Effects of zoledronate versus placebo on spine bone mineral density and microarchitecture assessed by the trabecular bone score in postmenopausal women with osteoporosis: A three‐year study

The trabecular bone score (TBS) is an index of bone microarchitectural texture calculated from anteroposterior dual‐energy X‐ray absorptiometry (DXA) scans of the lumbar spine (LS) that predicts fracture risk, independent of bone mineral density (BMD). The aim of this study was to compare the effects of yearly intravenous zoledronate (ZOL) versus placebo (PLB) on LS BMD and TBS in postmenopausal women with osteoporosis. Changes in TBS were assessed in the subset of 107 patients recruited at the Department of Osteoporosis of the University Hospital of Berne, Switzerland, who were included in the HORIZON trial. All subjects received adequate calcium and vitamin D3. In these patients randomly assigned to either ZOL (n = 54) or PLB (n = 53) for 3 years, BMD was measured by DXA and TBS assessed by TBS iNsight (v1.9) at baseline and 6, 12, 24, and 36 months after treatment initiation. Baseline characteristics (mean ± SD) were similar between groups in terms of age, 76.8 ± 5.0 years; body mass index (BMI), 24.5 ± 3.6 kg/m²; TBS, 1.178 ± 0.1 but for LS T‐score (ZOL–2.9 ± 1.5 versus PLB–2.1 ± 1.5). Changes in LS BMD were significantly greater with ZOL than with PLB at all time points (p < 0.0001 for all), reaching +9.58% versus +1.38% at month 36. Change in TBS was significantly greater with ZOL than with PLB as of month 24, reaching +1.41 versus–0.49% at month 36; p = 0.031, respectively. LS BMD and TBS were weakly correlated (r = 0.20) and there were no correlations between changes in BMD and TBS from baseline at any visit. In postmenopausal women with osteoporosis, once‐yearly intravenous ZOL therapy significantly increased LS BMD relative to PLB over 3 years and TBS as of 2 years. © 2013 American Society for Bone and Mineral Research.     

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.

     

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.

     

Bone involvement in aldosteronism

In rats with aldosteronism, a reduction of bone mineral density (BMD) and cortical bone strength has been reported. Our study was aimed to evaluate bone involvement in patients with primary aldosteronism (PA). A total of 188 consecutive subjects with adrenal incidentaloma, observed between November 2009 and October 2011, were screened for PA with aldosterone‐to‐renin ratio. After confirmatory tests, in those who screened positive, 11 patients were diagnosed as PA and 15 patients were not (nPA). A serum/urinary biochemical profile, parathyroid hormone (PTH), BMD measured at lumbar spine (LS) and total and femoral neck (TN and FN) by dual X‐ray absorptiometry, and conventional spinal radiographs (T₄–L₄) were obtained in all subjects. PA patients had a significantly higher 24‐hour urinary calcium (6.28 ± 1.85 versus 4.28 ± 1.18 mmol/d; p < 0.01), and PTH (9.8 [5.8‐14.6], median [range] versus 5.3 [2.5‐10.8] pmol/L; p < 0.01) than nPA patients. BMD expressed as Z‐value at LS (?1.18 ± 0.99 versus 0.22 ± 1.12), FN (?0.85 ± 0.73 versus 0.01 ± 0.82), and TN (?0.49 ± 0.61 versus 0.39 ± 0.93) was lower in PA than in nPA (p = 0.003, p = 0.011, and p = 0.012, respectively). The prevalence of osteoporosis was higher in PA than in nPA (8/11, 72.7% versus 3/15, 20.0%; Fisher's exact test: p = 0.015). Vertebral fractures tended to be more prevalent in PA than in nPA (5/11, 45.5% versus 2/15, 13.3%; Fisher's exact test: p = 0.095). Logistic regression analysis showed that osteoporosis and morphometric vertebral fractures were associated with PA (odds ratio [OR], 15.4; 95% confidence interval [CI] = 1.83–130, p = 0.012; and OR, 30.4; 95%CI, 1.07–862, p = 0.045, respectively) regardless of age, body mass index (BMI), and LS‐BMD. In 9 of 11 PA patients, 6 months after beginning of treatment (surgery or spironolactone) there was a significant reduction of urinary calcium excretion (p < 0.01) and PTH (p < 0.01), whereas in 5 of 11 PA patients, 1 year after beginning of treatment, BMD was significantly increased at LS, p < 0.01). In conclusion, PA is associated with osteoporosis, vertebral fractures, and increased urinary calcium excretion. © 2012 American Society for Bone and Mineral Research.     

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.

     

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.     

Sporadic and MEN1‐Related Primary Hyperparathyroidism: Differences in Clinical Expression and Severity

Primary hyperparathyroidism (PHPT) is a common endocrine disease that is associated with multiple endocrine neoplasia type 1 (MEN1) in ～2% of PHPT cases. Lack of a family history and other specific expressions may lead to underestimated MEN1 prevalence in PHPT. The aim of this study was to identify clinical or biochemical features predictive of MEN1 and to compare the severity of the disease in MEN1‐related versus sporadic PHPT (sPHPT). We performed a 36‐mo cross‐sectional observational study in three tertiary referral centers on an outpatient basis on 469 consecutive patients with sporadic PHPT and 64 with MEN1‐related PHPT. Serum calcium, phosphate, PTH, 25(OH)D₃, and creatinine clearance were measured, and ultrasound examination of the urinary tract/urography was performed in all patients. In 432 patients, BMD was measured at the lumbar spine (LS) and femoral neck (FN). MEN1 patients showed lower BMD Z‐scores at the LS (?1.33 ± 1.23 versus ?0.74 ± 1.4, p = 0.008) and FN (?1.13 ± 0.96 versus ?0.6 ± 1.07, p = 0.002) and lower phosphate (2.38 ± 0.52 versus 2.56 ± 0.45 mg/dl, p = 0.003) and PTH (113.8 ± 69.5 versus 173.7 ± 135 pg/ml, p = 0.001) levels than sPHPT patients. Considering probands only, the presence of MEN1 was more frequently associated with PTH values in the normal range (OR, 3.01; 95% CI, 1.07–8.50; p = 0.037) and younger age (OR, 1.61; 95% CI, 1.28–2.02; p = 0.0001). A combination of PTH values in the normal range plus age <50 yr was strongly associated with MEN1 presence (OR, 13.51; 95% CI, 3.62–50.00; p = 0.0001). In conclusion, MEN1‐related PHPT patients show more severe bone but similar kidney involvement despite a milder biochemical presentation compared with their sPHPT counterparts. Normal PTH levels and young age are associated with MEN1 presence.     

Overlapping and Continued Alendronate or Raloxifene Administration in Patients on Teriparatide: Effects on Areal and Volumetric Bone Mineral Density—The CONFORS Study

Nine month teriparatide (TPTD) monotherapy followed by co‐administration of raloxifene (RAL) or alendronate (ALN) for another nine 9 months resulted in incremental bone mineral density (BMD) increase. The aim of this study was to investigate the effects of continued antiresorptive treatments for 12 months in the extension phase. Postmenopausal women (n = 125) with severe osteoporosis on ongoing TPTD treatment for 9 months were randomized into three open‐label groups for another 9 months: ALN (70 mg/week, n = 41), RAL (60 mg/d, n = 37) in addition to TPTD or no additional medication (n = 47) except Ca and vitamin D. After discontinuation of TPTD the respective antiresorptives were continued for a further 12 months, while patients in the TPTD monotherapy group received Ca and vitamin D. Amino‐terminal propeptide of type I procollagen (P1NP) and cross‐linked C‐telopeptide (CTX), areal and volumetric BMD at the lumbar spine (LS) and hip were assessed. ALN resulted in continued BMD increase in LS (4.3 ± 1.5%; mean ± SD), femoral neck (4.2 ± 1.6%) and total hip (4 ± 1.6%; p < 0.001 for all), while RAL was only effective at the LS (2.4 ± 1.7%, p < 0.001) but no changes at the femoral neck (0.4 ± 1.4%) or total hip (?0.8 ± 1.5%) were observed. Cortical bone only increased in the ALN group (femoral neck 6.7 ± 2.7% and ?1.3 ± 2.5%; total hip 13.8 ± 2.9% and ?2.3 ± 2.5% for ALN and RAL, p < 0.001 for all; respectively). Analyzing the entire 30 months of therapy, the ALN group revealed the largest BMD increase in all regions. Our results suggest that the addition of ALN to ongoing TPTD and continuing ALN after TPTD was stopped may be beneficial for patients in terms of areal and volumetric BMD increase. Further research is warranted to determine the optimal timing of the initiation of the combination treatment, the respective antiresorptive medication and the potential benefit of this BMD increase regarding fracture prevention. © 2014 American Society for Bone and Mineral Research     

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.     

The Association Between Trabecular Bone Score and Lumbar Spine Volumetric BMD Is Attenuated Among Older Men With High Body Mass Index

Trabecular bone score (TBS) has been proposed as a dual‐energy X‐ray absorptiometry (DXA) derived measure of underlying quality of trabecular bone; however, TBS is not considered valid for those with body mass index (BMI) >37 kg/m². Our objective was to determine the association between TBS and lumbar spine (trabecular) volumetric BMD (LS‐VBMD) and to examine whether the association varied by BMI and body composition among older men below this clinical threshold. We used regression models to study 3479 men age ≥65 years enrolled in the Osteoporotic Fractures in Men (MrOS) study who had TBS from spine DXA scans, LS‐VBMD from central quantitative computed tomography, measures of trunk fat and lean mass from DXA, and BMI <37 kg/m². TBS was categorized as normal (n = 925), partially degraded (n = 1747), and degraded (n = 807). TBS was inversely related to BMI, trunk fat mass, and trunk lean mass (all p < 0.001). The relationship between TBS and LS‐VBMD was nonlinear with magnitude of effect (slope of regression line using standardized variables) ranging from 0.07 (95% CI, –0.02 to 0.15) among those with degraded TBS up to 0.71 (95% CI, 0.54 to 0.89) among those with normal TBS. The relationship was still nonlinear after adjusting for age, clinical site, and either BMI, trunk lean mass, or trunk fat mass. The magnitude of effect relating TBS and LS‐VBMD also decreased with increasing BMI (interaction, p = 0.090) and increasing trunk lean mass (interaction, p = 0.001), but not with increasing trunk fat mass (interaction, p = 0.224). In summary, the strength of the association between TBS and LS‐VBMD among older men was variable and dependent on BMI and body composition, particularly trunk lean mass. The clinical utility of TBS among older men may be somewhat limited among men with high BMI or high trunk lean mass. © 2016 American Society for Bone and Mineral Research.     

Bone marrow fat composition as a novel imaging biomarker in postmenopausal women with prevalent fragility fractures

The goal of this magnetic resonance (MR) imaging study was to quantify vertebral bone marrow fat content and composition in diabetic and nondiabetic postmenopausal women with fragility fractures and to compare them with nonfracture controls with and without type 2 diabetes mellitus. Sixty‐nine postmenopausal women (mean age 63 ± 5 years) were recruited. Thirty‐six patients (47.8%) had spinal and/or peripheral fragility fractures. Seventeen fracture patients were diabetic. Thirty‐three women (52.2%) were nonfracture controls. Sixteen women were diabetic nonfracture controls. To quantify vertebral bone marrow fat content and composition, patients underwent MR spectroscopy (MRS) of the lumbar spine at 3 Tesla. Bone mineral density (BMD) was determined by dual‐energy X‐ray absorptiometry (DXA) of the hip and lumbar spine (LS) and quantitative computed tomography (QCT) of the LS. To evaluate associations of vertebral marrow fat content and composition with spinal and/or peripheral fragility fractures and diabetes, we used linear regression models adjusted for age, race, and spine volumetric bone mineral density (vBMD) by QCT. At the LS, nondiabetic and diabetic fracture patients had lower vBMD than controls and diabetics without fractures (p = 0.018; p = 0.005). However, areal bone mineral density (aBMD) by DXA did not differ between fracture and nonfracture patients. After adjustment for age, race, and spinal vBMD, the prevalence of fragility fractures was associated with ?1.7% lower unsaturation levels (confidence interval [CI] ?2.8% to ?0.5%, p = 0.005) and +2.9% higher saturation levels (CI 0.5% to 5.3%, p = 0.017). Diabetes was associated with ?1.3% (CI –2.3% to ?0.2%, p = 0.018) lower unsaturation and +3.3% (CI 1.1% to 5.4%, p = 0.004) higher saturation levels. Diabetics with fractures had the lowest marrow unsaturation and highest saturation. There were no associations of marrow fat content with diabetes or fracture. Our results suggest that altered bone marrow fat composition is linked with fragility fractures and diabetes. MRS of spinal bone marrow fat may therefore serve as a novel tool for BMD‐independent fracture risk assessment.     

Deleterious Effect of Late Menarche on Distal Tibia Microstructure in Healthy 20‐Year‐Old and Premenopausal Middle‐Aged Women

Late menarche is a risk factor for fragility fractures. We hypothesized that pubertal timing–dependent alterations in bone structural components would persist from peak bone mass to menopause, independent of premenopausal bone loss. We studied the influence of menarcheal age (MENA) on femoral neck BMD (FN aBMD) by DXA and microstructure of distal tibia by HR‐pQCT in healthy young adult (YAD; 20.4 ± 0.6 [SD] yr, n = 124) and premenopausal middle‐aged (PREMENO; 45.8 ± 3.4 yr, n = 120) women. Median of MENA was 13.0 ± 1.2 and 13.1 ± 1.7 yr in YAD and PREMENO, respectively. In YAD and PREMENO (n = 244), FN aBMD (R = ?0.29, p = 0.013), as well as total volumetric BMD (Dtot; R = ?0.23, p = 0.006) and cortical thickness (Ct.Th; R = ?0.18, p = 0.011) of distal tibia were inversely correlated to MENA. After segregation by the median of MENA in EARLY and LATE subgroups, the significant influences of both MENA (p = 0.004) and chronological age (p < 0.0001) were observed for FN aBMD and trabecular bone volume fraction of the distal tibia with similar differences in T‐scores between LATE and EARLY subgroups in YAD (?0.36 and ?0.31 T‐scores) and PREMENO (?0.35 and ?0.42 T‐scores) women. Ct.Th was negatively influenced by MENA, whereas trabecular thickness (Tb.Th) was negatively influenced by chronological age. There was a striking inverse relationship between cross‐sectional area and Ct.Th (R = ?0.57, p < 0.001). In conclusion, the negative influence of late menarcheal age at weight‐bearing sites as observed by the end of skeletal growth remains unattenuated a few years before menopause and is independent of premenopausal bone loss. Alterations in both bone mineral mass and microstructural components may explain the increased risk of fragility fractures associated with later menarcheal age.     

The effects of zinc supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized,double‐blind,placebo‐controlled trial

This study was performed to determine the effects of zinc supplementation on wound healing and metabolic status in patients with diabetic foot ulcer. The current randomized, double‐blind, placebo‐controlled trial was conducted among 60 patients (aged 40–85 years old) with grade 3 diabetic foot ulcer. Participants were randomly divided into two groups (30 participants in each group) to take either 220 mg zinc sulfate supplements containing 50 mg elemental zinc or placebo daily for 12 weeks. After the 12‐week intervention, compared with the placebo, zinc supplementation was associated with significant reductions in ulcer length (?1.5 ± 0.7 vs. ?0.9 ± 1.2 cm, p = 0.02) and width (?1.4 ± 0.8 vs. ?0.8 ± 1.0 cm, p = 0.02). In addition, changes in fasting plasma glucose (?40.5 ± 71.0 vs. ?3.9 ± 48.5 mg/dl, p = 0.02), serum insulin concentration (?8.0 ± 15.4 vs. +1.1 ± 10.3 µIU/ml, p = 0.009), homeostasis model of assessment‐estimated insulin resistance (?3.9 ± 7.1 vs. +0.8 ± 5.9, p = 0.007), the quantitative insulin sensitivity check index (+0.01 ± 0.03 vs. ?0.002 ± 0.02, p = 0.04) and HbA1c (?0.5 ± 0.8 vs. ?0.1 ± 0.5%, p = 0.01) in the supplemented group were significantly different from the changes in these indicators in the placebo group. Additionally, significant increases in serum HDL‐cholesterol (+4.1 ± 4.3 vs. +1.1 ± 5.1 mg/dl, p = 0.01), plasma total antioxidant capacity (+91.7 ± 213.9 vs. ?111.9 ± 188.7 mmol/L, p < 0.01) and total glutathione (+68.1 ± 140.8 vs. ?35.0 ± 136.1 µmol/L, p = 0.006), and significant decreases in high sensitivity C‐reactive protein (?20.4 ± 24.6 vs. ?6.8 ± 21.3 µg/ml, p = 0.02) and plasma malondialdehyde concentrations (?0.6 ± 0.9 vs. ?0.2 ± 0.7 µmol/L, p = 0.03) were seen following supplementation with zinc compared with the placebo. Zinc supplementation for 12 weeks among diabetic foot ulcer patients had beneficial effects on parameters of ulcer size and metabolic profiles.     

Bone Loss After Bariatric Surgery: Discordant Results Between DXA and QCT Bone Density

Several studies, using dual‐energy X‐ray absorptiometry (DXA), have reported substantial bone loss after bariatric surgery. However, profound weight loss may cause artifactual changes in DXA areal bone mineral density (aBMD) results. Assessment of volumetric bone mineral density (vBMD) by quantitative computed tomography (QCT) may be less susceptible to such artifacts. We assessed changes in BMD of the lumbar spine and proximal femur prospectively for 1 year using DXA and QCT in 30 morbidly obese adults undergoing Roux‐en‐Y gastric bypass surgery and 20 obese nonsurgical controls. At 1 year, subjects who underwent gastric bypass surgery lost 37 ± 2 kg compared with 3 ± 2 kg lost in the nonsurgical controls (p < 0.0001). Spine BMD declined more in the surgical group than in the nonsurgical group whether assessed by DXA (?3.3 versus ?1.1%, p = 0.034) or by QCT (?3.4 versus 0.2%, p = 0.010). Total hip and femoral neck aBMD declined significantly in the surgical group when assessed by DXA (?8.9 versus ?1.1%, p < 0.0001 for the total hip and ?6.1 versus ?2.0%, p = 0.002 for the femoral neck), but no changes in hip vBMD were noted using QCT. Within the surgical group, serum P1NP and CTX levels increased by 82% ± 10% and by 220% ± 22%, respectively, by 6 months and remained elevated over 12 months (p < 0.0001 for all). Serum calcium, vitamin D, and PTH levels remained stable in both groups. We conclude that moderate vertebral bone loss occurs in the first year after gastric bypass surgery. However, striking declines in DXA aBMD at the proximal femur were not confirmed with QCT vBMD measurements. These discordant results suggest that artifacts induced by large changes in body weight after bariatric surgery affect DXA and/or QCT measurements of bone, particularly at the hip. © 2014 American Society for Bone and Mineral Research.     

Associations between dietary flavonoid intakes and bone health in a scottish population

Flavonoids are bioactive polyphenols found particularly in fruit and vegetables, but little is known about their role in bone health in humans. The aim of this observational study was to investigate whether dietary flavonoid intake was associated with bone mineral density (BMD) and bone resorption in a large group of perimenopausal Scottish women. Over 3000 women completed a food frequency questionnaire as part of an osteoporosis screening study. The diets were analyzed for flavonoid intake using a food composition database. BMD was measured at the femoral neck (FN) and lumbar spine (LS) by dual‐energy X‐ray absorptiometry (DXA). Free pyridinoline (PYD) and deoxypyridinoline (DPD) were measured by high‐performance liquid chromatography (HPLC) in second early morning fasted urine samples. The mean flavonoid intake of the diet was 307 ±199 mg/d. The catechin family contributed the most to flavonoid intakes (55%), and the flavones the least (<1%). Associations were found between energy‐adjusted total flavonoid intakes and BMD at the FN and LS (FN r = 0.054, LS r = 0.036, p ≤ .05). Annual percent change in BMD was associated with intakes of procyanidins and catechins (p ≤ .05), and flavanones were negatively associated with bone‐resorption markers (PYD r = ?0.049, DPD r = –0.057, p ≤ .001). These associations were still seen after adjusting for confounders. It is concluded that dietary flavonoid intakes are associated with BMD, supporting the evidence from animal and cellular studies. © 2011 American Society for Bone and Mineral Research.     

Use of risedronate to prevent bone loss following a single course of glucocorticoids: findings from a proof-of-concept study in inflammatory bowel disease

Summary

We performed a randomised controlled trial (RCT) to determine whether risedronate 35 mg once weekly prevents bone loss following an 8-week reducing course of prednisolone given for an exacerbation of inflammatory bowel disease (IBD). The greatest change in bone mineral density (BMD) was at Ward’s triangle (WT), which fell by 2.2% in the placebo group, compared with a reduction of 0.8% in the risedronate group.

Introduction

Whether bisphosphonates can prevent bone loss associated with intermittent glucocorticoid (GC) therapy is unknown, reflecting the difficulty in performing RCTs in this context.

Method

To explore the feasibility of RCTs to examine this question, lumbar spine (LS; L2–4) and hip dual X-ray absorptiometry (DXA) scans were performed in 78 patients commencing a GC therapy course for a relapse of IBD. They were then randomised to receive placebo or risedronate 35 mg weekly for 8 weeks, after which the DXA scan was repeated.

Results

For LS BMD, there was no change in the placebo group (0.1?±?0.4, p?=?0.9), but there was an increase after risedronate (0.8?±?0.4, p?=?0.04; mean%?±?SEM by paired Student’s t test). There were small decreases in both groups at the total hip (?0.5?±?0.3, p?=?0.04; ?0.5?±?0.3, p?<?0.05, placebo and risedronate, respectively). At WT, BMD fell after placebo (?2.2?±?0.5, p?=?0.001) but not risedronate (?0.8?±?0.5, p?=?0.09; p?=?0.05 for between-group comparison).

Conclusion

RCTs can be used to examine whether bisphosphonates prevent bone loss associated with intermittent GC therapy, providing metabolically active sites such as WT are employed as the primary outcome.     

Higher Milk Requirements for Bone Mineral Accrual in Adolescent Girls Bearing Specific Caucasian Genotypes in the VDR Promoter

Low milk intakes hamper bone mineral acquisition during adolescence, especially in European girls. We hypothesized that ethnic‐specific polymorphisms of the vitamin D receptor gene promoter (VDRp) influence this milk/bone association. We evaluated lumbar spine BMC and BMD, milk/dairy products and calcium intakes, markers of P‐Ca metabolism, and VDRp polymorphisms at the Cdx‐2 binding (rs11568820) and ?1012 (rs4516035) loci in 117 healthy European peri‐ and postmenarcheal girls (14.9 ± 1.6 yr) during a 4‐yr follow‐up. Calcium intakes from milk, nonmilk dairy products, and nondairy products averaged 199, 243, and 443 mg/d at the initiation of the study. Results show no association between milk intakes and bone mass accrual in girls bearing an A/A genotype at the ?1012 VDRp locus (30% of the cohort). In contrast, A/G or G/G girls had lower spine BMC (?13%, p = 0.031), BMD (?10%, p = 0.004), and BMD Z‐score (?0.84 SD, p = 0.0003) when their milk intakes were <260 ml/d compared with genotype‐matched girls with higher milk intakes and with girls with an A/A genotype. The negative impact of low milk intake persisted up to 19.0 ± 1.7 yr. These findings suggest that European girls bearing a ?1012 A/G or G/G VDRp genotype should have higher milk/calcium intakes for optimal vertebral mass accrual during adolescence than girls bearing an A/A genotype, a genotype found in 30% of European and 98% of Asian and Sub‐Saharan African populations. VDRp genotype diversity may contribute to the ethnic differences observed in milk requirements for bone health during adolescence.     

Advanced Vertebral Fracture Among Newly Diagnosed Children With Acute Lymphoblastic Leukemia: Results of the Canadian Steroid‐Associated Osteoporosis in the Pediatric Population (STOPP) Research Program

Vertebral compression is a serious complication of childhood acute lymphoblastic leukemia (ALL). The prevalence and pattern of vertebral fractures, as well as their relationship to BMD and other clinical indices, have not been systematically studied. We evaluated spine health in 186 newly diagnosed children (median age, 5.3 yr; 108 boys) with ALL (precursor B cell: N = 167; T cell: N = 19) who were enrolled in a national bone health research program. Patients were assessed within 30 days of diagnosis by lateral thoraco‐lumbar spine radiograph, bone age (also used for metacarpal morphometry), and BMD. Vertebral morphometry was carried out by the Genant semiquantitative method. Twenty‐nine patients (16%) had a total of 75 grade 1 or higher prevalent vertebral compression fractures (53 thoracic, 71%; 22 lumbar). Grade 1 fractures as the worst grade were present in 14 children (48%), 9 patients (31%) had grade 2 fractures, and 6 children (21%) had grade 3 fractures. The distribution of spine fracture was bimodal, with most occurring in the midthoracic and thoraco‐lumbar regions. Children with grade 1 or higher vertebral compression had reduced lumbar spine (LS) areal BMD Z‐scores compared with those without (mean ± SD, ?2.1 ± 1.5 versus ?1.1 ± 1.2; p < 0.001). LS BMD Z‐score, second metacarpal percent cortical area Z‐score, and back pain were associated with increased odds for fracture. For every 1 SD reduction in LS BMD Z‐score, the odds for fracture increased by 80% (95% CI: 10–193%); the presence of back pain had an OR of 4.7 (95% CI: 1.5–14.5). These results show that vertebral compression is an under‐recognized complication of newly diagnosed ALL. Whether the fractures will resolve through bone growth during or after leukemia chemotherapy remains to be determined.     

Smoking is associated with impaired bone mass development in young adult men: A 5-year longitudinal study

It has previously been shown that smoking is associated with reduced bone mass and increased fracture risk, but no longitudinal studies have been published investigating altered smoking behavior at the time of bone mass acquisition. The aim of this study was to investigate the development of bone density and geometry according to alterations in smoking behavior in a 5‐year, longitudinal, population‐based study of 833 young men, age 18 to 20 years (baseline). Furthermore, we aimed to examine the cross‐sectional, associations between current smoking and parameters of trabecular microarchitecture of the radius and tibia, using high‐resolution peripheral quantitative computed tomography (HR‐pQCT), in young men aged 23 to 25 years (5‐year follow‐up). Men who had started to smoke since baseline had considerably smaller increases in areal bone mineral density (aBMD) at the total body (mean ± SD, 0.020 ± 0.047 mg/cm² versus 0.043 ± 0.040 mg/cm², p < 0.01) and lumbar spine (0.027 ± 0.062 mg/cm² versus 0.052 ± 0.065 mg/cm², p = 0.04), and substantially greater decreases in aBMD at the total hip (?0.055 ± 0.058 mg/cm² versus ?0.021 ± 0.062 mg/cm², p < 0.01) and femoral neck (?0.077 ± 0.059 mg/cm² versus ?0.042 ± 0.070 mg/cm², p < 0.01) than men who were nonsmokers at both the baseline and follow‐up visits. At the tibia, subjects who had started to smoke had a smaller increment of the cortical cross‐sectional area (CSA) than nonsmokers (8.1 ± 4.3 mm² versus 11.5 ± 8.9 mm², p = 0.03), and a larger decrement of trabecular volumetric BMD (vBMD) than nonsmokers (?13.9 ± 20.5 mg/mm³ versus ?4.1 ± 13.9 mg/mm³, p < 0.001). In the cross‐sectional analysis at follow‐up (23–25 years of age), smokers had significantly lower trabecular vBMD at the tibia (7.0%, p < 0.01) due to reduced trabecular thickness (8.9%, p < 0.001), as assessed using HR‐pQCT, than nonsmokers. In conclusion, this study is the first to report that men who start to smoke in young adulthood have poorer development of their aBMD at clinically important sites such as the spine and hip than nonsmokers, possibly due to augmented loss of trabecular density and impaired growth of cortical cross‐sectional area. © 2012 American Society for Bone and Mineral Research.     

Impact of bone-active drugs and underlying disease on bone health after lung transplantation: A longitudinal study

Introductionthe effect of bone-active drugs on the risk of fragility fractures (Fx), bone mineral density (BMD) and trabecular bone score (TBS) changes in patients receiving lung transplantation (LTx) is largely unknown. This study assessed the bone-active drugs effect in patients undergoing LTx both with (CF) and without (nCF) cystic-fibrosis.MethodsWe evaluated incident Fx, both clinical and morphometric vertebral Fx by spinal X-ray, BMD and trabecular bone score (TBS) in 117 patients (CF=50, nCF n = 67) before and 24-months after LTx. A bone-active therapy was proposed to all LTx candidates.Results83.8% of patients started a bone-active drug. Lumbar-spine (LS) T-score improved significantly only in treated patients (-1.4 ± 1.0 vs -2.0±1.0, p = 0.0001), whereas femur BMD and TBS remained stable in treated and not treated subjects. The rate of incident Fx was 15.3%, with no difference between treated and not treated patients. After LTx, LS T-score improved significantly only in nCF group (-1.3 ± 1.0 vs -1.8 ± 1.1, p = 0.0001), while femur remained stable in both nCF and CF groups. Patients with CF showed a significant Z-TBS increase (-3.6 ± 1.7 vs -3.0 ± 1.7, p = 0.019) and a lower Fx incidence as compared with nCF patients (4.1% vs 24.2%, p  =0.003). Incident Fx were associated with nCF diagnosis (OR 7.300, CI95% 1.385–38.461, p = 0.019) regardless of prevalent Fx, previous glucocorticoid therapy and bone-active therapy introduced at least 6 months before LTx.ConclusionsA prompt medical intervention helps in preventing BMD loss after LTx. As compared with nCF patients, CF patients show a TBS increase and a lower Fx risk after LTx.