Bone metabolism in relation to alterations in systemic growth hormone

Ueland, Thor

doi:10.1016/j.ghir.2004.06.002

Cited by 45 publications

(27 citation statements)

References 192 publications

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“…A negative correlation between markers of bone formation and resorption to BMD also was reported in one study [33], whereas in another study this correlation was seen only concerning bone resorption [17]. Increased growth hormone and insulinlike growth factor-1, both important for bone growth (childhood) and maintenance (adulthood), further correlated with higher bone metabolism [10,32,38], documenting the growth period of some of our patients.…”

Section: Discussionsupporting

confidence: 80%

Osteoporosis in Children and Young Adults: A Late Effect After Chemotherapy for Bone Sarcoma

Pirker-Frühauf

Friesenbichler

Urban

et al. 2012

Clinical Orthopaedics &Amp; Related Research

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Background Premature bone loss after childhood chemotherapy may be underestimated in patients with bone sarcoma. Methotrexate (MTX), a standard agent in osteosarcoma protocols, reportedly reduces bone mineral density (BMD). The literature, however, has reported cases of BMD reduction in patients with Ewing's sarcoma treated without MTX. Thus, it is unclear whether osteoporosis after chemotherapy relates to MTX or to other factors. Questions/purposes We therefore asked whether (1) young patients with a bone sarcoma had BMD reduction, (2) patients treated with MTX had lower BMD, and (3) other factors (eg, lactose intolerance or vitamin D deficiency) posed additional risks for low BMD. Methods We retrospectively reviewed 43 patients with malignancies who had dual-energy x-ray absorptiometry (DEXA) (lumbar, femoral); 18 with Ewing's sarcoma (mean age, 26 ± 8 years), and 25 with an osteosarcoma (mean age, 27 ± 10 years). The mean time since diagnosis was 8 ± 4 years in the group with Ewing's sarcoma and 7 ± 5 years in the group with osteosarcoma. At last followup we determined BMD (computing z-scores), fracture rate, and lifestyle, and performed serum analysis. Results BMD reduction was present in 58% of patients (37% had a z-score between À1 and À2 SD, 21% had a z-score less than À2 SD) in at least one measured site. Seven of the 43 patients (16%) had nontrauma or tumor-associated fractures after chemotherapy. Findings were similar in the Ewing and osteosarcoma subgroups. We found vitamin D deficiency in 38 patients (88%) and borderline elevated bone metabolism; lactose intolerance was present in 16 patients (37%). Conclusion Doctors should be aware of the possibility of major bone loss after chemotherapy with a risk of pathologic fracture. Vitamin D deficiency, calcium malnutrition, and lactose intolerance may potentiate the negative effects of chemotherapy, and should be considered in long-term patient management. Level of Evidence Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

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Section: Discussionsupporting

confidence: 80%

Osteoporosis in Children and Young Adults: A Late Effect After Chemotherapy for Bone Sarcoma

Pirker-Frühauf

Friesenbichler

Urban

et al. 2012

Clinical Orthopaedics &Amp; Related Research

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“…Accordingly, increased cortical bone mass seems to be due to a direct effect of GH (periosteal apposition (11)) followed by an increase in bone size, but might have a detrimental effect on trabecular bone structure (10,12,39). Prospective studies have demonstrated a high rate of incident vertebral fractures both in patients with active and controlled acromegaly despite a normal BMD (7,34), suggesting that BMD has a limited usefulness in discriminating the patients who are posed to a high risk of fracture.…”

Section: Discussionmentioning

confidence: 99%

Treatment of acromegaly increases BMD but reduces trabecular bone score: a longitudinal study

Godang

Olarescu

Bollerslev

et al. 2016

European Journal of Endocrinology

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Context: Bone turnover is increased in acromegaly. Despite normalization of bone turnover after treatment, the risk for vertebral fractures remains increased. Gonadal status, but not BMD, is correlated with vertebral fractures. Trabecular bone score (TBS) is related to bone microarchitecture. Objective: The aim of this study is to assess the longitudinal change in TBS and BMD following treatment for acromegaly. Results: Following treatment, the mean TBS decreased by 3.0 (±7.0) %, whereas the BMD at the lumbar spine (LS) increased by 3.2 (±4.9) % (both P < 0.01). The changes in BMD LS and TBS were not correlated (P = 0.87). The TBS change was found to be −4.5 % (±6.7; P = 0.003) in men and −0.3 % (±6.8; P = 0.85) in women (P = 0.063 for interaction men vs women). The mean BMD LS increased in men +4.2 g/cm 2 (±4.3; P < 0.001), but not in women +1.5 g/ cm 2 (±5.6; P = 0.36); (P = 0.073 for interaction). BMD increased in the ultradistal radius and total body (both P < 0.01).The increase in BMD LS was associated with a decrease in P1NP and CTX-1 (P < 0.001) and with lower P1NP and CTX-1 at the follow-up (P < 0.02). Conclusion: Treatment of acromegaly affects TBS and BMD at LS in different manners. The reduction of bone turnover markers predicts the increase in BMD but not the decrease in TBS. The DXA changes were more pronounced in men. Alterations in trabecular bone architecture may explain the persistent fracture risk despite the increase in BMD after disease control.

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“…The reason for the discrepancy between GH and IGF-I effects on OPG secretion is unclear, particularly by considering that GH raises IGF-I serum levels by inducing hepatic IGF-I synthesis. However, it should be considered that the final effect on bone cells is the balance between circulating levels of GH, IGFs, IGFBP, and locally produced IGFs and IGFBPs, acting in an autocrine and paracrine way (Ueland 2004). OPG is important in maintaining bone mass, as transgenic mice without OPG develop osteoporosis (Mizuno et al 1998), whereas mice overexpressing OPG develop osteopetrosis (Yamashita et al 2002).…”

Section: Discussionmentioning

confidence: 99%

“…Besides growth hormone (GH) effect on skeletal growth, the hormone plays a regulatory role on bone remodeling through the concerted action of GH itself, insulin-like growth factors (IGFs), and IGF-binding protein (IGFBP) produced either by the liver or locally (Ohlsson et al 1998, Ueland 2004. The GH regulatory role in bone remodeling and maintenance of bone mass has been clearly established in clinical studies, where patients with acquired GH deficiency in adulthood (GHD) were found to have secondary osteoporosis, characterized by reduced bone mass, increased fracture risk, and decreased bone remodeling (Holmes et al 1994, Wuster et al 2001.…”

Section: Introductionmentioning

confidence: 99%

“…In osteoblasts, binding of GH to its receptor leads to the activation of a cytoplasmic tyrosine kinase, Janus kinase 2 (Jak2), that phosphorylates its own and GHR tyrosine residues (Argetsinger et al 1993), which in turn activates several members of the STAT family of transcriptional factors (Gerland et al 2000). As summarized by Ueland (2004), GH and IGF-I/-II may regulate osteoblast proliferation (Kassem et al 1993, Nilsson et al 1995, while GH has IGF-independent effects on differentiation. In fact, the hormone induces an increase in the markers of osteoblast differentiation, such as osteocalcin and alkaline phosphatase (Kassem et al 1993).…”

Section: Introductionmentioning

confidence: 99%

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Growth hormone stimulates osteoprotegerin expression and secretion in human osteoblast-like cells

Mrak

Villa²,

Lanzi

et al. 2007

Journal of Endocrinology

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It is presently thought that osteoprotegerin (OPG) is a cytokine involved in the regulation of osteoblast/osteoclast crosstalk and maintenance of bone mass. Recent studies showed that GH replacement therapy in GH-deficient patients was able to induce a significant increase of OPG in the plasma, as well as in the cortical and the trabecular bone. In order to determine whether GH could directly modulate OPG secretion, the effect of GH on human osteoblast-like cells (hOB) in primary culture was studied. After detecting the presence of the mRNA for the GH receptor (GHR) by RT-PCR, hOB were exposed to increasing concentrations of GH, from 0 . 1 to 25 ng/ml, for 24 h. The results showed that GH exposure was able to stimulate OPG secretion in a concentration-dependent manner. In addition, the OPG mRNA levels were increased, indicating that the hormone has a stimulatory effect on gene expression. The stimulatory effect on OPG expression and production was prevented by exposing the cells to tyrphostin AG490 (10 mM), an inhibitor of Janus kinase 2, which is one of the kinases involved in the intracellular pathway activated by the binding of GH to its receptor. Similar results were obtained when the cells were exposed to a receptor antagonist of GH, pegvisomant at 50 nM. GH exposure neither induced an increase in IGF-I expression nor secretion in hOB. These results suggest that the stimulation of OPG production induced by GH in hOB is specific and receptor mediated and further support the view that GH is able to modulate bone remodeling by directly influencing osteoblast-osteoclast crosstalk.

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Bone metabolism in relation to alterations in systemic growth hormone

Cited by 45 publications

References 192 publications

Osteoporosis in Children and Young Adults: A Late Effect After Chemotherapy for Bone Sarcoma

Osteoporosis in Children and Young Adults: A Late Effect After Chemotherapy for Bone Sarcoma

Treatment of acromegaly increases BMD but reduces trabecular bone score: a longitudinal study

Growth hormone stimulates osteoprotegerin expression and secretion in human osteoblast-like cells

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