Vertebral Fractures in Patients With Acromegaly: A 3-Year Prospective Study

Mazziotti, Gherardo; Bianchi, Antonio; Porcelli, Teresa; Mormando, Marilda; Maffezzoni, Filippo; Cristiano, Alessandra; Giampietro, Antonella; Marinis, Laura De; Giustina, Andrea

doi:10.1210/jc.2013-1460

Cited by 146 publications

(129 citation statements)

References 53 publications

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“…It is therefore to be expected that disease control in acromegaly will be followed by a decrease in bone turnover and a filling of the remodeling space followed by a relative increase in BMD (11,27), as seen in other endocrine disorders with coupled bone remodeling, following treatment (37,38). The decrease in TBS following treatment in this study, despite the increase in BMD, reflects that the two measures describe different properties of bone, especially in other conditions than postmenopausal osteoporosis (4), but are in alignment with the observed high incidence and prevalence of vertebral fractures seen in acromegaly (5,31,32,33,34).…”

Section: Discussionsupporting

confidence: 72%

“…Recently, several studies have shown a marked increase in vertebral fracture prevalence and incidence for both sexes in acromegaly (5,31,32,33,34), related to the duration of disease activity and gonadal status among others. These observations underscore the complexity of a chronic and devastating disease as acromegaly, for bone as a target organ with fracture as the ultimate end point (2).…”

Section: Discussionmentioning

confidence: 99%

“…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. Moreover, patients with acromegaly often have degenerative changes in the spine giving a false high BMD (5).…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

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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Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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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“…Exclusion criteria from the study were: i) diagnosis of active neoplastic disease; ii) ongoing treatment with antiosteoporotic drugs with the exception of calcium and vitamin D supplements; iii) treatment with drugs causing osteoporosis with the exception of glucocorticoid replacement therapy in hypopituitaric patients; iv) clear history of moderate or high-energy VFs; v) history of surgical intervention on the spine; and vi) prolonged immobilization (more than 6 weeks). Out of the 109 enrolled patients, 84 had been already evaluated in previously published studies from our research group (14,15,16). Both surgically treated and medically treated patients were included.…”

Section: Subjectsmentioning

confidence: 99%

“…Fracture risk correlates with the activity of the disease and the presence of concomitant additional risk factors, such as hypogonadism (14,15,16). Nonetheless, it is still largely unclear as to whether GHR polymorphisms are implicated in this phenomenon and have an impact on skeletal fragility in acromegaly.…”

Section: Introductionmentioning

confidence: 99%

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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