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1.
Osteoporos Int ; 33(3): 659-672, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34665288

ABSTRACT

We examined serum IGF-1 in premenopausal IOP, finding relationships that were opposite to those expected: higher IGF-1 was associated with lower bone formation and higher body fat, and lower BMD response to teriparatide. These paradoxical relationships between serum IGF-1, bone, and fat may contribute to the mechanism of idiopathic osteoporosis in premenopausal women. INTRODUCTION: Premenopausal women with idiopathic osteoporosis (IOP) have marked deficits in bone microarchitecture but variable bone remodeling. We previously reported that those with low tissue-level bone formation rate (BFR) are less responsive to teriparatide and have higher serum IGF-1, a hormone anabolic for osteoblasts and other tissues. The IGF-1 data were unexpected because IGF-1 is low in other forms of low turnover osteoporosis-leading us to hypothesize that IGF-1 relationships are paradoxical in IOP. This study aimed to determine whether IOP women with low BFR have higher IGF-1 and paradoxical IGF-1 relationships in skeletal and non-skeletal tissues, and whether IGF-1 and the related measures predict teriparatide response. METHODS: This research is an ancillary study to a 24 month clinical trial of teriparatide for IOP. Baseline assessments were related to trial outcomes: BMD, bone remodeling. SUBJECTS:  Premenopausal women with IOP(n = 34); bone remodeling status was defined by baseline cancellous BFR/BS on bone biopsy. MEASURES:  Serum IGF-1 parameters, compartmental adiposity (DXA, CT, MRI), serum hormones, and cardiovascular-risk-markers related to fat distribution. RESULTS: As seen in other populations, lower BFR was associated with higher body fat and poorer teriparatide response. However, in contrast to observations in other populations, low BFR, higher body fat, and poorer teriparatide response were all related to higher IGF-1: IGF-1 Z-score was inversely related to BFR at all bone surfaces (r = - 0.39 to - 0.46; p < 0.05), directly related to central fat (p = 0.05) and leptin (p = 0.03). IGF-1 inversely related to 24 month hip BMD %change (r = - 0.46; p = 0.01). CONCLUSIONS: Paradoxical IGF-1 relationships suggest that abnormal or atypical regulation of bone and fat may contribute to osteoporosis mechanisms in premenopausal IOP.


Subject(s)
Bone Density Conservation Agents , Osteoporosis , Adipose Tissue , Bone Density , Bone Density Conservation Agents/therapeutic use , Female , Humans , Insulin-Like Growth Factor I , Osteogenesis , Osteoporosis/drug therapy , Osteoporosis/etiology , Teriparatide/therapeutic use
2.
Diabetes Metab ; 47(6): 101267, 2021 11.
Article in English | MEDLINE | ID: mdl-34332112

ABSTRACT

AIM: - Patients with diabetes have increased morbidity and mortality from COVID-19. Case reports describe patients with simultaneous COVID-19 and diabetic acidosis (DKA), however there is limited data on the prevalence, predictors and outcomes of DKA in these patients. METHODS: - Patients with COVID-19 were identified from the electronic medical record. DKA was defined by standardized criteria. Proportional hazard regression models were used to determine risk factors for, and mortality from DKA in COVID-19. RESULTS: - Of 2366 patients admitted for COVID-19, 157 (6.6%) patients developed DKA, 94% of whom had antecedent type 2 diabetes, 0.6% had antecedent type 1 diabetes, and 5.7% patients had no prior diagnosis of diabetes. Patients with DKA had increased hospital length of stay and in-patient mortality. Higher HbA1c predicted increased risk of incident DKA (HR 1.47 per 1% increase, 95% CI 1.40-1.54). Risk factors for mortality included older age (HR 1.07 per 5 years, 95% CI 1.06-1.08) and need for pressors (HR 2.33, 95% CI 1.82-2.98). Glucocorticoid use was protective in patients with and without DKA. CONCLUSION: - The combination of DKA and COVID-19 is associated with greater mortality, driven by older age and COVID-19 severity.


Subject(s)
COVID-19 , Diabetic Ketoacidosis , Aged , COVID-19/mortality , Diabetic Ketoacidosis/epidemiology , Humans
3.
Osteoporos Int ; 29(11): 2581, 2018 11.
Article in English | MEDLINE | ID: mdl-30155687

ABSTRACT

The second name of the ninth author, X.E. Guo, was incorrectly coded as part of his surname. The publisher apologises for the inconvenience caused.

4.
Osteoporos Int ; 28(7): 2147-2154, 2017 07.
Article in English | MEDLINE | ID: mdl-28341899

ABSTRACT

Hispanic men have smaller bone size but thicker and denser cortices compared to white men, leading to similar mechanical competence. INTRODUCTION: The purpose of this study was to assess differences in vBMD and microarchitecture in young Caribbean Hispanic (n = 30) and non-Hispanic Caucasian (n = 30) men. METHODS: We measured areal bone mineral density (aBMD) at the spine, total hip (TH), femoral neck (FN), and forearm by dual-energy X-ray absorptiometry (DXA) and bone geometry, mass, microarchitecture, and mechanical competence by high-resolution peripheral quantitative computed tomography (HRpQCT), individual trabecula segmentation (ITS), and finite element analysis (FEA). RESULTS: Hispanic men were slightly older, shorter, and heavier and had higher BMI compared with white men. aBMD, measured by DXA, did not differ at the spine, TH, or forearm before or after adjustment for age, height, weight, and the interaction of height and weight. At the FN, marginally significant higher BMD in Hispanics prior to adjustment was attenuated and no longer differed after adjustment for covariates. Adjusted HRpQCT indices indicated smaller total and trabecular area at the radius but greater total volumetric density and cortical thickness in Hispanic versus white men. The adjusted difference in cortical density at the radius was of borderline significance. Trabecular and ITS microstructure tended not to differ at the radius. At the tibia, results were similar. Bone size tended to be smaller and covariate-adjusted cortical density and cortical thickness were greater in Hispanic versus white men. Additionally, cortical porosity was lower at the tibia in Hispanic compared to white men. Stiffness and failure load did not differ at either skeletal site by ethnicity. CONCLUSION: In conclusion, greater cortical thickness and density as well as lower cortical porosity tend to compensate for smaller bone size in Hispanic men, leading to similar mechanical competence compared with white men.


Subject(s)
Bone Density/physiology , Hispanic or Latino/statistics & numerical data , Absorptiometry, Photon , Adult , Anthropometry/methods , Femur Neck/physiology , Finite Element Analysis , Hip Joint/physiology , Humans , Lumbar Vertebrae/physiology , Male , Radius/anatomy & histology , Radius/physiology , Tibia/anatomy & histology , Tibia/physiology , Tomography, X-Ray Computed , White People/statistics & numerical data
5.
Osteoporos Int ; 28(2): 549-558, 2017 02.
Article in English | MEDLINE | ID: mdl-27638138

ABSTRACT

This is a cross-sectional study to assess differences in bone quality in young Asian and Caucasian (n = 30/group) men between 25 and 35 years. We found that Asians had smaller bones, thicker and denser cortices, and more plate-like trabeculae, but stiffness did not differ between groups. INTRODUCTION: We conducted a cross-sectional study to assess differences in bone quality in young Asian and Caucasian (n = 30/group) men between 25 and 35 years. METHODS: We measured bone mineral density (BMD) at the spine, total hip (TH), femoral neck (FN), and forearm by dual energy X-ray absorptiometry (DXA), and bone geometry, density, microarchitecture, and mechanical competence at the radius and tibia by high-resolution peripheral quantitative computed tomography (HR-pQCT) with application of individual trabecula segmentation (ITS) and trabecular and whole bone finite element analysis (FEA). We measured load-to-strength ratio to account for differences in bone size and height, respectively. We used Wilcoxon rank sum and generalized linear models adjusted for height, weight, and their interaction for comparisons. RESULTS: Asians were 3.9 % shorter and weighed 6.5 % less than Caucasians. In adjusted models: by DXA, there were no significant race-based differences in areal BMD; by HR-pQCT, at the radius, Asians had smaller total and trabecular area (p = 0.003 for both), and denser (p = 0.01) and thicker (p = 0.04) cortices at the radius; by ITS, at the radius Asians, had more plate-like than rod-like trabeculae (PR ratio p = 0.01), greater plate trabecular surface (p = 0.009) and longer rod length (p = 0.002). There were no significant race-based differences in FEA or the load-to-strength ratio. CONCLUSIONS: Asians had smaller bones, thicker and denser cortices, and more plate-like trabeculae, but biomechanical estimates of bone strength did not differ between groups. Studies are needed to determine whether these differences persist later in life.


Subject(s)
Asian People/statistics & numerical data , Bone Density/physiology , White People/statistics & numerical data , Absorptiometry, Photon/methods , Adult , Cross-Sectional Studies , Femur Neck/anatomy & histology , Femur Neck/diagnostic imaging , Femur Neck/physiology , Finite Element Analysis , Hip Joint/anatomy & histology , Hip Joint/diagnostic imaging , Hip Joint/physiology , Humans , Lumbar Vertebrae/anatomy & histology , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/physiology , Male , Radius/anatomy & histology , Radius/diagnostic imaging , Radius/physiology , Tomography, X-Ray Computed/methods
6.
Osteoporos Int ; 26(10): 2471-8, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25986383

ABSTRACT

UNLABELLED: Measurement of marrow fat (MF) is important to the study of bone fragility. We measured MF on iliac biopsies and by spine/hip magnetic resonance spectroscopy in the same subjects. Noninvasively assessed spine MF and histomorphometrically assessed MF correlated well. MF quantity and relationships with bone volume differed by measurement site. INTRODUCTION: Excess marrow fat has been implicated in the pathogenesis of osteoporosis in several populations. In the bone marrow, adipocytes and osteoblasts share a common precursor and are reciprocally regulated. In addition, adipocytes may secrete toxic fatty acids and adipokines that adversely affect osteoblasts. Measurement of marrow fat is important to the study of mechanisms of bone fragility. Marrow fat can be quantified on bone biopsy samples by histomorphometry and noninvasively by proton magnetic resonance spectroscopy ((1)H-MRS). In this study, we evaluate relationships between marrow fat assessed using both methods in the same subjects for the first time. METHODS: Sixteen premenopausal women, nine with idiopathic osteoporosis and seven normal controls, had marrow fat measured at the iliac crest by bone biopsy and at the lumbar spine (L3) and proximal femur by (1)H-MRS. RESULTS: At L3, fat fraction by (1)H-MRS correlated directly and significantly with marrow fat variables on iliac crest biopsies (r = 0.5-0.8). In contrast, there were no significant correlations between fat fraction at the femur and marrow fat on biopsies. Marrow fat quantity (%) was greater at the femur than at L3 and the iliac crest and correlated inversely with total hip and femoral neck BMD by DXA. CONCLUSIONS: In summary, measurement of marrow fat in transiliac crest biopsies correlates with marrow fat at the spine but not the proximal femur by (1)H-MRS. There were site-specific differences in marrow fat quantity and in the relationships between marrow fat and bone volume.


Subject(s)
Adiposity/physiology , Bone Marrow/pathology , Femur/pathology , Lumbar Vertebrae/pathology , Adipocytes/pathology , Adipose Tissue/pathology , Adolescent , Adult , Biopsy , Bone Density/physiology , Bone Marrow Examination/methods , Case-Control Studies , Female , Humans , Ilium/pathology , Middle Aged , Premenopause/physiology , Proton Magnetic Resonance Spectroscopy/methods , Reproducibility of Results , Young Adult
7.
Calcif Tissue Int ; 95(4): 332-9, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25134800

ABSTRACT

Bone mineralization density distribution (BMDD) is an important determinant of bone mechanical properties. The most available skeletal site for access to the BMDD is the iliac crest. Compared to cancellous bone much less information on BMDD is available for cortical bone. Hence, we analyzed complete transiliac crest bone biopsy samples from premenopausal women (n = 73) aged 25-48 years, clinically classified as healthy, by quantitative backscattered electron imaging for cortical (Ct.) and cancellous (Cn.) BMDD. The Ct.BMDD was characterized by the arithmetic mean of the BMDD of the cortical plates. We found correlations between Ct. and Cn. BMDD variables with correlation coefficients r between 0.42 and 0.73 (all p < 0.001). Additionally to this synchronous behavior of cortical and cancellous compartments, we found that the heterogeneity of mineralization densities (Ct.Ca(Width)), as well as the cortical porosity (Ct.Po) was larger for a lower average degree of mineralization (Ct.Ca(Mean)). Moreover, Ct.Po correlated negatively with the percentage of highly mineralized bone areas (Ct.Ca(High)) and positively with the percentage of lowly mineralized bone areas (Ct.Ca(Low)). In conclusion, the correlation of cortical with cancellous BMDD in the iliac crest of the study cohort suggests coordinated regulation of bone turnover between both bone compartments. Only in a few cases, there was a difference in the degree of mineralization of >1wt % between both cortices suggesting a possible modeling situation. This normative dataset of healthy premenopausal women will provide a reference standard by which disease- and treatment-specific effects can be assessed at the level of cortical bone BMDD.


Subject(s)
Bone Density , Bone and Bones/pathology , Calcification, Physiologic , Ilium/pathology , Adult , Biopsy , Cohort Studies , Electrons , Female , Healthy Volunteers , Humans , Middle Aged , Porosity , Premenopause , Probability , Scattering, Radiation
8.
Am J Transplant ; 14(2): 404-15, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24472195

ABSTRACT

Half of the recovered expanded criteria donor (ECD) kidneys are discarded in the United States. A new kidney allocation system offers kidneys at higher risk of discard, Kidney Donor Profile Index (KDPI)>85%, to a wider geographic area to promote broader sharing and expedite utilization. Dual kidney transplantation (DKT) based on the KDPI is a potential option to streamline allocation of kidneys which otherwise would have been discarded. To assess the clinical utility of the KDPI in kidneys at higher risk of discard, we analyzed the OPTN/UNOS Registry that included the deceased donor kidneys recovered between 2002 and 2012. The primary outcomes were allograft survival, patient survival and discard rate based on different KDPI categories (<80%, 80-90% and >90%). Kidneys with KDPI>90% were associated with increased odds of discard (OR=1.99, 95% CI 1.74-2.29) compared to ones with KDPI<80%. DKTs of KDPI>90% were associated with lower overall allograft failure (HR=0.74, 95% CI 0.62-0.89) and better patient survival (HR=0.79, 95% CI 0.64-0.98) compared to single ECD kidneys with KDPI>90%. Kidneys at higher risk of discard may be offered in the up-front allocation system as a DKT. Further modeling and simulation studies are required to determine a reasonable KDPI cutoff percentile.


Subject(s)
Donor Selection , Graft Rejection/etiology , Kidney Failure, Chronic/surgery , Kidney Transplantation/statistics & numerical data , Tissue and Organ Procurement/statistics & numerical data , Aged , Female , Follow-Up Studies , Graft Rejection/diagnosis , Graft Rejection/mortality , Graft Survival , Humans , Kidney Failure, Chronic/mortality , Kidney Transplantation/adverse effects , Male , Middle Aged , Prognosis , Registries , Retrospective Studies , Risk Factors , Tissue Donors
9.
Osteoporos Int ; 25(1): 71-6, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24114399

ABSTRACT

UNLABELLED: We assessed the ability of the World Health Organization's fracture risk assessment tool (FRAX), bone mineral density (BMD), and age to discriminate fracture status in adults with pre-dialysis chronic kidney disease (CKD). In adults with CKD, FRAX was able to discriminate fracture status but performed no better than BMD alone. INTRODUCTION: Patients with CKD are at increased risk for fracture but the best method to assess fracture risk is not known. METHODS: We assessed the ability of the World Health Organization's FRAX, compared with BMD at the femoral neck (FN), and age to discriminate fracture status (prevalent clinical nonspine and/or morphometric vertebral) in men and women, 18 years and older with pre-dialysis CKD. Results are presented as area under receiver operator characteristic curves (AUC) with 95% confidence intervals (CI). RESULTS: We enrolled 353 subjects; mean age was 65 ± 14 years; weight was 79 ± 18 kg, and estimated glomerular filtration rate was 28 ml/min/1.73 m(2). About one third of the subjects had a prevalent clinical nonspine and/or morphometric vertebral fracture. FRAX was able to discriminate among those with prevalent clinical nonspine fractures (AUC, 0.72; 95% CI, 0.65-0.78), morphometric vertebral fractures (AUC, 0.66; 95% CI, 0.59-0.73), and any fracture (AUC, 0.71; 95% CI, 0.65-0.77). The discriminative ability of BMD at the FN alone was similar to FRAX for morphometric vertebral and any fractures; FRAX performed better than BMD for prevalent clinical nonspine fractures (AUC for BMD alone, 0.66; 95% CI, 0.60-0.73). Compared to FRAX, the AUC for age alone was lower for all fracture types. CONCLUSIONS: Among men and women with CKD, FRAX is able to discriminate fracture status but performs no better than BMD alone.


Subject(s)
Osteoporotic Fractures/etiology , Renal Insufficiency, Chronic/complications , Absorptiometry, Photon/methods , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Bone Density/physiology , Cross-Sectional Studies , Female , Femur Neck/physiopathology , Humans , Male , Middle Aged , Osteoporotic Fractures/diagnosis , Osteoporotic Fractures/physiopathology , Renal Insufficiency, Chronic/physiopathology , Risk Assessment/methods , Spinal Fractures/diagnosis , Spinal Fractures/etiology , Spinal Fractures/physiopathology , Young Adult
10.
Am J Transplant ; 12(3): 649-59, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22151430

ABSTRACT

Corticosteroid use after kidney transplantation results in severe bone loss and high fracture risk. Although corticosteroid withdrawal in the early posttransplant period has been associated with bone mass preservation, there are no published data regarding corticosteroid withdrawal and risk of fracture. We hypothesized lower fracture incidence in patients discharged from the hospital without than with corticosteroids after transplantation. From the United States Renal Data System (USRDS), 77, 430 patients were identified who received their first kidney transplant from 2000 to 2006. Fracture incidence leading to hospitalization was determined from 2000 to 2007; discharge immunosuppression was determined from United Networks for Organ Sharing forms. Time-to-event analyses were used to evaluate fracture risk. Median (interquartile range) follow-up was 1448 (808-2061) days. There were 2395 fractures during follow-up; fracture incidence rates were 0.008 and 0.0058 per patient-year for recipients discharged with and without corticosteroid, respectively. Corticosteroid withdrawal was associated with a 31% fracture risk reduction (HR 0.69; 95% CI 0.59-0.81). Fractures associated with hospitalization are significantly lower with regimens that withdraw corticosteroid. As this study likely underestimates overall fracture incidence, prospective studies are needed to determine differences in overall fracture risk in patients managed with and without corticosteroids after kidney transplantation.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Fractures, Bone/chemically induced , Fractures, Bone/prevention & control , Graft Rejection/prevention & control , Kidney Diseases/therapy , Kidney Transplantation , Adolescent , Adult , Aged , Female , Follow-Up Studies , Hospitalization , Humans , Immunosuppressive Agents , Male , Middle Aged , Risk Factors , Young Adult
11.
Osteoporos Int ; 21(2): 263-73, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19455271

ABSTRACT

UNLABELLED: We compared microarchitecture and mechanical competence parameters measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite-element analysis of radius and tibia to those measured by histomorphometry, micro-CT, and finite-element analysis of transiliac bone biopsies. Correlations were weak to moderate between parameters measured on biopsies and scans. INTRODUCTION: HR-pQCT is a new imaging technique that assesses trabecular and cortical bone microarchitecture of the radius and tibia in vivo. The purpose of this study was to determine the extent to which microarchitectural variables measured by HR-pQCT reflect those measured by the "gold standard," transiliac bone biopsy. METHODS: HR-pQCT scans (Xtreme CT, Scanco Medical AG) and iliac crest bone biopsies were performed in 54 subjects (aged 39 +/- 10 years). Biopsies were analyzed by 2D quantitative histomorphometry and 3D microcomputed tomography (microCT). Apparent Young's modulus, an estimate of mechanical competence or strength, was determined by micro-finite-element analysis (microFE) of biopsy microCT and HR-pQCT images. RESULTS: The strongest correlations observed were between trabecular parameters (bone volume fraction, number, separation) measured by microCT of biopsies and HR-pQCT of the radius (R 0.365-0.522; P < 0.01). Cortical width of biopsies correlated with cortical thickness by HR-pQCT, but only at the tibia (R = 0.360, P < 0.01). Apparent Young's modulus calculated by microFE of biopsies correlated with that calculated for both radius (R = 0.442; P < 0.001) and tibia (R = 0.380; P < 0.001) HR-pQCT scans. CONCLUSIONS: The associations between peripheral (HR-pQCT) and axial (transiliac biopsy) measures of microarchitecture and estimated mechanical competence are significant but modest.


Subject(s)
Osteoporosis/diagnostic imaging , Radius/diagnostic imaging , Tibia/diagnostic imaging , Adult , Aged , Biopsy , Bone Density/physiology , Case-Control Studies , Elastic Modulus , Female , Humans , Hypoparathyroidism/diagnostic imaging , Hypoparathyroidism/pathology , Hypoparathyroidism/physiopathology , Male , Middle Aged , Osteoporosis/pathology , Osteoporosis/physiopathology , Radius/pathology , Radius/physiopathology , Reproducibility of Results , Tibia/pathology , Tibia/physiopathology , Tomography, X-Ray Computed/methods , X-Ray Microtomography/methods , Young Adult
12.
J Biomed Mater Res ; 50(3): 365-74, 2000 Jun 05.
Article in English | MEDLINE | ID: mdl-10737878

ABSTRACT

Using a rodent air pouch, the inflammatory responses to biomaterials with distinct physical properties and chemical compositions were compared. The polymers examined were expanded poly(tetrafluoroethylene) (ePTFE), silicone, low-density polyethylene (LDPE), poly(L-lactic acid) (PLLA), poly(desaminotyrosyl-tyrosine ethyl carbonate) [poly(DTE carbonate)], and poly(desaminotyrosyl-tyrosine benzyl carbonate) [poly(DTBzl carbonate)]. We found that implantation of disks (4.5-4.8 mm) of these materials into rodent air pouches for 2 days had no effect on the number or type of cells recovered relative to sham controls. With each of the materials, macrophages were the predominant cell type identified (60-75%), followed by granulocytes (20-25%) and lymphocytes (10%). Implantation of poly(DTE carbonate), ePTFE, LDPE, or poly(DTBzl carbonate) into the pouches for 2 days caused an increase in release of superoxide anion by the pouch cells. Cells from pouches containing poly(DTE carbonate) also released more hydrogen peroxide and were more phagocytic. In contrast, PLLA and silicone had no effect on the functional activity of cells recovered from the pouches. Prolonging the implantation time of poly(DTE carbonate) or PLLA to 7 days did not alter the number or type of cells isolated from the pouches. However, cells from pouches containing poly(DTE carbonate) for 7 days continued to produce increased quantities of superoxide anion relative to sham control pouch cells. These results suggest that the air pouch model is a highly sensitive method and therefore useful for evaluating the functional responses of inflammatory cells to biomaterials.


Subject(s)
Biocompatible Materials , Inflammation/chemically induced , Polymers , Animals , Biocompatible Materials/adverse effects , Female , Microscopy, Electron, Scanning , Polymers/adverse effects , Rats , Rats, Sprague-Dawley
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