Daily or monthly ibandronate prevents or restores deteriorations of bone mass, architecture, biomechanical properties and markers of bone turnover in androgen-deficient aged rats.

AIM: The aim of this study was to investigate the effects of the bisphosphonate ibandronate (IBN) in a male osteoporosis animal model. METHODS: Two studies were performed in 9-month-old orchidectomised (ORX) or sham-operated rats. In prevention study, subcutaneous IBN was administered daily (1 µg/kg) or monthly (28 µg/kg every 28 days) starting on day of surgery for 5 months. In treatment study, the same treatment started 6 months after ORX. After sacrifice, bone analyses by dual-energy X-ray absorptiometry, 3-dimensional micro-computed tomography, and 3-point bending were performed in femora or vertebrae. Serum tartrate-resistant acid phosphatase 5b (TRAP-5b) and aminoterminal propeptide of collagen I (PINP) were analysed for resorption and osteocalcin (BGP) for bone formation. RESULTS: In both studies, ORX resulted in significant femoral and vertebral bone loss and microarchitectural deterioration after 5 months of ORX, and became more pronounced after 11 months. Biomechanical strength was also decreased. Serum levels for TRAP-5b and BGP increased while PINP levels were reduced or unchanged. Both daily and monthly IBN prevented or even restored ORX-induced changes in both studies, with the intermittent regimen showing a improvement in efficacy with respect to many of the biomechanical parameters.

The C-terminal fragment of parathyroid hormone-related peptide promotes bone formation in diabetic mice with low-turnover osteopaenia.

BACKGROUND AND PURPOSE: Current data suggest that parathyroid hormone (PTH)-related peptide (PTHrP) domains other than the N-terminal PTH-like domain contribute to its role as an endogenous bone anabolic factor. PTHrP-107-139 inhibits bone resorption, a fact which has precluded an unequivocal demonstration of its possible anabolic action in vivo. We thus sought to characterize the osteogenic effects of this peptide using a mouse model of diabetic low-turnover osteopaenia. EXPERIMENTAL APPROACH: PTHrP-107-139 was administered to streptozotocin-induced diabetic mice, with or without bone marrow ablation, for 13 days. Osteopaenia was confirmed by dual-energy X-ray absorptiometry and microcomputed tomography analysis. Histological analysis was performed on paraffin-embedded bone tissue sections by haematoxylin/eosin and Masson's staining, and tartrate-resistent acid phosphatase immunohistochemistry. Mouse bone marrow stromal cells and osteoblastic MC3T3-E1 cells were cultured in normal and/or high glucose (HG) medium. Osteogenic and adipogenic markers were assessed by real-time PCR, and PTHrP and the PTH(1) receptor protein expression by Western blot analysis. KEY RESULTS: PTHrP-107-139 reversed the alterations in bone structure and osteoblast function, and also promoted bone healing after marrow ablation without affecting the number of osteoclast-like cells in diabetic mice. This peptide also reversed the high-glucose-induced changes in osteogenic differentiation in both bone marrow stromal cells and the more differentiated MC3T3-E1 cells. CONCLUSIONS AND IMPLICATIONS: These findings demonstrate that PTHrP-107-139 promotes bone formation in diabetic mice. This mouse model and in vitro cell cultures allowed us to identify various anabolic effects of this peptide in this scenario.

Comparative effects of 17beta-estradiol, raloxifene and genistein on bone 3D microarchitecture and volumetric bone mineral density in the ovariectomized mice.

UNLABELLED: This study assessed the effect of estradiol, raloxifene and genistein on the preservation of bone 3D-microarchitecture and volumetric bone mineral density (vBMD) in the ovariectomized mouse model. Our results indicated that raloxifene was more effective in preserving bone ovariectomized-induced changes, the advantage being concentrated in both bone microarchitecture and vBMD. INTRODUCTION: This study assessed the effect of different estrogen receptor (ER) agonists on the preservation of bone 3D-microarchitecture and volumetric bone mineral density (vBMD) in the ovariectomized (OVX) mouse model. METHODS: Twelve-week-old female C57BL/6 mice were randomly assigned to one of five groups: (1) SHAM-operated + vehicle; (2) OVX + vehicle; (3) OVX + 17beta-estradiol (5 microg/kg); (4) OVX + raloxifene (1 mg/kg); (5) OVX + genistein (25 mg/kg), during 4-weeks. Bone microarchitecture and trabecular, cortical and total vBMD of distal femur were imaged by ex vivo microcomputed tomography (micro-CT). RESULTS: Ovariectomy produced a global deterioration involving both trabecular and cortical 3D-microarchitecture and vBMD. Raloxifene maintained both microarchitecture and vBMD, whereas estradiol prevented deterioration of some microstructural parameters, such as trabecular thickness (Tb.Th), trabecular bone pattern factor (Tb.Pf), and cortical periosteal perimeter (Ct.Pe.Pm), but did not completely block the loss in vBMD. Mice treated with genistein exhibited the less favourable profile in both vBMD and microstructural parameters preserving only cross-sectional bone area (B.Ar) and Ct.Pe.Pm in cortical bone. CONCLUSION: Our data indicate that, at the selected doses, raloxifene was more effective in preserving bone OVX-induced changes than either estradiol or genistein, the advantage being concentrated in both bone microarchitecture and vBMD.

Carboxymethylcellulose from totally chlorine-free-bleached milox pulps.

High purity cellulose pulp was obtained from Eucalyptus globulus wood by using an environmentally friendly delignification technique (Milox pulping) and subsequent bleaching by totally chlorine free technology. The pulp obtained under optimised experimental conditions was used for the manufacture of carboxymethylcellulose in a heterogeneous medium. By means of an experimental design, the effects of selected operational variables on the composition and chemical properties of reaction products from the carboxymethylation reaction were assessed for optimisation purposes. The distribution of the different carboxymethylglucose mole fractions (un-, mono-, di- and tri-substituted) was determined and compared with theoretical predictions. The maximum average degree of substitution (1.26) was determined at a NaOH/cellulose mole ratio of 4.8 and at a MCA/cellulose mole ratio of 2.0.