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Adi Cohen,
Emily M Stein,
Robert R Recker,
Joan M Lappe,
David W Dempster,
Hua Zhou,
Serge Cremers,
Donald J McMahon,
Thomas L Nickolas,
Ralph Müller,
Alexander Zwahlen,
Polly Young,
Julie Stubby,
Elizabeth Shane
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ABSTRACT: Context:Premenopausal women with idiopathic osteoporosis (IOP) have abnormal cortical and trabecular bone microarchitecture.Objective:The purpose of this study was to test the hypotheses that teriparatide increases bone mineral density (BMD) and bone formation and improves trabecular microarchitecture and stiffness in women with IOP.Design:This was an open-label pilot study.Setting:The setting was a tertiary care referral center.Patients:Participants were 21 premenopausal women with unexplained fragility fractures or low BMD.Intervention:Teriparatide was administered at 20 μg daily for 18 to 24 months.Main Outcome Measures:The primary endpoint was within-subject percent change in lumbar spine BMD. Secondary endpoints included percent change in hip and forearm BMD, transiliac biopsy parameters (trabecular bone volume, microarchitecture, stiffness, and adipocytes), serum N-terminal propeptide of procollagen type 1 (P1NP), and C-telopeptide.Results:BMD increased at the spine (10.8 ± 8.3% [SD]), total hip (6.2 ± 5.6%), and femoral neck (7.6 ± 3.4%) (all P < .001). Serum P1NP doubled by 1 month, peaked at 6 months, and returned to baseline by 18 to 24 months. Transiliac biopsies demonstrated significant increases in cortical width and porosity and trabecular bone volume and number increased, mirrored by a 71% increase in trabecular bone stiffness (P < .02-.001). Adipocyte area, perimeter, and volume/marrow volume decreased, with no change in adipocyte number. Four women had no increase in BMD and a blunted, delayed increase in serum P1NP. Nonresponders had markedly lower baseline bone formation rate (0.002 ± 0.001 vs 0.011 ± 0.006 mm(2)/mm/y; P < .001) and higher serum IGF-1 (208 ± 54 vs 157± 44 ng/mL; P = .03).Conclusions:Teriparatide was associated with increased spine and hip BMD and improved trabecular microarchitecture and stiffness at the iliac crest in the majority of women with IOP.
The Journal of clinical endocrinology and metabolism 03/2013; · 6.50 Impact Factor
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Adi Cohen,
David W Dempster,
Robert R Recker,
Joan M Lappe,
Hua Zhou,
Alexander Zwahlen,
Ralph Müller,
Binsheng Zhao,
Xiaotao Guo,
Thomas Lang,
Isra Saeed,
X Sherry Liu,
X Edward Guo,
Serge Cremers,
Clifford J Rosen,
Emily M Stein,
Thomas L Nickolas,
Donald J McMahon,
Polly Young,
Elizabeth Shane
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ABSTRACT: Context:The conventional view that obesity is beneficial for bone strength has recently been challenged by studies that link obesity, particularly visceral obesity, to low bone mass and fractures. It is controversial whether effects of obesity on bone are mediated by increased bone resorption or decreased bone formation.Objective:To evaluate bone microarchitecture and remodeling in healthy premenopausal women of varying weight.Design:We measured bone density and trunk fat by DXA in 40 women, and by quantitative computed tomography (QCT) in a subset. Bone microarchitecture, stiffness, remodeling and marrow fat were assessed in labeled transiliac bone biopsies.Results:Body mass index (BMI) ranged from 20.1 to 39.2 kg/m(2). DXA-trunk fat was directly associated with BMI (r=0.78, p<0.001) and visceral fat by QCT (r=0.79, p<0.001). Compared to women in the lowest tertile of trunk fat, those in the highest tertile had inferior bone quality: lower trabecular bone volume (20.4±5.8 versus 29.1±6.1%; p=0.001) and stiffness (433±264 versus 782±349 MPa; p=0.01), higher cortical porosity (8.8±3.5 versus 6.3±2.4%; p=0.049). Bone formation rate (0.004±0.002 versus 0.011±0.008 mm(2)/mm/year; p=0.006) was 64% lower in the highest tertile. Trunk fat was inversely associated with trabecular bone volume (r=-0.50; p<0.01) and bone formation rate (r=-0.50; p<0.001). The relationship between trunk fat and bone volume remained significant after controlling for age and BMI.Conclusions:At the tissue level, premenopausal women with more central adiposity had inferior bone quality and stiffness, and markedly lower bone formation. Given the rising levels of obesity, these observations require further investigation.
The Journal of clinical endocrinology and metabolism 03/2013; · 6.50 Impact Factor
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Elizabeth Shane, Adi Cohen,
Emily M Stein,
Donald J McMahon,
Chiyuan Zhang,
Polly Young,
Kavita Pandit,
Ronald B Staron,
Elizabeth C Verna,
Robert Brown,
Susan Restaino,
Donna Mancini
[show abstract]
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ABSTRACT: Context:The first year after transplantation is characterized by rapid bone loss.Objective:The aim of this study was to compare zoledronic acid (zoledronate) and alendronate for prevention of transplantation bone loss.Design and Setting:A randomized clinical trial was conducted at a transplantation center.Patients:The study included 84 adults undergoing heart or liver transplantation and a concurrently transplanted, nonrandomized reference group of 27 adults with T scores greater than -1.5.Interventions:Alendronate (70 mg weekly for 12 months) or one 5-mg infusion of zoledronate were both initiated 26 ± 8 d after transplantation.Main Outcome Measures:The primary outcome was total hip bone mineral density (BMD) 1 yr after transplantation. Secondary outcomes included femoral neck and lumbar spine BMD and serum C-telopeptide, a bone resorption marker.Results:In the reference group, BMD declined at the spine and hip (P < 0.001). In the randomized groups, hip BMD remained stable. Spine BMD increased in the zoledronate group and did not change in the alendronate group; at 12 months, the 2.2% difference between groups (95% confidence interval, 0.6 to 3.9%; P = 0.009) favored zoledronate. In heart transplant patients, spine BMD declined in the alendronate and increased in the zoledronate group (-3.0 vs. +1.6%, respectively; between-group difference, 4.2%; 95% confidence interval, 2.1 to 6.3%; P < 0.001). In liver transplant patients, spine BMD increased comparably in both groups. Twelve-month C-telopeptide was lower in the zoledronate group than in the alendronate group (79 vs. 49%; P = 0.04).Conclusions:One 5-mg infusion of zoledronate and weekly alendronate prevent bone loss at the hip and, in liver transplant patients, increase spine BMD. In heart transplant patients, spine bone BMD remained stable with zoledronate but decreased with alendronate.
The Journal of clinical endocrinology and metabolism 09/2012; · 6.50 Impact Factor
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Adi Cohen,
Thomas F Lang,
Donald J McMahon,
X Sherry Liu,
X Edward Guo,
Chiyuan Zhang,
Emily M Stein,
David W Dempster,
Polly Young,
Isra Saeed,
Joan M Lappe,
Robert R Recker,
Elizabeth Shane
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ABSTRACT: Context:Idiopathic osteoporosis (IOP) affects otherwise healthy young individuals with intact gonadal function and no secondary cause of bone fragility. In premenopausal women with IOP, a low trauma fracture is evidence of impaired bone quality and strength. The extent to which low bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) reflects low volumetric BMD, bone microstructure, and strength is uncertain in the absence of low trauma fracture.Objective:The objective of the study was to compare three-dimensional volumetric BMD and bone stiffness in premenopausal women with IOP based on fracture history, those with idiopathic low BMD (Z score ≤ -2.0) and no low trauma fracture, and normal age-matched controls.Design:We measured volumetric BMD and bone geometry by central quantitative computed tomography (cQCT) scans of the spine and hip and estimated bone stiffness by finite element analysis of cQCT data sets in 32 premenopausal women with IOP, 12 with idiopathic low BMD, and 34 controls.Results:Subjects had comparable decreases in total and trabecular volumetric BMD, cortical thickness, and whole-bone stiffness compared with controls, regardless of fracture history. These differences remained significant after controlling for age, body mass index, and bone size. The positive predictive values of a DXA Z score of -2.0 or less for a cQCT volumetric BMD Z score of -2.0 or less were 95% at the lumbar spine, 90% at the total hip, and 86% at the femoral neck.Conclusion:Women with idiopathic low BMD alone and those with low trauma fractures had comparable deficits in bone mass, structure, and stiffness. Low areal BMD by DXA is fairly accurate for predicting low volumetric BMD by cQCT. These results are consistent with three-dimensional bone imaging at the iliac crest, radius, and tibia in premenopausal IOP and suggest that the term osteoporosis may be appropriate in women with Z scores below -2.0, whether or not there is a history of fracture.
The Journal of clinical endocrinology and metabolism 09/2012; · 6.50 Impact Factor
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Emily M Stein,
X Sherry Liu,
Thomas L Nickolas, Adi Cohen,
Donald J McMahon,
Bin Zhou,
Chiyuan Zhang,
Mafo Kamanda-Kosseh,
Felicia Cosman,
Jeri Nieves,
X Edward Guo,
Elizabeth Shane
[show abstract]
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ABSTRACT: Background: Abnormal bone microarchitecture predisposes postmenopausal women to fragility fractures. Whether women with vertebral fractures have worse microarchitecture than those with nonvertebral fractures is unknown. Methods: Postmenopausal women with a history of low trauma vertebral fracture (n = 30) and nonvertebral fracture (n = 73) and controls (n = 120) had areal bone mineral density of lumbar spine, total hip, femoral neck, 1/3 radius, and ultradistal radius measured by dual-energy x-ray absorptiometry. Trabecular and cortical volumetric bone mineral density and microarchitecture were measured by high-resolution peripheral quantitative computed tomography of the distal radius and tibia. Finite element analysis estimated whole bone stiffness. Results: Mean age of subjects was 68 ± 7 yr. Groups were similar with respect to age, race, and body mass index. Mean T-scores did not differ from controls at any site except the ultradistal radius (vertebral fracture, 0.6 sd lower; nonvertebral fracture, 0.4 sd lower). Compared to controls, women with vertebral fractures had lower total, cortical, and trabecular volumetric density, lower cortical thickness, trabecular number and thickness, greater trabecular separation and network heterogeneity, and lower stiffness at both radius and tibia. Differences between women with nonvertebral fractures and controls were similar but less pronounced. Compared to women with nonvertebral fractures, women with vertebral fractures had lower total and trabecular density, lower cortical thickness and trabecular number, and greater trabecular separation and heterogeneity at the tibia. Whole bone stiffness tended to be lower (P = 0.06). Differences between fracture groups at the radius were not statistically significant. Conclusion: Women with vertebral fractures have more severe trabecular and cortical microarchitectural deterioration than those with nonvertebral fractures, particularly at the tibia.
The Journal of clinical endocrinology and metabolism 07/2012; 97(10):E1918-26. · 6.50 Impact Factor
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Adi Cohen,
David W Dempster,
Emily M Stein,
Thomas L Nickolas,
Hua Zhou,
Donald J McMahon,
Ralph Müller,
Thomas Kohler,
Alexander Zwahlen,
Joan M Lappe,
Polly Young,
Robert R Recker,
Elizabeth Shane
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ABSTRACT: We have previously reported that premenopausal women with idiopathic osteoporosis based on fractures (IOP) or idiopathic low bone mineral density (ILBMD) exhibit markedly reduced bone mass, profoundly abnormal trabecular microstructure, and significant deficits in trabecular bone stiffness. Bone remodeling was heterogeneous. Those with low bone turnover had evidence of osteoblast dysfunction and the most marked deficits in microstructure and stiffness.
Because osteoblasts and marrow adipocytes derive from a common mesenchymal precursor and excess marrow fat has been implicated in the pathogenesis of bone fragility in anorexia nervosa, glucocorticoid excess, and thiazolidinedione exposure, we hypothesized that marrow adiposity would be higher in affected women and inversely related to bone mass, microarchitecture, bone formation rate, and osteoblast number.
We analyzed tetracycline-labeled transiliac biopsy specimens in 64 premenopausal women with IOP or ILBMD and 40 controls by three-dimensional micro-computed tomography and two-dimensional quantitative histomorphometry to assess marrow adipocyte number, perimeter, and area.
IOP and ILBMD subjects did not differ with regard to any adipocyte parameter, and thus results were combined. Subjects had substantially higher adipocyte number (by 22%), size (by 24%), and volume (by 26%) than controls (P < 0.0001 for all). Results remained significant after adjusting for age, body mass index, and bone volume. Controls demonstrated expected direct associations between marrow adiposity and age and inverse relationships between marrow adiposity and bone formation, volume, and microstructure measures. No such relationships were observed in the subjects.
Higher marrow adiposity and the absence of expected relationships between marrow adiposity and bone microstructure and remodeling in women with IOP or ILBMD suggest that the relationships between fat and bone are abnormal; excess marrow fat may not arise from a switch from the osteoblast to the adipocyte lineage in this disorder. Whether excess marrow fat contributes to the pathogenesis of this disorder remains unclear.
The Journal of clinical endocrinology and metabolism 06/2012; 97(8):2782-91. · 6.50 Impact Factor
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X Sherry Liu,
Emily M Stein,
Bin Zhou,
Chiyuan A Zhang,
Thomas L Nickolas, Adi Cohen,
Valerie Thomas,
Donald J McMahon,
Felicia Cosman,
Jeri Nieves,
Elizabeth Shane,
X Edward Guo
[show abstract]
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ABSTRACT: Osteoporosis is typically diagnosed by dual-energy X-ray absorptiometry (DXA) measurements of areal bone mineral density (aBMD). Emerging technologies, such as high-resolution peripheral quantitative computed tomography (HR-pQCT), may increase the diagnostic accuracy of DXA and enhance our mechanistic understanding of decreased bone strength in osteoporosis. Women with (n = 68) and without (n = 101) a history of postmenopausal fragility fracture had aBMD measured by DXA, trabecular plate and rod microarchitecture measured by HR-pQCT image-based individual trabecula segmentation (ITS) analysis, and whole bone and trabecular bone stiffness by microfinite element analysis (µFEA) of HR-pQCT images at the radius and tibia. DXA T-scores were similar in women with and without fractures at the spine, hip, and 1/3 radius, but lower in fracture subjects at the ultradistal radius. Trabecular microarchitecture of fracture subjects was characterized by preferential reductions in trabecular plate bone volume, number, and connectivity over rod trabecular parameters, loss of axially aligned trabeculae, and a more rod-like trabecular network. In addition, decreased thickness and size of trabecular plates were observed at the tibia. The differences between groups were greater at the radius than the tibia for plate number, rod bone volume fraction and number, and plate-rod and rod-rod junction densities. Most differences between groups remained after adjustment for T-score by DXA. At a fixed bone volume fraction, trabecular plate volume, number, and connectivity were directly associated with bone stiffness. In contrast, rod volume, number, and connectivity were inversely associated with bone stiffness. In summary, HR-pQCT-based ITS and µFEA measurements discriminate fracture status in postmenopausal women independent of DXA measurements. Moreover, these results suggest that preferential loss of plate-like trabeculae contribute to lower trabecular bone and whole bone stiffness in women with fractures. We conclude that HR-pQCT-based ITS and µFEA measurements increase our understanding of the microstructural pathogenesis of fragility fracture in postmenopausal women.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 11/2011; 27(2):263-72. · 6.04 Impact Factor
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Adi Cohen,
David W Dempster,
Robert R Recker,
Emily M Stein,
Joan M Lappe,
Hua Zhou,
Andreas J Wirth,
G Harry van Lenthe,
Thomas Kohler,
Alexander Zwahlen,
Ralph Müller,
Clifford J Rosen,
Serge Cremers,
Thomas L Nickolas,
Donald J McMahon,
Halley Rogers,
Ronald B Staron,
Jeanette LeMaster,
Elizabeth Shane
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ABSTRACT: Idiopathic osteoporosis (IOP) in premenopausal women is an uncommon disorder of uncertain pathogenesis in which fragility fractures occur in otherwise healthy women with intact gonadal function. It is unclear whether women with idiopathic low bone mineral density and no history of fragility fractures have osteoporosis.
The objective of the study was to elucidate the microarchitectural and remodeling features of premenopausal women with IOP. Design: We performed transiliac biopsies after tetracycline labeling in 104 women: 45 with fragility fractures (IOP), 19 with idiopathic low bone mineral density (Z score ≤-2.0) and 40 controls. Biopsies were analyzed by two-dimensional quantitative histomorphometry and three-dimensional microcomputed tomography. Bone stiffness was estimated using finite element analysis.
Compared with controls, affected women had thinner cortices; fewer, thinner, more widely separated, and heterogeneously distributed trabeculae; reduced stiffness; and lower osteoid width and mean wall width. All parameters were indistinguishable between women with IOP and idiopathic low bone mineral density. Although there were no group differences in dynamic histomorphometric remodeling parameters, serum calciotropic hormones, bone turnover markers, or IGF-I, subjects in the lowest tertile of bone formation rate had significantly lower osteoid and wall width, more severely disrupted microarchitecture, lower stiffness, and higher serum IGF-I than those in the upper two tertiles, suggesting that women with low turnover IOP have osteoblast dysfunction with resistance to IGF-I. Subjects with high bone turnover had significantly higher serum 1,25 dihydroxyvitamin D levels and a nonsignificant trend toward higher serum PTH and urinary calcium excretion.
These results suggest that the diagnosis of IOP should not require a history of fracture. Women with IOP may have high, normal or low bone turnover; those with low bone turnover have the most marked deficits in microarchitecture and stiffness. These results also suggest that the pathogenesis of idiopathic osteoporosis is heterogeneous and may differ according to remodeling activity.
The Journal of clinical endocrinology and metabolism 08/2011; 96(10):3095-105. · 6.50 Impact Factor
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Thomas L Nickolas,
Serge Cremers,
Amy Zhang,
Valeri Thomas,
Emily Stein, Adi Cohen,
Ryan Chauncey,
Lucas Nikkel,
Michael T Yin,
Xiaowei S Liu,
Stephanie Boutroy,
Ronald B Staron,
Mary B Leonard,
Donald J McMahon,
Elzbieta Dworakowski,
Elizabeth Shane
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ABSTRACT: Patients with chronic kidney disease (CKD) have higher rates of fracture than the general population. Increased bone remodeling, leading to microarchitectural deterioration and increased fragility, may accompany declining kidney function, but there are no reliable methods to identify patients at increased risk for fracture. In this cross-sectional study of 82 patients with predialysis CKD, high-resolution imaging revealed that the 23 patients with current fractures had significantly lower areal density at the femoral neck; total, cortical, and trabecular volumetric bone density; cortical area and thickness; and trabecular thickness. Compared with levels in the lowest tertile, higher levels of osteocalcin, procollagen type-1 N-terminal propeptide, and tartrate-resistant acid phosphatase 5b were associated with higher odds of fracture, even after adjustment for femoral neck T-score. Discrimination of fracture prevalence was best with a femoral neck T-score of -2.0 or less and a value in the upper two tertiles for osteocalcin, procollagen type-1 N-terminal propeptide, or tartrate-resistant acid phosphatase 5b; these values corresponded to the upper half of the normal premenopausal reference range. In summary, these cross-sectional data suggest that measurement of bone turnover markers may increase the diagnostic accuracy of densitometry to identify patients with CKD at high risk for fracture.
Journal of the American Society of Nephrology 08/2011; 22(8):1560-72. · 9.66 Impact Factor
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Emily M Stein,
X Sherry Liu,
Thomas L Nickolas, Adi Cohen,
Valerie Thomas,
Donald J McMahon,
Chiyuan Zhang,
Felicia Cosman,
Jeri Nieves,
Justin Greisberg,
X Edward Guo,
Elizabeth Shane
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ABSTRACT: Ankle fractures are not typically considered osteoporotic fractures. However, bone quality in patients with low trauma ankle fractures has not been explored.
Women with (n = 17) and without (n = 112) a history of low trauma ankle fracture after menopause had areal bone mineral density measured by dual-energy x-ray absorptiometry, trabecular (Tb) and cortical volumetric bone mineral density, and Tb microarchitecture measured by high-resolution peripheral computed tomography of the radius and tibia. Finite element analysis was performed to estimate bone stiffness.
Women with fractures were older (72 ± 2 vs. 68 ± 1 yr; P < 0.02) but similar with respect to race and body mass index. Mean T-scores by dual-energy x-ray absorptiometry of fracture subjects were above the osteoporotic range and did not differ from controls. By high-resolution peripheral computed tomography at the radius, fracture subjects had preferentially lower central trabecular bone density, lower Tb number, and increased separation compared with controls (P < 0.0001-0.04). At the tibia, fracture subjects had lower total and Tb density, lower Tb number, and increased Tb separation and network heterogeneity (P < 0.02). Whole-bone stiffness was 13-17% lower at the radius and tibia in fracture subjects (P < 0.003-0.01).
Postmenopausal women with ankle fractures have disrupted microarchitecture and decreased stiffness compared with women with no fracture history, suggesting that low trauma ankle fractures should be considered similarly to other classical osteoporotic fractures.
The Journal of clinical endocrinology and metabolism 04/2011; 96(7):2041-8. · 6.50 Impact Factor
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Emily M Stein,
X Sherry Liu,
Thomas L Nickolas, Adi Cohen,
Valerie Thomas,
Donald J McMahon,
Chiyuan Zhang,
Perry T Yin,
Felicia Cosman,
Jeri Nieves,
X Edward Guo,
Elizabeth Shane
[show abstract]
[hide abstract]
ABSTRACT: Measurement of areal bone mineral density (aBMD) by dual-energy x-ray absorptiometry (DXA) has been shown to predict fracture risk. High-resolution peripheral quantitative computed tomography (HR-pQCT) yields additional information about volumetric BMD (vBMD), microarchitecture, and strength that may increase understanding of fracture susceptibility. Women with (n = 68) and without (n = 101) a history of postmenopausal fragility fracture had aBMD measured by DXA and trabecular and cortical vBMD and trabecular microarchitecture of the radius and tibia measured by HR-pQCT. Finite-element analysis (FEA) of HR-pQCT scans was performed to estimate bone stiffness. DXA T-scores were similar in women with and without fracture at the spine, hip, and one-third radius but lower in patients with fracture at the ultradistal radius (p < .01). At the radius fracture, patients had lower total density, cortical thickness, trabecular density, number, thickness, higher trabecular separation and network heterogeneity (p < .0001 to .04). At the tibia, total, cortical, and trabecular density and cortical and trabecular thickness were lower in fracture patients (p < .0001 to .03). The differences between groups were greater at the radius than at the tibia for inner trabecular density, number, trabecular separation, and network heterogeneity (p < .01 to .05). Stiffness was reduced in fracture patients, more markedly at the radius (41% to 44%) than at the tibia (15% to 20%). Women with fractures had reduced vBMD, microarchitectural deterioration, and decreased strength. These differences were more prominent at the radius than at the tibia. HR-pQCT and FEA measurements of peripheral sites are associated with fracture prevalence and may increase understanding of the role of microarchitectural deterioration in fracture susceptibility. © 2010 American Society for Bone and Mineral Research.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 12/2010; 25(12):2572-81. · 6.04 Impact Factor
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[show abstract]
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ABSTRACT: Patients with predialysis chronic kidney disease (CKD) have increased risk for fracture, but the structural mechanisms underlying this increased skeletal fragility are unknown. We measured areal bone mineral density (aBMD) by dual-energy x-ray absorptiometry at the spine, hip, and radius, and we measured volumetric BMD (vBMD), geometry, and microarchitecture by high-resolution peripheral quantitative computed tomography (HR-pQCT) at the radius and tibia in patients with CKD: 32 with fracture and 59 without fracture. Patients with fracture had lower aBMD at the spine, total hip, femoral neck, and the ultradistal radius, the last having the strongest association with fracture. By HR-pQCT of the radius, patients with fracture had lower cortical area and thickness, total and trabecular vBMD, and trabecular number and greater trabecular separation and network heterogeneity. At the tibia, patients with fracture had significantly lower cortical area, thickness, and total and cortical density. Total vBMD at both radius and tibia most strongly associated with fracture. By receiver operator characteristic curve analysis, patients with longer duration of CKD had area under the curve of >0.75 for aBMD at both hip sites and the ultradistal radius, vBMD and geometry at the radius and tibia, and microarchitecture at the tibia. In summary, patients with predialysis CKD and fractures have lower aBMD by dual-energy x-ray absorptiometry and lower vBMD, thinner cortices, and trabecular loss by HR-pQCT. These density and structural differences may underlie the increased susceptibility to fracture among patients with CKD.
Journal of the American Society of Nephrology 08/2010; 21(8):1371-80. · 9.66 Impact Factor
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X Sherry Liu, Adi Cohen,
Elizabeth Shane,
Perry T Yin,
Emily M Stein,
Halley Rogers,
Shannon L Kokolus,
Donald J McMahon,
Joan M Lappe,
Robert R Recker,
Thomas Lang,
X Edward Guo
[show abstract]
[hide abstract]
ABSTRACT: High-resolution peripheral quantitative computed tomography (HR-pQCT) is a new in vivo imaging technique for assessing 3D microstructure of cortical and trabecular bone at the distal radius and tibia. No studies have investigated the extent to which measurements of the peripheral skeleton by HR-pQCT reflect those of the spine and hip, where the most serious fractures occur. To address this research question, we performed dual-energy X-ray absorptiometry (DXA), central QCT (cQCT), HR-pQCT, and image-based finite-element analyses on 69 premenopausal women to evaluate relationships among cortical and trabecular bone density, geometry, microstructure, and stiffness of the lumbar spine, proximal femur, distal radius, and distal tibia. Significant correlations were found between the stiffness of the two peripheral sites (r = 0.86), two central sites (r = 0.49), and between the peripheral and central skeletal sites (r = 0.56-0.70). These associations were explained in part by significant correlations in areal bone mineral density (aBMD), volumetric bone mineral density (vBMD), and cross-sectional area (CSA) between the multiple skeletal sites. For the prediction of proximal femoral stiffness, vBMD (r = 0.75) and stiffness (r = 0.69) of the distal tibia by HR-pQCT were comparable with direct measurements of the proximal femur: aBMD of the hip by DXA (r = 0.70) and vBMD of the hip by cQCT (r = 0.64). For the prediction of vertebral stiffness, trabecular vBMD (r = 0.58) and stiffness (r = 0.70) of distal radius by HR-pQCT were comparable with direct measurements of lumbar spine: aBMD by DXA (r = 0.78) and vBMD by cQCT (r = 0.67). Our results suggest that bone density and microstructural and mechanical properties measured by HR-pQCT of the distal radius and tibia reflect the mechanical competence of the central skeleton.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 04/2010; 25(10):2229-38. · 6.04 Impact Factor
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Adi Cohen
Maturitas 03/2010; 66(1):3-4. · 2.77 Impact Factor
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X Sherry Liu, Adi Cohen,
Elizabeth Shane,
Emily Stein,
Halley Rogers,
Shannon L Kokolus,
Perry T Yin,
Donald J McMahon,
Joan M Lappe,
Robert R Recker,
X Edward Guo
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[hide abstract]
ABSTRACT: Idiopathic osteoporosis (IOP) in premenopausal women is a poorly understood entity in which otherwise healthy women have low-trauma fracture or very low bone mineral density (BMD). In this study, we applied individual trabeculae segmentation (ITS)-based morphological analysis to high-resolution peripheral quantitative computed tomography (HR-pQCT) images of the distal radius and distal tibia to gain greater insight into skeletal microarchitecture in premenopausal women with IOP. HR-pQCT scans were performed for 26 normal control individuals and 31 women with IOP. A cubic subvolume was extracted from the trabecular bone compartment and subjected to ITS-based analysis. Three Young's moduli and three shear moduli were calculated by micro-finite element (microFE) analysis. ITS-based morphological analysis of HR-pQCT images detected significantly decreased trabecular plate and rod bone volume fraction and number, decreased axial bone volume fraction in the longitudinal axis, increased rod length, and decreased rod-to-rod, plate-to-rod, and plate-to-plate junction densities at the distal radius and distal tibia in women with IOP. However, trabecular plate and rod thickness did not differ. A more rod-like trabecular microstructure was found in the distal radius, but not in the distal tibia. Most ITS measurements contributed significantly to the elastic moduli of trabecular bone independent of bone volume fraction (BV/TV). At a fixed BV/TV, plate-like trabeculae contributed positively to the mechanical properties of trabecular bone. The results suggest that ITS-based morphological analysis of HR-pQCT images is a sensitive and promising clinical tool for the investigation of trabecular bone microstructure in human studies of osteoporosis.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 02/2010; 25(7):1496-505. · 6.04 Impact Factor
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12/2009: pages 289 - 293; , ISBN: 9780470623992
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[show abstract]
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ABSTRACT: Idiopathic osteoporosis (IOP) is an uncommon disorder in which low areal bone mineral density (aBMD) and/or fractures occur in otherwise healthy premenopausal women.
Our objectives were to characterize bone mass, microarchitecture, and trabecular bone stiffness in premenopausal IOP and to determine whether women with low aBMD who have never fractured have abnormal microarchitecture and stiffness.
We conducted a prospective cohort study of 27 normal controls and 31 women with IOP defined by low trauma fracture (n = 21) or low BMD (Z score <or=-2.0; n = 10).
We assessed aBMD by dual-energy x-ray absorptiometry; volumetric BMD and cortical and trabecular microarchitecture of the radius and tibia by high-resolution (82 microm) peripheral quantitative computed tomography; and trabecular bone stiffness (elastic moduli), estimated by micro-finite element analysis.
Fracture subjects did not differ from controls by age or body mass index, which was lower in low-BMD subjects than controls. Fracture subjects also had lower aBMD than controls at all sites (P < 0.05-0.0001). Bone size was similar in controls and fracture subjects but 10.6% smaller in low-BMD subjects (P < 0.05). Every trabecular parameter in both fracture and low-BMD groups was markedly worse than controls (P < 0.01-0.0001). Cortical thickness was significantly lower in both fracture and low-BMD groups at the tibia but not radius. Bone stiffness estimated by micro-finite element analysis was comparably reduced in low-BMD and fracture groups.
Premenopausal women with IOP had marked trabecular microarchitectural deterioration at the radius and tibia. Cortical parameters were affected only at the tibia. Although they had not fractured, microarchitectural deterioration was similar in IOP women with low BMD and those with fractures.
The Journal of clinical endocrinology and metabolism 11/2009; 94(11):4351-60. · 6.50 Impact Factor
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Emily M Stein, Adi Cohen,
Matthew Freeby,
Halley Rogers,
Shannon Kokolus,
Vanessa Scott,
Donna Mancini,
Susan Restaino,
Robert Brown,
Donald J McMahon,
Elizabeth Shane
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ABSTRACT: Although patients with end-stage organ failure are at high risk for vitamin D deficiency because of limited sunlight exposure and hepatic dysfunction, few studies have measured 25-hydroxy vitamin D (25OHD) at the time of transplantation.
We measured serum 25OHD immediately after transplantation in 69 heart and liver transplant recipients.
Forty-six heart and 23 liver transplant recipients were evaluated (mean age 53 yr). Mean 25OHD was well below the lower limit of the normal range (43.2 +/- 21.2 nmol/L). Ninety-one percent had levels below 75 nmol/L, the threshold commonly used to denote sufficiency, and 71% had levels below 50 nmol/L. Severe deficiency (25OHD <25 nmol/L) was found in 16%. Vitamin D levels did not differ by race, age, gender, or season. Mean 25OHD was lower among liver than heart transplant recipients (34.4 +/- 17.5 vs. 47.7 +/- 20.7 nmol/L; p < 0.03). Among liver transplant recipients, 22% had undetectable levels (<17 nmol/L).
Vitamin D deficiency is highly prevalent among heart and liver transplant recipients; those with liver failure are at greatest risk. As vitamin D deficiency has many serious skeletal and extra-skeletal sequelae, physicians who treat transplant patients should maintain a high degree of vigilance for this problem.
Clinical Transplantation 05/2009; 23(6):861-5. · 1.67 Impact Factor
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ABSTRACT: The overall objective of this research is to develop an ultrasonic method for non-invasive assessment of the distal radius. The specific objective of this study was to examine the propagation of ultrasound through the distal radius and determine the relationships between bone mass and architecture and ultrasound parameters. Twenty-six high-resolution peripheral-CT clinical images were obtained from a set of subjects that were part of a larger study on secondary osteoporosis. A single mid-section binary slice from each image was selected and used in the 2D simulation of an ultrasound wave propagating from the anterior to the posterior surfaces of each radius. Mass and architectural parameters associated with each radius, including total bone mass, volume fraction, trabecular number, and trabecular thickness were computed. Ultrasound parameters, including net time delay (NTD), broadband ultrasound attenuation (BUA), and ultrasound velocity (UV) were also evaluated. Significant correlations were found between NTD and total bone mass (R2 = 0.92), BUA and trabecular number (R2 = 0.78), and UV and trabecular bone volume fraction (R2 = 0.82). The study shows that ultrasound measurements are correlated with bone mass and architecture at the distal radius, and thus ultrasound may prove useful as a method for non-invasive assessment of osteoporosis and fracture risk.
The Journal of the Acoustical Society of America 06/2008; 123(5):3513. · 1.55 Impact Factor
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ABSTRACT: Interpretation of bone mineral density (BMD) results in premenopausal women is particularly challenging, because the relationship between BMD and fracture risk is not the same as for postmenopausal women. Z scores rather than T scores should be used to define "low BMD" in premenopausal women. The finding of low BMD in a premenopausal woman should prompt an evaluation for secondary causes of bone loss. If a secondary cause is found, management should focus on treatment of this condition. In some cases in which the secondary cause cannot be addressed, such as glucocorticoid therapy or cancer chemotherapy, treatment with a bone-active agent to prevent bone loss should be considered. In women with no fractures and no known secondary cause, low BMD may not signify compromised bone strength. BMD is likely to remain stable in these women, and pharmacologic therapy is rarely justified. Assessment of markers of bone turnover and follow-up bone density measurements can help to identify those with an ongoing process of bone loss that may indicate a higher risk for fracture, and possible need for pharmacologic intervention.
Current Osteoporosis Reports 04/2008; 6(1):39-46.
