The association between coronary artery calcification progression and loss of bone density in non-dialyzed CKD patients

Background: Coronary artery calcification (CAC) and low bone density are coexisting deleterious conditions commonly shared by chronic kidney disease (CKD) patients. In the present study, we aimed to investigate whether the progression of CAC was associated with overtime reduction in bone density in non-dialyzed CKD patients. Methods: This is a prospective study of 24 months including 72 non-dialyzed CKD patients Stages 2 - 4 (age 57.6 +/- 10.3 years, 62% male, 22% diabetics). CAC and vertebral bone density (VBD) were measured by computed tomography. Results: At baseline, 46% of the patients had CAC (calcified group) and calcification was not identified in 54% of the patients (non-calcified group). The calcified group was older, predominantly male, and had lower VBD in comparison to non-calcified group. CAC progression was observed only in the calcified group (91% of the patients increased calcium score). The multiple regression analysis revealed loss of VBD as the independent determinant of CAC progression in these patients. Conclusion: CAC progression was associated with loss of VBD in non-dialyzed CKD patients.

DensiProbe Spine: a novel instrument for intraoperative measurement of bone density in transpedicular screw fixation

STUDY DESIGN.: Cadaver study. OBJECTIVE.: To determine bone strength in vertebrae by measuring peak breakaway torque or indentation force using custom-made pedicle probes. SUMMARY OF BACKGROUND DATA.: Screw performance in dorsal spinal instrumentation is dependent on bone quality of the vertebral body. To date no intraoperative measuring device to validate bone strength is available. Destructive testing may predict bone strength in transpedicular instrumentations in osteoporotic vertebrae. Insertional torque measurements showed varying results. METHODS.: Ten human cadaveric vertebrae were evaluated for bone mineral density (BMD) measurements by quantitative computed tomography. Peak torque and indentation force of custom-made probes as a measure for mechanical bone strength were assessed via a transpedicular approach. The results were correlated to regional BMD and to biomechanical load testing after pedicle screw implementation. RESULTS.: Both methods generated a positive correlation to failure load of the respective vertebrae. The correlation of peak breakaway torque to failure load was r = 0.959 (P = 0.003), therewith distinctly higher than the correlation of indentation force to failure load, which was r = 0.690 (P = 0.040). In predicting regional BMD, measurement of peak torque also performed better than that of indentation force (r = 0.897 [P = 0.002] vs. r = 0.777 [P = 0.017]). CONCLUSION.: Transpedicular measurement of peak breakaway torque is technically feasible and predicts reliable local bone strength and implant failure for dorsal spinal instrumentations in this experimental setting.

[Bone density and laboratory parameters of bone metabolism in patients with terminal heart disease]

The purpose of this study was to assess bone mineral density (BMD) and parameters for bone metabolism in patients with end-stage heart disease awaiting heart transplantation to determine whether these patients are at increased risk of bone disease.

Non-invasive quantitative estimation of bone density in rats throughout the life cycle and in arthritic osteopenia: preliminary results

A longitudinal bone survey was conducted in 86 female Wistar rats in order to assess mineral density kinetics from young age (5 weeks: 115 g) till late adulthood (64 weeks: 586 g). In vivo quantitative radiographic scanning was performed on the caudal vertebrae, taking trabecular mass as the parameter. Measurements were expressed as Relative Optical Density (ROD) units by means of a high resolution densitometric device. Results showed a progressive increase in mineral density throughout the life cycle, with a tendency to level in the higher weight range, indicating that progressive mineral aposition occurs in rats in dependency of age. This phenomenon, however, should be always considered within the context of continuous skeletal growth and related changes typical of this species. Twelve different animals were also examined following induction of articular inflammation with Freund's adjuvant in six of them. Bone survey conducted 12 to 18 days after inoculation revealed a significant (P less than 0.01) reduction in trabecular bone mass of scanned vertebrae in comparison with the weight-matched untreated controls. It is concluded that the in vivo quantitative assessment of bone density illustrated in this report represents a sensitive and useful tool for the long-term survey of naturally occurring or experimentally induced bone changes. Scanning of the same part of the skeleton can be repeated, thereby avoiding sacrifice of the animal and time-consuming preparation of post-mortem material.

Dual-energy X-ray absorptiometry for measuring total bone mineral content in the rat: study of accuracy and precision

Sequential studies of osteopenic bone disease in small animals require the availability of non-invasive, accurate and precise methods to assess bone mineral content (BMC) and bone mineral density (BMD). Dual-energy X-ray absorptiometry (DXA), which is currently used in humans for this purpose, can also be applied to small animals by means of adapted software. Precision and accuracy of DXA was evaluated in 10 rats weighing 50-265 g. The rats were anesthetized with a mixture of ketamine-xylazine administrated intraperitoneally. Each rat was scanned six times consecutively in the antero-posterior incidence after repositioning using the rat whole-body software for determination of whole-body BMC and BMD (Hologic QDR 1000, software version 5.52). Scan duration was 10-20 min depending on rat size. After the last measurement, rats were sacrificed and soft tissues were removed by dermestid beetles. Skeletons were then scanned in vitro (ultra high resolution software, version 4.47). Bones were subsequently ashed and dissolved in hydrochloric acid and total body calcium directly assayed by atomic absorption spectrophotometry (TBCa[chem]). Total body calcium was also calculated from the DXA whole-body in vivo measurement (TBCa[DXA]) and from the ultra high resolution measurement (TBCa[UH]) under the assumption that calcium accounts for 40.5% of the BMC expressed as hydroxyapatite. Precision error for whole-body BMC and BMD (mean +/- S.D.) was 1.3% and 1.5%, respectively. Simple regression analysis between TBCa[DXA] or TBCa[UH] and TBCa[chem] revealed tight correlations (n = 0.991 and 0.996, respectively), with slopes and intercepts which were significantly different from 1 and 0, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Modelo numérico mecanobiológico para a obtenção da matriz de rigidez estrutural e da densidade mineral na remodelagem óssea

Neste trabalho é proposto um modelo mecanobiológico de remodelagem óssea para a estimativa de variações, provocadas por perturbações mecânicas ou biológicas, na matriz de rigidez estrutural da escala macroscópica e na densidade mineral em uma região do osso. Na cooperação entre as áreas da saúde e da engenharia, como nos estudos estruturais de biomecânica no sistema esquelético, as propriedades mecânicas dos materiais devem ser conhecidas, entretanto os ossos possuem uma constituição material altamente complexa, dinâmica e variante entre indivíduos. Sua dinâmica decorre dos ciclos de absorção e deposição de matriz óssea na remodelagem óssea, a qual ocorre para manter a integridade estrutural do esqueleto e adaptá-lo aos estímulos do ambiente, sejam eles biológicos, químicos ou mecânicos. Como a remodelagem óssea pode provocar alterações no material do osso, espera-se que suas propriedades mecânicas também sejam alteradas. Na literatura científica há modelos matemáticos que preveem a variação da matriz de rigidez estrutural a partir do estímulo mecânico, porém somente os modelos mais recentes incluíram explicitamente processos biológicos e químicos da remodelagem óssea. A densidade mineral óssea é um importante parâmetro utilizado no diagnóstico de doenças ósseas na área médica. Desse modo, para a obtenção da variação da rigidez estrutural e da densidade mineral óssea, propõe-se um modelo numérico mecanobiológico composto por cinco submodelos: da dinâmica da população de células ósseas, da resposta das células ao estímulo mecânico, da porosidade óssea, da densidade mineral óssea e, baseado na Lei de Voigt para materiais compósitos, da rigidez estrutural. Os valores das constantes das equações dos submodelos foram obtidos de literatura. Para a solução das equações do modelo, propõe-se uma implementação numérica e computacional escrita em linguagem C. O método de Runge-Kutta-Dorman-Prince, cuja vantagem consiste no uso de um passo de solução variável, é utilizado no modelo para controlar o erro numérico do resultado do sistema de equações diferenciais. Foi realizada uma avaliação comparativa entre os resultados obtidos com o modelo proposto e os da literatura dos modelos de remodelagem óssea recentes. Conclui-se que o modelo e a implementação propostos são capazes de obter variações da matriz de rigidez estrutural macroscópica e da densidade mineral óssea decorrentes da perturbação nos parâmetros mecânicos ou biológicos do processo de remodelagem óssea.

The muscle strength and bone density relationship in young women: dependence on exercise status

Aim. Numerous studies report an association between muscle strength and bone mineral density (BMD) in young and older women. However, the participants are generally non-athletes, thus it is unclear if the relationship varies by exercise status. Therefore, the purpose was to examine the relationships between BMD and muscle strength in young women with markedly different exercise levels. Methods. Experimental design: cross-sectional. Setting: a University research laboratory. Participants: 18 collegiate gymnasts and 22 age- and weight-matched recreationally active control women. Measures: lumbar spine, femoral neck, arm, leg and whole body BMD (g/cm(2)) were assessed by dual X-ray absorptiometry. In addition, lumbar spine and femoral neck bone mineral apparent density (BMAD, g/cm(3)) was calculated. Handgrip strength and knee extensor and flexor torque (60degrees/s) were determined by dynamometry, and bench press and leg press strength (1-RM) using isotonic equipment. Results. BMD at all sites and bench press, leg press and knee flexor strength were greater in gymnasts than controls (p

Treadmill walking exercise modulates bone mineral status and inflammatory cytokines in obese asthmatic patients with long term intake of corticosteroids.

Background: Obesity and asthma are an important public health problem in Saudi Arabia. An increasing body of data supports the hypothesis that obesity is a risk factor for asthma. Asthma appears to be associated with low bone mineral density (BMD) due to long-term use of corticosteroids. Studies recently showed that weight bearing exercise training can increase mineral bone density, reduce weight and improve metabolic control. Objective: The present study aimed to measure the effects of treadmill walking exercises on bone mineral status and inflammatory cytokines in obese asthmatic patients treated with long term intake of corticosteroids. Methods: Eighty obese asthmatic patients of both sexes, their age ranged from 41 to 53 years. Subjects were divided into two equal groups: training group (group A) received aerobic exercise training on treadmill for six months in addition to the medical treatment where, the control group (group B) received only the medical treatment. Results: The results of this study indicated a significant increase in BMD of the lumbar spine & the radius, serum calcium and high density lipoprotein cholesterol (HDL-c) & significant reduction in parathyroid hormone, leptin, tumor necrosis factor– alpha(TNF-α), interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), low density lipoprotein cholesterol (LDL-c), triglycerides (TG) and body mass index (BMI) in group (A), while these changes were not significant in group (B).Also; there was a significant difference between both groups at the end of the study. Conclusion: Treadmill walking exercise training is an effective treatment policy to improve bone mineral status and modulates inflammatory cytokines and blood lipids profile in obese asthmatic patients with long term intake of corticosteroids.

Comparison of 3D finite element analysis derived stiffness and BMD to determine the failure load of the excised proximal femur

Introduction: Bone mineral density (BMD) is currently the preferred surrogate for bone strength in clinical practice. Finite element analysis (FEA) is a computer simulation technique that can predict the deformation of a structure when a load is applied, providing a measure of stiffness (Nmm−1). Finite element analysis of X-ray images (3D-FEXI) is a FEA technique whose analysis is derived froma single 2D radiographic image. Methods: 18 excised human femora had previously been quantitative computed tomography scanned, from which 2D BMD-equivalent radiographic images were derived, and mechanically tested to failure in a stance-loading configuration. A 3D proximal femur shape was generated from each 2D radiographic image and used to construct 3D-FEA models. Results: The coefficient of determination (R2%) to predict failure load was 54.5% for BMD and 80.4% for 3D-FEXI. Conclusions: This ex vivo study demonstrates that 3D-FEXI derived from a conventional 2D radiographic image has the potential to significantly increase the accuracy of failure load assessment of the proximal femur compared with that currently achieved with BMD. This approach may be readily extended to routine clinical BMD images derived by dual energy X-ray absorptiometry. Crown Copyright © 2009 Published by Elsevier Ltd on behalf of IPEM. All rights reserved

Generation of a 3D proximal femur shape from a single projection 2D radiographic image.

Summary Generalized Procrustes analysis and thin plate splines were employed to create an average 3D shape template of the proximal femur that was warped to the size and shape of a single 2D radiographic image of a subject. Mean absolute depth errors are comparable with previous approaches utilising multiple 2D input projections. Introduction Several approaches have been adopted to derive volumetric density (g cm-3) from a conventional 2D representation of areal bone mineral density (BMD, g cm-2). Such approaches have generally aimed at deriving an average depth across the areal projection rather than creating a formal 3D shape of the bone. Methods Generalized Procrustes analysis and thin plate splines were employed to create an average 3D shape template of the proximal femur that was subsequently warped to suit the size and shape of a single 2D radiographic image of a subject. CT scans of excised human femora, 18 and 24 scanned at pixel resolutions of 1.08 mm and 0.674 mm, respectively, were equally split into training (created 3D shape template) and test cohorts. Results The mean absolute depth errors of 3.4 mm and 1.73 mm, respectively, for the two CT pixel sizes are comparable with previous approaches based upon multiple 2D input projections. Conclusions This technique has the potential to derive volumetric density from BMD and to facilitate 3D finite element analysis for prediction of the mechanical integrity of the proximal femur. It may further be applied to other anatomical bone sites such as the distal radius and lumbar spine.

Comparison of 3D finite element analysis derived stiffness and BMD to determine the failure load of the excised proximal femur

Bone mineral density (BMD) is currently the preferred surrogate for bone strength in clinical practice. Finite element analysis (FEA) is a computer simulation technique that can predict the deformation of a structure when a load is applied, providing a measure of stiffness (N mm− 1). Finite element analysis of X-ray images (3D-FEXI) is a FEA technique whose analysis is derived from a single 2D radiographic image. This ex-vivo study demonstrates that 3D-FEXI derived from a conventional 2D radiographic image has the potential to significantly increase the accuracy of failure load assessment of the proximal femur compared with that currently achieved with BMD.

Clinical efficacy and safety of zoledronic acid in osteoporosis and Paget's disease

Osteoporosis and Paget’s bone disease are the most common diseases of the bone. In addition to glucocorticoid treatment, there are many other secondary causes of osteoporosis. Bisphosphonates are used to treat these bone conditions. Zoledronic acid is the most potent bisphosphonate at inhibiting bone resorption. In osteoporosis, zoledronic acid increases bone mineral density for at least 1 year following a single intravenous administration. The efficacy and safety of zoledronic acid in the treatment of osteoporosis and Paget’s bone disease are reviewed. This article also covers the studies of the effects of zoledronic acid in the bone loss associated with the secondary osteoporosis.

Clinical efficacy and safety of zoledronic acid in prostate and breast cancer

The anti-estrogen treatment for hormone-sensitive breast cancer and the androgen deprivation therapy for prostate cancer can lead to the development of osteoporosis and bone fractures. Metastases associated with prostate and breast cancer can also occur in bone. Bisphosphonates are used in these types of bone dysfunction. Zoledronic acid is the most potent bisphosphonate. In osteoporosis, zoledronic acid inhibits bone reabsorption and increases bone mineral density for at least a year after intravenous administration. The efficacy and safety of zoledronic acid in osteoporosis secondary to hormone-sensitive cancers (prostate and breast), and in the bone metastases associated with these cancers are reviewed.

Good clinical endpoints with denosumab in osteoporosis and cancer

Background: Bone loss associated with low oestrogen levels in postmenopausal women, and with androgen deprivation therapy in men with hormone-sensitive prostate cancer, result in an increased incidence of fractures. Denosumab has been shown to increase bone mineral density in these two conditions. Objectives/methods: The objective of this evaluation is to review the clinical trials that have studied clinical endpoints in these conditions. Results: FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months) was an International Phase III clinical trial that measured the clinical endpoints with denosumab in postmenopausal women with osteoporosis. At 36 months, new vertebral fractures had occurred in 7.2% of subjects in the placebo group and this was lowered to 2.3% of subjects treated with denosumab. HALT (Denosumab Hormone Ablation Bone Loss Trial) studied the clinical endpoints in men with non-metastatic prostate cancer receiving androgen-deprivation therapy. The incidence of vertebral fractures was significantly lower in the denosumab group (1.5%) than in the placebo group (3.9%). The incidence of adverse effects with denosumab in both clinical trials was low. Conclusions: Denosumab reduces the incidence of fractures in postmenopausal women with osteoporosis and in men with non-metastatic prostate cancer receiving androgen-deprivation therapy. Denosumab is well tolerated.