Influence of diabetes mellitus on vertebral fractures in men with acromegaly

Mazziotti, Gherardo; Gola, M; Bianchi, Antonio; Porcelli, Teresa; Giampietro, Antonella; Cimino, Vincenzo; Doga, Mauro; Gazzaruso, Carmine; Marinis, Laura De; Giustina, Andrea

doi:10.1007/s12020-011-9486-x

Cited by 59 publications

(26 citation statements)

References 41 publications

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“…Our study confirmed previous cross-sectional observations in which acromegalic patients developed VFs independent of normal BMD and there were no significant differences in terms of BMD values between fractured and non-fractured patients (14,15,32). For this reason, X-ray assessment is of paramount importance in establishing the real fracture risk in patients affected by acromegaly (33,34) as well as in all patients affected by other forms of secondary osteoporosis (35). In accordance with previous studies (14,15), fracture rate in our population was 43% and the biochemical control of acromegaly appeared effective in reducing the risk of fractures.…”

Section: European Journal Of Endocrinologysupporting

confidence: 90%

GH receptor isoforms and skeletal fragility in acromegaly

Mormando¹,

Nasto²,

Bianchi³

et al. 2014

European Journal of Endocrinology

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Objective: Acromegaly is associated with an increased prevalence of vertebral fractures (VFs) in close relationship with GH hypersecretion. Two isoforms of the GH receptor (GHR) have been identified; the two isoforms differ or not by the expression of the protein fragment encoded by exon 3 of the GHR gene. Deletion of the exon 3 may influence the functional properties of the GHR and affect fracture risk in acromegalic patients. Design: A cross-sectional study was designed to investigate the association between the d3-GHR isoform and the prevalence of VFs in patients with acromegaly. Methods: In this study, 109 acromegalic patients were included (M/F, 48/61): 73 with controlled/cured acromegaly and 36 with active disease. GHR genotype was assessed in each patient. All patients were evaluated for VFs and bone mineral density at lumbar spine and hip. Serum IGF1 levels and bone metabolism markers were measured. A multivariate analysis was performed to establish risk factors for VFs in our population. Results: d3-GHR carriers showed an increased prevalence of VFs when compared with patients expressing full-length GHR (35/55 vs 12/54; P!0.001). The association between GHR deletion and VFs was demonstrated both in patients with active disease and in those with controlled/cured disease. Out of 35 patients who were prospectively evaluated, 13 (37.1%) developed incident VFs. The incidence of VFs was significantly higher in patients for whom the GHR gene has been deleted when compared with those harboring the fl gene (PZ0.04). In multivariate analysis, male sex (odds ratio (OR), 3.250; PZ0.041), IGF1 levels (OR, 1.183; PZ0.031), length of active diseases (OR, 1.038; PZ0.001), and d3-GHR genotype (OR, 3.060; PZ0.015) were all confirmed as risk factors of VFs in our population. Conclusions: This study suggests for the first time that exon 3 deletion of GHR may predispose patients with active and controlled acromegaly to a higher risk of VFs.

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Section: European Journal Of Endocrinologysupporting

confidence: 90%

GH receptor isoforms and skeletal fragility in acromegaly

Mormando¹,

Nasto²,

Bianchi³

et al. 2014

European Journal of Endocrinology

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“…A normal to increased BMD has been reported in patients with type 2 diabetes, and it is not entirely explained by overweight [99]. However, an increased risk of fragility fractures occurs in patients with type 2 diabetes, confirming that fractures in secondary osteoporosis cannot be predicted by BMD [99][100][101][102][103][104][105][106]. The risk of fractures in type 2 diabetes is lower than in type 1 diabetes but affects both vertebral and non-vertebral sites [98,107].…”

Section: Diabetes Mellitus and Bonementioning

confidence: 85%

New understanding and treatments for osteoporosis

et al. 2011

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To summarize promising areas of investigation in osteoporosis and to stimulate further research in this area, as discussed in a recent international conference. Over the recent years, there has been an improvement in the knowledge of molecular pathways involved in bone formation and resorption with the development of new drugs to treat osteoporosis. Intact parathyroid hormone, teriparatide, and anti-sclerostin monoclonal antibody are anabolic drugs, whereas denosumab and odanacatib are anti-resorptive drugs with more reversible effects as compared to bisphosphonates. Anabolic and anti-resorptive agents have different effects on bone, and research in this area includes the efficacy of combination and sequential therapies with them. New insights in the molecular pathways of bone remodeling have clarified the mechanisms responsible for skeletal fragility in several forms of secondary osteoporosis, such as that occurring in type 2 diabetes, following drug exposure and systemic inflammatory diseases. Future research is needed to address the efficacy of anti-osteoporotic drugs in these more recently recognized conditions of skeletal fragility. Osteoporosis continues to be an important field of biomedical research.

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“…Data on BMD in acromegaly are conflicting; however, the effects of non-physiological secretion of GH and IGF-1 appear to affect the bone quality negatively (5,6). Despite normalization of bone turnover following treatment of acromegaly, the risk for vertebral fractures is still increased (5,7).…”

Section: Introductionmentioning

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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Influence of diabetes mellitus on vertebral fractures in men with acromegaly

Cited by 59 publications

References 41 publications

GH receptor isoforms and skeletal fragility in acromegaly

GH receptor isoforms and skeletal fragility in acromegaly

New understanding and treatments for osteoporosis

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

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