Bone Microarchitecture Phenotypes Identified in Older Adults Are Associated With Different Levels of Osteoporotic Fracture Risk

Prevalence of osteoporosis is more than 50% in older adults, yet current clinical methods for diagnosis that rely on areal bone mineral density (aBMD) fail to detect most individuals who have a fragility fracture. Bone fragility can manifest in different forms, and a “one-size-fits-all” approach to diagnosis and management of osteoporosis may not be suitable. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides additive information by capturing information about volumetric density and microarchitecture, but interpretation is challenging because of the complex interactions between the numerous properties measured. In this study, we propose that there are common combinations of bone properties, referred to as phenotypes, that are predisposed to different levels of fracture risk. Using HR-pQCT data from a multinational cohort (n = 5873, 71% female) between 40 and 96 years of age, we employed fuzzy c-means clustering, an unsupervised machine-learning method, to identify phenotypes of bone microarchitecture. Three clusters were identified, and using partial correlation analysis of HR-pQCT parameters, we characterized the clusters as low density, low volume, and healthy bone phenotypes. Most males were associated with the healthy bone phenotype, whereas females were more often associated with the low volume or low density bone phenotypes. Each phenotype had a significantly different cumulative hazard of major osteoporotic fracture (MOF) and of any incident osteoporotic fracture (p < 0.05). After adjustment for covariates (cohort, sex, and age), the low density followed by the low volume phenotype had the highest association with MOF (hazard ratio = 2.96 and 2.35, respectively), and significant associations were maintained when additionally adjusted for femoral neck aBMD (hazard ratio = 1.69 and 1.90, respectively). Further, within each phenotype, different imaging biomarkers of fracture were identified. These findings suggest that osteoporotic fracture risk is associated with bone phenotypes that capture key features of bone deterioration that are not distinguishable by aBMD. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Quantitative evaluation of cerebral metabolites and cerebral blood flow in patients with carotid stenosis

Abstract

We examined the metabolic and hemodynamic status of patients with severe carotid stenosis and evaluated the effectiveness of carotid endarterectomy (CEA) by comparing pre- and post-operative results of quantitative proton magnetic resonance spectroscopy (¹H-MRS) and single-photon emission computed tomography (SPECT). Quantitative ¹H-MRS and SPECT were performed in 17 patients with severe carotid stenosis before CEA; in 10 patients the examinations were repeated after CEA. There was a significant correlation between the degree of internal carotid artery (ICA) stenosis and the N-acetyl-aspartate (NAA) concentration, and between CBF and NAA in the basal ganglia. In 10 of the 17 patients (58.8%) we noted a decrease of NAA on ¹H-MRS. After CEA in these patients, NAA was significantly increased, and in 7 of 8 patients whose pre-operative SPECT had indicated impairment of cerebral vasoreactivity, it was improved. Quantitative ¹H-MRS and CBF measurements can indicate the severity of metabolic and hemodynamic impairment in patients with severe carotid stenosis, and can help to assess the effectiveness of CEA. [Neurol Res 2001; 23: 573-580]     

Assessment of Hepatic Functional Reserve in Cirrhotic Patients by Computed Tomography of the Caudate Lobe

In order to investigate whether the size of thecaudate lobe of the cirrhotic liver is related to thehepatic functional reserve, the morphometric analysis ofthe caudate lobe was preformed retrospectively using computed tomography in 106 consecutivepatients of whom 67 had compensated (group 1), and 39uncompensated (group 2) liver cirrhosis. In 51 patients,hepatic measurements were repeated in follow-up. Age- and gender-matched controls were studied.The size of the caudate lobe and the ratio of thecaudate to right lobe were correlated with liverfunction. The caudate lobe was larger in the studypatients than in the controls, and larger in group 1than in group 2 (P < 0.01). The caudate to right loberatios were also greater in the study patientsespecially in group 1 (P < 0.01). In follow-up, the regression coefficient for the caudate to rightlobe ratio was positive in group 1 and negative in group2 (P < 0.05). Even though the caudate lobe ofpatients with uncompensated liver cirrhosis was larger than that of the controls, patients withcompensated liver cirrhosis had a larger caudate lobeand higher caudate to right lobe ratio compared to thepatients with uncompensated liver cirrhosis. The caudate lobe may have played an importantrole in maintaining proper liver function in thesepatients.     

Improved Fracture Risk Assessment Based on Nonlinear Micro‐Finite Element Simulations From HRpQCT Images at the Distal Radius

More accurate techniques to estimate fracture risk could help reduce the burden of fractures in postmenopausal women. Although micro‐finite element (µFE) simulations allow a direct assessment of bone mechanical performance, in this first clinical study we investigated whether the additional information obtained using geometrically and materially nonlinear µFE simulations allows a better discrimination between fracture cases and controls. We used patient data and high‐resolution peripheral quantitative computed tomography (HRpQCT) measurements from our previous clinical study on fracture risk, which compared 100 postmenopausal women with a distal forearm fracture to 105 controls. Analyzing these data with the nonlinear µFE simulations, the odds ratio (OR) for the factor‐of‐risk (yield load divided by the expected fall load) was marginally higher (1.99; 95% confidence interval [CI], 1.41–2.77) than for the factor‐of‐risk computed from linear µFE (1.89; 95% CI, 1.37–2.69). The yield load and the energy absorbed up to the yield point as computed from nonlinear µFE were highly correlated with the initial stiffness (R² = 0.97 and 0.94, respectively) and could therefore be derived from linear simulations with little loss in precision. However, yield deformation was not related to any other measurement performed and was itself a good predictor of fracture risk (OR, 1.89; 95% CI, 1.39–2.63). Moreover, a combined risk score integrating information on relative bone strength (yield load‐based factor‐of‐risk), bone ductility (yield deformation), and the structural integrity of the bone under critical loads (cortical plastic volume) improved the separation of cases and controls by one‐third (OR, 2.66; 95% CI, 1.84–4.02). We therefore conclude that nonlinear µFE simulations provide important additional information on the risk of distal forearm fractures not accessible from linear µFE nor from other techniques assessing bone microstructure, density, or mass. © 2013 American Society for Bone and Mineral Research.     

Increased cortical porosity in type 2 diabetic postmenopausal women with fragility fractures

The primary goal of this study was to assess peripheral bone microarchitecture and strength in postmenopausal women with type 2 diabetes with fragility fractures (DMFx) and to compare them with postmenopausal women with type 2 diabetics without fractures (DM). Secondary goals were to assess differences in nondiabetic postmenopausal women with fragility fractures (Fx) and nondiabetic postmenopausal women without fragility fractures (Co), and in DM and Co women. Eighty women (mean age 61.3 ± 5.7 years) were recruited into these four groups (DMFx, DM, Fx, and Co; n = 20 per group). Participants underwent dual‐energy X‐ray absorptiometry (DXA) and high‐resolution peripheral quantitative computed tomography (HR‐pQCT) of the ultradistal and distal radius and tibia. In the HR‐pQCT images volumetric bone mineral density and cortical and trabecular structure measures, including cortical porosity, were calculated. Bone strength was estimated using micro–finite element analysis (µFEA). Differential strength estimates were obtained with and without open cortical pores. At the ultradistal and distal tibia, DMFx had greater intracortical pore volume (+52.6%, p = 0.009; +95.4%, p = 0.020), relative porosity (+58.1%, p = 0.005; +87.9%, p = 0.011) and endocortical bone surface (+10.9%, p = 0.031; +11.5%, p = 0.019) than DM. At the distal radius DMFx had 4.7‐fold greater relative porosity (p < 0.0001) than DM. At the ultradistal radius, intracortical pore volume was significantly higher in DMFx than DM (+67.8%, p = 0.018). DMFx also displayed larger trabecular heterogeneity (ultradistal radius: +36.8%, p = 0.035), and lower total and cortical BMD (ultradistal tibia: ?12.6%, p = 0.031; ?6.8%, p = 0.011) than DM. DMFx exhibited significantly higher pore‐related deficits in stiffness, failure load, and cortical load fraction at the ultradistal and distal tibia, and the distal radius than DM. Comparing nondiabetic Fx and Co, we only found a nonsignificant trend with increase in pore volume (+38.9%, p = 0.060) at the ultradistal radius. The results of our study suggest that severe deficits in cortical bone quality are responsible for fragility fractures in postmenopausal diabetic women. © 2013 American Society for Bone and Mineral Research     

Changes in Skeletal Microstructure Through Four Continuous Years of rhPTH(1–84) Therapy in Hypoparathyroidism

Bone remodeling is reduced in hypoparathyroidism, resulting in increased areal bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) and abnormal skeletal indices by transiliac bone biopsy. We have now studied skeletal microstructure by high-resolution peripheral quantitative computed tomography (HR-pQCT) through 4 years of treatment with recombinant human PTH(1–84) (rhPTH[1–84]) in 33 patients with hypoparathyroidism (19 with postsurgical disease, 14 idiopathic). We calculated Z-scores for our cohort compared with previously published normative values. We report results at baseline and 1, 2, and 4 years of continuous therapy with rhPTH(1–84). The majority of patients (62%) took rhPTH(1–84) 100 μg every other day for the majority of the 4 years. At 48 months, areal bone density increased at the lumbar spine (+4.9% ± 0.9%) and femoral neck (+2.4% ± 0.9%), with declines at the total hip (−2.3% ± 0.8%) and ultradistal radius (−2.1% ± 0.7%) (p < .05 for all). By HR-pQCT, at the radius site, very similar to the ultradistal DXA site, total volumetric BMD declined from baseline but remained above normative values at 48 months (Z-score + 0.56). Cortical volumetric BMD was lower than normative controls at baseline at the radius and tibia (Z-scores −1.28 and − 1.69, respectively) and further declined at 48 months (−2.13 and − 2.56, respectively). Cortical porosity was higher than normative controls at baseline at the tibia (Z-score + 0.72) and increased through 48 months of therapy at both sites (Z-scores +1.80 and + 1.40, respectively). Failure load declined from baseline at both the radius and tibia, although remained higher than normative controls at 48 months (Z-scores +1.71 and + 1.17, respectively). This is the first report of noninvasive high-resolution imaging in a cohort of hypoparathyroid patients treated with any PTH therapy for this length of time. The results give insights into the effects of long-term rhPTH(1–84) in hypoparathyroidism. © 2020 American Society for Bone and Mineral Research.     

Utility of Optical Coherence Tomography in the Diagnosis and Management of Optic Neuropathy in Patients with Fibrous Dysplasia

Optic neuropathy (ON) is a highly disabling complication of fibrous dysplasia (FD). The optimal test for identifying and monitoring ON in FD is unknown. Optical coherence tomography (OCT) is an imaging modality that detects retinal nerve fiber layer (RNFL) thinning, a sign of optic nerve atrophy. The purpose of this study was to (i) assess the ability of OCT RNFL thickness measurements to identify ON in FD; (ii) compare the performance of RNFL thickness to computed tomography measurements; and (iii) examine changes in RNFL thickness over time to assess disease progression. A retrospective cohort study was performed to assess subjects (n = 70) who underwent neuro-ophthalmologic examination, including OCT. The diagnostic utility of RNFL thickness was determined using receiver operator characteristic (ROC) curve analysis, and the accuracy was compared with computed tomography measurements. The relationship between RNFL thickness and age was assessed cross-sectionally, using generalized estimating equation methodology, and longitudinally, using a generalized mixed model. Eleven subjects were identified with ON. RNFL thickness identified ON (area under curve = 0.997, p < 0.0001) with sensitivity and specificity of 100% and 95%, respectively, when using the diagnostic criterion of ≤71 μm. RNFL thickness outperformed computed tomography measurements of optic canal narrowing and optic nerve stretch. Subjects with ON exhibited a greater decrease in RNFL thickness with each year of age (−0.70 μm/year, p < 0.001) than subjects with normal vision (−0.16 μm/year, p < 0.05). When assessed longitudinally, subjects with normal vision demonstrated an increase in RNFL thickness until approximately age 20 years that decreased thereafter. In contrast, subjects with ON exhibited an earlier decrease in RNFL thickness during adolescence. In conclusion, RNFL thickness of ≤71 μm accurately identified ON in this population. By establishing the difference in rate of RNFL thinning in patients with and without ON, clinicians may distinguish between patients at risk for ON and intervene before irreversible damage. © 2020 American Society for Bone and Mineral Research.     

Computed Tomography Patterns in Small Bowel Obstruction after Open Distal Gastric Bypass

Background: Life-threatening small bowel obstruction (SBO) after Roux-en-Y gastric bypass can present with surprisingly minimal laboratory and plain x-ray findings. Based on a 10-year (1994-2003) experience of 1,409 open distal gastric bypasses, we present clinical and radiological findings in 29 patients with unusual forms of bowel obstruction. Methods: A retrospective chart review was conducted. A radiologist experienced in reviewing these in gastric bypass patients reviewed all computed tomography (CT) scans. Results: CT findings: The normal appearance and 7 recurring patterns of small bowel obstruction were identified. These include: 1) intussusception, 2) internal hernia through Petersen's space, 3) through Petersen's space and the mesenteric defect at enteroenterostomy, 4) through the mesenteric defect from the entero-enterostomy, 5) isolated biliary limb obstruction, 6) segmental non-anastomotic ischemia, and 7) internal hernia through bands. Clinical findings: 1 had peritonitis, and 1 had free air on plain film. WBC count was normal in 20/27 patients (74%) including 5/6 (83%) with dead bowel. 9/14 patients (62%) had "non-specific" findings on x-rays. 7 of these had an internal hernia (2 with volvulus and 2 with dead bowel), 1 had biliopancreatic limb obstruction, and 1 had peritonitis. Conclusion: Patients with SBO after distal gastric bypass may present with vague complaints and confusing laboratory and non-specific findings on x-rays. Delayed diagnosis can have catastrophic consequences. CT imaging with oral and intravenous contrast can be life-saving, and should be obtained in all gastric bypass patients with abdominal pain, particularly when all other parameters seem "normal". Unexplained abdominal pain should prompt exploration.     

早期电针治疗缺血性与出血性中风头颅CT分析

观察１００例中风急性期患者,结果表明电针对急性中风疗效肯定（显效率７６７％,有效率９７０％）。结合ＣＴ分析,中风患者病情程度及疗效与病灶性质关系不明显（Ｐ＞００５）,而与病灶大小,部位深浅有关（Ｐ＜００１）。