The effect of osteoprotegerin administration on the intra-tibial growth of the osteoblastic LuCaP 23.1 prostate cancer xenograft

Osteoprotegerin (OPG) plays a central role in controlling bone resorption. Exogenous administration of OPG has been shown to be effective in preventing osteolysis and limiting the growth of osteolytic metastasis. The objective of this study was to investigate the effects of OPG on osteoblastic prostate cancer (CaP) metastases in an animal model. LuCaP 23.1 cells were injected intra-tibially and Fc-OPG (6.0 mg/kg) was administered subcutaneously three times a week starting either 24 hours prior to cell injection (prevention regimen) or at 4 weeks post-injection (treatment regimen). Changes in bone mineral density at the tumor site were determined by dual x-ray absorptiometry. Tumor growth was monitored by evaluating serum prostate specific antigen (PSA). Fc-OPG did not inhibit establishment of osteoblastic bone lesions of LuCaP 23.1, but it decreased growth of the tumor cells, as determined by decreases in serum PSA levels of 73.0 ± 44.3% ( P < 0.001) and 78.3 ± 25.3% ( P < 0.001) under the treatment and prevention regimens, respectively, compared to the untreated tumor-bearing animals. Administration of Fc-OPG decreased the proliferative index by 35.0% ( P = 0.1838) in the treatment group, and 75.2% ( P = 0.0358) in the prevention group. The results of this study suggest a potential role for OPG in the treatment of established osteoblastic CaP bone metastases.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42587/1/10585_2004_Article_2869.pd

[Pharmacist's interventions on proton pump inhibitor prescriptions in a University Hospital].

International audienceIn France, efforts to optimize prescribing of proton-pump inhibitors (PPIs) are rare. Various studies have shown that the prescription of these drugs is excessive. This has consequences regarding costs and iatrogenesis. The objective of this study was to describe the type of drug related problems (DRP) and pharmaceutical interventions reported by pharmacists practicing in a university hospital.Methods: Drug related problems and pharmaceutical interventions (PI) made, were recorded on a database. They were classified according to the grid code of the French Society of Clinical Pharmacy.Results and discussion: Over a 3 years period, 132.890 prescriptions were analysed. 15.347 generated PI. Among them 701 (4.6%) concerned PPIs. Most frequently reported problems were: lack of indication or patients without a documented indication (24.4%), drug-drug interactions (22.4%) and inappropriate route or mode of administration (19.8%). Discontinuation has been proposed in 40.5% of cases, followed by substitution (22.0%) and dosage titration (17.3%). Physicians modified the prescription according to 51.3% of PI. The main PI, discontinuation therapy, is associated with over-prescription of this drug class. Nevertheless, the rate of DRP recorded (0.5%) is low compared to the high exposure of patients on PPIs and misuse (or overuse?) reported in the literature.Conclusion: PI made during the analysis of prescription contributes to rationalizing the use of PPIs. The action of the pharmacist must be strengthened through training of health professionals, and communication strategies to improve practices

Peripheral and axial measurements of trabecular bone density in patients suspected of idiopathic vertebral osteoporosis.

In 18 patients with idiopathic crush fracture syndrome, iliac trabecular bone volume measured in 8 mm trephine biopsies correlated well with trabecular bone density as estimated in low thoracic or high lumbar vertebrae by computed tomography (CT). The CT of trabecular bone in the radius correlated poorly with the other two measurements, but it discriminated fairly well between patients and age-matched controls. These results suggest that abnormally low trabecular bone density values in the radius may be useful in predicting some patients at risk for crush fractures, but ranking patients in order of severity of axial bone loss after they have acquired a fracture requires measurements on the spine or iliac crest

Calcium-47 kinetic measurements of bone turnover compared to bone histomorphometry in osteoporosis: the influence of human parathyroid fragment (hPTH 1-34) therapy.

Nineteen patients with involutional osteoporosis have been studied by means of combined 47Ca kinetic and calcium balance studies and morphometric analysis of iliac crest bone biopsies taken after double tetracycline labelling. Fifteen of them, together with three additional patients, were restudied after at least six months treatment with human parathyroid hormone fragment (hPTH 1-34). A close inverse relationship was found in the untreated patients between trabecular resorption surfaces (RS%) and calcium balance. The kinetically determined resorption rate showed a significant positive correlation with RS%, while the product of surface osteoid (SO%) and calcification rate (CR), determined from the tetracycline double label, correllated significantly with the 47Ca accretion rate. When the data from the patients on treatment were examined the relationship between calcium balance and RS% persisted; but the increased scatter in values for trabecular bone volume (TBV%) following the positive response of some patients to therapy appeared to contribute to a weakening in all these relationships. This was partially corrected by allowing for variations in TBV in calculating the remaining regressions. Osteoclast numbers correlated well with both accretion and resorption rates but not with calcium balance. Only a minor part of the scatter associated with these statistical associations could be accounted for by methodological uncertainties; nevertheless in this homogeneous group of patients fair predictions of kinetic indices could be made from histomorphometric data and vice versa. The remainder of the scatter is likely to be due to variations in turnover between different sites in the skeleton, particularly between cortical and trabecular bone; and to the tendency of kinetic parameters to include a variable contribution from exchange processes which can only be corrected by more sophisticated techniques for measuring the formation rate of new bone with radioisotopes. © 1981 S.N.P.M.D. Paris

Peripheral and axial measurements of trabecular bone density in patients suspected of idiopathic vertebral osteoporosis.

In 18 patients with idiopathic crush fracture syndrome, iliac trabecular bone volume measured in 8 mm trephine biopsies correlated well with trabecular bone density as estimated in low thoracic or high lumbar vertebrae by computed tomography (CT). The CT of trabecular bone in the radius correlated poorly with the other two measurements, but it discriminated fairly well between patients and age-matched controls. These results suggest that abnormally low trabecular bone density values in the radius may be useful in predicting some patients at risk for crush fractures, but ranking patients in order of severity of axial bone loss after they have acquired a fracture requires measurements on the spine or iliac crest