Mariska Vlot

Effect of pubertal suppression and cross-sex hormone therapy on bone turnover markers and bone mineral apparent density (BMAD) in transgender adolescents

Puberty is highly important for the accumulation of bone mass. Bone turnover and bone mineral density (BMD) 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). We aimed to investigate the effect of GnRHa and CSHT on bone turnover markers (BTMs) and bone mineral apparent density (BMAD) in transgender adolescents. Gender dysphoria was diagnosed based on diagnostic criteria according to the DSM-IV (TR). Thirty four female-to-male persons (transmen) and 22 male-to-female persons (transwomen)were included. Patients were allocated to a young (bone age of <15years in transwomen or <14 in transmen) or old group (bone age of ≥15years in transwomen or ≥14years in transmen). All were treated with GnRHa triptorelin and CSHT was added in incremental doses from the age of 16years. Transmen received testosterone esters (Sustanon, MSD) and transwomen received 17-β estradiol. P1NP, osteocalcin, ICTP and BMD of lumbar spine (LS) and femoral neck (FN) were measured at three time points. In addition, BMAD and Z-scores were calculated. We found a decrease of P1NP and 1CTP during GnRHa treatment, indicating decreased bone turnover (young transmen 95% CI -74 to -50%, p=0.02, young transwomen 95% CI -73 to -43, p=0.008). The decrease in bone turnover upon GnRHa treatment was accompanied by an unchanged BMAD of FN and LS, whereas BMAD Z-scores of predominantly the LS decreased especially in the young transwomen. Twenty-four months after CSHT the BTMs P1NP and ICTP were even more decreased in all groups except for the old transmen. During CSHT BMAD increased and Z-scores returned towards normal, especially of the LS (young transwomen CI 95% 0.1 to 0.6, p=0.01, old transwomen 95% CI 0.3 to 0.8, p=0.04). To conclude, suppressing puberty by GnRHa leads to a decrease of BTMs in both transwomen and transmen 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 24months of CSHT. Therefore, the added value of evaluating BTMs seems to be limited and DXA-scans remain important in follow-up of bone health of transgender adolescents.

Bone Mineral Density Increases in Trans Persons After 1 Year of Hormonal Treatment: A Multicenter Prospective Observational Study

Sex steroids are important determinants of bone acquisition and bone homeostasis. Cross‐sex hormonal treatment (CHT) in transgender persons can affect bone mineral density (BMD). The aim of this study was to investigate in a prospective observational multicenter study the first‐year effects of CHT on BMD in transgender persons. A total of 231 transwomen and 199 transmen were included who completed the first year of CHT. Transwomen were treated with cyproterone acetate and oral or transdermal estradiol; transmen received transdermal or intramuscular testosterone. A dual‐energy X‐ray absorptiometry (DXA) was performed to measure lumbar spine (LS), total hip (TH), and femoral neck (FN) BMD before and after 1 year of CHT. In transwomen, an increase in LS (+3.67%, 95% confidence interval [CI] 3.20 to 4.13%, p < 0.001), TH (+0.97%, 95% CI 0.62 to 1.31%, p < 0.001), and FN (+1.86%, 95% CI 1.41 to 2.31%, p < 0.001) BMD was found. In transmen, TH BMD increased after 1 year of CHT (+1.04%, 95% CI 0.64 to 1.44%, p < 0.001). No changes were observed in FN BMD (–0.46%, 95% CI –1.07 to 0.16%, p = 0.144). The increase in LS BMD was larger in transmen aged ≥50 years (+4.32%, 95% CI 2.28 to 6.36%, p = 0.001) compared with transmen aged <50 years (+0.68%, 95% CI 0.19 to 1.17%, p = 0.007). In conclusion, BMD increased in transgender persons after 1 year of CHT. In transmen of postmenopausal age, the LS BMD increased more than in younger transmen, which may lead to the hypothesis that the increase in BMD in transmen is the result of the aromatization of testosterone to estradiol.

Effect of antiretroviral therapy on bone turnover and bone mineral density in men with primary HIV-1 infection

Introduction Previous studies indicate that human immunodeficiency virus (HIV)-infection and combination antiretroviral therapy (cART) can affect bone turnover. Furthermore, HIV-infected patients have lower bone mineral density (BMD) compared to a healthy reference population. Objective To evaluate the longitudinal effect of HIV-infection and cART on bone turnover markers (BTMs) and BMD in men with primary HIV-infection (PHI). Design, methods Thirty-five PHI-men were divided into two groups, those that received cART for the first time (n = 26) versus no-cART (n = 9). Dual-energy X-ray absorptiometry (DXA) was performed on femoral neck (FN), total hip (TH) and lumbar spine (LS) and BTMs (P1NP, alkaline phosphatase, osteocalcin, ICTP and CTX) were measured at baseline and follow-up. Results At baseline, the median CD4+ T-cell count was 455 cells/mm3 (IQR 320–620) and plasma viral load 5.4 log10 copies/mL (IQR 4.7–6.0) in the cART treated group, compared to 630 (IQR 590–910) and 4.8 (IQR 4.2–5.1) in the untreated group. The median follow-up time was 60.7 weeks (IQR 24.7–96.0). All BTMs, except ICTP, showed a significant increase during cART versus no changes of BTMs in the untreated group. FN and TH BMD showed a significant decrease in both groups. LS BMD did not change in both groups. Conclusion Bone turnover increased in PHI-men treated with cART which was accompanied by a decrease in FN and TH BMD. No increase of bone turnover was seen in untreated PHI-men. Our study suggests that cART results in increased bone turnover and decreased BMD of the hip in PHI-men.

Clinical utility of bone markers in various diseases.

Measurements of bone markers (BMs) in peripheral blood or urine are a pivotal part of bone research within modern clinical medicine. In recent years the use of BMs increased substantially as they can be useful either to diagnose bone (related) disease and to follow its natural history, but also to monitor the effects of interventions. However, the use of BMs is still complicated mainly due to (pre)analytical variability of these substances, limited accessibility of assays, variable cut-off values in different countries and laboratories and heterogeneous results with regard to clinical implications of measuring BMs in several studies. This review will provide the clinician with a practical guide, based on current evidence, in which circumstances to test which bone markers for optimal diagnostic purposes, in order to improve patient care in different areas of bone diseases including Pagets disease, primary osteoporosis, tumor induced osteomalacia, hypophosphatemic rickets, van Buchem disease, chronic kidney disease, rheumatoid arthritis, neoplasma/multiple myeloma, type 2 diabetes mellitus and primary hyperparathyroidism. The clinician should consider fasting state, recent fractures, aging, menopausal status, concomitant liver and kidney disease when ordering and interpreting BM measurements as these factors might result in misleading BM concentrations. We found that BMs are clearly useful in the current diagnosis of tumor induced osteomalacia, van Buchem disease, Pagets disease and hypophosphatemic rickets. In addition, BMs are useful to monitor disease activity in chronic kidney disease, Pagets disease and are useful to monitor treatment adherence in osteoporosis.