Publications by authors named "Catherine M Gordon"

175 Publications

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J Adolesc Health 2021 Jan;68(1):221-222

Geneva, Switzerland.

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http://dx.doi.org/10.1016/j.jadohealth.2020.09.016DOI Listing
January 2021

Is Ovarian Reserve Impacted in Anorexia Nervosa?

J Pediatr Adolesc Gynecol 2020 Dec 3. Epub 2020 Dec 3.

Division of Adolescent Medicine, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.

Study Objectives: Hypothalamic amenorrhea is common in adolescents and young adults (AYAs) with anorexia nervosa (AN), and ovarian reserve is not routinely assessed. AN increases rates of fertility problems, but how or when AN negatively influences future fertility is unclear. We sought to determine whether biomarkers of ovarian reserve were impacted in AYA with AN.

Design: Cross-sectional study.

Setting: Tertiary care center.

Participants: Females with AN and amenorrhea (n = 97) at the pre-intervention visit of a clinical trial, n = 19 females without an eating disorder or menstrual dysfunction.

Main Outcome Measures: Serum anti-Müllerian hormone (AMH) concentrations.

Results: AMH levels were higher in AYA with AN than unaffected adolescents (4.7 vs. 3.2 ng/mL; P = .03). Neither FSH nor inhibin B differed between groups. In 19.6% of participants with AN, AMH levels were elevated above the normal range (>6.78 ng/mL). These subjects had a longer disease duration than those with normal AMH levels (9 vs. 3 mos; P = .03); age or degree of malnutrition did not differ between AN subjects with normal or elevated AMH.

Conclusions: AMH levels appear to be normal or elevated in AYA with AN. Low AMH in a patient with AN should raise clinical concern regarding ovarian reserve, and should not be attributed to degree of malnutrition alone. Currently, AMH is not regularly assessed during routine AN clinical care. However, our findings suggest some clinical utility in identifying those patients with reduced ovarian reserve. Potential links between the hypothalamic amenorrhea suffered by patients with AN and PCOS should be explored.
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http://dx.doi.org/10.1016/j.jpag.2020.11.021DOI Listing
December 2020

The Effects of Ivacaftor on Bone Density and Microarchitecture in Children and Adults with Cystic Fibrosis.

J Clin Endocrinol Metab 2020 Dec 1. Epub 2020 Dec 1.

Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA.

Context: Cystic fibrosis transmembrane conductance (CFTR) dysfunction may play a role in CF-related bone disease (CFBD). Ivacaftor is a CFTR potentiator effective in improving pulmonary and nutritional outcomes in patients with the G551D-CFTR mutation. The effects of ivacaftor on bone health are unknown.

Objective: To determine the impact of ivacaftor on bone density and microarchitecture in children and adults with CF.

Design: Prospective observational multiple cohort study.

Setting: Outpatient clinical research center within a tertiary academic medical center.

Patients Or Other Participants: Three cohorts of age-, race-, and gender-matched subjects were enrolled: 26 subjects (15 adults and 11 children) with CF and the G551D-CFTR mutation who were planning to start or had started treatment with ivacaftor within three months (Ivacaftor cohort); 26 subjects with CF were not treated with ivacaftor (CF Control cohort); and 26 healthy volunteers.

Interventions: All treatments, including ivacaftor, were managed by the subjects' pulmonologists.

Main Outcome Measures: Bone microarchitecture by high resolution peripheral quantitative computed tomography (HR-pQCT), areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) and bone turnover markers at baseline, 1, and 2 years.

Results: Cortical volume, area, and porosity at the radius and tibia increased significantly in adults in the Ivacaftor cohort. No significant differences were observed in changes in aBMD, trabecular microarchitecture, or estimated bone strength in adults or in any outcome measures in children.

Conclusions: Treatment with ivacaftor was associated with increases in cortical microarchitecture in adults with CF. Further studies are needed to understand the implications of these findings.
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http://dx.doi.org/10.1210/clinem/dgaa890DOI Listing
December 2020

Pubertal Growth, IGF-1, and Windows of Susceptibility: Puberty and Future Breast Cancer Risk.

J Adolesc Health 2021 Mar 1;68(3):517-522. Epub 2020 Sep 1.

Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, Ohio.

Purpose: Risk markers for breast cancer include earlier onset of menarche (age at menarche [AAM]) and peak height velocity (PHV). Insulin-like growth factor-1 (IGF-1) is associated with pubertal milestones, as well as cancer risk. This study examined the relationships between pubertal milestones associated with breast cancer risk and hormone changes in puberty.

Methods: This is a longitudinal study of pubertal maturation in 183 girls, recruited at ages 6-7, followed up between 2004 and 2018. Measures included age at onset of puberty, and adult height attained; PHV; AAM; adult height, and serum IGF-1, and estrone-to-androstenedione (E:A) ratio.

Results: PHV was greatest in early, and least in late maturing girls; length of the pubertal growth spurt was longest in early, and shortest in late maturing girls. Earlier AAM was related to greater PHV. IGF-1 concentrations tracked significantly during puberty; higher IGF-1 was related to earlier age of PHV, earlier AAM, greater PHV, and taller adult height. Greater E:A ratio was associated with earlier AAM.

Conclusions: Factors driving the association of earlier menarche and pubertal growth with breast cancer risk may be explained through a unifying concept relating higher IGF-1 concentrations, greater lifelong estrogen exposure, and longer pubertal growth period, with an expanded pubertal window of susceptibility.
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http://dx.doi.org/10.1016/j.jadohealth.2020.07.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902462PMC
March 2021

Adolescents and Bone Health.

Clin Obstet Gynecol 2020 09;63(3):504-511

Division of Endocrinology.

Adolescence is a critical time for the acquisition of peak bone mass. There are modifiable factors that may influence bone health in an adolescent. For those at risk for bone fragility, initial management includes optimization of calcium and vitamin D, weight-bearing exercise, and maintenance of a normal body weight. In certain scenarios, bisphosphonate treatment is indicated, as is reviewed. How hormonal contraceptives affect bone mineral density is unclear, but in patients with risk factors or known bone fragility, prescribers should consider their skeletal effects. Some conditions, including restrictive eating disorders and primary ovarian insufficiency, warrant long-term monitoring of bone health.
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http://dx.doi.org/10.1097/GRF.0000000000000548DOI Listing
September 2020

Lessons Learned in Caring for Adolescents With Eating Disorders: The Singapore Experience.

J Adolesc Health 2020 Jul 8;67(1):5-6. Epub 2020 Apr 8.

Division of Adolescent Medicine, Department of Pediatrics, Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1016/j.jadohealth.2020.03.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141451PMC
July 2020

Diagnosis and Management of Polycystic Ovary Syndrome in Adolescents.

Pediatrics 2020 05;145(Suppl 2):S210-S218

Division of Adolescent/Young Adult Medicine, Harvard Medical School, Harvard University and Boston Children's Hospital, Boston, Massachusetts

Polycystic ovary syndrome (PCOS) is a common female reproductive disorder that often manifests during adolescence and is associated with disruptions in health-related quality of life. Prompt evaluation and clinical support after diagnosis may prevent associated complications and optimize overall health management. This article incorporates the most recent evidence and consensus guidelines to provide an updated review of the pathogenesis, clinical presentation, diagnostic evaluation, and management strategies for adolescents with this complex condition. We will review the recent international guidelines on PCOS; because the diagnosis of PCOS remains controversial, management of this condition is inconsistent. In 2019, PCOS remains a common, yet neglected, condition, in part, because of the lack of agreement around both diagnosis and management.
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http://dx.doi.org/10.1542/peds.2019-2056JDOI Listing
May 2020

Correlation of Functional Magnetic Resonance Imaging Response to Visual Food Stimuli With Clinical Measures in Adolescents With Restrictive Eating Disorders.

J Adolesc Health 2020 Aug 6;67(2):209-217. Epub 2020 Apr 6.

Division of Adolescent/Young Adult Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.

Purpose: Previous reports have shown limbic dysregulation in patients with restrictive eating disorders (EDs). This study investigated functional responses in brain systems to visual food stimuli and their correlation with psychological and behavioral outcomes.

Methods: A total of 18 females, aged 13-18 years, who were diagnosed with anorexia nervosa (n = 11) or atypical anorexia nervosa (n = 7), completed functional magnetic resonance imaging during a visual food paradigm. Stimuli included four food types and one nonfood. Anxiety and disordered eating cognitions were assessed using the State-Trait Anxiety Inventory and Eating Attitude Test (EAT-26). Analyses were performed to obtain contrasts among different food categories and test their correlations with cognitive and behavioral scores.

Results: Contrasts of foods versus nonfood generally resulted in positive responses in occipital regions and negative responses in temporal and parietal gyri. Contrast of sweets versus nonfood, in particular, elicited additional activation in the hippocampus. Contrasting sweet to nonsweet food, the orbitofrontal cortex and anterior cingulate cortex (ACC) were activated. Contrast of all foods versus nonfood had a positive correlation with State-Trait Anxiety Inventory-state scores in the orbitofrontal cortex and ACC. Finally, the sweet versus nonsweet contrast correlated positively with EAT-26 in ACC and other frontal areas.

Conclusions: Visual food stimuli elicited brain responses in limbic centers, and sweet foods extended activation to other limbic domains. Sweet food contrast correlated to EAT-26 in regions comprising the default mode network tied to introspection. Thus, we conclude that visual food stimuli produce activation in limbic-regulating regions in patients with restrictive EDs that correlate with disordered-eating cognitions and behaviors.
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http://dx.doi.org/10.1016/j.jadohealth.2020.01.028DOI Listing
August 2020

DXA in Children and Adolescents.

J Clin Densitom 2021 Jan-Mar;24(1):28-35. Epub 2020 Jan 25.

Boston Children's Hospital, Division of Adolescent/Young Adult Medicine, Boston, MA, USA; Boston Children's Hospital, Division of Endocrinology, Boston, MA, USA; Harvard Medical School, Department of Pediatrics, Boston, MA, USA; DXA Center and Bone Health Program, Boston, MA, USA.

DXA plays a critical role in assessing skeletal health and disease, as well as, fat and muscle status in children and adolescents. Quality DXA requires training, expertise and attention to details, as in adults, but there are key differences in performing and interpretations in children. These include choice of measurement site, skills required, reference data and software, and considerations for indications and underlying disorders to facilitate correct interpretation. The International Society for Clinical Densitometry (ISCD) has been pivotal in establishing official positions and training for people who are interested in performing or interpreting such examinations, and guiding clinicians who may request such studies. However training in the performance and interpretation of scans of individuals with more complex needs falls outside the scope of this review, and consideration should be given to refer such examinations to a specialist pediatric DXA unit. Others may be scanned and reported by those with expertise in densitometry, as long as due diligence is paid to standard quality procedures, as well as knowledge of the special circumstances and training required for this field. In this invited review we outline some of these considerations, highlight key messages, and provide some appropriate references to help guide clinicians, technologists and scientists involved or interested in DXA use in children and adolescents.
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http://dx.doi.org/10.1016/j.jocd.2020.01.006DOI Listing
January 2020

Per- and Polyfluoroalkyl Substance Plasma Concentrations and Bone Mineral Density in Midchildhood: A Cross-Sectional Study (Project Viva, United States).

Environ Health Perspect 2019 08 21;127(8):87006. Epub 2019 Aug 21.

Center for Outcomes Research and Evaluation, Maine Medical Center Research Institute, Portland, Maine, USA.

Background: Identifying factors that impair bone accrual during childhood is a critical step toward osteoporosis prevention. Exposure to per- and polyfluoroalkyl substances (PFASs) has been associated with lower bone mineral density, but data are limited, particularly in children.

Methods: We studied 576 children in Project Viva, a Boston-area cohort of mother/child pairs recruited prenatally from 1999 to 2002. We quantified plasma concentrations of several PFASs and measured areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) in midchildhood. We used linear regression to examine associations between plasma concentrations of individual PFASs and aBMD -score. We used weighted quantile sum (WQS) regression to examine the association of the PFAS mixture with aBMD -score. All models were adjusted for maternal age, education, annual household income, census tract median household income, and child age, sex, race/ethnicity, dairy intake, physical activity, and year of blood draw.

Results: Children were [[Formula: see text]] [Formula: see text] of age. The highest PFAS plasma concentrations were of perfluorooctanesulfonic acid (PFOS) {median [interquartile range (IQR)]: 6.4 (5.6) ng/mL} and perfluorooctanoic acid (PFOA) [median (IQR): 4.4 (3.2) ng/mL]. Using linear regression, children with higher plasma concentrations of PFOA, PFOS, and perfluorodecanoate (PFDA) had lower aBMD -scores [e.g., [Formula: see text]: [Formula: see text]; 95% confidence interval (CI): [Formula: see text], [Formula: see text] per doubling of PFOA]. The PFAS mixture was negatively associated with aBMD -score ([Formula: see text]: [Formula: see text]; 95% CI: [Formula: see text], [Formula: see text] per IQR increment of the mixture index).

Conclusions: PFAS exposure may impair bone accrual in childhood and peak bone mass, an important determinant of lifelong skeletal health. https://doi.org/10.1289/EHP4918.
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http://dx.doi.org/10.1289/EHP4918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6792359PMC
August 2019

BMI, Waist Circumference, and Risk of Incident Vertebral Fracture in Women.

Obesity (Silver Spring) 2019 09 18;27(9):1513-1519. Epub 2019 Jul 18.

Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Objective: The study aimed to investigate the association between BMI, waist circumference, and vertebral fracture (VF) risk in women.

Methods: This prospective study was conducted in 54,934 Nurses' Health Study participants. BMI was assessed biennially, and waist circumference was assessed in the year 2000. Self-reports of VF were confirmed by record review. BMI reflects lean body mass, and waist circumference reflects abdominal adiposity when included in the same regression model.

Results: This study included 536 VF cases (2002 to 2014). Compared with women with BMI of 21.0 to 24.9 kg/m , the multivariable-adjusted relative risk (RR) of VF for women with BMI ≥ 32.0 was 0.84 (95% CI: 0.61-1.14; P  = 0.08). After further adjustment for waist circumference, the multivariable-adjusted RR of VF for women with BMI ≥ 32.0 was 0.70 (95% CI: 0.49-0.98; P  = 0.003). Compared with women with waist circumference < 71.0 cm, the multivariable-adjusted RR of VF for women with waist circumference ≥ 108.0 cm was 1.76 (95% CI: 1.06-2.92; P  = 0.01), and after further adjustment for BMI, the multivariable-adjusted RR of VF was 2.49 (95% CI: 1.44-4.33; P  < 0.001).

Conclusions: Greater lean body mass was independently associated with lower VF risk. Larger waist circumference was independently associated with higher VF risk. These findings suggest that fat distribution is an important predictor of VF and that avoiding central adiposity, as well as maintaining muscle mass, may potentially confer reduced risk of VF in older women.
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http://dx.doi.org/10.1002/oby.22555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707901PMC
September 2019

Impact of Adrenal Hormone Supplementation on Bone Geometry in Growing Teens With Anorexia Nervosa.

J Adolesc Health 2019 10 18;65(4):462-468. Epub 2019 Jun 18.

Division of Adolescent/Young Adult Medicine, Boston Children's Hospital, Boston, Massachusetts; Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts.

Purpose: Adolescents with anorexia nervosa (AN) have decreased dehydroepiandrosterone (DHEA) and estrogen concentrations that may contribute to skeletal deficits. We sought to determine whether DHEA + estrogen replacement (ERT) prevented bone loss in young adolescents with AN.

Methods: We recruited females with AN (n = 70, ages 11-18 years) into a 12-month, randomized, double-blind placebo-controlled trial. Participants were randomized to oral micronized DHEA 50 mg + 20 mcg ethinyl estradiol/.1 mg levonorgestrel daily (n = 35) or placebo (n = 35). Outcomes included serial measures of bone mineral density (BMD) by dual-energy X-ray absorptiometry (total body, hip, spine) and peripheral quantitative computed tomography (pQCT; tibia). Magnetic resonance imaging of T1-weighted images of the left knee determined physeal status (open/closed).

Results: Sixty-two subjects completed the trial. Physeal closure status was the strongest predictor of aBMD changes. Among girls with open physes, those who received DHEA + ERT showed a decline in BMD Z-scores compared with those receiving placebo, whereas there was no effect in those with at least one closed physis. Treatment did not affect any pQCT measures, regardless of physeal closure status.

Conclusions: Combined DHEA + ERT did not significantly improve dual-energy X-ray absorptiometry or pQCT BMD measurements in young adolescent girls with AN, in contrast to an earlier trial showing benefit in older adolescents and young women. In girls with open physes, the mean change in the placebo arm was greater than that of the DHEA + ERT group. We conclude that DHEA + ERT is ineffective for preserving bone health in growing young adolescents with AN at the dose and route of administration described in this report.
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http://dx.doi.org/10.1016/j.jadohealth.2019.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001735PMC
October 2019

Long-term Skeletal Consequences of Anorexia Nervosa: A "Wake up Call".

J Adolesc Health 2019 03;64(3):283-285

Division of Adolescent/Young Adult Medicine, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.

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http://dx.doi.org/10.1016/j.jadohealth.2018.12.008DOI Listing
March 2019

Outcomes following intravenous bisphosphonate infusion in pediatric patients: A 7-year retrospective chart review.

Bone 2019 04 4;121:60-67. Epub 2019 Jan 4.

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, United States; Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, United States.

Introduction: Intravenous bisphosphonates (IV BP) have been used to treat children with osteoporosis for many years. Favorable side effect profile and improvements in bone mineral density (BMD) have been demonstrated in patients with osteogenesis imperfecta (OI), a primary form of osteoporosis in pediatrics. Less is known about the safety of IV BP in children with secondary osteoporosis or glucocorticoid-induced osteoporosis (GIO). We aimed to determine the prevalence of both acute and long-term side effects and assess the efficacy of IV BP treatment to increase bone mineral density in pediatric patients with varying presentations of compromised bone health.

Methods: We conducted a retrospective chart review of pediatric patients (<21 years old) treated for osteoporosis with intravenous pamidronate (PAM) or zoledronic acid (ZA) at Cincinnati Children's Hospital Medical Center from 2010 to 2017. Patient demographics, diagnosis, infusion type and dose, acute phase reactions (APR), electrolyte abnormalities, and bone density measurements were collected from the electronic medical records. Diagnoses were grouped into 3 categories: primary osteoporosis, secondary osteoporosis, and GIO. Descriptive characteristics and adverse events were compared among categories. Change in bone mineral density (BMD) over time was compared among groups.

Results: 123 patients (56% male) received 942 infusions (83% PAM and 17% ZA). APR was reported in 7% of all infusions and more common in secondary osteoporosis (16%, p < 0.0001). There was a higher percentage of acute adverse events after the first infusion (27% vs 5%, p < 0.0001). Hypocalcemia following IV BP infusions occurred in 7% (27/379) of infusions and was significantly associated with ZA use (p = 0.04). Severity of hypocalcemia was generally mild, requiring intravenous calcium in 3% (13/379) of infusions. Hypophosphatemia occurred frequently, however rarely required intravenous supplementation. In 468 patient years of IV BP exposure, there were no reports of osteonecrosis of the jaw (ONJ) nor atypical femoral fracture (AFF). Lumbar spine (LS) aBMD Z-score 1 year after IV BP initiation increased overall for all groups (p < 0.0001) but did not significantly differ for those who did or did not fracture following IV BP treatment.

Conclusions: APR due to intravenous BP treatment for pediatric osteoporosis were infrequent and generally mild. APR were more likely to occur in patients with secondary osteoporosis, a group who may require closer monitoring. A higher proportion of hypophosphatemia occurred in the patients with GIO. Long-term serious adverse events including ONJ and AFF were not identified in our patient population. LS aBMD Z-score increased following initiation of IV BP. However, the change in BMD was not associated with risk of fracture during the follow-up interval. These data provide reassurance and suggest that IV BP can be safely used in pediatric patients with osteoporosis.
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http://dx.doi.org/10.1016/j.bone.2019.01.003DOI Listing
April 2019

Short Communication: Association of Vitamin D Insufficiency and Protective Tenofovir Diphosphate Concentrations with Bone Toxicity in Adolescent Boys and Young Men Using Tenofovir Disoproxil Fumarate/Emtricitabine for HIV Pre-Exposure Prophylaxis.

AIDS Res Hum Retroviruses 2019 02 5;35(2):123-128. Epub 2018 Nov 5.

11 Department of Medicine, University of California at San Francisco, Zuckerberg San Francisco General Hospital, San Francisco, California.

We examined associations of 25-hydroxy vitamin D (25-OHD), tenofovir disoproxil fumarate (TDF), and bone toxicity. We studied TDF/emtricitabine (FTC) HIV pre-exposure prophylaxis (PrEP) in young men who have sex with men (YMSM). Bone toxicity was predefined using bone mineral density/content change from baseline to week 48. Baseline serum 25-OHD was dichotomized as <20 ng/mL (insufficient/deficient) versus ≥20 (sufficient), and week 48 dried blood spot tenofovir diphosphate (TFV-DP) as >700 fmol/punch (protective against HIV acquisition) versus ≤700. Associations were examined by univariate and multivariable logistic regression, reporting crude and adjusted odds ratios (ORs), with 95% confidence intervals (CIs). Of 101 enrolled, 69 had complete bone assessments and 25-OHD; of these, 59 had week 48 TFV-DP data. Median (Q1-Q3) age was 20 (18-21) years; 54% were black/African American. In univariate analysis, participants with baseline 25-OHD <20 ng/mL (OR = 5.4; 95% CI = 1.9-16.5) and blacks (OR = 4.9; 95% CI = 1.7-15.2) had greater odds of bone toxicity than those with 25-OHD ≥20 or other races. TFV-DP was not associated with bone toxicity (OR = 1.6; 95% CI = 0.5-5.5). In multivariable analysis, compared with those with 25-OHD ≥20 and TFV-DP ≤700, those with 25-OHD ≥20 and TFV-DP >700 (OR = 11.5; 95% CI = 1.4-169.6), 25-OHD <20 and TFV-DP ≤700 (OR = 19.4; 95% CI = 3.0-228.7), and 25-OHD <20 and TFV-DP >700 (OR = 32.3; 95% CI = 3.3-653.6) had greater odds of bone toxicity after adjusting for race. In multivariable models, 25-OHD insufficiency, protective TFV-DP concentrations, and black race were significantly associated with bone toxicity after 48 weeks of TDF/FTC PrEP in YMSM. Clinical Trials Registration: NCT01769469.
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http://dx.doi.org/10.1089/AID.2018.0096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360393PMC
February 2019

Tenofovir disoproxil fumarate appears to disrupt the relationship of vitamin D and parathyroid hormone.

Antivir Ther 2018 27;23(7):623-628. Epub 2018 Sep 27.

USDA, Agricultural Research Service, Western Human Nutrition Research Center, Davis, CA, USA.

Background: Tenofovir disoproxil fumarate (TDF) increases serum parathyroid hormone (PTH) and 1,25 dihydroxy vitamin D (1,25-(OH)D), and decreases bone mineral density (BMD). Optimal treatment of TDF-associated BMD loss requires an understanding of the primary cause of these abnormalities.

Methods: Secondary review of data from two studies of TDF use in youth, comparing the relationship of PTH, 25-hydroxy vitamin D (25-OHD) and 1,25-(OH)D in three groups with varying exposures to TDF: youth without HIV enrolled in a trial of TDF/emtricitabine (FTC) for HIV pre-exposure prophylaxis (PrEP) at baseline (no TDF exposure) and after 12 weeks of TDF (short-term TDF exposure); and youth with HIV treated with TDF-containing combination antiretroviral therapy (cART) for at least 6 months at study entry (long-term TDF exposure). Relationships were evaluated by correlation analyses.

Results: Participants ranged in age from 17 to 24 years and >50% were Black/African American. In persons not treated with TDF, PTH had the physiologically appropriate negative correlation with 25-OHD (r=-0.3504, P=0.004). Correlations between PTH and 25-OHD in groups treated with TDF were weaker or absent. With longer term TDF treatment in persons with HIV, 25-OHD and 1,25-(OH)D had the positive correlation similar to that found in vitamin D deficiency.

Conclusions: TDF changes the relationship of 25-OHD to PTH, suggesting that in persons using TDF for PrEP or cART, a higher than usual target for serum 25-OHD concentration might be needed to reduce PTH and optimize bone health.

Clinical Trials Registration: NCT01751646 (ATN 109) and NCT01769469 (ATN 117).
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http://dx.doi.org/10.3851/IMP3269DOI Listing
September 2019

Vitamin D and associated perinatal-neonatal outcomes among extremely low-birth-weight infants.

J Perinatol 2018 10 14;38(10):1318-1323. Epub 2018 Aug 14.

Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Objective: To evaluate vitamin D inadequacy among extremely low-birth-weight (ELBW, <1000 g) infants and the association between circulating vitamin D concentrations and perinatal-neonatal outcomes.

Study Design: Prospective cohort study of ELBW infants in the neonatal ICU. Blood was collected within the first 3 days after birth after obtaining informed consent. Circulating 25-hydroxyvitamin D concentrations (25(OH)D) were quantified using liquid chromatography-tandem mass spectroscopy and classified as vitamin D deficient, insufficient, or adequate ( < 20, 20-30, or > 30 ng/mL, respectively). Associations between 25(OH)D and perinatal-neonatal outcomes were determined by multivariable regression, adjusted for covariates that differ in the bivariate analysis.

Results: Of the 60 ELBW infants enrolled, 13 (22%) were vitamin D deficient, 15 (25%) were insufficient, and 32 (53%) were adequate. 25(OH)D levels were positively associated with fetal growth restriction and prolonged rupture of the membranes.

Conclusions: Vitamin D inadequacy was frequent among ELBW infants. Circulating vitamin D concentrations were significantly associated with perinatal outcomes in this contemporary cohort.
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http://dx.doi.org/10.1038/s41372-018-0203-yDOI Listing
October 2018

A Qualitative Study Exploring Contraceptive Practices and Barriers to Long-Acting Reversible Contraceptive Use in a Sample of Adolescents Living in the Southern United States.

J Pediatr Adolesc Gynecol 2018 Dec 20;31(6):605-609. Epub 2018 Aug 20.

Division of Adolescent Medicine, University of Alabama at Birmingham, Birmingham, Alabama.

Study Objective: To understand contraceptive practices of female adolescents in the Deep South and determine barriers to their use of long-acting reversible contraception (LARC).

Design: Semistructured interviews were conducted that addressed current contraceptive choice, factors influencing choice, LARC awareness, concerns, and barriers to using LARC. Interviews were audio recorded, transcribed, and analyzed using qualitative content analysis to identify themes.

Setting: Adolescent medicine clinic in an urban academic medical center in the Deep South region of the United States.

Participants: Sexually active girls between the ages of 14 and 21 years who were not currently using LARC.

Interventions And Main Outcome Measures: Themes generated during semistructured interviews.

Results: Fifteen participants were interviewed with a mean age of 17 years. Fourteen of 15 were African American. Thirteen of 15 were currently using non-LARC methods and 2 of 15 were not using any contraceptive method. Contraceptive choice was driven by perceived ease of use, desire for pregnancy prevention, and seeking relief of menstrual concerns. Thirteen of 15 participants were aware of LARC with 11 of 15 (73%) noting information came from a health care provider. Barriers to current and future LARC use included concerns about side effects, LARC ineffectiveness, device longevity, and LARC invasiveness. Sixty-three percent of participants noted that they would not consider using a LARC in the future.

Conclusion: Increasing use of LARC goes beyond awareness. Concerns about effectiveness, future fertility, duration of devices, and perceived invasiveness represent barriers for adolescents. Further research is needed to determine how to address these barriers because it pertains to counseling of sexually active girls on the use of LARC.
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http://dx.doi.org/10.1016/j.jpag.2018.07.006DOI Listing
December 2018

Single Ultra-High-Dose Cholecalciferol to Prevent Vitamin D Deficiency in Pediatric Hematopoietic Stem Cell Transplantation.

Biol Blood Marrow Transplant 2018 09 18;24(9):1856-1860. Epub 2018 May 18.

Division of Endocrinology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, Ohio. Electronic address:

Vitamin D deficiency is prevalent among childhood hematopoietic stem cell transplantation (HSCT) recipients and associated with inferior survival at 100 days after transplantation. Achieving and maintaining therapeutic vitamin D levels in HSCT recipients is extremely challenging in the first 3 to 6 months after transplantation due to poor compliance in the setting of mucositis and the concomitant use of critical transplantation drugs that interfere with vitamin D absorption. We sought to evaluate the safety and efficacy of a single, ultra-high-dose of vitamin D given before childhood HSCT to maintain levels in a therapeutic range during the peritransplantation period. Ten HSCT recipients with pretransplantation 25-OH vitamin D (25OHD) level <50 ng/mL and with no history of hypercalcemia, nephrolithiasis, or pathological fractures were enrolled on this pilot study. A single enteral vitamin D dose (maximum 600,000 IU) was administered to each patient based on weight and pretransplantation vitamin D level before the day of HSCT. Vitamin D levels between 30 and 150 ng/mL were considered therapeutic. All patients received close clinical observation and monitoring of 25OHD levels, calcium, phosphate, parathyroid hormone, urine calcium/creatinine ratio, and n-telopeptide for safety and efficacy assessment. The mean age of the study subjects was 5.8 ± 4.9 years, and the mean pretransplantation 25OHD level was 28.9 ± 13.1 ng/mL. All patients tolerated single, ultra-high-oral dose of vitamin D under direct medical supervision. No other oral vitamin D supplements were administered during the observation window of 8 weeks. Three of 10 patients received 400 IU/day of vitamin D in parenteral nutrition only for 5 days during the study window. A mean peak serum vitamin D level of 80.4 ± 28.6 ng/mL was reached at a median of 9 days after the vitamin D dose. All patients achieved a therapeutic vitamin D level of >30 ng/mL. Mean vitamin D levels were sustained at or above 30 ng/mL during the 8-week observation window. There were no electrolyte abnormalities attributed to the ultra-high-dose of vitamin D. Most patients had mildly elevated urine calcium/creatinine ratios during treatment, but none showed clinical or radiologic signs of nephrocalcinosis or nephrolithiasis. Our findings indicate that single ultra-high-oral dose vitamin D treatment given just before HSCT is safe and well tolerated in the immediate peritransplant period in children. Patients in our study were able to achieve and sustain therapeutic vitamin D levels throughout the critical period during which vitamin D insufficiency is associated with decreased overall survival. Larger prospective studies are needed to address the impact of single ultra-high-dose vitamin D treatment on HSCT outcomes.
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http://dx.doi.org/10.1016/j.bbmt.2018.05.019DOI Listing
September 2018

Proton Pump Inhibitor Use, H-Receptor Antagonist Use, and Risk of Incident Clinical Vertebral Fracture in Women.

Calcif Tissue Int 2018 10 12;103(4):380-387. Epub 2018 May 12.

Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

The few prospective studies examining the relation between proton pump inhibitor (PPI) use and risk of vertebral fracture (VF) suggest a higher risk, but the magnitude of the association has been inconsistent. Moreover, no prospective studies have examined the association between substantially longer duration of PPI use and VF risk. Our objective was to determine the association between PPI use, HRA use, and incident clinical VF in women. We conducted a prospective study in 55,545 women participating in the Nurses' Health Study. PPI and HRA use was assessed by questionnaire every 4 years. Self-reports of VF were confirmed by medical record. Our analysis included 547 incident VF cases (2002-2014). The multivariate adjusted relative risk (MVRR) of VF for women taking PPIs was 1.29 (95% CI 1.04-1.59) compared with non-users. Longer duration of PPI use was associated with higher VF risk (MVRR 1.16 [0.90-1.49] for < 4 years; 1.27 [0.93-1.73] for 4-7.9 years; 1.64 [1.02-2.64] for ≥ 8 years; p = 0.01). The MVRR of VF for women taking HRAs was 1.22 (0.90-1.67) compared with non-users. Longer duration of HRA use was not associated with VF risk (MVRR 1.16 [0.88-1.53] for < 4 years; 0.98 [0.60-1.59] for ≥ 4 years; p = 0.72). PPI use is independently associated with a modestly higher risk of VF and the risk increases with longer duration of use. There was no statistically significant association between HRA use and VF risk. Our findings add to the growing evidence suggesting caution with PPI use, particularly with longer duration of use.
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http://dx.doi.org/10.1007/s00223-018-0432-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6231994PMC
October 2018

Bone fragility in Turner syndrome: Fracture prevalence and risk factors determined by a national patient survey.

Clin Endocrinol (Oxf) 2018 07 8;89(1):46-55. Epub 2018 May 8.

Division of Endocrinology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Objective: Osteoporosis is considered a comorbidity of adult women with Turner syndrome (TS). Limited data are available on fracture prevalence in girls and women with this diagnosis. We aimed to determine the prevalence of fractures in individuals with TS in the United States and identify risk factors for fracture.

Design: Girls and women with TS were invited to participate in an anonymous, self-report, national survey from November 2016 to March 2017. Non-TS controls were obtained through direct contacts of TS participants.

Results: During childhood (0-12 years), adolescence (13-25 years) and young adulthood (26-45 years), there was no difference between TS and controls in fracture prevalence. Girls and women with TS were more likely to report upper extremity fractures, whereas controls were more likely to report phalangeal fractures. Older women (>45 years) with TS were more likely to fracture than non-TS controls (P = .01). Balance problems were more common in individuals with TS than controls (26.5% vs 14.8%, P = .0006). In TS, those reporting balance problems were 54% more likely to have a prior fracture than those without balance problems (OR=1.54, 95% CI 1.03, 2.30), even after controlling for age. There was no significant association between balance problems and fractures among controls.

Conclusions: In a nationwide survey, there was no difference in fracture prevalence in younger women with TS compared with controls. However, the location of fractures differed. After controlling for age, impaired balance was associated with an increased fracture risk in TS and may be an underrecognized risk factor for fracture in this population.
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http://dx.doi.org/10.1111/cen.13614DOI Listing
July 2018

Long-Term Effects of Gonadotropin-Releasing Hormone Agonists and Add-Back in Adolescent Endometriosis.

J Pediatr Adolesc Gynecol 2018 Aug 15;31(4):376-381. Epub 2018 Mar 15.

Boston Center for Endometriosis, Boston Children's Hospital and Brigham and Women's Hospital, Boston, Massachusetts; Division of Adolescent and Young Adult Medicine, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts; Division of Gynecology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.

Study Objective: To explore the potential occurrence of long-term side effects and tolerability of gonadotropin-releasing hormone agonist (GnRHa) plus 2 different add-back regimens in adolescent patients with endometriosis.

Design: Follow-up questionnaire sent in 2016 to patients who participated in a drug trial between 2008 and 2012.

Setting: Tertiary care center in Boston, Massachusetts.

Participants: Female adolescents with surgically confirmed endometriosis (n = 51) who enrolled in a GnRHa plus add-back trial as adolescents.

Interventions: Leuprolide depot 11.25 mg intramuscular injection every 3 months, plus oral norethindrone acetate 5 mg daily or oral norethindrone acetate 5 mg daily and oral conjugated equine estrogens 0.625 mg daily.

Main Outcome Measures: Side effects during and after treatment, irreversible side effects, changes in pain, overall satisfaction.

Results: The response rate was 61% (25 of 41; 10 subjects could not be located). Almost all (24 of 25) reported side effects during treatment; 80% (16 of 21) reported side effects lasting longer than 6 months after stopping treatment. Almost half (9 of 20) reported side effects they considered irreversible, including memory loss, insomnia, and hot flashes. Despite side effects, participants rated GnRHa plus add-back as the most effective hormonal medication for treating endometriosis pain; two-thirds (16 of 25) would recommend it to others. More participants who received a modified 2-drug add-back regimen vs standard 1-drug add-back would recommend GnRHa and believed it was the most effective hormonal medication.

Conclusion: Subjects believed that GnRHa used with add-back was effective and would recommend it to others, despite significant side effects. Those who received 2-drug add-back reported more success than those who received standard add-back. A subset of patients reported side effects they consider to be irreversible.
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http://dx.doi.org/10.1016/j.jpag.2018.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5997553PMC
August 2018

Magnetic resonance imaging and spectroscopy evidence of efficacy for adrenal and gonadal hormone replacement therapy in anorexia nervosa.

Bone 2018 05 26;110:335-342. Epub 2018 Feb 26.

Division of Adolescent and Transition Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. Electronic address:

Purpose: Dehydroepiandrosterone (DHEA)+estrogen/progestin therapy for adolescent girls with anorexia nervosa (AN) has the potential to arrest bone loss. The primary aim of this study was to test the effects of DHEA+estrogen/progestin therapy in adolescent girls with AN on bone marrow in the distal femur using magnetic resonance imaging (MRI) and spectroscopy.

Methods: Seventy adolescent girls with AN were enrolled in a double blind, randomized, placebo-controlled trial at two urban hospital-based programs.

Intervention: Seventy-six girls were randomly assigned to receive 12months of either oral micronized DHEA or placebo. DHEA was administered with conjugated equine estrogens (0.3mg daily) for 3months, then an oral contraceptive (20μg ethinyl estradiol/ 0.1mg levonorgestrel) for 9months. The primary outcome measure was bone marrow fat by MRI and magnetic resonance spectroscopy (MRS).

Results: T2 of the water resonance dropped significantly less in the active vs. placebo group over 12months at both the medial and lateral distal femur (p=0.02). Body mass index (BMI) was a significant effect modifier for T1 and for T2 of unsaturated (T2) and saturated fat (T2) in the lateral distal femur. Positive effects of the treatment of DHEA+estrogen/progestin were seen primarily for girls above a BMI of about 18kg/m.

Conclusions: These findings suggest treatment with oral DHEA+estrogen/progestin arrests the age- and disease-related changes in marrow fat composition in the lateral distal femur reported previously in this population.
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http://dx.doi.org/10.1016/j.bone.2018.02.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5879439PMC
May 2018

Pubertal Progression in Female Adolescents with Progeria.

J Pediatr Adolesc Gynecol 2018 Jun 16;31(3):238-241. Epub 2017 Dec 16.

Department of Pediatrics, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio. Electronic address:

Study Objective: This study identified the prevalence of menarche and coincident sexual characteristics in female adolescents with Hutchinson-Gilford Progeria Syndrome (HGPS).

Design: Data were examined to determine the prevalence of menarche in female adolescents older than 12 years; all were participants in clinical trials between 2007 and 2016.

Setting: Pediatric hospital in Boston, Massachusetts.

Participants: Fifteen female adolescents, median age 15 (range, 12.0-20.3) years with a confirmed diagnosis of HGPS.

Interventions And Main Outcome Measures: Report of menarche, anthropometric and serum hormonal measures, Tanner pubertal staging, and body composition using dual-energy x-ray absorptiometry.

Results: Nine of 15 (60%) participants reported spontaneous menarche at a median age of 14.4 years (range, 12.0-16.5 years). In those experiencing menarche vs not, median age was older (16.5 vs 13.6 years; P = .02), whereas body mass index did not differ (10.5 vs 10.4; P = .53) nor percentage body fat (19.4% vs. 19.3%; P = .98) or serum leptin levels (0.40 vs 0.40 ng/mL; P = .23). Among those who achieved menarche, 2 of 9 (22%) had Tanner II breast development and 2 of 9 (22%) exhibited Tanner II Pubic hair, all reflecting minimal pubertal development. Only early signs of puberty were similarly seen in the non-menstruating group, including 1 of 6 (17%) with Tanner II breasts and 2 of 6 (33%) with Tanner II pubic hair, and Tanner staging did not differ between those who reported menarche vs those who did not (each P = 1.0). None of the participants achieved Tanner IV or V thelarche over the course of the study.

Conclusion: Menarche was achieved in more than half of adolescent girls with HGPS, in the setting of little to no physical signs of pubertal development and minimal body fat.
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http://dx.doi.org/10.1016/j.jpag.2017.12.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6671321PMC
June 2018

Proceedings of the 2017 Santa Fe Bone Symposium: Insights and Emerging Concepts in the Management of Osteoporosis.

J Clin Densitom 2018 Jan - Mar;21(1):3-21. Epub 2017 Nov 20.

Flagship Pioneering, Cambridge, MA, USA.

The 18th Annual Santa Fe Bone Symposium was held on August 4-5, 2017, in Santa Fe, New Mexico, USA. The symposium convenes health-care providers and clinical researchers to present and discuss clinical applications of recent advances in research of skeletal diseases. The program includes lectures, oral presentations by endocrinology fellows, case-based panel discussions, and breakout sessions on topics of interest, with emphasis on participation and interaction of all participants. Topics included the evaluation and treatment of adult survivors with pediatric bone diseases, risk assessment and management of atypical femur fractures, nonpharmacologic strategies in the care of osteoporosis, and skeletal effects of parathyroid hormone with opportunities for therapeutic intervention. Management of skeletal complications of rheumatic diseases was discussed. Insights into sequential and combined use of antiresorptive agents were presented. Individualization of patient treatment decisions when clinical practice guidelines may not be applicable was covered. Challenges and opportunities with osteoporosis drug development were discussed. There was an update on progress of Bone Health TeleECHO (Bone Health Extension for Community Healthcare Outcomes), a teleconferencing strategy for sharing knowledge and expanding capacity to deliver best-practice skeletal health care.
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http://dx.doi.org/10.1016/j.jocd.2017.10.041DOI Listing
July 2019

Investigation of the C-3-epi-25(OH)D of 25-hydroxyvitamin D in urban schoolchildren.

Appl Physiol Nutr Metab 2018 Mar 20;43(3):259-265. Epub 2017 Oct 20.

a Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA 02111, USA.

The physiological relevance C-3 epimer of 25-hydroxyvitamin D (3-epi-25(OH)D) is not well understood among youth. The objective of this study was to assess whether demographic/physiologic characteristics were associated with 3-epi-25(OH)D concentrations in youth. Associations between 3-epi-25(OH)D and demographics and between 3-epi-25(OH)D, total 25-hydroxyvitamin (25(OH)D) (25(OH)D + 25(OH)D), total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides were examined in racially/ethnically diverse schoolchildren (n = 682; age, 8-15 years) at Boston-area urban schools. Approximately 50% of participants had detectable 3-epi-25(OH)D (range 0.95-3.95 ng/mL). The percentage of 3-epi-25(OH)D of total 25(OH)D ranged from 2.5% to 17.0% (median 5.5%). Males were 38% more likely than females to have detectable 3-epi-25(OH)D concentrations. Both Asian and black race/ethnicity were associated with lower odds of having detectable 3-epi-25(OH)D compared with non-Hispanic white children (Asian vs. white, odds ratio (OR) 0.28, 95% confidence interval (CI) 0.14-0.53; black vs. white, OR 0.38, 95%CI 0.23-0.63, p < 0.001). Having an adequate (20-29 ng/mL) or optimal (>30 ng/mL) 25(OH)D concentration was associated with higher odds of having detectable 3-epi-25(OH)D than having an inadequate (<20 ng/mL) concentration (OR 4.78, 95%CI 3.23-6.94 or OR 14.10, 95%CI 7.10-28.0, respectively). There was no association between 3-epi-25(OH)D and blood lipids. However, when considering 3-epi-25(OH)D as a percentage of total 25(OH)D, total cholesterol was lower in children with percent 3-epi-25(OH)D above the median (mean difference -7.1 mg/dL, p = 0.01). In conclusion, among schoolchildren, sex, race/ethnicity, and total serum 25(OH)D concentration is differentially associated with 3-epi-25(OH)D. The physiological relevance of 3-epi-25(OH)D may be related to the 3-epi-25(OH)D as a percentage of total 25(OH)D and should be considered in future investigations.
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http://dx.doi.org/10.1139/apnm-2017-0334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563605PMC
March 2018

Pharmacokinetics of IGF-1 in PAPP-A2-Deficient Patients, Growth Response, and Effects on Glucose and Bone Density.

J Clin Endocrinol Metab 2017 12;102(12):4568-4577

Division of Endocrinology, Cincinnati Children's Hospital Medical Center.

Context: The pregnancy-associated plasma protein A2 (PAPP-A2) cleaves insulinlike growth factor binding proteins 3 and 5, releasing free insulinlike growth factor 1 (IGF-1). Homozygous mutations in PAPP-A2 result in growth failure with elevated total but low free IGF-1.

Objective: To determine the 24-hour pharmacokinetic (PK) profile of free and total IGF-1 after a dose of recombinant human insulinlike growth factor 1 (rhIGF-1). We describe the growth response and effects on glucose metabolism and bone mineral density (BMD) after 1 year of rhIGF-1 therapy.

Design And Patients: Three affected siblings, their heterozygous parents, and two healthy controls participated. The subjects received a dose of rhIGF-1, followed by serial blood samples collected over 24 hours. The two younger siblings were started on rhIGF-1 treatment. An oral glucose tolerance test and dual-energy X-ray absorptiometry scans were obtained at baseline and after 1 year of treatment.

Results: Subcutaneous administration of rhIGF-1 increased the concentration of free and total IGF-1 in patients with PAPP-A2 deficiency. The PK profile was comparable in all participants. At baseline, all three subjects demonstrated insulin resistance and below-average BMD. Treatment with rhIGF-1 is ongoing in the youngest patient but was discontinued in his brother because of the development of pseudotumor cerebri. The treated patient had an increase in height velocity from 3.0 to 6.2 cm/y, resolution of insulin resistance, and an increase in total body BMD.

Conclusions: rhIGF-1 at standard dosages resulted in similar PK characteristics in patients with PAPP-A2 deficiency, heterozygous relatives, and healthy controls. The youngest affected patient experienced a modest growth response to therapy with rhIGF-1, as well as beneficial effects on glucose metabolism and bone mass.
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http://dx.doi.org/10.1210/jc.2017-01411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5718699PMC
December 2017