Sarah Pitts

Prevalence and predictive factors for regional osteopenia in women with anorexia nervosa.

Anorexia nervosa is highly prevalent among U.S. women (1, 2) and is associated with substantial bone loss (3-6). Bone loss in women with this disorder is multifactorial; is related in part to estrogen deficiency and to direct effects of undernutrition (3, 4, 7); and is rapid, often occurring within 6 months of disease onset (4) and persisting to some degree after weight recovery (8). It is important to determine the prevalence of regional bone loss at different skeletal sites because it may predict site-specific fracture rates (9). We therefore measured bone mineral density (BMD) at several skeletal sites to determine the prevalence rates and predictive factors of regional osteopenia and osteoporosis in a large community-based sample of women with anorexia nervosa. Methods We studied 130 women with anorexia nervosa recruited through community advertisements and community physician referral. Telephone screening interviews were used to exclude patients who reported normal weight and menses; use of bisphosphonates, calcitonin, or glucocorticoids; or medical conditions other than anorexia nervosa that are known to affect BMD. Women who had regular uterine withdrawal bleeding while receiving estrogen therapy and women with concomitant bulimia nervosa were permitted to participate. Eligible patients underwent a 3-hour outpatient visit at the General Clinical Research Center of the Massachusetts General Hospital in Boston. Height, weight, age at menarche, time since last menstrual period, previous and current estrogen use, fracture history, and frame size were determined. Calcium and vitamin D intake were determined by diet history in a subset of 60 patients. The diagnosis of anorexia nervosa, according to criteria specified in Diagnostic and Statistical Manual of Mental Disorders, fourth edition, was confirmed in all patients (10). All patients gave written consent, as required by the Subcommittee on Human Studies. Bone mineral density at the anteriorposterior lumbar spine (L1L4), lateral spine, left total hip, femoral neck, and greater trochanter was determined with dual-energy x-ray absorptiometry using a Hologic 4500 densitometer (Hologic, Inc., Waltham, Massachusetts) (lumbar spine SD, 0.01 g/cm2) (11). At each skeletal site, patients were categorized as having normal BMD (T-score>1.0 SD), osteopenia (1.0 SD T-score>2.5 SD), or osteoporosis (T-score 2.5 SD), according to World Health Organization criteria. Data on BMD in a subset of 30 patients were published previously (7). Wrist and frame size were determined (12, 13), and body mass index and percentage of ideal body weight were calculated (14). Age at menarche and time since last menstrual period were assessed for all patients. Whenever possible, total duration of amenorrhea since menarche was determined (n =78). Current and previous lifetime estrogen use, including type of estrogen, was quantified and categorized for each patient. We used the MantelHaenszel test to compare BMD at the anteriorposterior and lateral spine, stratifying on patients. Standard least-squares multivariate regression models were constructed for each skeletal site by using age, age at menarche, time since last menstrual period, weight, height, wrist size, and fracture history as covariates. Covariates were chosen in advance as important clinical variables affecting BMD. Adjusted regression coefficients and confidence intervals were determined for each covariate. Data are expressed as the mean SE. The funding source had no role in the collection, analysis, or interpretation of the data or in the decision to submit the paper for publication. Results Clinical data and data on BMD are shown in Table 1. Ninety-eight percent of patients were white and 2% were Asian. Mean T-scores were 1.4 0.1 SD for the anteriorposterior spine, 1.8 0.1 SD for the lateral spine, and 1.4 0.1 SD for the total hip. Twenty-six percent of patients (n =34) reported a history of fracture (foot or ankle [n =6], hand or wrist [n =7], leg [n =1], arm or elbow [n =4], stress fracture [n =5], and other fracture [n =11]). Table 1. Clinical Characteristics of Study Patients and Comparison by Estrogen Use and Menstrual History Osteopenia and osteoporosis, respectively, were seen at the anteriorposterior spine in 50% and 13% of patients, at the lateral spine in 57% and 24% of patients, and at the total hip in 47% and 16% of patients. Normal BMD was seen at the anteriorposterior spine in only 37% of patients, at the lateral spine in 19% of patients, and at the total hip in 37% of patients. Results of lateral and anteriorposterior spinal tests of BMD were discordant in 36 patients, of whom 31 had normal BMD at the anteriorposterior spine (T-score>1.0) but low BMD at the lateral spine (T-score 1.0) (P<0.001). Bone mineral density was reduced by at least 1.0 SD at one or more skeletal sites in 92% of patients and by at least 2.5 SD in 38% of patients. No differences in BMD were observed between patients with anorexia nervosa alone and patients with anorexia nervosa and concomitant bulimia nervosa (P>0.05 at all sites; data not shown). Twenty-three percent of patients were current estrogen users (mean duration, 25.3 5.4 months) and 58% were previous estrogen users (mean duration, 23.9 3.1 months). Bone mineral density did not differ at any site according to current or previous estrogen use (Table 1). Age, body mass index, and age at menarche were similar in the subgroup comparisons according to estrogen status. Oral contraceptives were used in all but 3 of the current estrogen users (10%) and all but 7 of the ever-estrogen users (10%); these 10 women received conjugated estrogen. Similar results were obtained in a subanalysis limited to the patients receiving oral contraceptives (data not shown). Total duration of estrogen use was not correlated with BMD at the anteriorposterior spine, lateral spine, femoral neck, total hip, trochanter, or total body (P>0.10 for all comparisons). Patients with primary amenorrhea (n =7) weighed less and had lower BMD at all sites than patients with secondary amenorrhea (n =123) (Table 1), although sample size was small in the primary amenorrhea group. Total calcium intake was not correlated with BMD at any site (P>0.1 for all sites). Fifty-seven percent of patients were receiving calcium supplements, 53% were receiving a multivitamin containing 400 IU of vitamin D, and 43% were receiving both. Bone mineral density did not differ in patients receiving nutritional supplements (data not shown). Weight was a significant independent predictor of BMD at all skeletal sites (Table 2). Patients with normal BMD, osteopenia, and osteoporosis at the total hip weighed 48.7 0.8 kg, 45.9 0.8 kg, and 39.0 0.7 kg, respectively. Similar trends were seen at other skeletal sites (data not shown). Age at menarche was a significant independent predictor of BMD measured by anteriorposterior spinal densitometry. Time since last menstrual period was a significant predictor of BMD at the anteriorposterior and lateral spine. Our results were similar when we used multivariate regression models with total duration of amenorrhea instead of last menstrual period in patients for whom this information was available (n =78) (data not shown). Table 2. Univariate and Multivariate Regression Analyses Discussion Our data demonstrate the high prevalence and profound degree of site-specific bone loss in women with anorexia nervosa. Our study design had advantages: Patients were recruited from the community and were not preselected for bone loss, and we evaluated bone loss at several skeletal sites. Although weight was highly significant as a predictor of bone loss at all sites, time since last menstrual period and age at menarche were significant predictive factors for BMD at the anteriorposterior spine, suggesting a greater relative influence of estrogen deficiency at this site. Other mechanisms may also contribute to reduced BMD in patients with anorexia nervosa, such as failure to achieve peak BMD, hypercortisolemia, and reduced vitamin D intake (4). However, we did not see any association between calcium or vitamin D intake and BMD. Increased risk for fracture is the major clinical implication of bone loss in women with anorexia nervosa. Fracture risk doubles with each decrease of 1 SD in BMD (9). Our data therefore suggest that patients with anorexia are at a markedly increased risk for fracture at many skeletal sites. A relatively high percentage of patients reported a previous history of fracture, but because radiologic confirmation was not obtained, relative risk for fracture was not determined. Bone mineral density was reduced by at least 1.0 SD at one or more skeletal sites in 97% of women with fractures, but fracture site was not correlated with the location of osteopenia. Although our study was not designed to prospectively investigate the efficacy of estrogen use in women with anorexia nervosa, no effect of previous or current estrogen use on BMD was demonstrated at any skeletal sites. These retrospective data stand in partial contrast to cross-sectional data from a previous study, which suggested an effect of estrogen exposure at the lumbar spine but not at other sites (15). The minimal effect of estrogen exposure on BMD in our study is consistent with that seen in a previous randomized study, which showed no effect of estrogenprogestin replacement therapy on BMD in patients with anorexia nervosa (16). The effectiveness of estrogen in increasing or preserving BMD in women with anorexia nervosa may be mitigated by continued undernutrition, which may act to uncouple bone formation and resorption. We have previously shown that women with anorexia nervosa exhibit low bone formation rates and increased resorption rates (3). Hotta and colleagues (17) have shown that low rates of bone formation in patients with anorexia nervosa increase with feeding, suggesting a mechanism whereby bone formation is reduced by undernutrition and

Percentage Body Fat by Dual-Energy X-Ray Absorptiometry Is Associated With Menstrual Recovery in Adolescents With Anorexia Nervosa

PURPOSE To evaluate mediators of resumption of menses (ROM) in adolescents with anorexia nervosa (AN). METHODS Anthropometrics, body composition by dual-energy X-ray absorptiometry, hormonal studies, and responses to mental health screens were obtained at 6-month intervals for 18 months in 37 adolescents with AN randomized to the placebo arm of a double-blind treatment trial. Outcomes were compared between subjects with menstrual recovery and those without. RESULTS Twenty-four subjects (65%) had ROM. Higher percentage body fat was associated with ROM (odds ratio, 1.19; 95% confidence interval, 1.06, 1.33; p < .01), as was body mass index and percent median body weight. Estradiol ≥30 ng/mL alone did not predict menses (p = .08) but was associated with ROM when coupled with percent mean body weight (odds ratio, 2.49; 95% confidence interval, 1.09, 5.65; p = .03). Changes in leptin, cortisol, and mental health were not associated with return of menses. CONCLUSIONS Percentage body fat may be an additional, useful clinical assessment to follow in caring for adolescents with AN.

Approach to the Adolescent Requesting Contraception

It is essential to develop contraceptive counseling skills given the potential complications associated with an unplanned pregnancy, especially for adolescents. Multiple factors must be considered when reviewing contraceptive options with an adolescent: maturity, finances, access to care and prescriptions, confidentiality, medical risks and benefits, and contraindications to use of certain hormonal agents. Many adolescents will be concerned about the possibility of weight gain or the development of acne associated with the use of certain contraceptive agents. They are usually unaware of the risks of thrombosis, stroke, or adverse bone health effects. Providers must be able to speak to these issues using an evidence-based approach.

Controversies in contraception.

Purpose of review New research is constantly being published regarding hormonal contraceptives and bone health, migraine headaches, thrombosis risk, hypertension, weight gain, and obesity, as well as emergency contraception. At times, these studies can be clarifying, but they can also raise new controversies and questions. It is important for providers to be aware of the emerging issues regarding contraceptive care for adolescent patients. Recent findings Research suggests that Depo-Provera (depot medroxyprogesterone acetate; Pfizer, New York City, New York, USA) and, perhaps, low-dose oral contraceptive pills can have adverse effects on adolescent bone health, although the data demonstrating reversibility of bone loss after discontinuation of these contraceptives are reassuring. Additionally, estrogen-containing contraceptives pose risks for patients, including the onset of or exacerbation of migraine headaches, venous thromboembolism, and hypertension. Depo-Provera has been implicated in weight gain, especially in girls who are already overweight. Obesity may decrease the efficacy of some hormonal contraceptives. Finally, the mechanism of action of emergency contraception is still unknown, although studies continue to suggest that it has primarily preovulatory, not postovulatory, effects. Summary Adolescent health providers need to be aware of the new research and controversies in contraceptive care in order to counsel and care for patients effectively.

A randomized clinical trial of vitamin D supplementation in healthy adolescents.

PURPOSE The most safe and effective dose of vitamin D supplementation for healthy adolescents is currently unknown. The aim of this study was to compare the efficacy of 200 IU versus 1,000 IU of daily vitamin D3 for supplementation in healthy adolescents with baseline vitamin D sufficiency. METHODS We conducted a double-blind, randomized clinical trial. Fifty-six subjects, ages 11-19 years, with baseline vitamin D sufficiency received 1,000 IU or 200 IU of daily vitamin D3 for 11 weeks. Compliance was assessed using MEMS6 Trackcaps and pill counts. RESULTS Fifty-three subjects completed the clinical trial. Subjects in the two treatment arms were similar in terms of age, race, gender, body mass index, and dietary calcium and vitamin D intake. Serum 25(OH)D level in the 200 IU treatment arm was 28.1 ± 6.2 ng/mL at baseline (mean ± SD) and 28.9 ± 7.0 ng/mL at follow-up. In the 1,000 IU treatment arm, 25(OH)D levels were 29.0 ± 7.3 and 30.1 ± 6.6 at baseline and follow-up, respectively. Mean change in 25(OH)D level did not differ significantly between treatment arms (p = .87), nor did mean change in parathyroid hormone, calcium, phosphate, bone turnover markers, fasting glucose, or fasting insulin. CONCLUSIONS In healthy adolescents with baseline vitamin D sufficiency, supplementation with vitamin D3 doses of 200 and 1,000 IU for 11 weeks did not increase serum 25(OH)D levels, with no significant difference observed between treatment arms.

Perspectives of adolescent girls with cystic fibrosis and parents on disease-specific sexual and reproductive health education

Adolescent girls with cystic fibrosis (CF) face significant disease‐specific sexual and reproductive health (SRH) concerns that are not typically addressed in routine clinical care. Additionally, there is a paucity of developmentally appropriate CF‐specific SRH educational resources for this population. The goal of this study was to explore patient and parent attitudes toward SRH educational resources for adolescent girls with CF.

Contraceptive Counseling: Does It Make a Difference?

Approximately half of all pregnancies in the United States are unintended, with adolescents and young adult women being at highest risk [1]. Ninety-five percent of all unintended pregnancies occur in 35% of U.S. womenwho are not using contraception consistently or at all [2]. Prevention of unintended pregnancy requires a multifaceted approach including sexual health education and contraceptive counseling, reducing health disparities, and improving access to effective contraception. The Centers for Disease Control and Prevention recommends that all women be “counseled about the full range and effectiveness of contraceptive options for which they are medically eligible” [1]. However, this does not ensure understanding or adherence. Counseling adolescents to achieve true understanding of a given contraceptive method and to promote adherence can be challenging [3]. There are often confidentiality and access concerns. Knowledge about reproductive physiology and anatomy varies widely among adolescents and young adult women [4]. A teen’s ability to properly use a contraceptive consistently over time and manage minor side effects is also variable. While some adolescents seemingly know which contraceptive they want, this is often driven by misconceptions about certain contraceptives. Providers have the responsibility to dispel myths and guide their patients with evidence-based information. Providers must be careful that bias regarding the efficacy and acceptability of certain forms of contraception does not inappropriately steer them away from or toward certain options [5]. In this issue of the Journal of Adolescent Health, Merki-Feld and Gruber [6] report on the experience of over 1,000 15to 20-yearold Swisswomen considering a combined hormonal contraceptive (CHC), a subgroup from the 11-European country Contraceptive Health Research of Informed Choice Experience (CHOICE) study. A detailed leaflet provided consistent information across study sites with almost all counseling performed by gynecologists (93%). While provider opinion regarding optimal contraceptive options for a given subject was collected, this information was not directly communicated to the participant. Interestingly, if the provider had a preference, women without a preference for a CHC method before counseling typically opted for the provider preferred method, yet 91.2% of participants felt that counseling was “very fair” and “balanced.” Efficacy, menstrual cycle control, ease of use, lower likelihood to forget use, and peer use of a given agent were important considerations for these women.

Advance Provision of Emergency Contraception in an Urban Pediatric Emergency Department

STUDY OBJECTIVE To assess whether a policy and educational intervention in an urban, pediatric emergency department (ED) increases advance provision of emergency contraception (EC) to patients. DESIGN/SETTING/PARTICIPANTS A pre- and post-intervention, retrospective chart review was conducted in an urban, pediatric ED assessing provider care of sexually active female adolescents and young adults. INTERVENTION/MAIN OUTCOME MEASURES: A policy was instituted recommending that ED providers prescribe EC and provide an educational handout to all sexually active female adolescents and young adults. ED providers were educated about EC and this policy. Charts, subsequently reviewed, included sexually active female patients, age 13-21 years, presenting to the ED status post sexual assault, seeking EC, or with an abdominal, gynecologic, or urologic complaint. Students t-tests, Pearsons chi-square and Fishers Exact tests compared pre- and post-intervention provider and patient characteristics and outcomes. RESULTS The mean age of the patient sample was 18.8 years (SD=1.7), 83% were Black or Hispanic, 43% were previously pregnant, 25% reported not using birth control. Last unprotected sexual intercourse was not documented for 87% of patients presenting with medical complaints. There was no difference in the advance prescribing of EC or the provision of the educational handout to patients pre- (3.3%) or post- (5.6%) intervention (P = 0.73). CONCLUSIONS Despite a policy and an educational intervention for providers, little change occurred in advance EC prescribing in an urban, pediatric ED. Additionally, many providers were not documenting last unprotected sexual intercourse, potentially missing an opportunity to treat patients with EC at the time of their visit.

Acceptability of peer clinical observation by faculty members

Most doctors are not observed in the actual practice of medicine after they complete training. Direct observation and feedback are seen as invaluable in learning in most other professions, at formative stages of medical training and in other aspects of academic medicine, yet are not performed at the level of the independently practicing clinician. Creating an opportunity for faculty member development based on observation of clinical practice is needed for continued growth and competence as a clinician.

Conclusion: A Clinical Bone Perspective

This text has reviewed adolescent bone pathophysiology and provided evidence to support strategies to optimize bone mass accrual during this critical developmental period. In this concluding chapter, we attempt to bring these concepts together to illustrate how they play out in day-to-day practice.