Biomedical subjects

P Chavassieux

Publications and source records attributed to P Chavassieux.

At least 19 recordsLinked to original sources

PubMed2001

Histomorphometric approach of bone loss in men.

From a review of the published literature the authors have described the histomorphometric changes observed in human iliac bone corresponding to the age-related bone loss in 'males and in "idiopathic" male osteoporosis. Age-related bone loss of about 30% is histomorphometrically characterized in males by a reduction in iliac cancellous bone volume between ages 20 and 70-80 years, less marked than in women (-42%). The age-related thinning of trabecular packets wall width is the same between males and females, but trabecular separation is lower in aged males than in aged females, suggesting a better preservation of the trabecular microarchitecture in elderly males. Trabecular eroded surfaces increase with age in females but not in males. The rare studies comparing bone formation parameters in males and females did not show any major difference, with a trend for a decrease in mineralization apposition rate and an increase in activation frequency in both sexes. Bone histomorphometry in "idiopathic" male osteoporosis is characterized by a mean decrease in cancellous bone volume of 35% compared with age-matched controls, similar to the mean decrease observed in females (-38%). Most, but not all authors have found an increase in bone resorption parameters and a decrease in bone static and dynamic formation indices (osteoid surfaces, mineralizing surfaces, bone formation rate).

Adult↗

PubMed2001

Effects of a new selective estrogen receptor modulator (MDL 103,323) on cancellous and cortical bone in ovariectomized ewes: a biochemical, histomorphometric, and densitometric study.

The aims of this study performed in ewes were: (1) to confirm in this animal model the effects on bone of ovariectomy (OVX) alone or associated with Lentaron (L), a potent peripheral aromatase inhibitor, used to amplify the effects of OVX and (2) to evaluate the effects of a new selective estrogen receptor modulator (SERM; MDL 103,323) on bone remodeling. Thirty-nine old ewes were divided into five groups: sham (n = 7); OVX (n = 8); OVX + L (n = 8); OVX + L + MDL; 0.1 mg/kg per day (n = 8); and OVX + L + MDL 1 mg/kg per day (n = 8). The animals were treated for 6 months. Biochemical markers of bone turnover (urinary excretion of type 1 collagen C-telopeptide [CTX], serum osteocalcin [OC], and bone alkaline phosphatase [BAP]) were measured each month. Bone biopsy specimens were taken at the beginning and after death at the end of the experiment. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) on the lumbar spine and femur. OVX induced a significant increase in biochemical markers. This effect was the highest after 3 months for CTX (+156% vs. sham) and after 4 months for OC and BAP (+74% and +53% vs. sham, respectively). L tended to amplify the effect of OVX on OC and BAP. OVX induced significant increases in the porosity, eroded, and osteoid surfaces in cortical bone but no effect was observed in cancellous bone. MDL treatment reduced the bone turnover as assessed by bone markers, which returned to sham levels as well as histomorphometry both in cortical and in cancellous bone. Cancellous osteoid thickness decreased by 27% (p < 0.05), mineralizing perimeter by 81% (p < 0.05), and activation frequency by 84% (p < 0.02) versus OVX + L. Femoral and spinal BMD were increased by MDL and tended to return to the sham values. The effects of OVX on bone turnover were different on cortical and cancellous bone. These effects on cortical bone were reflected by changes in biochemical markers. MDL markedly reduces bone turnover and increases BMD suggesting that this new agent may prevent postmenopausal bone loss.

Alkaline Phosphatase↗

PubMed2000

Activity increase after extraction of alkaline phosphatase from human osteoblastic membranes by nonionic detergents: influence of age and sex.

The solubilization of alkaline phosphatase (AP) from osteoblastic cell membranes obtained from human primary bone cell cultures was studied according to the age and sex of the donors (17 females, 11 males; age range: 2-77 years). Cell membranes were treated by non-ionic (n-octyl beta-D-glucopyranoside, OG), ionic or zwitterionic detergents, then centrifuged. When OG was used almost all the AP was solubilized. AP activity in supernatant of solubilization was compared to the activity of the suspension before centrifugation. The activity ratio (AR) increased in function of age for subjects between 65 and 74. Neither total nor specific AP activities were influenced by age or sex. Electrophoresis studies showed that the AP released was a GPI (glycosyl phosphatidylinositol)-anchored protein, amphipathic form, with 140 kDa as apparent molecular mass. The activity change of AP in the presence of OG may result from age-related modifications either in the AP structure or in the constituents of the plasma membranes (proteins or phospholipids).

Adolescent↗

PubMed1998

Influence of magnesium substitution on a collagen-apatite biomaterial on the production of a calcifying matrix by human osteoblasts.

The induction of a calcifying matrix is of great interest in the restoration of bone defects. In a previous in vitro study we demonstrated that a collagen sponge constituted of type I collagen fibrils, chondroitin sulfates, and hydroxyapatite crystals induces an earlier and a more abundant synthesis of a new extracellular calcifying matrix than do other biomaterials such as collagen or hydroxyapatite alone. Bone mineral contains various amounts of magnesium ions, either adsorbed at the surface of apatite crystals or incorporated inside the crystal structure. Magnesium is known to reduce the degradation rate of tricalcium phosphate ceramics and to influence the crystallization of mineral substance. Thus we evaluated two sponges modified with different substituted apatites. The substituted low magnesium-containing apatite sample decreased the osteoinductive properties of the sponge whereas the substituted high magnesium-containing apatite sample had a toxic effect on bone cells and prevented the formation of any extracellular matrix. Such a toxic effect can be explained by the presence of large numbers of magnesium ions released into the culture medium even though at physiological level magnesium is able to promote bone mineralization and to control the growth of hydroxyapatite crystals. Thus collagen sponges containing hydroxyapatite remain one of the most appropriately evaluated biomaterials used for the restoration of periodontal pockets and bone defects.

Apatites↗

PubMed1997

Short-term effects of corticosteroids on trabecular bone remodeling in old ewes.

This study was an attempt to develop an animal model of steroid-induced low bone formation, potentially suitable for testing bone forming agents. The short-term effects of corticosteroids on bone remodeling were analyzed in ewes. One group of 16 animals (mean age: 9 +/- 1 years) received a daily intramuscular injection of 16 mg of methylprednisone (MP group) for 3 months. The other group of 16 animals was considered the control group. At the end of treatment, significant decreases of osteoblastic (-50%) and mineralizing (-64%) perimeters and wall width (-5%) were noted in the MP group. The bone formation rate at the tissue level was significantly decreased by 91%. In contrast, at the cell level, there was no reduction in the daily production of matrix by the osteoblasts: Aj.AR was 40% lower than in controls, but the difference was not significant. At the end of the treatment, a significant increase in eroded perimeter (+97%) was associated with a significant decrease of osteoclast number. Biochemical markers of bone formation (osteocalcin and bone-specific alkaline phosphatase) and urinary cAMP were unchanged. Due to the short duration of the treatment, neither bone volume nor microarchitecture parameters were modified. The decreases of both the activation frequency and osteoclast number associated with the increase in eroded surfaces suggest a prolongation of the reversal phase due to an inhibition of osteoblast differentiation. Changes of bone formation in ewes induced by short-term administration of MP were similar to those reported after 3 months of treatment in humans. Thus, corticosteroid-treated ewes may represent a suitable animal model of low bone formation.

Alkaline Phosphatase↗

PubMed1996

Differential solubilization of osteoblastic alkaline phosphatase from human primary bone cell cultures.

Mineralization of cartilage and bone requires alkaline phosphatase activity. In order to study the enzymatic properties of bone alkaline phosphatase in bone disease and more particularly in patients with osteoporosis and osteoarthritis, we investigated the solubilization of alkaline phosphatase from primary bone cell cultures derived from human bone explants. To study the release of alkaline phosphatase from membranes, several detergents at a concentration above the critical micellar concentration and cholesterol were used. Solubilized alkaline phosphatase was characterized by enzymatic activity and electrophoresis analysis. Almost all the alkaline phosphatase was solubilized using non-ionic detergent as n-octylglucoside and hecameg. In comparison with initial membranous activity, the solubilized activity was increased by a factor, i.e. 2 +/- 0.05 (SEM, n = 3) (with n-octylglucoside), i.e. 2.1 +/- 0.05 (SEM, n = 3) (with Hecameg). With an ionic detergent (sodium dodecylsulfate), zwitterionic detergent ((cholamido propyl) dimethylammonio 1 propane sulfonate) and cholesterol, a fraction of alkaline phosphatase was resistant to solubilization. Electrophoresis studies showed that released alkaline phosphatase was a glycosylphosphatidylinositol protein (amphipatic form) with 140 kDa as apparent molecular weight. A hydrophilic form was obtained by treatment with a specific lipase. This study showed differential solubilization of osteoblastic alkaline phosphatase from human primary bone cell cultures. Better extractibility and higher activation of this membrane anchored enzyme were obtained with non-ionic detergents.

Alkaline Phosphatase↗

PubMed1995

[Mechanisms of bone loss in osteoporosis].

Aging and menopause are the two main determinants of osteoporosis, a rarifying osteopathy due to bone loss. Type I osteoporosis observed in post-menopausal women is characterized mainly by trabecular bone loss results from an unbalanced coupling between resorption and formation inducing a thinning of trabeculae and from an increased osteoclast activation resulting in irreversible trabecular perforation. Anti-osteoclastic drugs prevent trabecular and cortical bone loss. Drugs that stimulate osteoblastic proliferation thicken trabecular plates but do not restore the normal trabecular microarchitecture after complete destruction of a large number of trabeculae. In type II osteoporosis, cortical bone loss is favoured by secondary hyperparathyroidism and is responsible for hip fracture. Calcium and vitamin D supplementations decrease the risk of hip fractures by reducing the secondary hyperparathyroidism.

Aged↗

PubMed1995

[Benefits and risks of fluoride supplements].

Fluoride is an essential trace element. It is incorporated in calcified tissues. At doses lower than 1.5 mg/day, fluoride has a prophylactic action against dental caries by absorption on the enamel surface. At doses ranging from 15 to 25 mg/day, it is used as a therapeutic agent in adults, in the treatment of post-menopausal osteoporosis with vertebral crush fractures. At high doses, fluoride may induce skeletal fluorosis leading in children to pseudorachitism. In children, fluoride supplement has been recommended for several years, as a prophylactic agent against dental caries. It may be given either as dentifrices and toothwash solutions, easy to use and economic but contraindicated in very young children; or as tablets, sure and effective but requiring a daily intake; or as domestic salts supplemented with 250 mg/kg. Fluoride supplement may also be given through drinking water. Fluoride content is limited to 1.5 mg/l but some mineral waters contain high amounts of fluoride and may have a beneficial effect on bone mass. In order to prevent an excessive fluoride intake in children and in adults, different forms of fluoride supplements must not be associated.

Adolescent↗

PubMed1993

In vitro exposure to sodium fluoride does not modify activity or proliferation of human osteoblastic cells in primary cultures.

The anabolic effects of sodium fluoride (NaF) on trabecular bone mass in osteoporosis is now well established. In vivo histologic studies performed in humans and other animals have shown that fluoride induces an increase in osteoblast number at the tissue level. To determine the mechanisms of action of fluoride on osteoblasts, we studied the effects of NaF on short- and long-term cultures of human osteoblastic cells derived from bone explants obtained from 21 donors. In short-term experiments, bone-derived cells were exposed to NaF for 4 days. At doses ranging from 10(-11) to 10(-5) M, NaF did not modify the alkaline phosphatase (AP) activity or osteocalcin secretion. In long-term experiments, half the bone samples from 15 donors were cultured for 4 months in the presence of 10(-5) M NaF and the other half were maintained in NaF-free medium. Observations by light and electron microscopy disclosed no morphologic modification in bone explants after 4 months of exposure to NaF, despite an increase in the bone fluoride content. After the first month of culture, slight but not significant increases were noted in 6 of 10 cases for AP activity, 4 of 10 for osteocalcin secretion, and 5 of 7 for [3H]thymidine incorporation. After 4 months of culture in the presence of NaF, no change in AP activity or cell proliferation was noted. In contrast, the osteocalcin secretion significantly decreased (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Evidence for a direct effect of growth hormone on osteoblasts.

In order to determine whether growth hormone (GH) exerts a direct effect on osteoblasts, in vitro and in vivo immunocytological studies were carried out on newborn rat calvaria and a clonal osteoblast-like cell line (MC3T3-E1) isolated from newborn mouse calvaria. After exposure to human growth hormone (hGH) or 1,25 dihydroxyvitamin D3 (1,25(OH)2D3), a significant increase in alkaline phosphatase activity was observed in MC3T3-E1 cells. Simultaneous exposure of MC3T3-E1 cells to hGH and 10 nM 1,25(OH)2D3 showed a synergistic effect of the two hormones on this activity. The optimal dose of hGH was 0.1 nM. An immunocytological procedure was performed on ultrathin frozen sections from 7-day-old rat calvaria and MC3T3-E1 cells cultured with hGH. GH-like immunoreactivity was observed in both cases. In calvaria, endogenous GH-like immunoreactivity was localized at the same ultrastructural level (plasma membrane, cytoplasmic and nuclear matrices) as exogenous GH-like immunoreactivity in MC3T3-E1 cells. Following the initial step of binding to the plasma membrane, GH may be internalized in the cytoplasmic matrix and nucleus. In situ hybridization revealed the presence of mRNA coding for GH receptor in calvaria cells. The density of these receptors seemed to be lower in osteoblasts than in hepatocytes. In MC3T3-E1 cells, hGH induced a dose-dependent secretion of insulin-like growth factor 1. In conclusion, these results indicate that GH may act directly on osteoblasts.

Alkaline Phosphatase↗

PubMed1993

Glucocorticoid-induced inhibition of osteoblastic bone formation in ewes: a biochemical and histomorphometric study.

The mechanisms underlying glucocorticoid-induced osteoporosis in humans are a defect in bone formation associated with increased bone resorption. The latter may be due to elevated parathyroid hormone (PTH) levels induced by the impairment of intestinal calcium absorption caused by corticosteroids. In this study we analysed the effects of corticosteroids in old ewes, a potential model for the study of human bone turnover. Two groups of seven 9-year-old female sheep were selected. The first group was injected intramuscularly with a daily dose of 30 mg methylprednisone (MP) during the first 2 months and 15 mg during the last month. After 2 and 3 months of treatment, blood samples were taken. At the end of the experiment the animals were slaughtered and the iliac crest kept for bone histomorphometry. Serum osteocalcin (sOC) rapidly and markedly decreased in the MP-treated group compared with controls (-77%; p < 0.01). In contrast, at the end of the experiment serum calcium and PTH levels were similar in both groups. Histomorphometric analysis showed a significant reduction in the wall width of trabecular packets. Dynamic parameters reflecting bone formation at the tissue and cell levels were significantly lower in the MP-treated group than in controls, with a highly significant decrease in the mineralization rate (MAR: -63%, p < 0.05) and double-labeled perimeter (dLPm/B.Pm: -92% p < 0.05). The bone formation rate (BFR/B.Pm) also decreased by 84% and the adjusted apposition rate (Aj.AR) by 80%. The increase in the total formation period was mainly due to an increase in the inactive period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

In vitro induction of a calcifying matrix by biomaterials constituted of collagen and/or hydroxyapatite: an ultrastructural comparison of three types of biomaterials.

The induction of a calcifying matrix was studied in vitro and compared for three biomaterials (collagen sponge, hydroxyapatite material and a mixture of both (Biostite)) cultured with human osteoblast-like cells. The influence of biomaterials on organic matrix synthesis and the calcification process was analysed at the ultrastructural level (transmission electron microscopy and X-ray microanalysis). Biomaterials were well tolerated by bone cells. Whichever biomaterial was used, osteoblasts proliferated and synthesized a new matrix constituted of fibrillar and non-fibrillar elements. This activity appeared earlier and was more intense with Biostite than with collagen sponge alone. A deposition of a mineral substance in this newly formed matrix was observed with the collagen sponge and Biostite, but never with hydroxyapatite alone. The mineral deposits were identified as hydroxyapatite crystals, similar to those observed and analysed in bone tissue. These in vitro observations clearly demonstrated the property of Biostite to produce a calcified collagenous matrix similar to bone tissue. However, in vivo confirmation is required before extending the use of this biomaterial to periodontology.

Biocompatible Materials↗

PubMed1993

In vitro evaluation of dose-effects of ethanol on human osteoblastic cells.

Chronic alcoholism represents a high risk for fractures and osteopenia. Previous histomorphometric studies reported a decreased bone formation, but it has never been established whether ethanol has a direct toxic effect on osteoblasts. This present in vitro study was performed on human osteoblast cells derived from bone explants after collagenase digestion. The direct effect of ethanol was determined after 4 days of exposure to various doses, ranging from 0.01 to 5 g/l on the alkaline phosphatase (AP) activity, osteocalcin secretion and [3H]thymidine incorporation. The influence of the duration of exposure to 0.8 g/l ethanol was also determined. A significant and dose-dependent decrease in the cell proliferation was observed. AP activity was significantly decreased by high doses of ethanol (2-5 g/l). A biphasic effect of ethanol was noted on osteocalcin secretion according to the dose: it decreased at doses lower than 0.8 g/l and increased at the highest concentrations. At the dose of 0.8 g/l, whatever the duration of exposure, the decrease of the proliferation was of the same magnitude and no significant change in AP activity was observed. Significant ethanol-induced effects on osteocalcin secretion were observed only after 4 and 8 days of exposure. These data demonstrate that ethanol may have a direct toxic effect on osteoblast activity and proliferation. This could be one of the mechanisms of alcohol-induced osteopenia which has a multifactorial pathophysiology.

Alcoholism↗

PubMed1991

Fluoride-induced bone changes in lambs during and after exposure to sodium fluoride.

The evolution of bone changes induced by fluoride after the end of exposure was investigated in lambs. Sodium fluoride (NaF) was given orally at a dose of 3.5 mg/kg per day to 14 animals for 120 days. A group of 7 control and 7 treated lambs was slaughtered at the end of NaF administration (T120) and another group 120 days after the end of NaF exposure (T240). At T120, the bone fluoride content (BFC) was very significantly increased in treated animals. The histomorphometric analysis confirmed that fluoride induces an increase in bone formation (the osteoid perimeter and area were 3-fold and 4.5-fold higher respectively in treated than in control animals). The number of osteoblasts was significantly augmented. Serum osteocalcin level was twice as high in treated animals compared with controls. The bone formation rate at the tissue level (BFR) doubled after treatment, but the apposition rate (Aj.AR) was half that in the control group. The mineralization lag time (Mlt) was 120 days in treated animals compared with 42 days in controls. At T240, BFC had decreased by 50% compared with the level at T120, but it was still significantly higher than in controls. The osteoid and osteoblastic parameters were 2 and 1.3 times higher than in control animals. BFR remained significantly increased in treated animals, but Aj.AR and Mlt were similar in control and treated animals. In conclusion, after 4 months of NaF exposure fluoride induced an increase in osteoblast natality and bone formation at the tissue level, associated with a toxic effect at the individual cell level.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Effects of ossein-hydroxyapatite compound on ewe bone remodeling: biochemical and histomorphometric study.

Ossein-hydroxyapatite compound (OHC) is a protein-mineral complex derived from bovine bone. Its effects on bone remodeling were studied in old ewes which have seasonal variations in bone remodeling. Seven animals received 200 mg OHC/kg b.w./day for 90 days from July to September. The control group consisted of 7 untreated animals followed for the same period of time. OHC was administered through a fistula into the fourth stomach. A significant decrease of bone histomorphometric parameter values was noted in controls at the end of the experiment, due to seasonal variations: the cancellous eroded perimeter decreased by 45%, the osteoblastic perimeter by 60% and the bone formation rate at the cell level by 20%. In contrast, in the treated-group, these parameters tended to increase or did not change. In conclusion, counteracting the significant seasonal reduction of bone remodeling in ewes, OHC seems able to stimulate directly or indirectly bone metabolism, especially when osteoblast activity is reduced and may partly prevent the seasonal reduction of bone turnover.

Animals↗

PubMed1991

Dose effects on ewe bone remodeling of short-term sodium fluoride administration--a histomorphometric and biochemical study.

The early effects of two doses of sodium fluoride (NaF) on bone remodeling was studied in 14 ewes divided into two groups. Group I received orally 1 mg NaF/kg/day and group II received a five-fold greater dose. No calcium supplement was given. Transiliac bone biopsies and blood samples were taken before treatment (T0) and after 45 (T45) days of treatment. Bone fluoride content significantly increased in group II. In both groups, a significant decrease of serum calcium and phosphorus, and a slight but nonsignificant augmentation in serum parathyroid hormone were noted. Osteoid perimeter and area were significantly increased. The osteoid width significantly increased in both groups, but was twice higher in group II than I. At T45, the osteoblast perimeter increased in both groups. Osteoid perimeter was significantly correlated with serum osteocalcin values (r = 0.74; p less than 0.001) and bone fluoride content (r = 0.64; p less than 0.01). The bone formation rate at tissue level tended to increase in both groups. Concerning the apposition rate, a decrease was noted which was 1.5-fold higher in group II than in I. The increased formation period resulted from a prolonged inactive period in group II. These results point out a stimulatory effect of fluoride on the birth rate of osteoblasts. However, fluoride prolonged the lifespan of osteoblasts that had reduced activity.

Animals↗

PubMed1990

Bone effects of fluoride in animal models in vivo. A review and a recent study.

The effects of fluoride on bone in various animal models are reviewed. In these studies, the doses of fluoride varied from those equivalent to therapeutic doses to toxic doses, and the duration of the treatment was from 15 days to 33 months. No significant modification in serum calcium, phosphorus, and alkaline phosphatase was reported. An increased serum osteocalcin level was noted in ewes. Evidence for hyperparathyroidism was found in some but not all animal models. Studies performed in the rat reported that fluoride had different effects on the periosteal and endosteal bone. An increase in the extent of eroded surfaces was observed in all experimental studies, except one in the mouse. Increases in osteoid parameters and in the number of osteoblasts were noted in mouse, cat, pig, and ewe. Only one study, carried out in dogs, mentioned a decrease in osteoid parameters. Most of the authors reported a mineralization defect due either to a modification in the composition of the bone matrix or to a low calcium intake. The formation period was augmented during fluoride treatment but, at a fluoride dose equivalent to therapeutic doses, this augmentation was mainly due to an increased active formation period. In contrast, at a fivefold greater dose, it was due to an increased inactive formation period. The augmentation of bone volume after fluoride treatment was attributed to an unbalanced coupling between resorption and formation in favor of formation. All these experimental studies support the conclusion that fluoride induces a stimulation of the birthrate of osteoblasts, but at high doses decreases their activity.

Animals↗

PubMed1990

Skeletal fluorosis: histomorphometric findings.

Histomorphometric analysis of undecalcified sections was performed in transiliac biopsy cores taken from 29 patients (16 men, 13 women, aged 51 +/- 17 years) suffering from skeletal fluorosis due to chronic exposure to fluoride. The origin of the exposure, known in 20 patients, was either by water (endemic or sporadic), or industrial, or in a few cases iatrogenic. Measured on calcified bone using a specific ion electrode, bone fluoride content was significantly high in each specimen (mean +/- SD: 0.79 +/- 0.36% of bone ash) as compared to control values (less than 0.10%). The radiologically evident osteosclerosis observed in each patient was confirmed by the significant increase of cancellous bone volume (40.1 +/- 11.2 vs. 19.0 +/- 2.8% in controls, p less than 0.0001). There were significant increases in cortical width (1292 +/- 395 vs. 934 +/- 173 microns, p less than 0.0001) and porosity (14.4 +/- 6.4 vs. 6.5 +/- 1.7%, p less than 0.002), but without reduction of cortical bone mass. Osteoid parameters were significantly increased in fluorotic patients. The increase in cancellous osteoid perimeter was almost threefold greater than that noted in cancellous eroded perimeter. The fluorotic group had a greater number of osteoblasts than controls, with a very high proportion of flat osteoblasts. In 15 patients doubly labeled with tetracycline, the mineral apposition rate was significantly decreased, while mineralization lag time significantly increased. Bone formation rate and adjusted apposition rate were significantly decreased in skeletal fluorosis. Cancellous wall width was normal in fluorosis but the formation period and active formation period were significantly increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗