Severity of aortic calcification is positively associated with vertebral fracture in older men—a densitometry study in the STRAMBO cohort

Summary

In older men, severe abdominal aortic calcification and vertebral fracture (both assessed using dual-energy X-ray absorptiometry) were positively associated after adjustment for confounders including bone mineral density.

Introduction

Abdominal aortic calcification (AAC) is associated with higher fracture risk, independently of low bone mineral density (BMD). Dual-energy X-ray absorptiometry (DXA) can be used to assess both vertebral fracture and AAC and requires less time, cost, and radiation exposure.

Methods

We conducted a cross-sectional study of the association between AAC and prevalent vertebral fractures in 901 men ≥50 years old. We used DXA (vertebral fracture assessment) to evaluate BMD, vertebral fracture, and AAC.

Results

Prevalence of vertebral fracture was 11 %. Median AAC score was 1 and 12 % of men had AAC score >6. After adjustment for age, weight, femoral neck BMD, smoking, ischemic heart disease, diabetes, and hypertension, AAC score >6 (vs ≤6) was associated with 2.5 (95 % CI, 1.4–4.5) higher odds of vertebral fracture. Odds of vertebral fracture for AAC score >6 increased with vertebral fracture severity (grade 1, OR?=?1.8; grade 2, OR?=?2.4; grade 3, OR?=?4.4; trend p?<?0.01) and with the number of vertebral fractures (1 fracture, OR?=?2.0, >1 fracture, OR?=?3.5). Prevalence of vertebral fracture was twice as high in men having both a T-score?<??2.0 and an AAC score?>?6 compared with men having only one of these characteristics.

Conclusions

Men with greater severity AAC had greater severity and greater number of vertebral fractures, independently of BMD and co-morbidities. DXA can be used to assess vertebral fracture and AAC. It can provide a rapid, safe, and less expensive alternative to radiography. DXA may be an important clinical tool to identify men at high risk of adverse outcomes from osteoporosis and cardiovascular disease.     

Diffuse idiopathic skeletal hyperostosis (DISH): relation to vertebral fractures and bone density

Summary

Radiographs and spinal bone mineral density (BMD) were evaluated from 342 elderly men regarding possible effects of diffuse idiopathic skeletal hyperostosis (DISH) on vertebral fractures and densitometry measurements. Prevalent vertebral fractures were more frequent among men with DISH compared to men with no DISH even after fracture prevalence was adjusted for BMD. Paravertebral calcifications should be considered in patients with DISH when interpreting BMD measurements because both dual X-ray absorptiometry (DXA) and quantitative CT (QCT) densitometry may not be reliable.

Introduction

The purpose of this study is to evaluate the prevalence of DISH in older men and its association with vertebral fractures and with BMD determined by DXA and QCT.

Methods

Lateral radiographs of the spine were analyzed in a sample of 342 men aged ??65?years participating in the MrOS Study concerning the presence and grade of DISH and vertebral fractures. Lumbar BMD was measured by both DXA (areal, grams per square centimeter) and QCT (volumetric, grams per cubic centimeter). The association between DISH, BMD, and presence of fractures was studied using ?? ² and t tests.

Results

DISH was present in 52% (178/342) of the men. Men with DISH were older (mean, 75.1 vs 73.3, p?<?0.05) and more likely to have prevalent fractures (28% vs 20%, p?<?p?=?0.09). BMD assessed with DXA (1.08 vs 1.00?g/cm², p????0.0001), but not with QCT (0.11 vs 0.11?g/cm3, p?=?0.65), was significantly higher in men with DISH compared to men without DISH. Significantly lower BMD of men with both DISH and fractures compared to men with DISH but without fractures was only detected by QCT (?25%, 0.09 vs 0.12, p?<?0.05). Both DXA BMD and QCT BMD were significantly higher in severe lumbar DISH (+22% and +31%, p?<?0.0001), respectively.

Conclusion

DISH was associated with a higher prevalence of vertebral fractures in elderly men. Lumbar ossifications related to DISH should be considered when interpreting BMD measurements to predict their fracture risk.     

Prevalence and risk factors of radiographic vertebral fracture in Brazilian community-dwelling elderly

Summary

The prevalence and risk factors of radiographic vertebral fracture were determined among Brazilian community-dwelling elderly. Vertebral fractures were a common condition in this elderly population, and lower hip bone mineral density was a significant risk factor for vertebral fractures in both genders.

Introduction

The aim of the study was to estimate the prevalence of radiographic vertebral fracture and investigate factors associated with this condition in Brazilian community-dwelling elderly.

Methods

This cross-sectional study included 943 elderly subjects (561 women and 382 men) living in São Paulo, Brazil. Thoracic and lumbar spine radiographs were obtained, and vertebral fractures were evaluated using Genant's semiquantitative method. Bone mineral density (BMD) was measured by dual X-ray absorptiometry, and bone biochemical markers were also evaluated. Female and male subjects were analyzed independently, and each gender was divided into two groups based on whether vertebral fractures were present.

Results

The prevalence of vertebral fracture was 27.5% (95% CI 23.8–31.1) in women and 31.8% in men (95% CI 27.1–36.5) (P?=?0.116). Cox regression analyses using variables that were significant in the univariate analysis showed that age (prevalence ratio?=?1.03, 95% CI 1.01–1.06; p?=?0.019) and total femur BMD (PR?=?0.27, 95% CI 0.08–0.98; p?=?0.048) were independent factors in predicting vertebral fracture for the female group. In the male group, Cox regression analyses demonstrated that femoral neck BMD (PR?=?0.26, 95% CI 0.07–0.98; p?=?0.046) was an independent parameter in predicting vertebral fractures.

Conclusions

Our results suggest that radiographic vertebral fractures are common in Brazilian community-dwelling elderly and that a low hip BMD was an important risk factor for this condition in both genders. Age was also significantly correlated with the presence of vertebral fractures in women.     

Effects of long-term strontium ranelate treatment on vertebral fracture risk in postmenopausal women with osteoporosis

Summary

Vertebral fractures are a major adverse consequence of osteoporosis. In a large placebo-controlled trial in postmenopausal women with osteoporosis, strontium ranelate reduced vertebral fracture risk by 33% over 4 years, confirming the role of strontium ranelate as an effective long-term treatment in osteoporosis.

Introduction

Osteoporotic vertebral fractures are associated with increased mortality, morbidity, and loss of quality-of-life (QoL). Strontium ranelate (2 g/day) was shown to prevent bone loss, increase bone strength, and reduce vertebral and peripheral fractures. The preplanned aim of this study was to evaluate long-term efficacy and safety of strontium ranelate.

Methods

A total of 1,649 postmenopausal osteoporotic women were randomized to strontium ranelate or placebo for 4 years, followed by a 1-year treatment-switch period for half of the patients. Primary efficacy criterion was incidence of patients with new vertebral fractures over 4 years. Lumbar bone mineral density (BMD) and QoL were also evaluated.

Results

Over 4 years, risk of vertebral fracture was reduced by 33% with strontium ranelate (risk reduction?=?0.67, p?<?0.001). Among patients with two or more prevalent vertebral fractures, risk reduction was 36% (p?<?0.001). QoL, assessed by the QUALIOST®, was significantly better (p?=?0.025), and patients without back pain were greater (p?=?0.005) with strontium ranelate than placebo over 4 years. Lumbar BMD increased over 5 years in patients who continued with strontium ranelate, while it decreased in patients who switched to placebo. Emergent adverse events were similar between groups.

Conclusion

In this 4- and 5-year study, strontium ranelate is an effective and safe treatment for long-term treatment of osteoporosis in postmenopausal women.     

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

Summary

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

Introduction

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

Methods

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

Results

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

Conclusions

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

Low holotranscobalamin and cobalamins predict incident fractures in elderly men: the MrOS Sweden

Summary

In a population-based study on cobalamin status and incident fractures in elderly men (n?=?790) with an average follow-up of 5.9 years, we found that low levels of metabolically active and total cobalamins predict incident fractures, independently of body mass index (BMI), bone mineral density (BMD), plasma total homocysteine (tHcy), and cystatin C.

Introduction

Cobalamin deficiency in elderlies may affect bone metabolism. This study aims to determine whether serum cobalamins or holotranscobalamin (holoTC; the metabolic active cobalamin) predict incident fractures in old men.

Methods

Men participating in the Gothenburg part of the population-based Osteoporotic Fractures in Men (MrOS) Sweden cohort and without ongoing vitamin B medication were included in the present study (n?=?790; age range, 70–81 years).

Results

During an average follow-up of 5.9 years, 110 men sustained X-ray-verified fractures including 45 men with clinical vertebral fractures. The risk of fracture (adjusted for age, smoking, BMI, BMD, falls, prevalent fracture, tHcy, cystatin C, 25-OH-vitamin D, intake of calcium, and physical activity (fully adjusted)), increased per each standard deviation decrease in cobalamins (hazard ratio (HR), 1.38; 95 % confidence intervals (CI), 1.11–1.72) and holoTC (HR, 1.26; 95 % CI, 1.03–1.54), respectively. Men in the lowest quartile of cobalamins and holoTC (fully adjusted) had an increased risk of all fracture (cobalamins, HR?=?1.67 (95 % CI, 1.06–2.62); holoTC, HR?=?1.74 (95 % CI, 1.12–2.69)) compared with quartiles 2–4. No associations between folate or tHcy and incident fractures were seen.

Conclusions

We present novel data showing that low levels of holoTC and cobalamins predicting incident fracture in elderly men. This association remained after adjustment for BMI, BMD, tHcy, and cystatin C. However, any causal relationship between low cobalamin status and fractures should be explored in a prospective treatment study.     

Bone mineral density by DXA and HR pQCT can discriminate fracture status in men and women with stages 3 to 5 chronic kidney disease

Summary

Fractures are common in chronic kidney disease (CKD). We determined if bone mineral density testing by dual energy X-ray absorptiometry (DXA) and high resolution peripheral quantitative computed tomography (HR pQCT) could discriminate fracture status in CKD patients. Both tests were able to discriminate fracture status. Further, the addition of HR pQCT measurements to DXA measurements did not improve fracture discrimination.

Introduction

The optimal method to identify individuals with CKD at high fracture risk is unknown.

Methods

We determined if bone mineral density (BMD) by DXA and HR pQCT could discriminate fracture status in 211 adult men and women with stages 3 to 5 CKD, attending predialysis clinics in Toronto Canada, using logistic regression. Results are expressed as the odds ratio (OR) of fracture (prevalent vertebral and/or low trauma since age 40?years) per standard deviation decrease in the predictor adjusted for age, weight, sex, and CKD stage. We constructed receiver operating characteristic curves to examine the discriminative ability of BMD measures for fracture.

Results

Most participants were Caucasian men with a mean age of 63.3?±?15.5?years. There were 77 fractures in 74 participants. Decreases in BMD were associated with increased fracture risk: OR?=?1.56 (95% confidence interval (CI), 1.41 to 1.71) for BMD by DXA at the ultradistal radius, and OR?=?1.24 (95% CI, 1.12 to 1.36) for cortical area by HR pQCT. Further, while both tests were able to discriminate fracture status, the addition of HR pQCT measures to BMD by DXA did not improve fracture discrimination ability.

Conclusions

Among CKD patients not yet requiring renal replacement therapy, BMD by DXA is able to discriminate fracture status.     

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.     

Reliability of vertebral fracture assessment using multidetector CT lateral scout views: the Framingham Osteoporosis Study

Summary

Two radiologists evaluated images of the spine from computed tomography (CT) scans on two occasions to diagnose vertebral fracture in 100 individuals. Agreement was fair to good for mild fractures, and agreement was good to excellent for more severe fractures. CT scout views are useful to assess vertebral fracture.

Introduction

We investigated inter-reader agreement between two radiologists and intra-reader agreement between duplicate readings for each radiologist, in assessment of vertebral fracture using a semi-quantitative method from lateral scout views obtained by CT.

Methods

Participants included 50 women and 50 men (age 50-87?years, mean 70?years) in the Framingham Study. T4-L4 vertebrae were assessed independently by two radiologists on two occasions using a semi-quantitative scale as normal, mild, moderate, or severe fracture.

Results

Vertebra-specific prevalence of grade ??1 (mild) fracture ranged from 3% to 5%. We found fair (???=?56-59%) inter-reader agreement for grade ??1 vertebral fractures and good (???=?68-72%) inter-reader agreement for grade ??2 fractures. Intra-reader agreement for grade ??1 vertebral fracture was fair (???=?55%) for one reader and excellent for another reader (???=?77%), whereas intra-reader agreement for grade ??2 vertebral fracture was excellent for both readers (???=?76% and 98%). Thoracic vertebrae were more difficult to evaluate than the lumbar region, and agreement was lowest (inter-reader ???=?43%) for fracture at the upper (T4-T9) thoracic levels and highest (inter-reader ???=?76-78%) for the lumbar spine (L1-L4).

Conclusions

Based on a semi-quantitative method to classify vertebral fractures using CT scout views, agreement within and between readers was fair to good, with the greatest source of variation occurring for fractures of mild severity and for the upper thoracic region. Agreement was good to excellent for fractures of at least moderate severity. Lateral CT scout views can be useful in clinical research settings to assess vertebral fracture.     

Effects of exercise on fracture reduction in older adults

Summary

In this meta-analysis, we evaluated the effect of exercise on fracture reduction in the elderly. Our results determined a significantly positive effect on overall fractures, whereas the possibility of a publication bias indicates the need for well-designed (multi-center) trials that generate enough power to focus on osteoporotic fractures.

Introduction

The preventive effect of exercise on fracture incidence has not been clearly determined yet. Thus, the purpose of this study is to evaluate the effectiveness of exercise in preventing overall and vertebral fractures in older adults by meta-analyses technique.

Methods

This study followed the PRISMA recommendations for systematic reviews and meta-analyses. A systematic review of English articles between 1980 and March 2012 was performed. Terms used were: “exercise”, “fractures”, “bone”, “falls”, “osteoporosis”, “BMD”, “BMC”, “bone turnover”, while the search was limited to “clinical trial” and “humans”. Controlled exercise trials that reported fracture number as endpoint or observation in subjects 45 years and older were included.

Results

Ten controlled exercise trials that reported overall fractures and three exercise trials that reported vertebral fractures met our inclusion criteria. Overall fracture number in the exercise group was 36 (n?=?754) compared with 73 fractures in the CG (n?=?670) (relative risk [RR]?=?0.49; 95 % confidence interval [CI], 0.31–0.76). No significant heterogeneity of trial results (p?=?0.28; I ²?=?17) was determined; however, there was some evidence to suggest a publication bias. The overall RR for vertebral fracture number (0.56; 95 % CI, 0.30–1.04) (EG: 19 fractures/103 subjects vs. CG: 31 fractures/102 subjects) was borderline non-significant while the heterogeneity of trial results also cannot be ruled out.

Conclusion

Although there is evidence that exercise reduces overall and, to a lesser degree, vertebral fractures in the elderly, the possibility of publication bias weakens our result and demonstrates the imperative for large exercise studies with dedicated exercise protocols that focus on fractures as a primary endpoint.     

The assessment of vertebral fractures in elderly women with recent hip fractures: the BREAK Study

Summary

This study aimed to evaluate the prevalence of vertebral fractures in elderly women with a recent hip fracture. The burden of vertebral fractures expressed by the Spinal Deformity Index (SDI) is more strictly associated with the trochanteric than the cervical localization of hip fracture and may influence short-term functional outcomes.

Introduction

This study aimed to determine the prevalence and severity of vertebral fractures in elderly women with recent hip fracture and to assess whether the burden of vertebral fractures may be differently associated with trochanteric hip fractures with respect to cervical hip fractures.

Methods

We studied 689 Italian women aged 60 years or over with a recent low trauma hip fracture and for whom an adequate X-ray evaluation of spine was available. All radiographs were examined centrally for the presence of any vertebral deformities and radiological morphometry was performed. The SDI, which integrates both the number and the severity of fractures, was also calculated.

Results

Prevalent vertebral fractures were present in 55.7 % of subjects and 95 women (13.7 %) had at least one severe fracture. The women with trochanteric hip fracture showed higher SDI and higher prevalence of diabetes with respect to those with cervical hip fracture, p?=?0.017 and p?=?0.001, respectively. SDI, surgical menopause, family history of fragility fracture, and type2 diabetes mellitus were independently associated with the risk of trochanteric hip fracture. Moreover, a higher SDI was associated with a higher percentage of post-surgery complications (p?=?0.05) and slower recovery (p?<?0.05).

Conclusions

Our study suggests that the burden of prevalent vertebral fractures is more strictly associated with the trochanteric than the cervical localisation of hip fracture and that elevated values of SDI negatively influence short term functional outcomes in women with hip fracture.     

Long-term fracture rates seen with continued ibandronate treatment: pooled analysis of DIVA and MOBILE long-term extension studies

Summary

Ibandronate reduces the risk of vertebral and non-vertebral fractures versus placebo in postmenopausal women with osteoporosis. This analysis, in which fractures were reported as safety events, showed that long-term use of ibandronate was associated with low fracture rates over 5 years of treatment.

Introduction

A previous post-hoc meta-analysis of 2–3 year studies found that ibandronate regimens with annual cumulative exposure (ACE) of ≥10.8 mg reduced the risk of vertebral and nonvertebral fractures (NVFs) versus placebo in postmenopausal women. This post-hoc analysis used individual patient data from the 2-year monthly oral ibandronate in ladies (MOBILE) and dosing intravenous administration (DIVA) studies, including the 3-year long-term extensions (LTEs), to assess fracture risk in patients treated with ibandronate for 5 years.

Methods

Patients treated for 2 years in MOBILE with monthly oral ibandronate 150 mg (n?=?176) and in DIVA with IV ibandronate every 2 months 2 mg (n?=?253) or quarterly 3 mg (n?=?263) who continued on the same regimens for 3 additional years in the LTEs were included. Three-year placebo data (n?=?1,924) were obtained from the ibandronate osteoporosis vertebral fracture trial in North America and Europe (BONE) and IV Fracture Prevention trials. The primary endpoint was clinical fracture rate; clinical fracture data were collected as adverse events. Time to fracture was analyzed using Kaplan–Meier and statistical analysis was conducted using the log-rank test. All clinical fractures included all NVFs and symptomatic vertebral fractures.

Results

For ibandronate regimens with ACE ≥10.8 mg, time to fracture was significantly longer for all clinical fractures, NVFs, and clinical vertebral fractures versus placebo (P?=?0.005). For all fracture types, the rate of fracture appeared stable during the 5-year treatment period.

Conclusion

In women with postmenopausal osteoporosis, continuous treatment with ibandronate over 5 years results in low sustained clinical fracture rate.     

Femur ultrasound (FemUS)—first clinical results on hip fracture discrimination and estimation of femoral BMD

Summary

A quantitative ultrasound (QUS) device for measurements at the proximal femur was developed and tested in vivo (Femur Ultrasound Scanner, FemUS). Hip fracture discrimination was as good as for DXA, and a high correlation with hip BMD was achieved. Our results show promise for enhanced QUS-based assessment of osteoporosis.

Introduction

Dual X-ray absorptiometry (DXA) at the femur is the best predictor of hip fractures, better than DXA measurements at other sites. Calcaneal quantitative ultrasound (QUS) can be used to estimate the general osteoporotic fracture risk, but no femoral QUS measurement has been introduced yet. We developed a QUS scanner for measurements at the femur (Femur Ultrasound Scanner, FemUS) and tested its in vivo performance.

Methods

Using the FemUS device, we obtained femoral QUS and DXA on 32 women with recent hip fractures and 30 controls. Fracture discrimination and the correlation with femur bone mineral density (BMD) were assessed.

Results

Hip fracture discrimination using the FemUS device was at least as good as with hip DXA and calcaneal QUS. Significant correlations with total hip bone mineral density were found with a correlation coefficient R ² up to 0.72 and a residual error of about one half of a T-score in BMD.

Conclusions

QUS measurements at the proximal femur are feasible and show a good performance for hip fracture discrimination. Given the promising results, this laboratory prototype should be reengineered to a clinical applicable instrument. Our results show promise for further enhancement of QUS-based assessment of osteoporosis.     

Association of serum sclerostin with bone mineral density, bone turnover, steroid and parathyroid hormones, and fracture risk in postmenopausal women: the OFELY study

Summary

Sclerostin is a key regulator of bone formation. In a population of 572 postmenopausal women (mean age, 67 years) followed prospectively for a median of 6 years, there was no significant association between baseline levels of serum sclerostin and incidence of all fractures which occurred in 64 subjects.

Introduction

Sclerostin, an osteocyte soluble factor, is a major negative regulator of osteoblastic activity. Circulating sclerostin levels were reported to increase with age and to be modestly associated with bone mineral density (BMD) and bone turnover, but there are no data on the association with fracture risk.

Methods

We investigated 572 postmenopausal women (mean age, 67?±?8.5 years) from the OFELY population-based cohort. The associations of serum sclerostin measured with a new two-site ELISA and spine and hip BMD by DXA, serum β-isomerized C-terminal crosslinking of type I collagen (CTX), intact N-terminal propeptide of type I collagen (PINP), intact PTH, 25-hydroxyvitamin D [25(OH)D], estradiol, testosterone, and fracture risk were analyzed. At the time of sclerostin measurements, 98 postmenopausal women had prevalent fractures. After a median of 6 years (interquartile range, 5–7 years) follow-up, 64 postmenopausal sustained an incident fracture.

Results

Serum sclerostin correlated positively with spine (r?=?0.35, p?<?0.0001) and total hip (r?=?0.25, <0.0001) BMD. Conversely, serum sclerostin was weakly negatively associated with the bone markers PINP (r?=??0.10, p?=?0.014) and CTX (r?=??0.13, p?=?0.0026) and with intact PTH (r?=??0.13, p?=?0.0064). There was no significant association of serum sclerostin with 25(OH)D, estradiol, free estradiol index, or testosterone. Serum sclerostin considered as a continuous variable or in quartiles was not significantly associated with the risk of prevalent or incident fracture.

Conclusion

Serum sclerostin is weakly correlated with BMD, bone turnover, and PTH in postmenopausal women. It was not significantly associated with the risk of all fractures, although the number of incident fractures recorded may not allow detecting a modest association.     

What analytic method should clinicians use to derive spine T-scores and predict incident fractures in men? Results from the MrOS study

Summary

In this study, the area under the curve was highest when using the lowest vertebral body T-score to diagnose osteoporosis. In men for whom hip imaging is not possible, the lowest vertebral body T-score improves the ability to diagnose osteoporosis in men who are likely to have an incident fragility fracture.

Introduction

Spine T-scores have limited ability to predict fragility fracture. We hypothesized that using lowest vertebral body T-score to diagnose osteoporosis would better predict fracture.

Methods

Among men enrolled in the Osteoporotic Fractures in Men Study, we identified cases with incident clinical fracture (n?=?484) and controls without fracture (n?=?1,516). We analyzed the lumbar spine bone mineral density (BMD) in cases and controls (n?=?2,000) to record the L1–L4 (referent), the lowest vertebral body, and International Society for Clinical Densitometry (ISCD)-determined T-scores using a male normative database and the L1–L4 T-score using a female normative database. We compared the ability of method to diagnose osteoporosis and, therefore, to predict incident clinical fragility fracture, using area under the receiver operator curves (AUCs) and the net reclassification index (NCI) as measures of diagnostic accuracy. ISCD-determined T-scores were determined in only 60 % of participants (n?=?1,205).

Results

Among 1,205 men, the AUC to predict incident clinical fracture was 0.546 for L1–L4 male, 0.542 for the L1–L4 female, 0.585 for lowest vertebral body, and 0.559 for ISCD-determined T-score. The lowest vertebral body AUC was the only method significantly different from the referent method (p?=?0.002). Likewise, a diagnosis of osteoporosis based on the lowest vertebral body T-score demonstrated a significantly better net reclassification index (NRI) than the referent method (net NRI +0.077, p?=?0.005). By contrast, the net NRI for other methods of analysis did not differ from the referent method.

Conclusion

Our study suggests that in men, the lowest vertebral body T-score is an acceptable method by which to estimate fracture risk.     

Thoracic kyphosis and rate of incident vertebral fractures: the Fracture Intervention Trial

Summary

Biomechanical analyses support the theory that thoracic spine hyperkyphosis may increase risk of new vertebral fractures. While greater kyphosis was associated with an increased rate of incident vertebral fractures, our analysis does not show an independent association of kyphosis on incident fracture, after adjustment for prevalent vertebral fracture. Excessive kyphosis may still be a clinical marker for prevalent vertebral fracture.

Introduction

Biomechanical analyses suggest hyperkyphosis may increase risk of incident vertebral fracture by increasing the load on vertebral bodies during daily activities. We propose to assess the association of kyphosis with incident radiographic vertebral fracture.

Methods

We used data from the Fracture Intervention Trial among 3038 women 55–81 years of age with low bone mineral density (BMD). Baseline kyphosis angle was measured using a Debrunner kyphometer. Vertebral fractures were assessed at baseline and follow-up from lateral radiographs of the thoracic and lumbar spine. We used Poisson models to estimate the independent association of kyphosis with incident fracture, controlling for age and femoral neck BMD.

Results

Mean baseline kyphosis was 48° (SD?=?12) (range 7–83). At baseline, 962 (32 %) participants had a prevalent fracture. There were 221 incident fractures over a median of 4 years. At baseline, prevalent fracture was associated with 3.7° greater average kyphosis (95 % CI 2.8–4.6, p?<?0.0005), adjusting for age and femoral neck BMD. Before adjusting for prevalent fracture, each 10° greater kyphosis was associated with 22 % increase (95 % CI 8–38 %, p?=?0.001) in annualized rate of new radiographic vertebral fracture, adjusting for age and femoral neck BMD. After additional adjustment for prevalent fracture, estimated increased annualized rate was attenuated and no longer significant, 8 % per 10° kyphosis (95 % CI ?4 to 22 %, p?=?0.18).

Conclusions

While greater kyphosis increased the rate of incident vertebral fractures, our analysis does not show an independent association of kyphosis on incident fracture, after adjustment for prevalent vertebral fracture. Excessive kyphosis may still be a clinical marker for prevalent vertebral fracture.

     

Prevalence of vertebral fracture in oldest old nursing home residents

Summary

We evaluated vertebral fracture prevalence using DXA-based vertebral fracture assessment and its influence on the Fracture Risk Assessment (FRAX) tool-determined 10-year fracture probability in a cohort of oldest old nursing home residents. More than one third of the subjects had prevalent vertebral fracture and 50% osteoporosis. Probably in relation with the prevailing influence of age and medical history of fracture, adding these information into FRAX did not markedly modify fracture probability.

Introduction

Oldest old nursing home residents are at very high risk of fracture. The prevalence of vertebral fracture in this specific population and its influence on fracture probability using the FRAX tool are not known.

Methods

Using a mobile DXA osteodensitometer, we studied the prevalence of vertebral fracture, as assessed by vertebral fracture assessment program, of osteoporosis and of sarcopenia in 151 nursing home residents. Ten-year fracture probability was calculated using appropriately calibrated FRAX tool.

Results

Vertebral fractures were detected in 36% of oldest old nursing home residents (mean age, 85.9?±?0.6?years). The prevalence of osteoporosis and sarcopenia was 52% and 22%, respectively. Ten-year fracture probability as assessed by FRAX tool was 27% and 15% for major fracture and hip fracture, respectively. Adding BMD or VFA values did not significantly modify it.

Conclusion

In oldest old nursing home residents, osteoporosis and vertebral fracture were frequently detected. Ten-year fracture probability appeared to be mainly determined by age and clinical risk factors obtained by medical history, rather than by BMD or vertebral fracture.     

Fracture risk in children with a forearm injury is associated with volumetric bone density and cortical area (by peripheral QCT) and areal bone density (by DXA)

Summary

Children who sustain a forearm fracture when injured have lower bone density throughout their skeleton, and have a smaller cortical area and a lower strength index in their radius. Odds ratios per SD decrease in bone characteristics measured by peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA) were similar (1.28 to 1.41).

Introduction

Forearm fractures are common in children. Bone strength is affected by bone mineral density (BMD) and bone geometry, including cross-sectional dimensions and distribution of mineral. Our objective was to identify bone characteristics that differed between children who sustained a forearm fracture compared to those who did not fracture when injured.

Methods

Children (5–16 years) with a forearm fracture (cases, n?=?224) and injured controls without fracture (n?=?200) were enrolled 28?±?8 days following injury. Peripheral QCT scans of the radius (4% and 20% sites) were obtained to measure volumetric BMD (vBMD) of total, trabecular and cortical bone compartments, and bone geometry (area, cortical thickness, and strength strain index [SSI]). DXA scans (forearm, spine, and hip) were obtained to measure areal BMD (aBMD) and bone area. Receiver operating characteristic (ROC) analyses were used to assess screening performance of bone measurements.

Results

At the 4% pQCT site, total vBMD, but not trabecular vBMD or bone area, was lower (?3.4%; p?=?0.02) in cases than controls. At the 20% site, cases had lower cortical vBMD (?0.9%), cortical area (?2.8%), and SSI (?4.6%) (p?<?0.05). aBMD, but not bone area, at the 1/3 radius, spine, and hip were 2.7–3.3% lower for cases (p?<?0.01). Odds ratios per 1 SD decrease in bone measures (1.28–1.41) and areas under the ROC curves (0.56–0.59) were similar for all bone measures.

Conclusions

Low vBMD, aBMD, cortical area, and SSI of the distal radius were associated with an increased fracture risk. Interventions to increase these characteristics are needed to help reduce forearm fracture occurrence.