18F-fluoride Positron Emission Tomography Measurements of Regional Bone Formation in Hemodialysis Patients with Suspected Adynamic Bone Disease

¹⁸F-fluoride positron emission tomography (¹⁸F-PET) allows the assessment of regional bone formation and could have a role in the diagnosis of adynamic bone disease (ABD) in patients with chronic kidney disease (CKD). The purpose of this study was to examine bone formation at multiple sites of the skeleton in hemodialysis patients (CKD5D) and assess the correlation with bone biopsy. Seven CKD5D patients with suspected ABD and 12 osteoporotic postmenopausal women underwent an ¹⁸F-PET scan, and bone plasma clearance, K _i, was measured at ten skeletal regions of interest (ROI). Fifteen subjects had a transiliac bone biopsy following double tetracycline labeling. Two CKD5D patients had ABD confirmed by biopsy. There was significant heterogeneity in K _i between skeletal sites, ranging from 0.008 at the forearm to 0.028 mL/min/mL at the spine in the CKD5D group. There were no significant differences in K _i between the two study groups or between the two subjects with ABD and the other CKD5D subjects at any skeletal ROI. Five biopsies from the CKD5D patients had single tetracycline labels only, including the two with ABD. Using an imputed value of 0.3 μm/day for mineral apposition rate (MAR) for biopsies with single labels, no significant correlations were observed between lumbar spine K _i corrected for BMAD (K _i/BMAD) and bone formation rate (BFR/BS), or MAR. When biopsies with single labels were excluded, a significant correlation was observed between K _i/BMAD and MAR (r = 0.81, p = 0.008) but not BFR/BS. Further studies are required to establish the sensitivity of ¹⁸F-PET as a diagnostic tool for identifying CKD patients with ABD.     

Metabolic disturbances identified by SPECT-CT in patients with a clinical diagnosis of sacroiliac joint incompetence

Purpose

To establish the sensitivity and specificity of cross-sectional scintigraphy [single photon emission computed tomography (SPECT)] combined with computed X-ray tomography (CT) in the detection of sacroiliac joint (SIJ) mechanical dysfunction and evaluate reproducibility of reporting.

Methods

Patients with pelvic girdle pain either on the basis of peri-partum SIJ dysfunction or trauma were included. These patients were imaged with bone scintigraphy with hybrid imaging with SPECT/CT.

Results

The study group comprised 100 patients (72 females, 28 males). Trauma accounted for 52 % and the remainder were patients with peri-partum pain. Average age was 43 years and average length of history was >2 years. The major finding was increased uptake in the upper SIJ and posterior soft-tissues/ligaments. Hybrid imaging had a sensitivity of 95 % and specificity of 99 %. Positive predictive value was 99 % and negative predictive value 94 %. Power of the test was 1.0. Reproducibility of the test was good with kappa values of 0.85.

Conclusion

Hybrid imaging with SPECT/CT reproducibly demonstrates metabolic alterations around the SIJ in patients with SIJ dysfunction, which we have termed SIJ incompetence. The condition is more common than previously recognised and frequently occurs after trauma, which has not been reported previously.     

18F‐fluoride PET as a noninvasive imaging biomarker for determining treatment efficacy of bone active agents at the hip: A prospective,randomized, controlled clinical study

The functional imaging technique of ¹⁸F‐fluoride positron emission tomography (¹⁸F‐PET) allows the noninvasive quantitative assessment of regional bone formation at any skeletal site, including the spine and hip. The aim of this study was to determine if ¹⁸F‐PET can be used as an early biomarker of treatment efficacy at the hip. Twenty‐seven treatment‐naive postmenopausal women with osteopenia were randomized to receive teriparatide and calcium and vitamin D (TPT group, n = 13) or calcium and vitamin D only (control group, n = 14). Subjects in the TPT group were treated with 20 µg/day teriparatide for 12 weeks. ¹⁸F‐PET scans of the proximal femur, pelvis, and lumbar spine were performed at baseline and 12 weeks. The plasma clearance of ¹⁸F‐fluoride to bone, K_i, a validated measurement of bone formation, was measured at four regions of the hip, lumbar spine, and pelvis. A significant increase in K_i was observed at all regions of interest (ROIs), including the total hip (+27%, p = 0.002), femoral neck (+25%, p = 0.040), hip trabecular ROI (+21%, p = 0.017), and hip cortical ROI (+51%, p = 0.001) in the TPT group. Significant increases in K_i in response to TPT were also observed at the lumbar spine (+18%, p = 0.001) and pelvis (+42%, p = 0.001). No significant changes in K_i were observed for the control group. Changes in BMD and bone turnover markers were consistent with previous trials of teriparatide. In conclusion, this is the first study to our knowledge to demonstrate that ¹⁸F‐PET can be used as an imaging biomarker for determining treatment efficacy at the hip as early as 12 weeks after initiation of therapy.     

Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein.

Our group has previously demonstrated that oxidized phospholipids in mildly oxidized LDL (MM-LDL) produced by oxidation with lipoxygenase, iron, or cocultures of artery wall cells increase monocyte-endothelial interactions and this sequence of events is blocked by HDL. To obtain further insight into the mechanism by which HDL abolishes the activity of MM-LDL we investigated the effect of the HDL-associated ester hydrolase paraoxonase (PON). Treatment of MM-LDL with purified PON significantly reduced the ability of MM-LDL to induce monocyte-endothelial interactions. Inactivation of PON by pretreating HDL with heat or EDTA reduced the ability of HDL to inhibit LDL modification. HPLC analysis of phospholipids isolated from MM-LDL before and after treatment with purified PON showed that the 270 nm absorbance of phospholipids was decreased, while no effect was observed on 235 nm absorbance. Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (Ox-PAPC) and specific fractions of Ox-PAPC isolated by HPLC induced the same monocyte-endothelial interactions as did MM-LDL. Biologically active and inactive HPLC fractions of Ox-PAPC were compared by fast atom bombardment-mass spectrometry which revealed that active fractions possessed ions with a mass to charge [correction of change] ratio greater than native PAPC by multiples of 16 D suggesting the addition of 3 and 4 oxygen atoms to PAPC. Comparison of Ox-PAPC by fast atom bombardment-mass spectrometry before and after PON treatment showed that PON destroyed these multi-oxygenated molecules found in biologically active fractions of Ox-PAPC. These results suggest that PON in HDL may protect against the induction of inflammatory responses in artery wall cells by destroying biologically active lipids in mildly oxidized LDL.     

Exercise myocardial perfusion scintigraphy with technetium-99m methoxy isobutylisonitrile: a comparative study with thallium-201

The evaluation of technetium-99m methoxy isobutylisonitrile for the diagnosis of coronary artery disease requires comparative validation against thallium-201, the established perfusion imaging agent. We have compared myocardial and lung uptake of both radiotracers following maximal exercise in 52 patients: 40 with angiographically proven coronary disease. Qualitative and quantitative image analysis showed the diagnostic sensitivity of technetium-99m methoxy isobutylisonitrile to compare favourably with that of thallium-201 as reflected by the mean number of ischaemic segments identified: 5.6 +/- 2.5 vs 4.8 +/- 2.1 by qualitative analysis, and 5.7 +/- 3.2 vs 5.0 +/- 2.6 segments by quantitative analysis. More reversibly ischaemic segments per patient were identified with technetium-99m methoxy isobutylisonitrile than with thallium-201: 3.6 +/- 2.3 vs 1.8 +/- 1.9. There was a higher exercise myocardial to background count ratio with technetium-99m methoxy isobutylisonitrile: 3.16:1 vs 2.58:1, and the mean exercise lung uptake normalised to left ventricular uptake ('lung index'), was lower for technetium-99m methoxy isobutylisonitrile than for thallium-201 (36 +/- 8% vs 40 +/- 10%). Five of the six patients with abnormal elevation of the thallium-201 exercise lung index also had elevation of the technetium-99m methoxy isobutylisonitrile exercise lung index, and all had extensive coronary artery disease. These results indicate that technetium-99m methoxy isobutylisonitrile is at least as effective as thallium-201 for detecting exercise induced myocardial ischaemia. However, technetium-99m methoxy isobutylisonitrile provides a better image quality and may be a more sensitive marker of defect reversibility. For both radiotracers lung uptake is increased with extensive coronary artery disease and measurement of this variable provides prognostic information.     

Risedronate reverses bone loss in postmenopausal women with low bone mass: results from a multinational, double-blind, placebo-controlled trial. BMD-MN Study Group

Our objective was to investigate the efficacy and tolerability of risedronate in postmenopausal women with low bone mass. Women with a mean lumbar spine T-score of -2 or less (n = 543) received 24 months of placebo or risedronate (2.5 or 5 mg/day). All received calcium (1 g/day). The principal outcome measures were bone mineral density (BMD) at the lumbar spine, femoral neck, and femoral trochanter. At 24 months, lumbar spine BMD increased from baseline by 4% with 5 mg risedronate and 1.4% in the 2.5-mg group, compared with no change with placebo. Efficacy was similar in women who were less than 5 yr and more than 5 yr postmenopausal. At 24 months, risedronate (5 mg) had also increased BMD at the femoral neck and trochanter, whereas BMD decreased in the placebo group. BMD increases were seen at all three sites with risedronate (5 mg) after only 6 months of therapy. Risedronate was well tolerated; upper gastrointestinal adverse events were similar to placebo. We conclude that risedronate (5 mg) increases BMD rapidly and effectively and is well tolerated in postmenopausal women with low bone mass, regardless of time since menopause.     

Genetic-dietary regulation of serum paraoxonase expression and its role in atherogenesis in a mouse model.

In an effort to identify genetic factors contributing to atherogenesis, we have studied inbred strains of mice that are susceptible (C57BL/6J) and resistant (C3H/HeJ) to diet-induced aortic fatty streak lesions. When maintained on a low-fat diet, HDL isolated from both strain C57BL/6J (B6) and C3H/HeJ (C3H) mice protect against LDL oxidation in a coculture model of the artery wall. However, when maintained on an atherogenic diet high in fat and cholesterol, the HDL isolated from B6 mice lose the capacity to protect, whereas HDL from C3H mice protect equally well. Associated with the loss in the ability of HDL to protect is a decrease in the activity of serum paraoxonase, a serum esterase carried on HDL that has previously been shown to protect against LDL oxidation in vitro. The levels of paraoxonase mRNA decreased in B6 mice upon challenge with the atherogenic diet but increased in C3H, indicating that paraoxonase production is under genetic control. In a set of recombinant inbred strains derived from the B6 and C3H parental strains, low paraoxonase mRNA levels segregated with aortic lesion development, supporting a role for paraoxonase in atherogenesis.     

Spontaneous hematoma of the iliac psoas muscle in chronic myeloid leukemia. A case report

Spontaneous hematoma in the ilio-psoas muscle is an uncommon condition, usually observed as a complication of anticoagulation or hemophilia. Clinically, the onset is marked by violent pain in the territory of femoral nerve and/or psoitis. The diagnosis is confirmed by echography or CT-scan. The most serious complications are loss of self-sufficiency and neuro-muscular after-effect. Surgery is recommended in patients with neurological suffering, followed by early physiotherapy. We report the case of a 42-year-old man, with an ilio-psoas muscle hematoma, revealing chronic myeloid leukemia, without any hemostasis disorder.