiently acknowledge the current evidence that unequivocally demonstrates the therapeutic efficacy of existing pharmacologic therapies for osteoporosis, which has the potential to exacerbate the current crises in osteoporosis diagnosis and treatment. © 2019 American Society for Bone and Mineral Research.

7.
J Biomech Eng ; 2019 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-30703208

RESUMO

The high-resolution peripheral quantitative computed tomography (HRpQCT) provides unprecedented visualization of bone microstructure and the basis for constructing patient-specific micro-finite element (µFE) models. Based on HRpQCT images, we have developed a plate rod µFE (PRµFE) method for whole bone segments using individual trabecula segmentation (ITS) and an adaptive cortical meshing technique. In contrast to the conventional voxel approach, the complex microarchitecture of the trabecular compartment is simplified into shell and beam elements based on the trabecular plate-and-rod configuration. Compared to voxel-based µFE models of µCT and mechanical testing, nonlinear analyses of stiffness and yield strength using the HRpQCT-based PRµFE models demonstrated high correlation and accuracy, indicating that the combination of segmented trabecular plate-rod morphology and adjusted cortical mesh adequately captures mechanics of the whole bone segment. Meanwhile, the PRµFE approach reduced model size by nearly 300-fold and shortened computation time for nonlinear analysis from days to within hours, permitting broader clinical application of HRpQCT-based nonlinear µFE modeling. Furthermore, the presented approach was tested using a subset of radius and tibia HRpQCT scans of patients with prior vertebral fracture from a previous study. Results indicated that yield strength for radius and tibia predicted by the PRµFE model was effective in discriminating vertebral fracture subjects from non-fractured controls. In conclusion, the PR µFE model of HRpQCT images accurately predicted mechanics for whole bone segments and can serve as a valuable clinical tool to evaluate musculoskeletal diseases.

8.
Lancet Diabetes Endocrinol ; 7(1): 5-7, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30503162
9.
J Acquir Immune Defic Syndr ; 80(3): 342-349, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30531305

RESUMO

BACKGROUND: Prevalence of osteoporosis and fracture is increased among older people with HIV. We compared the effects of low (1000 IU) vs moderate (3000 IU) vitamin D3 (VitD) supplementation on areal bone mineral density (aBMD) and volumetric bone mineral density (vBMD) in African American and Hispanic postmenopausal women with HIV on antiretroviral therapy. METHODS: We performed a 12-month prospective, randomized, double-blind, placebo-controlled study with primary outcomes of change in aBMD by dual-energy X-ray absorptiometry (DXA) and secondary outcomes of change in vBMD by quantitative computed tomography and bone turnover markers. An intent-to-treat analysis was performed on 85 randomized subjects (43 low and 42 moderate) for primary DXA outcomes, and complete case analysis was performed for secondary outcomes. RESULTS: Mean age was 56 ± 5 years, median CD4 count was 722 cells/mm, and 74% had HIV RNA ≤ 50 copies/mL. Serum 25-OHD was higher in the moderate than low VitD group at 6 months (33.1 ± 10.3 vs 27.8 ± 8.1 ng/mL, P = 0.03) and 12 months, but parathyroid hormone levels remained similar. Percent change in aBMD, vBMD, and bone turnover markers did not differ between low and moderate VitD groups before or after adjustment for baseline aBMD. CONCLUSIONS: VitD supplementation at 3000 IU daily increased mean total 25-OHD levels in postmenopausal women with HIV, but we did not find evidence of an effect on BMD beyond those observed with 1000 IU daily. Future studies are necessary to determine whether VitD supplementation is beneficial in this patient population, and if so, what dose is optimal for skeletal health.


Assuntos
Densidade Óssea/efeitos dos fármacos , Colecalciferol/administração & dosagem , Colecalciferol/farmacologia , Infecções por HIV , Vitamina D/análogos & derivados , Adulto , Idoso , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Cálcio/administração & dosagem , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Vitamina D/sangue
10.
Clin Breast Cancer ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31926840

RESUMO

BACKGROUND: Ovarian suppression from chemotherapy results in bone loss in premenopausal women with breast cancer (BC). Less is known about bone microarchitecture changes. We used high-resolution peripheral quantitative computed tomography (HR-pQCT) to measure volumetric bone density and trabecular and cortical microarchitecture in this population. MATERIALS AND METHODS: The primary endpoint was to assess changes in cortical thickness and trabecular bone density by HR-pQCT. Premenopausal women with stage I to III BC undergoing adjuvant chemotherapy underwent a bone mineral density (BMD) dual energy x-ray absorptiometry scan and HR-pQCT (voxel size, 82 microns) at baseline and 12 months. Paired t tests were used to observe the change over time in bone microarchitecture and areal and volumetric density. RESULTS: Eighteen patients were evaluated, of which 12 patients had baseline and matched 12-month imaging. The mean age was 45.2 years (range, 35-51 years), 17 (94%) patients had hormone receptor-positive BC, and 16 (89%) initiated tamoxifen. At 12 months, there was a significant decrease in femoral neck (P < .05) and lumbar spine and total hip (P < .01) BMD. Changes detected by HR-pQCT at 12 months included significant decreases in cortical thickness and area at the tibia (P < .05), and total and cortical volumetric BMD at the radius and tibia (P < .01), as well as an increase in tibial trabecular area (P < .05). CONCLUSION: Premenopausal women undergoing chemotherapy experience BMD decline and trabecular and cortical bone microarchitecture deterioration. In this population, future efforts should focus on therapy-induced bone loss and optimizing bone density-related management.

11.
Obesity (Silver Spring) ; 26(10): 1576-1583, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30260099

RESUMO

OBJECTIVE: The objective of this study is to determine whether resistance training is similarly effective in reducing skeletal muscle efficiency and increasing strength in weight-reduced and maximal weight subjects. METHODS: This study examined the effects of supervised resistance exercise on skeletal muscle in 14 individuals with overweight and obesity sustaining a 10% or greater weight loss for over 6 months and a phenotypically similar group of 15 subjects who had not reduced weight and were weight stable at their maximal lifetime body weight. We assessed skeletal muscle work efficiency and fuel utilization (bicycle ergometry), strength (dynamometry), body composition (dual energy x-ray absorptiometry), and resting energy expenditure (indirect calorimetry) before and after 12 weeks of thrice-weekly resistance training. RESULTS: Non-weight-reduced subjects were significantly (10%-20%) stronger before and after the intervention than reduced-weight subjects and gained significantly more fat-free mass with a greater decline in percentage of body fat than weight-reduced subjects. Resistance training resulted in similar significant decreases (~10%) in skeletal muscle work efficiency at low-level exercise and ~10% to 20% increases in leg strength in both weight-reduced and non-weight-reduced subjects. CONCLUSIONS: Resistance training similarly increases muscle strength and decreases efficiency regardless of weight loss history. Increased resistance training could be an effective adjunct to reduced-weight maintenance therapy.


Assuntos
Músculo Esquelético/fisiopatologia , Obesidade/terapia , Treinamento de Resistência/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Perda de Peso/fisiologia
12.
Curr Osteoporos Rep ; 16(4): 519-529, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29951870

RESUMO

PURPOSE OF REVIEW: To summarize reports published since the 2013 American Society of Bone and Mineral Research Task Force Report on atypical femoral fractures (AFF). RECENT FINDINGS: The absolute incidence of AFFs remains low. AFFs are primarily associated with prolonged bisphosphonate (BP) exposure, but have also been reported in unexposed patients and those receiving denosumab for osteoporosis and metastatic bone disease. Asians may be more susceptible to AFFs. Lateral femoral bowing and varus hip geometry, which increase loading forces on the lateral femoral cortex, may increase AFF risk. Altered bone material properties associated with BP therapy may predispose to AFFs by permitting initiation and increasing propagation of micro-cracks. Relevant genetic mutations have been reported in patients with AFFs. Single X-ray absorptiometry femur scans permit early detection of incomplete and/or asymptomatic AFFs. Orthopedists recommend intramedullary rods for complete AFFs and for incomplete, radiologically advanced AFFs associated with pain and/or marrow edema on MRI. Teriparatide may advance AFF healing but few data support its efficacy. Greater understanding of biological and genetic predisposition to AFF may allow characterization of individual risk prior to initiating osteoporosis therapy and help allay fear in those at low risk for this complication, which remains rare in comparison to the osteoporotic fractures prevented by antiresorptive therapy.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Denosumab/uso terapêutico , Difosfonatos/uso terapêutico , Fraturas do Fêmur/epidemiologia , Fixação Intramedular de Fraturas , Osteoporose/tratamento farmacológico , Teriparatida/uso terapêutico , Absorciometria de Fóton , Grupo com Ancestrais do Continente Asiático , Fraturas do Fêmur/etnologia , Fraturas do Fêmur/fisiopatologia , Fraturas do Fêmur/terapia , Predisposição Genética para Doença , Humanos , Incidência , Fraturas por Osteoporose/prevenção & controle , Fatores de Risco
13.
J Bone Miner Res ; 33(2): 316-327, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29044705

RESUMO

Developing effective treatment for osteoarthritis (OA), a prevalent and disabling disease, has remained a challenge, primarily because of limited understanding of its pathogenesis and late diagnosis. In the subchondral bone, rapid bone loss after traumatic injuries and bone sclerosis at the advanced stage of OA are well-recognized hallmarks of the disease. Recent studies have further demonstrated the crucial contribution of subchondral bone in the development of OA. However, the microstructural basis of these bone changes has not been examined thoroughly, and the paradox of how abnormal resorption can eventually lead to bone sclerosis remains unanswered. By applying a novel microstructural analysis technique, individual trabecula segmentation (ITS), to micro-computed tomography (µCT) images of human OA knees, we have identified a drastic loss of rod-like trabeculae and thickening of plate-like trabeculae that persisted in all regions of the tibial plateau, underneath both severely damaged and still intact cartilage. The simultaneous reduction in trabecular rods and thickening of trabecular plates provide important insights to the dynamic and paradoxical subchondral bone changes observed in OA. Furthermore, using an established guinea pig model of spontaneous OA, we discovered similar trabecular rod loss and plate thickening that preceded cartilage degradation. Thus, our study suggests that rod-and-plate microstructural changes in the subchondral trabecular bone may play an important role in the development of OA and that advanced microstructural analysis techniques such as ITS are necessary in detecting these early but subtle changes. With emerging high-resolution skeletal imaging modalities such as the high-resolution peripheral quantitative computed tomography (HR-pQCT), trabecular rod loss identified by ITS could potentially be used as a marker in assessing the progression of OA in future longitudinal studies or clinical diagnosis. © 2017 American Society for Bone and Mineral Research.


Assuntos
Reabsorção Óssea/patologia , Osso Esponjoso/patologia , Osteoartrite do Joelho/patologia , Idoso , Animais , Reabsorção Óssea/diagnóstico por imagem , Osso Esponjoso/diagnóstico por imagem , Cartilagem/patologia , Feminino , Cobaias , Humanos , Masculino , Modelos Biológicos , Osteoartrite do Joelho/diagnóstico por imagem , Microtomografia por Raio-X
14.
Bone ; 107: 181-187, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29154969

RESUMO

Individuals with cystic fibrosis (CF) have lower bone mineral density (BMD) by DXA and are at higher risk of fracture than healthy controls. However, the 2-dimensional measurement of areal BMD (aBMD) provided by DXA is influenced by bone size and the true extent of the bone deficit is unclear. Our objective was to use high-resolution peripheral quantitative computed tomography (HR-pQCT) and individual trabecula segmentation (ITS) analysis to compare volumetric BMD (vBMD), microarchitecture and estimated strength at the distal radius and tibia in 26 young adults with CF and 26 controls matched for age, gender, and race. To assess the effect of limb length and minimize the confounding effects of size on HR-pQCT outcomes, we scanned participants at both the standard fixed HR-pQCT measurement sites and at a subject-specific relative site that varied according to limb length. CF participants did not differ significantly in age, height, weight, or BMI from controls. Ulnar and tibial lengths were 9mm shorter in CF patients, though differences were not significant. CF patients had significantly lower BMI-adjusted aBMD by DXA at the lumbar spine (8.9%, p<0.01), total hip (11.5%, p<0.01) and femoral neck (14.5%, p<0.01), but not at the forearm. At the fixed radius site, thickness of trabecular plates and torsional stiffness were significantly lower in CF participants than controls. At the relative radius site, only torsional stiffness was significantly lower in CF participants. At the tibia, total, trabecular and cortical vBMD were significantly lower at both fixed and relative sites in CF participants, with fewer, more widely-spaced trabecular plates, lower trabecular connectivity, and lower axial and torsional stiffness. Our results confirm that aBMD is lower at the spine and hip in young adults with CF, independent of BMI and body size. We also conclude that vBMD and stiffness are lower at the weight-bearing tibia. The pathogenesis of these differences in bone density and strength at the tibia appear to be related to trabecular drop-out and reduced trabecular connectivity and to be independent of differences in limb length, as assessed by scanning participants at both standard and relative sites. We concluded that significant deficits in bone structure and strength persist in young adults with CF, despite advances in care that permit them to attain relatively normal height and weight.


Assuntos
Osso e Ossos/patologia , Fibrose Cística/complicações , Fibrose Cística/patologia , Adulto , Densidade Óssea , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/fisiopatologia , Feminino , Humanos , Masculino , Rádio (Anatomia) , Coluna Vertebral , Tíbia , Tomografia Computadorizada por Raios X
15.
J Bone Miner Res ; 32(6): 1388, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28370490

Assuntos
Osteoporose , Humanos
16.
Clin J Am Soc Nephrol ; 12(4): 644-652, 2017 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-28348031

RESUMO

BACKGROUND AND OBJECTIVES: Studies using high-resolution peripheral quantitative computed tomography showed progressive abnormalities in cortical and trabecular microarchitecture and biomechanical competence over the first year after kidney transplantation. However, high-resolution peripheral computed tomography is a research tool lacking wide availability. In contrast, the trabecular bone score is a novel and widely available tool that uses gray-scale variograms of the spine image from dual-energy x-ray absorptiometry to assess trabecular quality. There are no studies assessing whether trabecular bone score characterizes bone quality in kidney transplant recipients. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: Between 2009 and 2010, we conducted a study to assess changes in peripheral skeletal microarchitecture, measured by high-resolution peripheral computed tomography, during the first year after transplantation in 47 patients managed with early corticosteroid-withdrawal immunosuppression. All adult first-time transplant candidates were eligible. Patients underwent imaging with high-resolution peripheral computed tomography and dual-energy x-ray absorptiometry pretransplantation and 3, 6, and 12 months post-transplantation. We now test if, during the first year after transplantation, trabecular bone score assesses the evolution of bone microarchitecture and biomechanical competence as determined by high-resolution peripheral computed tomography. RESULTS: At baseline and follow-up, among the 72% and 78%, respectively, of patients having normal bone mineral density by dual-energy x-ray absorptiometry, 53% and 50%, respectively, were classified by trabecular bone score as having high fracture risk. At baseline, trabecular bone score correlated with spine, hip, and ultradistal radius bone mineral density by dual-energy x-ray absorptiometry and cortical area, density, thickness, and porosity; trabecular density, thickness, separation, and heterogeneity; and stiffness and failure load by high-resolution peripheral computed tomography. Longitudinally, each percentage increase in trabecular bone score was associated with increases in trabecular number (0.35%±1.4%); decreases in trabecular thickness (-0.45%±0.15%), separation (-0.40%±0.15%), and network heterogeneity (-0.48%±0.20%); and increases in failure load (0.22%±0.09%) by high-resolution peripheral computed tomography (all P<0.05). CONCLUSIONS: Trabecular bone score may be a useful method to assess and monitor bone quality and strength and classify fracture risk in kidney transplant recipients.


Assuntos
Absorciometria de Fóton , Osso Esponjoso/diagnóstico por imagem , Transplante de Rim , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Idoso , Fenômenos Biomecânicos , Densidade Óssea , Feminino , Cabeça do Fêmur/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Porosidade , Rádio (Anatomia)/diagnóstico por imagem , Coluna Vertebral/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto Jovem
17.
J Bone Miner Res ; 32(6): 1267-1273, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28218468

RESUMO

We have previously reported that premenopausal women with idiopathic osteoporosis (IOP) have profound microarchitectural deficiencies and heterogeneous bone remodeling. Those with the lowest bone formation rate have higher baseline serum insulin-like growth factor-1 (IGF-1) levels and less robust response to teriparatide. Because IGF-1 stimulates bone formation and is critical for teriparatide action on osteoblasts, these findings suggest a state of IGF-1 resistance in some IOP women. To further investigate the hypothesis that osteoblast and IGF-1-related mechanisms mediate differential responsiveness to teriparatide in IOP, we studied circulating osteoblast progenitor (COP) cells and their IGF-1 receptor (IGF-1R) expression. In premenopausal women with IOP, peripheral blood mononuclear cells (PBMCs) were obtained at baseline (n = 25) and over 24 months of teriparatide treatment (n = 11). Flow cytometry was used to identify and quantify COPs (non-hematopoetic lineage cells expressing osteocalcin and RUNX2) and to quantify IGF-1R expression levels. At baseline, both the percent of PBMCs that were COPs (%COP) and COP cell-surface IGF-1R expression correlated directly with several histomorphometric indices of bone formation in tetracycline-labeled transiliac biopsies. In treated subjects, both %COP and IGF-1R expression increased promptly after teriparatide, returning toward baseline by 18 months. Although neither baseline %COP nor increase in %COP after 3 months predicted the bone mineral density (BMD) response to teriparatide, the percent increase in IGF-1R expression on COPs at 3 months correlated directly with the BMD response to teriparatide. Additionally, lower IGF-1R expression after teriparatide was associated with higher body fat, suggesting links between teriparatide resistance, body composition, and the GH/IGF-1 axis. In conclusion, these assays may be useful to characterize bone remodeling noninvasively and may serve to predict early response to teriparatide and possibly other bone formation-stimulating medications. These new tools may also have utility in the mechanistic investigation of teriparatide resistance in premenopausal IOP and perhaps in other populations. © 2017 American Society for Bone and Mineral Research.


Assuntos
Osteoblastos/metabolismo , Osteogênese , Osteoporose/tratamento farmacológico , Osteoporose/fisiopatologia , Pré-Menopausa/fisiologia , Receptor IGF Tipo 1/metabolismo , Células-Tronco/metabolismo , Teriparatida/uso terapêutico , Tecido Adiposo/efeitos dos fármacos , Adolescente , Adulto , Biópsia , Composição Corporal/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Pré-Menopausa/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Teriparatida/farmacologia , Adulto Jovem
18.
J Bone Miner Res ; 32(3): 424-430, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28099754

RESUMO

Considerable data and media attention have highlighted a potential "crisis" in the treatment of osteoporosis. Specifically, despite the availability of several effective drugs to prevent fractures, many patients who need pharmacological therapy are either not being prescribed these medications or if prescribed a medication, are simply not taking it. Although there are many reasons for this "gap" in the treatment of osteoporosis, a major factor is physician and patient concerns over the risk of side effects, especially atypical femur fractures (AFFs) related to bisphosphonate (and perhaps other antiresorptive) drug therapy. In this perspective, we review the current state of undertreatment of patients at increased fracture risk and suggest possible short-, intermediate-, and long-term approaches to address patient concerns, specifically those related to AFF risk. We suggest improved patient and physician education on prodromal symptoms, extended femur scans using dual-energy X-ray absorptiometry (DXA) to monitor patients on antiresorptive treatment, better identification of high-risk patients perhaps using geometrical parameters from DXA and other risk factors, and more research on pharmacogenomics to identify risk markers. Although not the only impediment to appropriate treatment of osteoporosis, concern over AFFs remains a major issue and one that needs to be resolved for effective dissemination of existing treatments to reduce fracture risk. © 2017 American Society for Bone and Mineral Research.

19.
J Womens Health (Larchmt) ; 26(3): 241-248, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27611626

RESUMO

OBJECTIVE: To characterize and compare cardiovascular disease (CVD) risk in HIV-infected and uninfected postmenopausal minority women using the Framingham Risk Score (FRS) as an assessment measure. METHODS: A cross-sectional analysis was performed in 152 (109 HIV+, 43 HIV-) subjects from an existing study cohort of postmenopausal Hispanic and African American women. Data necessary to calculate FRS and menopause features were retrieved by retrospective chart review. Bivariate statistics was used to compare CVD risk factors. Multivariable linear regression was used to determine factors associated with FRS in HIV-infected women. RESULTS: The HIV-infected group was younger, less obese, and with lower rates of diabetes versus controls. In a subset of age-matched participants, median FRS did not differ between groups (14.6 [IQR = 9.1, 21.6] vs. 15.5 [IQR = 12.3, 22.1]; p = 0.73). Fourteen percent of HIV-infected women meeting criteria for the low-risk FRS category (<10%) had a history of CVD, a similar rate as controls. HIV-infected women at intermediate/high CVD risk had higher rates of surgical menopause. According to 2013 clinical guidelines, more than half of HIV-infected women not prescribed statin therapy (52%) were eligible for treatment; however, statin therapy was similarly under-prescribed in uninfected women. CONCLUSIONS: In this study, CVD risk as assessed by the FRS was not significantly different by HIV status. Performance of the FRS may be compromised in postmenopausal HIV-infected minority women. HIV-infected and uninfected women may be undertreated with statin therapy. Large longitudinal cohorts and inclusion of subclinical measures of CVD are necessary to better characterize risk.


Assuntos
Doenças Cardiovasculares/epidemiologia , Infecções por HIV/complicações , Pós-Menopausa , Afro-Americanos/estatística & dados numéricos , Idoso , Estudos Transversais , Feminino , Hispano-Americanos/estatística & dados numéricos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Modelos Logísticos , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Estados Unidos
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