Effect of growth hormone on bone: Bone mineral density, trabecular bone volume, and alkaline phosphatase improve or are restored in the dwarf rat treated with growth hormone

Activation of β2-adrenergic receptors inhibits osteoblastic bone formation and enhances osteoclastic bone resorption. Whether β-blockers inhibit ovariectomy-induced bone loss and decrease fracture risk remains controversial. To further explore the role of β-adrenergic signaling in skeletal acquisition and response to estrogen deficiency, we evaluated mice lacking the three known β-adrenergic receptors (β-less). Body weight, percent fat, and bone mineral density were significantly higher in male β-less than wild-type (WT) mice, more so with increasing age. Consistent with their greater fat mass, serum leptin was significantly higher in β-less than WT mice. Mid-femoral cross-sectional area and cortical thickness were significantly higher in adult β-less than WT mice, as were femoral biomechanical properties (+28 to +49%, P < 0.01). Young male β-less had higher vertebral (1.3-fold) and distal femoral (3.5-fold) trabecular bone volume than WT (P < 0.001 for both) and lower osteoclast surface. With aging, these differences lessened, with histological evidence of increased osteoclast surface and decreased bone formation rate at the distal femur in β-less vs. WT mice. Serum tartrate-resistance alkaline phosphatase-5B was elevated in β-less compared with WT mice from 8–16 wk of age (P < 0.01). Ovariectomy inhibited bone mass gain and decreased trabecular bone volume/total volume similarly in β-less and WT mice. Altogether, these data indicate that absence of β-adrenergic signaling results in obesity and increased cortical bone mass in males but does not prevent deleterious effects of estrogen deficiency on trabecular bone microarchitecture. Our findings also suggest direct positive effects of weight and/or leptin on bone turnover and cortical bone structure, independent of adrenergic signaling. Mice lacking ß-adrenergic receptors have increased body weight, bone mineral density, and bone turnover versus controls, but are not protected from bone loss due to deficiency of estrogens..

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P-23 Bone mineral density and alkaline phosphatase in growth hormone-treated GH-deficient young adults

Growth Hormone & IGF Research ◽

10.1016/s1096-6374(08)70108-4 ◽

2008 ◽

Vol 18 ◽

pp. S33-S34

Author(s):

G.S. Conway ◽

M. Szarras-Czapnik ◽

K. Racz ◽

A. Keller ◽

P. Chanson ◽

...

Keyword(s):

Bone Mineral Density ◽

Growth Hormone ◽

Alkaline Phosphatase ◽

Young Adults ◽

Bone Mineral ◽

Mineral Density

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The Long-Term Effects of Growth Hormone Replacement on Bone Mineral Density and Trabecular Bone Score: Results of the 10-Year Prospective Follow-up

Physiological Research ◽

10.33549/physiolres.934775 ◽

2021 ◽

pp. S61-S68

Author(s):

P. Vaňuga ◽

M. Kužma ◽

D. Stojkovičová ◽

J. Smaha ◽

P. Jackuliak ◽

...

Keyword(s):

Bone Mineral Density ◽

Growth Hormone ◽

Trabecular Bone ◽

Replacement Therapy ◽

Bone Mineral ◽

Trabecular Bone Score ◽

Mineral Density ◽

Gh Replacement

There are only few studies concerning about long-term effect of growth hormone (GH) replacement therapy on bone mineral density and bone microstructure. To assess effect of GH replacement therapy on bone mineral density (BMD) and trabecular bone score (TBS) in adult GH deficient (AGHD) subjects over period of 10 years. From 2005 to 2018, a prospective study of AGHD patients was conducted in national referral center for treatment of GHD. All patients received subcutaneous recombinant human GH in an IGF 1-normalizing regimen once a day. Lumbar spine (L-spine) and total hip (TH) BMD using Hologic densitometers were measured at baseline and every two years during treatment with rhGH. TBS was derived from L1-L4 DXA using iNsight® software (Medimaps, France) at each time point. Periods of measurement were baseline, year 2; 4; 6; 8 and 10. In total, 63 patients (38 males, 25 females, mean age 25.1±16 years) were included in the study. After 10 years of GH treatment, IGF-1 significantly increased (~35 %), with greatest increase at year 2. During 10-year follow-up, L-spine BMD increased approximately of 7 % (NS). TH BMD increase of 11 % during follow-up (p=0.0003). The greatest increment of BMD was achieved at year 6 on both sites, L-spine (+6 %) and TH BMD (+13 %) (p<0.05). There was no significant change of TBS during whole follow-up. In this study, sustaining positive effect of GH replacement therapy on bone density in subjects with adult GH deficiency over 10 years of follow-up was observed. The study did not show effect on TBS, as indirect measure of trabecular bone microarchitecture.

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Bone turnover and bone mineral density in young adult patients with panhypopituitarism before and after long-term growth hormone therapy

Acta Endocrinologica ◽

10.1530/eje.0.1320042 ◽

1995 ◽

Vol 132 (1) ◽

pp. 42-46 ◽

Cited By ~ 31

Author(s):

Rina Balducci ◽

Vincenzo Toscano ◽

Anna M Pasquino ◽

Adele Mangiantini ◽

Giovanna Municchi ◽

...

Keyword(s):

Bone Mineral Density ◽

Growth Hormone ◽

Alkaline Phosphatase ◽

Bone Turnover ◽

Bone Mineral ◽

Serum Levels ◽

Creatinine Ratio ◽

Mineral Density ◽

Urinary Hydroxyproline ◽

Igf I

Balducci R, Toscano V, Pasquino AM, Mangiantini A, Municchi G, Armenise P, Terracina S, Prossomariti G, Boscherini B. Bone turnover and bone mineral density in young adult partients with panhypopituitarism before and after long-term growth hormone therapy. Eur J Endocrinol 1995;132:42–6. ISSN 0804–4643 We examined the effects of biosynthetic growth hormone (GH) on biochemical indices of bone turnover and on bone mineral density in a group of GH-deficient adults. Thirteen patients (eight males and five females) aged 24 ± 5 years (range 16–35) were studied before and 12 and 24 months after GH treatment (0.1 IU, kg− day−1, 6 days a week). Serum levels of insulin-like growth factor I (IGF-I), calcitonin, parathyroid hormone, alkaline phosphatase, intact osteocalcin, fasting urinary hydroxyproline/creatinine ratio and bone mineral density (BMD), measured at the lumbar spine by dualphoton absorptiometry, were evaluated. After 12 months of treatment, IGF-I, alkaline phosphatase, osteocalcin and the fasting urinary hydroxyproline/creatinine ratio increased significantly. However, after 24 months of therapy, serum levels of osteocalcin decreased to pretreatment values while IGF-I, fasting urinary hydroxyproline/creatinine ratio and alkaline phosphatase remained elevated significantly. No changes were found in parathyroid hormone and calcitonin plasma levels or in BMD either after 12 or 24 months of treatment. These data demonstrate that GH, at the dosage that we used, activates bone turnover during 24 months of therapy in adults with panhypopituitarism, even if a downward trend for osteocalcin became apparent at 24 months. However, this activation in bone turnover was not accompanied by an increase in BMD. We can hypothesize that GH, at the relatively high dosage used, may stimulate osteoclastic activity to a greater extent than osteoblastic activity. It is probable that the dose of GH replacement therapy in adults plays a key role R Balducci, Dipartimento di Sanita Pubblica, Universita "Tor Vergata", Via di Tor Vergata 38, 00173 Roma, Italy

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Effect of Senolytic to alleviating Osteoporosis in Mice induced by Retinoic Acid

E3S Web of Conferences ◽

10.1051/e3sconf/202018504016 ◽

2020 ◽

Vol 185 ◽

pp. 04016

Author(s):

Jia Liu ◽

Yazhe Xiao ◽

Jing Xie ◽

Lian He

Keyword(s):

Bone Mineral Density ◽

Trabecular Bone ◽

Bone Mineral ◽

Volume Fraction ◽

Bone Volume ◽

Control Group ◽

Mineral Density ◽

Blank Control Group ◽

Bone Volume Fraction ◽

Group A

Senolytic is a potential new anti-aging drug, and it is worth exploring whether it has an inhibitory effect on osteoporosis. Osteoporosis models in mice were established by gavage of retinoic acid(RA), and Senolytic drugs (dasatinib and quercetin) were used to treat for 8w. Serological indexes were measured, and bone mineral density was detected by dual-energy X-ray absorptiometry, then parameters of trabecular bone were quantified by μCT, by which three-dimensional images of lumbar trabecular bone were rebuild for comprehensive analysis. In osteoporosis model mice the content of serum calcium and alkaline phosphatase in mice were increased, the bone mineral density decreased, bone volume fraction and trabecular number decreased significantly, and the trabecular separation increased significantly. After applying the Senolytic drug, the serum calcium of group A and B were significantly lower than that of the blank control group. The alkaline phosphatase content in the two groups was (272.5±42.7)U/L and (258.4±90.2)U/L, which was also significantly lower than that in the blank control group (389.0±31.1)U/L. After the treatment of Senolytic, the bone mineral density of group A and group B were improved, the bone volume fraction were increased compared with the blank control group. The trabecular bone separation of the two groups was significantly reduced. Therefore, these reduced osteoporosis. From our study, it can be confirmed that the senolytic drug has a certain alleviating effect on osteoporosis.

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