Bone outcomes in virally suppressed youth with HIV switching to tenofovir disoproxil fumarate

Background: Tenofovir disoproxil fumarate (TDF) is included in first-line antiretroviral treatment (ART) for adolescents living with HIV (ALWH). Associated toxicities remain a concern.Objective: We evaluated bone and renal safety outcomes in virologically suppressed South African ALWH after switching to TDF.Method: We recruited virally suppressed ( 100 copies/mL) adolescents, aged 15–20 years, who switched from an abacavir (ABC)-based to a TDF-based efavirenz regimen. Bone mass and renal function were assessed at Week 0 and at Week 24 after the switch to TDF using dual-energy X-ray absorptiometry (DXA) and serum renal markers. A change in the lumbar spine (LS) and the whole-body less head (WBLH) bone mineral density (BMD) Z-scores and the estimated glomerular filtration rate (eGFR) between the two measures were compared (paired t-tests) and stratified by sex.Results: Fifty participants (48% male), with a median duration of prior ART of 11.4 years, were enrolled. Among 47 participants with 24-week DXA results, 15 (32%) had either no change or a decreased LS-BMD after the switch, with a mean change of –1.6%. Overall, more female participants experienced this outcome: 58% versus 4%, P 0.0001. The mean change (standard deviation) in the LS-Z-score was –0.03 (0.25) and in the WBLH-Z-score was 0.02 (0.24). A decrease in the eGFR from 132.2 to 120.4 was observed (P = 0.0003); however, the levels remained clinically acceptable.Conclusion: South African ALWH switching from abacavir to TDF-based ART experienced statistically significant decreases in eGFR but not in LS and WBLH BMD. Female ALWH were more likely to experience a decrease in LS-BMD and may require closer monitoring.

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Changes in Bone Mass After Discontinuation of Preexposure Prophylaxis With Tenofovir Disoproxil Fumarate/Emtricitabine in Young Men Who Have Sex With Men: Extension Phase Results of Adolescent Trials Network Protocols 110 and 113

Clinical Infectious Diseases ◽

10.1093/cid/ciz486 ◽

2019 ◽

Vol 70 (4) ◽

pp. 687-691 ◽

Cited By ~ 5

Author(s):

Peter L Havens ◽

Suzanne E Perumean-Chaney ◽

Amit Patki ◽

Stacey S Cofield ◽

Craig M Wilson ◽

...

Keyword(s):

Bone Mineral Density ◽

Human Immunodeficiency Virus ◽

Tenofovir Disoproxil Fumarate ◽

Network Protocols ◽

Whole Body ◽

Mineral Density ◽

Preexposure Prophylaxis ◽

Immunodeficiency Virus ◽

Z Scores ◽

Sex With Men

AbstractHuman immunodeficiency virus–seronegative men aged 15–22 years who lost bone mineral density (BMD) during tenofovir disoproxil fumarate/emtricitabine preexposure prophylaxis (PrEP) showed BMD recovery 48 weeks following PrEP discontinuation. Lumbar spine and whole body BMD z-scores remained below baseline 48 weeks off PrEP in participants aged 15–19 years.Clinical Trials Registration. NCT01772823 (ATN 110) and NCT01769456 (ATN 113).

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Diet Quality and Bone Density in Youth with Healthy Weight, Obesity, and Type 2 Diabetes

Nutrients ◽

10.3390/nu13093288 ◽

2021 ◽

Vol 13 (9) ◽

pp. 3288

Author(s):

Joseph M. Kindler ◽

Sina Gallo ◽

Philip R. Khoury ◽

Elaine M. Urbina ◽

Babette S. Zemel

Keyword(s):

Bone Mineral Density ◽

Type 2 Diabetes ◽

Diet Quality ◽

Whole Body ◽

Areal Bone Mineral Density ◽

Healthy Weight ◽

Z Score ◽

Mineral Density ◽

Z Scores

Purpose: To assess relationships between diet quality and areal bone mineral density (aBMD) in youth with healthy weight, obesity, and type 2 diabetes (T2D). Methods: We performed a secondary analysis of cross-sectional data from youth (55% African American, 70% female) ages 10–23 years with T2D (n = 90), obesity (BMI > 95th; n = 128), or healthy weight (BMI < 85th; n = 197). Whole body (less head) areal bone mineral density (aBMD) was assessed by dual-energy X-ray absorptiometry (DXA). aBMD was expressed as age-, sex-, and ancestry-specific standard deviation scores (Z-scores). Whole body aBMD Z-scores were adjusted for height-for-age Z-score. Diet was assessed via three-day diaries, and the Healthy Eating Index (HEI) was computed. Total HEI score and HEI subcomponent scores were compared across groups, and associations with aBMD Z-scores were assessed via linear regression adjusted for group, age, sex, and ancestry. Results: Mean HEI was similar between the healthy weight, obesity, and T2D groups. Several HEI sub-components differed between groups, including meats and beans, total vegetables, milk, saturated fat, sodium, oils, and empty calories. The obesity and T2D group had significantly greater aBMD Z-scores compared to the healthy weight group. Multiple linear regression analyses revealed a significant positive association between HEI and aBMD Z-score (p < 0.05). The HEI sub-components for whole grains (p = 0.052) and empty calories (p < 0.05) were positively associated with aBMD Z-score. Conclusions: Individuals that followed a dietary pattern more closely aligned with the Dietary Guidelines for Americans had greater bone density. Since few studies have investigated the role of diet on bone in youth with obesity-related conditions, additional research is required among these populations.

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Effect of serum cholesterol on bone mineral density in normal-weight children and adolescents

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2014-0360 ◽

2015 ◽

Vol 28 (11-12) ◽

Author(s):

Han Hyuk Lim

Keyword(s):

Bone Mineral Density ◽

Children And Adolescents ◽

Bone Mineral ◽

Serum Cholesterol ◽

Normal Weight ◽

Whole Body ◽

Inverse Association ◽

Z Score ◽

Mineral Density ◽

Z Scores

AbstractWe investigated whether there is a relationship between serum cholesterol and bone mineral density (BMD), independent of BMI in children and adolescents. This study was based on data from the KNHANES 2009–2010. The data for 1557 children and adolescents were analyzed and classified into three groups: underweight, normal-weight, and overweight. We analyzed the relationships between serum cholesterol and BMD z-scores. Whole body BMD z-score was revealed as an inverse association with the serum cholesterol quartile in only normal-weight group (p=0.008). Serum cholesterol level correlated more inversely with BMD z-score in normal-weight boys (

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Bone mineral density and explanatory factors in children and adults with juvenile dermatomyositis at long term follow-up; a cross sectional study

Pediatric Rheumatology ◽

10.1186/s12969-021-00543-z ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Henriette Schermacher Marstein ◽

Kristin Godang ◽

Berit Flatø ◽

Ivar Sjaastad ◽

Jens Bollerslev ◽

...

Keyword(s):

Bone Turnover ◽

Inflammatory Markers ◽

Juvenile Dermatomyositis ◽

Inflammatory Myopathy ◽

Disease Onset ◽

Whole Body ◽

Mineral Density ◽

Z Scores

Abstract Background Juvenile dermatomyositis (JDM) is the most common idiopathic inflammatory myopathy in children and adolescents. Both the disease and its treatment with glucocorticoids may negatively impact bone formation. In this study we compare BMD in patients (children/adolescence and adults) with long-standing JDM with matched controls; and in patients, explore how general/disease characteristics and bone turnover markers are associated with BMD. Methods JDM patients (n = 59) were examined median 16.8y (range 6.6–27.0y) after disease onset and compared with 59 age/sex-matched controls. Dual-energy X-ray absorptiometry (DXA) was used to measure BMD of the whole body and lumbar spine (spine) in all participants, and of ultra-distal radius, forearm and total hip in participants ≥20y only. Markers of bone turnover were analysed, and associations with outcomes explored. Results Reduced BMD Z-scores (<−1SD) were found in 19 and 29% of patients and 7 and 9% of controls in whole body and spine, respectively (p-values < 0.05). BMD and BMD Z-scores for whole body and spine were lower in all patients and for < 20y compared with their respective controls. In participants ≥20y, only BMD and BMD Z-score of forearm were lower in the patients versus controls. In patients, BMD Z-scores for whole body and/or spine were found to correlate negatively with prednisolone use at follow-up (yes/no) (age < 20y), inflammatory markers (age ≥ 20y) and levels of interferon gamma-induced protein 10 (IP-10) (both age groups). In all patients, prednisolone use at follow-up (yes/no) and age ≥ 20y were independent correlates of lower BMD Z-scores for whole body and spine, respectively. Conclusion In long-term JDM, children have more impairment of BMD than adults in spine and whole-body. Associations with BMD were found for both prednisolone and inflammatory markers, and a novel association was discovered with the biomarker of JDM activity, IP-10.

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EVALUATION OF GLUTATHIONE-S-TRANSFERASE P1 POLYMORPHISM AND ITS RELATION TO BONE MINERAL DENSITY IN EGYPTIAN CHILDREN AND ADOLESCENTS WITH BETA- THALASSEMIA MAJOR

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2016.004 ◽

2016 ◽

Vol 8 ◽

pp. 2016004 ◽

Cited By ~ 3

Author(s):

Seham Ragab

Keyword(s):

Bone Mineral Density ◽

Bone Mineral ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Z Score ◽

Glutathione S Transferase ◽

Mineral Density ◽

Beta Thalassemia Major ◽

Egyptian Children ◽

Z Scores

Background:Osteoporosis is a major problem in beta thalassemia major (TM) patients. Increased oxidative stress and its controlling genes were linked to osteoporosis. Glutathione S-transferase P1 (GSTP1),Ile105 Val variant is a functional mutation with reduced ant-oxidative property .No data are available about this variant or its association with osteoporosis among thalassemia patients yet. Objectives: The aim of this study was to investigate Ile105Val polymorphism and its possible association with bone mineral density (BMD) values in a group of TM children. Methods:Thirty five TM patients and 30 age and sex matched healthy controls were included. Liver and renal functions, serum ferritin, calcium, phosphorous, alkaline phosphatase and osteocalcin were assayed. BMD was determined by DXA with calculation of Z-scores at lumbar spine (Ls) and femoral neck (Fn).Height for age z- score (HAZ) adjusted BMD Z-scores were considered . GSTP1 Ile105Val polymorphism was studied by polymerase chain reaction-restriction fragment length polymorphism. Results:The relative frequency of 105 Val allele was significantly higher in TM patients than the controls (P<0.0001). Significant association between genotype subgroups and BMD parameters was detected. Mutant homozygotes had significant lower BMD , Z –score and haz -adjusted BMD Z-score at both Ls and Fn compared to wild homozygotes ( Ps =0.029, 0.008, 0.011, 0.001,0.02, 0.001) with significant higher osteocalcin level compared to heterozygotes and wild homozygotes (P=0.012 and P=0.013,respectively). Conclusion: The results indicated that 105Val allele was frequent among TM patients and could increase their susceptibility to osteoporosis. Large sample studies are required to confirm these findings.

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Sleep and BMI in South African urban and rural, high and low-income preschool children

BMC Public Health ◽

10.1186/s12889-021-10591-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Dale E. Rae ◽

Simone A. Tomaz ◽

Rachel A. Jones ◽

Trina Hinkley ◽

Rhian Twine ◽

...

Keyword(s):

Physical Activity ◽

Preschool Children ◽

South African ◽

Low Income ◽

Urban Environments ◽

Z Score ◽

Cross Sectional ◽

Rural And Urban ◽

Sleep Parameters ◽

Z Scores

Abstract Background The extent to which income setting or rural and urban environments modify the association between sleep and obesity in young children is unclear. The aims of this cross-sectional observational study were to (i) describe and compare sleep in South African preschool children from rural low-income (RL), urban low-income (UL) and urban high-income (UH) settings; and (ii) test for associations between sleep parameters and body mass index (BMI). Methods Participants were preschoolers (5.2 ± 0.7y, 49.5% boys) from RL (n = 111), UL (n = 65) and UH (n = 22) settings. Height and weight were measured. Sleep, sedentary behaviour and physical activity were assessed using accelerometery. Results UL children had higher BMI z-scores (median: 0.39; interquartile range: − 0.27, 0.99) than the UH (− 0.38; − 0.88, 0.11) and RL (− 0.08; − 0.83, 0.53) children (p = 0.001). The UL children had later bedtimes (p < 0.001) and wake-up times (p < 0.001) and shorter 24 h (p < 0.001) and nocturnal (p < 0.001) sleep durations than the RL and UH children. After adjusting for age, sex, setting, SB and PA, for every hour less sleep obtained (24 h and nocturnal), children were 2.28 (95% CI: 1.28–4.35) and 2.22 (95% CI: 1.27–3.85) more likely, respectively, to belong to a higher BMI z-score quartile. Conclusions Shorter sleep is associated with a higher BMI z-score in South African preschoolers, despite high levels of PA, with UL children appearing to be particularly vulnerable.

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Evaluation of Bone Mineral Density in Children with Sickle Cell Anemia.

Blood ◽

10.1182/blood.v104.11.106.106 ◽

2004 ◽

Vol 104 (11) ◽

pp. 106-106

Author(s):

Ashutosh Lal ◽

Ellen Fung ◽

Bamidele Kammen ◽

Zahra Pakbaz ◽

Nancy Sweeters ◽

...

Keyword(s):

Bone Mineral Density ◽

Lumbar Spine ◽

Sickle Cell ◽

Bone Mineral ◽

Reference Data ◽

Growth Failure ◽

Red Cell ◽

Z Score ◽

Mineral Density ◽

Z Scores

Abstract Background : Reduced bone mineral density (BMD) has been reported in adults and children with sickle cell anemia (SCA). Dual energy x-ray absorptiometry (DXA) is routinely used for measuring BMD because of less radiation exposure and lower cost. However, changes in vertebral body shape, marrow hyperplasia and bone infarction due to SCA may affect the evaluation of BMD with DXA. Hence, we compared DXA with quantitative computerized tomography (QCT), which measures true volumetric density, and may be less influenced by bone changes. Methods : The study enrolled children between 9–19 years of age with SCA, and one or more severe manifestations: >2 hospital admissions/year, growth failure, avascular necrosis, or regular red cell transfusions for sickle cell-related complications. BMD of lumbar spine was determined by performing DXA of lumbar spine (Hologic Delphi-A, Bedford, MA). The apparent volumetric bone mineral density (BMAD) was calculated from bone mineral content, and compared to age, sex and ethnicity-matched reference data. BMD of the lumbar spine was also measured by QCT (Mindways Software, San Francisco, CA), and compared to age and sex-appropriate reference data. Results : The study has enrolled 25 patients (13 females and 12 males), of which 16 were younger than 14 years. In 6 children the height was <10th centile for age. Thirteen patients were on regular transfusions for >6 months, including 10 who had been transfused for >2 years. Calcium intake, assessed by a standardized questionnaire, was less than recommended dietary allowance in 13 patients. The z-score for BMAD determined by DXA was > −1.0 in 8, between −1.0 and −2.0 in 5, and < −2.0 in 12 patients. The z-score for lumbar spine by QCT was > −1.0 in 20, between −1.0 and −2.0 in 1 and < −2.0 in 4 patients. DXA-derived BMD (areal density) and BMAD (apparent volumetric density) z-scores did not differ significantly (p=0.16). On the other hand, the paired values of z-scores by DXA (BMAD) and QCT were significantly different (p=.002). When z-scores were categorized as greater or less than −1.0, the results were concordant in 13 (both DXA and QCT normal in 8, and both DXA and QCT abnormal in 5), and discordant in 12 cases (abnormal DXA with normal QCT in every case). Among patients in discordant group, 9/12 had been on regular red cell transfusions for >6 months, compared to 4/13 with concordant results (p=.047). There was no difference in the serum ferritin values between the two groups (p=.685). No significant difference in the prevalence of low BMAD z-scores was detected between groups based upon age, calcium intake, or growth failure. Five out of the 12 patients with BMAD z-score < −2.0 were not on regular transfusion program. Conclusions : Almost half of the children with SCA had BMD below −2 standard deviations compared to age-matched controls. Low BMD was observed in chronically transfused as well as non-transfused children. In comparison, 16% of the patients were classified as low BMD (z < −2.0) by QCT. The paired DXA/QCT results were discordant in half of the sample, with patients on regular transfusions for >6 months more likely to have normal QCT results. It is likely that the reduction in marrow hyperplasia following initiation of regular transfusions may disproportionately affect the trabecular BMD measured by QCT. Longitudinal evaluation of BMD in patients starting on transfusion program could help to define the effect of transfusions on measures of BMD in SCA.

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Tracking of Bone Mass and Density during Childhood and Adolescence

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2009-2319 ◽

2010 ◽

Vol 95 (4) ◽

pp. 1690-1698 ◽

Cited By ~ 73

Author(s):

Heidi J. Kalkwarf ◽

Vicente Gilsanz ◽

Joan M. Lappe ◽

Sharon Oberfield ◽

John A. Shepherd ◽

...

Keyword(s):

Bone Mineral Density ◽

Bone Density ◽

Bone Mineral ◽

Sexual Maturation ◽

Childhood And Adolescence ◽

Z Score ◽

Mineral Density ◽

Growth Status ◽

Low Bone Density ◽

Z Scores

Abstract Context: Whether a child with low bone mineral density (BMD) at one point in time will continue to have low BMD, despite continued growth and maturation, is important clinically. The stability of a characteristic during growth is referred to as “tracking.” Objective: We examined the degree of tracking in bone mineral content (BMC) and BMD during childhood and adolescence and investigated whether tracking varied according to age, sexual maturation, and changes in growth status. Design: We conducted a longitudinal study with measurements at baseline and annually for 3 yr. Setting: The Bone Mineral Density in Childhood Study was conducted at five clinical centers in the United States. Study Participants: A total of 1554 girls and boys, ages 6–16 yr at baseline, participated in the study. Main Outcome Measures: Whole body, spine, hip, and forearm BMC and BMD were measured by dual-energy x-ray absorptiometry, and age-, sex-, and race-specific Z-scores were calculated. Deviation from tracking was calculated as the Z-score at yr 3 minus baseline. Results: Correlations between Z-scores at baseline and yr 3 ranged from 0.76–0.88. Among children with a Z-score below −1.5 at baseline, 72–87% still had a Z-score below −1 after 3 yr. Age, sexual maturation, and deviations in growth status (P < 0.01) were associated with deviation from tracking; however, tracking was strongly evident even after adjusting for the effects of age, maturation, and growth. Conclusions: Bone density showed a high degree of tracking over 3 yr in children and adolescents. Healthy children with low bone density will likely continue to have low bone density unless effective interventions are instituted.

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OR27-04 Risk Factors For Low Baseline Bone Mineral Density In Gender Diverse Youth

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1296 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Juanita K Hodax ◽

Charles Brady ◽

Sara A DiVall ◽

Kristen Carlin ◽

Hedieh Khalatbari ◽

...

Keyword(s):

Bone Mineral Density ◽

Vitamin D ◽

Hormone Therapy ◽

Bone Mineral ◽

Calcium Intake ◽

Z Score ◽

Mineral Density ◽

Transgender Youth ◽

Z Scores ◽

Dxa Scans

Abstract Background Sex steroids such as testosterone and estrogen are necessary for accumulation of bone mass. Transgender youth treated with gonadotropin releasing hormone analogues (GnRHa) to block natal puberty for gender-affirming care are at risk of low bone mineral density (BMD). Previous studies indicate that transfemale patients assigned male at birth (AMAB) have low BMD at baseline, during and after GnRHa treatment despite cross hormone treatment. Transmales assigned female at birth (AFAB), however, have normal BMD at baseline that decreases upon GnRHa treatment, with normalization upon cross hormone therapy. The reason(s) for the low baseline BMD in transfemales is unclear. We aimed to assess the baseline characteristics of transgender youth at a single multidisciplinary gender clinic prior to medical intervention and determine factors associated with BMD. Methods This is a retrospective chart review of patients <19 years old evaluated in the gender clinic. Dual-energy x-ray absorptiometry (DXA) scans were obtained prior to initiation of GnRHa or cross-hormone therapy per Endocrine Society guidelines for the treatment of gender dysphoria. We included patients with DXA scans completed prior to initiation of treatment with GnRHa or cross gender hormones and excluded those with concurrent medical diagnoses that may affect bone density. Data collected were bone mineral density (BMD) Z-scores, anthropometric data, vitamin D and calcium levels, and calcium intake. Multivariable linear regression models were used to assess the impact of vitamin D levels, height Z-score, weight Z-score, and BMI Z-score on subtotal body BMD Z-score, adjusted for sex assigned at birth and age. Results Sixty-four patients were included in our analysis. Of these, 73% were AMAB and 27% AFAB. Gender identity was male in 14%, female in 44%, and non-binary in 42%. Average height Z-score was 0.12, weight Z-score 0.27, and BMI Z-score 0.22 (using sex assigned at birth). Subtotal body BMD Z-scores were greater than zero in 11%, between zero and greater than -2 in 59%, and less than or equal to -2 in 30% of tested patients. AMAB patients had lower BMD Z-scores compared to those AFAB (p<0.05 for all Z-scores). There was a positive association with BMI, height, and weight Z-scores and increasing BMD Z-scores after adjusting for sex assigned at birth and age (p<0.05 for all Z-scores). Patients who consumed <2 servings of calcium per day had lower BMD Z-scores (p<0.05 for all Z-scores). Average vitamin D level was 24 ng/ml (+/- 9.5 SD) with no significant association with BMD Z-scores (adjusted for sex assigned at birth). Conclusions Patients AMAB and patients with calcium intake of < 2 servings/day are associated with lower baseline BMD in a cohort of adolescents seen in a multidisciplinary gender clinic. Height, weight, and BMI are associated linearly with BMD Z-score, following patterns previously described in other populations.

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Older age at Initiation of Antiretroviral Therapy Predicts Low Bone Mineral Density in Children with perinatally-infected HIV in Zimbabwe

10.1101/565143 ◽

2019 ◽

Author(s):

Celia L Gregson ◽

April Hartley ◽

Edith Majonga ◽

Grace Mchugh ◽

Nicola Crabtree ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Bone Density ◽

Bone Mineral ◽

Lean Mass ◽

Muscle Development ◽

Z Score ◽

Mineral Density ◽

Bone Mineral Apparent Density ◽

Art Initiation ◽

Z Scores

AbstractBackgroundPerinatally-acquired HIV infection commonly causes stunting in children, but how this affects bone and muscle development is unclear. We investigated differences in bone and muscle mass and muscle function between children with HIV (CWH) and uninfected children.SettingCross-sectional study of CWH (6–16 years) receiving antiretroviral therapy (ART) for >6 months and children in the same age-group testing HIV-negative at primary health clinics in Zimbabwe.MethodsFrom Dual-energy X-ray Absorptiometry (DXA) we calculated total-body less-head (TBLH) Bone Mineral Content (BMC) for lean mass adjusted-for-height (TBLH-BMCLBM) Z-scores, and lumbar spine (LS) Bone Mineral Apparent Density (BMAD) Z-scores.ResultsThe 97 CWH were older (mean age 12.7 vs. 10.0 years) and therefore taller (mean height 142cm vs. 134cm) than those 77 uninfected. However, stunting (height-for-age Z-score≤-2) was more prevalent in CWH (35% vs. 5%, p<0.001). Amongst CWH, 15% had low LS-BMAD (Z-score ≤-2) and 13% had low TBLH-BMCLBM, vs. 1% and 3% respectively in those uninfected (both p≤0.02). After age, sex, height and puberty adjustment, LS-BMAD was 0.33 SDs (95%CI −0.01, 0.67; p=0.06) lower in CWH, with no differences in TBLH-BMCLBM, lean mass or grip strength by HIV status. However, there was a strong relationship between age at ART initiation and both LS-BMAD Z-score (r=-0.33, p=0.001) and TBLH-BMCLBM Z-score (r=-0.23, p=0.027); for each year ART initiation was delayed a 0.13 SD reduction in LS-BMAD was seen.ConclusionSize-adjusted low bone density is common in CWH. Delay in initiating ART adversely affects bone density. Findings support immediate ART initiation at HIV diagnosis.

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