Efstratios Moralidis

Scintigraphic, biochemical, and clinical response to zoledronic acid treatment in patients with Paget's disease of bone

Bisphosphonates have long been used with success in the treatment of Paget’s disease of bone (PDB). The aim of this study was to evaluate the early (up to 3 months) and late (at 12 months) scintigraphic, biochemical, and clinical response to a single intravenous infusion of zoledronic acid (ZOL) in patients with PDB serially assessed for 1 year. Nine patients with 30 bone lesions caused by PDB were prospectively evaluated. Total serum alkaline phosphatase (SAP) was serially measured. Scintigraphy was performed before and at 3 and 12 months after ZOL administration, and bone lesions were assessed quantitatively. After treatment, pain was alleviated in five of six patients starting from the first month. At 3 months, a significant decrease of SAP levels compared to baseline values was found (322 ± 211 IU/l before vs. 101 ± 36 IU/l 3 months after; P < 0.05), with normal values attained in all except one patient. The scintigraphic index of involvement (SII), a marker for the perpatient activity of the disease, was reduced from 14.4 ± 7.6 to 7.2 ± 1.8 (P = 0.01). The scintigraphic ratio (SR), a marker for the per-lesion activity of the disease, was reduced from 12.8 ± 7.7 to 7.0 ± 2.9 (P < 0.001). The values of markers of disease activity remained unchanged up to 12 months. A single intravenous administration of ZOL leads to a favorable clinical, biochemical, and scintigraphic response in patients with PDB starting as early as 3 months after treatment and lasting no less than 12 months (i.e., considerably longer than the other existing therapies).

The effect of zoledronic acid on serum dickkopf-1, osteoprotegerin, and RANKL in patients with Paget's disease of bone.

Overexpression of dickkopf (DKK)-1 in pagetic osteoblast cultures resulted in stimulation of osteoclast proliferation and inhibition of osteoblast growth. The aim of this study was to evaluate for the first time in Pagets disease of bone (PDB): 1) the serum levels of DKK1; 2) the association of DKK-1 with receptor activator of nuclear factor kappa B (RANKL) and osteoprotegerin (OPG); and 3) the effect of zoledronic acid (ZOL) on serum DKK-1, RANKL, and OPG. The study was conducted as a prospective open-label cohort study. Eleven patients with PDB (median age 60 years) were recruited. Twelve age- gender- and body mass index (BMI)-matched healthy individuals were used as controls at baseline. Blood samples were obtained before treatment (baseline) and after 3, 6, 12, and 18 months following ZOL infusion in patients with PDB. Patients with PDB had significantly higher RANKL (p=0.002), OPG (p=0.001), and bone markers (total alkaline phosphatase and C-terminal cross-linking telopeptide of type I collagen) compared with controls at baseline. There was no difference between groups in DKK-1 at baseline. Bone markers were both significantly decreased after therapy. Serum OPG, RANKL, RANKL:OPG ratio, and DKK-1 remained unaffected throughout the study. No correlations were found between OPG, RANKL, RANKL:OPG ratio, and DKK-1 at baseline nor between their changes during the study. Although both OPG and RANKL were increased in patients with PDB, ZOL had no effect on their serum levels. Serum DKK-1 was neither increased in patients with PDB nor related to OPG and RANKL, and was unaffected by ZOL.

Profound hypocalcemia following effective response to zoledronic acid treatment in a patient with juvenile Paget’s disease

Juvenile Paget’s disease (JPD) is a rare, autosomal recessive osteopathy. Although it has phenotypic overlap with Paget’s disease of bone (PDB), it is probably a distinct entity. Because of its rarity, optimal disease management has not yet been established by randomized controlled trials. However, clinical, biochemical, and radiographic improvement has been reported after treatment with antiresorptive agents, including calcitonin and bisphosphonates (BPs). Compared with other BPs, zoledronic acid (ZOL) has a higher affinity to bone mineral and is a stronger inhibitor of the enzyme farnesyl pyrophosphate synthase (the main target of nitrogen-containing BPs), properties that explain the prolonged effect of ZOL on bone turnover and render it a therapeutic option for JPD, similar to PDB. We describe hereby, for the first time in the literature, the case of a patient with JPD who developed severe hypocalcemia and secondary hyperparathyroidism following effective treatment with ZOL.

Myocardial perfusion scintigraphy in asymptomatic diabetic patients: a critical review

The increasing prevalence of diabetes mellitus and the associated high cardiovascular risk has made the non‐invasive identification of silent coronary heart disease in diabetic individuals an important issue. This strategy could identify higher risk asymptomatic patients with diabetes mellitus in whom coronary revascularization may improve the outcome beyond that achieved by currently recommended medical management. Stress myocardial perfusion imaging has been shown to be effective in detecting coronary heart disease and predicting adverse cardiac events in asymptomatic diabetic patients. However, the clinical utility of myocardial perfusion scintigraphy is debated intensively due to the paucity of prospective and outcome based evidence. The controversy stems from several observational studies, epidemiologic data and cost‐effectiveness analyses. Thus, although several authors and professional organizations advocate the use of stress imaging for screening higher risk asymptomatic diabetic patients, others are cautious in recommending any kind of stress testing in that population. This review is based on a broad survey of the literature and discusses the potential role of stress myocardial perfusion scintigraphy in screening asymptomatic diabetic subjects for coronary heart disease in the current era and in relation with other non‐invasive screening tools. Copyright

Yttrium-90 radiation synovectomy in knee osteoarthritis: a prospective assessment at 6 and 12 months

ObjectiveTo assess the outcome of yttrium-90 radiation synovectomy at 6 and 12 months in patients with knee osteoarthritis unresponsive to systematic or local medical treatment. MethodsConsecutive patients with osteoarthritic knee pain resistant to conventional therapy and submitted to intraarticular yttrium-90 treatment because of synovial inflammation, as demonstrated by early-phase bone scintigraphy, were prospectively evaluated at 6 and/or 12 months. The assessment of the outcome of treatment was based on self-reporting of relief of knee pain limiting daily activities, measured as percentage reduction of the pretherapeutic joint discomfort with a Visual Analogue Scale. Resting and nocturnal pain also were considered, together with knee flexibility and ultrasonographic changes. ResultsAmong a total of 97 patients, a ≥50% Visual Analogue Scale pain palliation was experienced by 64 of 90 (71.1%) patients at 6 months and 50 of 69 (72.5%) at 12 months (P = 0.992). Moreover, nocturnal and resting pain alleviation, gain in knee flexibility and regression of large joint effusions and Bakers cysts were observed in considerable proportions. In the evaluation of the outcome of treatment in 62 patients with serial assessments using a composite criterion, 42 (67.7%) versus 40 (64.5%) had a satisfactory response at 6 and 12 months, respectively (P = 0.850). The probability of a favourable therapeutic result was inversely related to the severity of radiographic joint changes. ConclusionYttrium-90 synovectomy exerts a beneficial therapeutic effect in a substantial proportion of patients with osteoarthritic knee pain and synovial inflammation, inadequately controlled by pharmacotherapy. Clinical improvement is inversely related to radiographic knee damage.

123I-Metaiodobenzylguanidine accumulation in a urinoma and cortex of an obstructed kidney after surgical resection of an abdominal neuroblastoma

Surgical ureteric injury is rare and often unsuspected for a long time. We present a child in whom an abdominal neuroblastoma was completely excised, but during surgery the left ureter was transected and anastomosed. One month later, during postoperative disease staging, abnormal 123I-MIBG accumulation was observed in the left renal cortex and the left side of the abdomen. These findings were consistent with acute total obstruction and urinoma formation and were subsequently confirmed by renography and MRI. Despite treatment efforts, a significant amount of left renal mass and function were lost over the following months. These unusual findings are new additions to the literature regarding potential false-positive interpretations of 123I-MIBG scans.

Hypertrophic osteoarthropathy manifested with isolated calcaneal periostitis in bone scintigraphy

Hypertrophic osteoarthropathy (HOA) is an incompletely understood syndrome characterized by digital clubbing and periosteal proliferation of long bones and it is commonly associated with primary lung tumors. Bone scintigraphy is a sensitive method in detecting HOA and characteristic findings have been reported. We present the case of a man with newly diagnosed non-small cell lung cancer, unremarkable clinical examination and blood tests and no digital clubbing. During disease staging, however, bone scintigraphy showed intense calcaneal cortical proliferation bilaterally without involvement of other parts of the skeleton. Cortical reaction of both calcanei resolved significantly after chemotherapy. This case indicates that HOA may manifest with isolated calcaneal periostitis bilaterally, which is a new addition to the literature.

Radionuclide parathyroid imaging: a concise, updated review

The hypercalcemia of hyperparathyroidism (HPT) can cause devastating effects to the patient and only surgical removal of the hyperfunctioning parathyroid tissue can definitely cure the disease. Radionuclide parathyroid imaging has no role in the diagnosis of hyperparathyroidism or in the selection of the type of treatment. However, once surgery is decided (99m)Tc-sestamibi scanning can localize abnormal parathyroid glands preoperatively. In primary HPT radionuclide assessment may occasionally be helpful before bilateral neck exploration, it can identify patients suitable for focused surgery and is a prerequisite of the minimally invasive radioguided parathyroidectomy. In secondary and tertiary HPT the clinical value of parathyroid scintigraphy remains debatable, but in persistent or recurrent disease this modality is a first line examination before reoperation. In conclusion, (99m)Tc-sestamibi assessment has a well defined clinical role in the surgical management of patients with primary hyperparathyroidism and in recurrent disease, but its usefulness in cases of secondary hyperparathyroidism is not clearly established.

Identification of advanced coronary artery disease with exercise myocardial perfusion imaging: the clinical value of a novel approach for assessing lung thallium-201 uptake

IntroductionThe precise clinical utility of lung 201Tl uptake in exercise SPECT myocardial perfusion imaging remains open to research. This study validates an optimal index for lung 201Tl uptake measurement and assesses its value in the prediction of higher-risk coronary artery disease (CAD).MethodThree hundred and ninety-eight patients underwent exercise SPECT myocardial perfusion imaging. They were separated into derivation (n = 217) and validation (n = 186) groups, both including sub-populations of lower- and higher-risk CAD, according to coronary angiography. Another 56 individuals with a low probability of CAD comprised the control group. From a planar, anterior, post-exercise acquisition, the lung (L) to heart (H) maximal (L/Hmax), total (L/Hmean) and background-subtracted total (L/Hnet) ratios were calculated. These were also adjusted for confounding variables, as assessed from the control group. ROC analysis was used to compare the L/H ratios and define thresholds of abnormality. The performance of the optimal index was assessed in the derivation group and was then tested in the validation population. Subsequently, it was compared with other scintigraphic, exercise electrocardiography and clinical variables.ResultsIn the derivation group L/Hnet was a better discriminator for higher-risk CAD than both L/Hmax and L/Hmean. Similarly, the adjusted L/Hnet was a better discriminator than both the adjusted L/Hmax and the adjusted L/Hmean. No significant difference was attained between L/Hnet and the adjusted L/Hnet. At the upper defined threshold of abnormality, sensitivity and specificity of L/Hnet in the detection of higher-risk CAD in the derivation and the validation cohorts were 52% and 92% versus 47% and 94%, respectively (p =  ns). The results were similar at other defined thresholds. Moreover, L/Hnet was found to be a significant predictor of higher-risk CAD, superior to myocardial perfusion images, transient ventricular dilation measurements, and clinical and exercise testing variables (ROC analysis and logistic regression). By raising the threshold of abnormality of L/Hnet, specificity and positive predictive value increased, whereas sensitivity and negative predictive value decreased.ConclusionLung 201Tl assessment assists substantially in the identification of higher-risk CAD in exercise SPECT myocardial perfusion imaging and this is best achieved by L/Hnet. This index is a significant predictor of higher-risk CAD, superior to myocardial perfusion images, and its value is associated with the probability of a disease state.

Left ventricular systolic and diastolic function in normotensive type 2 diabetic patients with or without autonomic neuropathy: a radionuclide ventriculography study.

We investigated the relation between diabetic autonomic neuropathy (DAN) and left ventricular (LV) function in 59 patients with type 2 diabetes mellitus (T2DM) free of coronary artery disease (CAD) or hypertension. Diabetic autonomic neuropathy was established by ≥2 abnormal autonomic nervous function tests. Left ventricular systolic and diastolic functions were assessed by resting radionuclide ventriculography. Compared with non-DAN patients (n = 24), patients with DAN (n = 35) had an increased adjusted atrial contribution to ventricular filling (A/V%, 30.1% ± 8.2% vs 26.5% ± 5.1%; P = .031), suggestive of diastolic dysfunction (DD). There were no differences between the 2 groups in peak filling rate, first 1/3 filling fraction, ejection fraction, cardiac output, and cardiac index. Patients with diabetic autonomic neuropathy had an increased heart rate (77.8 ± 6.3 vs 69.3 ± 3.3 bpm; P < .0001) and a higher rest LV workload (10 072 ± 1165 vs 8606 ± 1075 bpm mm Hg; P < .0001). Patients with DAN T2DM without CAD or hypertension have DD, increased A/V index, and a higher LV working load than non-DAN patients.