Effects of promethazine on bone mass and on bone remodeling in ovariectomized rats: A morphometric, densitometric, and histomorphometric experimental study.

The effect of promethazine on bone is debated. We studied the effect of promethazine on bone and the mechanism of action involved by densitometric and histomorphometric measurements in female Wistar rats (100 days old, mean weight 25 +/- 20 g). A control group of 15 rats was not manipulated. An experimental group of 15 rats were ovariectomized (OVX) at 100 days of life and fed a diet supplemented with 4.8 mg/kg promethazine hydrochloride (OVX + Prom). The group that underwent OVX and a group of 15 rats that underwent sham ovariectomy (Sham-OVX) were not treated with promethazine. After 30 days, all the rats were killed. Their femur and 5th lumbar vertebra were dissected and cleaned of soft tissue. Femoral length and vertebral height were measured with a caliper and bones were weighed on a precision balance. The bone mineral content (BMC) and bone mineral density (BMD) of the whole right femurs and 5th lumbar vertebras were measured by dual-energy X-ray absorptiometry (DXA). Trabecular bone volume (Cn-BV-TV%), trabecular number (Tb-N mm(-1)), trabecular thickness (Tb-Th microm), and trabecular separation (Tb-Sp microm) were measured in the femurs by histomorphometric study of nondecalcified bone. Our results showed that promethazine significantly inhibited postovariectomy loss of bone mass (P < 0. 0001) by significantly reducing bone resorption, as shown by the smaller trabecular spaces observed in the treated OVX rats (P < 0. 0001).

Effects of zinc supplementation on vertebral and femoral bone mass in rats on strenuous treadmill training exercise.

The hypothesis that a zinc (Zn) deficit may cause osteopenia in athletes is well founded. In rats exposed to strenuous exercise, we evaluated the effect of a zinc supplement on femoral and vertebral bone mass determined by dual-energy X-ray absorptiometry. Four lots of 93-day-old female Wistar rats were studied. A control group of 30 rats were not manipulated (Zn- Ex- group). The experimental group of 40 rats was fed a diet supplemented with an additional 20% of Zn/kg of feed; this group was divided into two groups of 20 rats each, one that did not exercise (Zn+ Ex-) and one that did (Zn+ Ex+). A group of 15 rats exercised but did not receive a zinc supplement (Zn- Ex+ group). Training consisted of treadmill running for 5 out of 7 days over an 11-week period. Initial speed, running time, and treadmill speed were increased gradually. Analysis of variance with the Bonferroni/Dunn test showed that the length, weight, bone mineral content (BMC), and bone mineral density (BMD) of the femur were less in the Zn- Ex+ group than in the others (p < 0.008), and the weight, BMC, and BMD of the fifth lumbar vertebra also were lower in the Zn- Ex+ group than in the others (p < 0.008). These findings confirm the adverse effects of strenuous exercise (treadmill running) on bone tissue in rats and the effectiveness of zinc supplementation in preventing it.

Influence of electromagnetic fields on bone mass and growth in developing rats: a morphometric, densitometric, and histomorphometric study.

The effect of electromagnetic fields on bone is debated. In an experimental study of this effect, we compared two lots of growing female rates (both lots n = 15, age 3 weeks, average weight 23.2 +/- 3.3 g), one of which was exposed to a 3-mT, 100-Hz, Helmholtz-type electromagnetic field for 24 hours a day for 30 days, and the other of which served as the control. Bone development and bone mass were evaluated by morphometry, densitometry, and histomorphometry. The rats were killed at 30 days and weighed. The right femurs were dissected, measured, and weighed; bone densitometry was used to determine femoral bone mineral content (BMC) and density (BMD), and histomorphometry of the nondecalcified bone was used to determine trabecular bone volume (Cn-BV-TV%), number (Tb-N mm) and thickness (Tb-Th microm), intertrabecular space (Tb-Sp microm) and growth cartilage thickness (Gc-Th microm). In the rats exposed to the electromagnetic field, BMC and BMD (P = 0.019 and P = 0.002, respectively) and Cn-BV-TV, Tb-N, Tb-Th (P = 0.005, P = 0.036, and P = 0.027, respectively) all were decreased, whereas Tb-Sp was increased (P = 0.002). There were no significant differences in initial and final body weight, or in final femur weight, femur length, and GC-Th. These findings indicate that electromagnetic fields of the type used here reduced bone formation and increased bone resorption without affecting bone development in rats.

Effect of lead on bone development and bone mass: a morphometric, densitometric, and histomorphometric study in growing rats.

The effect of exposure to lead on the longitudinal development of bone and on bone mass was studied in rats. A group of 35, 50-day-old female Wistar rats was divided into a control group of 15 rats and an experimental group of 20 rats fed a diet supplemented with 17 mg of lead acetate per kg feed for 50 days. Total body bone densitometry (TBBMC) was performed the day before ending the 50-day experiment. On day 50, all rats were killed and their right femur and 5th lumbar vertebra were dissected. The bones were cleaned of soft tissue and femoral length and vertebral length were measured with a caliper and all bones were weighed on a precision scale. Final body weight (P < 0.05), TBBMC (P < 0.005), and femur weight (P < 0.005) were significantly lower in the control group. Femur length did not differ between groups, but the length of the 5th lumbar vertebra was greater in the control group (P < 0.05). Histomorphometry of the femur showed that Cn-BV/TV, Tb-N, Tb-Th were lower (P < 0.05 in all) and Tb-Sp was higher (P < 0.05) in the group given the lead-supplemented diet. These findings suggested lead-induced inhibition of axial bone development and a histomorphometric decrease in bone mass, produced mainly by enhanced resorption, and a densitometric increase in bone mass, produced by lead accumulation in bone.

Comparison of the bone robusticity index and bone weight/bone length index with the results of bone densitometry and bone histomorphometry in experimental studies.

In experimental studies of bone in rats, two morphometric indices reflecting bone density have been proposed, the bone robusticity index and bone weight/bone length index. In rats, the bone mineral content (BMC) and bone mineral density (BMD) of a selected bone can be determined using dual-energy X-ray absorptiometry (DXA); bone volume can be measured by histomorphometry and other techniques. This study was undertaken to compare two morphometric indices (bone robusticity and bone weight/bone length) with the results of DXA and histomorphometry. Forty female Wistar rats (100 days old, mean weight 239+/-12 g) were studied: 20 controls and 20 ovariectomized rats (OVX). The morphometric indices and BMD differed significantly (Friedman test) in the overall group of rats; no differences were observed in the control group, but significant differences were apparent in the OVX group (p<0.0001). The morphometric indices correlated more closely with BMC than with BMD; the femur length/ femur weight index had closer correlations than the robusticity index. Nonetheless, both morphometric indices differed significantly from BMD determined by DXA under abnormal conditions, which makes them unreliable for use in these circumstances.

Effect of lead on bone and cartilage in sexually mature rats: a morphometric and histomorphometry study.

The effect of exposure to lead on the longitudinal development of the femur and of its cartilage growth plate was studied in rats. A group of forty-five 50-day-old female Wistar rats was divided into a control group of 20 rats and an experimental group of 25 rats fed a diet supplemented with 17 mg of lead acetate per kilogram of feed for 50 days. On Day 50 all rats were killed and their right femurs were dissected. The femurs were cleaned of soft tissue and femoral lengths were measured with a Vernier caliper and thickness of growth cartilage (GPC-Th micron) by histomorphometry. Final body weights were significantly (P < 0.05) lower in the control group than in the rats given the lead-supplemented diet. Femur length did not differ between groups. Histomorphometry of the femur showed that the thickness of growth cartilage was higher (P < 0.05) in the control group. These findings suggested lead-induced inhibition of growth plate development. The growth plate may be one of the key target tissues accounting for the adverse effects of chronic lead exposure on skeletal development.

Correlation of ultrasound bone velocity with dual-energy X-ray bone absorptiometry in rat bone specimens.

RATIONALE AND OBJECTIVES: To investigate bone mass measurements by ultrasound bond velocity (UBV) in bone specimens obtained from experimental animals. METHODS: The authors made UBV measurements in 40 femurs and tibias dissected from Sprague-Dawley rats (14 weeks-old, mean weight 290 g) and compared them with bone densitometric measurements made on the same material using dual-energy x-ray absorptiometry (DXA). RESULTS: The coefficient of variation for UBV measurements, based on values obtained in five femurs and five tibias at different times, was 0.2% and 0.3% respectively. Regression studies yielded a correlation between UBV and bone mineral density in femur of r = 0.87 (P < 0.0001) and with bone mineral content of r = 0.65 (P < 0.0001); in the tibia similar levels of significance were obtained. The correlation between femur weight and UBV was r = 0.51 (P < 0.0005) and with bone mineral content it was r = 0.79 (P < 0.0001). Partial correlation between UBV and femur bone mineral density, with respect to bone weight, was r = 0.68 (P < 0.001), and with femur bone mineral content was r = 0.71 (P < 0.0001). In the tibia measurements were similarly significant. CONCLUSIONS: Measurements of bone mass made with ultrasound transmission velocity are precise correlate well with DXA measurements.

Evaluation of bone density with peripheral quantitative computed tomography in healthy premenopausal, perimenopausal, and postmenopausal women.

We compared bone mass in premenopausal, perimenopausal, and postmenopausal women using peripheral quantitative computed tomography to measure separately cortical, trabecular, and total bone density. Trabecular bone density was lower (p < 0.05) in the perimenopausal women than in the healthy premenopausal women. In perimenopausal women, trabecular bone density showed a significant linear regression with age (r = 0.554, p < 0.001), but cortical bone density did not (r = 0.130, p = 0.447). The group of postmenopausal women had significantly lower bone mass in all three bone compartments than the premenopausal and perimenopausal women. These findings confirm the existence of a significant loss of trabecular bone mass in the perimenopausal period.

Cortical versus trabecular bone mass: influence of activity on both bone components.

Motivated by the controversy in the literature concerning the influence of activity on bone mass and on its cortical and trabecular components, a study was made using computed peripheral tomography (Stratec XCT 900) of the total, cortical, and trabecular bone mass of the dominant and nondominant upper extremities of 50 apparently normal subjects (average age 26 +/- 6 years). No differences were observed in the trabecular bone compartment, but the cortical compartment was greater (P < 0.001) in the dominant extremity. There was also a significantly greater total bone mass in the dominant extremity which we attributed to greater cortical mass (P < 0.025) given the highly significant correlation (r2 = 0.904, P = 0.0001) between total and cortical bone mass and the less significant correlation between total and trabecular bone mass (r2 = 0.479, P = 0.0001).

Etidronate versus clodronate in the prevention of postovariectomy bone loss. An experimental study in rats.

OBJECTIVE: We compared the diphosphonates etidronate and clodronate to find out which was more effective in inhibiting the loss of bone mass after ovariectomy in rats. METHODS: Five lots of female Sprague Dawley rats, each containing 15 rats (14 wks old; mean weight 290 g), were kept under identical living conditions (12 hrs of light and 12 hrs of darkness), habitat, and diet following the current norms of the European Economic Community. One lot was kept as a control; one lot underwent sham ovariectomy (Sham-OVX); and the remaining 3 lots were anesthesized and underwent double ovariectomy (OVX). One lot of ovariectomized rats was given etidronate by esophageal tube, 5 mg/kg/day (OVX-E); one lot was treated with intraperitoneal clodronate, 5 mg/kg/3 days (OVX-Cl). The remaining lot was not manipulated (OVX). The animals' right femurs were then dissected for measurements of the bone mineral content. RESULTS AND CONCLUSION: Bone densitometry revealed that loss of bone mass 2 months after ovariectomy in the OVX-Cl group was 2.3%, not differing from that of the control group; bone loss in the OVX-E group was 11.7%, significantly different from the control group and from the OVX-Cl group (p < 0.001). These results show that clodronate is superior to etidronate in inhibiting osteopenia after ovariectomy in rats.

Bone mineral content and anthropometric variables in men: a cross-sectional study in 324 normal subjects.

Total body bone mineral content (TBBMC), total body bone mineral density (TBBMD), and regional bone mineral content (BMC) were determined with dual energy X-ray absorptiometry and correlated with different anthropometric variables in 324 normal male subjects aged 15 to 85 years, in order to obtain further knowledge of the controversial course of bone mass in males. These subjects showed increased TBBMC and TBBMD up to the age of 25-29 years. A positive and significant (p < 0.001) correlation was observed between TBBMC and TBBMD and with BMC with age (p < 0.001), as well as between age and body weight (p < 0.001) and between the latter and body fat (p < 0.001). Age did not correlate with weight or TBBMC, TBBMD, and regional BMC in subjects older than 29 years, while a significant and positive correlation between body weight and muscle mass was observed with bone mass (p < 0.001). By multiple regression analysis, TBBMC was significantly independent of fat-free mass (FFM) and lean body mass (LBM) (p < 0.01). These findings led us to point out that bone mass increases until the age of 29 years and that changes depend more on weight that on age in men. The rate of bone mass loss with age was 0.23%, that of soft tissue 0.35%, while fat mass increased 0.7% per year.

Four-compartment model of body composition of normal elderly women.

A group of 186 apparently normal women was divided into three age groups (average ages 65.3 +/- 4.4, 74.7 +/- 5.5, and 80.9 +/- 4.2 years, respectively) and their body composition was studied using dual-energy X-ray absorptiometry. The fat, fat-free, and mineral components were quantitated, and the fat-free compartment was calculated to define a four-compartment model of body composition (fat, fat-free, mineral, and water). Fat decreases with age, as shown by the comparison of the group whose average age was 75 years with the 65-year-old group (p < 0.01) and 80-year-old group (p < 0.005). Soft-tissue mass was greater in the 80-year-old group (p < 0.025) than in the 75-year-old group. Water was lower in the two older groups (p < 0.02 and p < 0.005, respectively), and the mineral component showed no differences. The decreased fat, increased soft tissues, and absence of changes in the mineral component may be related to an improvement in habits and lifestyle in recent years.