Joaquin Cortés

Heterogeneity of trabecular and cortical postmenopausal bone loss: A longitudinal study with pQCT

Eighty-one women were studied longitudinally to measure trabecular bone mineral density (BMDTrab) and cortical bone mineral density (BMDCorti) in the distal radius by peripheral quantitative computed tomography (pQCT) at intervals of about 1 year and to calculate the rate of percent change/year. Fifty-three women were naturally postmenopausal [mean age 63.3 +/- 5.3 years, age at menopause 50.7 +/- 3.8 years, 13 years since menopause (YSM)] and 28 had been ovariectomized (mean age 52.7 +/- 5.8 years, age at menopause 39.5 +/- 5.0 years, 13 YSM). There was no difference between groups (ANOVA) in the rate of percent change/years in BMDTrab (p = 0.692), but there was in BMDCorti (p = 0.020). When the women who had either gained or lost bone mass were compared (chi-square test), only BMDCorti differed significantly (p = 0.018). Considering > -2.5% change/years as the limit for rapid bone mass loss, BMDTrab values showed that 43% of the naturally postmenopausal women and 42.7% of the ovariectomized women had rapid bone loss (p ns). On the basis of BMDCorti values, 45% of the naturally postmenopausal women and 28.4% of the ovariectomized women had rapid bone loss (p = 0.018). Height, weight, body mass index (BMI), age, YSM, and years of reproductive life did not differ (ANOVA) between the women who gained or lost either BMDTrab or BMDCorti. Using Fishers r to z and partial correlation adjusted for age and YSM of the percent change/year in BMDTrab and BMDCorti in the overall group and in each menopausal group, only BMDCorti differed.

Changes in body composition in women treated with gonadotropin-releasing hormone agonists

OBJECTIVE The changes that agonists of gonadotropin-releasing hormone (GnRH) produce in mineral bone mass are known, but, as far as we know, those produced by these agents in other body compartments are unknown. METHODS We studied these changes using dual-energy X-ray absorptiometry in 50 eugonadal women treated with decapeptyl (Triptoreline), 3.75 mg injected intramuscularly, at 28-day intervals for 6 months. RESULTS There were significant increases in fat content (9.5%, P < 0.0005) and weight (1.3%, P < 0.01), and significant decreases in fat-free mass (-1.9%, P < 0.0001) and water content (-1.8%, P < 0.0002). Bone mass was lost in the axial skeleton (-3.6%, P < 0.0001) but not in the peripheral skeleton. CONCLUSIONS The changes induced in body composition by the GnRH agonists are similar to those of natural menopause.

Pituitary adenylate cyclase-activating peptide/vasoactive intestinal peptide receptors in human normal mammary gland and breast cancer tissue.

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) bind similarly to VPAC1 and VPAC2 receptors, whereas PACAP binds with higher affinity than VIP to PAC1 receptors. Here we demonstrate by different approaches the expression of the three subclasses of PACAP/VIP receptors in human normal and malignant breast tissue. At the mRNA level, reverse transcription–polymerase chain reaction experiments showed VPAC1 and VPAC2 receptors as well as various isoforms (null, hip/hop) of PAC1 receptors due to alternative splicing. At the protein level, Western blot experiments revealed the three subclasses of receptor although no conclusive differences could be established when comparing control, peritumoral and tumoral tissue samples. Immunohistochemistry showed the distribution of these receptors: they were located at epithelial cells in normal and cancer conditions but also in leukocytes at the stromal level in carcinomatous tissue. A weaker immunostaining of PAC1 receptors in normal tissue and a strong density of the three PACAP/VIP receptor subclasses in cancer tissue may be related to differential expression patterns during breast tumor progression but more samples need to be studied to validate this hypothesis. PAC1, VPAC1 and VPAC2 receptors were functional, as shown by their coupling to adenylate cyclase stimulation: VIP, PACAP-27 and PACAP-38 behaved similarly at this level, whereas both VPAC receptors acted alike as shown by means of specific peptide agonists and antagonists. The present results together with the known presence of PACAP and VIP in the mammary gland support a paracrine/autocrine involvement of both peptides at this level in physiological and pathological conditions, i.e. during malignant transformation.

INFLUENCE OF SOFT TISSUE (FAT AND FAT-FREE MASS) ON ULTRASOUND BONE VELOCITY : AN IN VIVO STUDY

RATIONALE AND OBJECTIVES The authors determine the relative effect of soft-tissue compartments, body fat (percent [%Bfat] and weight [Bfat kg]) and fat-free mass (FFM kg), on measurements of ultrasound bone velocity (UBV m/second). METHODS The authors measured UBV in proximal phalanxes and body fat and fat-free mass by near infrared interactance in 40 healthy premenopausal women (mean age +/- standard deviation 28.2 +/- 3.8 years). RESULTS Correlation study (Fishers r to z) showed that UBV correlated negatively with %Bfat (r = -0.61, P < 0.0001), Bfat kg (r = -0.56, P = 0.0001) and marginally with body weight (r = -0.33, P = 0.0403), but did not correlate with FFM kg or H2O L (both r = -0.08, P not significant). When the correlation test was adjusted for weight and age (partial correlation), the negative correlation between UBV and %Bfat persisted (r = -0.54, P < 0.0005; and r = -0.63, P < 0.0001, respectively) and the correlation with FFM kg, adjusted for weight, became positive and significant (r = 0.55, P < 0.0005). CONCLUSIONS These results, to our knowledge, are the first to be obtained by in vivo evaluation of UBV in relation to body fat and fat-free mass. Body fat, but not fat-free mass, was the main factor affecting UBV. This confirms the deficiency of UBV measurements, considering that obesity is a protective factor for bone mass.

Influence of weight and gonadal status on total and regional bone mineral content and on weight-bearing and non-weight-bearing bones, measured by dual-energy X-ray absosorptiometry

OBJECTIVE To evaluate the influence of weight on total body bone mineral content (BMCTB) and regional body bone mineral content (head, arms, trunk and legs). This was studied in accordance with gonadal status and the weight-bearing or non-weight-bearing status of each region. METHODS The study included 94 postmenopausal women (mean age 60.6 +/- 10.5 years), 36 perimenopausal women (mean age 49.0 +/- 2.3 years) and 60 premenopausal women (mean age 36.1 +/- 6.9 years). Full-body bone densitometry (DXA), for measuring total body bone and regional bone mineral content, was carried out in all the women. RESULTS Among these groups, the influence of 1 kg of body weight on total and regional bone mineral content (percent) did not differ (paired test P ns). In the overall group of women, paired comparison showed differences between the head and other zones measured (P = 0.036-0.004). In the overall group of women, no differences were found in the percent influence of 1 kg body weight on bone mineral content in any study zone (by ANOVA, Fishers PLSD post hoc test and the Kruskal-Wallis test). In the overall group of women, Fishers r to z test revealed a non-significant relationship between weight and the bone mineral content of the head (r = 0.49, P ns) but in every other region the relationship between weight and bone mineral content was significant (r = 0.36-0.54, P < 0.0001 in all). CONCLUSIONS The effect of body weight on BMCTB and regional did not differ significantly with either gonadal status or weight-bearing (legs) and non-weight-bearing bones (arms).

Impact of weight in obese subjects on bone speed of sound.

RATIONALE AND OBJECTIVES The authors determined the effect of obesity on measurements of amplitude-dependent speed of bone ultrasound (Ad-SOS [m/sec]) and compared them to the total body bone mineral content (TBBMC/g). METHODS A total of 25 women were studied (mean age 41.8 +/- 10.2 years). In all the subjects, body mass index (BMI) exceeded 30 kg/m2 (range, 31.12-47.47 kg/m2); mean body weight was 104 +/- 17 kg. Ad-SOS was measured at the proximal phalanges and TBBMC in whole body with dual-energy x-ray absorptiometry. RESULTS Correlation study (Fishers r to z) showed that Ad-SOS correlated negatively with weight (r = -0.85, P < 0.0001) and with TBBMC (r = -0.71, P < 0.0001). The correlation between TBBMC and weight was r = 0.76, P < 0.0001. Body fat percentage correlated partially with TBBMC (r = 0.40, P < 0.05) and negatively with Ad-SOS (r = -0.75, P < 0.0001). When the correlation test was adjusted for weight (partial correlation), the correlation between Ad-SOS and TBBMC was not significant (r = -0.21, P = NS), and the correlation between Ad-SOS and weight continued to be inversely significant (r = -0.67, P < 0.0001). CONCLUSIONS The results showed a clearly negative effect of weight on Ad-SOS measurements and indicated the limitations of this technique when employed in overweight and obese patients. Broad-band ultrasound attenuation and speed of sound, two commonly measured variables in bone ultrasound studies, may be differently affected by soft tissue.

Changes in the cortical and trabecular bone compartments with different types of menopause measured by peripheral quantitative computed tomography

Our objective was to study the changes in the bone mineral density of the cortical and trabecular compartments with different types of menopause. A total of 153 normal postmenopausal women (mean age 48 +/- 5 years) were studied. The women were divided into three groups based on mean age at menopause: early menopause (menopause before 43 years), normal menopause (menopause at 44-52 years), and late menopause (menopause after 52 years). The number of years since menopause was similar in all three groups (+/- 5 years). Cortical and trabecular bone mineral density was determined in all the women using peripheral quantitative computed tomography. Our results show that only the trabecular bone mineral density differed significantly among the groups (Kruskal-Wallis: P = 0.0029). The women with early menopause had a lower trabecular bone density than the women with normal and late menopause (P = 0.0019 and P < 0.0001, respectively). Among the women with early menopause, 22 had experienced menopause before the age of 40 and 25 after the age of 40; there were significant differences in trabecular bone mineral density between these two subgroups (P < 0.05). Trabecular bone mineral density, the only variable studied that varied among the groups, correlated significantly with the duration of reproductive life (simple linear regression: r = 0.340, P < 0.0001). In conclusion, these findings emphasize the importance of the duration of reproductive life as a determinant of bone mass in women.

Fetal cardiotocography and acid-base status during cesarean section

OBJECTIVE To assess the fetal well-being during cesarean section, in relation to the previous fetal condition. DESIGN Observational study. SETTING University Hospital. PATIENTS PARTICIPANTS: 204 women undergoing cesarean section (203 intrapartum cesarean sections): 177 with general anesthesia and 27 with spinal anesthesia. MATERIAL AND METHODS We compared the fetal heart records of the last 30 min before cesarean section (during the first stage of labor) with those during cesarean section. Scalp blood analysis 30 min before the beginning of anesthesia induction was compared with umbilical artery analysis at delivery. MAIN OUTCOME MEASURES Cardiotocography. Acid-base analysis. Apgar scores. RESULTS During cesarean section there was a reduction in uterine activity, an increase in silent tracings and a decrease in late decelerations. Umbilical artery pH was lower than scalp pH (7.23+/-0.06 vs 7.30+/-0.06). Oxygen saturation was also lower (14.43+/-8.58% vs 18.99+/-8.4%). The values of pCO2 and of base deficit were higher. During cesarean section low values of modified Fischer scores were associated with low pH values of umbilical artery and low Apgar scores. CONCLUSION Silent tracings appearing during cesarean section usually do not indicate fetal distress. Poor intracesarean fetal heart tracings were associated with worse indicators of neonatal well-being. Although umbilical pH were lower than scalp values, when the correction described in the literature was applied, the difference was of little clinical relevance. It is concluded that anesthesic, pharmacological and surgical events have slight repercussion in fetal well being. However, in a few cases fetal heart monitoring during cesarean section could detect otherwise undiagnosed cases of transient acidemia or depression in the fetus.

Effect of uterine horn ligation on bone mass: an experimental study in rats.

OBJECTIVE After tubal ligation, normal bone mass in the presence of gonadal deficit has been reported. These incongruent results motivated us to examine the topic. STUDY DESIGN Bone mass was assessed by densitometry and ultrasonography 60 days after surgery on 100-day-old female Wistar rats. Fifteen Wistar rats with uterine horn ligation (TL) were compared with 15 unoperated, 15 with a sham uterine horn ligation (Sham-TL), and 15 ovariectomized (OVX), using ANOVA and a correlation test to determine the relations between results. RESULTS Femoral and vertebral bone mass were significantly lower in the OVX y TL groups than in unoperated and controls groups (P<0.0001). CONCLUSIONS Our study revealed significantly lower axial and peripheral bone mass in rats with uterine horn ligation.

Effect of induced uterine retroversion on bone mass in rats

OBJECTIVE To evaluate the effect of surgical uterine retroversion on bone mass in rats. STUDY DESIGN Forty-five female Wistar rats were assigned randomly to three groups: 15 unmanipulated rats, 15 rats that underwent uterine retroversion, and 15 rats that underwent sham uterine retroversion (exposure of the uterus to air followed by closure of the abdominal cavity). Sixty days later the rats were killed and their femurs were dissected. Femurs were weighed and measured, and femoral bone mineral content (BMC) and bone mineral density (BMD) were determined by dual energy X-ray absorptiometry. RESULTS In the group of rats that underwent uterine retroversion, BMC, BMD, and BMC corrected for final body weight were significantly lower (P<0.001) than in the unmanipulated control and sham uterine retroversion groups. CONCLUSION Our findings indicate that uterine retroversion induced a loss of bone mass. We could not determine the mechanism of bone loss; in our opinion, these problem merits further investigations, which currently occupy our interest.