Tratamiento con hormona del crecimiento recombinante para la hipofosfatemia ligada al cromosoma X en niños
Información
- DOI:
- https://doi.org/10.1002/14651858.CD004447.pub3Copiar DOI
- Base de datos:
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- Cochrane Database of Systematic Reviews
- Versión publicada:
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- 07 octubre 2021see what's new
- Tipo:
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- Intervention
- Etapa:
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- Review
- Grupo Editorial Cochrane:
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Grupo Cochrane de Fibrosis quística y enfermedades genéticas
- Copyright:
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- Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Cifras del artículo
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Autores
Contributions of authors
Versions up to 2011
Professor Meng Mao served as a consultant and gave important help in the update.
Associate Professor Fan Yang together with Huiming Yang extracted and analysed the data.
Professor Chaomin Wan gave guidance in statistics and data analysis.
Huiming Yang acts as guarantor of the review.
Version published 2021
Sherie Smith and Tracey Remmington undertook study selection and data extraction and both authors contributed to updating the text of the review.
Sources of support
Internal sources
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Chinese Cochrane Centre, Chinese Centre of Evidence‐based Medicine, West China Hospital of Sichuan University, China
Support for original version of review.
External sources
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China Medical Board of New York, USA
Support for original version of review.
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National Institute for Health Research, UK
This systematic review was supported by the National Institute for Health Research, via Cochrane Infrastructure funding to the Cochrane Cystic Fibrosis and Genetic Disorders Group.
Declarations of interest
Both authors: none known.
Acknowledgements
Many thanks to the Cochrane Cystic Fibrosis and Genetic Disorders Review Group.
The new author team (SS and TR) would like to thank the previous author team (Hui Ming Yang, Meng Mao, Fan Yang, Chaomin Wan) for their contributions to this review up to the 2021 update.
Version history
| Published | Title | Stage | Authors | Version |
| 2021 Oct 07 | Recombinant growth hormone therapy for X‐linked hypophosphatemia in children | Review | Sherie Smith, Tracey Remmington | |
| 2005 Jan 24 | Recombinant growth hormone therapy for X‐linked hypophosphatemia in children | Review | Hui Ming Yang, Meng Mao, Fan Yang, Chaomin Wan | |
| 2003 Oct 20 | Recombinant growth hormone therapy for X‐linked hypophosphatemia in children | Protocol | Yang Huiming, Wan Chaomin | |
Differences between protocol and review
At the 2021 update, we added a summary of findings table to the review.
Keywords
MeSH
Medical Subject Headings (MeSH) Keywords
Medical Subject Headings Check Words
Child; Humans;
PICO
Study flow diagram.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Comparison 1: Growth hormone (GH) versus control (no treatment), Outcome 1: Height (SDS)
Comparison 1: Growth hormone (GH) versus control (no treatment), Outcome 2: Measures of mineral metabolism: serum phosphate (mmol/L)
Comparison 1: Growth hormone (GH) versus control (no treatment), Outcome 3: Measures of endocrine function: serum alkaline phosphatase activity (IU/L)
Comparison 1: Growth hormone (GH) versus control (no treatment), Outcome 4: Measures of endocrine function: serum IGF (SDS)
Comparison 1: Growth hormone (GH) versus control (no treatment), Outcome 5: Measures of renal function: TmP/GFR (mmol/L)
Comparison 1: Growth hormone (GH) versus control (no treatment), Outcome 6: BMD: determination of bone age (years) (change from baseline)
Comparison 1: Growth hormone (GH) versus control (no treatment), Outcome 7: Body proportions: sitting height (SDS)
Comparison 1: Growth hormone (GH) versus control (no treatment), Outcome 8: Body proportions: arm length (SDS)
Comparison 1: Growth hormone (GH) versus control (no treatment), Outcome 9: Body proportions: leg length (SDS)
| Recombinant growth hormone compared with placebo/no intervention for X‐linked hypophosphataemia | ||||||
| Patient or population: children with X‐linked hypophosphataemia Settings: outpatient Intervention: rhGH (0.08 mg/kg/day given daily by SI (Seikaly 1997); 0.4 mg/kg/week by SI (Živičnjak 2011)) Comparison: placebo SI (Seikaly 1997) or no treatment (Živičnjak 2011) | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No of Participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Assumed risk | Corresponding risk | |||||
| Control | rhGH | |||||
| Longitudinal growth: change in height SDS
Follow‐up: 1 to 3 years | Both studies reported within‐group differences and found height SDS score to be significantly improved from baseline in the rhGH groups compared with no change in the control groups. Between group analysis of the study results from the larger parallel study showed there to be no difference between groups after one year of treatment, MD 0.00 SDS (95 % CI ‐1.04 to 1.04) and a slight improvement at 2 years, MD 0.30 SDS (95 % CI ‐0.74 to 1.34) and 3 years, MD 0.50 SDS (95 % CI ‐0.54 to 1.54), but this was not statistically significant (Živičnjak 2011). | 20 | ⊕⊕⊝⊝ Due to risk of bias and imprecision | Both studies reported within‐group differences which may enhance the effects seen (Seikaly 1997; Živičnjak 2011) | ||
| Measures of mineral metabolism: change in serum phosphate mmol/L
Follow‐up: 1 to 3 years | One study reported no significant change in serum phosphate levels in either group by the end of the study (Seikaly 1997). Serum phosphate was significantly increased after 3 years in the second study, MD 0.18 mmol/L (95 % CI 0.08 to 0.28) (P = 0.0007) (Živičnjak 2011). | 20 | ⊕⊝⊝⊝ Due to risk of bias, imprecision and inconsistency | The Seikaly studiy reports within‐group differences only. Results appear to be opposing for this outcome but the Seikaly study was only reported at one year (Seikaly 1997) The Živičnjak study was 3 years duration and showed an effect at the three year time point (Živičnjak 2011). | ||
| Measures of endocrine function function: change in levels of alkaline phosphatase IU/L
Follow‐up: 1 to 3 years | No difference was reported in levels of alkaline phosphatase at the end of the studies (Seikaly 1997; Živičnjak 2011). | 20 | ⊕⊕⊝⊝
| There was a transient increase in ALP after one year of treatment compared to control in the Živičnjak study, MD 91.00 IU/L (95 % CI 25.21 to 156.79) (Živičnjak 2011) | ||
| Measures of renal function: change in TmP/GFR
Follow‐up: 1 to 3 years | There was no statistically significant difference in TmP/GFR between the rhGH and control groups at either 6 months, MD ‐0.05 mmol/L (95 % CI ‐0.15 to 0.05); 1 year, MD 0.01 mmol/L (95 % CI ‐0.16 to 0.18); 2 years, MD 0.12 mmol/L (95 % CI ‐0.14 to 0.38); or 3 years, MD 0.00 mmol/L (95 % CI ‐0.25 to 0.25) (Seikaly 1997; Živičnjak 2011). | 20 | ⊕⊝⊝⊝ Due to risk of bias, imprecision and publication bias | Both studies reported transient increases in TmP/GFR in the rhGH treated group compared to baseline (within‐group difference) (Seikaly 1997; Živičnjak 2011). Seikaly found an increase in TmP/GFR at 3 months but not thereafter, whilst Živičnjak found a transient increase in the rhGH group and not in the control group.
No results were presented in the published paper for the control group in the Seikaly study (Seikaly 1997).
| ||
| Body proportions: sitting height SDS
Follow‐up: 3 years | There was no difference in sitting height SDS after 1 year, MD ‐0.15 SDS (95 % CI ‐1.03 to 0.73) and a slight but non‐significant improvement in sitting height favouring the rhGH treated group after 3 years (Živičnjak 2011). | 15 | ⊕⊕⊕⊝ Due to imprecision | This outcome was only reported in one of the studies (Živičnjak 2011).
| ||
| Adverse effects
Follow‐up: 1 to 3 years | rhGH was well tolerated in both studies with one study reporting three participants with adverse effects (Seikaly 1997; Živičnjak 2011). One participant developed transient glucosuria that was not associated with hyperglycemia, one participant developed transient splenomegaly and one participant developed muscular protruberance. The Živičnjak study reported that there were no side effects observed. | 20 | ⊕⊕⊝⊝ Due to risk of bias and imprecision |
| ||
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1. High risk of bias due to one of the studies being a small cross‐over study where the results have been reported as if it were a parallel trial and where the risk of bias is unclear due to the randomisation process not being reported. 2. Imprecision due to very small numbers of participants in both studies. 3. Inconsistency due to studies reporting opposing results for this outcome 4. Selective reporting of results for this outcome as no data were given in the published paper for the control group | ||||||
| longitudinal growth | baseline | 3 months | 12 months |
|---|---|---|---|
| height z score (treatment) | ‐2.66 (0.21) | ‐2.02 (0.25) | ‐1.46 (0.28) |
| height z score (control) | ‐2.27 (0.30) | ‐2.22 (0.16) | |
| growth velocity (treatment) | 4.04 (1.50) | ||
| growth velocity (control) | ‐1. 90 (0.40) |
| Outcome | Baseline | 3 months | 12 months |
|---|---|---|---|
| Serum phosphate (mmol/L) (treatment) | 0.88 (0.07) | 1.17 (0.14) | |
| Serum calcium (mmol/L) (treatment) | 2.4 (0.1) | 2.3 (0.1) | |
| Serum calcium (mmol/L) (control) | 2.3 (0.1) | 2.3 (0.1) | |
| Insulin‐like growth factor 1 (ng/mL) (treatment) | 114.0 (25.0) | 354.0 (51.0) | |
| Insulin‐like growth factor 1 (ng/mL) (control) | 224.0 (60.0) | 157.0 (32.0) | |
| Urinary calcium/creatinine ratio (treatment) | 0.10 (0.06) | 0.17 (0.02) | |
| Urinary calcium/creatinine ratio (control) | 0.15 (0.03) | 0.20 (0.04) | |
| Tubular maximum for phosphate reabsorption (mg/dL) (treatment) | 2.12 (0.15) | 3.41 (0.25) | |
| 24 hr urinary albumin excretion (mg) (treatment) | 4.0 (1.0) | 5.0 (2.0) | |
| 24 hr urinary albumin excretion (mg) (control) | 2.0 (1.0) | 3.0 (1.0) | |
| Change of bone mass (g/cm) (treatment) | 0.04 (0.02) | ||
| Change of bone mass (g/cm) (control) | 0.02 (0.01) | ||
| Change of bone width (cm) (treatment) | 0.18 (0.06) | ||
| Change of bone width (cm) (control) | 0.02 (0.08) | ||
| Change of bone density (g/cm2) (treatment) | 0.04 (0.06) | ||
| Change of bone density (g/cm2) (control) | 0.01 (0.01) |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 Height (SDS) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.1.1 1 year | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.1.2 2 years | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.1.3 3 years | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.2 Measures of mineral metabolism: serum phosphate (mmol/L) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.2.1 6 months | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.2.2 1 year | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.2.3 2 years | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.2.4 3 years | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.3 Measures of endocrine function: serum alkaline phosphatase activity (IU/L) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.3.1 6 months | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.3.2 1 year | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.3.3 2 years | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.3.4 3 years | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.4 Measures of endocrine function: serum IGF (SDS) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.4.1 6 months | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.4.2 1 year | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.4.3 2 years | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.4.4 3 years | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.5 Measures of renal function: TmP/GFR (mmol/L) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.5.1 6 months | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.5.2 1 year | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.5.3 2 years | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.5.4 3 years | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.6 BMD: determination of bone age (years) (change from baseline) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.6.1 3 years | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.7 Body proportions: sitting height (SDS) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 1.7.1 1 year | 1 | 15 | Mean Difference (IV, Fixed, 95% CI) | ‐0.15 [‐1.03, 0.73] |
| 1.7.2 2 years | 1 | 15 | Mean Difference (IV, Fixed, 95% CI) | 0.40 [‐0.37, 1.17] |
| 1.7.3 3 years | 1 | 15 | Mean Difference (IV, Fixed, 95% CI) | 0.35 [‐0.14, 0.84] |
| 1.8 Body proportions: arm length (SDS) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.8.1 1 year | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.8.2 2 years | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.8.3 3 years | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.9 Body proportions: leg length (SDS) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.9.1 1 year | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.9.2 2 years | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 1.9.3 3 years | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
