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PubMed2005

Ovariectomy fails to augment bone resorption and marrow B lymphopoiesis in granulocyte colony-stimulating factor transgenic mice.

The mechanism of pathological bone loss induced by estrogen deficiency has not been fully elucidated. It has been shown in recent animal studies that increased B lymphopoiesis induced by estrogen deficiency is involved in the mechanism of stimulated bone resorption. Mice transgenic for granulocyte colony-stimulating factor (G-CSF) (G-Tg) exhibit generalized osteopenia with an increase in osteoclast number and enhancement of bone resorption, which coexists with enhanced hematopoiesis. When ovariectomy was performed on G-Tg, it did not further reduce bone mass as revealed by radiography, dual-energy X-ray absorptiometry, and peripheral quantitative computed tomography. Ovariectomy increased the amount of colony-forming units of interleukin 7 (CFU-IL-7) by threefold in the marrow of normal mice in association with an increase in the number of B220-positive cells expressing the receptor activator of nuclear factor-kappaB ligand (RANKL). In contrast, the number of B220-positive cells expressing RANKL and CFU-IL-7 remarkably decreased in the marrow of G-Tg. Ovariectomy induced neither CFU-IL-7 nor B220-positive cells expressing RANKL in the marrow of G-Tg. Strong inhibition of B lymphopoiesis by G-CSF resulted in depletion of B cells expressing RANKL from the marrow, which may lead to resistance to bone loss due to ovariectomy. This observation suggests that B lymphopoiesis plays a possible role in bone loss in a condition of acute estrogen deficiency.

Analysis of Variance↗
PubMed1988

Ultrastructural evidence suggests variations in biosynthesis and processing within LH-RH neurons as a function of ovariectomy in rats.

We have demonstrated that populations of luteinizing hormone-releasing hormone (LH-RH)-immunopositive neuronal perikarya change following gonadectomy of male and female rats in a sex-dependent manner related to rises in plasma luteinizing hormone (LH). In this study we characterize the ultrastructural state of organelles involved in protein synthesis, primarily within perikarya of rostral preoptic area LH-RH neurons surrounding the organum vasculosum of the lamina terminalis (OVLT). One day following ovariectomy little rough endoplasmic reticulum (RER) was evident, however, the cisternae were heavily laden with ribosomes and numerous polysomes were present free in the cytoplasm. Six days and 3 weeks post-ovariectomy the cisternae of RER were progressively more abundant and dilated; the multiple Golgi apparati, located in close proximity to the RER, were composed of many lamelae and extensive associated vesicles. We propose that increased pools of messenger ribonucleic acid (mRNA) are generated by 1 day post-ovariectomy prior to increased synthesis of precursor, 6 days and 3 weeks post-ovariectomy. Axodendritic synaptic profiles in the neuropil surrounding LH-RH perikarya increased in number in the rostral medial preoptic area and lateral anterior hypothalamic area. We conclude that removal of gonadal steroids results in greater biosynthetic activity in LH-RH neurons, and suggest that the enhanced biosynthesis is related to increases in afferent activity.

Animals↗
PubMed1986

Effects of ovariectomy, social instability and social status on female Macaca fascicularis social behavior.

The effects of ovariectomy, social instability and social status on affiliative and agonistic behavior were studied in 44 females housed in 10 unimale groups. Five of the groups contained ovariectomized females and five groups contained intact females. The membership among three groups of intact females (n = 13) and three groups of ovariectomized females (n = 13) was reorganized every three months (unstable), and the other groups were left undisturbed (stable) for the 22 month study. The behavior of each female was recorded during 160 (stable) or 190 (unstable) 15 min focal observations of each subject. The social status of each female was determined by outcomes of agonistic interactions. It was hypothesized that the effects of social instability and status would be more pervasive than the effects of ovariectomy. It was found that ovariectomy reduced interfemale affiliation and increased male-female agonism. Social instability increased submissions to males and females and time spent alone, and decreased interfemale affiliation. Dominant animals were more aggressive and less submissive than subordinates. Thus, ovariectomy influenced both isosexual and heterosexual social interaction, implying mediation of these behaviors, at least in part, by ovarian hormones.

Animals↗
PubMedDate not supplied

Neurokinin A in the anterior pituitary of female rats: effects of ovariectomy and estradiol.

The effect of acute and chronic ovariectomy and the substitutive treatment with 17-beta estradiol and/or progesterone on anterior pituitary levels of neurokinin A (NKA) was studied in female rats. Acute ovariectomy did not result in significant changes of NKA in the anterior pituitary gland as compared with the levels in diestrous intact rats, but a single injection of 5 micrograms of estradiol in ovariectomized rats significantly decreased NKA levels in the anterior pituitary gland. Progesterone was without effect and did not modify the decrease of NKA in the anterior pituitary gland induced by estradiol. In rats examined 11 to 17 days after ovariectomy, NKA in the anterior pituitary gland was significantly higher than in diestrous intact rats. In the hypothalamus, ovariectomy resulted in decreased levels of NKA in the median eminence-arcuate nucleus. Estradiol significantly reduced NKA stores in the anterior pituitary gland but increased them in the whole hypothalamus and in the median eminence-arcuate nucleus. Thus, estradiol seems to be a powerful regulator of NKA stores in the adenohypophysis and also in the hypothalamus.

Animals↗
PubMed1990

Effect of the rat estrous cycle at ovariectomy on striatal D-1 dopamine receptors.

We have investigated the effect of the surgical suppression of gonadal steroid hormones by ovariectomy on striatal D-1 dopamine (DA) receptors, in relation with the stage of the estrous cycle at the time of surgery. Plasma levels of 17 beta-estradiol and progesterone declined rapidly to a minimum one and two days after ovariectomy, respectively. Ovariectomy of female rats in proestrus led to an increased density of striatal D-1 DA from the first to the fourth day following surgery with a return to control values on the 7th day. Rats ovariectomized (OVX) in estrus showed an increased striatal D-1 DA receptor density from the second to the fourth day following surgery with a return to control values 7 days following ovariectomy. Striatal D-1 DA receptor density of rats OVX in diestrus remained constant up to 7 days after surgery. The affinity of striatal D-1 DA receptors remained unchanged in all cases. Therefore, this report illustrates that steroid hormonal fluctuations as occurring during the 4-day estrous cycle of the rat can modulate striatal D-1 DA receptors.

Animals↗
PubMed1995

The effects of clodronate on increased bone turnover and bone loss due to ovariectomy in rats.

The present study was carried out to investigate the ability of clodronate to inhibit ovariectomy-induced bone loss and increased bone turnover in rats. Estradiol was administered as a reference compound. Seventy Sprague-Dawley rats were ovariectomized (OVX) or sham-operated (Sham) at the age of 90 days and divided into seven groups. Two Sham and two OVX groups received subcutaneously either the vehicle of clodronate or the vehicle of estradiol. Other OVX groups were given s.c. either disodium clodronate at two dose levels (5 mg/kg or 12.5 mg/kg twice a week) or 17 beta-estradiol (10 micrograms/kg five times a week) for 8 weeks. Femur length, volume, dry weight, and ash weight were determined, and proximal ends of tibiae were used for bone histomorphometry. Markers of bone metabolism were measured from urine and serum. A significant loss of 54% of trabecular bone area of proximal tibial metaphysis was found at 8 weeks after ovariectomy. Clodronate and estradiol inhibited (p < 0.001) this osteopenia. Both drugs prevented the decrease in ash weight/volume of the femur. The inhibitory effect of clodronate and estradiol on bone resorption in OVX rats could be detected also in decreased urinary excretion of hydroxyproline and lysylpyridinoline (p < 0.001). Clodronate and estradiol decreased (p < 0.001) the ovariectomy-induced enhanced tibial endocortical mineral apposition rate (Ec.MAR) on the lateral cortex to the level of the Sham group. In contrast, periosteal MAR analyzed on the medial side of tibial cortical bone did not change significantly in the OVX/Veh group. Estradiol decreased periosteal MAR to below the level in the Sham group (p < 0.01). These results suggest that ovariectomy of growing rats resulted in tibial and femoral osteopenia two months later. Clodronate as well as estradiol can suppress bone resorption and turnover in ovariectomized rats, inhibiting the development of osteopenia. Both clodronate doses (5 and 12.5 mg/kg) had beneficial effects in ovariectomized animals.

Analgesics, Non-Narcotic↗
PubMed2006

Laparoscopic ovariectomy for whole human ovary cryopreservation: technical aspects.

OBJECTIVE: To describe the technique of laparoscopic ovariectomy with a view to cryopreservation of a whole ovary with its vascular pedicle. DESIGN: Descriptive study. SETTING: Gynecology research unit in a department of gynecology in a university hospital. PATIENT(S): Women with indications for chemotherapy or radiotherapy who are at high risk of premature ovarian failure. INTERVENTION(S): Laparoscopic ovariectomy for whole ovary cryopreservation in nine patients. MAIN OUTCOME MEASURE(S): Feasibility of laparoscopic ovariectomy for whole ovary cryopreservation and later autotransplantation without delaying chemotherapy. RESULT(S): The whole ovary was successfully removed by laparoscopy and cryopreserved by arterial catheterization in all nine patients. CONCLUSION(S): Ovariectomy with a view to whole ovary cryopreservation for future transplantation may be performed by laparoscopy. Great care must be taken to remove the ovary, together with a large part (> or =5 cm) of the infundibulopelvic ligament, allowing dissection of the ovarian vessels, perfusion with a cryoprotective medium, and cryopreservation for subsequent autografting of the whole ovary. The period of ischemia between ligation of the ovarian pedicle and ovarian cryopreservation must be as short as possible.

Cryopreservation↗
PubMed2006

Effects of ovariectomy and chronic estradiol administration on pituitary-thyroid axis in adult rats.

The effects of ovariectomy (Ovx) and of ovariectomy followed by chronic estradiol dipropionate administration (Ovx EDP) on the structure and function of the pituitary-thyroid axis were examined in the rat. Pituitary TSH cells and thyroid tissue were histologically, immunohistochemically and stereologically investigated. Serum TSH and T(4) levels were determined by RIA. Ovx did not affect pituitary weight, but subsequent treatment with EDP led to its more than two-fold increase (p<0.05). After ovariectomy, the cellular volume of pituitary TSH-immunoreactive cells increased by 28%, p<0.05 compared to sham-operated animals (SO). Treatment of Ovx rats with EDP partially reversed this change. However, the relative volume density of thyrotrophs decreased in comparison to the Ovx and SO groups (by 18% and 23%, p<0.05, respectively). No statistically significant differences in serum TSH levels were observed between the experimental groups. In thyroid tissue both peripheral and central follicles responded to Ovx and EDP treatments. Compared to SO rats, the relative volume densities of the follicles and colloid were increased (by 14% and 30%, p<0.05, respectively) in Ovx rats. Chronic EDP treatment of Ovx rats reversed these changes to the pre-ovariectomy state. Hyperplasia of thyroid follicular cells and a significant reduction (by 21%, p<0.05) of the serum level of T(4) were detected. In conclusion, estradiol deficiency and chronic treatment affected pituitary TSH cells and thyroid tissue. The sum effect of Ovx on the pituitary-thyroid axis was slightly stimulatory. Subsequent EDP treatment decreased thyroid functioning but at the same time preserved serum TSH at the control level.

Animals↗
PubMed2005

Vitamins E and C pretreatment prevents ovariectomy-induced memory deficits in water maze.

We investigated whether the pretreatment with vitamins E (alpha-tocopherol) and C (ascorbic acid) would act on ovariectomy-induced memory deficits in Morris water maze tasks. Adult female Wistar rats were divided into three groups: (1) naive (control), (2) sham (submitted to surgery without removal of ovaries) and (3) ovariectomized. Thirty days after surgery, they were trained in the Morris water maze in order to verify ovariectomy effects both on reference and working memory tasks. Results show that ovariectomized rats presented impairment in spatial navigation in the acquisition phase, as well as in the time spent in target quadrant and in the latency to cross over the location of the platform in test session, when compared to naive and sham groups (controls), in the reference memory task. Ovariectomy did not affect performance in the working memory task. Confirming our hypothesis, ovariectomized rats pretreated for 30 days with vitamins E and C had those impairments prevented. We conclude that ovariectomy significantly impairs spatial reference learning/memory and that pretreatment with vitamins E and C prevents such effect. Assuming this experimental memory impairment might mimic, at least in part, the cognitive deficit sometimes present in the human condition of lack of reproductive hormones, our findings lend support to a novel therapeutic strategy, based on vitamins E and C, to cognitive impairments in post-menopausal women.

Animals↗
PubMed2005

Circulating estradiol and hypothalamic corticotrophin releasing hormone enhances along with time after ovariectomy in rats: effects of electroacupuncture.

Repeated electroacupuncture (EA) stimulation is known to enhance the circulating level of estrogen in the ovariectomized rats by stimulating the activity of the hypothalamus-pituitary-adrenal axis. To explore the mechanism of EA in promoting the homeostasis in ovariectomized rats, the hypothalamic CRH content and its mRNA expression as well as the circulating estradiol in the rats along with time after ovariectomy were detected. Female rats were divided into fourteen groups: 1 month after ovariectomy (OVX1M), OVX2M, OVX3M, OVX4M, OVX5M, OVX6M; intact 1 month (INT1M), INT2M, INT3M, INT4M, INT5M, INT6M; OVX1M with EA (OVX1M+EA) and intact 1 month with EA (INT1M+EA). The blood concentrations of estradiol (E2) and total contents of hypothalamic CRH were measured by radioimmunoassay. The expressions of CRHmRNA were semiquantified by RT-PCR. The results showed that the blood E(2) concentrations increased gradually along with time after ovariectomy in the rats. The level was higher in OVX1M+EA than those in OVX1M, 2M, 3M (p < 0.05), which was near to the level in OVX6M. The total content (ng/g tissue) of hypothalamic CRH and the CRHmRNA expressions in the OVX6M rats were higher than other groups (p < 0.05). The CRH content or mRNA expression in the OVX1M+EA increased significantly compared with that in OVX1M (p < 0.05), and it was close to the level in the OVX4M and OVX5M. The results suggested that the circulating E2 and hypothalamic CRH enhances along with time after ovariectomy in rats, and the EA stimulation might speedup the process.

Animals↗
PubMed1993

Growth hormone secretion in premenopausal women before and after ovariectomy: effect of hormone replacement therapy.

OBJECTIVE: To evaluate the GH response to growth hormone-releasing hormone (GH-RH) stimulation in premenopausal women before and after ovariectomy and after 1 month of estrogen replacement therapy (ERT). PATIENTS: Ten women 42 to 49 years of age awaiting combined hysterectomy and ovariectomy for a variety of benign gynecological conditions. INTERVENTION: Endocrine status was determined by assay of basal levels of gonadotropins (LH, FSH), E2, P, and PRL. Stimulation with GH-RH was performed before and 8 to 10 days after ovariectomy, and after a month of ERT. RESULTS: A significant reduction in GH response to GH-RH was observed after ovariectomy. Estrogen replacement therapy restored GH response to presurgical levels. CONCLUSIONS: The results support the role of E2 in the stimulated secretion of GH and suggest that ERT increases pituitary stores of GH.

Adult↗
PubMed1993

Prostaglandin E2 increased rat cortical bone mass when administered immediately following ovariectomy.

To investigate the effects of ovariectomy and the simultaneous administration of prostaglandin E2 (PGE2) on rat tibial shaft cortical bone histomorphometry, thirty-five 3-month-old female Sprague-Dawley rats were either ovariectomized (OVX), or sham ovariectomy (sham-OVX). The OVX rats were divided into three groups and treated with 0, 1 and 6 mg PGE2/kg/day for 90 days. The double fluorescent labeled undecalcified tibial shaft cross sections (proximal to the tibiofibular junction) of all the subjects were used for histomorphometry analysis. No differences in cross-sectional area and cortical bone area were found between sham-OVX and OVX controls, but OVX increased marrow area, intracortical porosity area and endocortical eroded perimeter. Periosteal and endocortical bone formation rates decreased with aging yet OVX prevented these changes. These OVX-induced increases in marrow area and endocortical eroded perimeter were prevented by 1 mg PGE2/kg/day treatment and added bone to periosteal and endocortical surfaces and to the marrow cavity. At the 6 mg/kg/day dose level, PGE2-treated OVX rats increased total tissue area, cortical bone area, marrow trabecular bone area, minimal cortical width and intracortical porosity area, and decreased marrow area compared to basal, sham-OVX and OVX controls. In addition, periosteal bone formation was elevated in the 6 mg PGE2/kg/day-treated OVX rats compared to OVX controls. Endocortical eroded perimeter increased from basal and sham-OVX control levels, but decreased from OVX control levels in the 6 mg PGE2/kg/day-treated OVX rats. Our study confirmed that ovariectomy does not cause osteopenia in tibial shaft cortical bone in rats, but it does stimulate endocortical bone resorption and enlarges marrow area. The new findings from the present study demonstrate that PGE2 prevents the OVX-induced increases in endocortical bone resorption and marrow area and adds additional bone to periosteal and endocortical surfaces and to marrow cavity to increase total bone mass in the tibial shaft of OVX rats when given immediately following ovariectomy.

Animals↗
PubMed1994

Effects of ovariectomy and estrogen on the serum levels of insulin-like growth factor-I and insulin-like growth factor binding protein-3.

To determine the effects of ovariectomy and 17 beta-estradiol (E2) on serum IGF-I and its binding proteins, female Sprague-Dawley rats, aged 95 days, were divided into four groups. Group 1 was sham-operated; groups 2, 3, and 4 were ovariectomized. Groups 3 and 4 received daily injections of 200 ng (low dose) and 5000 ng (high dose) E2/kg body wt./day, respectively and the others were given solvent vehicle. Ovariectomy resulted in a significant increase in serum IGF-I (P < 0.001) at 30 and 35 days post-surgery; the increase was prevented in animals that received low-dose E2 while high-dose E2 reduced serum IGF-I levels below those of the sham-operated controls (P < 0.01). Serum IGF-binding proteins (IGFBPs) were determined by IGF-ligand blot analysis, and the resulting autoradiograms quantified by laser densitometry. The intensity of the IGFBP-3 bands changed in parallel with serum IGF-I levels. Ovariectomy increased, low-dose E2 restored, and high-dose E2 reduced serum IGFBP-3 levels compared to the levels for the sham-operated controls. The intensities of binding protein bands smaller than those of IGFBP-3 appeared unchanged by the treatment regimens. A Western immunoblot analysis with IGFBP-3 antiserum confirmed the ligand-blot data. The changes in the levels of IGF-I and its binding proteins were accompanied by ovariectomy-induced increase in osteoblast and osteoclast numbers and loss of cancellous bone that were attenuated by E2 administration. We conclude that there is a possible role for IGF-I in the pathogenesis of the increased bone turnover that occurs early in ovarian hormone deficiency.

Animals↗
PubMed2003

Number of pregnancies and ovariectomy modify mammary carcinoma development in transgenic HER-2/neu female mice.

We studied effect of pregnancy and ovariectomy on the development of mammary tumors in homozygous female HER-2/neutransgenic mice. The mean life span of uniparous mice was decreased by 16% in comparison to the control (P<0.05) and of mice which have two pregnancies decreased by 11% (P<0.05). Ovariectomy at the age of 2 months was followed by 32.7% increase in mean life span of mice. The incidence or multiplicity of mammary adenocarcinomas did not change in uniparous mice, whereas the size of the tumors and metastatic potential were decreased as compared to the virgins. When mice have two full-time pregnancies, there was an increase in multiplicity of mammary carcinomas and significant (2.1-fold) decrease in the survival time of tumor-bearing mice. Ovariectomy significantly decreased the total incidence of mammary carcinomas, the number of tumors per tumor-bearing animal, and inhibited metastasizing into lungs. Our results indicate that pregnancy accelerated the development of mammary adenocarcinomas in transgenic HER-2/neu mice whereas ovariectomy inhibits their development.

Age Factors↗
PubMed2002

Estrogen replacement reverses ovariectomy-induced vaginal hyperalgesia in the rat.

OBJECTIVES: The loss of ovarian function in women through aging or oophorectomy is often associated with the development of vaginal hyperalgesia that can be alleviated with estrogen replacement. This study examined if ovariectomy in rats would similarly give rise to vaginal hyperalgesia, and, if so, whether estrogen replacement would alleviate it. METHODS: Female rats were trained to perform an operant response to escape vaginal distention delivered by inflating a balloon located in mid-vaginal canal. Percent escape responses to eight different volumes of distention measured in normally cycling rats were compared with measures made in the same rats following ovariectomy (OVX) or sham ovariectomy (shamOVX), and then, in the OVX group, estrogen replacement (OVX+E2). Pressures exerted by the eight volumes on the vaginal wall were also measured, thereby permitting assessment of vaginal tone. RESULTS: Whereas overall escape response percentages after OVX, but not shamOVX, were significantly higher to the largest six distention volumes compared with responses during cycling, there were individual differences in the amount of hyperalgesia. Following OVX+E2, escape response percentages decreased in all but one rat. Vaginal tone after OVX, shamOVX or OVX+E2 did not differ from overall vaginal tone in cycling rats. CONCLUSIONS: Ovariectomy in rats evokes a variable amount of vaginal hyperalgesia that can be alleviated by estrogen replacement in most cases. Thus, the ovariectomized rat appears to provide a useful model for the study of mechanisms underlying the dyspareunia that is associated with loss of ovarian function in women.

Animals↗
PubMed2003

Long-term effects of ovariectomy and estrogen replacement treatment on endothelial function in mature rats.

OBJECTIVES: Estrogen replacement therapy (ERT) improves blood flow through various mechanisms including an augmented release of nitric oxide (NO). We report on the long-term effects of estrogen loss on vascular function and endothelial regulation. METHODS: Male, female, ovariectomized and ovariectomized+ERT treated rats were used. Female rats were ovariectomized at 12 weeks of age and received ERT via subcutaneously implanted 90-day release pellets. Vasodilation to acetylcholine (ACh) was studied in tail artery segments; arterial blood was collected for measurements of 17-beta-estradiol and stable metabolites of NO (nitrate/nitrite). Some arterial segments were harvested for TUNEL staining to determine endothelial apoptosis. RESULTS: Ovariectomy caused a rapid loss of estradiol that was negated by ERT. Likewise, there was also a loss in plasma NO. Loss of ACh-mediated dilations were age-dependent and were significant in males and untreated ovariectomized rats, with the change being maximal after 12 weeks of ovariectomy. After 12 weeks post-ovariectomy, there were no time dependent changes in ACh sensitivity in either group. Dilations to ACh were maintained in females and age-matched ERT ovariectomized rats over time. TUNEL staining of the endothelium (at 6 months of age) revealed apoptotic changes with the rank order male>ovariectomized>female, or ERT treated ovariectomized female rats. CONCLUSIONS: In a rat model of surgical menopause, loss of endothelial function is maximal 12 weeks after ovariectomy. Apoptosis of endothelial cells is greatest in arteries from male rats. Our data suggests that early ERT treatment may be an important consideration for reducing endothelium-dependent vascular dysfunction.

Acetylcholine↗
PubMed2003

Central and peripheral temperature changes in sheep following ovariectomy.

OBJECTIVES: To determine if ovariectomized ewes undergo periodic body temperature rises (hot flashes) similar to women at menopause. METHODS: Eighteen mature ewes were assigned to ovariectomy (OVX), ovariectomy+17 beta-estradiol implant (OVXE) or Sham. Electronic temperature loggers placed subcutaneously over the carotid artery and within the abdomen (core) and subcutaneously in the thigh and axilla (peripheral) were programmed to record body temperatures every 2.5 min for 59 days. Circadian rhythm changes were avoided by dividing readings into 1 h intervals. Hot flashes were defined as a 0.2 or 0.4 degrees C increase over the minimum temperature recorded for a 1 h interval for each sheep. RESULTS: Logger placement did not reflect core and peripheral temperatures. The carotid and abdominal sites were most useful. The percentage of readings considered HF at the carotid site was 63% OVX, 54% OVXE and 37% Sham (P<0.001), and at the abdominal site were 32% OVX, 15% OVE and 17% Sham (P<0.001). When only the first 7 days after ovariectomy were analyzed, the percentage of readings considered to be HF at the carotid site was 75% OVX, 63% OVXE, and 49% Sham (P<0.001), and at the abdominal site was 35% OVX, 15% OVXE and 17% Sham (P<0.001). CONCLUSIONS: Ovariectomy in the ewe does illicit changes in body temperature compared with control ewes, which may be interpreted as HF. However, shifts in the circadian rhythm were not apparent. Estradiol treatment led to milder and less frequent HF. Periodic HF in species other than rats have heretofore not been reported.

Animals↗
PubMed2001

Age and ovariectomy impair both the normalization of mechanical properties and the accretion of mineral by the fracture callus in rats.

The impact of age and ovariectomy on the healing of femoral fractures was studied in three groups of female rats at 8, 32 and 50 weeks of age at fracture. In the two older groups, the rats had been subjected to ovariectomy or sham surgery at random at 26 weeks of age. At fracture, all rats received unilateral intramedullary pinning of one femur and a middiaphyseal fracture. Rigidity and breaking load of the femora were evaluated at varying times up to 24 weeks after fracture induction by three-point bending to failure. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. In the youngest group, 8-week-old female rats regained normal femoral rigidity and breaking load by 4 weeks after fracture. They exceeded normal contralateral values by 8 weeks after fracture. In the middle group, at 32 weeks of age, fractures were induced, and the femora were harvested at 6 and 12 weeks after fracture. At 6 weeks after fracture there was partial restoration of rigidity and breaking load. At 12 weeks after fracture, only the sham-operated rats had regained normal biomechanical values in their fractured femora, while the fractured femora of the ovariectomized rats remained significantly lower in both rigidity and breaking load. In contrast, for the oldest group of rats, 50 weeks old at fracture, neither sham-operated nor ovariectomized rats regained normal rigidity or breaking load in their fractured femora within the 24 weeks in which they were studied. In all fractured bones, there was a significant increase in BMD over the contralateral intact femora due to the increased bone tissue and bone mineral in the fracture callus. Ovariectomy significantly reduced the BMD of the intact femora and also reduced the gain in BMD by the fractured femora. In conclusion, age and ovariectomy significantly impair the process of fracture healing in female rats as judged by measurements of rigidity and breaking load in three-point bending and by accretion of mineral into the fracture callus.

Absorptiometry, Photon↗