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Biomedical subjects

M E Cohen-Solal

Publications and source records attributed to M E Cohen-Solal.

8 recordsLinked to original sources
PubMed1998

Cytokine release from marrow mononuclear cells is negatively correlated to cortical elasticity in non-osteoporotic postmenopausal women.

Activation of bone remodeling is likely to be under the control of mechanical factors acting, in part, through soluble local factors. We therefore investigated a relationship between cytokine production by marrow cells and bone elasticity. We studied 36 non-osteoporotic postmenopausal women undergoing hip arthroplasty for hip arthrosis (mean age: 68 +/- 8 years; lumbar BMD Z-score: +0.54 +/- 0.33 SD). Adherent marrow mononuclear cells were cultured for 48 hours with autologous plasma, and supernatants were harvested for PGE2, IL-1, TNF-alpha, and IL-6 measurements. Femoral neck cortical bones were removed during surgery for cortical histomorphometric evaluation and determination of elasticity indices (C33) using ultrasonic transmission method. In this nonosteoporotic population, femoral neck longitudinal elasticity indices were inversely correlated to both cortical thickness (r = -0.58, P < 0.01) and cortical porosity (r = -0.33, P < 0.01). The longitudinal elasticity indices were also negatively correlated to basal IL-1 and TNF-alpha release by adherent mononuclear marrow cells (r = -0.59, P < 0.01; r = -0.60, P < 0.01, respectively). However, no relationship was found between the three cytokines tested and either cortical thickness or porosity. These data show a link between cortical biomechanical properties and local factors involved in bone remodeling. We suggest that increased bone elasticity decreases transmission of strain, which in turn decreases cytokine release from marrow cells. However, whether cytokines influence bone elasticity or vice versa remains to be demonstrated.

Aged↗
PubMed1995

Bone resorption at the femoral neck is dependent on local factors in nonosteoporotic late postmenopausal women: an in vitro-in vivo study.

Local mediators of bone resorption may be involved in bone loss in recently postmenopausal women and in osteoporosis. In the present study, we investigated the production of cytokines and the formation of osteoclast-like cells in marrow cultures from 16 late postmenopausal nonosteoporotic women (mean age: 66 +/- 8 years; time after menopause: 15 +/- 8 years) undergoing hip replacement for arthrosis. Marrow adherent mononuclear cells (MMNC) isolated from femoral diaphysis marrow were cultured for 10 days in the absence or in the presence of 1,25(OH)2D3. In vivo bone resorption was concomitantly assessed by histomorphometry on femoral neck bone sections. The number of TRAP+ multinucleated cells obtained after 10 days in MMNC cultured in the presence of 1,25(OH)2D3 correlated with the number of osteoclasts measured on the bone femoral neck biopsies (r = 0.65, p < 0.01), suggesting that the formation of multinucleated cells in vitro could reflect the osteoclast differentiation in vivo. Furthermore, the number of osteoclasts was related to the eroded volume and the trabecular separation of the femoral neck bone biopsies. Finally, the release of interleukin-1 (IL-1), IL-6, and TNF-alpha by cultures of peripheral blood mononuclear cells (PBMC) and MMNC was measured by radioimmunoassay. The cytokine levels of basal and 1,25(OH)2D3-treated MMNC decreased from days 2 to 5 and then reached a plateau to day 10. The number of TRAP+ multinucleated cells obtained after 10 days in MMNC cultures correlated with the basal IL-6 release in the same cultures determined at day 2 (r = 0.55, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1995

1,25 dihydroxyvitamin D and dexamethasone decrease in vivo Walker carcinoma growth, but not parathyroid hormone related protein secretion.

Parathyroid hormone related protein (PTHrP) is produced by several breast cancers. 1,25 dihydroxyvitamin D (1,25[OH]2D) and Dexamethasone (DEX) have been shown to decrease PTHrP mRNA expression in several cell lines. We therefore tested the in vivo effect of both steroids on PTHrP secretion and tumor development of the Walker carcinoma (WC). WC cells were injected subcutaneously in Fisher rats which were simultaneously treated with either vehicle, or 1,25(OH)2D (0.5 micrograms/kg/d) or DEX (2 mg/kg/d). After 7 days, tumor weight was significantly decreased in the 2 treated-groups as compared to the control group. Vehicle treated-rats developed hypercalcemia, which was also observed in rats treated with 1,25(OH)2D; by contrast, the plasma calcium was significantly decreased in the DEX-treated group compared to vehicle-treated rats. In a dose-effect experiment, this dose of 1,25(OH)2D induced marked hypercalcemia in rats not implanted with WC, but was required to decrease the tumor weight in implanted rats. In both 1,25(OH)2D and DEX-treated groups, plasma PTHrP levels were significantly decreased, but there was a similar correlation between PTHrP plasma level and tumor weight in the three groups. Indeed, the cytosolic PTHrP content/mg tumor was identical in the 3 groups. By contrast, the PTHrP/Actin mRNA in the tumor was significantly decreased in the 1,25(OH)2D group, comparatively to the vehicle and DEX groups. Our results show that Dexamethasone and 1,25(OH)2D decrease WC tumor development in vivo, but do not change the PTHrP secretion by the remaining tumor although steady state PTHrP mRNA content level is decreased by 1,25(OH)2D.

Animals↗
PubMed1993

Peripheral monocyte culture supernatants of menopausal women can induce bone resorption: involvement of cytokines.

Increased bone resorption is a mechanism contributing to bone loss in the postmenopausal period. Cytokines are involved in osteoclastic differentiation and, therefore, may play a role in the regulation of bone resorption. Several previous works showed the implication of interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF alpha) in the modulation of bone remodeling. This study determines the concomitant production of the three cytokines and tests the bone-resorbing activity of peripheral monocyte supernatants. Four groups of women were studied: premenopausal women (n = 13; mean age, 47 +/- 0.9 yr), untreated postmenopausal women (n = 21; mean age, 52 +/- 0.6 yr), postmenopausal women treated with estrogens (n = 14; mean age, 54.2 +/- 1.1 yr), or postmenopausal women treated with ethanehydroxydiphosphonate (n = 12; mean age, 53.2 +/- 2 yr). Assignment to clinical groups was verified by plasma FSH and estradiol determinations. Lumbar spine bone mineral density was significantly higher in the premenopausal women group than in the three postmenopausal groups. Peripheral blood monocytes were cultured for 48 h with 20% autologous plasma, and after stimulation with lipopolysaccharides. IL-1, IL-6, and TNF alpha levels were measured by RIA in the monocyte surpernatants. The three cytokines were highly correlated to each other, IL-1 with IL-6 (r = 0.76; P < 0.001), IL-1 with TNF alpha (r = 0.89; P < 0.001), and IL-6 with TNF alpha (r = 0.89; P < 0.001). The mean levels of the three cytokines could not be compared because of the variations in the values. However, a trend toward lower levels in the three cytokines was noted in estrogen-treated women compared to the untreated postmenopausals. The bone-resorbing activity of monocyte supernatants, assessed by fetal long bone-resorbing assay, increased in untreated postmenopausal compared to that in premenopausal women (1.22 +/- 0.08 vs. 0.87 +/- 0.11; P < 0.05). In estrogen-treated patients, this activity decreased to premenopausal levels (0.89 +/- 0.04 vs. 0.87 +/- 0.11; P = NS). The resorbing activity was correlated to IL-1 (r = 0.28; P = 0.03), IL-6 (r = 0.52; P < 0.01), and TNF alpha (r = 0.48; P < 0.01). The addition of cytokine inhibitors and IL-1 receptor antagonist and TNF alpha antibodies to the supernatant bone culture medium induced a significant decrease in the calcium release. Those data show the involvement of several cytokines in the bone resorption process after estrogen deficiency.

Bone Resorption↗
PubMed1992

Non-aluminic adynamic bone disease in non-dialyzed uremic patients: a new type of osteopathy due to overtreatment?

Adynamic bone disease, characterized by a low bone formation rate with normal or reduced amount of unmineralized osteoid, is supposed to be the consequence of aluminum intoxication in uremic patients. However, the emergence of adynamic bone disease has been recently reported in hemodialyzed patients in the total absence of aluminum overload. This study was aimed to assess whether such a histological pattern of adynamic bone disease was already present in uremic patients not yet on dialysis. Twenty-seven asymptomatic uremic patients (mean age +/- SD 43 +/- 10 years, mean creatinine clearance 19 +/- 3 ml/mm) were studied and bone biopsies were repeated in 16 of them after 18 +/- 10 months of treatment with oral calcium carbonate (1-3 g of elemental calcium/day) and calcidiol (21 +/- 14 micrograms/day). None of the patients received aluminum hydroxide, and the search for bone aluminum deposits was negative in all patients both before and after treatment. Two patients fulfilled the criteria of adynamic bone disease on their post-treatment biopsies. They originated from patients classified as having normal bone histology before treatment. Comparison with the other patients showed that they had comparable plasma C-terminal PTH but higher plasma creatinine than patients with normal bone histology and lower plasma C-terminal PTH than patients with osteitis fibrosa but comparable plasma creatinine. The plasma levels of 1,25(OH)2D reached values above normal after treatment in these two patients. It is suggested that adynamic bone disease not related to aluminum intoxication can develop in uremic patients independently of dialysis, and is favored by a relative hypoparathyroidism for the degree of renal failure, possibly induced by elevated plasma concentrations of calcitriol.

Adult↗
PubMed1991

A new method for measuring cancellous bone erosion depth: application to the cellular mechanisms of bone loss in postmenopausal osteoporosis.

We have devised a new method for measurement of final depth of erosion in cancellous bone with an intra-individual precision of 4.3% and applied it to determine the mechanism of continuing reduction in trabecular thickness after menopause. Mean erosion depth (SD) was 40.8 (2.0) microns in 10 healthy postmenopausal women and 41.4 (2.1) microns in 10 age-matched patients with postmenopausal osteoporosis; the difference was not statistically significant. In contrast, wall thickness, using a method based on density differences between new and old bone, was 39.5 (2.0) microns in the normal subjects and 35.3 (2.0) microns in the patients with osteoporosis (p less than 0.0001). The balance per remodeling cycle (delta BMU) was -1.34 (2.49) microns in the normal subjects and -6.11 (1.95) microns in the patients with osteoporosis. This difference was also highly significant (p less than 0.001). Indirect estimations of erosion depth and delta BMU, based on the fall in trabecular thickness from an assumed premenopausal value of 147 microns and the number of remodeling cycles accumulated since menopause, agreed closely with the measured values. Erosion depth measured by the Eriksen method also showed no significant difference between the two groups, but because the values were substantially higher delta BMU was improbably high in both groups, did not differ significantly between groups, and was inconsistent with the observed difference in trabecular thickness.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗