Avraam Avramidis

The citizen health system (CHS): a Modular medical contact center providing quality telemedicine services

In the context of the Citizen Health System (CHS) project, a modular Medical Contact Center (MCC) was developed, which can be used in the monitoring, treatment, and management of chronically ill patients at home, such as diabetic or congestive heart failure patients. The virtue of the CHS contact center is that, using any type of communication and telematics technology, it is able to provide timely and preventive prompting to the patients, thus, achieving better disease management. In this paper, we present the structure of the CHS system, describing the modules that enable its flexible and extensible architecture. It is shown, through specific examples, how quality of healthcare delivery can be increased by using such a system.

The effect of teriparatide on serum Dickkopf-1 levels in postmenopausal women with established osteoporosis.

Objective  Parathyroid hormone increases the differentiation of osteoblast precursors through canonical wingless (Wnt) signalling, resulting in an osteoanabolic effect. We aimed to evaluate serum levels of the Wnt‐inhibitor Dickkopf‐1 (Dkk‐1) in postmenopausal women with established osteoporosis and their changes with teriparatide (TPTD – human recombinant PTH 1–34).

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.

Acute changes in serum osteoprotegerin and receptor activator for nuclear factor-κB ligand levels in women with established osteoporosis treated with teriparatide

OBJECTIVE The mechanisms regulating the anabolic response of the skeleton to intermittent exogenous parathyroid hormone (PTH) administration are not fully elucidated. The aim of this prospective study was to evaluate the acute effect (up to 1 month) of teriparatide (TPTD; human recombinant PTH 1-34) on serum levels of osteoprotegerin (OPG) and receptor activator for nuclear factor-kappaB ligand (RANKL) in women with established osteoporosis. DESIGN Twenty-three postmenopausal Caucasian women with established osteoporosis (mean age 66.7+/-1.6 years) received daily injections of 20 microg TPTD for 12 months. METHODS Serum samples for total calcium (Ca), phosphate, alkaline phosphatase, N-terminal propeptide of type I collagen, intact PTH (iPTH), OPG, and RANKL were obtained at baseline, 1 h, 1 day, and 1 month after initiation of therapy. Lumbar spine bone mineral density (BMD) was measured before and 12 months after TPTD treatment. RESULTS Serum total Ca increased and iPTH gradually decreased with TPTD treatment. Serum OPG levels remained unchanged, while RANKL increased gradually during the study (P<0.001). There was no correlation between OPG or RANKL and BMD changes or iPTH levels. CONCLUSIONS TPTD therapy in women with postmenopausal osteoporosis results in acute increase in serum RANKL levels but does not affect serum OPG. These changes may reflect an increase in the number of active osteoblasts with therapy and might be responsible for the acceleration of bone turnover rate that characterizes TPTD.

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.

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.

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.

No difference between strontium ranelate (SR) and calcium/ vitamin D on bone turnover markers in women with established osteoporosis previously treated with teriparatide : a randomized controlled trial

Objective   To evaluate the effect of strontium ranelate (SR) on bone turnover markers in women with established osteoporosis previously treated with teriparatide (TPTD – recombinant human PTH 1–34).