PubMed Health⌕ Search

Biomedical subjects

M H Lafage-Proust

Publications and source records attributed to M H Lafage-Proust.

At least 19 recordsLinked to original sources
PubMed2002

Relationships between trabecular bone remodeling and bone vascularization: a quantitative study.

Beside its well-known role in bone development, vascularization plays a major role in bone cell migration for bone remodeling and metastatic tumor invasion. However, the various techniques used to identify vessels in bone have never been tested for trabecular bone vessel quantification, whereas bone remodeling quantitative parameters are commonly assessed. In this context, we developed and compared various histological techniques used to visualize blood vessels in rat bone in order to quantify them. First, several products were tested by intracardiac infusion to opacify the bone vascular network. The best results were obtained using either an India ink-1% agarose solution or an India ink-saturated barium sulfate solution followed by X-ray microradiography. Second, to identify the types of vessels, we also performed histoenzymology and immunohistochemistry stainings. Neither alkaline phosphatase (for endothelial cells) nor adenosine triphosphatase (ATPase) stainings (for smooth muscle cells) provided a low enough background to allow for vessel identification and quantification. For immunohistochemistry, various specific vessel constituents were analyzed: laminin, smooth muscle cell alpha-actin, factor VIII, and lectin Griffonia simplifolia. Anti-laminin and anti-smooth muscle cell alpha-actin antibodies gave the best results for quantification. Third, after optimization of these techniques, we performed quantitative bone and vessel histomorphometry on two groups of 12 rats each, for which bone remodeling and vessel number and area parameters were measured. No statistical differences were observed between the two groups, confirming the reproducibility of our measurements. A significant relationship was found between vessel number and histodynamic parameters; that is, bone formation rate correlated positively with India ink-positive vessel area (p < 0.009, r2 = 0.54) and alpha-actin-positive vessel number (p < 0.05, r2 = 0.66). Furthermore, we report reproducible techniques for visualization and quantification of vessels in bone that also allowed for simultaneous conventional bone histomorphometry. This methodology should help researchers to better understand the functional and anatomical relationship between trabecular bone and its vascularization during normal or pathological processes.

Adenosine Triphosphatases↗
PubMed2002

Synchrotron radiation microtomography allows the analysis of three-dimensional microarchitecture and degree of mineralization of human iliac crest biopsy specimens: effects of etidronate treatment.

Quantitative microcomputed tomography using synchrotron radiation (SR microCT) was used to assess the effects of a sequential etidronate therapy on both three-dimensional (3D) microarchitecture and degree of mineralization of bone (DMB) in postmenopausal osteoporosis. Thirty-two iliac crest biopsy specimens were taken from 14 patients with osteoporosis (aged 64 +/- 1.8 years) before (baseline) and after 1 year of etidronate treatment, and after 2 years of treatment for four of the patients. The samples were imaged at high spatial resolution (voxel size = 10 microm) using the microtomography system developed at the European Synchrotron Radiation Facility (ESRF), Grenoble, France. Three-dimensional microarchitecture parameters were calculated and compared with those obtained from conventional histomorphometry. In addition, the DMB was evaluated also in 3D. No significant statistical changes regarding bone mass and structural parameters were observed in histomorphometry or 3D analyses. The distribution of the DMB in cortical and trabecular bone showed a trend to a shift toward highest mineralization values after 1 year of etidronate treatment (3.88% and 1.24% in cortical and trabecular bone, respectively). This trend was more evident after 2 years. The study also showed that SR microCT is an accurate technique and the only one for quantifying both the mineralization and the microarchitecture of bone samples at the same time in 3D.

Aged↗
PubMed2001

Cell cycling determines integrin-mediated adhesion in osteoblastic ROS 17/2.8 cells exposed to space-related conditions.

Six days of microgravity (Bion10 mission) induced dramatic shape changes in ROS 17/2.8 osteoblasts (7). During the Foton 11 and 12 space flights, we studied the kinetics (0-4 days) of ROS 17/2.8 morphology and adhesion, the relationships between adhesion and cell cycle progression after 4 days in space, and osteoblastic growth and activity after 6 days in space. Quantitative analysis of high-resolution adhesion [focal adhesion area imaged by total interference reflection fluorescent microscopy (TIRFM)] and integrin-dependent adhesion (imaged on confocal microscope by vinculin and phosphotyrosine staining) as well as cell cycle phase classification [Ki-67 staining, S-G2, mitotic cells and G1 (postmitotic cells)] were performed using programs validated in parabolic flight and clinostat. We observed disorganization of the cytoskeleton associated with disassembling of vinculin spots and phosphorylated proteins within focal contacts with no major change in TIRFM adhesion after 2 and 4 days of microgravity. Postmitotic cells, alone, accounted for the differences observed in the whole population. They are characterized by immature peripheral contacts with complete loss of central spots and decreased spreading. Osteocalcin, P1CP and alkaline phosphatase, and proliferation were similar in flight cells and 1 g centrifuge and ground controls after 6 days. In conclusion, microgravity substantially affected osteoblastic integrin-mediated cell adhesion. ROS17/2.8 cells responded differently, whether or not they were cycling by reorganizing adhesion plaque topography or morphology. In ROS 17/2.8, this reorganization did not impair osteoblastic phenotype.

Actins↗
PubMed2001

MAPK and SRC-kinases control EGR-1 and NF-kappa B inductions by changes in mechanical environment in osteoblasts.

Bone loss occurs in microgravity whereas an increase in bone mass is observed after skeletal loading. This tissue adaptation involves changes in osteoblastic proliferation and differentiation whose mechanisms remain largely unknown. In this context, we investigated the expression and the nuclear translocation of Egr-1 and NF-kappa B, in a simulated microgravity model (clinostat) and in a model of mechanical strain (Flexcell). We performed RT-PCR and immunocytochemistry analyses at baseline and up to 2 h after stimulation (a mitogenic regimen, 1% stretch, 0.05 Hz, 10 min, or clinorotation 50 rpm, 10 min) in osteoblastic ROS17/2.8 cells. Egr-1 induction as well as NF-kappa B nuclear translocation were activated by mechanical changes. PKC downregulation and COX1/2 inhibition did not alter these inductions. In contrast, ERK1/2, p38(MAPK) and src-kinases pathways were differentially involved in both models. Thus, we demonstrated that changes in the mechanical environment induced an activation of Egr-1 and NF-kappa B with specific kinetics and involved various transduction pathways including MAPKs and src-kinases. These could partially explain the later alterations of proliferation observed.

Animals↗
PubMed2000

Effects of long-term microgravity exposure on cancellous and cortical weight-bearing bones of cosmonauts.

BACKGROUND: Microgravity has been thought to induce osteoporosis because of reduced weight-bearing. However, up to now, few data have been available about its precise nature and timecourse. METHODS: We measured bone mineral density (BMD) at the distal radius and tibia in 15 cosmonauts of the Russian MIR space station who sojourned in space either 1 (n=two), 2 (two), or 6 months (11). After recovery periods of similar duration to the space missions, BMD was measured for the 2-month and 6-month crews. FINDINGS: Neither cancellous nor cortical bone of the radius was significantly changed at any of the timepoints. On the contrary, in the weight-bearing tibial site, cancellous BMD loss was already present after the first month and deteriorated with mission duration. In tibial cortices, bone loss was noted after a 2-month flight. In the 6-month group, cortical bone loss was less pronounced than that for cancellous bone. In some individuals, tibial deterioration was great. Actual BMD did not depend on preceding cumulative periods spent in space. During recovery, tibial bone loss persisted, suggesting that the time needed to recover is longer than the mission duration. INTERPRETATION: In space, despite physical training, bone loss is an adaptive process that can become pathological after recovery on Earth. Striking interindividual variations in bone responses seem to suggest a need for adequate crew preselection. Targeted treatment or prevention strategies would be useful, not only for space purposes, but also for the increasing number of osteoporotic patients on Earth.

Adult↗
PubMed2000

3D micro-computed tomography of trabecular and cortical bone architecture with application to a rat model of immobilisation osteoporosis.

Bone mass and microarchitecture are the main determinants of bone strength. Three-dimensional micro-computed tomography has the potential to examine complete bones of small laboratory animals with very high resolution in a non-invasive way. In the presented work, the proximal part of the tibiae of hindlimb unloaded and control rats were measured with 3D MicroCT, and the secondary spongiosa of the scanned region was evaluated using direct evaluation techniques that do not require model assumptions. For determination of the complete bone status, the cortex of the tibiae was evaluated and characterised by its thickness. It is shown that with the proposed anatomically conforming volume of interest (VOI), up to an eight-fold volume increase can be evaluated compared to cubic or spherical VOIs. A pronounced trabecular bone loss of -50% is seen after 23 days of tail suspension. With the new evaluation techniques, it is shown that most of this bone loss is caused by the thinning of trabeculae, and to a lesser extent by a decrease in their number. What changes most radically is the structure type: the remaining bone is more rod-like than the control group's bone. Cortical bone decreases less than trabecular bone, with only -18% after 23 days.

Animals↗
PubMed2000

Various evaluation techniques of newly formed bone in porous hydroxyapatite loaded with human bone marrow cells implanted in an extra-osseous site.

The purpose of this work was to develop qualitative methods for in situ analysis of bone formation in an osteoconductive hydroxyapatite matrix (ENDOBON), loaded with human bone marrow cells (HBMSC) implanted subcutaneously in athymic mice. Samples were taken before implantation (T0), 1, 2, 4 and 6 weeks after implantation. Bone-biomaterial interaction were investigated on undecalcified sections by histological, cytochemical, immunological and molecular biology methodologies. Histological observations were performed in order to observe inflammatory cells, vessels, newly formed bone, woven and lamellar bone. Enzymohistochemistry was carried out to detect positive tartrate resistant acid phosphatase activity (TRAP+). Immunohistochemistry using antibodies against type I collagen and osteocalcin permitted us to characterize the content of the matrix elaborated within the implant. Moreover, in situ hybridization was carried out to discriminate, the implanted human cells from the murine cells, and to evaluate the function of these human cells in osteogenesis. Results demonstrated an early formation of lamellar bone only in the pores of the studied HAP loaded with HBMSC. This bone contained a matrix showing positive reaction for type I collagen and osteocalcin. In situ hybridization identified some of these cells as human cells. At 6 weeks, examination of histological results showed persistance of lamellar bone in the implants. We only found TRAP+ activity in the materials loaded with human bone marrow cells. Molecular hybridization no longer revealed positive cells for the human DNA probe. All these results indicate that the various evaluation techniques performed on undecalcified sections, permit us to evaluate the response of human bone marrow cells in HAP implanted into mice.

Animals↗
PubMed2000

Weight gain reverses bone turnover and restores circadian variation of bone resorption in anorexic patients.

OBJECTIVE: The present study was conducted in order to describe the variations and circadian rhythm of biochemical markers of bone remodelling at baseline and after weight gain in patients with anorexia nervosa (AN). SUBJECTS: We studied 9 women (mean age 21 years, range: 16-30) with established AN who remained amenorrhoeic during the study and with a low body mass index (BMI) after refeeding and 6 female controls (mean age 20 years, range, 18-24 and BMI: 20.6 +/- 1.1 kg/m2). Refeeding was not associated with any other intervention or treatment, especially oestrogen replacement or hormonal contraception. Serum levels of oestradiol remained below 70 pmol/l before and after refeeding. MEASUREMENTS: During the study, PTH and 25-hydroxyvitamin D measurements were performed. Markers of bone formation: serum intact osteocalcin (iBGP) and serum intact BGP + fragments (iBGP+F) and markers of bone resorption: urine C-teloptide of type I collagen (uCTX) and serum C-telopeptide ofvtype 1 collagen (s-CTX) were measured. RESULTS: At baseline, PTH and 25 OH-vitamin D concentrations were within the normal range in AN patients and no significant variation was observed after refeeding. Bone formation markers were found to be significantly different at baseline between AN patients and controls. After refeeding, iBGP and iBGP+F levels increased by 172% and 154%, respectively, to values no different from controls. Intact BGP and iBGP+F exhibited a significant circadian variation in controls (P < 0.05 and P < 0.002, respectively), whereas we did not find any such circadian rhythm in AN patients. After refeeding no significant circadian variation was observed; however, iGBP+F tended to peak in early morning and exhibited a nadir in the afternoon. At baseline, sCTX was 2-fold higher in AN patients than in controls. After weight gain sCTX decreased significantly and reached control values. Refeeding induced a non-significant 40% decrease in uCTX. We found positive correlations between uCTX and the 24-h mean value of sCTX levels (r2 = 0.93, P < 0.0001) and between uCTX and the mean value of sCTX peak levels at 0800 h (r2 = 0.65, P < 0.0003). Serum CTX exhibited a significant circadian variation in controls (P < 0.001) with a peak at 0800 h and a nadir at 1600 h with a 60% decrease between peak and nadir values. We found that anorexia nervosa suppressed the sCTX circadian variation which was restored by refeeding. We found a significant non-linear relationship between BMI and sCTX/iBGP ratio in AN (r2 = 0.6, P < 0.0001), thus illustrating the influence of nutritional status on bone remodelling. CONCLUSIONS: In this study we found that weight gain, related to refeeding only, reversed the anorexia nervosa-induced uncoupling of bone remodelling and restored circadian variation of a bone resorption marker.

25-Hydroxyvitamin D 2↗
PubMed2000

A role for N-cadherin in the development of the differentiated osteoblastic phenotype.

Cadherins are a family of cell surface adhesion molecules that play an important role in tissue differentiation. A limited repertoire of cadherins has been identified in osteoblasts, and the role of these molecules in osteoblast function remains to be elucidated. We recently cloned an osteoblast-derived N-cadherin gene from a rat osteoblast complementary DNA library. After in situ hybridization of rat bone and immunohistochemistry of human osteophytes, N-cadherin expression was localized prominently in well-differentiated (lining) osteoblasts. Northern blot hybridization in primary cultures of fetal rat calvaria and in human SaOS-2 and rat ROS osteoblast-like cells showed a relationship between N-cadherin messenger RNA expression and cell-to-cell adhesion, morphological differentiation, and alkaline phosphatase and osteocalcin gene expression. Treatment with a synthetic peptide containing the His-Ala-Val (HAV) adhesion motif of N-cadherin significantly decreased bone nodule formation in primary cultures of fetal rat calvaria and inhibited cell-to-cell contact in rat osteoblastic TRAB-11 cells. HAV peptide also regulated the expression of specific genes such as alkaline phosphatase and the immediate early gene zif268 in SaOS-2 cells. Transient transfection of SaOS-2 cells with a dominant-negative N-cadherin mutant (NCADdeltaC) significantly inhibited their morphological differentiation. In addition, aggregation of NCTC cells derived from mouse connective tissue stably transfected with osteoblast-derived N-cadherin was inhibited by either treatment with HAV or transfection with NCADdeltaC. Together, these results strongly support a role for N-cadherin, in concert with other previously identified osteoblast cadherins, in the late stages of osteoblast differentiation.

Animals↗
PubMed2000

Space flight is associated with rapid decreases of undercarboxylated osteocalcin and increases of markers of bone resorption without changes in their circadian variation: observations in two cosmonauts.

BACKGROUND: Microgravity induces bone loss by mechanism(s) that remain largely unknown. METHODS: We measured biochemical markers related to bone remodeling in two cosmonauts before, during, and after 21- and 180-day space flights, respectively. RESULTS: During both flights, type I procollagen propeptide and bone alkaline phosphatase decreased as early as 8 days after launch. Undercarboxylated osteocalcin percentage increased early and remained high during both flights. Vitamin K supplementation restored carboxylation of osteocalcin during the long-term flight. Urinary and serum C-telopeptide of type I collagen (CTX) increased as early as day 8 of the flights; the increase was greater in serum than in urine. Pyridinoline, free deoxypyridinoline, and N-telopeptide increased less than CTX during the short-term space flight. The circadian rhythm of bone resorption assessed by urine CTX and free deoxypyridinoline was not altered by microgravity. CONCLUSION: Vitamin K metabolism or action and bone remodeling may be altered in cosmonauts.

Adult↗
PubMed1999

Effects of static or dynamic mechanical stresses on osteoblast phenotype expression in three-dimensional contractile collagen gels.

Studies performed at tissular (three-dimensional, 3-D) or cellular (two-dimensional, 2-D) levels showed that the loading pattern plays a crucial role in the osteoblastic physiology. In this study, we attempted to investigate the response of a 3-D osteoblastic culture submitted to either no external stress or static or dynamic stresses. Rat osteosarcoma cells (ROS 17/2.8) were embedded within collagen type I lattices and studied for 3 weeks. Entrapment and proliferation of cells within the hydrated collagen gel resulted in the generation of contractile forces, which led to contraction of the collagen gel. We used this ability to evaluate the influence of three modes of mechanical stresses on the cell proliferation and differentiation: (1) the freely retracted gels (FRG) were floating in the medium, (2) the tense gels (TG) were stretched statically and isometrically, with contraction prevented in the longitudinal axis, and (3) the dynamic gels (DG) were floating gels submitted to periodic stresses (50 or 25 rpm frequency). Gels showed maximum contraction at day 12 in 50 rpm DG, followed by 25 rpm DG, then FRG (88%, 81%, 70%, respectively) and at day 16 in TG (33%). The proliferation rate was greater in TG than in FRG (+52%) but remained low in both DGs. Gel dimensions were related to the collagen concentration and on a minor extent to cell number. Cells in DG appeared rounder and larger than in other conditions. In TG, cells were elongated and oriented primarily along the tension axis. Scanning electron microscopy (SEM) showed that tension exerted by cells in TG led to reorientation of collagen fibers which, in turn, determined the spatial orientation and morphology of the cells. Transmission electron microscopy (TEM) performed at maximum proliferation showed a vast majority of cells with a distended well-developed RER filled with granular material and numerous mitochondria. Alkaline phosphatase activity peaked close to the proliferation peak in FRG, whereas in TG, a biphasic curve was observed with a small peak at day 4 and the main peak at day 16. In DG, this activity was lower than in the two other conditions. A similar time course was observed for alkaline phosphatase gene expression as assessed by Northern blots. Regardless of the conditions, osteocalcin level showed a triphasic pattern: a first increase at day 2, followed by a decrease from day 4 to 14, and a second increase above initial values at day 18. Microanalysis-x indicated that mineralization occurred after 14 days and TEM showed crystals within the matrix. We showed that static and dynamic mechanical stresses, in concert with 3-D collagen matrices, played a significant role on the phenotypic modulation of osteoblast-like cells. This experimental model provided a tool to investigate the significance and the mechanisms of mechanical activity of the 3-D cultured osteoblast-like cells.

Alkaline Phosphatase↗
PubMed1999

Retinoic acid effects on an SV-40 large T antigen immortalized adult rat bone cell line.

Clonal cell lines were established from adult rat tibia cells immortalized with SV-40 large T antigen. One clone (TRAB-11), in which retinoic acid (RA) induced alkaline phosphatase (AP) activity, was selected for further study. The TRAB-11 cells express high levels of type I collagen mRNA, type IV collagen, fibronectin, practically no type III collagen, little osteopontin, and no osteocalcin. RA stimulates proliferation of TRAB-11 cells (starting at 10 pM) and survival (starting at 100 pM). TRAB-11 cells synthesize fibroblast growth factor-2 (FGF-2), which has potent autocrine mitogenic effects on these cells and acts synergistically with RA. TRAB-11 cells attach better to type IV collagen than to fibronectin or laminin. Cell attachment to type IV collagen is increased by RA and decreased (65%) by an antibody directed against alpha1beta1 integrin. RA up-regulates steady-state levels of alpha1, mRNA without affecting beta1 mRNA expression. In conclusion, we report the establishment of a clonal cell line from the outgrowth of adult rat tibiae which is highly sensitive to RA in its growth and survival in culture, apparently as a result of integrin-mediated cell interaction with extracellular matrix proteins.

Alkaline Phosphatase↗
PubMed1999

Effects of centrifuging at 2g on rat long bone metaphyses.

Hypergravity may be considered as a means of counteracting the deleterious effects of microgravity on bone tissue. The effects of exposure to 4 days of hypergravity provided by centrifuging, on bone tissue were studied using histomorphometry. Young 53-day-old male Sprague Dawley rats were randomly divided into a centrifuged group (2g, n = 10), a rotated group (ROTATE, n = 6) of rats exposed to 1.03 g placed in cages near the centre of rotation of the centrifuge and a stationary control group (CONTROL, n = 10). The body mass of the 2g rats was decreased by this experience by 16% compared to CONTROL. The width of the tibial growth plate of 2g was decreased. In two out of ten 2g rats, the hypertrophic zone was injured. In both the tibial and humeral primary (1 degrees ) spongiosae, a reduced 1 degrees spongiosa width (-35% and -24%, ROTATE versus CONTROL respectively; -37% and -41%, 2g versus CONTROL respectively) associated with bone gain (+27% for tibia and humerus ROTATE versus CONTROL; + 16% and +20%, 2g versus CONTROL respectively) was observed in both ROTATE and 2g. In the tibial secondary (2 degrees) spongiosa, bone mass was increased in the 2g (+13% 2g versus CONTROL) rats due to thicker trabeculae, but was decreased in ROTATE rats (-12% versus CONTROL) due to thinner trabeculae. The parameters of formation and resorption activities were stimulated in the 2g and ROTATE groups, the formation activity being more enhanced in 2g. No structural changes were observed in the humeral 2 degrees spongiosa in any of the groups. Numeral bone formation parameters were decreased in 2g and ROTATE but resorption activity was increased in 2g and decreased in ROTATE compared to CONTROL. In conclusion, as early as the 4th day, 2g hypergravity induced reduced endochondral bone formation and increased cancellous bone mass. Rotation led to mixed results including reduced endochondral bone formation, increased bone volume in the 1 degrees spongiosa and bone loss in the 2 degrees spongiosa.

Animals↗
PubMed1999

Bone mass and dynamic parathyroid function according to bone histology in nondialyzed uremic patients after long-term protein and phosphorus restriction.

One year of a very low protein diet (VLPD) can reverse secondary hyperparathyroidism in uremic patients. We studied bone histology, bone mineral density (BMD), and dynamic parathyroid function (calcium/PTH curves) in 16 nondialyzed patients with advanced renal failure who had been receiving a VLPD for a mean of 5 yr (mean protein intake, 0.34 +/- 0.12 mg/kg x day; mean phosphorus intake, 8.2 +/- 2.1 mg/kg x day) and daily supplementation with essential amino acids and their ketoanalogs (1000 IU vitamin D2 and 1-2 g calcium carbonate). Three patients exhibited a high bone formation rate (BFR), 7 patients had normal bone remodeling, and 6 patients had a low BFR, including 2 with osteomalacia and 4 with adynamic bone disease without aluminum overload. A longer diet duration and lower caloric intake were associated with low BFR. More than half of the patients exhibited moderate or severe osteoporosis at the appendicular skeleton. The t score of femur BMD explained 65% of the BFR variance. Patients with a low BFR had a dynamic parathyroid function similar to that of patients with a normal BFR, except they had a lower capacity to buffer a calcium load, whereas patients with a high BFR had a higher basal PTH/maximum PTH and a steeper calcium/PTH curve slope; the calcium set-point was identical in the three groups.

Adult↗
PubMed1999

Recurrence of vertebral fracture with cyclical etidronate therapy in osteoporosis: histomorphometry and X-Ray microanalysis evaluation.

In an open prospective study, we evaluated differences between patients with (wRVF group) and without recurrence of vertebral fracture (woRVF group) during cyclical etidronate therapy for osteoporosis. Thirty-two patients (age 64 +/- 1.8 years) characterized by at least one osteoporotic VF were treated during 1 year. At baseline, body mass index was significantly lower (23.3 +/- 0.6 vs. 26.9 +/- 1.0 kg/m2, p< 0.05), the number of previous VFs was higher (4.0 +/- 0. 4 vs. 2.4 +/- 0.4, NS), and patients were older in the wRVF group as compared with the woRVF group (67.8 +/- 3 vs. 62.6+/- 2.2 year, NS). Trabecular bone volume (11.6 +/- 1.2 vs. 15 +/- 0.9%, p< 0.05) and trabecular number (1.06 +/- 0.08 vs. 1.27 +/- 0.05, p < 0.05) were significantly lower in the wRVF group. None of the baseline resorptive variables differed, whereas the bone formation rate (BFR) was 2-fold lower in the wRVF group (p< 0. 05). After 1 year of treatment, osteoclast number, active eroded surfaces, and resorption depth dramatically decreased in both groups (p< 0. 01). To a lesser extent, the mineral apposition rate and serum alkaline phosphatase level were significantly reduced (p< 0.05). No impaired mineralization was observed. Using X-ray microanalysis, we found no abnormality in bone mineral but a significant increase of the calcium/phosphorus ratio during treatment in the wRVF group. Our results demonstrate that recurrence of VFs within the first year of cyclical etidronate therapy was related neither to a lack of histologic response to the treatment nor induction of an abnormality of mineralization. VFs were more likely in the presence of a decreased BFR and lower trabecular connectivity, providing support for treating osteoporotic patients with etidronate early in the course of the disease.

Adult↗
PubMed1999

Bisphosphonate effects in rat unloaded hindlimb bone loss model: three-dimensional microcomputed tomographic, histomorphometric, and densitometric analyses.

The effects of antiresorptive drugs on bone loss remain unclear. Using three-dimensional microtomography, dual X-ray/densitometry, and histomorphometry, we evaluated tiludronate effects in the bone loss model of immobilization in tail-suspended rats after 7, 13, and 23 days. Seventy-eight 12-week-old Wistar male rats were assigned to 13 groups: 1 baseline group, and for each time point, 1 control group treated with vehicle and three tail-suspended groups treated with either tiludronate (0.5 or 5 mg/kg) or vehicle, administered s. c. every other day, during the last week before sacrifice. In primary spongiosa (ISP), immobilization-induced bone loss plateaued after day 7 and was prevented by tiludronate. In secondary spongiosa (IISP), bone loss appeared at day 13 with a decrease in trabecular thickness and trabecular number (Tb.N) as assessed by three-dimensional microtomography. Osteoclastic parameters did not differ in tail-suspended rats versus control rats, whereas bone formation showed a biphasic pattern: after a marked decrease at day 7, osteoblastic activity and recruitment normalized at days 13 and 23, respectively. At day 23, the 80% decrease in bone mass was fully prevented by high-dose tiludronate with an increase in Tb.N without preventing trabecular thinning. In summary, at day 7, tiludronate prevented bone loss in ISP. After day 13, tiludronate prevented bone loss in ISP and IISP despite a further decrease in bone formation. Thus, the preventive effects of tiludronate in this model may be related to the alteration in bone modeling with an increase in Tb.N in ISP and subsequently in IISP.

Analysis of Variance↗
PubMed1999

Contribution of genetically modified mouse models to the elucidation of bone physiology.

The development over the last few years of genetically modified mouse models has provided a wealth of new information on the intimate cellular mechanisms involved in bone physiology. This article reviews some of the new insights gained into non-collagenous bone proteins. The bone matrix is no longer viewed as a passive support for bone cells, but rather as a key factor in the regulation of cell recruitment, proliferation, and differentiation. Studies using genetically modified mouse models have demonstrated the central importance of transcription factors such as Cbfa1, c-Fos, and c-Src in the differentiation of osteoblasts or osteoclasts from bone marrow stem cells. They have also allowed to identify the main cytokines involved in the regulation of bone cell activities, particularly in estrogen-deprived individuals. A discussion is provided in this article of the studies that identified the main communication pathway between osteoblasts and osteoclasts, in which the mediators are osteoprotegerin and its ligand, and that demonstrated the central position of these two factors in the regulation of osteoclast differentiation and activity.

Animals↗