Osteoporosis: Gordon CM

Gordon CM, Baim S, Bianchi ML, Bishop NJ, Hans DB, Kalkwarf H, Langman C, Leonard MB, Plotkin H, Rauch F, Zemel BS, Anonymous00043. · Children's Hospital Boston, Boston, MA 02115, USA. · South Med J. · Pubmed #18580718 No free full text.

Abstract: The International Society for Clinical Densitometry periodically holds Position Development Conferences (PDCs) for the purpose of establishing standards and guidelines for the assessment of skeletal health, including nomenclature, indications, acquisition, analysis, quality control, interpretation, and reporting of bone density tests. Topics are selected for consideration according to criteria that include clinical relevancy, uncertainty in the application of medical evidence to clinical practice, and the likelihood of the expert panel to reach a consensus agreement. The first Pediatric PDC was June 20 to 21, 2007 in Montreal, Quebec, Canada. Topics included fracture prediction and definition of osteoporosis in children; dual-energy x-ray absorptiometry (DXA) assessment in children with chronic disease that may affect the skeleton; DXA interpretation and reporting in children and adolescents; and the use of peripheral quantitative computed tomography in children and adolescents. This report describes the methodology and presents the results of this recent PDC.

DiVasta AD, Gordon CM. · Division of Adolescent Medicine, Children's Hospital Boston, Boston, MA 02115, USA. · Adolesc Med Clin. · Pubmed #17030283 No free full text.

Abstract: Adolescence is a crucial period for the accrual of bone density and achievement of peak bone mass. Unique situations can arise during adolescence that place an adolescent at risk for bone loss or the failure to attain appropriate bone mass. Clinicians also are challenged by the limitations of currently available measurement tools to evaluate skeletal status in young patients. This article reviews medical approaches to prevent bone loss in patients with eating disorders and the skeletal effects of specific hormonal contraceptive agents. Adolescent medicine specialists and gynecologists caring for teenagers must recognize the potential implications of these clinical settings on bone health to provide appropriate patient guidance and direct management.

Binello E, Gordon CM. · Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA. · Curr Opin Pharmacol. · Pubmed #14644016 No free full text.

Abstract: Dehydroepiandrosterone is the most abundant adrenal androgen and also functions as a neurosteroid. Serum concentrations decline with age and can serve as a prognostic factor in both critical illnesses and breast cancer progression. Evidence is accruing in support of dehydroepiandrosterone supplementation in adrenal insufficiency, hypopituitarism, osteoporosis, systemic lupus erythematosus, depression and schizophrenia. Research is ongoing at both the basic and the clinical level to elucidate mechanisms of action and establish efficacy and safety, as well as to expand new areas of potential application for this multi-faceted hormone.

Gordon CM, Nelson LM. · Children's Hospital Bone Health Center and Department of Pediatrics, Harvard Medical School, Divisions of Adolescent/Young Adult Medicine and Endocrinology, Children's Hospital, Boston, Massachusetts 02115, USA. · Curr Opin Obstet Gynecol. · Pubmed #14501240 No free full text.

Abstract: PURPOSE OF REVIEW: We present an update on amenorrhea in adolescent girls and young women. Amenorrhea may herald the onset of estrogen deficiency, which can adversely affect peak bone mass and ultimate risk of osteoporosis. RECENT FINDINGS: Adolescence is a critical period for bone accretion. Important modifiable factors that optimize bone accretion during this time are calcium intake, vitamin D, nutrition, and exercise. Another modifiable factor in the hands of the clinician is the prompt recognition and therapy of amenorrhea associated with estrogen deficient states, caused by conditions such as hyperprolactinemia and ovarian failure. An important recent observation is that adolescents with amenorrhea who diet, but who do not meet diagnostic criteria for anorexia nervosa, are nonetheless at significant risk for low bone density. Also, multiple factors contribute to the bone loss experienced by patients with anorexia nervosa, and the associated estrogen deficiency may not be the major contributor. Recent evidence also suggests that the contraceptive depot medroxyprogesterone acetate may contribute to impaired bone accretion. While estrogen/progestin replacement therapy has a clear role in the management of girls and young women with primary ovarian insufficiency, the exact role of this therapy in the amenorrhea associated with anorexia nervosa or exercise remains controversial. SUMMARY: Increasingly, osteoporosis prevention is recognized as an important role for health care providers of adolescent girls and young women. Viewed from this perspective, there is a need for more aggressive evaluation and management of amenorrhea, and research is needed to define sound and cost effective strategies.

Gordon CM. · Department of Pediatrics, Harvard Medical School, and Divisions of Adolescent Medicine and Endocrinology, Children's Hospital, Boston, Massachusetts 02115, USA. · J Womens Health (Larchmt). · Pubmed #12737711 No free full text.

Abstract: Although osteoporosis is usually considered to be a health concern of the elderly, increased attention is being paid to children and adolescents who are at risk for developing this devastating disease. As osteoporosis is a preventable condition with no identified cure, focus has been placed on modifiable areas in a young person's life that may prevent the development of the disease. A child or adolescent's nutrition is an example of such an area. This review examines factors influencing normal bone development and emphasizes the importance of the adolescent years as a time for peak bone accretion. Current methods to evaluate skeletal status are examined, including the challenges that arise in interpreting bone densities in children who have growing bones. Children and adolescents who are at high risk for osteoporosis are discussed, with an emphasis on groups in whom poor nutrition likely mediates bone loss. Two models of malnutrition, anorexia nervosa and the female athlete triad, are discussed, with emphasis on the way in which each has deleterious effects on the adolescent skeleton. The promotion of skeletal health is ultimately the encouragement of good general health principles for all young people. Approaches for working with children and adolescents are reviewed, including literature supporting each strategy.

Gordon CM. · Divisions of Adolescent/Young Adult Medicine and Endocrinology, Children's Hospital, Boston, MA, USA. · J Pediatr Adolesc Gynecol. · Pubmed #11173016 No free full text.

Abstract: Because adolescence is a critical period for acquisition of peak bone mass, adolescent gynecology clinicians can play an important role in promoting and reinforcing skeletal health. Efforts should be focused on maximizing nutrition, exercise, and a normal sex steroid status during these formative years. Close attention should also be given to factors that jeopardize the attainment of peak bone mass: amenorrhea, malnutrition (e.g., anorexia nervosa), use of medications with deleterious effects on bone, and underlying medical conditions that may predispose a young woman to early bone loss. This review places special emphasis on a patient commonly seen in the adolescent and gynecology practice, the female athlete.

Gordon CM, Grace E, Emans SJ, Feldman HA, Goodman E, Becker KA, Rosen CJ, Gundberg CM, LeBoff MS. · Division of Adolescent/Young Adult Medicine, Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA. · J Clin Endocrinol Metab. · Pubmed #12414853 links to  free full text

Abstract: Young women with anorexia nervosa (AN) have subnormal levels of dehydroepiandrosterone (DHEA) and estrogen that may be mechanistically linked to the bone loss seen in this disease. The purpose of this study was to compare the effects of a 1-yr course of oral DHEA treatment vs. conventional hormonal replacement therapy (HRT) in young women with AN. Sixty-one young women were randomly assigned to receive oral DHEA (50 mg/d) or HRT (20 micro g ethinyl estradiol/0.1 mg levonorgestrel). Anthropometric, nutrition, and exercise data were acquired every 3 months, and bone mineral density (BMD) and body composition were measured by dual energy x-ray absorptiometry (DXA) every 6 months over 1 yr. Serum samples were obtained for measurements of hormones, proresorptive cytokines, and bone formation markers, and urine was collected for determinations of bone resorption markers at each visit. In initial analyses, total hip BMD increased significantly and similarly (+1.7%) in both groups. Hip BMD increases were positively correlated with increases in IGF-I (r = 0.44; P = 0.030) and the bone formation marker, bone-specific alkaline phosphatase increased significantly only in the DHEA treatment group (P = 0.003). However, both groups gained significant amounts of weight over the year of therapy, and after controlling for weight gain, no treatment effect was detectable. There was no significant change in lumbar BMD in either group. Both bone formation markers, bone-specific alkaline phosphatase and osteocalcin, increased transiently at 6-9 months in those subjects receiving DHEA compared with the estrogen-treated group (P < 0.05). Both DHEA and HRT significantly reduced levels of the bone resorption markers, urinary N-telopeptides (P < 0.05). There was a positive correlation between changes in IGF-I and changes in weight, body fat determined by DXA, and estradiol for both groups. In addition, patients receiving DHEA exhibited improvement on three validated psychological instruments (Eating Attitudes Test, Anorexia Nervosa Subtest, and Spielberger Anxiety Inventory). Both DHEA and HRT had similar effects on hip and spinal BMD. Over the year of treatment, maintenance of both hip and spinal BMD was seen, but there was no significant increase after accounting for weight gain. Compared with HRT, DHEA appeared to have anabolic effects, evidenced by the positive correlation between increases in hip DXA measurements and IGF-I and significant increases in bone formation markers. Both therapies significantly decreased bone resorption. Replicating results from studies of the elderly, DHEA resulted in improvements in specific psychological parameters in these young women.

Lewiecki EM, Gordon CM, Baim S, Binkley N, Bilezikian JP, Kendler DL, Hans DB, Silverman S, Bishop NJ, Leonard MB, Bianchi ML, Kalkwarf HJ, Langman CB, Plotkin H, Rauch F, Zemel BS. · New Mexico Clinical Research & Osteoporosis Center, 300 Oak Street NE, Albuquerque, NM 87106, USA. · Osteoporos Int. · Pubmed #18633664 No free full text.

Abstract: The International Society for Clinical Densitometry (ISCD) conducts Position Development Conferences (PDCs) for the purpose of establishing standards and guidelines in the field of bone densitometry. Topics for consideration are selected according to clinical relevance, a perceived need for standardization, and the likelihood of achieving agreement. Questions regarding nomenclature, indications, acquisition, analysis, quality control, interpretation, and reporting of bone density tests for each topic area are assigned to task forces for a comprehensive review of the scientific literature. The findings of the review and recommendations are then presented to an international panel of experts at the PDC. The expert panel votes on potential Official Positions for appropriateness, necessity, quality of the evidence, strength of the recommendation, and applicability (worldwide or variable according to local requirements). Recommendations that are approved by the ISCD Board of Directors become Official Positions. The first Pediatric PDC was 20-21 June 2007 in Montreal, QC, Canada. The most recent Adult PDC was held 20-22 July 2007, in Lansdowne, VA, USA. This Special Report summarizes the methodology of the ISCD PDCs and presents selected Official Positions of general interest.

Loud KJ, Micheli LJ, Bristol S, Austin SB, Gordon CM. · Division of Adolescent Medicine, Children's Hospital Medical Center, Akron, Ohio, USA. · Pediatrics. · Pubmed #17636110 links to  free full text

Abstract: OBJECTIVE: Increased physical activity and menstrual irregularity have been associated with increased risk for stress fracture among adult women active in athletics. The purposes of this study were to determine whether menstrual irregularity is also a risk factor for stress fracture in active female adolescents and to estimate the quantity of exercise associated with an increased risk for this injury. PATIENTS AND METHODS: A case-control study was conducted of 13- to 22-year-old females diagnosed with their first stress fracture, each matched prospectively on age and self-reported ethnicity with 2 controls. Patients with chronic illnesses or use of medications known to affect bone mineral density were excluded, including use of hormonal preparations that could alter menstrual cycles. The primary outcome, stress fracture in any extremity or the spine, was confirmed radiographically. Girls with stress fracture had bone mineral density measured at the lumbar spine by dual-energy x-ray absorptiometry. RESULTS: The mean +/- SD age of the 168 participants was 15.9 +/- 2.1 years; 91.7% were postmenarchal, with a mean age at menarche of 13.1 +/- 1.1 years. The prevalence of menstrual irregularity was similar among cases and controls. There was no significant difference in the mean hours per week of total physical activity between girls in this sample with stress fracture (8.2 hours/week) and those without (7.4 hours/week). In multivariate models, case subjects had nearly 3 times the odds of having a family member with osteoporosis or osteopenia. In secondary analyses, participants with stress fracture had a low mean spinal bone mineral density for their age. CONCLUSIONS: Among highly active female adolescents, only family history was independently associated with stress fracture. The magnitude of this association suggests that further investigations of inheritable skeletal factors are warranted in this population, along with evaluation of bone mineral density in girls with stress fracture.

Gordon CM, Binello E, LeBoff MS, Wohl ME, Rosen CJ, Colin AA. · Children's Hospital, Division of Endocrinology, Boston, MA 02115, USA. · Osteoporos Int. · Pubmed #16541207 No free full text.

Abstract: INTRODUCTION: Patients with cystic fibrosis (CF) are known to be at risk for early osteoporosis, and the mechanisms that mediate bone loss are still being delineated. The aim of the present investigation was to investigate if a correlation exists in these patients between skeletal measurements by dual-energy x-ray absorptiometry (DXA) and two anabolic factors, dehydroepiandrosterone (DHEA) and insulin-like growth factor I (IGF-I), and proresorptive factors such as the cytokines interleukin-1beta, tumor necrosis factor alpha, and interleukin-6. METHODS: We studied 32 outpatients (18 females; mean age: 26.2+/-7.9 years) at a tertiary care medical center. The subjects had venous samples obtained, underwent anthropometric and bone mineral density (BMD) measurements, and completed a health survey. Serum IGF-I concentrations were below the age-adjusted mean in 78% of the participants, and DHEA sulfate (DHEAS) concentrations were low in 72%. Serum concentrations of all cytokines were on the low side of normal; nonetheless, there was a modest inverse correlation between IL-1beta and BMD at all sites. RESULTS: In univariate analyses, IGF-I and DHEAS were significant correlates of BMD or bone mineral content. In final multivariate models controlling for anthropometric and other variables of relevance to bone density, only IGF-I was identified as a significant independent skeletal predictor. While alterations in DHEAS, IGF-I, and specific cytokines may contribute to skeletal deficits in patients with CF, of these factors a low IGF-I concentration appears to be most strongly correlated with BMD. CONCLUSIONS: These findings may have therapeutic implications for enhancing bone density in these patients.

Stoffman N, Schwartz B, Austin SB, Grace E, Gordon CM. · Division of Adolescent/Young Adult Medicine, Children's Hospital Boston, Boston, Massachusetts 02115, USA. · Int J Eat Disord. · Pubmed #15822087 No free full text.

Abstract: OBJECTIVE: Not reaching an optimal peak bone mass during adolescence puts young patients with anorexia nervosa (AN) at risk for osteoporosis. Qualitative techniques were employed to determine whether having a bone mineral density (BMD) measurement affected the attitudes and behaviors of young women with AN. METHODS: Nineteen adolescents with AN who had undergone BMD measurements were questioned about the experience of having the test and reactions to the results. Themes were identified and statistical analyses were performed. RESULTS: Participants perceived a normal or low BMD in healthy and unhealthy ways. Although not all healthy feelings led to behavioral change, they appeared to serve as driving forces later in their illness. DISCUSSION: Providing young women with BMD results is not always enough to change unhealthy behaviors and may generate some unhealthy thoughts. However, the experience may lead to positive behavioral changes and result in long-term improvement. Clinicians must be careful and sensitive when presenting these results.

Lewiecki EM, Gordon CM, Baim S, Leonard MB, Bishop NJ, Bianchi ML, Kalkwarf HJ, Langman CB, Plotkin H, Rauch F, Zemel BS, Binkley N, Bilezikian JP, Kendler DL, Hans DB, Silverman S. · New Mexico Clinical Research &Osteoporosis Center, 300 Oak Street NE, Albuquerque, NM 87106, USA. · Bone. · Pubmed #18793764 No free full text.

Abstract: The International Society for Clinical Densitometry (ISCD) periodically convenes Position Development Conferences (PDCs) in order to establish standards and guidelines for the assessment of skeletal health. The most recent Adult PDC was held July 20-22, 2007, in Lansdowne, Virginia, USA; the first Pediatric PDC was June 20-21, 2007 in Montreal, Quebec, Canada. PDC topics were selected according to clinical relevancy, perceived need for standardization, and likelihood of achieving agreement. Each topic area was assigned to a task force for a comprehensive review of the scientific literature. The findings of the review and recommendations were presented to adult and pediatric international panels of experts. The panels voted on the appropriateness, necessity, quality of the evidence, strength, and applicability (worldwide or variable according to local requirements) of each recommendation. Those recommendations that were approved by the ISCD Board of Directors become Official Positions. This is a review of the methodology of the PDCs and selected ISCD Official Positions.