Beneficial effects of extended growth hormone treatment after hospital discharge in pediatric burn patients

OBJECTIVE: To study the efficacy of growth hormone given to severely burned children from discharge to 12 months after burn and for 12 months after the drug was discontinued. SUMMARY BACKGROUND DATA: We have previously shown that low-dose recombinant human growth hormone (rhGH), given to children after a severe thermal injury, successfully improved lean muscle mass, bone mineral content, and growth. The aim of the present study was to investigate long-term functional improvements after treatment. METHODS: Forty-four pediatric patients with over 40% total body surface area burns were studied for 24 months after burn. Patients were randomized to receive either rhGH (0.05 mg/kg body weight) or placebo. Height, weight, body composition, serum hormones, resting energy expenditure, cardiac function, muscle strength, and number of reconstructive procedures performed were measured during rhGH treatment and for 12 months after treatment was discontinued. Statistical analysis used Tukey's multiple comparison test. Significance was accepted at P < 0.05. RESULTS: Height, weight, lean body mass, bone mineral content, cardiac function, and muscle strength significantly improved during rhGH treatment compared with placebo (P < 0.05). This treatment significantly increased GH, IGF-I, and IGFBP-3, whereas serum cortisol decreased (P < 0.05). The number of operative reconstructive procedures was significantly lower with rhGH (P < 0.05). Improvements in height, bone mineral content, and IGF-1 concentrations persisted after rhGH treatment (P < 0.05). No side effects with rhGH were observed. CONCLUSIONS: Administration of rhGH for 1 year after burn was safe and improved recovery. These salutary effects continued after rhGH treatment was discontinued.     

Recombinant human growth hormone treatment of children following renal transplantation

Nine growth-retarded renal allograft recipients received either thrice weekly or daily subcutaneous recombinant human growth hormone (rhGH) for 6–30 months. The annualized growth velocity for the initial year of rhGH treatment was significantly greater than that of the preceding year (2.5±2.1 vs 5.7±2.7;P<0.0001). There was no advancement in bone age greater than the increase in chronological age, no significant increase in the mean fasting serum glucose or insulin levels, nor significant decrease in the calculated creatinine clearance following rhGH treatment. However, two patients experienced rejection episodes following rhGH treatment indicating the potiental adverse consequences of the treatment on allograft function. This will require further delineation in prospective controlled studies. The serum insulin-like growth factor-1 levels significantly increased at 6 months (P<0.009) and 12 months (P<0.002) following rhGH treatment compared with baseline values. These preliminary data indicate that rhGH treatment may be effective in improving the growth velocity of growth-retarded renal allograft recipients.     

Effects of growth hormone on kidney function in pediatric transplant recipients

Recent evidence suggests that treatment with recombinant human growth hormone (rhGH) after a successful kidney transplant improves the growth rate of children with short stature. We prospectively investigated eight children (6 boys, 2 girls), focusing on acute rejection episodes and changes in serum creatinine levels during rhGH treatment. The children (mean age 11.6±3.4 years) received rhGH daily (0.04–0.05 mg/kg subcutaneously). Seven patients completed at least 12 months (20±8 months) of rhGH treatment. Their mean serum creatinine level was 1.3±0.7 mg/dl 12 months before, and increased to 3.4±4.2 mg/dl after 12 months of rhGH treatment, but did not achieve statistical significance (P=0.06). Their mean calculated glomerular filtration rate was 58±20 ml/min per 1.73 m² 12 months before, and decreased to 38±21 ml/min per 1.73 m² 12 months before, and decreased to 38±21 ml/min per 1.73 m² after 12 months of rhGH treatment, but did not achieve statistical significance (P=0.08). Of the seven patients, two developed acute rejection after 5 and 6 rejection-free years; three lost their grafts and returned to dialysis. These preliminary observations describe untoward renal events in children receiving rhGH treatment after a kidney transplant.     

X-linked hypophosphatemia: effects of treatment with recombinant human growth hormone

The impact of recombinant human growth hormone (rhGH) treatment on growth, bone mineral metabolism, and bone mineral density (BMD) was evaluated in six children (3 girls, 3 boys) with familial hypophosphatemic rickets (XLH). Five were prepubertal (aged 6–8.8 years), one 15.3-year-old boy had combined XLH and GH deficiency, but had not been treated with rhGH previously. rhGH was administered daily for 1 year, at a dose of 1 IU/kg per week, combined with 1,25-dihydroxyvitamin D₃ and oral phosphate therapy. Z scores for growth velocity and height improved significantly (–2.9 vs. 2.5, P <0.01, and –2.2 vs. –1.5, P <0.01, respectively). However, the ratio of Z score for height to that of subischial leg length decreased significantly (0.65 vs. 0.43, P <0.01), indicating disproportionate growth in favor of the trunk. The height-corrected BMD Z increased slightly (–0.99 vs. –0.94, P <0.05). A slight increase in serum phosphate occurred (0.78 vs. 0.88 mmol/l, P <0.02). Tubular reabsorption of phosphate/glomerular filtration rate increased from 0.45 mmol/l to 0.55 mmol at 6 months (P <0.02), but returned to the initial level at 12 months. These results indicate that children with XLH can benefit from the positive effect of rhGH on growth, however treatment could aggravate the already existing tendency to disproportionate growth. GH production should be evaluated in poorly growing patients with XLH, because it can mask GH deficiency. rhGH can be safely combined with conventional treatment in XLH. Further studies are needed to determine the effect of treatment on final height and maximal BMD. Received October 21, 1996; received in revised form March 21, 1997; accepted March 27, 1997     

Bone alkaline phosphatase in children with chronic renal failure

Background: With the introduction of a new immunoradiometric assay based on two monoclonal antibodies (Tandem®-Ostase, Hybritech) the determination of bone alkaline phosphatase (BAP) to evaluate bone metabolism in chronic renal failure has become easier and more valid. Subjects and methods: Using this test we investigated BAP in a total of 90 paediatric patients, 42 (9.2±5.5 years) with chronic renal failure on conservative treatment, 22 (9.5±5.4 years) under chronic dialysis, and 26 (16.2±5.9 years) after renal transplantation, compared to 203 controls (10.1±5.7 years). Results: The physiological age dependency found in controls including two peaks during infancy and puberty was distinctly disturbed in chronic renal failure. However, in patients BAP significantly correlated with height velocity rather reflecting the last 6 (r=0.56 P<0.001) than the last 12 months. Although BAP correlated well with total alkaline phosphatase (TAP; r=0.95 P<0.001), a significant correlation with the serum level of the intact parathyroid hormone could only be detected for BAP (r=0.45 P<0.001) but not for TAP (R=0.19 N.S.) Furthermore, BAP positively correlated with trabecular (n=40; r=0.40 P<0.05) and inversely with cortical bone density (n=19; r=-0.58 P<0.01) but no relationship was found with conventional X-ray. Conclusion: BAP determined by the new radioimmunoassay seems to represent an additional diagnostic tool to assess growth and bone turnover in paediatric patients with chronic renal failure that is complementary to the information provided by X-ray and total alkaline phosphatase. Key words: bone alkaline phosphatase; children; chronic renal failure      

An effective regimen of intranasal salmon calcitonin in early postmenopausal bone loss

Summary In order to devise a convenient and effective therapeutic regimen of intranasal salmon calcitonin (sCT) for the treatment of early postmenopausal bone loss, we studied the effects of a 1-year course of sCT nasal spray on vertebral mineral content (VMC), assessed by dual photon densitometry, and bone turnover in 21 early postmenopausal osteoporotic women. Subjects enrolled in the study had a value above the normal average of at least one index of bone turnover: whole body retention (WBR) of ^99mTc-methylenedichloro-bisphosphonate (^99mTc-MDP), serum bone gla protein (BGP), urinary hydroxyproline/creatinine excretion (HOP/Cr). After baseline evaluation, patients were randomized for treatment with either sCT (200 IU every other day) or plabebo. Treatment with sCT significantly increased VMC by 2.7±0.9% at 6 months, and 3.3±0.8% at 1 year, whereas a progressive decline was observed in the placebo group (-2.6±0.5%, and -3.5±0.5% after 6 and 12 months, respectively). These changes were associated with a progressive and significant reduction of all parameters of bone turnover in the sCT-treated patients, whereas no changes were detected in the control group during the study period. The differences between the two groups were significant after 1 year for VMC, BGP, and WBR (P<0.05, one-way analysis of variance). Thus, 200 IU intranasal sCT administered on alternate days is adequate to stop the fast bone loss occurring early after the menopause in women with high bone turnover rates. This therapeutical modality represents an important addition to the available pharmacologic spectrum for the prevention and treatment of postmenopausal osteoporosis.     

Effect of aromatase inhibition on bone metabolism in elderly hypogonadal men

Both estrogens and androgens play important roles in skeletal development and maintenance in men. The relative importance of estrogens and androgens in male bone metabolism, however, remains undefined. Anastrozole is an oral aromatase inhibitor that decreases estrogen production and increases androgen production in men. Currently, anastrozole is being investigated as a potential agent for the treatment of hypogonadism in aging men. Because anastrozole lowers estrogen levels and raises androgen levels, its effect on bone metabolism is difficult to predict. To assess the effects of anastrozole on bone turnover, we randomized 37 elderly (ages 62–74) mildly hypogonadal men (serum testosterone <350 ng/dl) to receive either anastrozole 1 mg daily ( n =12), anastrozole 1 mg twice weekly ( n =11), or daily placebo ( n =14) for 12 weeks. Serum gonadal steroid levels, serum and urine biochemical markers of bone turnover, serum osteoprotegerin, and total body bone mineral density were measured at baseline and week 12. Mean serum levels of total and bioavailable testosterone increased substantially in both treated groups. Specifically, mean ± SD bioavailable testosterone levels increased from 99±31 ng/dl to 207±65 ng/dl in the group receiving 1 mg of anastrozole daily and from 115±37 ng/dl to 178±55 ng/dl in the subjects receiving 1 mg of anastrozole twice weekly ( p <0.001 vs placebo for both groups). Serum estradiol levels decreased modestly in both treated groups (from 26±8 pg/ml to 17±6 pg/ml in the daily treatment group and from 27±8 pg/ml to 17±5 pg/ml in the twice-weekly treatment group, p <0.001 vs placebo for both groups). Despite these hormonal changes, no increases in biochemical markers of bone resorption were observed. Specifically, mean serum N-telopeptide and urinary deoxypyridinoline concentrations remained stable in both treated groups over the 12-week treatment period. Similarly, serum biochemical markers of bone formation (osteocalcin and amino-terminal propeptide of type 1 collagen), serum osteoprotegerin, and total body bone mineral density did not change. These data demonstrate that although short-term administration of anastrozole decreases serum estradiol levels in elderly men with mild hypogonadism, this intervention does not adversely affect bone metabolism over a 12-week period. This lack of an effect may be due to the concomitant increase in testosterone production, the relative modest effect on estradiol production, or a combination of both factors. These results suggest that anastrozole therapy is unlikely to have an adverse effect on bone metabolism when taken over extended periods and may prove to be a valuable method of normalizing testosterone production in older men.     

Recombinant human growth hormone in infants and young children with chronic renal insufficiency

Children with chronic renal insufficiency (CRI) secondary to congenital structural abnormalities frequently have significant growth retardation by 2 years of age. In a multicenter placebo-controlled study of the use of recombinant human growth hormone (rhGH), 30 of 125 (24%) participants were<2.5 years of age at enrollment. Since the treatment arms of the study were balanced for age at randomization, data for these patients were examined for efficacy and safety. During the first 2 years of the study, approximately two-thirds of the patients (n=19) received rhGH 0.05 mg/kg per day subcutaneously and one-third (n=11) received placebo injections. At entry into the study, the mean (± SD) calculated creatinine clearance was 29.2±14.3 (range 12.0–63.7) ml/min per 1.73 m² in the rhGH-treated group and 23.3±15.1 (range 8.0–59.4) ml/min per 1.73 m² in the placebo-treated group. The 1st year growth rate was 14.1±2.6 cm/year for the rhGH-treated group and 9.3±1.5 cm/year in the placebo-treated group (P<0.00005). During the 2nd year of the study, the growth rate was 8.6±1.2 cm/year in the rhGH-treated group compared with 6.9±1.0 in the placebo groupP=0.025). The height standard deviation score was +2.0±0.7 for the rhGH-treated group compared with –0.2±1.1 in the placebo-treated group (P<0.00005) during the 2 years of the study. Minor adverse events occurred with similar frequency in both groups. These data suggest that rhGH is efficacious and safe in children with CRI under age 2.5 years. rhGH therapy may correct significant loss of growth at this age when used in conjunction with optimal medical management.     

Cortical and trabecular bone mineral density in transsexuals after long-term cross-sex hormonal treatment: a cross-sectional study

The aim of this study was to explore the effect of long-term cross-sex hormonal treatment on cortical and trabecular bone mineral density and main biochemical parameters of bone metabolism in transsexuals. Twenty-four male-to-female (M-F) transsexuals and 15 female-to-male (F-M) transsexuals treated with either an antiandrogen in combination with an estrogen or parenteral testosterone were included in this cross-sectional study. BMD was measured by DXA at distal tibial diaphysis (TDIA) and epiphysis (TEPI), lumbar spine (LS), total hip (HIP) and subregions, and whole body (WB) and Z-scores determined for both the genetic and the phenotypic gender. Biochemical parameters of bone turnover, insulin-like growth factor-1 (IGF-1) and sex hormone levels were measured in all patients. M-F transsexuals were significantly older, taller and heavier than F-M transsexuals. They were treated by cross-sex hormones during a median of 12.5 years before inclusion. As compared with female age-matched controls, they showed a significantly higher median Z-score at TDIA and WB (1.7±1.0 and 1.8±1.1, P<0.01) only. Based on the WHO definition, five (who did not comply with cross-sex hormone therapy) had osteoporosis. F-M transsexuals were treated by cross-sex hormones during a median of 7.6 years. They had significantly higher median Z-scores at TEPI, TDIA and WB compared with female age-matched controls (+0.9±0.2 SD, +1.0±0.4 SD and +1.4±0.3 SD, respectively, P<0.0001 for all) and reached normal male levels except at TEPI. They had significantly higher testosterone and IGF-1 levels (p<0.001) than M-F transsexuals. We conclude that in M-F transsexuals, BMD is preserved over a median of 12.5 years under antiandrogen and estrogen combination therapy, while in F-M transsexuals BMD is preserved or, at sites rich in cortical bone, is increased to normal male levels under a median of 7.6 years of androgen treatment in this cross sectional study. IGF-1 could play a role in the mediation of the effect of androgens on bone in F-M transsexuals.     

重组人生长激素对严重烧伤后机体代谢的影响

目的　探讨重组人生长激素 (rhGH)对严重烧伤患者代谢的影响。　方法　烧伤患者2 4例 ,随机分为rhGH治疗组和对照组 ,每组 12例。分别于伤后第 3～ 17天皮下注射rhGH(9U/d)和等量等渗盐水。于伤后第 3、10、17天抽血检测血清生长激素 (GH)、胰岛素样生长因子 (IGF 1)、胰岛素样生长因子结合蛋白 3(IGFBP 3)、血清蛋白、血浆胰岛素、血浆胰高血糖素及血糖值 ,进行对比分析。　结果　伤后第 10、17天 ,rhGH治疗组血清GH、IGF 1、IGFBP 3、血清前白蛋白及转铁蛋白值均明显高于对照组 (P <0 .0 5～ 0 .0 1) ,两组各时相点血清白蛋白、血浆胰岛素、胰高血糖素及血糖浓度比较差异无显著性意义 (P >0 .0 5 )。　结论　严重烧伤后应用小剂量rhGH能促进机体蛋白质合成 ,对血糖无影响     

Effects of combined androgen blockade on bone metabolism and density in men with locally advanced prostate cancer

Objective: To investigate whether combined androgen blockade (CAB) produces any adverse effects on bone metabolism and mineral density in patients with locally advanced prostate cancer.Materials and methods: The study group consisted of 17 stage T4 prostate cancer patients treated with CAB and had no evidence of bone metastasis on bone scintigraphy. The mean duration of CAB and final total prostate specific antigen (PSA) level at the time of study were found at 28.5 ± 15.9 (6–58) months and 0.39 ± 0.5 (0.1–2) ngml, respectively. Twenty age and socioeconomically matched benign prostate hyperplasia (BPH) patients were taken as the control group. Both groups were compared with regard to lumbar bone mineral density (LBD), femur bone mineral density (FBD) and serum parameters of bone metabolism namely calcium (Ca), phosphate (P), magnesium (Mg) and alkaline phosphatase (ALP). Bone mineral density was measured with dual energy x-ray absorptiometry.Results: The mean FBD, LBD and serum Ca, P, Mg and ALP measurement of the patients treated with CAB were 0.85 ± 0.1 g/cm², 1.16 ± 0.2 g/cm², 9.1 ± 0.3 mg/dl, 3.6 ± 0.6 mg/dl, 1.95 ± 0.14 mg/dl, 187.5 ± 61 mg/dl, respectively. No significant difference was found between patients subjected to CAB and the age matched controls in any of the studied parameters namely age, FBD, LBD, Ca, Mg and ALP except serum phosphate. Serum phosphate levels were significantly (p =0.001) higher in patients treated with CAB suggesting a minor effect of CAB on bone metabolism.Conclusion: No convincing evidence was found about the detrimental effect of CAB on bone mineral density and metabolism in a highly selected group of patients with advanced prostate cancer without bone metastases.     

Growth hormone for children with chronic renal failure and on dialysis

We studied all children with CRF who received recombinant human growth hormone (rhGH) for more than a year (mean±SD duration of therapy 3.7±2.5 years) over an 11-year period. There were 32 children. Twenty-one children were conservatively managed, with a mean glomerular filtration rate (GFR) of 24±12 mL min^–1/1.73 m² at the start of rhGH. Their height standard deviation score improved from –2.5±1.4 to –2.1±0.7 at 1 year (P=0.3), –2.0±0.7 at 2 years (P=0.01), and –1.6±0.6 at 3 years (P=0.001). After that there was no improvement. Eleven children were on dialysis, six on haemodialysis (HD) and five on peritoneal (PD). Ht SDS improved from –2.7±0.5 to –2.3±0.5 at 1 year (P=0.02). Thereafter there was no further improvement. RhGH was stopped because of transplantation in 29 patients at a mean±SD age of 12.1±4.0 years. Mean Ht SDS was –1.8±0.8 at transplant and there was no change over the following 5 years. In conclusion, treatment with rhGH resulted in improvement in Ht SDS in conservatively managed CRF for up to 3.0 years and for 1 year in children on dialysis. Discontinuation of rhGH after transplantation resulted in little change in Ht SDS.     

Changes in bone mineral density, body composition and biochemical markers of bone turnover during weight gain in adolescents with severe anorexia nervosa: a 1-year prospective study

Osteoporosis is a serious complication of anorexia nervosa and in affected adolescents may result in a permanent deficit in bone mass. The pathophysiology of this bone disease has not been clearly defined. In this prospective study of 26 young women with anorexia nervosa aged 13–20 years (mean 16.5) we have measured changes in bone mineral density, total body composition and biochemical indices of bone turnover over 1 year. Over this period there was a mean weight gain of 10 kg and significant height gain with baseline and final values for body mass index of 14.2±1.7 and 17.6±2.3 kg/m² (P<0.001). However, no significant changes were seen in bone mineral density in the spine or proximal femur during the study; total body bone mineral content was significantly higher than baseline at 3 months and 12 months (P=0.001 and P<0.0001), but total body bone mineral density at 3 months was significantly lower than baseline (P=0.003). Serum osteocalcin and bone-specific alkaline phosphatase values increased significantly and remained higher than baseline at all time points whereas urinary NTX/creatinine excretion showed a non-significant increase over the first 6 months of the study, but at 12 months, the mean value was significantly lower than baseline. Mean serum 25-hydroxyvitamin D levels showed a significant decrease at 6 months (P<0.05), but returned towards baseline thereafter. There was a significant increase in serum parathyroid hormone levels at all time points compared to baseline, these occurring within the normal range. These results indicate that although weight gain in young anorexics is associated with linear growth, bone mineral density does not increase. Whether this deficit can be corrected subsequently requires longer-term prospective studies.     

Prophylactic calcium and vitamin D treatments in steroid-treated children with nephrotic syndrome

Steroid treatment has several side effects, including the deterioration of the bone and mineral metabolism in children with nephrotic syndrome. This randomized prospective study was conducted to determine the effects and prophylactic role of calcium plus vitamin D treatment on bone and mineral metabolism in children receiving prednisolone treatment. 40 children (27 boys and 13 girls) with NS (18 new onset and 22 relapsing) were included in the study. Their mean age was 4.6±1.8 years. All patients received prednisolone treatment (2 mg/kg/day for 4 weeks followed by alternate days at the same dose for 4 weeks). The patients were randomized into treatment (vitamin D 400 IU plus calcium 1 g daily) and non-treatment groups. Bone mineral density, serum Ca, P, alkaline phosphatase and urinary Ca and P excretions were analyzed at the beginning and 2 months after the treatment. The XR36 Norland device was used for bone mineral density analysis. Bone mineral density was significantly decreased in both the treatment (0.54±0.15 to 0.51±0.1 g/cm², P =0.001) and non-treatment (0.52±0.18 to 0.45±0.16 g/cm², P <0.001) group. But the percentage of bone mineral density decrease was found to be significantly lower in the treatment group than in the non-treatment group (4.6±2.1% vs. 13.0±4.0%, respectively; P <0.001). Serum calcium and urinary calcium excretion increased in the treatment group (8.0±1.0 to 10.0±0.5 mg/dl and 1.1±0.5 to 3.2±1.0 mg/kg/day) and non-treatment group (8.1±0.8 to 10.0±0.6 mg/dl and 1.4±0.9 to 3.8±3.3 mg/kg/day) after prednisolone treatment (P <0.001). Steroid treatment decreases bone mineral density in children with nephrotic syndrome. Vitamin D plus calcium therapy at the current doses reduces but does not completely prevent bone loss, with no additional adverse effects.     

The carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen in serum as a marker of bone resorption: The effect of nandrolone decanoate and hormone replacement therapy

Carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) in serum has recently been proposed as a new biochemical marker of bone resorption. In the present study we compared serum ICTP with radiopharmaceutical and histomorphometric measurements of bone turnover in postmenopausal women with mild osteoporosis, and assessed the effect of hormone replacement therapy (HRT) (2 mg 17-estradiol plus 1 mg norethisterone daily) and anabolic steroid therapy (50 mg nandrolone decanoate (ND) i.m. every 3 weeks) on serum ICTP in two double-blind placebo-controlled studies with 55 to 75-year-old women. Serum ICTP measured by radioimmunoassay (RIA) correlated significantly with the 24-hour whole body retention of 99m-technetium diphosphonate (Rho=0.47, P<0.001, n=66), but not with histomorphometric measurements of bone turnover in iliac crest biopsies. One year of HRT (n=16) versus placebo (n=15) did not produce significant changes in serum ICTP. Compared with placebo (n=17), 1 year of ND (n=19) produced an increase in serum ICTP of 90±16% (P<0.0001); 6 months after discontinuation of the treatment, serum ICTP had returned to pretreatment values. We conclude that serum ICTP does reflect bone metabolism in postmenopausal osteoporosis, but it is not a sensitive marker of the changes in bone resorption induced by hormone replacement therapy, and it does not correspond with other measures of bone resorption during anabolic steroid therapy.     

Parathyroid hormone levels in pubertal uremic adolescents treated with growth hormone

We have previously described severe hyperparathyroidism during the pubertal growth spurt in three uremic adolescents treated with recombinant human growth hormone (rhGH). Here we investigate the possible role of puberty in the genesis of hyperparathyroidism during rhGH treatment of a large cohort of patients. Data from 67 uremic patients treated with rhGH from five Italian pediatric nephrology centers were retrospectively recorded every 3 months starting 1 year before rhGH administration. The mean (±SD) rhGH treatment observation period was 19.9±5.9 months. The mean age at the start of rhGH treatment was 8.3±3.6 years. Of the 67 patients, 15 reached pubertal stage 2 during the 1st year of rhGH treatment and 12 of these 15 progressed to pubertal stage 3. The relative increase in parathyroid hormone (PTH) levels after rhGH initiation was greater in pubertal [1.95, 95% confidence interval (CI) 1.43–2.66] than in prepubertal patients (1.19, 95% CI 1.01–1.40). Increases in PTH levels were significantly different between the two groups (=1.64, 95% CI 1.16–3.19, P=0.007). Multiple regression analysis showed an inverse correlation between PTH and calcium levels and a positive correlation between PTH and pubertal stage 3. There was no correlation with phosphate levels and calcitriol dosage. In conclusion, these results suggest that in uremic adolescents treated with rhGH puberty may influence PTH levels.     

Differential effects of growth hormone therapy in malnourished hemodialysis patients

BACKGROUND: Malnutrition is common in chronic hemodialysis patients and is associated with increased morbidity and mortality. Several factors such as metabolic acidosis, hyperparathyroidism, and insulin as well as growth hormone (GH) resistance may lead to enhanced protein catabolism. Recombinant human growth hormone (rhGH) has been proposed as treatment of malnutrition because of its anabolic effects. METHODS: In the present placebo-controlled, double blind study, the effects of three months of rhGH therapy on nutritional and anthropometric parameters, on bone metabolism and bone mineral density (BMD), as well as on polymorphonuclear leukocyte (PMNL) function and quality of life (QoL) were evaluated in 19 malnourished hemodialysis patients (10 females and 9 males) with a mean age of 59.3 +/- 13.4 years. RhGH (0.125 IU/kg) was given three times a week during the first four weeks and 0.25 IU/kg thereafter three times a week after each dialysis session. RESULTS: Insulin-like growth factor I (IGF-I) concentration rose significantly from 169.2 +/- 95.6 ng/mL to 262.9 +/- 144.4 ng/mL (p< 0.01) in the group receiving rhGH. Albumin, prealbumin, transferrin, cholesterol, high-density lipoprotein (HDL) cholesterol, cholinesterase, predialytic creatinine, and blood urea nitrogen showed no significant changes during the three months in both groups. Total body fat (%TBF) was slightly reduced after three months (P = NS) in the patients receiving GH, whereas lean body mass (LBM) remained stable during therapy. Procollagen I carboxy terminal peptide (PICP), a marker of bone formation, increased significantly after three months from 250.1 +/- 112.6 to 478.5 +/- 235.2 microg/L (P < 0.01) in the GH-treated patients, whereas parameters of bone resorption like telopeptide ICTP showed only a slight increase (50.3 +/- 18.5 vs. 70.0 +/- 39.5 microg/L, P = NS). BMD at the lumbar spine decreased significantly after three months in the treatment group (0.8 +/- 0.17 vs. 0.77 +/- 0.16 g/cm2, P < 0.01), whereas BMD at the femoral neck remained stable in both groups. Phagocytic activity of PMNLs increased significantly after three months of therapy with rhGH, whereas other parameters of PMNL function were not affected by GH. QoL was slightly improved in the GH treated group, but decreased markedly in the placebo group. CONCLUSIONS: Three months of treatment with rhGH in malnourished patients on chronic hemodialysis causes a significant increase in IGF-I levels without significant changes in nutritional and anthropometric parameters. In contrast, bone turnover was enhanced with an initial decrease in BMD at the lumbar spine, and phagocytic activity of PMNLs was increased.     

Accelerated growth in short children with chronic renal failure treated with both strict dietary therapy and recombinant growth hormone

In a 12-month study, nine boys, aged 4.8–15.6 years, with bone ages 4.6–13 years, with moderate to severe chronic renal failure and resultant growth failure were treated with daily recombinant human growth hormone (rhGH), in conjunction with a strict low-protein/low-phosphate diet supplemented with keto and amino forms of the essential amino acids, histidine and additional energy. Improved growth had previously been observed with this dietary management over that obtained with conventional treatment for chronic renal failure. Each child had been on this diet for at least 2 years before rhGH was commenced. Mean height velocity increased from 4.6±1.3 to 9.0±1.3 cm/year (P<0.001) in the pre-pubertal group, and in the pubertal group from 5.4±1.4 to 10.4±1.8 cm/year (P<0.01). The mean height velocity standard deviation scores (SDSs) increased from –1.2±0.6 to +2.3±0.9 (P<0.001) in the pre-pubertal group and from –0.4±0.6 to +1.9±1.1 (P<0.01) in the pubertal group. Mean height SDS for chronological age increased from –2.2±0.7 to –1.5±0.5 (P<0.01) in the pre-pubertal group and from –1.9±0.7 to –1.3±0.9 in the pubertal group (P<0.02). There was no significant deterioration in renal function or renal bone disease, and bone age did not advance more than chronological age over the 12-month period.     

Short-term effect of alendronate on bone mass and bone remodeling in postmenopausal women

The short-term dose-response relationship between treatment with the bisphosphonate alendronate, biochemical markers of bone turnover, and changes in lumbar spine bone mineral density (BMD) over 9 months was assessed using a double-masked controlled study design in 65 postmenopausal women (mean age 51.6 years, mean 1.5 years since last menses) receiving 5, 20, 40 mg of alendronate or placebo for 6 weeks. After 6 weeks of alendronate, serum calcium phosphate and osteocalcin decreased, and intact parathyroid hormone increased significantly in dose-dependent fashions in the alendronate-treated groups (T) compared with placebo (P). Generally similar changes (decreases) were noted in 24-h urinary calcium and pyridinoline (deoxy- and hydroxylysl pyridoline); by 30 weeks post-treatment no significant changes from baseline or between T and P were noted. Lumbar BMD by dual-energy X-ray absorptiometry demonstrated a dose-dependent response over 9 months (median % change ±SD: –1.2±0.9 for 5 mg T, +0.7±0.8 for 20 mg T*, +1.2±1.1 for 40 mg T*;*p<0.01 vs=" p).=" alendronate=" was=" generally=" well=" tolerated=" over=" all=" dosages.=" these=" data=" demonstrate=" that=" short-term=" (6=" weeks)=" oral=" alendronate=" treatment=" (5–40=" mg=" daily)=" is=" well=" tolerated=" and=" effective=" in=" (reversibly)=" decreasing=" biochemical=" markers=" of=" bone=" turnover=" in=" early=" postmenopausal=" women,=" and=" in=" stabilizing=" spinal=" bmd=" over=" 9=" months.=" longer-term=" treatment=" with=" larger=" clinical=" populations=" is=" indicated=" to=" define=" more=" fully=" the=" potential=" efficacy=" and=" safety=" of=" chronic=" alendronate=">     

Changes in body composition of children with chronic renal failure on growth hormone

Body composition is altered in children with chronic renal failure (CRF) and contributes to the significant growth failure seen in these children. Recombinant human growth hormone (rhGH) has been used in the past several years to improve the somatic growth of children with CRF. To determine if the growth achieved in these children occurs concomitantly with body compositional changes, seven prepubertal (n=6) and pubertal (n=1) children with chronic renal insufficiency (n=4) and end-stage renal disease (n=3) underwent measurements of total body fat (FM), fat free mass (FFM), bone mineral density (BMD), total bone mineral mass (TBBM), total body water (TBW), and total body potassium (TBK) before and 6 months after initiation of subcutaneous recombinant human growth hormone (rhGH) at 0.35 mg/kg per week. The techniques used included dual- energy X-ray absorptiometry (for measurement of FM, BMD, and TBBM), total body potassium counting (for measurement of TBK), and deuterated water for assessment of TBW. Significant increases in both height and weight were seen following 6 months of rhGH therapy. These increases were accompanied by significant re- ductions in FM (4.4±1.4 kg vs. 3.6±1.2 kg, P=0.002) and percentage fat (18.6±3.9% vs. 14.5±3.4%, P=0.04), while FFM (17.9±3.0 kg vs. 20.7±3.6 kg, P=0.04) increased significantly as did TBBM (776±171 g vs. 844±177 g, P=0.001). Increases in TBK, a measure of body cell mass, were also seen. No difference in total BMD was observed. Thus, growth in CRF is occurring with repletion of the FFM and TBBM compartments. Despite these improvements, no change was observed in the body mass index (BMI). Measurement of BMI alone does not define the compartmental catabolic losses in FFM. Received: 20 September 1999 / Revised: 31 January 2000 / Accepted: 8 February 2000