A computer-based measure of irregularity in vertebral alignment is a BMD-independent predictor of fracture risk in postmenopausal women

SUMMARY: Prevalent fracture and BMD are core elements of fracture prediction. In this control study case, we demonstrate that a simple computer-based estimation of local irregularities in the alignment of the lumbar vertebrae independently contributes to the fracture risk, thus supplementing current diagnostic tools. INTRODUCTION: We tested the hypothesis that degree of lordosis and/or irregularity in the alignment of lumbar vertebrae could be contributors to the risk of fragility fractures. METHODS: This was a case-control analysis including 144 elderly women; 108 maintaining skeletal integrity, whereas 36 sustaining a lumbar vertebral fracture during a 7.5-year observation period. The two groups of women were carefully matched for age, BMI, spine BMD and numerous classic risk factors. Lateral X-rays of the lumbar spine were digitized and the four corner points of endplates on each vertebra from Th12 to L5 were annotated. The degree of lordosis and irregularity of vertebral alignment was assessed by image analysis software. RESULTS: Degree of lordosis was not predictive for fractures. In contrast, irregularity was significantly higher in those who later sustained a fracture (1.6 x 10(-2)vs. 2.0 x 10(-3) cm(-1), p < 0.001), and further increased upon a sustained fracture (2.8 x 10(-2) cm(-1), p < 0.001), but was unchanged in controls (1.6 x 10(-2) cm(-1)). The predictive value of irregularity was independent of classic risk factors of fractures, including BMD (p < 0.01). CONCLUSION: Our results suggest that the herein introduced simple measure of irregularities in vertebral alignment could provide useful supplement to the currently used diagnostic tools of fracture prediction in elderly women.     

Midbrain central gray GABAA receptor activation enhances,and blockade reduces,sexual behavior in the female rat

Summary The inhibitory neurotransmitter, GABA, has been implicated in the control of lordosis behavior. Previous studies indicate that modulation of GABA_A transmission can have dual effects on lordosis, being facilitative in the ventromedial hypothalamus and inhibitory in the preoptic area. The midbrain central gray (MCG) is also known to be an important neural site for regulating lordosis as well as defensive and escape behaviors, and plays an integral role in the control of nociception. Because of the multitude of behaviors regulated at the level of the MCG, we utilized a two-chamber testing apparatus that allowed simultaneous measurement of the females' proceptive (hopping and darting), receptive and rejection behaviors, as well as an index of nociception and general motor activity. We found that microinfusion of the GABA_A antagonist, bicuculline, into the MCG of steroid-primed female rats resulted in a significant decrease in lordosis and proceptive behaviors at 5 min post-infusion. There was full recovery to pretest levels by 60 min. Furthermore, microinfusion of the GABA_A agonist, muscimol, to estrogen-treated females that displayed low levels of receptivity and high levels of rejection behavior during a pretest, resulted in a significant increase in lordosis responding and a decrease in rejection behaviors. Neither drug significantly affected time spent in the vicinity of the male, motor activity or vocalizations. It is concluded that the decrease in lordosis resulting from blockade of GABA transmission is not solely due to the induction of antagonistic behaviors since there was no increase in rejections after bicuculline administration. The current findings are consistent with the interpretation that GABA facilitates lordosis in the MCG via disinhibition. When the retrograde tracer, Fluoro-gold, was infused into the same cannula sites in the MCG as the GABA_A drugs it demonstrated the presence of strong projections from the ventromedial nucleus, zona incerta, medullary reticular formation and spinal cord. These projections to the MCG may be important for the integration of the diverse behaviors regulated at the level of the MCG and GABAergic transmission may play a role in this integration.     

Dihydrotestosterone-induced inhibition of lordosis in estrogen-primed ovariectomized rats following 6-hydroxydopamine or electrolytic septal lesions

The dose-dependent inhibition of lordosis by 5α-dihydrotestosterone propionate in ovariectomized female rats treated concurrently with estradiol benzoate was attenuated neither by intracranial 6-hydroxydopamine injections which reduced dopamine concentrations by approximately 70% in septum or 75% in both septum and n. accumbens septi nor by electrolytic destruction of the lateral or medial septal nuclei or of both septal nuclei. These results suggest that the inhibitory effect of dihydrotestosterone on estrogen-induced lordosis does not critically depend on the mesolimbic dopaminergic innervation of the forebrain or on the septal nuclei.     

Neuronal activity in female rat preoptic area associated with sexually motivated behavior

Single unit activities were recorded from 31 neurons in the preoptic area (POA) of female rats engaging in sexual interactions. Concurrent videotape recordings were used to establish a relationship between neuronal activity and particular behavioral events. In 14 of the 31 neurons, the firing rate changed in association with bouts of sexual activity. The remaining 17 fired with more variability regardless of episodes of sexual interactions. Peri-event histograms identified four types of neurons: type 1 (n=4) increased their firing rate when the female rats initiated proceptive behavior; type 2 (n=4) showed a brief activation when the male mounted; type 3 (n=4) fired in response to intromission, and type 4 (n=2) were inhibited prior to and throughout the display of lordosis reflex. Type 1 neurons fired at significantly higher rates during the solicitatory period, from the initiation of solicitatory locomotion to the male mounts. Their activity was suppressed when the males mounted successfully with intromission. Types 1–3 neurons were recorded from the transitional region between the medial and lateral POAs. Type 4 neurons were located more medially in the medial POA. Systemic injection of pimozide, a dopamine receptor blocker, diminished firing in type 1 neurons and abolished proceptivity. The firing pattern in type 1 neurons appeared to embody the motivational state of the animal with an implication for a consummatory value of penile intromission. Visceral or somatosensory inputs may be responsible for short bursts in types 2 and 3 neurons. Type 4 neurons behaved exactly as if they inhibit the execution of the lordosis reflex. The results showed separate sets of POA neurons each specifically associated with proceptive and receptive components of female rat sexual behavior.     

Impairment or abolition of lordosis in the golden hamster by transection of spinal pathways

Lumbosacral and thoracic tactile stimulation elicits lordosis in sexually-receptive female hamsters. Because of the major dorsal column involvement in transmission of tactile activity, transection of this pathway was examined for effects on somatosensory elicitation of lordosis and compared with effects of lateral column (unilateral or bilateral) transections. Interruption of either pathway completely eliminated lordosis on some tests. Dorsal column section at cervical or lumbar levels produced a unique effect, however, where lumbosacral stimuli elicited the tail, rump and hindlimb manifestations of lordosis without evoking the usual immobility of the forelimbs, head and vibrissae. In animals with lumbar transections, the rostral, but not caudal, motoric components of lordosis could still be elicited by thoracic stimuli. Lateral column transection did not consistently prevent complete, sustained lordosis responses, but the response posture was abnormal. These results show the integrity of the hamster's dorsal columns to be essential for elicitation of complete lordosis responses and suggest that the caudal and rostral motor components differ significantly in the nature of their control by spinal and supraspinal levels of the central nervous system.     

Dissociation between female sexual behavior and luteinizing hormone release in old female rats

The relationship between lordosis behavior and LH release as measured by the response to mating or by the positive feedback response to estradiol benzoate (EB)/progesterone was studied in ovariectomized rats of three different age groups: young adult female rats (5 to 8 months old), middle age female rats (15 to 23 months old) and old female rats (over 24 months old). Middle age and old rats showed high levels of lordosis behavior regardless of the pattern of LH secretion in response to mating or the positive feedback response to EB/progesterone. The mean LH rise after mating as well as after EB/progesterone treatment in pooled middle age and old rats is significantly lower than that of young rats. A clear dissociation between lordosis behavior and LH release in middle age and old female rats suggests that they are regulated at least in part by different mechanisms.     

Dihydrotestosterone stimulates mounting behavior but not lordosis in female rats

The ability of androgens to stimulate masculine sexual behavior is thought to depend on the aromatization of such androgens to estrogens. In this scheme, reduced androgens such as dihydrotestosterone (DHT) which cannot be aromatized, are thought to exert major peripheral but little or no central nervous system influences on the display of masculine sexual behavior. Further, an early report that DHT can induce lordosis, an estrogen (E) dependent behavior, led to a notion that DHT may effect behavior through metabolic intermediates such as 5α-androstane-3β, 17β-diol (ADIOL) which then binds to estrogen receptors eliciting the E-dependent lordotic response. The present study reexamined and compared the relative effectiveness of a range of DHT dosages in stimulating a characteristic masculine (mounting) and feminine (lordosis) sexual behavior. Adult ovariectomized rats were randomly assigned to either 250 μg or 1 mg daily injections of DHT or DHTP. Other animals received OIL injections or crystalline DHT delivered by two different lengths (20 mm or 40 mm) of Silastic capsules. Animals were tested once weekly (for 5 weeks) for mounting behavior (20 minute test). Then animals were tested thrice (once weekly) for lordosis 4 hrs after the addition of 500 μg Progesterone (P). Finally, all females were tested for lordotic potential to respond to 10 μg EB plus P. 1 mg DHT or DHTP dosages and the 40 mm-Silastic condition significantly increased mounting behavior over that of lower dosages and OIL controls. A significant correlation existed between mounting frequency and circulating level of serum DHT. Treatment with DHTP was not different than DHT in eliciting mounting behavior. Lordosis was not enhanced by any treatment with DHT or DHTP over that of controls, although all females were capable of lordotically responding to EB. These data demonstrate that DHT can induce mounting behavior, but not lordosis, suggesting that whatever action DHT has may not occur via estrogen or estrogen receptors. A role for androgen and androgen receptors upon mounting behavior is discussed.     

Effects of dexamethasone, corticosterone, and ACTH on lordosis in ovariectomized and adrenalectomized-ovariectomized rats

The involvement of the pituitary-adrenocortical axis in the control of the lordosis reflex was investigated; In Experiment 1, estrogen-primed ovariectomized (ovx) and adrenalectomized-ovariectomized (adx-ovx) females were treated chronically with dexamethasone, a compound blocking ACTH release from the pituitary. Dexamethasone inhibited lordosis, effectively blocking an adrenalectomy-induced facilitation of the reflex. In Experiment 2, corticosterone was similarly administered chronically; this compound also inhibited lordosis in adx-ovx females. In Experiment 3, acute peripheral administration of synthetic ACTH caused a marked increase in lordosis in ovx females. The results suggest that in the adrenally intact animal, ACTH may exert its effect through adrenal steroids. An acute elevation of adrenal steroids may increase lordosis, whereas a chronic elevation may decrease it.