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.     

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.     

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.     

Accuracy of trabecular structure by HR-pQCT compared to gold standard μCT in the radius and tibia of patients with osteoporosis and long-term bisphosphonate therapy

Summary

Despite an increasing use of high-resolution peripheral quantitative computed tomography (HR-pQCT) to evaluate bone morphology in vivo, there are reservations about its applicability in patients with osteoporosis and antiresorptive therapy. This study shows that HR-pQCT provides acceptable in vivo accuracy for bone volume fraction (BV/TV) in patients with osteoporosis and bisphosphonate (BP) treatment.

Introduction

The primary aim was to analyze agreement of trabecular structure between HR-pQCT and gold standard microtomography (μCT) in patients with osteoporosis and long-term BP therapy.

Methods

In the BioAsset study, we analyzed cadaver radii and tibiae of 34 postmenopausal females (81.1?±?7.1 years) with osteoporosis (no BP n?=?22, 1–5 years BP n?=?5, >5 years BP n?=?7). Two HR-pQCT protocols (patient-mode and μCT-mode) were compared with gold standard μCT after image registration. Undecalcified histological sections were obtained to quantify nonmineralized bone matrix. Bland-Altman plots illustrated methodological agreement. Multiple regression analysis was used to test for variables associated with method agreement.

Results

In the radius and tibia, patient-mode HR-pQCT derived indices including bone volume fraction, trabecular number, and trabecular separation correlated well with gold standard μCT (R ²?=?0.78???0.88) except for trabecular thickness (R ²?=?0.11). Bland-Altman plots illustrated adequate agreement for bone volume fraction. Lower agreement of trabecular number and trabecular separation improved with decreasing structural impairment at the tibia only. Trabecular thickness was not appropriately assessed with HR-pQCT at both skeletal sites. Higher agreement for bone volume fraction was associated with increasing tissue mineral density in the tibia.

Conclusions

HR-pQCT provides acceptable in vivo accuracy for BV/TV in patients with osteoporosis and BP treatment. Higher TMD was associated with higher BV/TV accuracy in vivo. Overall, methodological agreement got less accurate with increasing structural impairment in the tibia.     

Characterizing microarchitectural changes at the distal radius and tibia in postmenopausal women using HR-pQCT

Summary

Limited prospective evidence exists regarding bone microarchitectural deterioration. We report annual changes in trabecular and cortical bone microarchitecture at the distal radius and tibia in postmenopausal women. Lost trabeculae with corresponding increase in trabecular thickness at the radius and thinning tibial cortex indicated trabecularization of the cortex at both sites.

Introduction

Osteoporosis is characterized by low bone mass and the deterioration of bone microarchitecture. However, limited prospective evidence exists regarding bone microarchitectural changes in postmenopausal women: a population prone to sustaining osteoporotic fractures. Our primary objective was to characterize the annual change in bone area, density, and microarchitecture at the distal radius and distal tibia in postmenopausal women.

Methods

Distal radius and tibia were measured using high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline and 1 year later in 51 women (mean age?±?SD, 77?±?7 years) randomly sampled from the Saskatoon cohort of the Canadian Multicentre Osteoporosis Study (CaMos). We used repeated measures analysis of variance (ANOVA) with Bonferroni adjustment for multiple comparisons to characterize the mean annual change in total density, cortical perimeter, trabecular and cortical bone area, density, content, and microarchitecture. Significant changes were accepted at P?<?0.05.

Results

At the distal radius in women without bone-altering drugs, total density (?1.7 %) and trabecular number (?6.4 %) decreased, while trabecular thickness (+6.0 %), separation (+8.6 %), and heterogeneity (+12.1 %) increased. At their distal tibia, cortical area (?4.5 %), density (?1.9 %), content (?6.3 %), and thickness (?4.4 %) decreased, while trabecular area (+0.4 %) increased.

Conclusions

The observed loss of trabeculae with concomitant increase in trabecular size at the distal radius and the declined cortical thickness, density, and content at the distal tibia indicated a site-specific trabecularization of the cortical bone in postmenopausal women.     

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.     

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.     

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.     

Sport-specific association between exercise loading and the density, geometry, and microstructure of weight-bearing bone in young adult men

Summary

In this population-based study of 24-year-old men, we have investigated the association between sport-specific exercise loading and different bone parameters. We reveal that the association between exercise loading and bone parameters is sport-specific, indicating that nonspecific resistance exercise does not impact bone density, geometry, or microstructure in young men.

Introduction

In this cross-sectional study, the association between nonspecific resistive exercise and areal and volumetric bone density, bone geometry, or bone microstructure was investigated in young adult men.

Methods

A total of 184 male athletes, 24.0?±?0.6 years of age (mean?±?SD), representing nonspecific resistive exercise and soccer (proportion of recreational athletes, 93.4 and 7.7 %, respectively), and 177 nonathletic age-matched controls were measured with dual-energy X-ray absorptiometry. Radius and tibia were measured by peripheral quantitative computed tomography (pQCT) at the diaphysis and by three-dimensional pQCT at the metaphysis.

Results

Men in the nonspecific resistive exercise group had higher grip strength(9.1 % or 0.4 SD) and higher lean mass(5.6 % or 0.5 SD) than those in the nonathletic group(p?<?0.01 and p?<?0.001, respectively). However, men who participated in nonspecific resistive exercise did not have higher bone density or a more favorable bone microstructure or geometry than their nonathletic referents. In contrast, men playing soccer had higher areal bone mineral density (aBMD) at the femoral neck (19.5 % or 1.2 SD) and lumbar spine (12.6 % or 1.0 SD), as well as larger cortical cross-sectional area (16.4 % or 1.1 SD) and higher trabecular bone volume fraction (14.5 % or 0.9 SD), as a result of increased trabecular number (8.7 % or 0.6 SD) and thickness (5.7 % or 0.4 SD) at the tibia than men in the nonathletic group(p?<?0.001).

Conclusions

Weight-bearing exercise with impacts from varying directions (playing soccer) is associated with aBMD and volumetric BMD, cortical bone geometry, as well as trabecular microstructure of weight-bearing bone. Nonspecific recreational resistance exercise does not appear to be a strong determinant of bone density, geometry, or microstructure in young adult men.     

Bone impairment assessed by HR-pQCT in juvenile-onset systemic lupus erythematosus

Summary

High-resolution peripheral quantitative computed tomography (HR-pQCT) analysis of female juvenile-onset systemic lupus erythematosus (JoSLE) patients revealed trabecular/cortical bone damage and reduced bone strength primarily at the distal radius compared to healthy controls. We demonstrated for the first time that JoSLE patients with vertebral fracture (VF) present trabecular impairment at the distal radius.

Introduction

This study investigated the volumetric bone mineral density (vBMD), microarchitecture, and biomechanical features at the distal radius and tibia using HR-pQCT and laboratory bone markers in JoSLE patients compared to controls to determine whether this method discriminates JoSLE patients with or without VF.

Methods

We compared 56 female JoSLE patients to age- and Tanner-matched healthy controls. HR-pQCT was performed at the distal radius and tibia. Serum levels of the amino-terminal pro-peptide of type I collagen, the C-terminal telopeptide of type I collagen, intact parathormone, sclerostin, and 25-hydroxyvitamin D (25OHD) were evaluated. VFs were analyzed using VFA-dual-energy X-ray absorptiometry (DXA) (Genant’s method).

Results

Reduced density and strength parameters and microarchitecture alterations of cortical and trabecular bones were observed in JoSLE patients compared to controls, primarily at the distal radius (p?<?0.05). Patients with VF exhibited a significant decrease in trabecular bone parameters solely at the distal radius (Total.BMD, p?=?0.034; Trabecular.BMD [Tb.BMD], p?=?0.034; bone volume (BV)/trabecular volume (TV), p?=?0.034; apparent modulus, p?=?0.039) and higher scores for disease damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI), p?=?0.002). Bone metabolism markers were similar in all groups. Logistic regression analysis of parameters that were significant in univariate analysis revealed that Tb.BMD (OR 0.98, 95 % CI 0.95–0.99, p?=?0.039) and SLICC/ACR-DI (OR 7.37, 95 % CI 1.75–30.97, p?=?0.006) were independent risk factors for VF.

Conclusion

In conclusion, this study is the first demonstration of bone microstructure and strength deficits in JoSLE patients, particularly at the distal radius. Our results demonstrated that VF was associated with trabecular radius alteration and emphasized the potential detrimental effect of disease damage on this condition.

     

Young adults with cystic fibrosis have altered trabecular microstructure by ITS-based morphological analysis

Summary

Young adults with cystic fibrosis have compromised plate-like trabecular microstructure, altered axial alignment of trabeculae, and reduced connectivity between trabeculae that may contribute to the reduced bone strength and increased fracture risk observed in this patient population.

Introduction

The risk of fracture is increased in patients with cystic fibrosis (CF). Individual trabecular segmentation (ITS)-based morphological analysis of high-resolution peripheral quantitative computed tomography (HR-pQCT) images segments trabecular bone into individual plates and rods of different alignment and connectivity, which are important determinants of trabecular bone strength. We sought to determine whether alterations in ITS variables are present in patients with CF and may help explain their increased fracture risk.

Methods

Thirty patients with CF ages 18–40 years underwent DXA scans of the hip and spine and HR-pQCT scans of the radius and tibia with further assessment of trabecular microstructure by ITS. These CF patients were compared with 60 healthy controls matched for age (±2 years), race, and gender.

Results

Plate volume fraction, thickness, and density as well as plate-plate and plate-rod connectivity were reduced, and axial alignment of trabeculae was lower in subjects with CF at both the radius and the tibia (p?<?0.05 for all). At the radius, adjustment for BMI eliminated most of these differences. At the tibia, however, reductions in plate volume fraction and number, axially aligned trabeculae, and plate-plate connectivity remained significant after adjustment for BMI alone and for BMI and aBMD (p?<?0.05 for all).

Conclusions

Young adults with CF have compromised plate-like and axially aligned trabecular morphology and reduced connectivity between trabeculae. ITS analysis provides unique information about bone integrity, and these trabecular deficits may help explain the increased fracture risk in adults with CF not accounted for by BMD and/or traditional bone microarchitecture measurements.

     

Clinical cone beam computed tomography compared to high-resolution peripheral computed tomography in the assessment of distal radius bone

Summary

Clinical cone beam computed tomography (CBCT) was compared to high-resolution peripheral quantitative computed tomography (HR-pQCT) for the assessment of ex vivo radii. Strong correlations were found for geometry, volumetric density, and trabecular structure. Using CBCT, bone architecture assessment was feasible but compared to HR-pQCT, trabecular parameters were overestimated whereas cortical ones were underestimated.

Introduction

HR-pQCT is the most widely used technique to assess bone microarchitecture in vivo. Yet, this technology has been only applicable at peripheral sites, in only few research centers. Clinical CBCT is more widely available but quantitative assessment of the bone structure is usually not performed. We aimed to compare the assessment of bone structure with CBCT (NewTom 5G, QR, Verona, Italy) and HR-pQCT (XtremeCT, Scanco Medical AG, Brüttisellen, Switzerland).

Methods

Twenty-four distal radius specimens were scanned with these two devices with a reconstructed voxel size of 75 μm for Newtom 5G and 82 μm for XtremeCT, respectively. A rescaling-registration scheme was used to define the common volume of interest. Cortical and trabecular compartments were separated using a semiautomated double contouring method. Density and microstructure were assessed with the HR-pQCT software on both modality images.

Results

Strong correlations were found for geometry parameters (r?=?0.98–0.99), volumetric density (r?=?0.91–0.99), and trabecular structure (r?=?0.94–0.99), all p?<?0.001. Correlations were lower for cortical microstructure (r?=?0.80–0.89), p?<?0.001. However, absolute differences were observed between modalities for all parameters, with an overestimation of the trabecular structure (trabecular number, 1.62?±?0.37 vs. 1.47?±?0.36 mm^?1) and an underestimation of the cortical microstructure (cortical porosity, 3.3?±?1.3 vs. 4.4?±?1.4 %) assessed on CBCT images compared to HR-pQCT images.

Conclusions

Clinical CBCT devices are able to analyze large portions of distal bones with good spatial resolution and limited irradiation. However, compared to dedicated HR-pQCT, the assessment of microarchitecture by NewTom 5G dental CBCT showed some discrepancies, for density measurements mainly. Further technical developments are required to reach optimal assessment of bone characteristics.

     

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.     

Bone quality assessment in type 2 diabetes mellitus

Summary

The increased risk for fractures in type 2 diabetes mellitus (T2DM) despite higher average bone density is unexplained. This study assessed trabecular bone quality in T2DM using the trabecular bone score (TBS). The salient findings are that TBS is decreased in T2DM and low TBS associates with worse glycemic control.

Introduction

Type 2 diabetes mellitus is a risk factor for osteoporotic fractures despite high average bone mineral density (BMD). The aim of this study was to compare BMD with a noninvasive assessment of trabecular microarchitecture, TBS, in women with T2DM.

Methods

In a cross-sectional study, trabecular microarchitecture was examined in 57 women with T2DM and 43 women without diabetes, ages 30 to 90 years. Lumbar spine BMD was measured by dual-emission x-ray absorptiometry (DXA), and TBS was calculated by examining pixel variations within the DXA images utilizing TBS iNsight software.

Results

Mean TBS was lower in T2DM (1.228?±?0.140 vs. 1.298?±?0.132, p?=?0.013), irrespective of age. Mean BMD was higher in T2DM (1.150?±?0.172 vs. 1.051?±?0.125, p?=?0.001). Within the T2DM group, TBS was higher (1.254?±?0.148) in subjects with good glycemic control (A1c?≤?7.5 %) compared to those (1.166?±?0.094; p?=?0.01) with poor glycemic control (A1c?>?7.5 %).

Conclusion

In T2DM, TBS is lower and associated with poor glycemic control. Abnormal trabecular microarchitecture may help explain the paradox of increased fractures at a higher BMD in T2DM. Further studies are needed to better understand the relationship between glycemic control and trabecular bone quality.     

Association between bone indices assessed by DXA,HR-pQCT and QCT scans in post-menopausal women

Quantitative computed tomography (QCT), high-resolution peripheral QCT (HR-pQCT) and dual X-ray absorptiometry (DXA) scans are commonly used when assessing bone mass and structure in patients with osteoporosis. Depending on the imaging technique and measuring site, different information on bone quality is obtained. How well these techniques correlate when assessing central as well as distal skeletal sites has not been carefully assessed to date. One hundred and twenty-five post-menopausal women aged 56–82 (mean 63) years were studied using DXA scans (spine, hip, whole body and forearm), including trabecular bone score (TBS), QCT scans (spine and hip) and HR-pQCT scans (distal radius and tibia). Central site measurements of areal bone mineral density (aBMD) by DXA and volumetric BMD (vBMD) by QCT correlated significantly at the hip (r = 0.74, p < 0.01). Distal site measurements of density at the radius as assessed by DXA and HR-pQCT were also associated (r = 0.74, p < 0.01). Correlations between distal and central site measurements of the hip and of the tibia and radius showed weak to moderate correlation between vBMD by HR-pQCT and QCT (r = ?0.27 to 0.54). TBS correlated with QCT at the lumbar spine (r = 0.35) and to trabecular indices of HR-pQCT at the radius and tibia (r = ?0.16 to 0.31, p < 0.01). There was moderate to strong agreement between measuring techniques when assessing the same skeletal site. However, when assessing correlations between central and distal sites, the associations were only weak to moderate. Our data suggest that the various techniques measure different characteristics of the bone, and may therefore be used in addition to rather than as a replacment for imaging in clinical practice.     

Lower leg arterial calcification assessed by high-resolution peripheral quantitative computed tomography is associated with bone microstructure abnormalities in women

Summary

In older women, the presence of lower leg arterial calcification assessed by high-resolution peripheral quantitative computed tomography is associated with relevant bone microstructure abnormalities at the distal tibia and distal radius.

Introduction

Here, we report the relationships of bone geometry, volumetric bone mineral density (BMD) and bone microarchitecture with lower leg arterial calcification (LLAC) as assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT).

Methods

We utilized the Hertfordshire Cohort Study (HCS), where we were able to study associations between measures obtained from HR-pQCT of the distal radius and distal tibia in 341 participants with or without LLAC. Statistical analyses were performed separately for women and men. We used linear regression models to investigate the cross-sectional relationships between LLAC and bone parameters.

Results

The mean (SD) age of participants was 76.4 (2.6) and 76.1 (2.5)?years in women and men, respectively. One hundred and eleven of 341 participants (32.6 %) had LLAC that were visible and quantifiable by HR-pQCT. The prevalence of LLAC was higher in men than in women (46.4 % (n?=?83) vs. 17.3 % (n?=?28), p?<?0.001). After adjustment for confounding factors, we found that women with LLAC had substantially lower Ct.area (β?=??0.33, p?=?0.016), lower Tb.N (β?=??0.54, p?=?0.013) and higher Tb.Sp (β?=?0.54, p?=?0.012) at the distal tibia and lower Tb.Th (β?=??0.49, p?=?0.027) at the distal radius compared with participants without LLAC. Distal radial or tibial bone parameter analyses in men according to their LLAC status revealed no significant differences with the exception of Tb.N (β?=?0.27, p?=?0.035) at the distal tibia.

Conclusion

In the HCS, the presence of LLAC assessed by HR-pQCT was associated with relevant bone microstructure abnormalities in women. These findings need to be replicated and further research should study possible pathophysiological links between vascular calcification and osteoporosis.

     

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).     

Exploring the determinants of fracture risk among individuals with spinal cord injury

Summary

In this cross-sectional study, we found that areal bone mineral density (aBMD) at the knee and specific tibia bone geometry variables are associated with fragility fractures in men and women with chronic spinal cord injury (SCI).

Introduction

Low aBMD of the hip and knee regions have been associated with fractures among individuals with chronic motor complete SCI; however, it is unclear whether these variables can be used to identify those at risk of fracture. In this cross-sectional study, we examined whether BMD and geometry measures are associated with lower extremity fragility fractures in individuals with chronic SCI.

Methods

Adults with chronic [duration of injury?≥?2 years] traumatic SCI (C1-L1 American Spinal Cord Injury Association Impairment Scale A-D) reported post injury lower extremity fragility fractures. Dual-energy X-ray absorptiometry (DXA) was used to measure aBMD of the hip, distal femur, and proximal tibia regions, while bone geometry at the tibia was assessed using peripheral quantitative computed tomography (pQCT). Logistic regression and univariate analyses were used to identify whether clinical characteristics or bone geometry variables were associated with fractures.

Results

Seventy individuals with SCI [mean age (standard deviation [SD]), 48.8 (11.5); 20 females] reported 19 fragility fractures. Individuals without fractures had significantly greater aBMD of the hip and knee regions and indices of bone geometry. Every SD decrease in aBMD of the distal femur and proximal tibia, trabecular volumetric bone mineral density, and polar moment of inertia was associated with fracture prevalence after adjusting for motor complete injury (odds ratio ranged from 3.2 to 6.1).

Conclusion

Low knee aBMD and suboptimal bone geometry are significantly associated with fractures. Prospective studies are necessary to confirm the bone parameters reported to predict fracture risk in individuals with low bone mass and chronic SCI.     

Sclerostin and Pref-1 have differential effects on bone mineral density and strength parameters in adolescent athletes compared with non-athletes

Summary

Excessive exercise can have detrimental effects on bone; however, the mechanisms leading to bone loss are not well understood. Sclerostin and preadipocyte factor (Pref)-1 are two hormones which inhibit bone formation. The present study demonstrates that these hormones may have differential effects in athletes as compared to non-athletes.

Introduction

Exercise activity is common in female adolescents, however, excessive exercise can have detrimental effects on bone mineral density (BMD). Mechanisms underlying this decrease in bone mass are not well understood. We investigated the effects of sclerostin, a potent inhibitor of bone formation via WNT signaling inhibition, and Pref-1, a suppressor of osteoblast differentiation, on BMD, bone turnover markers and bone strength in adolescent athletes.

Methods

We studied 50 adolescents between 15–21 years of age: 17 amenorrheic athletes (AA), 17 eumenorrheic athletes (EA), and 16 nonathletic controls (NA). We measured spine and hip BMD by dual energy x-ray absorptiometry and estimated failure load and stiffness at the distal radius and tibia using micro-finite element analysis. We also measured fasting sclerostin, Pref-1, N-terminal propeptide of type 1 procollagen, and C-terminal collagen cross-links levels.

Results

Sclerostin levels were higher in AA and EA compared with NA (AA: 0.42?±?0.15 ng/mL, EA: 0.44?±?0.09 ng/mL, NA: 0.33?±?0.14 ng/mL; p?=?0.047). In EA, sclerostin was positively associated with lumbar spine (LS) BMD and its Z-score (R?=?0.52, p?=?0.03 and R?=?0.55, p?=?0.02, respectively) whereas in NA, sclerostin was inversely associated with LS BMD (R?=??0.61, p?=?0.01). Pref-1 levels were similar in all three groups and there were significant inverse associations between Pref-1, BMD, and estimated bone strength in NA.

Conclusions

Sclerostin and Pref-1 may have differential effects on bone in adolescent athletes compared to non-athletes.     

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.