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.     

Chronic hemodialysis is associated with lower trabecular bone score,independent of bone mineral density: a case-control study

Summary

We measured trabecular bone score (TBS) in 98 patients on permanent hemodialysis (HD) and 98 subjects with similar bone mineral density and normal kidney function. TBS was significantly lower in HD patients, indicating deteriorated bone microarchitecture, independent of bone mass. This might partially explain the increased fracture risk in HD.

Purpose

In the general population, trabecular bone score (TBS) was shown to predict fracture independent of bone mineral density (BMD). In end-stage renal disease patients on hemodialysis (HD), the value of TBS is beyond that of BMD in currently unclear. Our aim was to assess lumbar spine (LS) TBS in HD patients compared with subjects with normal kidney function matched for age, sex, and LS BMD.

Methods

We assessed TBS and LS and femoral neck (FN) BMD in 98 patient on permanent HD (42.8% males; mean age 57.5?±?11.3 years; dialysis vintage 5.5?±?3.8 years) and 98 control subjects (glomerular filtration rate?>?60 mL/min) using DXA. We simultaneously controlled for sex, age (±?3 years), and LS BMD (±?0.03 g/cm²).

Results

HD patients had significantly lower LS TBS (0.07 [95% CI 0.03–0.1]; p?=?0.0004), TBS T-score (0.83 SD [95% CI 0.42–1.24]; p?=?0.0001)) and TBS Z-score (0.81 SD [95% CI 0.41–1.20]; p?=?0.0001) than matched controls. TBS significantly correlated with LS BMD in both HD patients (r?=?0.382; p?=?0.001) and controls (r?=?0.36; p?=?0.002). The two regression lines had similar slopes (0.3 vs. 0.28; p?=?0.84) with different intercepts (0.88 vs. 0.98). TBS adjustment significantly increased the 10-year fracture risk from 3.7 to 5.3 for major osteoporotic fracture and from 0.9 to 1.5 for hip fracture.

Conclusions

HD patients have lower TBS than controls matched for LS BMD, indicating altered bone microarchitecture. Also, the magnitude of TBS reduction in HD patients is constant at any LS BMD. Adjustment for TBS partially corrects the absolute 10-year fracture risk.

     

The utility of lumbar spine trabecular bone score and femoral neck bone mineral density for identifying asymptomatic vertebral fractures in well-compensated type 2 diabetic patients

Summary

The objective of the study was to evaluate the usefulness of trabecular bone score (TBS) and bone mineral density (BMD) for identifying vertebral fractures (VFx) in well-compensated type 2 diabetic (T2D) patients. TBS and femoral neck BMD below certain cutoffs may be useful for identifying VFx in well-compensated T2D patients.

Introduction

In T2D, the prevalence of VFx is increased, especially in poorly compensated and complicated diabetic patients. The possibility of predicting the fracture risk in T2D patients by measuring BMD and TBS, an indirect parameter of bone quality, is under debate. Therefore, the objective was to evaluate the usefulness of TBS and BMD for identifying VFx in well-compensated T2D patients.

Methods

Ninety-nine T2D postmenopausal women in good metabolic control (glycosylated haemoglobin 6.8?±?0.7 %) and 107 control subjects without T2D were evaluated. In all subjects, we evaluated the following: the BMD at the lumbar spine (LS) and the femoral neck (FN); the TBS by dual X-ray absorptiometry; and VFx by radiography. In T2D subjects, the presence of diabetic retinopathy, neuropathy, and nephropathy was evaluated.

Results

T2D subjects had increased VFx prevalence (34.3 %) as compared to controls (18.7 %) (p?=?0.01). T2D subjects presented higher BMD (LS ?0.8?±?1.44, FN ?1.06?±?1.08), as compared to controls (LS ?1.39?±?1.28, p?=?0.002; FN ?1.45?±?0.91, p?=?0.006, respectively). TBS was not different between diabetics and controls. In fractured T2D patients, LS-BMD, FN-BMD, and TBS were reduced (?1.2?±?1.44; ?1.44?±?1.04; 1.072?±?0.15) and the prevalence of retinopathy (15.4 %) was increased than in nonfractured T2D subjects (?0.59?±?1.4, p?=?0.035; ?0.87?±?1.05, p?=?0.005; 1.159?±?0.15, p?=?0.006; 1.8 %, p?=?0.04, respectively). The combination of TBS ≤1.130 and FN-BMD less than ?1.0 had the best diagnostic accuracy for detecting T2D fractured patients (SP 73.8 %, SN 63.6 %, NPV 78.9 %, PPV 56.8 %).

Conclusions

TBS and FN-BMD below certain cutoffs may be useful for identifying VFx in well-compensated T2D patients.

     

Trabecular bone score improves fracture risk prediction in non-osteoporotic women: the OFELY study

Summary

The use of areal bone mineral density (aBMD) for fracture prediction may be enhanced by considering bone microarchitectural deterioration. Trabecular bone score (TBS) helped in redefining a significant subset of non-osteoporotic women as a higher risk group.

Introduction

TBS is an index of bone microarchitecture. Our goal was to assess the ability of TBS to predict incident fracture.

Methods

TBS was assessed in 560 postmenopausal women from the Os des Femmes de Lyon cohort, who had a lumbar spine (LS) DXA scan (QDR 4500A, Hologic) between years 2000 and 2001. During a mean follow-up of 7.8?±?1.3 years, 94 women sustained 112 fragility fractures.

Results

At the time of baseline DXA scan, women with incident fracture were significantly older (70?±?9 vs. 65?±?8 years) and had a lower LS_aBMD and LS_TBS (both ?0.4SD, p?<?0.001) than women without fracture. The magnitude of fracture prediction was similar for LS_aBMD and LS_TBS (odds ratio [95 % confidence interval]?=?1.4 [1.2;1.7] and 1.6 [1.2;2.0]). After adjustment for age and prevalent fracture, LS_TBS remained predictive of an increased risk of fracture. Yet, its addition to age, prevalent fracture, and LS_aBMD did not reach the level of significance to improve the fracture prediction. When using the WHO classification, 39 % of fractures occurred in osteoporotic women, 46 % in osteopenic women, and 15 % in women with T-score?>??1. Thirty-seven percent of fractures occurred in the lowest quartile of LS_TBS, regardless of BMD. Moreover, 35 % of fractures that occurred in osteopenic women were classified below this LS_TBS threshold.

Conclusion

In conclusion, LS_aBMD and LS_TBS predicted fractures equally well. In our cohort, the addition of LS_TBS to age and LS_aBMD added only limited information on fracture risk prediction. However, using the lowest quartile of LS_TBS helped in redefining a significant subset of non-osteoporotic women as a higher risk group which is important for patient management.     

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.     

Effects of anti-resorptive agents on trabecular bone score (TBS) in older women

Summary

We evaluated the longitudinal effects of anti-resorptive agents (534 treated women vs. 1,150 untreated) on lumbar spine bone mineral density (BMD) and trabecular bone score (TBS). TBS was responsive to treatment in women over age 50. The treatment-related increase in TBS was less than the increase in BMD, which is consistent with bone texture preservation.

Introduction

In addition to inducing an increase in BMD, anti-resorptive agents also help to preserve bone architecture. TBS, a new gray-level texture measurement, correlates with 3D parameters of bone micro-architecture independent of BMD. Our objective was to evaluate the longitudinal effects of anti-resorptive agents on lumbar spine BMD and TBS.

Methods

Women (≥50 years), from the BMD program database for the province of Manitoba, Canada, who had not received any anti-resorptive drug prior to their initial dual X-ray absorptiometry (DXA) exam were divided into two groups: untreated, those without any anti-resorptive drug over the course of follow-up, and treated, those with a non-estrogen anti-resorptive drug (86 % bisphosphonates, 10 % raloxifene, and 4 % calcitonin). Lumbar spine TBS was calculated for each lumbar spine DXA examination. Changes in TBS and BMD between baseline and follow-up (mean follow-up 3.7 years), expressed in percentage per year, were compared between the two groups.

Results

A total of 1,150 untreated women and 534 treated women met the inclusion criteria. Only a weak correlation was seen between BMD and TBS in either group. Significant intergroup differences in BMD change and TBS change were observed over the course of follow-up (p?<?0.001). Similar mean decreases in BMD and TBS (?0.36 %/year and ?0.31 %/year, respectively) were seen for untreated subjects (both p?<?0.001). Conversely, treated subjects exhibited a significant mean increase in BMD (+1.86 %/year, p?<?0.002) and TBS (+0.20 %/year, p?<?0.001).

Conclusion

TBS is responsive to treatment with non-estrogen anti-resorptive drug therapy in women over age 50. The treatment-related increase in TBS is less than the increase in BMD, which is consistent with bone texture preservation.     

Changes in Bone Mineral Density After Sleeve Gastrectomy or Gastric Bypass: Relationships with Variations in Vitamin D,Ghrelin, and Adiponectin Levels

Background

A major long-term concern after gastric bypass (GBP) is the risk of osteoporosis; however, little is known about this complication in patients undergoing sleeve gastrectomy (SG).

Objective

To evaluate changes in bone mineral density (BMD) after GBP and SG, and its relationship with changes in vitamin D, parathyroid hormone (PTH), ghrelin, and adiponectin.

Methods

Twenty-three women undergoing GBP (BMI 42.0?±?4.2 kg/m²; 37.3?±?8.1 years) and 20 undergoing SG (BMI 37.3?±?3.2 kg/m²; 34.2?±?10.2 years) were studied before and 6 and 12 months after surgery. BMD was measured by dual-energy X-ray absorptiometry. Plasma PTH, 25-hydroxyvitamin D (25-OHD), ghrelin, and adiponectin concentrations were determined. Food as well as calcium and vitamin D supplement intake was recorded.

Results

Excess weight loss (mean?±?SE), adjusted by baseline excess weight, was 79.1±3.8 % and 74.9?±?4.1 % 1 year after GBP and SG, respectively (p?=?0.481). Significant reduction in BMD for total body (TB), lumbar spine (LS), and femoral neck (FN) was observed after GBP. In the SG group, reduction in BMD was significant only for TB. Adjusted by baseline BMD, the difference between change in BMD for GBP vs. SG was not significant for TB, LS, or FN. Percent reduction in ghrelin concentration was a main factor related to total BMD loss (GBP group) and LS BMD loss (GBP and SG groups).

Conclusions

One year after gastric bypass, bone mineral density was significantly affected, mainly at the femoral neck. Decreases in bone mineral density were more dramatic among patients who had greater baseline BMD and greater reduction in ghrelin concentrations.     

Bone involvement in adult patients affected with Ehlers-Danlos syndrome.

Summary

The Ehlers-Danlos syndrome is characterized by abnormal connective tissue but bone involvement is debated. We found a reduced BMD and bone quality and increased prevalence of asymptomatic vertebral fractures in eugonadal patients with Ehlers-Danlos syndrome. These findings suggest the need of a bone health evaluation in these patients.

Introduction

The Ehlers-Danlos (EDS) syndrome is characterized by abnormalities of the connective tissue leading to ligamentous laxity and skin and tissue fragility. We evaluated the bone metabolism, bone mineral density (BMD) and bone quality (measured by trabecular bone score, TBS), and the prevalence of vertebral fractures (VFx) in a group of eugonadal adult EDS patients.

Methods

Fifty consecutive Caucasian patients, aged 30–50 years (36 females, 14 males) with classical or hypermobility EDS and 50 age-, gender-, and body mass index (BMI)-matched control subjects were enrolled. In all subjects’ calcium-phosphorous metabolism, bone turnover, BMD at the lumbar spine (LS) and femur (femoral neck, FN and total femur, FT) and TBS by dual-energy X-ray absorptiometry, and the VFx presence by spine radiograph were assessed.

Results

Patients showed reduced BMD (Z-scores LS ?0.45?±?1.00, FN ?0.56?±?1.01, FT ?0.58?±?0.92) and TBS (1.299?±?0.111) and increased prevalence of morphometric VFx (32 %) than controls (Z-scores LS 0.09?±?1.22, FN 0.01?±?0.97, FT 0.08?±?0.89; TBS 1.382?±?0.176; VFx 8 %, p <0.05 for all comparisons), while vitamin D levels, calcium-phosphorous metabolism, and bone turnover were comparable. Fractured EDS patients showed lower TBS values than non-fractured ones (1.245?±?0.138 vs 1.325?±?0.086, p?<?0.05), despite comparable BMD. In EDS patients, the VFx presence was significantly associated with TBS even after adjusting for sex, age, BMD, EDS type, and falls frequency.

Conclusions

EDS patients have reduced BMD and bone quality (as measured by TBS) and increased prevalence of VFx.

     

Skeletal findings in the first 12 months following initiation of glucocorticoid therapy for pediatric nephrotic syndrome

Summary

Incident vertebral fractures and lumbar spine bone mineral density (BMD) were assessed in the 12 months following glucocorticoid initiation in 65 children with nephrotic syndrome. The incidence of vertebral fractures was low at 12 months (6 %) and most patients demonstrated recovery in BMD Z-scores by this time point.

Introduction

Vertebral fracture (VF) incidence following glucocorticoid (GC) initiation has not been previously reported in pediatric nephrotic syndrome.

Methods

VF was assessed on radiographs (Genant method); lumbar spine bone mineral density (LS BMD) was evaluated by dual-energy X-ray absorptiometry.

Results

Sixty-five children were followed to 12 months post-GC initiation (median age, 5.4 years; range, 2.3–17.9). Three of 54 children with radiographs (6 %; 95 % confidence interval (CI), 2–15 %) had incident VF at 1 year. The mean LS BMD Z-score was below the healthy average at baseline (mean ± standard deviation (SD), ?0.5?±?1.1; p?=?0.001) and at 3 months (?0.6?±?1.1; p?<?0.001), but not at 6 months (?0.3?±?1.3; p?=?0.066) or 12 months (?0.3?±?1.2; p?=?0.066). Mixed effect modeling showed a significant increase in LS BMD Z-scores between 3 and 12 months (0.22 SD; 95 % CI, 0.08 to 0.36; p?=?0.003). A subgroup (N?=?16; 25 %) had LS BMD Z-scores that were ≤?1.0 at 12 months. In these children, each additional 1,000 mg/m² of GC received in the first 3 months was associated with a decrease in LS BMD Z-score by 0.39 at 12 months (95 % CI, ?0.71 to ?0.07; p?=?0.017).

Conclusions

The incidence of VF at 1 year was low and LS BMD Z-scores improved by 12 months in the majority. Twenty-five percent of children had LS BMD Z-scores ≤?1.0 at 12 months. In these children, LS BMD Z-scores were inversely associated with early GC exposure, despite similar GC exposure compared to the rest of the cohort.     

Impact of smoking on bone mineral density and bone metabolism in elderly men: the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) study

Summary

Our cross-sectional analysis of 1,576 men aged ??65?years examined smoking effects on bone status. Number of smoking years was associated with decreased bone mineral density (BMD), after adjusting for age, height, weight, and number of cigarettes smoked daily. Smoking did not affect biochemical marker serum values for bone turnover.

Introduction

The impact of smoking on bone status in men has not been conclusively established. We examined how smoking and its cessation influence bone status and metabolism in men.

Methods

We analyzed 1,576 men among a baseline survey of Japanese men aged ??65?years, the Fujiwara-kyo Osteoporosis Risk in Men study, conducted during 2007?C2008.

Results

Lumbar spine (LS) BMD values among never, former, and current smokers were 1.045?±?0.194, 1.030?±?0.189, and 1.001?±?0.182?g/cm² (P?=?0.005), respectively, while total hip (TH) BMD values were 0.888?±?0.120, 0.885?±?0.127, and 0.870?±?0.124 (P?=?0.078), respectively. The significant trend for LS BMD remained after adjusting for the covariates; age, height, weight, physical activity, milk consumption, and drinking habit (P?=?0.036). Among never and ever (current and former) smokers, LS and TH BMD decreased with the number of pack years or the number of smoking years, respectively, adjusted for those covariates. Among ever smokers, LS and TH BMD decreased with the number of smoking years after adjusting for age, height, weight, and number of cigarettes smoked daily. Smoking did not reveal significant effect for serum osteocalcin or tartrate resistant acid phosphatase isoenzyme 5b.

Conclusion

The impact of smoking on bone status is mainly associated with the number of smoking years in elderly men.     

Circulating irisin is associated with osteoporotic fractures in postmenopausal women with low bone mass but is not affected by either teriparatide or denosumab treatment for 3 months

Summary

In vitro data suggest that myokine irisin may affect bone metabolism by promoting osteoblast differentiation while inhibiting osteoclast differentiation. In this study, circulating irisin levels were associated with previous osteoporotic fractures but not with bone mass and were not affected by denosumab or teriparatide treatment for 3 months.

Introduction

This study aimed to evaluate predictors of circulating irisin in postmenopausal women with low bone mass and to assess a potential effect of denosumab or teriparatide treatment for 3 months.

Methods

Serum samples for irisin measurement were obtained from (a) postmenopausal women with low bone mass (lumbar spinal [LS] or femoral neck [FN] bone mineral density [BMD] T-score ≤?2.0) and their age-matched controls at baseline and 3 months after denosumab (Dmab) injection (Dmab group, n?=?50; Dmab control group, n?=?25) and (b) women with more severe disease (LS or FN BMD T-score ≤?2.8) and their age-matched controls at the above-mentioned time points after teriparatide (TPTD) initiation (TPTD group, n?=?25; TPTD control group, n?=?25).

Results

At baseline, irisin levels were inversely correlated with age (partial coefficient (r _p )?=??0.24; p?=?0.009), parathyroid hormone (PTH) (r _p ?=??0.30; p?=?0.001), and creatinine (r _p ?=??0.23; p?=?0.016) in univariate analysis, and were lower in women with (n?=?26; 41.6?±?2.7 ng/dL) than without previous osteoporotic fracture(s) (n?=?99; 51.0?±?1.6 ng/dL; p?=?0.007). In multiple linear regression, previous osteoporotic fracture(s) and PTH were independently negatively associated with irisin [p?=?0.04, CI ?16.1 to ?0.4 and p?=?0.002, CI ?0.3 to ?0.07, respectively], but only the association with PTH remained after controlling for creatinine levels. Serum irisin levels were not different between women with or without low bone mass and were not affected by either Dmab or TPTD treatment for 3 months.

Conclusions

Circulating irisin levels were associated with previous osteoporotic fracture(s); whether this association is independent or is due to confounding by lower muscle mass, potentially reflected by lower creatinine levels, remains to be fully clarified.     

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.     

The predictive value of trabecular bone score (TBS) on whole lumbar vertebrae mechanics: an ex vivo study

Summary

We investigated the association of trabecular bone score (TBS) with microarchitecture and mechanical behavior of human lumbar vertebrae. We found that TBS reflects vertebral trabecular microarchitecture and is an independent predictor of vertebral mechanics. However, the addition of TBS to areal BMD (aBMD) did not significantly improve prediction of vertebral strength.

Introduction

The trabecular bone score (TBS) is a gray-level measure of texture using a modified experimental variogram which can be extracted from dual-energy X-ray absorptiometry (DXA) images. The current study aimed to confirm whether TBS is associated with trabecular microarchitecture and mechanics of human lumbar vertebrae, and if its combination with BMD improves prediction of fracture risk.

Methods

Lumbar vertebrae (L3) were harvested fresh from 16 donors. The anteroposterior and lateral bone mineral content (BMC) and areal BMD (aBMD) of the vertebral body were measured using DXA; then, the TBS was extracted using TBS iNsight software (Medimaps SA, France). The trabecular bone volume (Tb.BV/tissue volume, TV), trabecular thickness (Tb.Th), degree of anisotropy, and structure model index (SMI) were measured using microcomputed tomography. Quasi-static uniaxial compressive testing was performed on L3 vertebral bodies to assess failure load and stiffness.

Results

The TBS was significantly correlated to Tb.BV/TV and SMI (r?=?0.58 and ?0.62; p?=?0.02, 0.01), but not related to BMC and BMD. TBS was significantly correlated with stiffness (r?=?0.64; p?=?0.007), independently of bone mass. Using stepwise multiple regression models, we failed to demonstrate that the combination of BMD and TBS was better at explaining mechanical behavior than either variable alone. However, the combination TBS, Tb.Th, and BMC did perform better than each parameter alone, explaining 79 % of the variability in stiffness.

Conclusions

In our study, TBS was associated with microarchitecture parameters and with vertebral mechanical behavior, but TBS did not improve prediction of vertebral biomechanical properties in addition to aBMD.     

Bone mineral density (BMD) and vertebral trabecular bone score (TBS) for the identification of elderly women at high risk for fracture: the SEMOF cohort study

Purpose

To determine the predictive value of the vertebral trabecular bone score (TBS) alone or in addition to bone mineral density (BMD) with regard to fracture risk.

Methods

Retrospective analysis of the relative contribution of BMD [measured at the femoral neck (FN), total hip (TH), and lumbar spine (LS)] and TBS with regard to the risk of incident clinical fractures in a representative cohort of elderly post-menopausal women previously participating in the Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture Risk study.

Results

Complete datasets were available for 556 of 701 women (79 %). Mean age 76.1 years, LS BMD 0.863 g/cm², and TBS 1.195. LS BMD and LS TBS were moderately correlated (r ² = 0.25). After a mean of 2.7 ± 0.8 years of follow-up, the incidence of fragility fractures was 9.4 %. Age- and BMI-adjusted hazard ratios per standard deviation decrease (95 % confidence intervals) were 1.58 (1.16–2.16), 1.77 (1.31–2.39), and 1.59 (1.21–2.09) for LS, FN, and TH BMD, respectively, and 2.01 (1.54–2.63) for TBS. Whereas 58 and 60 % of fragility fractures occurred in women with BMD T score ≤?2.5 and a TBS <1.150, respectively, combining these two thresholds identified 77 % of all women with an osteoporotic fracture.

Conclusions

Lumbar spine TBS alone or in combination with BMD predicted incident clinical fracture risk in a representative population-based sample of elderly post-menopausal women.

     

Added value of trabecular bone score over bone mineral density for identification of vertebral fractures in patients with areal bone mineral density in the non-osteoporotic range

Summary

Detection of patients with vertebral fracture is similar for areal bone mineral density (aBMD) and trabecular bone score (TBS) in patients with non-vertebral fracture. In non-osteoporotic patients, TBS adds information to lumbar spine aBMD and is related to an index of spine deterioration.

Introduction

Vertebral fractures (VFs) are more predictive of future fracture than aBMD. The number and severity of VFs are related to microarchitecture deterioration. TBS has been shown to be related to microarchitecture. The study aimed at evaluating TBS in the prediction of the presence and severity of VFs.

Methods

Patients were selected from a Fracture Liaison Service (FLS): aBMD and vertebral fracture assessment (VFA) were assessed after the fracture, using dual-energy X-ray-absorptiometry (DXA). VFs were classified using Genant's semiquantitative method and severity, using the spinal deformity index (SDI). TBS was obtained after analysis of DXA scans. Performance of TBS and aBMD was assessed using areas under the curves (AUCs).

Results

A total of 362 patients (77.3 % women; mean age 74.3?±?11.7 years) were analysed. Prevalence of VFs was 36.7 %, and 189 patients (52.2 %) were osteoporotic. Performance of TBS was similar to lumbar spine (LS) aBMD and hip aBMD for the identification of patients with VFs. In the population with aBMD in the non-osteoporotic range (n?=?173), AUC of TBS for the discrimination of VFs was higher than the AUC of LS aBMD (0.670 vs 0.541, p?=?0.035) but not of hip aBMD; there was a negative correlation between TBS and SDI (r?=??0.31; p?<?0.0001).

Conclusion

Detection of patients with vertebral fracture is similar for aBMD and TBS in patients with non-vertebral fracture. In patients with aBMD in the non-osteoporotic range, TBS adds information to lumbar spine aBMD alone and is related to an index of spine deterioration.     

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.     

An algorithm using the early changes in PINP to predict the future BMD response for patients treated with daily teriparatide

Summary

About two thirds of patients with a procollagen type I N-terminal propeptide (PINP) increase of >80 μg/l at 1 month after starting teriparatide therapy showed a ≥10 % increase in lumbar spine (LS) bone mineral density (BMD) from baseline at 12 months. We recommend this algorithm as an aid in the clinical management of patients treated with daily teriparatide.

Introduction

An algorithm using PINP is provided in osteoporotic patients with teriparatide treatment. The correlations between the early changes in PINP and the subsequent BMD changes after daily teriparatide therapy were studied to develop an algorithm to monitor patients.

Methods

We evaluated whether early changes in PINP correlated with the changes in BMD at 12 months and developed an algorithm using the early changes in PINP to predict the upcoming BMD increases.

Results

The highest correlation coefficient for the relationship between PINP and LS BMD response was determined for the absolute change in PINP at 1 month and the percent change in LS BMD at 12 months (r?=?0.36, p <0.01). Using a receiver operator curve analysis, we determined that an 80 μg/l increase in PINP was the most convenient predictor of a 10 % increase in LS BMD from baseline (area under curve?=?0.72). Using a cut-off value of 80 μg/l, the positive predictive value for predicting a 10 % increase in LS BMD from baseline to 12 months was 65 %.

Conclusion

Greater short-term changes in PINP with teriparatide therapy are associated with greater 12-month increases in LS BMD. About two thirds of patients with a PINP increase of >80 μg/l at 1 month after starting treatment showed a ≥10 % increase in LS BMD from baseline at 12 months. We recommend this algorithm as an aid in the clinical management of patients treated with teriparatide.     

Cold-activated brown adipose tissue is an independent predictor of higher bone mineral density in women

Summary

In animals, defective brown adipogenesis leads to bone loss. Whether brown adipose tissue (BAT) mass relates to bone mineral density (BMD) in humans is unclear. We determined the relationship between BAT mass and BMD by cold-stimulated positron-emission tomography (PET) and dual-energy X-ray absorptiometry (DXA) in healthy volunteers. Higher BAT mass was associated with higher BMD in healthy women, but not in men, independent of age and body composition.

Introduction

Contrary to the traditional belief that BAT is present only in infants, recent studies revealed significant depots of BAT present in adult humans. In animals, defective brown adipogenesis leads to bone loss. While white adipose tissue mass is a known determinant of BMD in humans, the relationship between BAT and BMD in humans is unclear. We thus examined the relationship between BAT and BMD in healthy adults.

Methods

BAT volume (ml) and activity (standard uptake value) were determined by ¹⁸F-fluorodeoxyglucose PET after overnight mild cold exposure at 19 °C, and BMD was determined by DXA.

Results

Among 24 healthy adults (age 28?±?1 years, F?=?10), BAT volumes were 82.4?±?99.5 ml in women and 49.7?±?54.5 ml in men. Women manifested significantly higher BAT activity, by 9.4?±?8.1 % (p?=?0.03), than men. BAT volume correlated positively with total and spine BMD (r ²?=?0.40 and 0.49, respectively, p?<?0.02) in women and remained a significant predictor after adjustment for age, fat, and lean body mass (p?<?0.05). Total and spine BMD were higher in women who harbored visually detectable BAT on PET images than those without by 11?±?2 % (p?=?0.02) and 22?±?2 % (p?<?0.01), respectively. No associations were observed between BAT parameters and BMD in men.

Conclusions

This study demonstrated higher BMD among healthy women with more abundant BAT, independent of age and other body compositional parameters. This was not observed in men. The data suggest that brown adipogenesis may be physiologically related to modulation of bone density.     

Impact + resistance training improves bone health and body composition in prematurely menopausal breast cancer survivors: a randomized controlled trial

Summary

Our randomized controlled trial in prematurely menopausal breast cancer survivors showed that impact + resistance training prevented increases in percentage of body fat compared with controls and also improved BMD at the hip and prevented BMD loss at the spine among exercise-trained women who were menopausal for >1 year.

Introduction

Cancer treatment-related menopause worsens bone health and body composition in breast cancer survivors (BCS). We investigated whether impact + resistance training could improve bone mineral density (BMD), reduce bone turnover, build muscle, and decrease fat mass in BCS with premature menopause.

Methods

We conducted a randomized controlled trial in 71 BCS (mean age, 46.5 years) within 5 years of treatment-related menopause. Women were randomly assigned to one of two groups: (1) impact + resistance training (prevent osteoporosis with impact + resistance (POWIR)) or (2) exercise placebo (FLEX) 3×/week for 1 year. Outcomes were hip and spine BMD (in grams per square centimeter) and body composition (percent body fat (%BF) and lean and fat mass (in kilograms)) by DXA and bone turnover markers (serum osteocalcin (in nanograms per milliliter) and urinary deoxypryrodinoline (in nanomoles per milliliter).

Results

There were no significant group × time interactions for bone outcomes when using an intent-to-treat approach on the full sample. In analyses restricted to BCS who were menopausal for ≥1 year, POWIR increased BMD at the hip and slowed BMD loss at the spine compared with FLEX (femoral neck—POWIR, 0.004?±?0.093 g/cm² vs. FLEX, ?0.010?±?0.089 g/cm²; p?<?0.01; spine—POWIR, ?0.003?±?0.114 g/cm² vs. FLEX, ?0.020?±?0.110 g/cm²; p?=?0.03). POWIR prevented increases in %BF (POWIR, 0.01 % vs. FLEX, 1.3 %; p?<?0.04). Women with attendance to POWIR at ≥64 % had better improvements in %BF than women attending less often (p?<?0.03).

Conclusion

Impact + resistance training may effectively combat bone loss and worsening body composition from premature menopause in BCS.     

Bone status and fractures in 85 adults with Wilson’s disease

Summary

Wilson’s disease is characterized by copper deposition, especially in the liver and central nervous system. We assessed the prevalent fractures and bone mineral density (BMD) and related risk factors in 85 patients. BMD was normal, but patients with severe neurological involvement, low BMI, and/or amenorrhea are at risk for fractures.

Introduction

Wilson’s disease (WD) is characterized by copper deposition, especially in the liver and central nervous system. Two studies showed a high prevalence of osteoporosis in WD patients. We wanted to assess the prevalent fractures and bone mineral density (BMD) and to identify risk factors for bone loss and fractures in a large group of WD patients.

Methods

In this prospective cross-sectional survey at National center of reference for WD, we included 85 patients, 47 women, and 38 men, with a mean age of 35?±?10 years, and mean time from diagnosis to study of 21?±?9 years; 57 (67 %) patients had neurological signs. Peripheral fractures, prevalent radiological vertebral fractures (VFx), and dual-energy X-ray absorptiometry BMD measurements at the femoral neck (FN) and lumbar spine (LS) were studied.

Results

Mean LS and FN Z-score was normal (?0.37?±?1.20 at LS and ?0.06?±?1.20 at FN). BMI <19 kg/m² and amenorrhea were associated with low BMD. Prevalent peripheral fractures were noted in 43 (51 %) and VF in 7 (8 %) patients. Severity of neurological involvement and male sex was associated with peripheral fractures, whereas older age, severe neurological involvement, and low BMD and Z-score values were associated with VF.

Conclusion

Our data showing normal BMD overall do not support routine bone status evaluation in adults with WD. However, patients with severe neurological involvement, low BMI, and/or amenorrhea are at risk factors for fractures and may require specific monitoring.