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Prospective study of diet and decline in lung function in a general population.

We have investigated the relationship between decline in lung function and dietary intakes of magnesium, vitamin C, and other antioxidant vitamins in a general population cohort in Nottingham, United Kingdom. In 1991, we measured dietary intake by semiquantitative food frequency questionnaire, forced expiratory volume in 1 second (FEV1), and respiratory symptoms in a cross-sectional survey of 2,633 adults aged 18-70. Nine years later we repeated these measures in 1,346 of these individuals. In cross-sectional analyses, after adjustment for smoking and other confounders, higher intakes of vitamin C and magnesium, but not vitamins A or E, were associated with higher levels of FEV1 in both 1991 and 2000. In longitudinal analysis with adjustment for confounders, decline in FEV1 between 1991 and 2000 was lower amongst those with higher average vitamin C intake by 50.8 ml (95% confidence interval, 3.8-97.9) per 100 mg of vitamin C per day, but was unrelated to magnesium intake. There was no relationship between decline in FEV1 and intake of vitamins A or E. This study suggests that a high dietary intake of vitamin C, or of foods rich in this vitamin, may reduce the rate of loss of lung function in adults and thereby help to prevent chronic obstructive pulmonary disease.

Adult↗

Interleukin-12 induction of Th1 cytokines is important for viral clearance in chronic hepatitis B.

Interleukin-12, a cytokine with an important role against intracellular pathogens, promotes Th1 cell development, cellmediated cytotoxicity, and interferon-gamma production. We investigated the immunoregulatory role of IL-12 in 72 chronic hepatitis B virus (HBV) carriers, 33 of whom were monitored longitudinally during interferon-alpha treatment. Serum levels of IL-12 heterodimer, IL-12 p40 subunit, IL-4, and Th1 cytokines were determined by specific ELISAs, and hepatitis B core antigen-specific T cell response by a proliferation assay. Chronic HBV carriers had higher serum levels of IL-12 and IL-12 p40 in comparison with controls (P < 0.01), suggesting that IL-12 production is not impaired. The longitudinal analysis revealed a further substantial increase (> 2.5x baseline level) of bioactive IL-12 and Th1 cytokines in patients who cleared HBV and seroconverted to anti- hepatitis B e, unlike the 23 nonresponders with persistent HBV replication (P < 0.01). The IL-12 peak followed the peak of hepatocytolysis by 9.8+/-2.8 wk and occurred either before or simultaneously with hepatitis B e seroconversion. Hepatitis B core antigen-specific T cell proliferation closely correlated with hepatocytolysis and increased significantly in all patients (8 responders and 15 nonresponders) who developed hepatitis flare, irrespective of the virological outcome. These results provide in vivo evidence that IL-12 may have an important role for viral clearance in chronic HBV infection.

Adult↗

Effects of caregivers' perceived stigma and causal beliefs on patients' adherence to antidepressant treatment.

OBJECTIVE: Nonadherence to prescribed medications is a significant problem in the treatment of mood disorders. Previously proposed adherence models have not been sufficiently accurate in identifying patients who do not adhere to treatment. This study evaluated the importance of the social context in adherence by using a prospective, longitudinal analysis. Specifically, this study evaluated the effects of caregivers' causal beliefs about depression and their perceptions of stigma on three-month treatment adherence among patients with depression. METHODS: Fifty patients with major depressive disorder and their primary caregivers were identified at a psychiatric hospital's outpatient clinic. Attributions for the causes of depression (either cognitive and attitudinal or medical and biological) and perceived stigma were assessed among caregivers at baseline, and patients' adherence was evaluated three-months after treatment began. RESULTS: Data were available for 47 patients at follow-up. Caregivers' attribution of depression to cognitive and attitudinal problems significantly predicted patients' decreased adherence. However, the degree of patients' adherence was not predicted by caregivers' attributions to medical and biological causes and caregivers' perceived stigma. CONCLUSIONS: The findings stress the importance of patients' social environment in determining treatment adherence and the necessity of educating caregivers about the impact that their causal attributions have on patients' behavior. Involving caregivers in treatment may improve their attitude toward patients with depression and, in doing so, enhance patients' adherence and outcome.

Adult↗

Internal capsule size in good-outcome and poor-outcome schizophrenia.

Converging lines of research suggest that white matter abnormalities may be central to the pathophysiology of schizophrenia. The purpose of this study was to examine regional white matter in the anterior limb of the internal capsules in patients with schizophrenia. The authors obtained high-resolution magnetic resonance imaging in 106 patients with schizophrenia and 42 age and sex-matched healthy comparison subjects. The area of the anterior limb of the internal capsule was measured at five proportionately spaced dorsal-to-ventral levels. Schizophrenia patients were divided into good-outcome and poor-outcome groups, based on longitudinal analysis of self-care deficits. Patients with poor-outcome had significantly smaller dorsal areas than healthy comparison subjects, but good-outcome patients did not differ from healthy comparison subjects. Larger relative volumes of the caudate, putamen, and thalamus tended to be associated with relatively larger volumes of the internal capsule in healthy comparison subjects and good-outcome patients, consistent with the known frontal-striatal-thalamic pathways. Larger ventricles were associated with smaller internal capsules, particularly in healthy comparison subjects. The findings suggest disruption of internal capsule fibers in poor-outcome patients with schizophrenia. These abnormalities may be independent of other structural changes in schizophrenia.

Adult↗

Exercise behavior in a community sample with diabetes: understanding the determinants of exercise behavioral change.

PURPOSE: The purpose of this study was to investigate the factors associated with exercise behavior among adults with diabetes. METHODS: Exercise behavior (stage of exercise readiness and energy expenditure) and potential determinants were measured on a subsample (n = 46) of adults with type 1 or type 2 diabetes from a randomized population-based telephone survey. Participants were assessed at baseline and at a 6-month follow-up. RESULTS: Sociodemographic and biomedical characteristics did not significantly differ between the stages of exercise behavior. Scores on the psychosocial constructs of self-efficacy, behavioral processes, self-concept, and social support were significantly higher for those in the action stage than those in the preaction stage of exercise readiness. Self-efficacy and behavioral process of change were significantly associated with energy expenditure; self-efficacy was the strongest predictor in the longitudinal analysis. CONCLUSIONS: These findings may generate direction for theory development and guide health and medical practitioners when intervening on the specific constructs. Population- and community-based surveys have utility for assessing diabetes health-related behavior (e.g., exercise behavior).

Adolescent↗

Neuroimaging correlates of dementia rating scale performance at baseline and 12-month follow-up among patients with vascular dementia.

The authors previously reported that subcortical hyperintensity (SH) and whole-brain volume (WBV) each covary with different subscale scores of the Mattis Dementia Rating Scale (MDRS) among vascular dementia (VaD) patients. The present longitudinal analysis examined these relationships for change. The authors found that SH volume increased and WBV decreased significantly over 12 months. At baseline, SH volume accounted for significant variance in MDRS total score and every subscale score, except Memory. WBV was unrelated to any MDRS measure. After 12 months, SH volume was related only to the Construction subscale score, whereas WBV accounted for the majority of variance in Attention and Memory subscale performance. These findings indicate that although SH volume increases with disease progression, the relative impact of SH volume on cognitive status decreases among patients with advanced VaD.

Aged↗

APOE epsilon4 as a predictor of subjective quality of life in a biracial older person community sample.

UNLABELLED: The epsilon4 allele of apolipoprotein E (APOE) has been associated with health-related outcomes that may adversely affect quality of life (QOL) in older adults. In the absence of published information, we sought to determine whether the epsilon4 allele was associated with subjective QOL across 5 parameters in a community sample of older adults. DESIGN: Prospective cohort study. SETTING: Community-based sample of older adults in North Carolina (Duke site of the Established Populations for Epidemiologic Studies of the Elderly [Duke EPESE]). PARTICIPANTS: Self-responding genotyped sample members (n = 1,880) of whom 1,254 provided longitudinal data. MEASUREMENTS: APOE genotype and five newly constructed, reliable, and valid measures of subjective QOL derived from the Duke EPESE questionnaire. The 5 parameters measured were social, economic, mental and physical health, and functional status. Control variables included age, gender, race (African American or White), education and urban/rural residence. RESULTS: Among those with good baseline QOL, there was no significant association between the epsilon4 allele and any of the parameters of subjective QOL in longitudinal analyses. In controlled longitudinal analysis, older age women predicted poorer functional status; being African American, and reporting lower education predicted poorer subjective economic well-being; and being African American predicted better self-assessed mental health. CONCLUSIONS: This study is among the first to explore the association of the epsilon4 allele with overall QOL. Considered from a public health perspective, these findings challenge the uncritical assumption that the presence of this susceptibility gene in the population implies an excess burden of poor QOL. The findings do not contradict the previous association of epsilon4 with Alzheimer's disease (AD) and other conditions. Such conditions continue to merit full attention.

Aged↗

Three-dimensional intravascular ultrasound assessment of abdominal aortic aneurysm necks.

PURPOSE: To document the accuracy of an automated analysis system for measuring lumen diameter and neck lengths of abdominal aortic aneurysms (AAAs) from intravascular ultrasound (IVUS) images and to describe additional features associated with 3-dimensional (3D) IVUS imaging. METHODS: Twenty-two aortic aneurysms were studied with IVUS. Lumen diameters obtained using the automated analysis system were compared with manual measurements from axial IVUS scans, as were neck lengths obtained using automated analysis versus those measured with the aid of a displacement sensing device. Automated analyses were repeated by a second observer. Agreement was expressed as the coefficient of variation (CV). RESULTS: Twenty proximal aortic, 6 distal aortic, and 3 iliac necks were available for analysis. Comparison between automated analysis and manual measurements for lumen diameter revealed a difference of 0.45 +/- 0.42 mm (mean +/- SD, Pearson's r = 0.99, p < 0.001, CV = 2.1%) and a difference of 0.05 +/- 0.12 cm (r = 0.99, p = 0.04, CV = 4.1%) for neck length. Interobserver difference for lumen diameter was 0.13 +/- 0.66 mm (r = 0.99, p < 0.001, CV = 3.4%) and 0.05 +/- 0.11 cm for length measurements (r = 0.99, p = 0.02, CV = 3.5%). The 3D IVUS imaging facilitated the identification of neck configuration. CONCLUSIONS: Automated analysis of IVUS images allows accurate measurement of the lumen diameter of proximal and distal AAA necks and gives length measurements comparable to those of manual analysis. Longitudinal display of IVUS images aids in the elucidation of neck anatomy.

Aged↗

Urinary neopterin in malignant lymphoma.

Urinary neopterin levels were studied in 96 patients with malignant lymphomas. Twenty-eight had Hodgkin's disease and 68 non-Hodgkin's lymphoma. Neopterin excretion was significantly related to the clinical stage of the disease. Mean neopterin excretion in patients with active disease (634 +/- 527 mumol neopterin/mol creatinine) was significantly higher (p = 0.000) than in patients in complete remission (198 +/- 105 mumol neopterin/mol creatinine). Mean neopterin levels of patients in stage III-IV were higher than for patients in stage I-II. These findings were the same in patients with Hodgkin's disease and those with non-Hodgkin's lymphoma (659 +/- 593-425 +/- 316 mumol neopterin/mol creatinine), regardless of the histological subtype. A significant correlation was found between neopterin excretion, ESR (r = 0.31; p = 0.003) and hemoglobin (r = -0.40; p = 0.000). Longitudinal analysis showed a trend towards a correlation between response to therapy and neopterin excretion. These findings suggest that neopterin may be a useful prognostic marker in non-Hodgkin's lymphoma.

Adult↗

Computed tomographic imaging of the airways: relationship to structure and function.

Alterations in the structure of the airways, collectively termed airway remodelling, contribute to airflow obstruction in a variety of chronic lung diseases. While histology has provided valuable insights into the structure of airway wall remodelling, this technique is invasive and does not allow the longitudinal analysis of airway wall dimensions. Technical advances in computed tomography allow the assessment of airway wall dimensions, and are ideally suited for the noninvasive investigation of the pathogenesis of airway wall remodelling and the evaluation of new therapeutic interventions. The aim of this article is to review the use of computed tomography in the investigation of airway structure and function in health and disease.

Airway Obstruction↗

Transverse propagation in an expanded PSpice model for cardiac muscle with gap-junction ion channels.

Transverse propagation was previously found to occur in a two-dimensional model of cardiac muscle using the PSpice software program for electronic circuit design and analysis. Longitudinal propagation within each chain, and transverse propagation between parallel chains, occurred even when there were no gap-junction (g-j) channels inserted between the simulated myocardial cells either longitudinally or transversely. In those studies, there were pronounced edge (boundary) effects and end-effects even within single chains. Transverse velocity increased with increase in model size. The present study was performed to examine boundary effects on transverse propagation velocity when the length of the chains was held constant at 10 cells and the number of parallel chains was varied from 3 to 5, to 7, to 10, and to 20. The number of g-j channels was either zero, both longitudinally and transversely (0/0), or 100/100. Some experiments were also made at 100/0, 1/1, and 10/10. Transverse velocity and overall velocity (both longitudinal and transverse components) was calculated from the measured total propagation time (TPT), i.e., the elapsed time between when the first action potential (AP) and the last AP crossed the zero potential level. The transverse g-j channels were placed only at the ends of each chain, such that propagation would occur in a zigzag pattern. Electrical stimulation was applied intracellularly between cells A1 and A2. It was found that, with no g-j channels (0/0), overall velocity increased almost linearly when more and more chains were placed in parallel. In contrast, with many g-j channels (100/100), there was a much flatter relationship between overall velocity and number of parallel chains. The difference in velocities with 0/0 channels and 100/100 channels was reduced as the number of chains was increased. In conclusion, edges have important effects on propagation velocity (overall and transverse) in cardiac muscle simulations.

Action Potentials↗

Thyroid function in Danish greenhouse workers.

BACKGROUND: From animal studies it is known that currently used pesticides can disturb thyroid function. METHODS: In the present study we investigated the thyroid function in 122 Danish greenhouse workers, to evaluate if greenhouse workers classified as highly exposed to pesticides experiences altered thyroid levels compared to greenhouse workers with lower exposure. Serum samples from the greenhouse workers were sampled both in the spring and the fall to evaluate if differences in pesticide use between seasons resulted in altered thyroid hormone levels. RESULTS: We found a moderate reduction of free thyroxine (FT4) (10-16%) among the persons working in greenhouses with a high spraying load both in samples collected in the spring and the fall, but none of the other measured thyroid hormones differed significantly between exposure groups in the cross-sectional comparisons. However, in longitudinal analysis of the individual thyroid hormone level between the spring and the fall, more pronounced differences where found with on average 32% higher thyroid stimulating hormone (TSH) level in the spring compared to the fall and at the same time a 5-9% lower total triiodthyroxin (TT3), free triiodthyroxine (FT3) and FT4. The difference between seasons was not consistently more pronounced in the group classified as high exposure compared to the low exposure groups. CONCLUSION: The present study indicates that pesticide exposure among Danish greenhouse workers results in only minor disturbances of thyroid hormone levels.

Adolescent↗

Autoantibodies specific for apoptotic U1-70K are superior serological markers for mixed connective tissue disease.

Modifications occurring on autoantigens during cell death have been proposed to have a role in the initiation of autoimmune diseases. Patients suffering from mixed connective tissue disease (MCTD) produce autoantibodies directed to U1 small nuclear ribonucleoprotein (snRNP), and antibodies against a 70 kDa protein component, the U1-70K (70K) protein, are the most prominent. During apoptosis, 70K is cleaved by caspase-3 to a 40 kDa product, which remains associated with the complex. Autoantibodies preferentially recognizing the apoptotic form of 70K have been described previously, and an apoptosis-specific epitope on 70K has been identified. This study shows that 29 of 53 (54%) MCTD sera preferentially recognize the apoptotic form of 70K over intact 70K. Moreover, we show that antibodies directed to an apoptosis-specific epitope on 70K are more specifically associated with MCTD than other anti-70K antibodies, suggesting that apoptotic 70K is a better antigen for the detection of these antibodies in MCTD patients. Longitudinal analysis of 12 MCTD patients showed in several patients that early sera are relatively enriched with antibodies recognizing an apoptosis-specific epitope, and that the levels of these apoptosis-specific antibodies decrease in time. These findings indicate that the early detection of apoptotic 70K is of considerable interest for anti-U1 snRNP-positive patients.

Anisomycin↗

Intellectual and functional outcome of children 3 years old or younger who have CNS malignancies.

PURPOSE: To evaluate the impact of tumor location, clinical parameters, and therapy on neurocognitive, neuroendocrine, and functional outcomes in children < or = 3 years old with intracranial CNS malignancies who survived at least 2 years after diagnosis. PATIENTS AND METHODS: Records were retrospectively reviewed for 194 children diagnosed from 1985 to 1999 at St Jude Children's Research Hospital (Memphis, TN). RESULTS: The median age at diagnosis was 1.8 years (range, 0.1 to 3.5 years). Median follow-up was 7.64 years (2.0 to 19.4 years). Tumors were infratentorial (102), diencephalic (53), and hemispheric (39); 47% required ventriculoperitoneal shunts, 36% developed seizure disorders, and 20% developed severe ototoxicity. Therapy included no radiation therapy (RT) in 57 (30%), local RT in 87 (45%), and craniospinal irradiation (CSI) in 49 (25%). Overall survival at 10 years was 78 +/- 4%. In a longitudinal analysis of 126 patients with at least one neurocognitive evaluation (NE), the mean rate of intelligence quotient (IQ) change for patients who received CSI (-1.34 points per year) and local RT (-0.51 points per year) was significantly different from the no RT group (0.91 points per year; P = .005 and P = .036, respectively). Patients with hemispheric tumors had a significantly greater IQ decline (-1.52 points per year) than those with midline tumors (0.59 points per year; P = .038). Among those with NE > or = 5 years after diagnosis, 71.4% of CSI recipients compared with 23% of local RT recipients had IQ less than 70 (P = .021). Patients undergoing CSI were more likely to develop endocrinopathies (P < .0001) and to require special education (P = .0007). CONCLUSION: In young children with CNS tumors, CSI and hemispheric location are associated with significant declines in IQ scores.

Age of Onset↗

Ontogeny of luteinizing hormone secretion and first ovulation in seasonal breeding rhesus monkeys.

A longitudinal analysis assessed the role of nongonadal control and estradiol (E2) inhibition of LH secretion during puberty in female rhesus monkeys and examined how maturational changes in LH release were related to GH secretion, ponderal growth, and seasonal changes in the environment. Three groups of spring-born monkeys housed outdoors were studied from 12 months of age in May 1982 through 43 months of age in December 1984: gonadally intact (INT; n = 8), ovariectomized (OVX; n = 5), and OVX E2 treated (E2OVX; n = 5; E2, approximately 45 pg/ml). Suppression of bioactive levels of LH by E2 was functional once changes in nongonadal control of LH release occurred, as basal LH levels increased significantly earlier in OVX (23.7 +/- 2.1 months) than either E2OVX (29.6 +/- 0.4 months) or INT (29.6 +/- 1.0 months). Although these increases in LH were not seasonally limited, higher levels were achieved if these initial increases occurred during the fall. Menarche in INT females occurred after the initial increases in LH (30.9 +/- 0.1 months). First ovulation for INT females was seasonally restricted, occurring either at 31.5 +/- 0.4 months in December/January (n = 3) or 11 months later at 42.5 +/- 0.4 months in October/November (n = 5). No ovulations occurred during the intervening spring and summer period, as serum levels of LH were significantly lower than in the preceding perimenarchial fall months. After the initial maturational increases, LH levels declined significantly in OVX and E2OVX females in late winter at 33 months before rising again the next fall. The timing and extent of the maturational decrease in E2 inhibition of LH secretion were related to developmental increases in serum GH and not to body weight. Furthermore, females who had a normal first ovulation shortly after menarche at 31 months had significantly higher serum GH levels yet similar growth rates and body weights compared to their age-mates. First ovulation at 43 months in the remaining females occurred after sustained elevations in serum GH, similar to those observed in the early ovulating females. These data indicate that both nongonadal control and steroid inhibition of LH secretion operate during puberty in female rhesus monkeys and support the hypothesis that the final stages of puberty are characterized by a maturational decrease in E2 negative feedback of LH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Influence of age on the associations among insulin autoantibodies, islet cell antibodies, and HLA DAQ1*0301-DQB1*0302 in siblings of patients with type 1 (insulin-dependent) diabetes mellitus. Belgian Diabetes Registry.

In recent-onset type 1 (insulin-dependent) diabetes mellitus (IDDM), insulin autoantibodies (IAA) and islet cell antibodies (ICA) occur preferentially in young (< 10 yr) patients with the HLA DQA1*0301-DQB1*0302 risk haplotype. We investigated whether this association also exists in siblings of IDDM patients. In our group of 310 siblings, aged 0-39 yr, 6% were positive for IAA, 7% for ICA 12 Juvenile Diabetes Foundation units (JDFU) or more, 5% for ICA 20 JDFU or more, and 2% for high titer ICA (> or = 80 JDFU). The occurrence of IAA and ICA (> or = 20 JDFU) was significantly associated, with a preferential relationship to the HLA DQA1*0301-DQB1*0302 susceptibility haplotype. In the present group of siblings, IAA and DQA1*0301-DQB1*0302 were significantly associated under age 10 yr (26% positivity for IAA vs. 4% in relatives without this haplotype). In this age group, IAA were more prevalent than (high titer) ICA (6%) in the presence of the haplotype. The association between (high titer) ICA and DQA1*0301-DQB1*0302 was not restricted to subjects under age 10 yr. High titer ICA (n = 5) occurred exclusively in homozygotes for the latter haplotype and in carriers of the heterozygous DQA1*0301-DQB1*0302/DQA1*0501-DQB1*0201 high risk genotype, mostly under age 20 yr (four of five). The preferential occurrence of IAA in DQA1*0301-DQB1*0302-positive siblings under age 10 yr was caused by their high prevalence (47%) in subjects with the heterozygous high risk genotype in this age group. As in patients at onset, IAA and high titer ICA are preferentially associated with the DQA1*0301-DQB1*0302 haplotype in siblings of IDDM patients, but, unlike at onset, these associations are observed with specific genotypes only and are more pronounced in subjects under age 10 yr for IAA only. Longitudinal analysis in first degree relatives and other normal controls carrying the DQA1*0301-DQB1*0302 haplotype should assess the hypothesis that IAA qualify as earlier predictive markers for IDDM than high titer ICA.

Adolescent↗

Prostaglandin endoperoxide-H synthase (PGHS) activity and immunoreactive PGHS-1 and PGHS-2 levels in human amnion throughout gestation, at term, and during labor.

Prostaglandins (PGs) are of primary importance in the initiation and maintenance of labor in women. A major intrauterine source of prostaglandins is the amnion, which synthesizes increased amounts of PGE2 at term labor. Because PG endoperoxide-H synthase (PGHS) catalyzes the rate-limiting step of PG synthesis from arachidonic acid, we investigated the changes in amniotic PGHS specific activity during gestation and at term and preterm labor. Also, we determined the level of immunoreactive PGHS protein in the amnion to evaluate the mechanisms by which PGHS activity may be regulated. PGHS specific activity, measured at the amount of PGE2 produced by amnion microsomes under optimal conditions, was 18.2 +/- 3.7 pg PGE2/micrograms protein.min (mean +/- SE; n = 19) at term (37-42 weeks gestation) before the spontaneous onset of labor. PGHS specific activity was significantly higher after spontaneous term labor (38.9 +/- 6.0 pg PGE2/micrograms protein.min; n = 19; P < 0.05). Amnion samples from preterm (< 36 weeks gestation) nonlaboring patients contained low levels of PGHS specific activity (5.9 +/- 1.8 pg PGE2/micrograms protein.min; n = 9), which increased significantly with spontaneous preterm labor (28.3 +/- 6.8 pg PGE2/micrograms protein.min; n = 10; P < 0.05). Longitudinal analysis of the data showed that PGHS specific activity was low in the first and second trimesters of gestation, but increased dramatically before labor onset at term. We detected PGHS protein in all microsomal samples, with an antiovine PGHS antibody recognizing both PGHS-1 and -2 isoforms of the enzyme. However, there was no correlation between PGHS specific activity and the amount of immunoreactive PGHS protein. Using an antibody specific for PGHS-2, we detected immunoreactive protein in only 9 of the 25 tissues examined and found no correlation between PGHS specific activity and the amount of PGHS-2 protein. These results suggest that 1) PGHS specific activity in the amnion increases sharply before the onset of labor at term; 2) further increases in specific activity occur during term and preterm labor; and 3) the specific activity of PGHS in the amnion is not related directly to the amount of immunoreactive enzyme protein.

Amnion↗

Longitudinal follow-up of bone density and body composition in children with precocious or early puberty before, during and after cessation of GnRH agonist therapy.

We studied bone mineral density (BMD), bone metabolism, and body composition in 47 children with central precocious puberty (n = 36) or early puberty (n = 11) before, during, and after cessation of GnRH agonist. Bone density and body composition were measured with dual energy x-ray absorptiometry and expressed as SD scores. Bone age and biochemical parameters of bone turnover were assessed. Measurements were performed at baseline, after 6 months, and on a yearly basis thereafter. Mean lumbar spine BMD SD scores for chronological age were significantly higher than zero at baseline and decreased during treatment. Lumbar spine bone mineral apparent density and total body BMD did not differ from normal at baseline and showed no significant changes during treatment. In contrast, BMD SD scores for bone age were significantly lower than zero at baseline and at cessation of therapy. Two years after therapy, bone mineral apparent density and BMD SD scores for bone age and chronological age did not differ from normal. Markers of bone turnover decreased during treatment, mainly in the first 6 months. Patients had increased percentage of fat and lean body mass at baseline. After an initial increase of percentage body fat during treatment, percentage body fat decreased and normalized within 1 yr after cessation of treatment. Our longitudinal analysis suggests that peak bone mass or body composition will not be impaired in patients with precocious or early puberty after GnRH agonist therapy.

Aging↗