Bone turnover markers for osteoporotic status assessment? A systematic review of their diagnosis value at baseline in osteoporosis

ObjectiveOsteoporosis diagnosis is based on bone mineral density (BMD) but bone remodeling is also a crucial issue. It can be assessed by bone turnover markers (BTMs). Their interest for the positive and etiological diagnosis of osteoporosis at baseline, and their predictive value for past asymptomatic vertebral fractures, were evaluated by a systematic review of the literature.MethodsMedline database was searched to identify all published reports analyzing BTMs and BMD or fractures. We conducted meta-analyses on BTMs levels according to osteoporotic status using random effects models.ResultsModerate and negative correlations were found, mainly in postmenopausal women, between BTMs and BMD, especially with bone alkaline phosphatase (bone ALP), osteocalcin, serum C-terminal and urine N-terminal crosslinking telopeptides of type I collagen (sCTX and uNTX). Bone ALP and sCTX levels are higher in osteoporotic patients compared to controls. High levels of bone ALP in primary hyperparathyroidism and low levels of osteocalcin in endogenous hypercorticism are the most relevant data reported in endocrine diseases associated with osteoporosis. High levels of BTMs, especially osteocalcin, bone ALP or sCTX, may be associated with prevalent vertebral fractures.ConclusionThe diagnosis value of BTMs at baseline in osteoporosis is very low. The interest of BTMs for the etiological diagnostic of secondary osteoporosis has not been demonstrated. Data are lacking to address the interest of BTMs assessment to screen for vertebral fractures in asymptomatic patients with high risk factors of fractures.     

Assessing neuronal density in peri‐infarct cortex with PET: Effects of cortical topology and partial volume correction

The peri‐infarct cortex (PIC) is the site of long‐term physiologic changes after ischemic stroke. Traditional methods for delineating the peri‐infarct gray matter (GM) have used a volumetric Euclidean distance metric to define its extent around the infarct. This metric has limitations in the case of cortical stroke, i.e., those where ischemia leads to infarction in the cortical GM, because the vascularization of the cerebral cortex follows the complex, folded topology of the cortical surface. Instead, we used a geodesic distance metric along the cortical surface to subdivide the PIC into equidistant rings emanating from the infarct border and compared this new approach to a Euclidean distance metric definition. This was done in 11 patients with [F‐18]‐Flumazenil ([18‐F]‐FMZ) positron emission tomography (PET) scans at 2 weeks post‐stroke and at 6 month follow‐up. FMZ is a PET radiotracer with specific binding to the alpha subunits of the type A γ‐aminobutyric acid (GABAA) receptor. Additionally, we used partial‐volume correction (PVC) of the PET images to compensate for potential cortical thinning and long‐term neuronal loss in follow‐up images. The difference in non‐displaceable binding potential (BP_ND) between the stroke unaffected and affected hemispheres was 35% larger in the geodesic versus the Euclidean peri‐infarct models in initial PET images and 48% larger in follow‐up PET images. The inter‐hemispheric BP_ND difference was approximately 17–20% larger after PVC when compared to uncorrected PET images. PET studies of peri‐infarct GM in cortical strokes should use a geodesic model and include PVC as a preprocessing step. Hum Brain Mapp 38:326–338, 2017. © 2016 Wiley Periodicals, Inc.     

Ultrasound Measurements at the Proximal Phalanges in Healthy Women and Patients with Hip Fractures

Measurements of bone mineral density (BMD) are useful for the assessment of fracture risk in osteoporosis. First prospective studies showed that quantitative ultrasound as measured at the calcaneus also predicts future hip fracture risk, independently of BMD and as accurately as BMD. The aim of this study was to compile a reference population for a new ultrasound device that determines amplitude-dependent speed of sound (AD-SOS) through the proximal phalanges of the hand and to prove its ability to distinguish between health volunteers and osteoporotic patients. In a case–control study we examined 139 healthy women aged 21–94 years and a group of 24 female patients aged 69–94 years with recent hip fractures. In the healthy reference population additional BMD measurements were performed with dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound measurements at the calcaneus were carried out. In vivo precision of AD-SOS measurements through the phalanges was 0.52% CV. Simple regression analyses showed a negative correlation with age (r= 70.73, p50.001); modest significant correlations with BMD of the lumbar spine (r= 0.36, p50.001) and BMD of the femoral neck (r= 0.37, p= 0.002) as measured with DXA were shown. The comparison with another ultrasound device measuring SOS and broadband ultrasound attenuation (BUA) through the calcaneus showed correlation with SOS (r= 0.50, p50.001); no significant correlation was found with BUA measurements. Furthermore a dependency of AD-SOS values in anthropometric factors such as body mass index (r= 0.37, p50.001), height (r= 0.40, p50.001) and weight (r= 0.23, p50.05) was shown. First study results on 24 clinically diagnosed osteoporotic patients, defined as patients with recent (51 week) pertrochanteric or femoral neck fractures, showed a good separation between age- and sex-matched controls and osteoporotic patients (Z= 72.0 SD). Receiver operating characteristic (ROC) curves showed an area under the fitted curve of 0.83 + 0.06. These results are powerful for a device measuring AD-SOS through the proximal phalanges of the hand, and further prospective studies have proven the capability of phalangeal ultrasound in fracture risk assessment. Received: 4 January 1996 / Accepted: 15 January 1998     

Phase variations in the left coronary transstenotic pressure gradient before and after dilatation by percutaneous coronary angioplasty

The concept of significant coronary stenosis may be approached by studying the effects of the narrowing not in absolute values of pressure and flow but by studying the mode of blood flow across the stenosis. Ten patients with isolated stenosis of the LAD were studied for phasic variations of the transstenotic pressure gradient before and after dilatation. The material used was a ST 3.7 catheter with a 0.12 inch guide. Instantaneous pressure recording throughout the cardiac cycle were obtained using a computer. After dilatation, the area of the stenosis minus the area of transverse section of the dilating catheter increased from 0.5 +/- 0.3 to 2.2 +/- 0.3 mm2, the average gradient between the aorta and the post stenotic LAD decreased from 75 +/- 10 to 12 +/- 8 mmHg, and the ratio between the mean diastolic gradient and mean gradient increased from 75 +/- 7 to 245 +/- 30% (p less than 0.01 for the 3 parameters, paired t test). These results show that the LAD transstenotic pressure gradient is not phasic in severe stenosis. It becomes phasic, only in diastole, after dilatation of the stenosis (slight residual stenosis due to the catheter). This difference may be due to the type of flow, continuous and dependent on the stenosis before dilatation, or phasic dependent on the distal coronary circulation after dilatation. Analysis of the phasic changes of coronary flow may be useful for the evaluation of the severity of left coronary stenosis in the absence of pressure measurements.