Bone Development in Transgender Adolescents Treated With GnRH Analogues and Subsequent Gender-Affirming Hormones

Abstract Context Hormonal interventions in adolescents with gender dysphoria may have adverse effects, such as reduced bone mineral accrual. Objective To describe bone mass development in adolescents with gender dysphoria treated with gonadotropin-releasing hormone analogues (GnRHa), subsequently combined with gender-affirming hormones. Design Observational prospective study. Subjects 51 transgirls and 70 transboys receiving GnRHa and 36 transgirls and 42 transboys receiving GnRHa and gender-affirming hormones, subdivided into early- and late-pubertal groups. Main Outcome Measures Bone mineral apparent density (BMAD), age- and sex-specific BMAD z-scores, and serum bone markers. Results At the start of GnRHa treatment, mean areal bone mineral density (aBMD) and BMAD values were within the normal range in all groups. In transgirls, the mean z-scores were well below the population mean. During 2 years of GnRHa treatment, BMAD stabilized or showed a small decrease, whereas z-scores decreased in all groups. During 3 years of combined administration of GnRHa and gender-affirming hormones, a significant increase of BMAD was found. Z-scores normalized in transboys but remained below zero in transgirls. In transgirls and early pubertal transboys, all bone markers decreased during GnRHa treatment. Conclusions BMAD z-scores decreased during GnRHa treatment and increased during gender-affirming hormone treatment. Transboys had normal z-scores at baseline and at the end of the study. However, transgirls had relatively low z-scores, both at baseline and after 3 years of estrogen treatment. It is currently unclear whether this results in adverse outcomes, such as increased fracture risk, in transgirls as they grow older.

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The effect of GnRH analogue treatment on bone mineral density in young adolescents with gender dysphoria: findings from a large national cohort

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2019-0046 ◽

2019 ◽

Vol 32 (10) ◽

pp. 1077-1081 ◽

Cited By ~ 9

Author(s):

Tobin Joseph ◽

Joanna Ting ◽

Gary Butler

Keyword(s):

Bone Mineral Density ◽

Lumbar Spine ◽

Bone Mineral ◽

Gender Dysphoria ◽

Gnrh Analogue ◽

Reference Ranges ◽

Mineral Density ◽

Bone Mineral Apparent Density ◽

Z Scores ◽

The Impact

Abstract Background More young people with gender dysphoria (GD) are undergoing hormonal intervention starting with gonadotropin-releasing hormone analogue (GnRHa) treatment. The impact on bone density is not known, with guidelines mentioning that bone mineral density (BMD) should be monitored without suggesting when. This study aimed to examine a cohort of adolescents from a single centre to investigate whether there were any clinically significant changes in BMD and bone mineral apparent density (BMAD) whilst on GnRHa therapy. Methods A retrospective review of 70 subjects aged 12–14 years, referred to a national centre for the management of GD (2011–2016) who had yearly dual energy X-ray absorptiometry (DXA) scans. BMAD scores were calculated from available data. Two analyses were performed, a complete longitudinal analysis (n=31) where patients had scans over a 2-year treatment period, and a larger cohort over the first treatment year (n=70) to extend the observation of rapid changes in lumbar spine BMD when puberty is blocked. Results At baseline transboys had lower BMD measures than transgirls. Although there was a significant fall in hip and lumbar spine BMD and lumbar spine BMAD Z-scores, there was no significant change in the absolute values of hip or spine BMD or lumbar spine BMAD after 1 year on GnRHa and a lower fall in BMD/BMAD Z-scores in the longitudinal group in the second year. Conclusions We suggest that reference ranges may need to be re-defined for this select patient cohort. Long-term BMD recovery studies on sex hormone treatment are needed.

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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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Effect of suppression of puberty and cross-sex hormone therapy on bone turnover markers and BMAD in transgender adolescents

Problems of Endocrinology ◽

10.14341/probl201662522-23 ◽

2016 ◽

Vol 62 (5) ◽

pp. 22-23

Author(s):

Mariska Caroline Vlot ◽

Daniel T. Klink ◽

Martin Den Heijer ◽

Marinus A. Blankenstein ◽

Joost Rotteveel ◽

...

Keyword(s):

Bone Turnover ◽

Hormone Therapy ◽

Bone Mineral ◽

Bone Turnover Markers ◽

Sex Hormone ◽

Added Value ◽

Mineral Density ◽

Bone Mineral Apparent Density ◽

Z Scores ◽

Turnover Markers

Background: Puberty is highly important for the accumulation of bone mass. Bone turnover and bone mineral density can be affected in transgender adolescents when puberty is suppressed by gonadotropin-releasing hormone analogues (GnRHa), followed by treatment with cross-sex hormone therapy (CSHT).Objective: To investigate the effect of GnRHa and CSHT on bone turnover markers (BTMs) and bone mineral apparent density (BMAD) in transgender adolescents.Methods: Thirty four female-to-males (FtMs) and 22 male-to-females (MtFs) were divided into a young and old pubertal group, based on the bone age of 14 years in the FtMs and 15 years in the MtFs. All patients received GnRHa triptorelin. CSHT was prescribed in incremental doses from the age of 16 years. FtMs received testosterone ester mixture and MtFs were treated with 17-β estradiol. BTMs P1NP, osteocalcin and ICTP and the BMD of lumbar spine (LS) and femoral neck (FN) were measured at three time points. Furthermore, BMAD and Z-scores were calculated.Results: P1NP and 1CTP decreased during GnRHa treatment, indicating decreased bone turnover. Osteocalcin showed an aberrant pattern. A low BMAD Z-score of both FN and LS was observed in the MtFs at start of GnRHa treatment. The decrease in bone turnover upon GnRHa treatment was accompanied by an unchanged BMAD of both FN and LS, however BMAD Z-scores of predominantly the LS decreased. Twenty-four months after CSHT the BTMs P1NP and ICTP were even more decreased. During CSHT BMAD Z-scores increased and returned towards normal, especially of the LS.Conclusion: Suppressing puberty by GnRHa leads to a decrease of BTMs in transgender adolescents. The increase of BMAD and BMAD Z-scores predominantly in the LS as a result of treatment with CSHT is accompanied by decreasing BTM concentrations after 24 months of CSHT. Therefore, the added value of evaluating BTMs seems to be limited and DEXA-scans remain important in follow-up of transgender adolescents.

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Use of SSRIs May Impact Bone Density in Adolescent and Young Women With Anorexia Nervosa

CNS Spectrums ◽

10.1017/s1092852900000559 ◽

2010 ◽

Vol 15 (9) ◽

pp. 579-586 ◽

Cited By ~ 20

Author(s):

Madhusmita Misra ◽

Marie Le Clair ◽

Nara Mendes ◽

Karen K. Miller ◽

Elizabeth Lawson ◽

...

Keyword(s):

Anorexia Nervosa ◽

Bone Mineral ◽

Selective Serotonin Reuptake Inhibitors ◽

Mineral Content ◽

Whole Body ◽

Mineral Density ◽

Bone Mineral Apparent Density ◽

Hip Bmd ◽

Z Scores ◽

Negative Predictor

ABSTRACTObjectives: Alterations in serotonin impact bone metabolism in animal models, and selective serotonin reuptake inhibitors (SSRIs) have been associated with increased fracture risk in older adults. SSRIs are commonly used in anorexia nervosa (AN), a condition that predisposes to low bone mineral density (BMD). Our objective was to determine whether SSRI use is associated with low BMD in AN.Methods: We examined Z-scores for spine, hip, and whole body (WB) BMD, spine bone mineral apparent density, and WB bone mineral content/height (BMC/Ht) in females 12–21 years of age with AN who had never been on SSRIs, had been on SSRIs for <6 months (<6M), or had been on SSRIs for >6 months (>6M).Results: Subjects on SSRIs for >6M had lower spine, femoral-neck, and WBBMD Z-scores than those on SSRIs for <6M. Hip BMD and WBBMC/Ht Z-scores were lowest in subjects on SSRIs for >6M. Duration of SSRI use, duration since AN diagnosis and duration of amenorrhea inversely predicted BMD, whereas BMI was a positive predictor. In a regression model, duration of SSRI use remained an independent negative predictor of BMD.Discussion: Duration of SSRI use >6M is associated with low BMD in AN.Conclusion: It may be necessary to monitor BMD more rigorously when duration of SSRI use exceeds 6M.

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Fracture risk among men, in relation to osteopenia and osteoporosis defined by areal bone mineral density

Bone Abstracts ◽

10.1530/boneabs.1.pp343 ◽

2013 ◽

Author(s):

Julie Pasco ◽

Stephen Lane ◽

Sharon Brennan ◽

Elizabeth Timney ◽

Gosia Bucki-Smith ◽

...

Keyword(s):

Bone Mineral Density ◽

Fracture Risk ◽

Bone Mineral ◽

Areal Bone Mineral Density ◽

Mineral Density

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A Three-Year Longitudinal Study Comparing Bone Mass, Density, and Geometry Measured by DXA, pQCT, and Bone Turnover Markers in Children with PKU Taking L-Amino Acid or Glycomacropeptide Protein Substitutes

Nutrients ◽

10.3390/nu13062075 ◽

2021 ◽

Vol 13 (6) ◽

pp. 2075

Author(s):

Anne Daly ◽

Wolfgang Högler ◽

Nicola Crabtree ◽

Nick Shaw ◽

Sharon Evans ◽

...

Keyword(s):

Amino Acid ◽

Bone Density ◽

Bone Turnover ◽

Bone Mineral ◽

Bone Turnover Markers ◽

Blood Biochemistry ◽

Reference Ranges ◽

Mineral Density ◽

Bone Mineral Apparent Density ◽

Turnover Markers

In patients with phenylketonuria (PKU), treated by diet therapy only, evidence suggests that areal bone mineral density (BMDa) is within the normal clinical reference range but is below the population norm. Aims: To study longitudinal bone density, mass, and geometry over 36 months in children with PKU taking either amino acid (L-AA) or casein glycomacropeptide substitutes (CGMP-AA) as their main protein source. Methodology: A total of 48 subjects completed the study, 19 subjects in the L-AA group (median age 11.1, range 5–6 years) and 29 subjects in the CGMP-AA group (median age 8.3, range 5–16years). The CGMP-AA was further divided into two groups, CGMP100 (median age 9.2, range 5–16years) (n = 13), children taking CGMP-AA only and CGMP50 (median age 7.3, range 5–15years) (n = 16), children taking a combination of CGMP-AA and L-AA. Dual X-ray absorptiometry (DXA) was measured at enrolment and 36 months, peripheral quantitative computer tomography (pQCT) at 36 months only, and serum blood and urine bone turnover markers (BTM) and blood bone biochemistry at enrolment, 6, 12, and 36 months. Results: No statistically significant differences were found between the three groups for DXA outcome parameters, i.e., BMDa (L2–L4 BMDa g/cm2), bone mineral apparent density (L2–L4 BMAD g/cm3) and total body less head BMDa (TBLH g/cm2). All blood biochemistry markers were within the reference ranges, and BTM showed active bone turnover with a trend for BTM to decrease with increasing age. Conclusions: Bone density was clinically normal, although the median z scores were below the population mean. BTM showed active bone turnover and blood biochemistry was within the reference ranges. There appeared to be no advantage to bone density, mass, or geometry from taking a macropeptide-based protein substitute as compared with L-AAs.

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Cross-sectional and Longitudinal Evaluation of Bone Mass in Children and Young Adults with Juvenile Idiopathic Arthritis: The Role of Bone Mass Determinants in a Large Cohort of Patients

The Journal of Rheumatology ◽

10.3899/jrheum.091241 ◽

2010 ◽

Vol 37 (9) ◽

pp. 1935-1943 ◽

Cited By ~ 29

Author(s):

STEFANO STAGI ◽

LAURA MASI ◽

SERENA CAPANNINI ◽

ROLANDO CIMAZ ◽

GIULIA TONINI ◽

...

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Bone Mass ◽

Bone Mineral ◽

Large Cohort ◽

Close Monitoring ◽

Mineral Density ◽

Cross Sectional ◽

Bone Mineral Apparent Density ◽

Longitudinal Evaluation ◽

Enthesitis Related Arthritis

Objective.To assess the prevalence of reduced spine bone mineral apparent density (BMAD), and to identify the main predictors of reduced spine BMAD in a cross-sectional and longitudinal evaluation of the same large cohort of patients with juvenile idiopathic arthritis (JIA). There are few prospective data on bone mass evaluation in a large number of patients with JIA, and with enthesitis-related arthritis onset.Methods.Two hundred nineteen patients with JIA (median age 8.7 yrs, range 6.1–13.1 yrs; 104 oligoarticular JIA, 61 polyarticular, 20 systemic, and 34 enthesitis-related arthritis onset) were retrospectively evaluated. A dual-energy x-ray absorptiometry (DEXA) scan at the lumbar spine was performed in all subjects. Of these, 89 consecutive patients were followed up randomly and longitudinally with a second and a third DEXA evaluation. The data obtained were compared with 80 age-matched and sex-matched healthy subjects.Results.At the first DEXA, patients with JIA showed a reduced spine BMAD standard deviation score (SDS) in comparison to controls (p < 0.001). These results were confirmed when the subjects were divided into JIA subtypes (p < 0.005) with the exception of enthesitis-related arthritis onset. Spine BMAD SDS significantly correlated with JIA onset type (p < 0.01), age at JIA onset (p < 0.005), and flares (p = 0.008). The longitudinal evaluation showed that spine BMAD SDS did not significantly improve at the followup in comparison to controls, in all subsets with JIA except for systemic onset (p < 0.05). Spine BMAD correlated with sex (p < 0.01), systemic corticosteroid exposure (p < 0.01), the number of intraarticular corticosteroid injections (p < 0.01), the interval from last steroid injection (p < 0.05), erythrocyte sedimentation rate (p < 0.005), and C-reactive protein levels (p < 0.005).Conclusion.Patients with JIA have a low bone mass and, after a first increase due to therapy, do not reach a healthy condition over time despite our current more effective drugs. These patients have a high risk of osteoporosis in early adulthood. To reduce the risk and improve the bone mass, close monitoring of bone mineral density, better control of disease activity, physical activity, and intake of calcium and vitamin D are recommended. In patients with osteoporosis, therapeutic approaches including bisphosphonates should be considered.

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Evaluation of vertebral volumetric vs. areal bone mineral density during growth

Bone ◽

10.1016/s8756-3282(97)00057-4 ◽

1997 ◽

Vol 20 (6) ◽

pp. 553-556 ◽

Cited By ~ 22

Author(s):

S.M. Ott ◽

M. O'Hanlan ◽

E.W. Lipkin ◽

L. Newell-Morris

Keyword(s):

Bone Mineral Density ◽

Bone Mineral ◽

Areal Bone Mineral Density ◽

Mineral Density

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Relationship of age to bone microstructure independent of areal bone mineral density

Journal of Bone and Mineral Research ◽

10.1002/jbmr.1468 ◽

2012 ◽

Vol 27 (3) ◽

pp. 637-644 ◽

Cited By ~ 83

Author(s):

Kristy M Nicks ◽

Shreyasee Amin ◽

Elizabeth J Atkinson ◽

B Lawrence Riggs ◽

L Joseph Melton ◽

...

Keyword(s):

Bone Mineral Density ◽

Bone Mineral ◽

Bone Microstructure ◽

Areal Bone Mineral Density ◽

Mineral Density ◽

Relationship Of

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Hypovitaminosis D in Patients with Ankylosing Spondylitis: Frequency and Consequences

Current Rheumatology Reviews ◽

10.2174/1573397117666210308122515 ◽

2021 ◽

Vol 17 ◽

Author(s):

Gehan Elolemy ◽

Waleed Hassan ◽

Mohamed Nasr ◽

Eman Baraka

Keyword(s):

Vitamin D ◽

Ankylosing Spondylitis ◽

Disease Activity ◽

Bone Mineral ◽

Hypovitaminosis D ◽

Healthy Controls ◽

Mineral Density ◽

Z Scores ◽

The Impact ◽

Active Disease

Objectives: was to assess the frequency of hypovitaminosis D in patients with ankylosing spondylitis (AS) compared to healthy controls and to evaluate its association with disease activity, structural damage and bone mineral density (BMD). Methods: Serum 25(OH) D in 30 AS male patients was compared to 30 matched healthy controls. AS disease activity was assessed using AS Disease Activity Score and C - reactive protein (ASDAS-CRP). Bath AS Functional Index (BASFI) and Bath AS Metrology Index (BASMI) were used to assess the functional impairment and the spinal mobility respectively. Radiological damage was scored according to modified Stoke AS Spine Score (mSASSS) and BMD was measured in the lumbar spine and femoral neck. Results: The mean serum 25(OH)D levels in AS patients were significantly lower compared to healthy controls (27.73 ± 14.27 vs. 38.46 ± 8.11ng/ml, P <0.001). Among the patients, 60% exhibited hypovitaminosis D. AS patients with hypovitaminosis D had significantly higher ASDAS-CRP (p<0.001), BASFAI (p=0.0003) and mSASSS (p=0.04) scores. Additionally, BMD and Z scores at lumbar and femoral sites were significantly reduced in the patients with hypovitaminosis D (P < 0.05). Serum 25(OH)D was positively correlated with BMD (lumbar and femoral; p=0.002 and p=0.01 respectively) and Z scores (lumbar and femoral; p<0.001and p=0.01 respectively), whereas, negatively correlated with ASDAS-CRP (p<0.001), BASFI (p<0.001), mSASSS (p=0.003). ASDAS -CRP was the only significant predictor of hypovitaminosis D in AS patients. Conclusions: hypovitaminosis D is prevalent among AS patients and is associated with increased risk of active disease, impaired function, radiographic severity and bone mineral loss. Future studies with larger sample size are recommended to assess the impact of vitamin D deficiency on radiological progression in AS and to address whether or not vitamin D supplementation will help control active disease.

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