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OBJECTIVES: To explore adolescent students' use of school based health and medical care and mental health and substance abuse counseling services and to compare adolescents' patterns of use of medical, mental health, and substance abuse services located in school-based and traditional settings. DESIGN: Retrospective analysis of computer-stored, standardized data for all student visits during a 4-year period. SETTING: Three high school-based student health centers. SUBJECTS: A total of 3818 adolescent students who used services provided by the school-based health centers (SBHCs). OUTCOME MEASURES: Frequencies of student visits to medical providers and mental health and substance abuse counselors and frequencies of diagnostic assignments. RESULTS: During a 38-month period, 3818 students attending senior high school made a total of 27 886 visits to three SBHCs. They represented 63% of students enrolled in the SBHCs and approximately 42% of the total school population. There were no significant demographic differences between students attending the SBHCs and the overall student body. However, compared with students who were enrolled in the SBHCs but did not use them, users were more likely to be female and Hispanic. Ninety-four percent of students using the services had visits with medical providers; 25% had visits with mental health counselors; and 8% of students had visits with substance abuse counselors. The total annual mean number of student visits was 4.7, and the annual mean numbers of visits for students who used the following services were: medical, 3.3; mental health, 5.8; and substance abuse, 6.8. An average of 1.4 diagnoses were made per visit. The most common major diagnostic categories were emotional problems (29% of all diagnoses), health supervision (13%), respiratory problems (11%), reproductive health problems (11%), and substance abuse problems (8%). Almost one fourth of the students had contact with more than one of the three categories of service provicer. Visit frequency increased significantly for students who used two categories of provider (13 to 15 mean total visits compared with 4 to 5 mean total visits for students who used just one category of provider) and escalated to a mean of 32 total visits if all three categories of service were used. CONCLUSIONS: Adolescents attending SBHCs had higher rates of visits for health and medical care than adolescents using traditional sources of medical care. The proportions of student users of SBHC mental health and substance abuse counseling services were commensurate with the estimated prevalences of these problems in this country's adolescent population. In addition, the mean numbers of visits to mental health counselors in SBHCs compared favorably with adolescent visit rates for mental health services in other settings. Too little information is available about adolescent use of substance abuse services in non-school-based settings to make similar comparisons. In summary, adolescent users of SBHCs seemed to have a higher use of medical, mental health, and probably substance abuse counseling services than did adolescents in the general populations. These findings are consistent with the interpretation that SBHCs do enhance adolescents' access to care for medical, mental health, and substance abuse problems. [ABSTRACT FROM AUTHOR]

Postmenopausal osteoporosis is characterised by increased bone turnover and an imbalance between bone resorption and formation. Bisphosphonate treatment reduces bone turnover but their effect on bone balance is yet to be fully investigated. Using the T-score approach our aims were to: i) investigate the effects of oral nitrogen-containing bisphosphonates on bone balance and turnover in postmenopausal women with osteoporosis and ii) determine the relationship of the change in bone balance and turnover with the change in BMD at the lumbar spine and total hip. Women were recruited, mean age 67 years, and randomised to receive: ibandronate (n = 55, 150 mg/month), alendronate (n = 54, 70 mg/week) or risedronate (n = 56, 35 mg/week). They also received calcium and vitamin D daily. A fasting serum sample was collected at baseline and weeks 1, 2, 4, 12, 13, 48 and 96. The control group were 226 healthy premenopausal women receiving no treatments. PINP and CTX were measured using the iSYSIDS analyser and BMD (in g/cm2) of the lumbar spine and total hip were measured by DXA (Hologic Inc). PINP and CTX values were log10-transformed and normalised. T-scores were calculated using the mean and standard deviation from the premenopausal group. Bone turnover and bone balance were calculated from the T-scores. Mean levels (95% CI) of balance and turnover are shown in the table. The change in turnover at weeks 4, 12 and 48 was inversely correlated with the change in lumbar spine and total hip BMD at weeks 48 and 96, (p < .01 to p < .001). The change in balance at week 4 positively correlated with the change in total hip BMD at weeks 48, (p < .01). Bisphosphonates resulted in an initial positive balance and a reduction in turnover. Some of these changes were associated with increases in BMD. Bone turnover is a better predictor of BMD than bone balance., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Bone markers may be useful to monitor response to treatment withdrawal in osteoporosis. We used two criteria for investigating the change in BTMs after withdrawal of bisphosphonate treatment. A larger increase in BTMs was associated with greater bone loss. Bone markers may be useful in monitoring of patients taking a pause from treatment., Introduction: Measurement of bone turnover markers (BTMs) may be useful to monitor offset of treatment with bisphosphonates (BP) in osteoporosis. We assessed the effect of withdrawal of BP treatment by comparing the changes in BTMs and total hip (TH) bone density (BMD)., Methods: We studied postmenopausal osteoporotic women who had completed a randomised study of three oral BPs. After 2 years of treatment, participants with BMD T-score > - 2.5 and in whom it was considered clinically appropriate to discontinue treatment, were invited to participate in a further 2-year observational study. Biochemical response was assessed using BTMs (CTX and PINP) with offset being defined by two criteria: (1) an increase greater than the least significant change (LSC) and (2) an increase above the reference mean value., Results: Fifty women completed the study. At 48 weeks after stopping BPs, CTX was greater than the LSC for 66% of women and PINP 72%; CTX was above the reference mean for 64% of women and PINP 42%. The decrease in THBMD was greater for women with the largest increase in BTM compared to those with continued suppression (mean difference for CTX was - 2.98%, 95%CI - 4.75 to - 1.22, P < 0.001, PINP - 2.25%, 95% CI - 4.46 to - 0.032, P = 0.046)., Conclusion: The measurement of BTM after withdrawal of BPs is potentially useful to evaluate patients that are taking a pause from treatment. An increase in BTMs more than the LSC and/or reference mean reflects loss of treatment effect and identifies patients that are likely to have a decrease in BMD. Such changes could provide an indication for reintroduction of treatment.

Context: The optimal measure of vitamin D status is unknown., Objective: To directly measure circulating free 25-hydroxyvitamin D [25(OH)D] concentrations and relationships to total 25(OH)D in a clinically diverse sample of humans., Design: Cross-sectional analysis., Setting: Seven academic sites., Patients: A total of 1661 adults: healthy (n = 279), prediabetic (n = 479), outpatients (n = 714), cirrhotic (n = 90), pregnant (n = 20), nursing home resident (n = 79)., Interventions: Merge research data on circulating free 25(OH)D (directly-measured immunoassay), total 25(OH)D (liquid chromatography/tandem mass spectrometry), D-binding protein [DBP; by radial (polyclonal) immunodiffusion assay], albumin, creatinine, intact parathyroid hormone, and DBP haplotype., Main Outcome Measures: Distribution of free 25(OH)D (ANOVA with Bonferroni correction for post hoc comparisons) and relationships between free and total 25(OH)D (mixed-effects modeling incorporating clinical condition, DBP haplotype with sex, race, estimated glomerular filtration rate (eGFR), body mass index (BMI), and other covariates)., Results: Free 25(OH)D was 4.7 ± 1.8 pg/mL (mean ± SD) in healthy persons and 4.3 ± 1.9 pg/mL in outpatients, with levels of 0.5 to 8.1 pg/mL and 0.9 to 8.1 pg/mL encompassing 95% of healthy persons and outpatients, respectively. Free 25(OH)D was higher in patients with cirrhosis (7.1 ± 3.0 pg/mL; P < 0.0033) and nursing home residents (7.9 ± 2.1 pg/mL; P < 0.0033) than in other groups and differed between whites and blacks (P < 0.0033) and between DBP haplotypes (P < 0.0001). Mixed-effects modeling of relationships between free and total 25(OH)D identified clinical conditions (patients with cirrhosis > nursing home residents > patients with prediabetes > outpatients > pregnant women) and BMI (lesser effect) as covariates affecting relationships but not eGFR, sex, race, or DBP haplotype., Conclusions: Total 25(OH)D, health condition, race, and DBP haplotype affected free 25(OH)D, but only health conditions and BMI affected relationships between total and free 25(OH)D. Clinical importance of free 25(OH)D needs to be established in studies assessing outcomes.

The antiresorptive potency varies between different bisphosphonates. We investigated the effect of stopping oral bisphosphonate treatment for postmenopausal osteoporosis (ibandronate, alendronate, risedronate) on BTMs and BMD. After stopping treatment, all three groups showed an increase in BTMs and a decrease in hip BMD; however, none returned to pre-treatment baseline values., Introduction: Bisphosphonates (BPs) continue to suppress bone turnover markers (BTMs) after treatment has stopped, leading to the suggestion that a pause in treatment could be considered for low-risk patients. Indirect comparisons suggest that after cessation of treatment, the effects on bone may differ between drugs. We investigated the effects of stopping oral BP treatments for postmenopausal osteoporosis on BTMs and bone mineral density (BMD)., Methods: We studied postmenopausal osteoporotic women who had previously taken part in a 2-year randomised study of three oral BPs (ibandronate, alendronate, or risedronate). At the end of the study, women with hip BMD T-score > - 2.5 and considered clinically appropriate to discontinue treatment were invited to participate in a further 2-year observational study. Biochemical response was assessed using BTMs, and BMD was measured by dual-energy X-ray absorptiometry., Results: All BTMs increased after treatment withdrawal but remained below the pre-treatment baseline with less suppression of BTMs for the risedronate group compared to alendronate and ibandronate up to 48 weeks. There was no difference between the BP groups 96 weeks after stopping treatment. The change in BMD during the 96 weeks after stopping treatment was - 1.6% (95% CI - 1.9 to - 1.2, P < 0.001) for the total hip and - 0.6% (95% CI - 1.1 to - 0.2, P = 0.17) at the lumbar spine with no difference between the three BP groups (P = 0.85 and P = 0.48, respectively)., Conclusion: For all treatment groups, there was an increase in BTMs and a decrease in hip BMD after stopping BPs for 2 years; however, none returned to pre-treatment baseline values.

Context: Treatment of postmenopausal osteoporosis with teriparatide parathyroid hormone amino terminal 1-34 increases bone formation and improves bone microarchitecture. A possible modulator of action is periostin. In vitro experiments have shown that periostin might regulate osteoblast differentiation and bone formation through Wnt signaling. The effect of teriparatide on periostin is not currently known., Objectives: To determine the effect of teriparatide treatment on circulating levels of periostin and other regulators of bone formation and investigate how changes in periostin relate to changes in bone turnover markers, regulators of bone formation, and bone mineral density (BMD)., Participants and Design: Twenty women with osteoporosis; a 2-year open-label single-arm study., Intervention: Teriparatide 20 µg was administered by subcutaneous injection daily for 104 weeks. Periostin, sclerostin, and Dickkopf-related protein 1, procollagen type I N-terminal propeptide (PINP), and C-telopeptide of type I collagen were measured in fasting serum collected at baseline (two visits) and then at weeks 1, 2, 4, 12, 26, 52, 78, and 104. BMD was measured at the lumbar spine, total hip, and femoral neck using dual energy x-ray absorptiometry., Results: Periostin levels increased by 6.6% [95% confidence interval (CI), -0.4 to 13.5] after 26 weeks of teriparatide treatment and significantly by 12.5% (95% CI, 3.3 to 21.0; P < 0.01) after 52 weeks. The change in periostin correlated positively with the change in the lumbar spine BMD at week 52 (r = 0.567; 95% CI, 0.137 to 0.817; P < 0.05) and femoral neck BMD at week 104 (r = 0.682; 95% CI, 0.261 to 0.885; P < 0.01)., Conclusions: Teriparatide therapy increases periostin secretion; it is unclear whether this increase mediates the effect of the drug on bone.

Bone turnover markers (BTMs) are useful in clinical practice as they are inexpensive, and they have proven useful for treatment monitoring and identification of poor adherence. BTMs cannot be used in individual patients for identifying accelerated bone loss or an increase in fracture risk or in deciding on the optimal therapy. They are useful for monitoring both anti-resorptive and anabolic treatment. Response can be defined as a result that exceeds an absolute target, or by a change greater than the least significant change; if such a response is not present, then poor compliance or secondary osteoporosis are likely causes. A baseline BTM measurement is not always made; in that case, a value of BTM on anti-resorptive treatment that is low or low normal or above the reference interval for anabolic therapy may be taken to indicate a satisfactory response. We provide an approach to using these bone turnover markers in clinical practice by describing algorithms for anti-resorptive and anabolic therapy and describing the changes we observe in the clinical practice setting., (© 2018 European Society of Endocrinology.)

Bisphosphonates are used to treat bone disease characterised by increased bone resorption by inhibiting the activity of mature osteoclasts, resulting in decreased bone turnover. Bisphosphonates may also reduce the population of osteoclast precursor cells. Our aims were to investigate the effect of bisphosphonates on i) osteoclast precursor cells and ii) circulating cytokine and cytokine receptor in postmenopausal women with osteoporosis compared with healthy premenopausal women. Participants were 62 postmenopausal women (mean age 66) from a 48-week parallel group trial of bisphosphonates. They received ibandronate 150mg/month (n=22), alendronate 70mg/week (n=19) or risedronate 35mg/week (n=21). Fasting blood was collected at baseline, weeks 1 and 48. At baseline, blood was also collected from 25 healthy premenopausal women (mean age 37) to constitute a control group. Peripheral blood mononuclear cells were extracted and stained for CD14, M-CSFR, CD11b and TNFRII receptors. Flow cytometry was used to identify cells expressing CD14 + and M-CSFR + or CD11b + or TNFRII + . RANKL and OPG were measured to evaluate potential mediation of the bisphosphonate effect. After 48weeks of treatment, there was a decrease in the percentage of cells expressing M-CSFR and CD11b receptors by 53% and 49% respectively (p<0.01). Cells expressing M-CSFR and CD11b were decreased with ibandronate and risedronate after 48weeks to the lower part of the premenopausal reference interval. These effects were not significantly different between each of the treatment groups. There was no significant effect on RANKL and OPG throughout the study period. Bisphosphonates inhibit bone resorption in the short-term by direct action on mature osteoclasts. There is also a later effect mediated in part by a reduction in the population of circulating osteoclast precursors., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Unlabelled: We used two methods of identifying women who reached the target for raloxifene treatment with bone turnover markers. Both approaches identified women that responded to treatment but did not fully agree and may be complementary., Introduction: The change in bone turnover markers (BTMs) in response to osteoporosis therapy can be assessed by a decrease beyond the least significant change (LSC) or below the mean of the reference interval (RI). We compared the performance of these two approaches in women treated with raloxifene., Methods: Fifty postmenopausal osteopenic women (age 51-72 years) were randomised to raloxifene or no treatment for 2 years. Blood samples were collected for the measurement of BTM. The LSC for each marker was calculated from the untreated women and the RI obtained from healthy premenopausal women (age 35-40 years). Bone mineral density (BMD) was measured at the spine and hip., Results: There was a decrease in BTM in response to raloxifene treatment, percentage change at 12 weeks: C terminal telopeptide of type I collagen (CTX) -39 % (95 % CI -48 to -28) and N terminal propeptide of type I procollagen (PINP) -32 % (95 % CI -40 to -23) P < 0.001. The proportion of women classified as responding to treatment using LSC at 12 weeks was as follows: CTX 38 % and PINP 52 % and at 48 weeks CTX 60 % and PINP 65 %. For the RI approach, the proportion of women classified as responding to treatment at 12 weeks was CTX and PINP 38 % and at 48 weeks CTX 40 % and PINP 45 %. There was a significant difference in the change in spine BMD in the raloxifene-treated group compared to the no-treatment group at week 48: difference 0.031 g/cm(2) (95 % CI 0.016 to 0.046, P < 0.001)., Conclusions: The two approaches identified women that reached the target for treatment using BTM. Both LSC and RI criteria appear useful in identifying treatment response, but the two approaches do not fully overlap and may be complementary.

Background: The mechanism and clinical significance of low circulating 25-hydroxyvitamin D [25(OH)D] in obese people are unknown. Low total 25(OH)D may be due to low vitamin D-binding proteins (DBPs) or faster metabolic clearance. However, obese people have a higher bone mineral density (BMD), which suggests that low 25(OH)D may not be associated with adverse consequences for bone., Objective: We sought to determine whether 1) vitamin D metabolism and 2) its association with bone health differ by body weight., Design: We conducted a cross-sectional observational study of 223 normal-weight, overweight, and obese men and women aged 25-75 y in South Yorkshire, United Kingdom, in the fall and spring. A subgroup of 106 subjects was also assessed in the winter. We used novel techniques, including an immunoassay for free 25(OH)D, a stable isotope for the 25(OH)D3 half-life, and high-resolution quantitative tomography, to make a detailed assessment of vitamin D physiology and bone health., Results: Serum total 25(OH)D was lower in obese and overweight subjects than in normal-weight subjects in the fall and spring (geometric means: 45.0 and 40.8 compared with 58.6 nmol/L, respectively; P < 0.001) but not in the winter. Serum 25(OH)D was inversely correlated with body mass index (BMI) in the fall and spring and in the winter. Free 25(OH)D and 1,25-dihydroxyvitamin D [1,25(OH)2D] were lower in obese subjects. DBP, the DBP genotype, and the 25(OH)D3 half-life did not differ between BMI groups. Bone turnover was lower, and bone density was higher, in obese people., Conclusions: Total and free 25(OH)D and 1,25(OH)2D are lower at higher BMI, which cannot be explained by lower DBP or the shorter half-life of 25(OH)D3 We speculate that low 25(OH)D in obesity is due to a greater pool of distribution. Lower 25(OH)D may not reflect at-risk skeletal health in obese people, and BMI should be considered when interpreting serum 25(OH)D as a marker of vitamin D status., (© 2016 American Society for Nutrition.)

Unlabelled: We used bone turnover markers to identify women who responded to bisphosphonate treatment for osteoporosis. Response was more likely with alendronate and ibandronate than risedronate. There was a greater decrease in bone markers if baseline bone turnover markers were higher and if the patient took more than 80 % of her medication., Introduction: Biochemical response to bisphosphonate therapy can be assessed using either a decrease in bone turnover marker beyond the least significant change (LSC) or a reduction to within a reference interval (RI). We compared the performance of these target responses and determined whether response was related to the type of bisphosphonate, compliance and baseline bone turnover markers., Methods: Biochemical responses to three oral bisphosphonates were assessed in an open, controlled trial comprising 172 postmenopausal osteoporotic women (age 53-84 years), randomised to alendronate, ibandronate or risedronate, plus calcium and vitamin D supplementation for 2 years. The LSC for each marker was derived within the study population, whereas RIs were obtained from a control group of healthy premenopausal women (age 35-40 years)., Results: Over 70 % of women achieved a target response for serum CTX and PINP, irrespective of the approach used. The percentage decrease at 12 weeks was greater for women with baseline PINP above the RI -63 % (difference 13 %, 95 % CI 0 to 27.1, P = 0.049) and good compliance -67 % (difference 15.9 %, 95 % CI 6.3 to 25.5, P = 0.001). Responders had a greater increase in spine bone density compared to nonresponders; for example 6.2 vs. 2.3 % (difference 3.9 %, 95 % CI 1.6 to 6.3, P = 0.0011) for PINP LSC. The magnitude of change in bone markers was greater with ibandronate and alendronate than risedronate., Conclusions: Both approaches to response identified similar proportions of women as responders. Nonresponders had smaller increases in BMD, and we suggest that biochemical assessment of response is a useful tool for the management of women with postmenopausal osteoporosis.

Bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) is used for clinical assessment of fracture risk; however, measurements that incorporate bone strength could improve predictive ability. The aim of this study was to determine whether bone strength derived from finite element (FE) analysis was associated with hip fracture risk in a longitudinal study. We studied 728 women (mean age 82 years), 182 with subsequent hip fracture. FE models were generated from baseline DXA scans of the hip to determine femoral bone strength and load-to-strength ratio (LSR). The baseline LSR was significantly higher in fracture cases (median 1.1) compared with controls (0.7, p < 0.0001). Femoral strength and BMD were also significantly lower in cases (median 1820 N, 0.557 g/cm(2)) compared with controls (2614 N, 0.618 g/cm(2) ) both p < 0.0001. Fracture risk increased per standard deviation decrease in femoral strength (odds ratio [OR] = 2.2, 95% confidence interval [CI] 1.8-2.8); femoral neck (FN) BMD (OR = 2.1, 95% CI 1.7-2.6); total hip BMD (OR = 1.8, 95% CI 1.5-2.1); and per SD increase in LSR (OR = 1.8, 95% CI 1.5-2.1). After adjusting for FN BMD, the odds ratio for femoral strength (OR = 1.7, 95% CI 1.2-2.4) and LSR (OR = 1.4, 95% CI 1.1-1.7) remained significantly greater than 1. The area under the curve (AUC) for LSR combined with FN BMD (AUC 0.69, 95% CI 0.64-0.73) was significantly greater than FN BMD alone (AUC 0.66, 95% CI 0.62-0.71, p = 0.004). Strength and LSR remained significant when adjusted for prevalent fragility fracture, VFA, and FRAX score. In conclusion, the DXA-based FE model was able to discriminate incident hip fracture cases from controls in this longitudinal study independently from FN BMD, prior fracture, VFA, and FRAX score. Such an approach may provide a useful tool for better assessment of bone strength to identify patients at high risk of hip fracture who may benefit from treatment to reduce fracture risk., (Copyright © 2013 American Society for Bone and Mineral Research.)

Raloxifene increases bone mineral density (BMD) and decreases vertebral fracture risk; the effects on quantitative ultrasound (QUS) variables, however, have been less well studied. We aimed to further evaluate the effectiveness of QUS for monitoring raloxifene treatment and withdrawal effects. Osteopenic, postmenopausal women (age=50-80 yr, n=125), who completed a 96-wk study (phase A) evaluating treatment compliance or monitoring, were invited to participate in a 96-wk raloxifene withdrawal study (phase B). Those originally receiving treatment were then randomized to continue on raloxifene (60 mg/d)+calcium (500 mg/d) (n=23) or to discontinue raloxifene and take placebo+calcium (500 mg/d) (n=23). Previously untreated women remained untreated (n=12). Yearly QUS and BMD measurements were performed. At the end of phase A, lumbar spine BMD (p=0.005), amplitude-dependent speed of sound (Ad-SoS) (p=0.006) and average SoS (p=0.040) decreased in untreated women but remained stable in treated women. Significant changes in Ad-SoS and ultrasonic bone profiler index had occurred in treated women by the end of phase B (p<0.01). All variables, except bone transmission time, were higher for those receiving any raloxifene treatment (p<0.05). Until further knowledge has been acquired, QUS measurement variables should only be used in conjunction with BMD when assessing changes in bone because of raloxifene therapy., (Copyright © 2010 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

There is evidence to suggest accelerated bone loss following estrogen cessation. The effect of cessation of raloxifene therapy on bone turnover is unknown. Our aim was to determine the effect of cessation of raloxifene treatment on bone turnover and bone mineral density (BMD) in postmenopausal, osteopenic women. Women aged 50 to 80 years received raloxifene for 96 weeks and were then randomized to continue raloxifene (group 1, n=20) or placebo (group 2, n=20) for a further 96 weeks. A third group (group 3, n=14) received no treatment. Bone turnover markers and bone density (BMD) were measured throughout the study. Raloxifene treatment for 96 weeks resulted in a decrease in bone turnover (PINP by 31%) and an increase in spine BMD (by 2%) but no change in hip BMD for groups 1 and 2. Continuation of raloxifene (group 1) maintained these changes. Following cessation of raloxifene (group 2), bone markers returned to baseline levels (by 120 weeks). Hip BMD was decreased by 2% at 192 weeks compared to baseline. Bone markers in the controls (group 3) remained at the upper limit of the reference range throughout, with decreases in BMD of 2.3% (spine) and 2.8% (hip). Bone loss following cessation of raloxifene therapy at 96 weeks was greater than in the control group, suggesting accelerated bone loss. The beneficial effect on bone turnover of 96 weeks of raloxifene was lost 6 months after cessation of treatment.

Osteoprotegerin (OPG) is a soluble decoy receptor that inhibits bone resorption by binding to receptor activator of nuclear factor kappa B ligand. Murine studies suggest that OPG is elevated in pregnancy, but its role in human pregnancy is unknown. We evaluated the relationship among OPG, bone turnover, and bone density in a longitudinal study of planned human pregnancy and lactation (n = 17; age, 20-36 yr). Samples were collected before conception; at 16, 26, and 36 wk gestation; and at 2 and 12 wk postpartum. Indexes of bone resorption included serum beta C-terminal and urinary N-terminal (uNTX) telopeptides of type I collagen. OPG increased by 110 +/- 16% (mean +/- SEM) at 36 wk (P < 0.001), followed by a rapid postpartum decline in both lactating and nonlactating women. Bone resorption was elevated at 36 wk (serum beta C-terminal telopeptides by 76 +/- 17%; urinary N-terminal telopeptides by 219 +/- 41%; P < 0.001). The tissue source of OPG in pregnancy is unknown. Human breast milk contains large amounts of OPG (162 +/- 58 ng/ml in milk vs. 0.42 +/- 0.03 ng/ml in nonpregnant serum). However, the rapid postpartum decline in serum OPG and the low serum OPG in neonates suggest a placental source. There was no correlation between change in OPG and bone turnover or bone mineral density (P > 0.05), and the physiological importance of elevated OPG in human pregnancy remains uncertain.

Unlabelled: The effect of season on bone turnover is controversial. No information is available on seasonality of new serum markers of bone resorption. In this study, we have been unable to confirm findings of a marked wintertime increase in bone formation and resorption within the general population. Seasonality was assessed by cosinor analysis., Introduction: We investigated the effect of season on seven markers of bone turnover in a longitudinal study (six men and six premenopausal women; age, 24-44 years) and a separate large population-based multicenter European study (n = 2780 women, Osteoporosis and Ultrasound Study [OPUS])., Materials and Methods: Measurements included serum Crosslaps, procollagen type I N-terminal propeptide (PINP), osteocalcin (OC), and the N-telopeptide fragment of type I collagen in urine (NTX). Seasonality was assessed by cosinor analysis with Hotelling's T2 test., Results: Serum 25(OH) vitamin D showed a marked seasonal rhythm. There was no significant seasonal component for any marker of bone turnover in the longitudinal analysis (cosinor analysis, p > 0.05). The percentage of within subject variance accounted for by any seasonal trend was very small for all markers (less than 2.5%). Less than 1% of the between-person variance was accounted for by seasonality in the cross-sectional analysis for all markers (n = 2780). There was a small but statistically significant summertime increase in OC and PINP in the healthy postmenopausal population after exclusions based on disease or medication use (remaining n = 1226, amplitudes 5.6% and 5.4%, respectively, p < 0.001)., Conclusions: We have been unable to confirm findings of a marked wintertime increase in bone formation and resorption within the general population. The absence of marked seasonality was irrespective of age, menopausal status, reported supplemental Vitamin D intake, age or geographical location. The small but statistically significant summertime increase in bone formation in this and other studies is unlikely to confound clinical interpretation of these measurements.

Past research has revealed that women, working or not, perform more family labor (i.e., housework and child care) than do men. Yet, women often do not perceive this as unfair. Drawing on the theoretical work of L. Thompson (1991) and B. Major (1993), the authors hypothesized that this paradox might be explained by women perceiving greater fairness in the lopsided division of family work (a) when they compare the amount of family work they do with other women (who perform similar amounts) rather than with the spouse; (b) when they enjoy performing family work; and/or (c) when they and their spouses believe that they are especially competent at family work. Data from a 3-panel, longitudinal study of married couples expecting their first child were consistent with the second and third predictions but not the first. Further, prospective analyses suggested that perceiving inequity in family work leads wives and husbands to make more frequent comparisons with the spouse and sometimes with same-sex others.

Objective: To evaluate the anabolic effect of oestrogen on bone by comparing the response of markers of bone formation (and resorption) and bone mineral density (BMD) to subcutaneous oestradiol implants., Design: One year double-blind placebo controlled randomised study., Setting: Clinical research unit within a teaching hospital., Population: Twenty-one hysterectomised postmenopausal women were randomised to 25 mg oestradiol implants at baseline and at six months or to have a sham procedure at baseline and six months., Methods: BMD and quantitative ultrasound (QUS) were assessed at baseline and one year. Bone alkaline phosphatase (bone ALP), procollagen type I N-terminal propeptide (PINP), osteocalcin (OC), free deoxypyridinoline (iFDPD), N-telopeptide of type I collagen (NTX), serum oestradiol and intact parathyroid hormone (PTH) were measured at baseline, 4, 8, 12 and 24 weeks., Main Outcome Measures: Percentage change markers of bone turnover and PTH and change in oestradiol levels over first six months and percentage of changes in DXA and QUS over one year., Results: PINP, bone ALP and OC increased by 28%, 7% and 9%, respectively (P < 0.01) during the first four weeks of treatment and then decreased significantly. Lumbar spine (LS) and total hip (TH) BMD increased by 5.4% and 6.0% (P < 0.001), respectively, and femoral neck (FN) BMD by 3.7% (P < 0.05) during the first year of treatment compared with control subjects. The peak serum oestradiol level was achieved four weeks after implant insertion. Mean PTH levels increased significantly in subjects receiving subcutaneous oestradiol., Conclusion: Subcutaneous oestrogen exerted an apparent anabolic effect on bone, which was initially reflected by an increase in bone formation markers and later by a large increase in BMD.

Data are presented on the whole-body retention of 133Ba (half-life 10.74 y), over periods of up to 13 y after injection into six healthy male volunteers aged 25-81, and on their levels of biochemical markers for bone turnover. The results are relevant to propositions underlying the ICRP's current (Publication 67) and former (Publication 20) models of alkaline earth metabolism. The tracer was predominantly skeletal within weeks of the injection, as predicted in the current model. The mean retention accorded satisfactorily throughout with predictions based on the current model, but this accord does not necessarily validate the model, for two reasons. First, parameter values attributed to barium were influenced by data emerging during the early years of this study. Second, bone resorption rates in these subjects, as indicated by urinary markers, appear insufficient to explain the long-term reductions in skeletal retention which, in the present model, arise exclusively through this mechanism.

During pregnancy, the mother adapts to meet the calcium demands of the fetus. The effect of this adaptation on the maternal skeleton is not fully understood. Our objectives were to evaluate changes in bone mineral density (BMD) and bone turnover during pregnancy. We studied 16 women longitudinally, with baseline measurements before pregnancy; then at 16, 26, and 36 weeks of pregnancy; and postpartum. We measured total-body BMD and biochemical markers of bone resorption (urinary pyridinium crosslinks and telopeptides of type I collagen) and bone formation (serum bone alkaline phosphatase, propeptides of type I procollagen [PINP] and osteocalcin). We also measured parathyroid hormone (PTH), insulin-like growth factor I (IGF-I), and human placental lactogen. Postpartum, BMD increased in the arms (2.8%, P < 0.01) and legs (1.9%, P < 0.01) but decreased in the pelvis (-3.2%, P < 0.05) and spine (-4.6%, P < 0.01) compared with prepregnancy values. All biochemical markers, with the exception of osteocalcin concentration, increased during pregnancy. The change in IGF-I at 36 weeks was related to the change in biochemical markers (e.g., PINP, r = 0.72, P = 0.002). Pregnancy is a high-bone-turnover state. IGF-I levels may be an important determinant of bone turnover during pregnancy. Elevated bone turnover may explain trabecular bone loss during pregnancy.

Total parenteral nutrition is associated with osteopenia in preterm infants. Insufficient calcium and phosphate are likely causes: aluminum contamination is another possible contributing factor as this adversely affects bone formation and mineralization. The study was designed to evaluate changes in biochemical markers of bone turnover in 22 preterm infants receiving total parenteral nutrition in comparison with 19 term infants. We collected urine and serum samples from 22 preterm infants, mean gestational age 29 wk, within 48 h and again at 3 wk of life. We also collected urine samples from 19 term infants, mean gestational age 39 wk, during the first day of life. Bone resorption was assessed by the measurement of urinary pyridinium cross-links by HPLC and ELISA and the N-telopeptide of type I collagen by ELISA. Bone formation was assessed in premature infants by the measurement of serum osteocalcin. The N-telopeptide of type I collagen was higher in the preterm infants compared with term at baseline (p < 0.01). There was no difference between the pyridinium cross-links in the preterm and term infants. All the biochemical markers of bone turnover increased significantly in the preterm infants during the first 3 wk of life, e.g. N-telopeptide was a 153% change from baseline (p < 0.001). Aluminum in the total parenteral nutrition solutions did not cause a decrease in bone formation at the level administered (3-6 microg, 0.1-0.2 micromol x kg(-1) x d(-1)).

Methods: Subjects were 102 self-identified gay, lesbian, and bisexual youth aged 18-23 years. A confidential self-administered survey elicited demographic information, sexual orientation information, health care experiences, subjects' understanding of medical confidentiality during ages 14-18 years, and their suggestions for improving care to gay and lesbian adolescents., Results: Two-thirds of subjects never discussed sexual orientation with their provider but reported a desire to do so. Fewer than one-half of subjects remembered being informed about their right to medical confidentiality; those who reported being so informed were three times more likely to have discussed their sexual orientation with their provider. Over 70% of subjects who reported not being informed about their right to medical confidentiality stated that they would have been more likely to discuss sexual orientation with their provider had they been so informed. Only 13 of subjects had disclosed their sexual orientation to their health care providers. Of these, only half of the males received information on human immunodeficiency virus prevention., Conclusions: Health care providers may be failing to fully address issues of confidentiality and sexual orientation with adolescents, despite a decade of increased information on adolescent homosexuality.

Background: The number of school-based health centers (SBHCs) has grown from 40 in 1985 to >900 in 1996. During the 1996-1997 school year there were 914 SBHCs, 32% of which were located in elementary schools. Despite the relatively large number of elementary SBHCs in existence, SBHCs serving elementary-aged students are not adequately represented in the literature., Objective: To analyze physical and mental primary health care utilization in a comprehensive elementary SBHC for an underserved Hispanic population., Design: Retrospective analyses of services used at an elementary SBHC during the 1995-1996 school year. We describe physical and mental health services utilization provided by SBHC staff who offered a range of primary medical and mental health services., Patients: The study population was predominately Hispanic, and comprised of 811 elementary school students (grades preschool through fifth) registered for SBHC use. Analyses were conducted on 591 students who used the SBHC., Results: The 591 SBHC users made 2443 visits, ranging between 1 and 54 visits/individual; mean 4 visits/student. Two thirds of visits (1638) were medical provider visits, and 33% (798) were mental health provider visits. Most students (75%) saw a medical provider exclusively, 9% saw a mental health provider exclusively, and 16% of students were seen by both. Mean duration of medical provider visits +/-SD was 15 +/- 13 minutes, mean for mental health provider visits +/-SD, 37 +/- 16 minutes. Of the 3035 diagnoses, 64% were medical and 36% were mental health diagnoses. These diagnostic frequencies are grouped as follows: acute medical (31%), health maintenance (22%), depression (10%), non-Diagnostic and Statistical Manual of Mental Disorders-IV mental health diagnoses (8%), conflict disorder/emotional disturbance (8%), chronic medical (8%), academic/learning disorder (7%), anxiety disorder (3%), and other (4%)., Conclusions: High rates of SBHC utilization by this population and the range of diagnoses recorded suggest health care delivered in a comprehensive, culturally-sensitive SBHC has the potential for impacting the health and well-being of underserved elementary-aged students.

We examined the response of different biochemical markers of bone resorption to bisphosphonate therapy (400 mg of etidronate daily for 6 months) in mild Paget disease (n = 14). Urinary markers included hydroxyproline (OHP), total (T) and free (F) pyridinolines (Pyds) determined by HPLC, immunoreactive FPyds, immunoreactive TPyds, and the N- and C-terminal telopeptides of type I collage (NTx, CL). Serum measurements included tartrate-resistant acid phosphatase (TRAcP) and the C-terminal telopeptide of type I collagen (ICTP). ICTP and TRAcP showed a minimal response to therapy (% change at 6 months, -13.1 +/- 6.8 and -6.7 +/- 3.4, respectively). The response was greatest for urinary telopeptides (NTx and CL; % change -75.7 +/- 7.5 and -73.4 +/- 8.9, respectively). The response was somewhat greater for TPyds than for FPyds. We conclude that: (a) ICTP and TRAcP are unreliable indicators of changes in bone turnover; (b) oligopeptide-bound Pyds and telopeptide fragments of type I collagen in urine show a somewhat greater response to therapy than do FPyds and may be more sensitive indicators of bone resorption; and (c) as yet no evidence suggests that these markers are substantially better predictors of the clinical response to therapy than serum total alkaline phosphatase or urinary OHP. There are several problems with the interpretation of these measurements in Paget disease, and the clinical utility of these measurements remains uncertain.

Severe burns in adults is associated with an uncoupling of normal remodeling, low bone formation without reduced resorption. The risk of osteopenia that may occur under such circumstances is heightened by our detection in a cross-sectional study of low bone mass in severely burned children. We report here the acute histomorphometric and biochemical response of bone to severe burn injury, as well as bone mass in severely burned children. We enrolled 24 patients ages 5.8 to 17.5 years following burns of 63 +/- 16% (SD) body surface area. Serum and urine were collected weekly until iliac crest bone biopsy was obtained 26 +/- 10 days postburn. Seventeen of 18 patients, including 5 patients receiving growth hormone treatment to accelerate wound healing, failed to take up doxycycline in trabecular bone, and had no detectable osteoblasts at the osteoid seam, while eroded surface was normal and osteoblasts were documented by staining. Thus, bone formation was virtually absent. There was an eightfold elevation in urinary free cortisol excretion and high serum levels of acute phase reactants and interleukin-1 beta and -6. Biochemical markers of bone formation, osteocalcin, and type I procollagen propeptide were low, as were resorptive markers urinary pyridinoline and deoxypyridinoline. However, there was no correlation with resorptive surface. Mean age-related z-score for bone mass was -1.06 +/- 1.05, 40 days postburn. Immobilization and endogenous corticosteroid production may be the main factors responsible for acutely reduced bone formation while inflammatory cytokines may mediate resorption.

Over the past two decades, the reported number of women and men who have had intercourse by age 18 has increased by approximately 20%. Concomitant increases occurred in the incidence of teen-age pregnancies and sexually transmitted diseases (STDs), including HIV. Increasing condom availability within schools has been proposed as one means of preventing the serious potential consequences of unprotected sexual intercourse. Although published surveys report 68% to 75% of adults have supported distributing condoms in schools, little is known about what students think about making condoms available at school. In this survey, high school students in Denver initiated and helped conduct a school-wide survey to assess student opinions about condom distribution in their school. Of 931 high school students responding to the survey, 85% replied that condoms should be distributed in their school, and 76% believed making condoms more accessible would not change the frequency of sexual activity among teens.

1 The binding of [(3)H]-oestradiol-17beta (0.08 mug) in the uterus, vagina, liver and heart of immature female rats has been studied in vivo and the effect of daily administrations of the non-steroidal anti-oestrogens, tamoxifen and monohydroxytamoxifen, on the 2 h accumulation of [(3)H]-oestradiol-17beta in the uterus has been determined.2 Doses of tamoxifen (8 mug daily) or monohydroxytamoxifen (1.28 mug daily), which have previously been found to antagonize completely the uterotrophic activity of oestradiol-17beta (0.08 mug daily), did not significantly reduce the total uterine binding of 0.08 mug [(3)H]-oestradiol-17beta administered on day 4 of a 3-day uterine weight test.3 The simultaneous administration of tamoxifen (8 mug) or monohydroxytamoxifen (1.28 mug) with [(3)H]-oestradiol-17beta (0.08 mug) on day 3 of a uterine weight test did not significantly reduce the total uterine binding of oestradiol-17beta. The binding of [(3)H]-oestradiol-17beta was reduced if monohydroxytamoxifen or tamoxifen was administered 4 h before the oestradiol.4 Tamoxifen (8 mug daily) or monohydroxytamoxifen (1.28 mug daily) did not prevent the translocation of [(3)H]-oestradiol (0.08 mug) to the uterine cell nucleus on day 3 of a 3-day uterine weight test.5 The measurement of total nuclear oestrogen receptors by an exchange assay technique demonstrated a higher concentration of oestrogen receptors in anti-oestrogen-treated animals compared with controls.6 Since the administration of anti-oestrogenic doses of non-steroidal anti-oestrogens during a 3-day uterine weight test did not inhibit the total binding of oestradiol in the uterus, or affect the translocation of the steroid to the nucleus, the mechanism of action of non-steroidal anti-oestrogens over the range of the partial agonist dose-response curve must involve an interaction, or competition of oestradiol-17beta- and anti-oestrogen-oestrogen receptor complexes for sites within the nucleus.

The uterotropic and antiuterotrapic effects of a variety of structural derivatives of the nonsteroidal antiestrogen tamoxifen have been determined in the rat and the mouse. One derivative, monohydroxytamoxifen, was found to be a potent antiestrogen in the rat, with a high affinity for the estrogen receptor. Various techniques of sucrose density gradient analysis were used to demonstrate that estradiol and tamoxifen bind to the rat uterine cytoplasmic estrogen receptor. Estrogens and antiestrogens provoke the translocation of estrogen receptors to the nucleus and deplete the cytoplasmic estrogen receptor pool for short or long periods depending on the dose administered. Estradiol stimulates endometrial hyperplasia with an increase in total uterine DNA content, whereas tamoxifen stimulates endometrial hypertrophy with only a slight increase in uterine DNA content. It is concluded that the molecular shape of the ligand that binds to the estrogen receptor determines antiestrogenic activity.