The Negative Impacts of Acromegaly on Bone Microstructure Not Fully Reversible

Duan, Lian; Yang, Shengmin; Wang, Lin jie; Zhang, Yuelun; Li, Ran; Yang, Hongbo; Zhao, Yutong; Du, Hanze; Zhai, Xiao; Gong, Fengying; Pan, Hui; Zhu, Huijuan; Xia, Weibo

doi:10.3389/fendo.2021.738895

Cited by 13 publications

(11 citation statements)

References 29 publications

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“…This suggests that, despite their possible greater exposure of bone to GH/IGF-1 excess, the pegvisomant-treated patients had similarly persistently impaired but no worse bone quality. The fact that pegvisomant-treated patients compared similarly to the remission and active disease comparison groups is consistent with prior studies showing that microstructural abnormalities do not vary with disease activity in surgically treated patients [ 10 , 41 ]. Although in a recent longitudinal HRpQCT study we found improved but persistent deficits in volumetric density and microarchitecture, Stiffness, and F.load in a group of acromegaly treated successfully with surgery or SRL therapy [ 10 ], the current cross-sectional study cannot determine if partial improvements also occurred with initiation of pegvisomant therapy.…”

Section: Discussionsupporting

confidence: 88%

Long-term Pegvisomant Therapy of Acromegaly: Effects on Bone Density, Turnover and Microstructure Using HRpQCT

Kuker,

Agarwal,

Shane

et al. 2024

Journal of the Endocrine Society

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Context Fracture rate is increased in patients with active acromegaly and those in remission. Abnormalities of bone microstructure are present in patients with active disease and persist despite biochemical control after surgery. Effects of treatment with the GH receptor antagonist pegvisomant on bone microstructure were unknown. Methods We studied 25 patients with acromegaly (15 men, 10 women). In 20, we evaluated arealBMD by DXA and bone turnover markers (BTMs) longitudinally, before and during pegvisomant treatment. After long-term pegvisomant in 17, we cross-sectionally assessed volumetric BMD, microarchitecture, stiffness and failure load of the distal radius and tibia using HRpQCT and compared these results to those of healthy controls and 2 comparison groups of non-pegvisomant treated acromegaly patients, remission and active disease, matched for other therapies and characteristics. Results In the longitudinal study, aBMD improved at the LS, but decreased at the hip in men after a median ∼7 years of pegvisomant. In the cross-sectional study, patients on a median ∼9 years of pegvisomant had significantly larger bones, lower trabecular and cortical volumetric density and disrupted trabecular microarchitecture compared to healthy controls. Microstructure was similar in the pegvisomant and acromegaly comparison groups. BTMs were lowered, then stable over time. Conclusions In this, the first study to examine bone microstructure in pegvisomant-treated acromegaly, we found deficits in volumetric BMD and microarchitecture of the peripheral skeleton. BTM levels remained stable with long-term therapy. Deficits in bone quality identified by HRpQCT may play a role in the pathogenesis of fragility in treated acromegaly.

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Section: Discussionsupporting

confidence: 88%

Long-term Pegvisomant Therapy of Acromegaly: Effects on Bone Density, Turnover and Microstructure Using HRpQCT

Kuker,

Agarwal,

Shane

et al. 2024

Journal of the Endocrine Society

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“…The early onset and the irreversibility of VFs requires strict screening and surveillance protocols since the time of acromegaly diagnosis [ 38 , 39 ], that includes the assay of markers of bone formation and resorption, calcium, vitamin D and parathyroid hormone (PTH), the vertebral morphometry and possibly the analysis of bone microstructure though the trabecular bone score (TBS) and the microindentation technique [ 40 ]. In addition, the vitamin D supplementation and the prescription of bone active drugs may improve the bone quality in acromegaly patients, in particular in those with active disease, together with the early normalization of GH and IGF-1 levels [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Impact of the diagnostic delay of acromegaly on bone health: data from a real life and long term follow-up experience

et al. 2022

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Introduction Acromegaly is a chronic disease with systemic complications. Disease onset is insidious and consequently typically burdened by diagnostic delay. A longer diagnostic delay induces more frequently cardiovascular, respiratory, metabolic, neuropsychiatric and musculoskeletal comorbidities. No data are available on the effect of diagnostic delay on skeletal fragility. We aimed to evaluate the effect of diagnostic delay on the frequency of incident and prevalent of vertebral fractures (i-VFs and p-VFs) in a large cohort of acromegaly patients. Patients and methods A longitudinal, retrospective and multicenter study was conducted on 172 acromegaly patients. Results Median diagnostic delay and duration of follow-up were respectively 10 years (IQR: 6) and 10 years (IQR: 8). P-VFs were observed in 18.6% and i-VFs occurred in 34.3% of patients. The median estimated diagnostic delay was longer in patients with i-VFs (median: 11 years, IQR: 3), in comparison to those without i-VFs (median: 8 years, IQR: 7; p = 0.02). Age at acromegaly diagnosis and at last follow-up were higher in patients with i-VFs, with respect to those without i-VFs. The age at acromegaly diagnosis was positively associated with the diagnostic delay (p < 0.001, r = 0.216). A longer history of active acromegaly was associated with a high frequency of i-VFs (p = 0.03). The logistic regression confirmed that patients with a diagnostic delay > 10 years had 1.5-folds increased risk of developing i-VFs (OR: 1.5; 95%CI: 1.1–2; p = 0.017). Conclusion Our data showed that the diagnostic delay in acromegaly has a significant impact on VF risk, further supporting the clinical relevance of an early acromegaly diagnosis.

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“…Patients with active acromegaly have been shown to be at higher risk of vertebral fractures compared to those with a controlled/cured disease [5]. However, in a recent HR-pQCT study, Duan et al [53] suggested that the negative impact of acromegaly on bone microstructure may still not be fully reversible. With respect to TBS values, our meta-analysis could not highlight any significant difference in the outcome measure according to acromegaly disease activity.…”

Section: Discussionmentioning

confidence: 99%

Trabecular Bone Score as an Index of Bone Fragility in Patients with Acromegaly: A Systematic Review and Meta-Analysis

Bioletto¹,

Barale²,

Prencipe³

et al. 2022

Neuroendocrinology

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Background. Acromegaly is characterized by impaired bone quality and increased fracture risk. However, due to the pathophysiology of acromegalic osteopathy, bone mineral density (BMD) does not represent a reliable predictor for fragility fractures in this setting. Trabecular bone score (TBS) has been recently evaluated as an alternative index of skeletal fragility in acromegalic patients. However, no conclusive data are still available in this regard. Methods. PubMed/Medline, EMBASE, Cochrane library, Ovid and CINAHL databases were systematically searched until June 2022 for studies reporting data either about the comparison of TBS values between acromegalic patients and non-acromegalic controls, or about the relationship – within acromegalic patients – between TBS values and fracture risk. Effect sizes were pooled through a random-effect model. Results. Eight studies were eligible for inclusion in the meta-analysis, encompassing 336 acromegalic patients and 490 non-acromegalic controls. Overall, TBS was significantly lower in acromegalic patients compared to controls (-0.089, 95%CI: {-0.111,-0.067}, p<0.01), irrespectively to acromegaly disease activity and gonadal status. With respect to fracture risk, TBS was significantly lower in acromegalic patients with vertebral fractures than in those without (-0.099, 95%CI: {-0.166,-0.032}, p<0.01). Conclusion. In this meta-analysis, we specifically assessed the role of TBS as an index of bone quality and fracture risk in patients with acromegaly. Our results support the notion that TBS could be of value in the assessment and management of skeletal fragility in acromegalic patients, especially in light of the poor information provided in this setting by BMD.

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The Negative Impacts of Acromegaly on Bone Microstructure Not Fully Reversible

Cited by 13 publications

References 29 publications

Long-term Pegvisomant Therapy of Acromegaly: Effects on Bone Density, Turnover and Microstructure Using HRpQCT

Long-term Pegvisomant Therapy of Acromegaly: Effects on Bone Density, Turnover and Microstructure Using HRpQCT

Impact of the diagnostic delay of acromegaly on bone health: data from a real life and long term follow-up experience

Trabecular Bone Score as an Index of Bone Fragility in Patients with Acromegaly: A Systematic Review and Meta-Analysis

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