Impaired trabecular and cortical microarchitecture in daughters of women with osteoporotic fracture: the MODAM study

Summary

We investigated the familial resemblance of bone microarchitecture parameters between postmenopausal mothers with fragility fracture and their premenopausal daughters using high-resolution peripheral quantitative computed tomography (HR-pQCT). We found that daughters of women with fracture have lower total volumetric bone mineral density (vBMD), thinner cortices, and impaired trabecular microarchitecture at the distal radius and tibia, compared to controls.

Introduction

Familial resemblance of areal bone mineral density (aBMD) in mothers and daughters has been widely studied, but not its morphological basis, including microarchitecture.

Methods

We compared aBMD, vBMD, bone size, and bone microarchitecture at the distal radius and tibia assessed by HR-pQCT in mothers and their premenopausal daughters. We included 115 women aged 43?±?8 years whose mothers had sustained a fragility fracture and 206 women aged 39?±?9 years whose mothers had never sustained a fragility fracture.

Results

Women whose mothers had fracture had significantly (p?<?0.05) lower aBMD at the lumbar spine, total hip, femoral neck, mid-distal radius, and ultradistal radius compared to controls. In similar multivariable models, women whose mothers had a fracture had lower total vBMD at the distal radius (?5 %, 0.3 standard deviation [SD]; p?<?0.005) and distal tibia (?7 %, 0.4 SD; p?<?0.005). They also had lower cortical thickness and area at the distal radius (?5 %, 0.3 SD and ?4 %, 0.2 SD, respectively; p?<?0.005) and at the distal tibia (?6 %, 0.3 SD and ?4 %, 0.3SD, respectively; p?<?0.005). Trabecular vBMD was lower at the distal radius (?5 %, 0.3 SD; p?<?0.05) and tibia (?8 %, 0.4 SD; p?<?0.005), with a more spaced and heterogeneous trabecular network (4 and 7 % at the radius and 5 and 9 %, at the tibia, p?<?0.05, for Tb.Sp and Tb.Sp.SD, respectively).

Conclusion

Premenopausal daughters of women who had sustained fragility fracture have lower total and trabecular vBMD, thinner cortices, as well as impaired trabecular microarchitecture at the distal radius and tibia, compared with premenopausal daughters of women without fracture.     

Effect of oral monthly ibandronate on bone microarchitecture in women with osteopenia—a randomized placebo-controlled trial

Summary

We have examined the effect of oral monthly ibandronate on distal radius and tibia microarchitecture with high-resolution peripheral quantitative tomography compared with placebo, in women with osteopenia, and found that ibandronate did not significantly affect trabecular bone but improved cortical density and thickness at the tibia.

Methods

We have examined the effect of ibandronate on bone microarchitecture with peripheral high-resolution quantitative computed tomography (HR-pQCT) in a randomized placebo-controlled trial among 148 women with osteopenia. Patients received either oral 150 mg monthly ibandronate or placebo over 24 months. Bone microarchitecture was assessed at baseline, 6, 12, and 24 months, using HR-pQCT at the distal radius and tibia; areal bone mineral density (aBMD) was measured with DXA at the spine, hip, and radius.

Results

At 12 months, there was no significant difference in trabecular bone volume at the radius (the primary end point) between women on ibandronate (10.8?±?2.5%) and placebo (10.5?±?2.9%), p?=?0.25. There was no significant difference in other radius trabecular and cortical microarchitecture parameters at 12 and 24 months. In contrast, at the tibia, cortical vBMD in the ibandronate group was significantly greater than in the placebo group at 6, 12, and 24 months, with better cortical thickness at 6, 12, and 24 months. With ibandronate, aBMD was significantly increased at the hip and spine at 12 and 24 months but at the radius was significantly superior to placebo only at 24 months. Most of the adverse events related to ibandronate were expected with bisphosphonate use, and none of them were serious.

Conclusion

We conclude that 12 months of treatment with ibandronate in women with osteopenia did not affect trabecular bone microarchitecture, but improved cortical vBMD at the tibia at 12 and 24 months, and preserved cortical thickness at the tibia.     

Monitoring time interval for pQCT-derived bone outcomes in postmenopausal women

Summary

Evidence of measurement precision, annual changes and monitoring time interval is essential when designing and interpreting longitudinal studies. Despite the precise measures, small annual changes in bone properties led to monitoring time intervals (MTIs) of 2–6 years in peripheral quantitative computed tomography (pQCT)-derived radial and tibial bone area, density, and estimated strength in postmenopausal women.

Introduction

The purpose of the study was to determine the precision error, annual change, and MTI in bone density, area, and strength parameters in postmenopausal women.

Methods

Postmenopausal women (n?=?114) from the Saskatoon cohort of the Canadian Multicentre Osteoporosis Study had annual pQCT scans of the distal and shaft sites of the radius and tibia for 2 years. Median annualized rates of percent change and the MTI were calculated for bone density, area, and strength parameters. Root mean squared coefficients of variation (CV%) were calculated from duplicate scans in a random subgroup of 35 postmenopausal women.

Results

CV% ranged from 1.4 to 6.1 % at the radius and 0.7 to 2.1 % at the tibia. MTIs for the distal radius were 3 years for total bone density (ToD) and 4 years for total bone cross sectional area (ToA), trabecular area, and bone strength index. At the diaphyseal radius, MTI was 3 years for ToA, 5 years for cortical density, and 6 years for polar stress strain index (SSI_p). Similarly, MTI for total and trabecular density was 3 years at the distal tibia. At the diaphyseal tibia, MTI for ToA was 3 years and SSI_p 4 years.

Conclusion

MTI for longitudinal studies in older postmenopausal women should be at least 2–6 years at the radius and tibia, with specific monitoring of the total and trabecular area, total density, and bone strength at the radius and total and trabecular density, total area, and bone strength at the tibia.     

Long-term HIV infection and antiretroviral therapy are associated with bone microstructure alterations in premenopausal women

Summary

We evaluated the influence of long-term HIV infection and its treatment on distal tibia and radius microstructure. Premenopausal eumenorrheic HIV-positive women displayed trabecular and cortical microstructure alterations, which could contribute to increased bone fragility in those patients.

Introduction

Bone fragility is an emerging issue in HIV-infected patients. Dual-energy X-ray absorptiometry (DXA) quantified areal bone mineral density (BMD) predicts fracture risk, but a significant proportion of fracture risk results from microstructural alterations.

Methods

We studied the influence of long-term HIV infection on bone microstructure as evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT) in 22 HIV-positive (+ve) premenopausal eumenorrheic women and 44 age- and body mass index (BMI)-matched HIV-negative (?ve) controls. All subjects completed questionnaires regarding calcium/protein intakes and physical activity, and underwent DXA and HR-pQCT examinations for BMD and peripheral skeleton microstructure, respectively. A risk factor analysis of tibia trabecular density using linear mixed models was conducted.

Results

In HIV+ve women on successful antiretroviral therapy (undetectable HIV-RNA, median CD4 cell count, 626), infection duration was 16.5?±?3.5 (mean ± SD)?years; median BMI was 22 (IQR, 21–26)?kg/m². More HIV+ve women were smokers (82 versus 50 %, p?=?0.013). Compared to controls, HIV+ve women had lower lumbar spine (spine T-score ?0.70 vs ?0.03, p?=?0.014), but similar proximal femur BMD. At distal tibia, HIV+ve women had a 14.1 % lower trabecular density and a 13.2 % reduction in trabecular number compared to HIV?ve women (p?=?0.013 and 0.029, respectively). HR-pQCT differences in distal radius were significant for cortical density (?3.0 %; p?=?0.029).

Conclusions

Compared with HIV?ve subjects, premenopausal HIV+ve treated women had trabecular and cortical bone alterations. Adjusted analysis revealed that HIV status was the only determinant of between group tibia trabecular density differences. The latter could contribute to increased bone fragility in HIV+ve patients.     

Postmenopausal women treated with combination parathyroid hormone (1–84) and ibandronate demonstrate different microstructural changes at the radius vs. tibia: the PTH and Ibandronate Combination Study (PICS)

Summary

In postmenopausal women receiving combination parathyroid hormone (PTH) (1–84) therapy and ibandronate, we evaluated bone microarchitecture and biomechanics using high-resolution peripheral quantitative computed tomography (HR-pQCT). Cortical and trabecular changes were different at the nonweight-bearing radius vs. the weight-bearing tibia, with more favorable overall changes at the tibia.

Introduction

PTH therapy and bisphosphonates decrease fracture risk in postmenopausal osteoporosis, but their effects on bone microstructure and strength have not been fully characterized, particularly during combination therapy. PTH increases trabecular bone mineral density (BMD) substantially but may decrease cortical BMD, possibly by stimulating intracortical remodeling. We evaluated bone microarchitecture and biomechanics with HR-pQCT at the radius (a nonweight-bearing site) and tibia (weight bearing) in women receiving combination PTH(1–84) and ibandronate.

Methods

Postmenopausal women with low bone mass (n?=?43) were treated with 6 months of PTH(1–84) (100 μg/day), either as one 6- or two 3-month courses, in combination with ibandronate (150 mg/month) over 2 years. HR-pQCT was performed before and after therapy.

Results

Because changes in HR-pQCT parameters did not differ between treatment arms, groups were pooled into one cohort for analysis. Trabecular BMD increased at both radius and tibia (p?<?0.01 for each). Cortical thickness and BMD decreased at the radius (p?<?0.01), consistent with changes in dual-energy X-ray absorptiometry, while these parameters did not change at the tibia (p?≤?0.02 for difference between radius and tibia). In contrast, cortical porosity increased at the tibia (p?<?0.01) but not radius. Stiffness and failure load decreased at the radius (p?<?0.0001) but did not change at the tibia.

Conclusions

Cortical and trabecular changes in response to the PTH/ibandronate treatment combinations utilized in this study were different at the nonweight-bearing radius vs. the weight-bearing tibia, with more favorable overall changes at the tibia. Our findings support the possibility that weight bearing may optimize the effects of osteoporosis therapy.     

Poor bone microarchitecture in older men with impaired physical performance—the STRAMBO study

Summary

In 810 men ≥60?years, poor physical performance of lower limbs was associated with lower areal bone mineral density (aBMD) of total hip and poor bone microarchitecture at the distal tibia (assessed by HR-pQCT). Men who reported falls had lower hip aBMD and lower cortical density at the distal tibia.

Introduction

The aim of this study was to assess the association between bone microarchitecture and physical performance in older men.

Methods

Volumetric bone mineral density (vBMD) and bone microarchitecture were assessed in 810 men ≥60?years at the distal radius and tibia by high resolution pQCT. aBMD was measured at the spine, hip, whole body, and distal radius by dual energy X-ray absorptiometry. Clinical tests included chair stands and tests of static and dynamic balance. We calculated a composite score summarizing abilities and time required to perform the tests.

Results

In multivariable models, men who failed in ≥one test had lower total hip aBMD than men who accomplished all the tests. They had lower total vBMD (Tt.vBMD), cortical thickness (Ct.Th), trabecular vBMD (Tb.vBMD), and more heterogenous trabecular distribution (Tb.Sp.SD) at the distal tibia (p?<?0.05). Men who failed in ≥two tests had lower aBMD at the total hip, femoral neck, and trochanter as well as lower Tt.vBMD, cortical vBMD (Ct.vBMD), Ct.Th and trabecular number (Tb.N), and higher Tb.Sp.SD at the distal tibia (p?<?0.05). Men in the lowest quartile of the composite score had lower aBMD (total hip, distal radius), lower Tb.vBMD and Tb.N at the distal radius, and lower Tt.vBMD, Ct.vBMD, Ct.Th, Tb.vBMD, and Tb.N, and higher Tb.Sp.SD at the distal tibia compared with the highest quartile. In multivariables models, men reporting falls had lower total hip aBMD and lower distal tibia Ct.vBMD (p?<?0.01).

Conclusion

In older men, poor physical performance is associated with lower hip aBMD and poor bone microarchitecture (mainly at the distal tibia).     

Changes in trabecular and cortical bone microarchitecture at peripheral sites associated with 18?months of teriparatide therapy in postmenopausal women with osteoporosis

Summary  

We used high-resolution peripheral quantitative computed tomography (HR-pQCT) to monitor changes in bone microarchitecture and strength at the distal radius and tibia associated with 18 months of teriparatide therapy in postmenopausal women with osteoporosis. Despite treatment-associated declines in total and cortical BMD, trabecular thinning and reduced trabecular bone volume, bone strength did not change significantly from baseline.     

Calcium and vitamin-D supplementation on bone structural properties in peripubertal female identical twins: a randomised controlled trial

Summary

A randomised controlled trial was used in assessing the impact of 6?months of daily calcium and vitamin-D supplementation on trabecular and cortical bone acquisition at distal tibial and radial sites using peripheral quantitative computed tomography (pQCT). Daily supplementation was associated with increased bone density and bone strength at the distal tibia and radius.

Introduction

pQCT has not been used to assess bone responses to calcium and vitamin-D supplementation on peripubertal children. This randomised controlled trial aimed to assess the impact of a 6-month daily calcium and vitamin-D supplementation on trabecular and cortical bone acquisition at distal tibial and radial sites using pQCT.

Methods

Twenty pairs of peripubertal female identical twins, aged 9 to 13?years, were randomly assigned to receive either 800?mg of calcium and 400?IU of vitamin D3, or a matched placebo. Bone structural properties at the distal tibia and distal radius were acquired at baseline and 6?months.

Results

The calcium-supplemented group showed greater gains in trabecular density, trabecular area and strength strain index at the 4% of distal tibial and radial sites compared with the placebo group (p?=?0.001). Greater gains in cortical area at the 38% and 66% of tibial sites were also found in twins receiving the calcium supplement (p?=?0.001).

Conclusions

Daily supplementation for a period of 6?months was associated with increased trabecular area, trabecular density and strength strain index at the ultra-distal tibia and radius and increased cortical area at tibial mid-shaft.     

Alterations of bone geometry, density, microarchitecture, and biomechanical properties in systemic lupus erythematosus on long-term glucocorticoid: a case–control study using HR-pQCT

Summary

Compared to controls, HR-pQCT at distal radius of SLE patients on chronic glucocorticoid (SLE/GC) revealed reduced bone area, vBMD, deteriorated microarchitecture, and unevenly distributed stresses limited to cortical bone. Despite similar trabecular quality, whole bone strength decreased in patients. These alterations may partly explain high fracture rates in SLE/GC.

Introduction

To assess bone geometric, densitometric, microarchitectural, and biomechanical properties in patients with systemic lupus erythematosus (SLE) on long-term glucocorticoid (GC) (SLE/GC) as compared with healthy controls.

Methods

A total of 180 female SLE patients and 180 healthy controls were in this cross-sectional study to assess areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry. High-resolution peripheral quantitative computed tomography (HR-pQCT) and microfinite element analysis (μFEA) was performed at distal radius.

Results

In addition to significantly lower aBMD at femoral neck, total hip and lumbar spine, cortical area, average volumetric BMD (vBMD) and cortical vBMD also significantly reduced by 5.3, 5.7, to 1.9 % in SLE patients, respectively. Deteriorations of cortical microarchitecture were pronounced in patients, with 6.3 % reduction in cortical thickness and 13.6 % higher in cortical porosity. Local stresses were more unevenly distributed through cortical bone in patients. SLE/GC patients had decreased whole bone stiffness, estimated failure load, and apparent modulus. Parameters related to trabecular bone density and microarchitecture were comparable between patients and controls.

Conclusion

In SLE/GC patients, despite a reduction in bone area, vBMD and deteriorated microarchitecture and unevenly distributed stresses limited to the cortical compartment, whole bone strength decreased. HR-pQCT and μFEA were promising in elucidating the potential underlying pathophysiology of bone loss and propensity to fracture in SLE/GC and provide us additional information about alterations of bone quality which might better predict fracture risk beyond aBMD in SLE/GC.     

Deterioration of trabecular plate-rod and cortical microarchitecture and reduced bone stiffness at distal radius and tibia in postmenopausal women with vertebral fractures

Postmenopausal women with vertebral fractures have abnormal bone microarchitecture at the distal radius and tibia by HR-pQCT, independent of areal BMD. However, whether trabecular plate and rod microarchitecture is altered in women with vertebral fractures is unknown. This study aims to characterize the abnormalities of trabecular plate and rod microarchitecture, cortex, and bone stiffness in postmenopausal women with vertebral fractures. HR-pQCT images of distal radius and tibia were acquired from 45 women with vertebral fractures and 45 control subjects without fractures. Trabecular and cortical compartments were separated by an automatic segmentation algorithm and subjected to individual trabecula segmentation (ITS) analysis for measuring trabecular plate and rod morphology and cortical bone evaluation for measuring cortical thickness and porosity, respectively. Whole bone and trabecular bone stiffness were estimated by finite element analysis. Fracture and control subjects did not differ according to age, race, body mass index, osteoporosis risk factors, or medication use. Women with vertebral fractures had thinner cortices, and larger trabecular area compared to the control group. By ITS analysis, fracture subjects had fewer trabecular plates, less axially aligned trabeculae and less trabecular connectivity at both the radius and the tibia. Fewer trabecular rods were observed at the radius. Whole bone stiffness and trabecular bone stiffness were 18% and 22% lower in women with vertebral fractures at the radius, and 19% and 16% lower at the tibia, compared with controls. The estimated failure load of the radius and tibia were also reduced in the fracture subjects by 13% and 14%, respectively. In summary, postmenopausal women with vertebral fractures had both trabecular and cortical microstructural deterioration at the peripheral skeleton, with a preferential loss of trabecular plates and cortical thinning. These microstructural deficits translated into lower whole bone and trabecular bone stiffness at the radius and tibia. Our results suggest that abnormalities in trabecular plate and rod microstructure may be important mechanisms of vertebral fracture in postmenopausal women.     

Increased cortical porosity in type 2 diabetic postmenopausal women with fragility fractures

The primary goal of this study was to assess peripheral bone microarchitecture and strength in postmenopausal women with type 2 diabetes with fragility fractures (DMFx) and to compare them with postmenopausal women with type 2 diabetics without fractures (DM). Secondary goals were to assess differences in nondiabetic postmenopausal women with fragility fractures (Fx) and nondiabetic postmenopausal women without fragility fractures (Co), and in DM and Co women. Eighty women (mean age 61.3 ± 5.7 years) were recruited into these four groups (DMFx, DM, Fx, and Co; n = 20 per group). Participants underwent dual‐energy X‐ray absorptiometry (DXA) and high‐resolution peripheral quantitative computed tomography (HR‐pQCT) of the ultradistal and distal radius and tibia. In the HR‐pQCT images volumetric bone mineral density and cortical and trabecular structure measures, including cortical porosity, were calculated. Bone strength was estimated using micro–finite element analysis (µFEA). Differential strength estimates were obtained with and without open cortical pores. At the ultradistal and distal tibia, DMFx had greater intracortical pore volume (+52.6%, p = 0.009; +95.4%, p = 0.020), relative porosity (+58.1%, p = 0.005; +87.9%, p = 0.011) and endocortical bone surface (+10.9%, p = 0.031; +11.5%, p = 0.019) than DM. At the distal radius DMFx had 4.7‐fold greater relative porosity (p < 0.0001) than DM. At the ultradistal radius, intracortical pore volume was significantly higher in DMFx than DM (+67.8%, p = 0.018). DMFx also displayed larger trabecular heterogeneity (ultradistal radius: +36.8%, p = 0.035), and lower total and cortical BMD (ultradistal tibia: ?12.6%, p = 0.031; ?6.8%, p = 0.011) than DM. DMFx exhibited significantly higher pore‐related deficits in stiffness, failure load, and cortical load fraction at the ultradistal and distal tibia, and the distal radius than DM. Comparing nondiabetic Fx and Co, we only found a nonsignificant trend with increase in pore volume (+38.9%, p = 0.060) at the ultradistal radius. The results of our study suggest that severe deficits in cortical bone quality are responsible for fragility fractures in postmenopausal diabetic women. © 2013 American Society for Bone and Mineral Research     

Women with previous fragility fractures can be classified based on bone microarchitecture and finite element analysis measured with HR-pQCT

Summary

High-resolution peripheral quantitative computed tomography (HR-pQCT) measurements of distal radius and tibia bone microarchitecture and finite element (FE) estimates of bone strength performed well at classifying postmenopausal women with and without previous fracture. The HR-pQCT measurements outperformed dual energy x-ray absorptiometry (DXA) at classifying forearm fractures and fractures at other skeletal sites.

Introduction

Areal bone mineral density (aBMD) is the primary measurement used to assess osteoporosis and fracture risk; however, it does not take into account bone microarchitecture, which also contributes to bone strength. Thus, our objective was to determine if bone microarchitecture measured with HR-pQCT and FE estimates of bone strength could classify women with and without low-trauma fractures.

Methods

We used HR-pQCT to assess bone microarchitecture at the distal radius and tibia in 44 postmenopausal women with a history of low-trauma fracture and 88 age-matched controls from the Calgary cohort of the Canadian Multicentre Osteoporosis Study (CaMos) study. We estimated bone strength using FE analysis and simulated distal radius aBMD from the HR-pQCT scans. Femoral neck (FN) and lumbar spine (LS) aBMD were measured with DXA. We used support vector machines (SVM) and a tenfold cross-validation to classify the fracture cases and controls and to determine accuracy.

Results

The combination of HR-pQCT measures of microarchitecture and FE estimates of bone strength had the highest area under the receiver operating characteristic (ROC) curve of 0.82 when classifying forearm fractures compared to an area under the curve (AUC) of 0.71 from DXA-derived aBMD of the forearm and 0.63 from FN and spine DXA. For all fracture types, FE estimates of bone strength at the forearm alone resulted in an AUC of 0.69.

Conclusion

Models based on HR-pQCT measurements of bone microarchitecture and estimates of bone strength performed better than DXA-derived aBMD at classifying women with and without prior fracture. In future, these models may improve prediction of individuals at risk of low-trauma fracture.     

Effects of Odanacatib on the Radius and Tibia of Postmenopausal Women: Improvements in Bone Geometry,Microarchitecture, and Estimated Bone Strength

The cathepsin K inhibitor odanacatib (ODN), currently in phase 3 development for postmenopausal osteoporosis, has a novel mechanism of action that reduces bone resorption while maintaining bone formation. In phase 2 studies, odanacatib increased areal bone mineral density (aBMD) at the lumbar spine and total hip progressively over 5 years. To determine the effects of ODN on cortical and trabecular bone and estimate changes in bone strength, we conducted a randomized, double‐blind, placebo‐controlled trial, using both quantitative computed tomography (QCT) and high‐resolution peripheral (HR‐p)QCT. In previously published results, odanacatib was superior to placebo with respect to increases in trabecular volumetric BMD (vBMD) and estimated compressive strength at the spine, and integral and trabecular vBMD and estimated strength at the hip. Here, we report the results of HR‐pQCT assessment. A total of 214 postmenopausal women (mean age 64.0 ± 6.8 years and baseline lumbar spine T‐score –1.81 ± 0.83) were randomized to oral ODN 50 mg or placebo, weekly for 2 years. With ODN, significant increases from baseline in total vBMD occurred at the distal radius and tibia. Treatment differences from placebo were also significant (3.84% and 2.63% for radius and tibia, respectively). At both sites, significant differences from placebo were also found in trabecular vBMD, cortical vBMD, cortical thickness, cortical area, and strength (failure load) estimated using finite element analysis of HR‐pQCT scans (treatment differences at radius and tibia = 2.64% and 2.66%). At the distal radius, odanacatib significantly improved trabecular thickness and bone volume/total volume (BV/TV) versus placebo. At a more proximal radial site, odanacatib attenuated the increase in cortical porosity found with placebo (treatment difference = –7.7%, p = 0.066). At the distal tibia, odanacatib significantly improved trabecular number, separation, and BV/TV versus placebo. Safety and tolerability were similar between treatment groups. In conclusion, odanacatib increased cortical and trabecular density, cortical thickness, aspects of trabecular microarchitecture, and estimated strength at the distal radius and distal tibia compared with placebo. © 2014 American Society for Bone and Mineral Research     

Alterations of bone microstructure and strength in end-stage renal failure

Summary

End-stage renal disease (ESRD) patients have a high risk of fractures. We evaluated bone microstructure and finite-element analysis-estimated strength and stiffness in patients with ESRD by high-resolution peripheral computed tomography. We observed an alteration of cortical and trabecular bone microstructure and of bone strength and stiffness in ESRD patients.

Introduction

Fragility fractures are common in ESRD patients on dialysis. Alterations of bone microstructure contribute to skeletal fragility, independently of areal bone mineral density.

Methods

We compared microstructure and finite-element analysis estimates of strength and stiffness by high-resolution peripheral quantitative computed tomography (HR-pQCT) in 33 ESRD patients on dialysis (17 females and 16 males; mean age, 47.0?±?12.6 years) and 33 age-matched healthy controls.

Results

Dialyzed women had lower radius and tibia cortical density with higher radius cortical porosity and lower tibia cortical thickness, compared to controls. Radius trabecular number was lower with higher heterogeneity of the trabecular network. Male patients displayed only a lower radius cortical density. Radius and tibia cortical thickness correlated negatively with bone-specific alkaline phosphatase (BALP). Microstructure did not correlate with parathyroid hormone (PTH) levels. Cortical porosity correlated positively with “Kidney Disease: Improving Global Outcomes” working group PTH level categories (r?=?0.36, p?<?0.04). BMI correlated positively with trabecular number (r?=?0.4, p?<?0.02) and negatively with trabecular spacing (r?=??0.37, p?<?0.03) and trabecular network heterogeneity (r?=??0.4, p?<?0.02). Biomechanics positively correlated with BMI and negatively with BALP.

Conclusion

Cortical and trabecular bone microstructure and calculated bone strength are altered in ESRD patients, predominantly in women. Bone microstructure and biomechanical assessment by HR-pQCT may be of major clinical relevance in the evaluation of bone fragility in ESRD patients.     

Assessment of trabecular and cortical architecture and mechanical competence of bone by high-resolution peripheral computed tomography: comparison with transiliac bone biopsy

Summary

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 (µCT). Apparent Young’s modulus, an estimate of mechanical competence or strength, was determined by micro-finite-element analysis (µFE) of biopsy µCT and HR-pQCT images.

Results

The strongest correlations observed were between trabecular parameters (bone volume fraction, number, separation) measured by µCT 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 µFE 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.     

Vertebral deformities and fractures are associated with MRI and pQCT measures obtained at the distal tibia and radius of postmenopausal women

Summary

We investigated the association of postmenopausal vertebral deformities and fractures with bone parameters derived from distal extremities using MRI and pQCT. Distal extremity measures showed variable degrees of association with vertebral deformities and fractures, highlighting the systemic nature of postmenopausal bone loss.

Introduction

Prevalent vertebral deformities and fractures are known to predict incident further fractures. However, the association of distal extremity measures and vertebral deformities in postmenopausal women has not been fully established.

Methods

This study involved 98 postmenopausal women (age range 60–88 years, mean 70 years) with DXA BMD T-scores at either the hip or spine in the range of ?1.5 to ?3.5. Wedge, biconcavity, and crush deformities were computed on the basis of spine MRI. Vertebral fractures were assessed using Eastell's criterion. Distal tibia and radius stiffness was computed using MRI-based finite element analysis. BMD at the distal extremities were obtained using pQCT.

Results

Several distal extremity MRI and pQCT measures showed negative association with vertebral deformity on the basis of single parameter correlation (r up to 0.67) and two-parameter regression (r up to 0.76) models involving MRI stiffness and pQCT BMD. Subjects who had at least one prevalent vertebral fracture showed decreased MRI stiffness (up to 17.9 %) and pQCT density (up to 34.2 %) at the distal extremities compared to the non-fracture group. DXA lumbar spine BMD T-score was not associated with vertebral deformities.

Conclusions

The association between vertebral deformities and distal extremity measures supports the notion of postmenopausal osteoporosis as a systemic phenomenon.     

Cortical and trabecular bone at the radius and tibia in male and female adolescents with Down syndrome: a peripheral quantitative computed tomography (pQCT) study

Summary

We aimed to describe the structure and strength of the tibia and radius of adolescents with Down syndrome. We observed that despite higher levels of volumetric bone mineral density in determined skeletal sites, they are at higher risk of developing osteoporotic fractures in the future due to their lower bone strength indexes.

Introduction

The aims of the study were to describe the cortical and trabecular volumetric bone mineral density (vBMD), bone mineral content (BMC), area, and bone strength in adolescents with Down syndrome (DS) and to compare them with adolescents without disabilities.

Methods

Thirty adolescents (11 girls) with DS and 28 without disabilities (10 girls) participated in the study. Peripheral quantitative computed tomography measurements were taken at proximal and distal sites of the tibia and radius. Values of total, trabecular, and cortical BMC; vBMD; and area were obtained of each scan. Cortical thickness and endosteal and periosteal circumferences were also measured, and different bone strength indexes were calculated. Student’s t tests were applied between groups.

Results

The DS group showed greater vBMD at distal radius, BMC at proximal radius, and total and cortical vBMD at proximal tibia. The non-DS group showed higher total and trabecular area at the distal radius and total, cortical, and trabecular BMC and area at distal tibia. Higher values of periosteal and endosteal circumference and bone strength were also found in non-DS group.

Conclusions

From these results, it can be believed that even with higher vBMD in determined skeletal sites, adolescents with DS are at higher risk of suffering bone fractures due to an increased fragility by lower resistance to load bending or torsion.     

Age-Related Changes in Bone Density,Microarchitecture, and Strength in Postmenopausal Black and White Women: The SWAN Longitudinal HR-pQCT Study

Higher fracture risk in White versus Black women is partly explained by lower BMD and worse bone microarchitecture in White women. However, whether rates of decline in bone density, microarchitecture and strength differ between postmenopausal Black and White women is unknown. Further, factors that influence rates of age-related bone microarchitecture deterioration remain ill-defined. Thus, over 6.7 years, longitudinal changes were measured in peripheral volumetric bone mineral density (vBMD), microarchitecture, and strength at the distal radius and tibia using HR-pQCT in postmenopausal Black (n = 80) and White (n = 137) women participating in the Study of Women's Health Across the Nation. It was assessed whether age-related changes in vBMD and microarchitecture were influenced by body weight, body composition, and/or weight change. It was found that at the radius, where White women appeared to have slightly greater rates of loss in total vBMD, cortical bone volume, and porosity than Black women, those differences were attenuated after adjusting for clinical covariates. At the tibia, Black and White women had similar rates of bone loss. Independent of race and other clinical covariates, women with the lowest baseline body weight experienced the greatest decline in total and trabecular vBMD at the radius. Furthermore, women who lost weight over the follow-up period had higher rates of bone loss, particularly at the tibia, compared with those who maintained or gained weight. Higher baseline total body fat mass was also protective of bone loss at both the radius and tibia. In conclusion, these findings indicate that lower fracture risk among postmenopausal Black women is not caused by slower rates of bone deterioration, and highlight the importance for postmenopausal women to avoid lower body weight and excessive weight loss to avert rapid bone loss and subsequent fractures. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Comparative effects of teriparatide and ibandronate on spine bone mineral density (BMD) and microarchitecture (TBS) in postmenopausal women with osteoporosis: a 2-year open-label study

Summary

Treatment effects over 2 years of teriparatide vs. ibandronate in postmenopausal women with osteoporosis were compared using lumbar spine bone mineral density (BMD) and trabecular bone score (TBS). Teriparatide induced larger increases in BMD and TBS compared to ibandronate, suggesting a more pronounced effect on bone microarchitecture of the bone anabolic drug.

Introduction

The trabecular bone score (TBS) is an index of bone microarchitecture, independent of bone mineral density (BMD), calculated from anteroposterior spine dual X-ray absorptiometry (DXA) scans. The potential role of TBS for monitoring treatment response with bone-active substances is not established. The aim of this study was to compare the effects of recombinant human 1–34 parathyroid hormone (teriparatide) and the bisphosphonate ibandronate (IBN), on lumbar spine (LS) BMD and TBS in postmenopausal women with osteoporosis.

Methods

Two patient groups with matched age, body mass index (BMI), and baseline LS BMD, treated with either daily subcutaneous teriparatide (N?=?65) or quarterly intravenous IBN (N?=?122) during 2 years and with available LS BMD measurements at baseline and 2 years after treatment initiation were compared.

Results

Baseline characteristics (overall mean ± SD) were similar between groups in terms of age 67.9?±?7.4 years, body mass index 23.8?±?3.8 kg/m², BMD L1–L4 0.741?±?0.100 g/cm², and TBS 1.208?±?0.100. Over 24 months, teriparatide induced a significantly larger increase in LS BMD and TBS than IBN (+7.6 %?±?6.3 vs. +2.9 %?±?3.3 and +4.3 %?±?6.6 vs. +0.3 %?±?4.1, respectively; P?<?0.0001 for both). LS BMD and TBS were only weakly correlated at baseline (r ²?=?0.04) with no correlation between the changes in BMD and TBS over 24 months.

Conclusions

In postmenopausal women with osteoporosis, a 2-year treatment with teriparatide led to a significantly larger increase in LS BMD and TBS than IBN, suggesting that teriparatide had more pronounced effects on bone microarchitecture than IBN.