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Osteoporosis is a chronic and progressive disease that can result in severe morbidity and mortality once falls and fractures occur. The objective was to develop a medication assessment tool (MAT) for use in the evaluation of implementation of evidencebased practice in the treatment and prevention of osteoporosis.

Although polyphosphonates (PPs) were introduced as bone imaging agents in nuclear medicine in the early 1970s, the mechanisms involved in their uptake still remain unclear. Suggested mechanisms range from mineral adsorption with disputed binding to the organic phase, over incorporation into the mineralisation process to a combination of both mechanisms. Thus, our investigations aimed to: (1) evaluate adsorption parameters of (99m)Tc-MDP, (153)Sm-EDTMP and (18)F-fluoride on mineralising osteoblast cultures, (2) correlate the radiotracer binding measured in the cell cultures with binding values from our previously presented mineral model and (3) compare binding with cell number.Primary osteoblasts were obtained by sequential digestion of foetal mice calvariae. The cells were incubated with 0.3 mumol of radiolabelled PPs or 25 MBq (18)F-fluoride for 120 min. Gamma signals from labelled samples were detected with a Millennium Hawkeye SPECT camera or with a dedicated Advance full-ring PET scanner and the binding percentages were calculated.From days 8 to 15 of culture, the percent binding of all evaluated tracers increased significantly, whereas the protein concentration showed insignificant changes. Additional comparisons of the binding values with our recently published pre-vivo model revealed remarkable agreement, suggesting solely bone-forming minerals to be responsible for radiotracer binding.This study provides evidence that binding of the evaluated radiotracers is not associated with osteoblast numbers but only with the concentration of bone-forming minerals. The presented correlations substantiate our recently presented pre-vivo model for the evaluation of bone-seekers: mechanisms associated with the uptake of bone-seekers are irreversible and mineral-associated processes.

Heme oxygenase 1 (HO-1) plays an important role in vascular disease, transplantation and inflammation. In animal models of acute and chronic inflammation, induction of HO-1 has anti-inflammatory and cytoprotective properties. Since inflammation is an important trigger of osteoclastogenesis, we hypothesized that HO-1 might play a role in osteoclastogenesis. When HO-1 was induced by hemin in vitro, a significant dose-dependent inhibitory effect on osteoclastogenesis was observed. Hemin primarily inhibited differentiation of mononuclear osteoclast precusors to osteoclasts. These effects were based on a downregulation of the expression of c-fms and RANK, the receptors for monocyte-colony stimulating factor and RANKL, whereas MAP kinase, NF-κB or Akt signalling were not affected. In vivo, HO-1 induction prevented endotoxin-induced calvarial bone resorption. Furthermore, assessment of synovial tissue from rheumatoid arthritis (RA) patients showed expression of HO-1 in monocytes and fibroblasts, whereas osteoclasts were rarely HO-1 positive. To further assess the role of HO-1 activity in RA patients, we correlated the presence of local bone erosions with serum bilirubin levels. We observed significant higher bilirubin levels in non-erosive than in erosive RA patients. Thus, an increase of HO-1 expression is anti-osteoclastogenic in vitro and might protect from increased bone resorption in vivo.