Treatment for 24 months with recombinant human GH has a beneficial effect on bone mineral density in young adults with childhood-onset GH deficiency

Conway, Gerard S.; Szarras‐Czapnik, Maria; Rácz, Kàroly; Keller, Alexandra; Chanson, Philippe; Tauber, Maïthé; Zacharin, Margaret

doi:10.1530/eje-08-0436

Cited by 61 publications

(40 citation statements)

References 64 publications

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“…During the last decade, there has been a growing body of literature describing the negative impact of GHD on body composition, bone health, metabolic profile, cardiovascular risk, and quality of life, in older adolescents and in adults, pleading for a maintenance of GHRT in young adults with persistent GHD (1,2). All of our knowledge on the long-term management of childhood onset GHD (CO-GHD) patients, once they become adults, relate to either large but multicentric studies (3,4,5,6,7,8) or to monocentric studies on small cohorts (9,10,11). There is a lack of large monocentric studies addressing this issue.…”

Section: Introductionmentioning

confidence: 99%

Monocentric study of 112 consecutive patients with childhood onset GH deficiency around and after transition

Courtillot

Baudoin²,

Souich³

et al. 2013

European Journal of Endocrinology

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ObjectivesOur aim was to analyze a large cohort of childhood onset GH deficiency (CO-GHD) adults from a unique adult center, in order to analyze their clinical management and to study the metabolic and bone status in relation to GHD and to the other pituitary deficits, and to evaluate these parameters during the long-term follow-up.Design and methodsObservational retrospective cohort study on 112 consecutive CO-GHD adults transferred to our unit from 1st January 1994 to 1st March 2012. Evaluation of GHD in pediatrics and after transition was conducted following consensus guidelines. Data recorded from pediatric and adult files were GH doses, pituitary magnetic resonance imaging and function, and metabolic and bone status.ResultsMost patients presented with severe CO-GHD (64%) associated with other pituitary deficits (66%). CO-GHD was acquired in 56%, congenital in 33%, and idiopathic in 11% cases. Most patients (83%) stopped GH before transfer, at 16.3 years (median), despite persistence of GHD. Median age at transfer was 19.4 years. After transfer, GHD persisted in 101 patients and four of the 11 resolutive GHD were non idiopathic. IGF1 level was <−2 SDS in 70% of treated patients at transfer and in 34% of them after 3 years of treatment. Follow-up showed improvement in lipid profile and bone mineral density in severely persistent GHD patients under GH therapy. In multivariate analysis, the associated pituitary deficits seemed stronger determinant factors of metabolic and bone status than GHD.ConclusionsThis study raises concern about discontinuation of GH replacement therapy in pediatrics in severely persistent GHD patients and about the often insufficient dose of GH in the treatment of adult patients.

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Section: Introductionmentioning

confidence: 99%

Monocentric study of 112 consecutive patients with childhood onset GH deficiency around and after transition

Courtillot

Baudoin²,

Souich³

et al. 2013

European Journal of Endocrinology

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“…Studies in these patients have particularly been investigating if continuous GH therapy results in a progressive increase in BMD after epiphyseal closure and final height (8,9,(29)(30)(31)(32) and whether stopping GH therapy causes a negative change in BMD. The longest follow-up in these patients is 2 years (9, 30-32), and five studies included a control group of non-GH-treated patients who had been off GH therapy for 1 week to 5 years before enrolment (8,9,(30)(31)(32). BMD increased between 5 and 8% on GH therapy and between 1 and 5% in the non-GH-treated patients (8,9,30,32), and in one study, no difference between groups was recorded (31).…”

Section: Discussionmentioning

confidence: 99%

“…The longest follow-up in these patients is 2 years (9, 30-32), and five studies included a control group of non-GH-treated patients who had been off GH therapy for 1 week to 5 years before enrolment (8,9,(30)(31)(32). BMD increased between 5 and 8% on GH therapy and between 1 and 5% in the non-GH-treated patients (8,9,30,32), and in one study, no difference between groups was recorded (31). One problem with these studies is the carry-over effect of previous GH therapy on BMD that will last for 1-2 years after stopping GH therapy (9).…”

Section: Discussionmentioning

confidence: 99%

“…One problem with these studies is the carry-over effect of previous GH therapy on BMD that will last for 1-2 years after stopping GH therapy (9). Furthermore, higher GH doses were used and some even used paediatric doses (9,30), and particularly females needed the higher doses (32), as they are less sensitive to standard GH doses (32,33). GH-deficient ALL patients are, however, different from patients in the above-mentioned studies, as most of the ALL patients are GH naïve and have changed from partial GHD to insufficient and more severely GHD later in life.…”

Section: Discussionmentioning

confidence: 99%

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Bone loss after childhood acute lymphoblastic leukaemia: an observational study with and without GH therapy

Follin¹,

Link²,

Wiebe³

et al. 2011

European Journal of Endocrinology

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Objective: Bone mineral density (BMD) in survivors of acute lymphoblastic leukaemia (ALL) seems to vary with time, type of treatments and GH status. We aimed to evaluate BMD in ALL patients with GH deficiency (GHD), with and without GH therapy. Design: Case-control study. Methods: We examined 44 (21 women) GHD patients (median 25 years) treated with cranial radiotherapy (18-24 Gy) and chemotherapy and matched population controls for BMD with dualenergy X-ray absorptiometry. For 5 and 8 years, two subgroups with (0.5 mg/day) (nZ16) and without GH therapy (nZ13) and matched controls were followed respectively. Results: At baseline, no significant differences in BMD or Z-scores at femoral neck and L2-L4 were recorded (all PO0.3). After another 8 years with GHD, the Z-scores at femoral neck had significantly decreased compared with baseline (0.0 to K0.5; P!0.03) and became lower at the femoral neck (PZ0.05), and at L2-L4 (P!0.03), compared with controls. After 5 years of GH therapy, only female ALL patients had a significantly lower femoral neck Z-scores (PZ0.03). The female ALL patients reached an IGF1 level of K0.7 S.D. and male patients reached the level of C0.05 S.D. Conclusions: On average, 25 years after diagnosis, GH-deficient ALL patients experienced a significant decrease in Z-scores at femoral neck, and if Z-scores continue to decrease, there could be a premature risk for osteoporosis. GH therapy was not shown to have a clear beneficial effect on BMD. Whether higher GH doses, particularly in women, will improve Z-scores needs further investigation.

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“…GH therapy in adolescents and adults with GHD reduces fat mass, increases lean mass and bone density, improves lipid profile and psychosocial well-being Conway et al, 2009;Nelson et al, 1988). …”

Section: Growth Hormonementioning

confidence: 99%

A systems biology approach towards child obesity and obesity-related diseases: integration of clinical, genetic, hormonal and NMR metabonomic factors

Rahman¹

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Systems biology has become a powerful scientific method using a more holistic perspective to tackle biological and biomedical research. Complex data obtained from different types of experiments using multiple interdisciplinary tools such as metabonomics and transcriptomics can be integrated and analysed to give a better understanding of the biological problem at hand. This PhD thesis comprises closely related project parts that utilise tools of systems biology (NMR-based metabonomics, gene expression profiling, and multivariate analysis) to investigate how growth hormone deficiency (GHD) and obesity can cause alterations in metabolism of children and adolescence. In addition, method development of collecting and storage of human urine samples for NMR-based metabonomic studies were also investigated to aid in achieving accurate metabolic fingerprints. The first project established a novel standard procedure of collection, storage and preservation of human urine samples to ensure the measurement of true metabolic fingerprints in NMR-based metabonomic studies. Human urine samples are susceptible to metabolite changes when left at room temperature for less than 24 hours even with the addition of different preservatives and I have successfully established the minimum requirements to maintain the stability of urine samples for 48 hours at room temperature. Once a standard procedure of sample handling was established, a NMR-based metabonomics pilot study was performed in which the metabolic profiles of a growth hormone (GH)-deficient adolescent subject were tracked with NMR-based urinary metabonomics during five years of GH therapy . Detection of urinary metabolites related to GHD provided a clearer picture of the impact GH therapy has on metabolism. Metabonomics was able to differentiate the metabolic profiles of healthy controls from the GHD subject indicating that metabonomics has the capability to be utilised as a platform to identify the effects of GH treatment on metabolism in humans. The main project of this PhD was a study of metabolic changes in children with obesity and used tools of systems biology such as NMR-based urinary metabonomics and peripheral blood mononuclear cell (PBMC) gene expression analysis to investigate samples collected as part of the KOALA childhood obesity program. Results from both metabonomics and gene expression profiling studies were combined with clinical data using multivariate analysis (O2PLS) to provide a clearer picture of how obesity can disrupt metabolism in children. The outcome(s) of this study support the utilisation of NMR-based metabonomics as a potential diagnostic and prognostic tool not only in the context of obesity, but make the technique also available for the study of other diseases. In addition, gene expression studies of PBMCs identified significant NRs and NR-dependent pathways that may improve our understanding of the underlying molecular mechanisms in metabolic dysfunction in obesity. In summary, using tools of systems biology, a better understand can b...

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Treatment for 24 months with recombinant human GH has a beneficial effect on bone mineral density in young adults with childhood-onset GH deficiency

Cited by 61 publications

References 64 publications

Monocentric study of 112 consecutive patients with childhood onset GH deficiency around and after transition

Monocentric study of 112 consecutive patients with childhood onset GH deficiency around and after transition

Bone loss after childhood acute lymphoblastic leukaemia: an observational study with and without GH therapy

A systems biology approach towards child obesity and obesity-related diseases: integration of clinical, genetic, hormonal and NMR metabonomic factors

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