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PubMed2002

Central neural mechanisms that interrelate sensory and affective dimensions of pain.

The perception of pain is highly complex, and requires neural integration from a variety of routes. Spinal pathways to the amygdala, hypothalamus, reticular formation, medial thalamic nuclei, and limbic cortical structures transmit information involved arousal, bodily regulation, and emotional responses. Other, albeit indirect, pathways can carry signals to these same structures, for example, from spinal pathways to somatosensory thalamic and cortical areas, and from these to cortical limbic structures. Indirect cortico-limbic pathways integrate nociception with information about the status of the body and indirect routes must culminate in the prioritization of emotions and responses to pain.

Animals↗
PubMed2003

Recombinant human parathyroid hormone (1-34) [teriparatide] improves both cortical and cancellous bone structure.

UNLABELLED: Histomorphometry and microCT of 51 paired iliac crest biopsy specimens from women treated with teriparatide revealed significant increases in cancellous bone volume, cancellous bone connectivity density, cancellous bone plate-like structure, and cortical thickness, and a reduction in marrow star volume. INTRODUCTION: We studied the ability of teriparatide (rDNA origin) injection [rhPTH(1-34), TPTD] to improve both cancellous and cortical bone in a subset of women enrolled in the Fracture Prevention Trial of postmenopausal women with osteoporosis after a mean treatment time of 19 months. This is the first report of a biopsy study after treatment with teriparatide having a sufficient number of paired biopsy samples to provide quantitative structural data. METHODS: Fifty-one paired iliac crest bone biopsy specimens (placebo [n = 19], 20 microg teriparatide [n = 18], and 40 microg teriparatide [n = 14]) were analyzed using both two-dimensional (2D) histomorphometry and three-dimensional (3D) microcomputed tomography (microCT). Data for both teriparatide treatment groups were pooled for analysis. RESULTS AND CONCLUSIONS: By 2D histomorphometric analyses, teriparatide significantly increased cancellous bone volume (median percent change: teriparatide, 14%; placebo, -24%; p = 0.001) and reduced marrow star volume (teriparatide, -16%; placebo, 112%; p = 0.004). Teriparatide administration was not associated with osteomalacia or woven bone, and there were no significant changes in mineral appositional rate or wall thickness. By 3D cancellous and cortical bone structural analyses, teriparatide significantly decreased the cancellous structure model index (teriparatide, -12%; placebo, 7%; p = 0.025), increased cancellous connectivity density (teriparatide, 19%; placebo, - 14%; p = 0.034), and increased cortical thickness (teriparatide, 22%; placebo, 3%; p = 0.012). These data show that teriparatide treatment of postmenopausal women with osteoporosis significantly increased cancellous bone volume and connectivity, improved trabecular morphology with a shift toward a more plate-like structure, and increased cortical bone thickness. These changes in cancellous and cortical bone morphology should improve biomechanical competence and are consistent with the substantially reduced incidences of vertebral and nonvertebral fractures during administration of teriparatide.

Aged↗
PubMed2005

Effects of temporary bilateral ligation of the internal carotid arteries on the low- and high-frequency somatic evoked potentials in the swine.

OBJECTIVE: We studied effects of a temporary bilateral ligation of the internal carotid arteries on the subcortical and cortical structures of the somatosensory system by examining the thalamic input and postsynaptic cortical responses contained in the somatic evoked potentials (SEPs) recorded from the primary somatosensory cortex (SI) of the juvenile piglets in vivo. We predicted that the ligation should differentially affect these structures due to differences in blood supply. METHODS: The SEPs between 1 and 3000 Hz were measured in the SI cortex with a multichannel electrode array before, during and after a 20 min bilateral ligation of the internal carotid arteries in the swine under a barbiturate anesthesia. RESULTS: The ligation differentially affected the thalamic input and the cortical responses contained in the high-frequency signals (HFSs) between 400 and 2000 Hz. The amplitude of the thalamic input did not change, but the amplitudes of the cortical HFS postsynaptic to the thalamic inputs decreased immediately after start of ligation, recovering over the next 30-90 min. The latency showed a small, but significant increase for several minutes after the start of ligation for both the thalamic input and cortical responses. The ligation increased the latency and reduced the amplitude of the peak of the first cortical response in the wideband SEP corresponding to human N20. CONCLUSIONS: The HFS is useful for distinguishing selective effects of the temporary ligation on the subcortical and cortical structures of the somatosensory system. Since the porcine N20 starts after the presynaptic HFS, it was not useful in differentiating thalamic and cortical effects. SIGNIFICANCE: The HFS may open a new window in studying the cortical physiology in humans.

Animals↗
PubMed1998

Characterization of neuronal migration disorders in neocortical structures: extracellular in vitro recordings.

The majority of patients showing neuronal migration disorders in cortical structures suffer from pharmaco-resistant epilepsy. In order to study the molecular and cellular mechanisms underlying this pronounced hyperexcitability, we used an animal model of focal cortical dysplasia demonstrating structural malformations which resemble the human pathology of microgyria. Neocortical slices prepared from adult rats, which at the day of birth received a cortical freeze lesion, were analysed in vitro with an array of eight extracellular recording electrodes to investigate the pattern and pharmacology of propagating epileptiform activity in microgyric cortex. In cortical slices exhibiting neuronal migration disorders, orthodromic synaptic stimulation elicited late recurrent activity and early epileptiform responses that spread with 0.06 m/s over > or = 3.5 mm across the cortex. Application of a N-methyl-D-aspartate (NMDA) antagonist blocked the late recurrent activity, but not the propagation of the early epileptiform responses. The latter were blocked by an (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) antagonist, indicating that the spread of this activity was predominantly mediated by activation of AMPA receptors. A very similar response pattern could be observed in neocortical slices obtained from untreated age-matched control rats, when the slice was partially disinhibited by bath-application of 5 microM bicuculline methiodide. Stimulus-evoked epileptiform signals recorded in disinhibited slices propagated with 0.08 m/s across the cortex and showed the same sensitivity to ionotropic glutamate antagonists as in dysplastic cortex. Our results indicate that widespread structural and/or functional modifications of the AMPA receptor and possibly also of the gamma-amino-butyric acid type A receptor contribute to the pronounced hyperexcitability in dysplastic cortex.

Animals↗
PubMed1990

Impairment of language is related to left parieto-temporal glucose metabolism in aphasic stroke patients.

Twenty-six aphasic patients who had an ischaemic infarct in the territory of the left middle cerebral artery (MCA) were investigated. Cranial computed tomography (CT) showed various lesion sites: infarcts restricted to cortical structures in 12 patients, combined cortical and subcortical infarcts in 7 and isolated subcortical infarcts sparing the left cortex in another 7 cases. 18F-2-fluoro-2-deoxyglucose positron emission tomography revealed remote hypometabolism of the left convexity cortex and of the left basal ganglia, which was extended further than the morphological infarct zone in all cases. Types and degrees of aphasia were classified using the Aachener Aphasie Test (AAT): 10 patients had global aphasia, 2 Broca's, 5 Wernicke's, and 5 amnesic aphasia. Four patients suffered from minimal or residual aphasic symptoms. The AAT results were compared with the regional cerebral metabolic rates of glucose of the left hemisphere. Irrespective of the infarct location all five AAT subtests (Token test, repetition, written language, confrontation naming, auditory and reading comprehension) were closely correlated among each other and with left parieto-temporal metabolic rates, whereas left frontal and left basal ganglia metabolism showed no significant correlation. The close relation between left temporo-parietal functional activity and all five AAT subtests suggests that the different aspects of aphasia tested by AAT can be related to a common disorder of language processing in those areas.

Adult↗
PubMed2001

Crossed effects of muscle vibration on motor-evoked potentials.

OBJECTIVES: Muscle vibration (MV) to a forearm muscle augments motor-evoked potentials (MEPs) following transcranial magnetic stimulation (TMS) and the underlying mechanism involves cortical structures. Although MV-induced cortical activation is bilateral, the effects of MV on MEPs in contralateral muscles have not been investigated. METHODS: Low-amplitude MV (80 Hz, amplitude 0.5 mm, duration 4 s), subthreshold for the tonic vibration reflex, was applied to the right extensor carpi radialis muscle (ECR). MEPs were elicited (0.5, 3 and 5 s after MV onset) in the left and right ECR and flexor carpi radialis muscle (FCR) by TMS (120% of threshold at rest) to the left and right hemisphere, respectively. RESULTS: During MV of right ECR the left ECR revealed a slight non-significant augmentation of MEPs. In contrast, the left FCR showed a gradual depression of MEPs with ongoing MV and at 3 s the reduction of MEPs was significant. The time course of MEP changes in left FCR correlated with the facilitation of the vibrated right ECR. Post-vibration MEPs at 1 s after the offset of MV were still significantly decreased. CONCLUSIONS: The study demonstrates crossed effects of MV on motor cortex excitability, suggesting transcallosal MEP modulation.

Adult↗
PubMed1994

[The clinical, neurophysiological and differential diagnostic aspects in a study of severe forms of early childhood autism].

Clinical, pathopsychological and neurophysiological studies have been carried out in 85 children with infantile autistic psychosis and in 38 girls with Rett's syndrome. New improved differential diagnostic criteria between these two forms of early childhood autism have been suggested. EEG spectral density values in alpha-1, alpha-2, beta and theta subbands are established to be their neurophysiological markers. Special attention was paid to close relationship between ontogenetic neuromorphogenesis of the brain cortical structures (e.g. physiological lysis of cortical cell populations at the age 8-30 months of the child's life) and the defect severity in the onset of illness at the same age range in patients with the studied forms of early childhood autism. The data obtained are discussed in terms of new approaches to understanding pathogenesis of different forms of early childhood autism.

Autistic Disorder↗
PubMed2003

Congenic mice reveal sex-specific genetic regulation of femoral structure and strength.

Genetic linkage studies in C3H/HeJ (C3H) and C57BL/6J (B6) mice identified several chromosomal locations or quantitative trait loci (QTL) linked to femoral volumetric bone mineral density (vBMD). From QTL identified on chromosomes (chr) 1, 4, 6, 13, and 18, five congenic mouse strains were developed. In each of these mice, genomic DNA from the QTL region of the donor C3H strain was transferred into the recipient B6 strain. Here we report the effects of donated C3H QTL on femoral structure, cortical vBMD and bending strength. Femoral structure was quantified by the polar moment of inertia (Ip) at the mid-diaphysis, which reflects the bending or torsional rigidity of the femur. Although the C3H progenitor mice have a smaller Ip than B6 progenitor mice, the congenic mice carrying the C3H segment at Chr 4 had significantly increased Ip in both males and females, giving these mice stronger femora. In female mice from the congenic Chr 1 strain, Ip was increased whereas male mice from the Chr 1 strain had smaller femoral cross-sections and significantly reduced Ip. This sex-specific effect on femoral structure was seen to a lesser extent in Chr 18 congenic mice. In addition, cortical vBMD was measured using peripheral quantitative computed tomography. Cortical vBMD was similar among most congenic strains except in Chr 6 congenic mice, where cortical vBMD was significantly less in females, but not in males. We conclude that (1) chromosomal QTL from C3H mice, which are genetically linked to total femoral vBMD, also regulate femoral structure; (2) the QTL on Chr 4 improves femoral structure and strength; (3) QTL on Chr 1 and 18 impart sex-specific effects on femoral structure; and (4) the QTL on Chr 6 imparts a sex-specific effect on cortical vBMD and femoral strength.

Animals↗
PubMed2000

Functional magnetic resonance imaging of mental strategy in a simulated aviation performance task.

BACKGROUND: The objective of this study was to analyze the sensory and cognitive functions associated with activated brain regions characterizing mental strategy relative to degree of expertise in aviation-related tasks. METHODS: We used echo-planar functional magnetic resonance imaging (fMRI) technique to examine brain activity in expert pilots (n = 6) compared with novice pilots (n = 6) during performance of a simulated aviation track-following task at 200 knots vs. 100 knots. RESULTS: Expert pilots showed reduced activity in visual and motor regions that contrasted with predominant activation within anterior structures including the frontal and prefrontal cortices; structures involved in visual working memory, planning, selective attention and decision making functions. Novice pilots showed widespread activation of anterior and posterior brain structures, with a rise in activity in the visual, parietal and motor cortices as task difficulty increased. CONCLUSIONS: A high level of performance in the track-following task related to a high degree of expertise in the aviation field. This corresponded to experts performing perceptual and mnemonic processing through a network of specialized functions from visual through multiple prefrontal areas. By contrast, the novice pilots predominantly show activity associated with non-specific perceptual processing and without subsequent representation of selective information in working memory.

Adult↗
PubMed1998

Crossed cerebellar diaschisis due to intracranial hematoma in basal ganglia or thalamus.

UNLABELLED: The purpose of our study was to evaluate the remote effects on the cerebellum and cerebral cortex from subcortical hematoma without cortical structural abnormality. METHODS: Our study included 23 patients with hematoma, strictly confined either to the basal ganglia (n = 12) or thalamus (n = 11) without cortical abnormality on CT or MRI. Twenty psychiatric patients without structural abnormality on MRI were selected as control subjects. Technetium-ethyl cysteinate dimer brain SPECT was performed in patients and control subjects. Regional cerebral blood flow (rCBF) was visually and semiquantitatively assessed. Asymmetry index (AI) was determined using data from regions of interest at the basal ganglia, thalamus, cerebellum, frontal, parietal and temporal cortex to support the semiquantitative analysis. The criteria for defining hypoperfusion that reflected diaschisis was based on an AI > the mean + 2 s.d. of AI in control subjects. RESULTS: In the basal ganglia hematoma, rCBF was reduced significantly in the contralateral cerebellum (10/12), ipsilateral thalamus (12/12), ipsilateral frontal (6/12), parietal (12/12) and temporal cortex (10/12). As for thalamic hematoma, significantly reduced perfusion was seen in the contralateral cerebellum (10/11), ipsilateral basal ganglia (7/11), ipsilateral frontal (5/11), parietal (11/ 11) and temporal cortex (3/11). CONCLUSION: Crossed cerebellar diaschisis (CCD) and cortical diaschisis frequently were observed in patients with subcortical hematoma without cortical structural abnormality. This suggested that CCD can develop regardless of interruption of the corticopontocerebellar tract, which is the principal pathway of CCD.

Adult↗
PubMed1969

Cortical ultrastructure of Paramecium aurelia. Studies on isolated pellicles.

Two methods have been devised for the isolation of large quantities of purified pellicles (cortical layers) of Paramecium aurelia. Pellicles isolated by both procedures, when examined by electron microscopy, were found to contain ciliary basal bodies, two types of cortical membranes, ribbons of microtubules, kinetodesmal fibers, and elements of the infraciliary lattice system. By electron microscopy, the extent of preservation of the various cortical structures when pellicles are isolated by each method has been characterized. Pellicles isolated in both ways have been utilized to investigate cortical morphology of Paramecium. Both phase-contrast and electron microscopic observations have been made. Many new ultrastructural features were observed and are reported herein. An interesting result of this study is the discovery in stock CD that the structure of cortical territories (the territory is the functional unit of cortical morphogenesis and physiology) may vary within a single organism. Features which show variation include number of parasomal sacs, microtubular ribbons, and basal bodies (and therefore cilia) per territory, number of microtubules per ribbon, and length of kinetodesmal fibers. The possible significance of these variations, with respect to territory replication, is discussed. In addition, preliminary observations on the solubility of various cortical organelles in the presence of a number of protein-denaturing agents are reported.

Cytoplasm↗
PubMed2000

Anatomical connectivity defines the organization of clusters of cortical areas in the macaque monkey and the cat.

The number of different cortical structures in mammalian brains and the number of extrinsic fibres linking these regions are both large. As with any complex system, systematic analysis is required to draw reliable conclusions about the organization of the complex neural networks comprising these numerous elements. One aspect of organization that has long been suspected is that cortical networks are organized into 'streams' or 'systems'. Here we report computational analyses capable of showing whether clusters of strongly interconnected areas are aspects of the global organization of cortical systems in macaque and cat. We used two different approaches to analyse compilations of corticocortical connection data from the macaque and the cat. The first approach, optimal set analysis, employed an explicit definition of a neural 'system' or 'stream', which was based on differential connectivity. We defined a two-component cost function that described the cost of the global cluster arrangement of areas in terms of the areas' connectivity within and between candidate clusters. Optimal cluster arrangements of cortical areas were then selected computationally from the very many possible arrangements, using an evolutionary optimization algorithm. The second approach, non-parametric cluster analysis (NPCA), grouped cortical areas on the basis of their proximity in multidimensional scaling representations. We used non-metric multidimensional scaling to represent the cortical connectivity structures metrically in two and five dimensions. NPCA then analysed these representations to determine the nature of the clusters for a wide range of different cluster shape parameters. The results from both approaches largely agreed. They showed that macaque and cat cortices are organized into densely intra-connected clusters of areas, and identified the constituent members of the clusters. These clusters reflected functionally specialized sets of cortical areas, suggesting that structure and function are closely linked at this gross, systems level.

Algorithms↗
PubMed2002

Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex.

OBJECTIVE: Studies of the neurobiological processes underlying drug addiction primarily have focused on limbic subcortical structures. Here the authors evaluated the role of frontal cortical structures in drug addiction. METHOD: An integrated model of drug addiction that encompasses intoxication, bingeing, withdrawal, and craving is proposed. This model and findings from neuroimaging studies on the behavioral, cognitive, and emotional processes that are at the core of drug addiction were used to analyze the involvement of frontal structures in drug addiction. RESULTS: The orbitofrontal cortex and the anterior cingulate gyrus, which are regions neuroanatomically connected with limbic structures, are the frontal cortical areas most frequently implicated in drug addiction. They are activated in addicted subjects during intoxication, craving, and bingeing, and they are deactivated during withdrawal. These regions are also involved in higher-order cognitive and motivational functions, such as the ability to track, update, and modulate the salience of a reinforcer as a function of context and expectation and the ability to control and inhibit prepotent responses. CONCLUSIONS: These results imply that addiction connotes cortically regulated cognitive and emotional processes, which result in the overvaluing of drug reinforcers, the undervaluing of alternative reinforcers, and deficits in inhibitory control for drug responses. These changes in addiction, which the authors call I-RISA (impaired response inhibition and salience attribution), expand the traditional concepts of drug dependence that emphasize limbic-regulated responses to pleasure and reward.

Behavior, Addictive↗
PubMed1995

Planum temporale and Brodmann's area 22. Magnetic resonance imaging and high-resolution positron emission tomography demonstrate functional left-right asymmetry.

OBJECTIVE: To describe the registered analysis of magnetic resonance imaging and glucose metabolic data acquired with positron emission tomography to determine the relationship between structure and function of temporal lobe cortical structures between the left and right hemispheres. BACKGROUND: The dominance of the left cerebral hemisphere is associated with a preponderance of the left planum temporale. SUBJECTS AND METHODS: Fifteen subjects without signs or symptoms of a neurological disorder. Three-dimensional-registered magnetic resonance imaging and positron emission tomography with the use of fludeoxyglucose F18 and a high-resolution positron emission tomography scanner. Analysis of regional metabolic activation during single-word repetition on matched parasagittal magnetic resonance imaging and positron emission tomography. RESULTS: The planum temporale was bilaterally activated without left-right asymmetry. The metabolic increase was asymmetric within the left Brodmann's area (BA) 22. The part of the left BA 22 that was buried in the superior temporal sulcus was significantly less activated than the part of BA 22 on the surface of the superior temporal gyrus. The metabolic activation in the sulcal part of the left BA 22 had a significant inverse correlation with the anatomical predominance of the left planum temporale (r = .71, P = .003) and a significant direct correlation with the metabolic activation in the surface aspects of the right BA 22 (r = .82, P < .001). CONCLUSION: Brodmann's area 22 is a critical feature of language dominance and is also important with regard to the exchange of information between the two hemispheres.

Adult↗
PubMed2000

Electroconvulsive therapy in the treatment of neuropsychiatric conditions and transcranial magnetic stimulation as a pathophysiological probe in neuropsychiatry.

It is a challenging task to review transcranial magnetic stimulation (TMS) studies in neuropsychiatric disorders alongside assessments of longstanding clinical applications of ECT as an empirical treatment. The task is challenging because TMS was developed as a probe of neural mechanisms, whereas, in marked contrast, ECT has been a clinical technique from its inception. Since the onset of modern psychopharmacology, the understanding of the potential applications of ECT to neuropsychiatric disorders is generally restricted to case reports of patients with intractable disease that have had at least a partial response to ECT. Studies of the possible efficacy of TMS in neuropsychiatric conditions have a significant advantage over ECT as the treatments are associated with less morbidity. The only serious known complication in TMS is a risk of seizures that may increase in patients with neuropsychiatric conditions such as course brain disease. Only cortical structures are themselves accessible to TMS using current technology. Present TMS techniques, however, seem capable of affecting activity in deeper brain structures that are functionally linked to cortical brain regions. TMS permits novel explorations of relationships between regional brain activity and symptoms of a number of neuropsychiatric disorders, as well as in research relating activity in functionally related brain regions to modulation of cognition and affective states in healthy individuals. This is particularly true at present because TMS and powerful neuroimaging and neuropsychological tools are all making rapid advances simultaneously.

Brain Diseases↗
PubMed2006

Efferent projections of reuniens and rhomboid nuclei of the thalamus in the rat.

The nucleus reuniens (RE) is the largest of the midline nuclei of the thalamus and exerts strong excitatory actions on the hippocampus and medial prefrontal cortex. Although RE projections to the hippocampus have been well documented, no study using modern tracers has examined the totality of RE projections. With the anterograde anatomical tracer Phaseolus vulgaris leuccoagglutinin, we examined the efferent projections of RE as well as those of the rhomboid nucleus (RH) located dorsal to RE. Control injections were made in the central medial nucleus (CEM) of the thalamus. We showed that the output of RE is almost entirely directed to the hippocampus and "limbic" cortical structures. Specifically, RE projects strongly to the medial frontal polar, anterior piriform, medial and ventral orbital, anterior cingulate, prelimbic, infralimbic, insular, perirhinal, and entorhinal cortices as well as to CA1, dorsal and ventral subiculum, and parasubiculum of the hippocampus. RH distributes more widely than RE, that is, to several RE targets but also significantly to regions of motor, somatosensory, posterior parietal, retrosplenial, temporal, and occipital cortices; to nucleus accumbens; and to the basolateral nucleus of amygdala. The ventral midline thalamus is positioned to exert significant control over fairly widespread regions of the cortex (limbic, sensory, motor), hippocampus, dorsal and ventral striatum, and basal nuclei of the amygdala, possibly to coordinate limbic and sensorimotor functions. We suggest that RE/RH may represent an important conduit in the exchange of information between subcortical-cortical and cortical-cortical limbic structures potentially involved in the selection of appropriate responses to specific and changing sets of environmental conditions.

Animals↗
PubMed1988

Evaluation of peripheral nerve conduction and central visual conduction in chronic alcoholics and in chronic alcoholics after prolonged abstention.

Classic statistical method (mean, standard deviation, variance) were used to analyze peripheral nerve conduction tests and visual evoked potentials in 13 chronic alcoholics and in 11 chronic alcoholics who had abstained for at least one year, in order to assess the repercussions of alcohol on the PNS and on the visual pathways and their reversibility. The sensory fibers were more affected than the motor fibers, and while the damage to the motor fibers was transient the damage to the sensory fibers was permanent and also significantly different, at least in the early stages, in the two lower limbs. Our results showed constant involvement, without clinical symptoms, of the visual potential, especially of the earliest component N70 and of the amplitude of the response. This would suggest greater involvement of the peripheral visual nervous structures, that is retino-geniculo-cortical, than of the more properly cortical structures, though these are also affected. For the visual damage too withdrawal of alcohol seems to determine a regression, though only partial, of the neurophysiological changes. The simultaneous involvement of VEP and peripheral nerve function is at variance with the assertion that optic nerve damage is a very rare event in alcoholism.

Adult↗
PubMed2003

The effects of hormone replacement therapy on cortical bone in postmenopausal women. A histomorphometric study.

Investigations of the actions of estrogen on the skeleton have mainly focused on cancellous bone and there are no reported histomorphometric studies of the effects of oestrogen on cortical bone in humans. The aim of this study was to investigate the effects of both conventional hormone replacement therapy (HRT) and high-dose oestradiol on cortical bone in postmenopausal women. Transiliac biopsies were obtained from nine postmenopausal women aged 54-71 yr before and after 2 yr (mean, 23.5 months) of conventional HRT and in seven postmenopausal women aged 52-67 yr after long-term, high-dose oestradiol implant therapy (at least 14 yr). Indices of bone turnover, remodeling, and cortical structure were assessed by image analysis. Cortical width was highest in the women treated with high-dose oestrogen therapy (2.29 +/- 0.78 mm; mean +/- SD) and lowest in untreated women (1.36 +/- 0.60 mm; P=0.014). The proportion of canals with an eroded surface was significantly lower in the high-dose oestrogen group than in women before or after conventional HRT (3.03 +/- 3.7% vs. 11.1 +/- 7.1% and 10.5 +/- 8.6%; P=0.017 and 0.05, respectively). Bone formation rate (microm2/microm/day) in untreated women was significantly higher than in the high-dose oestrogen group (0.121 +/- 0.072 vs. 0.066 +/- 0.045, respectively; P=0.05), values in women treated with conventional HRT being intermediate. Our results provide the first histomorphometric evidence in postmenopausal women of dose-dependent oestrogen-induced suppression of bone turnover in iliac crest cortical bone. There was also a trend toward higher wall width with increasing dose of oestrogen, consistent with the previously reported anabolic effect in cancellous bone.

Aged↗