Low dose recombinant human growth hormone normalizes bone metabolism and cortical bone density and improves trabecular bone density in growth hormone deficient adults without causing adverse effects

Amato, Giovanni; Izzo, Giovanni; Montagna, G.; Bellastella, Antonio

doi:10.1111/j.1365-2265.1996.tb02056.x

Cited by 52 publications

(36 citation statements)

References 60 publications

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“…Our findings are in line with the idea that a low GH dose seems optimal for restoring bone mass in GHD adults, as it avoids the initial decline in BMD frequently observed when higher doses are used (1,4,27,28). GH is a stimulator of both bone resorption and bone formation (29), and a low dose of GH may generate a more marked anabolic action than higher doses, as low IGF-I stimulates bone formation more markedly than bone resorption (30,31). Abrahamsen et al (28) have demonstrated that 0.004 mg/kg/day of GH stimulated bone remodeling and increased BMD over 12 months in GHD patients, irrespective of gender, while a higher dose of 0.015 mg/kg/day was associated with initial declines in forearm and whole-body BMD in their patients.…”

Section: Discussionsupporting

confidence: 75%

One year of GH replacement therapy with a fixed low-dose regimen improves body composition, bone mineral density and lipid profile of GH-deficient adults

Boguszewski¹,

Meister²,

Zaninelli³

et al. 2005

eur j endocrinol

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Objective: We have studied the effects on body composition and metabolism of a fixed low dose of growth hormone (GH), 0.6 IU (0.2 mg)/day, administered for 12 months to GH-deficient (GHD) adults. Design and methods: Prospective open-label study, using 18 GHD patients (11 women, 7 men; aged 21 -58 years). All investigations were performed at baseline and after 12 months. Body composition was determined by dual energy X-ray absorptiometry. Results: Total body fat decreased (2 1.74^2.87%) and lean body mass (LBM) increased (1.27^2.08 kg) after therapy (P , 0.05). Changes in truncal fat did not reach statistical significance, but a decrease varying from 0.72 to 2.78 kg (1 to 8.7%) was observed in 13 (72%) patients. Bone mineral density (BMD) increased at lumbar spine, total femur and femoral neck (P , 0.05). Levels of total and low-density lipoprotein (LDL)-cholesterol were lower after therapy (P , 0.05), and their changes were directly associated with values at baseline. Insulin levels increased and the insulin resistance index worsened at 12 months (P , 0.05). Median IGF-I S.D. score was 2 4.30 (range, 2 11.03 to 20.11) at baseline and 21.73 (range, 2 9.80 to 2.26) at 12 months. Normal ageadjusted IGF-I levels were obtained with therapy in 5 of 11 patients who had low IGF-I levels at baseline. Changes in IGF-I levels were not correlated with any biological end point, except changes in LBM (r ¼ 0.53, P ¼ 0.02). Side effects were mild and disappeared spontaneously. Conclusions: One-year of a fixed low-dose GH regimen in GHD adults resulted in a significant reduction in body fat, total cholesterol and LDL-cholesterol, and a significant increase in LBM and BMD at lumbar spine and femur, regardless of normalization of IGF-I levels. This regimen led to an elevation of insulin levels and a worsening of the insulin resistance index.European Journal of Endocrinology 152 67-75

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Section: Discussionsupporting

confidence: 75%

One year of GH replacement therapy with a fixed low-dose regimen improves body composition, bone mineral density and lipid profile of GH-deficient adults

Boguszewski¹,

Meister²,

Zaninelli³

et al. 2005

eur j endocrinol

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“…Because of these evidences, the authors did not consider GHD as a condition of vitamin D deficiency [25]. Similar evidences of normal vitamin D levels have been found by other authors in studies performed in both childhood and adult-onset GHD [26][27][28].…”

Section: Impact Of Ghd On Vitamin D Levelssupporting

confidence: 63%

“…Serum 25OH-D3 and other markers of bone metabolism were evaluated before, after 12 months of therapy and after 12 months off, using a low weekly dose (70 pg/kg/week divided into 3 injections). Despite a significant improvement in IGF-I levels and in bone mineral density, no significant changes were found during the study in vitamin D and in other bone markers, indicating that GH acts on bone structure and its effects can be direct or mediated by IGF-I and not by vitamin D [28]. However, the low dose used and the frequency of GH administration must be taken into account in the interpretation of these results.…”

Section: Impact Of Gh Treatment On Vitamin D Levelsmentioning

confidence: 72%

Vitamin D across growth hormone (GH) disorders: From GH deficiency to GH excess

Ciresi

Giordano

2017

Growth Hormone & IGF Research

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The interplay between vitamin D and the growth hormone (GH)/insulin-like growth factor (IGF)-I system is very complex and to date it is not fully understood. GH directly regulates renal 1 alpha-hydroxylase activity, although the action of GH in modulating vitamin D metabolism may also be IGF-I mediated. On the other hand, vitamin D increases circulating IGF-I and the vitamin D deficiency should be normalized before measurement of IGF-I concentrations to obtain reliable and unbiased IGF-I values. Indeed, linear growth after treatment of nutritional vitamin D deficiency seems to be mediated through activation of the GH/IGF-I axis and it suggests an important role of vitamin D as a link between the proliferating cartilage cells of the growth plate and GH/IGF-I secretion. Vitamin D levels are commonly lower in patients with GH deficiency (GHD) than in controls, with a variable prevalence of insufficiency or deficiency, and this condition may worsen the already known cardiovascular and metabolic risk of GHD, although this finding is not common to all studies. In addition, data on the impact of GH treatment on vitamin D levels in GHD patients are quite conflicting. Conversely, in active acromegaly, a condition characterized by a chronic GH excess, both increased and decreased vitamin D levels have been highlighted, and the interplay between vitamin D and the GH/IGF-I axis becomes even more complicated when we consider the acromegaly treatment, both medical and surgical. The current review summarizes the available data on vitamin D in the main disorders of the GH/IGF-I axis, providing an overview of the current state of the art.

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“…This finding showed that a low dose of GH could increase IGF1 levels and have a pronounced physical effect in the GH-deficient adult (an increase in exercise capacity and in fat-free mass, and a decline in fat mass), without the side effects observed at higher dosage schedules. In the study by Amato et al (34), the lowest dose so far used in trials focusing on bone metabolism and structure in AGHD was used in a dosing regimen of 70 mg/kg per week divided into three injections. Results suggested that 12 months of lowdose GH therapy normalised bone metabolism and cortical bone density, and improved trabecular bone density without causing adverse events.…”

Section: Weight-based Vs Individualised Regimensmentioning

confidence: 99%

“…Regimens employing three injections per week have been shown to improve and/or normalise heart structure and performance, together with lipid profile, body composition, and bone metabolism and structure (23,34). In a randomised, prospective, controlled study comparing daily vs tiw injections (37), the tiw injection regimen was effective in normalising IGF1 levels and improving lipid profile, body composition, bone metabolism and bone density; this effect was comparable with that observed in patients treated with daily injections, with few side effects and good compliance.…”

Section: Timing and Frequency Of Gh Administrationmentioning

confidence: 99%

THERAPY OF ENDOCRINE DISEASE: GH therapy in adult GH deficiency: A review of treatment schedules and the evidence for low starting doses

Gasco

Prodam

Grottoli

et al. 2013

European Journal of Endocrinology

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Recombinant human GH has been licensed for use in adult patients with GH deficiency (GHD) for over 15 years. Early weight-and surface area-based dosing regimens were effective but resulted in supraphysiological levels of IGF1 and increased incidence of side effects. Current practice has moved towards individualised regimens, starting with low GH doses and gradually titrating the dose according to the level of serum IGF1 to achieve an optimal dose. Here we present the evidence supporting the dosing recommendations of current guidelines and consider factors affecting dose responsiveness and parameters of treatment response. The published data discussed here lend support for the use of low GH dosing regimens in adult GHD. The range of doses defined as 'low dose' in the studies discussed here (w1-4 mg/week) is in accordance with those recommended in current guidelines and encompasses the dose range recommended by product labels. European Journal of Endocrinology 168 R55-R66

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Low dose recombinant human growth hormone normalizes bone metabolism and cortical bone density and improves trabecular bone density in growth hormone deficient adults without causing adverse effects

Abstract: Our results suggest that 12 months of rhGH treatment at the lowest doses so far used normalizes bone metabolism and cortical bone density, and improves trabecular bone density without causing adverse events.

Cited by 52 publications

References 60 publications

One year of GH replacement therapy with a fixed low-dose regimen improves body composition, bone mineral density and lipid profile of GH-deficient adults

One year of GH replacement therapy with a fixed low-dose regimen improves body composition, bone mineral density and lipid profile of GH-deficient adults

Vitamin D across growth hormone (GH) disorders: From GH deficiency to GH excess

THERAPY OF ENDOCRINE DISEASE: GH therapy in adult GH deficiency: A review of treatment schedules and the evidence for low starting doses

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