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 Paget's 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.

Effect of strontium ranelate on lumbar spine bone mineral density in women with established osteoporosis previously treated with teriparatide.

Teriparatide (TPTD - recombinant human parathyroid hormone 1-34) markedly increases bone mineral density (BMD) and reduces fracture risk. Sequential treatment with an antiresorptive agent is believed to preserve or further increase BMD. Strontium ranelate (SR) is thought to uncouple bone remodeling resulting in increased BMD and reduced fracture risk. We aimed to evaluate the effect of SR on BMD in women with established osteoporosis previously treated with TPTD. Nineteen out of the consecutive 23 initially recruited postmenopausal Caucasian women (aged 65.9+/-1.8 years) with established osteoporosis completed treatment with TPTD, 20 microg daily for 18 months, followed by SR 2 g daily for 12 months. Lumbar spine BMD was measured by dual-energy X-ray absorptiometry (DXA) pre- and post-TPTD administration, as well as twelve months post-SR administration. Blood samples for bone-specific alkaline phosphatase (BSAP) and C-terminal telopeptide of type 1 collagen (CTx) were obtained at the same time points. Lumbar spine BMD increased significantly after 18 months of TPTD (p<0.001) and further improved with sequential SR treatment (p=0.033). Serum BSAP and CTx increased significantly with TPTD (p=0.008 and 0.017, respectively) and reduced to baseline levels after SR treatment (p=0.031 and 0.019, respectively). The change in BSAP was positively correlated with the change in CTx during both TPTD (r=0.641, p=0.007) and SR treatment (r=0.539, p=0.026). In conclusion, our data suggest that SR following TPTD administration further increases BMD and could represent an effective sequential treatment.

The use of demographic, ultrasonographic and scintigraphic data in the diagnostic approach of thyroid nodules.

INTRODUCTION: Thyroid nodules are a common diagnostic challenge mainly because of the need to exclude thyroid malignancy. The aim of this study was to evaluate the usefulness of demographic, ultrasonographic and scintigraphic findings in differentiating benign from malignant thyroid lesions in patients presenting with thyroid nodules. MATERIALS AND METHODS: 941 patients, who presented with palpable thyroid nodules and underwent at least one fine-needle aspiration biopsy (FNAB), were retrospectively evaluated. RESULTS: The thyroid was assessed by ultrasonography (US) in 796 patients and by scintigraphy (SC) in 774 patients. The final diagnostic outcome was established after surgery (n=183) or after a minimum of one-year clinical follow-up period. Higher rates of malignancy were observed in male gender (p<0.001), in patients presenting with a solitary nodule in US (p<0.001), in nodules with maximum diameter > or =4.5 cm in US (p=0.024) and in nodules detectable by SC (p=0.006). There were no statistical differences in the rates of malignancy among cystic, solid or mixed nodules in US or among "hot", "warm" or "cold" nodules in SC. CONCLUSIONS: Male gender, solitary nodule and nodule diameter > or =4.5 cm can serve as adjuncts to FNAB in predicting the risk of thyroid malignancy in patients presenting with thyroid nodules.

Epidemiologic analysis of thyroid fine needle aspiration biopsies over a period of 18 years (1987-2004).

INTRODUCTION: Fine Needle Aspiration Biopsy (FNA) is a method widely used in the assessment of thyroid nodules. The main aim of this 18-year retrospective study was the investigation of the diagnostic value of FNA cytology in thyroid malignancy. SUBJECTS AND METHODS: We retrospectively reviewed 1376 patients who underwent 1938 FNAs from 1987 to 2004 in the Department of Endocrinology, "Hippokration" General Hospital, Thessaloniki, Greece. Of them 178 subsequently underwent total or subtotal thyroid resection and a pathology report was available. RESULTS: FNA cytology shows a sensitivity of 76.2% and a specificity of 90.5% for thyroid malignancy, with a significant agreement between FNA cytology and the histology following resection surgery (Cohen's method, p<0.05). There was a considerable improvement in the diagnostic value of FNA cytology during the sub-period 1996-2004 as compared to the sub-period 1987-1995. CONCLUSIONS: 1) FNA is a reliable diagnostic method in the assessment of thyroid malignancy, 2) a non-diagnostic FNA should always be repeated, 3) meticulous follow-up is mandatory, even after a cytological result of benign hyperplasia and 4) increased experience can improve the diagnostic value of FNA in thyroid malignancy.

Effect of exogenous intermittent recombinant human PTH 1-34 administration and chronic endogenous parathyroid hormone excess on glucose homeostasis and insulin sensitivity.

We aimed to evaluate the effects of exogenous intermittent teriparatide (rhPTH 1-34) administration versus the chronic exposure to excess endogenous parathyroid hormone (PTH), as in pHPT, on glucose homeostasis. Two patient groups were studied: Group 1 included 25 normocalcemic women with postmenopausal osteoporosis (age 65.2+/-1.6 years) studied before and six months after teriparatide initiation; Group 2 included 19 postmenopausal women with pHPT (age 55.2+/-2.5 years) studied before and six months after successful parathyroidectomy. Calcium - total (Ca) and corrected (CCa) - ALP, PTH, as well as glucose and insulin concentrations during an oral glucose tolerance test (OGTT) were determined before and six months after either intervention. Area under the curve for glucose (AUCglu) and insulin (AUCins) were calculated. DeltaIns30'/DeltaGlu30' was applied as an index of insulin secretion. The HOmeostasis Model of Assessment (HOMA) and Matsuda ISI (Insulin Sensitivity Index) were used to calculate insulin resistance (IR) and whole body insulin sensitivity, respectively. In Group 1 no difference was found in any OGTT-derived parameter. In Group 2 significant reductions in AUCins and DeltaIns30'/DeltaGlu30' were observed. No correlation between the change in DeltaCCa or DeltaPTH and DeltaAUCglu or DeltaAUCins was found in either group. Our data suggest that while subtle transient alterations of Ca and PTH within the normal range as in exogenous rhPTH 1-34 administration do not affect glucose homeostasis, the continuously elevated Ca and endogenous PTH levels as in pHPT affect insulin sensitivity and result in increased insulin secretion.

Head-to-head comparison of risedronate vs. teriparatide on bone turnover markers in women with postmenopausal osteoporosis: a randomised trial.

AIMS: We aimed to compare the effect of risedronate (RIS) and teriparatide (TPTD) (recombinant human parathyroid hormone 1-34) on bone turnover markers in women with postmenopausal osteoporosis. METHODS: Forty-four Caucasian women (age 65.1 +/- 1.6 years) with postmenopausal osteoporosis were randomly assigned to receive either RIS 35 mg once weekly (n = 22) or TPTD 20 microg once daily (n = 22) for 12 months. Serum N-terminal propeptide of type 1 collagen (P1NP), C-terminal telopeptide of type 1 collagen (CTx), total alkaline phosphatase (ALP) and intact parathyroid hormone (iPTH) were obtained from all women before, 3 and 6 months after treatment initiation. Lumbar spine bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry before and 12 months after treatment initiation. RESULTS: P1NP, CTx and total ALP levels decreased in RIS group (p < 0.001) and increased in TPTD group (p < 0.001) throughout the treatment. iPTH increased significantly in RIS group (p < 0.05) and decreased in TPTD group (p < 0.001). Finally, lumbar spine BMD increased significantly in both RIS (p = 0.003) and TPTD groups (p < 0.001) without significant differences between them. CONCLUSIONS: Our data suggest that both serum P1NP and CTx are reliable markers of RIS and TPTD action in women with postmenopausal osteoporosis. In a similar way, serum total ALP can be used as an alternative marker for monitoring both RIS and TPTD action, while iPTH can be used only for TPTD-treated women. The increase in P1NP and CTx after 3 months of treatment with RIS or TPTD can predict the increase in BMD after 12 months of treatment.

Serum osteoprotegerin and RANKL are not specifically altered in women with postmenopausal osteoporosis treated with teriparatide or risedronate: a randomized, controlled trial.

Risedronate and teriparatide have opposite actions on the osteoblast-osteoclast dipole and are expected to influence the RANK/RANKL/osteoprotegerin (OPG) system. We aimed to evaluate changes in serum OPG and RANKL after risedronate or teriparatide administration in postmenopausal osteoporotic women. Seventy-four postmenopausal Caucasian women (age 64.1+/-1.0 years) were studied. Women with osteopenia served as controls (group 1, n=30). Women with osteoporosis were randomly assigned to either risedronate 35 mg once weekly (group 2, n=21) or teriparatide 20 microg once daily (group 3, n=23) for six months. Blood samples for serum RANKL, OPG, N-terminal propeptide of type 1 collagen (P1NP), and C-terminal telopeptide of type 1 collagen (CTx) were obtained before treatment and three and six months after treatment. P1NP and CTx levels remained unchanged in group 1, decreased in group 2 (p<0.001), and increased in group 3 women (p<0.001) throughout the treatment. OPG levels remained unchanged while RANKL decreased gradually in all groups (p<0.001). There was no correlation between OPG or RANKL and P1NP or CTx. Our data suggest that neither antiresorptive nor osteoanabolic therapy causes specific alterations of serum OPG/RANKL levels; therefore, these cytokines cannot substitute for the established markers of bone turnover in the monitoring of response to osteoporosis treatment.

Acute and chronic effect of teriparatide on glucose metabolism in women with established osteoporosis.

There is indirect evidence of unfavorable effects of parathyroid hormone (PTH) on glucose metabolism. Teriparatide (recombinant human PTH 1-34-TPTD) has recently been available for the treatment of osteoporosis. The aim of this prospective study was to evaluate the acute and chronic effect of TPTD on blood glucose and insulin levels in women with established osteoporosis. Twenty-three postmenopausal women with established osteoporosis (mean age 65.6+/-1.8 years) received daily injections of 20 mg TPTD for six months. Three oral glucose tolerance tests (OGTT) were performed: one day before the first injection (OGTT-basal), one hour after (OGTT-acute) and six months after initiation of therapy (OGTT-chronic). There were significant differences between the OGTT-basal and OGTT-acute values in glucose at 90 min (168.3+/-9.8 vs. 180.6+/-9.2, p<0.05) and 120 min (152.0+/-8.7 vs. 170.5+/-7.8, p<0.01), between the OGTT-basal and OGTT-chronic values for glucose at 90 min (168.3+/-9.8 vs. 184.5+/-13.3, p<0.05) and between the OGTT-basal and OGTT-acute for insulin at 90 min (56.7+/-7.4 vs. 68.7+/-8.2, p<0.01). These differences remained significant for the subgroup of patients with normal (n=8) but not impaired glucose tolerance or diabetes mellitus (n=15). TPTD seems to have an acute, subclinical adverse impact on stimulated glucose levels, possibly due to insulin resistance. This impact tends to subside when TPTD is continued on a chronic basis.

Communication infrastructure in a contact center for home care monitoring of chronic disease patients.

The Citizen Health System (CHS) is a European Commission (EC) funded project in the field of IST for Health. Its main goal is to develop a generic contact center which in its pilot stage can be used in the monitoring, treatment and management of chronically ill patients at home in Greece, Spain and Germany. Such contact centers, which can use any type of communication technology, and can provide timely and preventive prompting to the patients are envisaged in the future to evolve into well-being contact centers providing services to all citizens. In this paper, we present the structure of such a generic contact center and in particular the telecommunication infrastructure, the communication protocols and procedures, and finally the educational modules that are integrated into this contact center. We discuss the procedures followed for two target groups of patients where two randomized control clinical trials are under way, namely diabetic patients with obesity problems, and congestive heart failure patients. We present examples of the communication means between the contact center medical personnel and these patients, and elaborate on the educational issues involved.