Biomedical subjects

A Nardi

Publications and source records attributed to A Nardi.

At least 19 recordsLinked to original sources

PubMed2006

Tissue-specific transcriptional initiation and activity of steroid sulfatase complementing dehydroepiandrosterone sulfate uptake and intracrine steroid activations in human adipose tissue.

Expression analysis by reverse transcriptase (RT)-PCR indicates that human adipose tissue is not likely to perform de novo synthesis of steroid hormones from cholesterol because the mRNAs of cytochromes P450scc and P450c17, and of the steroidogenic-related proteins, steroidogenic acute regulatory protein and steroidogenic factor 1, were not detected. Instead, our data support an intracrine role of adipose tissue, in which adrenal dehydroepiandrosterone sulfate (DHEA-S), the most abundant circulating androgen in man, is selectively uptaken, desulfated, and converted into bioactive androgens and estrogens. Three organic anion-transporting polypeptides-B, -D, and -E, presumably involved in DHEA-S transmembrane transport, were demonstrated at the mRNA level. While sulfotransferase expression was not found, the occurrence of steroid sulfatase (STS), converting DHEA-S to DHEA, was established at the mRNA, protein and catalytic activity levels. The 5'-rapid amplification of cDNA ends analysis showed that STS transcription in adipose tissue is regulated by the use of two promoters which differ from the prevalent placental one. The adipose transcripts contain a distinct untranslated first exon, 0a or 0b, followed by a common partially translated exon 1b, and nine other exons that are also shared by the main placental transcript. The presence of an upstream open reading frame in the new transcript variants could lead to an N-terminal divergence restricted to the cleavable signal peptide and thus not interfering with the catalytic activity of the mature STS protein. The adipose transcripts are also present in the placenta as minor isoforms. Western blotting revealed the characteristic approximately 64 kDa band of STS in both the placenta and adipose tissue. The specific enzymatic activity of STS in adipocytes was 118 pmol/10(6) cells per hour, about 50-100 times lower than in the placenta. A similar rate of [3H] DHEA-S uptake plus desulfation was measured in preadipocytes and adipocytes, equivalent to 40-45 pmol/10(6) cells per hour. Thus, an excessive accumulation of fat may out-compete other peripheral organs that are also dependent on intracrine DHEA-S utilization, especially when the adrenal production is low or declining with aging.

3' Untranslated Regions↗

PubMed2003

Short- and long-term changes in bone mineral density of the lumbar spine after parathyroidectomy in patients with primary hyperparathyroidism.

The aims of this study were (1) to analyze whether correlations exist between lumbar spine (LS) bone mineral density (BMD) and the main preoperative biochemical parameters in a large population of patients with primary hyperparathyroidism (HPT); and (2) to evaluate the LS-BMD changes after parathyroidectomy (PTx) at long-term follow-up. Sixty-two patients (median age 57 years, range 23-82 years) with confirmed primary HPT underwent LS osteodensitometry by dual-energy X-ray absorptiometry with BMD measurements at the L2-L4 region before surgery and at 1 year and 2 years after successful PTx. Three groups of patients were considered: Group A (men, n = 14, 22.6%), Group B (premenopausal women, n = 12, 19.3%), and Group C (postmenopausal women, n = 36, 58.1%). There were no linear correlations (P = NS) among the main biochemical parameters, the age of the patients, and their baseline LS-BMD values that were significantly (P < 0.01) lower in Group C patients. At 2-year follow-up the LS-BMD improved by 13.0%, 11.5%, and 11.7% in Groups A, B, and C, respectively (P = NS). In order to compare groups with the same linear relationship between age and LS-BMD, a subgroup of postmenopausal patients aged < or = 60 years (Group C2) was considered. ANOVA showed that the improvement of the LS-BMD at 1- and 2-year follow-up was higher (P = 0.002) in Group B than in Group C2 patients. The result was confirmed by using the Mann-Whitney U-test (P = 0.0078). Improvement of LS-BMD after successful PTx was significantly (P < 0.01) higher in premenopausal women, suggesting a possible role of estrogen hormone in complete bone remodeling.

Absorptiometry, Photon↗

PubMed2002

The use of the pyridostigmine growth hormone-releasing hormone stimulation test to detect growth hormone deficiency in patients with pituitary adenomas.

The pyridostigmine (PD)/growth hormone-releasing hormone (GHRH) stimulation test was used to determine growth hormone (GH) secretion in patients with pituitary adenomas prior to (n = 55) and after (n = 72) transsphenoidal adenomectomy, as well as in 98 controls. In controls, maximum concentrations of GH showed a strong negative relationship both with body mass index (BMI) and age. Having calculated the 95% confidence intervals for maximum GH concentrations to be expected for any given age and BMI according to a statistical model, we compared these individually predicted ranges to GH concentrations actually observed in patients with pituitary disease during PD/GHRH stimulation. Preoperatively and postoperatively, a maximum GH concentration below the calculated confidence intervals was seen in 29 of 55 (52%) and in 57 of 72 (79%) of these patients, respectively. In the remaining patients, maximum GH concentrations were in or above the range defined by these confidence intervals. Our results indicate that maximum concentrations of GH during the PD/GHRH test depend to a large extent on the individuals' age and BMI. The results obtained with the PD/GHRH stimulation must, in each individual patient, be compared with a large control group taking into account both age and BMI. In individuals older then 55 years and with a BMI greater than 35 kg/(2), the diagnosis of GH deficiency cannot safely be made, at least not with this test.

Adenoma↗

PubMed2002

Relationship between serum parathyroid hormone, serum calcium and arterial blood pressure in patients with primary hyperparathyroidism: results of a multivariate analysis.

OBJECTIVE: To evaluate the possible relationship between serum calcium, serum parathyroid hormone (PTH) levels and arterial blood pressure (BP) in patients with primary hyperparathyroidism (HPT). DESIGN: A retrospective population-based study. METHODS: Charts of 194 patients with proven primary HPT were reviewed, and the main clinical and biochemical parameters were recorded. There were 48 men (24.7%) and 146 women (75.3%), with a median age of 59 years (range 23-82 years). Patients who used antihypertensive drugs or hormone replacement therapy had been previously excluded. All patients underwent successful parathyroidectomy, and were cured of their disease. RESULTS: There were no differences (P=NS) between men and women in systolic (143.3+/-19.1 vs 145.4+/-17.1 mmHg) and diastolic (87.1+/-12.3 vs 88.4+/-9.9 mmHg) BP, and in the main biochemical parameters. A significant (P<0.01) correlation was found between (i) serum calcium and serum PTH levels (r=0.39, F=88.36), (ii) age and BP, both systolic (r=0.61, F=118.16) and diastolic (r=0.48, F=64.5), and (iii) body mass index (BMI) and BP (r=0.45 and 0.36 respectively). There was no significant association of serum calcium levels with systolic (r=0.0974, t=1.3422, P=0.18) or diastolic (r=0.1117, t=1.5409, P=0.12) BP, and of serum PTH levels with systolic (r=-0.0349, t=-0.4783, P=0.63) or diastolic (r=-0.0793, t=-1.0913, P=0.28) BP. Multivariate analysis confirmed that none of the independent biochemical parameters significantly correlated with BP, both systolic and diastolic. CONCLUSIONS: In patients with primary HPT there is no relationship between PTH, calcium and BP. Thus, in hyperparathyroid patients, BP should be considered as an independent variable, mainly related to age and BMI.

Aged↗

PubMed2001

The C-terminal half of the colicin A pore-forming domain is active in vivo and in vitro.

The pore-forming domain of colicin A (pfColA) fused to a prokaryotic signal peptide (sp-pfColA) is transported across and inserts into the inner membrane of Escherichia coli from the periplasmic side and forms a functional channel. The soluble structure of pfColA consists of a ten-helix bundle containing a hydrophobic helical hairpin. Here, we generated a series of mutants in which an increasing number of sp-pfColA alpha-helices was deleted. These peptides were tested for their ability to form ion channels in vivo and in vitro. We found that the shortest sp-pfColA mutant protein that killed Escherichia coli was composed of the five last alpha-helices of sp-pfColA, whereas the shortest peptide that formed a channel in planar lipid bilayer membranes similar to that of intact pfColA was the protein composed of the last six alpha-helices. The peptide composed of the last five alpha-helices of pfColA generated a voltage-independent conductance in planar lipid bilayer with properties very different from that of intact pfColA. Thus, helices 1 to 4 are unnecessary for channel formation, while helix 5, or some part of it, is important but not absolutely necessary. Voltage-dependence of colicin is evidently controlled by the first four alpha-helices of pfColA.

Amino Acid Sequence↗

PubMed2001

Behavioral phenotyping of GFAP-apoE3 and -apoE4 transgenic mice: apoE4 mice show profound working memory impairments in the absence of Alzheimer's-like neuropathology.

For the purpose of studying the potential neurobehavioral effects of different human apolipoprotein E (apoE) isoforms produced within the brain, transgenic (TG) mice were generated in which human apoE3 or apoE4 isoforms were under control of an astrocyte-specific, glial fibrillary acidic protein promoter and these TG mice were bred back to apoE knockout (KO) mice. Behavioral phenotypes of apoE3 and apoE4 TG mice were derived by conducting a longitudinal study in which apoE3 and apoE4 TG mice were compared with apoE KO and wild-type (WT) mice (all male) on several behavioral measures. Analysis of locomotor activity, "open-field" behaviors, acoustic startle/prepulse inhibition, and elevated plus maze data suggested that the apoE TG/KO groups were more "emotionally reactive" than WT mice, with apoE4 mice typically being the most reactive. The absence of performance differences among groups on the rotating holeboard and water navigation tasks suggested intact reference memory processing in apoE TG/KO mice. However, apoE4 mice were profoundly impaired on a working memory-based protocol in the radial arm maze (11-14 months). Nonassociative factors (sensorimotor capacities or emotionality differences) did not appear to confound interpretation of the learning/memory results. Western blot analysis revealed no alterations in the level of synaptic, neuronal, or glial markers in neocortex or hippocampus and histologic analysis revealed no evidence of Abeta deposition or neuritic plaques in the apoE KO/TG mice. Our findings suggest that apoE4 expression in the brain may have selective deleterious effects on memory function in the absence of typical Alzheimer's-like neuropathology.

Acoustic Stimulation↗

PubMed2001

Perinatal mortality and morbidity. Comparison between maternal transport, neonatal transport and inpatient antenatal treatment.

The purpose was to assess differences in neonatal morbidity and mortality between maternally transferred, neonatally transferred and inborn neonates. We evaluated a continuous series of all antenatal transported infants (ATI, n=247) and postnatal transported infants (PTI, n=34) to the NICU and all preterm inborns (NTI, n=120) delivered at the University Hospital of Vienna. Data collected included sociodemographic, obstetrical and neonatal data. Mild neonatal morbidity was defined as RDS, BPD, ROP, PDA, NEC or IVH I-II, whereas severe neonatal morbidity was defined as the presence of PVL or IVH III-IV. Data were analyzed statistically using the Spearman correlation Coefficient, the Kruskal-Wallis test, and a multivariate model. There was a substantial gain in gestational age from transfer to delivery in the ATI group and from admission to delivery in the NTI group (2.1 and 5.6 weeks, respectively). The neonatal survival rate was 88.7% in the ATI and 97.5% in the NTI group. No neonate died in the PTI group; there was a significantly higher percentage of severe neonatal morbidity than in the ATI group (11.8% vs. 4.9%). We could not observe a significant difference with respect to the risk of death among the three study groups. There was a strong trend towards higher probability of severe neonatal morbidity in the NTI group. The risk of severe neonatal morbidity is much higher in the PTI-group (rel. risk 0.19, 0.06). Antenatal transfer guaranteed a significantly better neonatal outcome concerning severe neonatal morbidity than postnatal transport, and compared favorably with inborn admissions, even given the higher gestational age and birth weight in the NTI-group.

Adult↗

PubMed2001

Colicin A immunity protein interacts with the hydrophobic helical hairpin of the colicin A channel domain in the Escherichia coli inner membrane.

The colicin A pore-forming domain (pfColA) was fused to a bacterial signal peptide (sp-pfColA). This was inserted into the Escherichia coli inner membrane in functional form and could be coimmunoprecipitated with epitope-tagged immunity protein (EpCai). We constructed a series of fusion proteins in which various numbers of sp-pfColA alpha-helices were fused to alkaline phosphatase (AP). We showed that a fusion protein made up of the hydrophobic alpha-helices 8 and 9 of sp-pfColA fused to AP was specifically coimmunoprecipitated with EpCai produced in the same cells. This is the first biochemical evidence that Cai recognizes and interacts with the colicin A hydrophobic helical hairpin.

Alkaline Phosphatase↗

PubMed2000

Impaired synaptic plasticity and cAMP response element-binding protein activation in Ca2+/calmodulin-dependent protein kinase type IV/Gr-deficient mice.

The Ca(2+)/calmodulin-dependent protein kinase type IV/Gr (CaMKIV/Gr) is a key effector of neuronal Ca(2+) signaling; its function was analyzed by targeted gene disruption in mice. CaMKIV/Gr-deficient mice exhibited impaired neuronal cAMP-responsive element binding protein (CREB) phosphorylation and Ca(2+)/CREB-dependent gene expression. They were also deficient in two forms of synaptic plasticity: long-term potentiation (LTP) in hippocampal CA1 neurons and a late phase of long-term depression in cerebellar Purkinje neurons. However, despite impaired LTP and CREB activation, CaMKIV/Gr-deficient mice exhibited no obvious deficits in spatial learning and memory. These results support an important role for CaMKIV/Gr in Ca(2+)-regulated neuronal gene transcription and synaptic plasticity and suggest that the contribution of other signaling pathways may spare spatial memory of CaMKIV/Gr-deficient mice.

Animals↗

PubMed2000

Altered stress-induced anxiety in adenylyl cyclase type VIII-deficient mice.

Stress results in alterations in behavior and physiology that can be either adaptive or maladaptive. To define the molecular pathways involved in the response to stress further, we generated mice deficient (KO) in the calcium-stimulated adenylyl cyclase type VIII (AC8) by homologous recombination in embryonic stem cells. AC8 KO mice demonstrate a compromise in calcium-stimulated AC activity in the hippocampus, hypothalamus, thalamus, and brainstem. Hippocampal slices derived from AC8 KO mice fail to demonstrate CA1-region long-term depression after low-frequency stimulation, and AC8 KO mice also fail to activate CRE-binding protein in the CA1 region after restraint stress. To define the behavioral consequences of AC8 deficiency, we evaluated AC8 KO mice in the elevated plus-maze and open field. Although naive AC8 KO mice exhibit indices of anxiety comparable with that of wild-type mice, AC8 KO mice do not show normal increases in behavioral markers of anxiety when subjected to repeated stress such as repetitive testing in the plus-maze or restraint preceding plus-maze testing. These results demonstrate a novel role for AC8 in the modulation of anxiety.

Adenylyl Cyclases↗

PubMed2000

Prevalence of paradoxically normal serum cholestrol in morbidly obese women.

The paradox that cholesterol may be lower in extremely obese subjects versus those who are less overweight, although originally observed more than 40 years ago, has never been documented in a systematic fashion. We have therefore prospectively determined the body mass index (BMI) and serum cholesterol concentration in 3,312 women. The percentage of women with serum cholesterol in the normal range (<200 mg/dL) decreased with an increasing BMI, from 55% in women with a BMI less than 20 kg/m2 to 28% in those with a BMI of 30 to 35 kg/m2. Serum cholesterol greater than 300 mg/dL was found in only 2% of individuals with a BMI less than 20 kg/m2 but in 6% of the group with a BMI between 30 and 35 kg/m2. However, among morbidly obese women (BMI >40 kg/m2, n = 46), 39% presented with serum cholesterol less than 200 mg/dL and only one woman had serum cholesterol more than 300 mg/dL. With the BMI, the fitted regression model shows an increase in cholesterol for low BMIs, while cholesterol appears to decrease with larger values for the BMI. The age-dependent increase in cholesterol is more evident in younger women versus older women, where it tends to disappear. It is concluded that among morbidly obese women (BMI >40 kg/m2), there is a substantial subgroup with normal serum cholesterol.

Adult↗

PubMed2000

Serum soluble Fas levels in ovarian cancer.

OBJECTIVE: To determine the value of serum soluble Fas levels as a prognostic marker for survival of women with ovarian cancer and as a discriminator between benign and malignant adnexal masses. METHODS: Serum soluble Fas levels were measured with an enzyme-linked immunosorbent assay in 52 women with ovarian cancer, 30 women with benign ovarian cysts, and 35 healthy women. RESULTS: Median serum soluble Fas levels in women with ovarian cancer, women with benign ovarian cysts, and healthy women were 3.7 (range 1.6-14.5), 2.3 (range 1.3-4.1), and 1.5 ng/mL (range 0.1-5.6), respectively (P <. 001). A univariate logistic regression model showed a significant influence of serum soluble Fas and CA 125 levels on the odds of presenting with ovarian cancer versus benign cysts (P <.001 and P =. 001, respectively). In a multivariable logistic regression model for soluble Fas and CA 125, both markers showed a statistically significant influence on the odds of presenting with ovarian cancer versus benign cysts (P =.01 and P =.01, respectively). Increased pretreatment serum soluble Fas levels were associated with shortened disease-free and overall survival (P =.002 and P =.001, respectively). A multivariable Cox regression model identified serum soluble Fas levels as a significant prognostic factor for disease-free and overall survival, independent of tumor stage (P =. 04 and P =.03, respectively). CONCLUSION: Soluble Fas levels might be useful as a discriminator between benign ovarian cysts and ovarian cancer, adding to the information obtained with the use of the established tumor marker CA 125. Pretreatment serum soluble Fas levels also might be an independent prognostic factor for disease-free and overall survival.

Adenocarcinoma, Mucinous↗

PubMed2000

Low-density lipoprotein cholesterol in subclinical hypothyroidism.

The significance of subclinical hypothyroidism in regard to ensuing hyperlipidemia remains unclear. Because an unfavorable lipid profile would provide a possible explanation for the reported association of coronary-heart disease with this syndrome, we have evaluated the relationship of thyrotropin (TSH) with total cholesterol, low-density-lipoprotein (LDL) cholesterol, and triglycerides in patients with normal thyroid function (n = 4886) as well as subclinical (n = 1055) and manifest (n = 92) hypothyroidism. Serum concentrations of LDL cholesterol were similar in euthyroid persons (134+/-39 mg/dL) and in patients with subclinical hypothyroidism (137+/-40 mg/dL) but were higher (178+/-70 mg/dL, p < 0.01) in overt hypothyroidism. Within the group of subjects with subclinical hypothyroidism there was no apparent relationship between serum concentrations of TSH ranging from 4.0 to 49.0 microU/mL and concentrations of LDL cholesterol. Thus, there is no "threshold value" of TSH in these patients per se necessitating substitution therapy with thyroxine.

Age Factors↗

PubMed1999

Parallel recovery of MK-801-induced spatial learning impairment and neuronal injury in male mice.

The relationship between spatial learning impairment and reversible neuronal injury in the posterior cingulate/retrosplenial (PC/RS) cortex induced by MK-801 in male mice was studied using a four-corner holeboard task. Mice were dosed with 1 mg/kg MK-801 and tested on acquisition of a new "baited" hole at 5 or 12 h posttreatment. Acquisition in drugged mice was impaired at 5 h, but not at 12 h posttreatment. Their retention performances were unaffected 24 h after either the 5 or 12 h posttreatment acquisition sessions. MK-801 (1 mg/kg) was found to induce locomotor hyperactivity and some sensorimotor impairment at 5 h posttreatment. which could have contributed to the acquisition deficit. However, nonassociative effects of the drug were not prominent because this same dose did not impair holeboard performance at 5 h posttreatment when the task was well learned. Histologic experiments showed that many injured neurons (containing cytoplasmic vacuoles) were present in the PC/RS cortex at 5 h posttreatment but the reaction was essentially reversed at 12 h posttreatment. The results suggest that the acquisition impairment and neuronal injury induced by MK-801 evolve and recover in parallel according to a similar time schedule.

Analysis of Variance↗

PubMed1999

New residuals for Cox regression and their application to outlier screening.

The identification of individuals who 'died far too early' or 'lived far too long' as compared to their survival probabilities from a Cox regression can lead to the detection of new prognostic factors. Methods to identify outliers are generally based on residuals. For Cox regression, only deviance residuals have been considered for this purpose, but we show that these residuals are not very suitable. Instead, we develop and propose two new types of residuals: the suggested log-odds and normal deviate residuals are simple and intuitively appealing and their theoretical properties and empirical performance make them very suitable for outlier identification. Finally, various practical aspects of screening for individuals with outlying survival times are discussed by means of a cancer study example.

Biometry↗

PubMed1998

Clonidine potentiates the neuropathic pain-relieving action of MK-801 while preventing its neurotoxic and hyperactivity side effects.

Antagonists of NMDA glutamate receptors have been shown to alleviate neuropathic pain in rats and humans. However, NMDA antagonists can cause significant side effects ranging from behavioral disturbances to injury of neurons in the posterior cingulate/retrosplenial (PC/RS) cortex. We have found that alpha-2 adrenergic agonists prevent the PC/RS neurotoxic side effects of NMDA antagonists. In the present study of adult female rats subjected to sciatic nerve ligation (Bennett neuropathic pain model) and tested for paw withdrawal latency (PWL) following a thermal stimulus, we evaluated the ability of the NMDA antagonist, MK-801, to alleviate neuropathic pain either by itself or when administered together with the alpha-2 adrenergic agonist, clonidine. We found that MK-801, at a dose (0.05 mg/kg s.c.) that is known to cause mild hyperactivity but is subthreshold for producing PC/RS neurotoxic changes, relieved the neuropathic pain state associated with sciatic nerve ligation. However, the relief at this dose was very transient, and no neuropathic pain-relieving effect was observed at a lower dose (0. 025 mg/kg s.c.) of MK-801. Clonidine, at a dose (0.05 mg/kg s.c.) that prevents the cerebrocortical neurotoxic effects of MK-801, decreased sensitivity to the thermal stimulus equally under all conditions (ligated, sham ligated, unoperated), but did not specifically relieve neuropathic pain in the ligated limb. Combining this dose of clonidine with an ineffective dose (0.025 mg/kg s.c.) of MK-801 provided specific, complete and long lasting (up to 4 h) relief from neuropathic pain. Rats receiving this drug combination did not display hyperactivity or any other behavioral disturbance typically associated with MK-801 treatment, nor show neurotoxic changes in cerebrocortical neurons. In separate experiments on normal unoperated rats, we found that clonidine (0.05 mg/kg s.c.) counteracted the hyperactivity induced by MK-801 (0.05 mg/kg s.c.) and returned activity levels to a normal range. These findings signify that clonidine, which does not specifically relieve neuropathic pain, can potentiate the neuropathic pain-relieving action of MK-801, while also protecting against neurotoxicity and hyperactivity side effects of MK-801. The potentiation is of a sufficient magnitude that it permits cutting the MK-801 dose requirement in half, thereby achieving prolonged neuropathic pain relief while doubling the margin of safety against any type of side effect that might be mediated by blockade of NMDA receptors.

Adrenergic alpha-Agonists↗

PubMed1998

Disseminated corticolimbic neuronal degeneration induced in rat brain by MK-801: potential relevance to Alzheimer's disease.

Blockade of N-methyl-D-aspartate (NMDA) glutamate receptors by MK-801 induces neuronal degeneration in the posterior cingulate/retrosplenial cortex and other corticolimbic regions although damage in the latter has not been adequately characterized. This disseminated corticolimbic damage is of interest since NMDA hypofunction, the mechanism that triggers this neurodegenerative syndrome, has been postulated to play a role in the pathophysiology of Alzheimer's disease (AD). Several histological methods, including electron microscopy, were used to evaluate the neurotoxic changes in various corticolimbic regions of rat brain following MK-801 or a combination of MK-801 plus pilocarpine. We found that MK-801 triggers neuronal degeneration in a widespread pattern similar to that induced by phencyclidine and that females showed more damage than males. The neurotoxic reaction involved additional brain regions when muscarinic receptors were hyperactivated by administering pilocarpine with MK-801. Ultrastructural evaluation revealed that a major feature of the neurotoxic action involves degeneration of dendritic spines which entails loss of synaptic complexes. The ultrastructural appearance of degenerating neurons was generally inconsistent with an apoptotic mechanism, although evidence equivocally consistent with apoptosis was observed in some instances. The cell death process evolved relatively slowly and was still ongoing 7 days posttreatment. Relevance of these results to AD is discussed.

Alzheimer Disease↗

PubMed1997

Decrease of bone formation in adult women with fragility fractures.

OBJECTIVES: To compare bone mineral density (BMD) and some markers of bone metabolism in women with fragility fractures and in normal age-matched subjects. METHODS: A 100 women with at least one vertebral deformity > 25%, and 219 age-, BMI- and parity-matched healthy women, were recruited for the study. In all the patients fractures were symptomatic and occurred at least 1 year before densitometric measurement. Forearm bone mineral density (BMD) as well as biochemical assessment of some markers of bone turnover were measured in all the subjects. RESULTS: BMD was significantly lower in the fracture than in the control group (0.326 +/- 0.073 vs. 0.379 +/- 0.079; P < 0.001). Fractured women showed alkaline phosphatase (ALP) and osteocalcin (OC) serum levels significantly lower than controls, while no differences were found in fasting urinary calcium and hydroxyproline excretion. Women without fractures showed a significant correlation between ALP and both age and years since menopause (YSM). Such a correlation is lacking in the fracture group. CONCLUSIONS: Women with vertebral deformities likely due to a fracture had a forearm BMD and markers of bone formation lower than normal. Whether low bone density is due to a low peak of bone mass or to an increased postmenopausal bone loss sustained by an uncoupling between the two bone remodelling processes is still unclear.

Aged↗