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

Abstract

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.

Trabecular Bone Score as a Reliable Measure of Lumbar Spine Bone Microarchitecture in Acromegalic Patients

“…Our data confirm the presence of silent VFs in acromegalic patients. In our cohort, the prevalence of VFs, assessed by morphometric examination, was 11.4%, similar to that reported by Madeira and colleagues, but lower compared to other studies [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 23 , 41 , 61 ]. Different methods have been used to identify VFs in different studies, performing a radiographic examination of the spine rather than a morphometric examination in most cases.…”

Acromegaly and Bone: An Update

“…Therefore, biochemical control appears to be an important protective factor for skeletal damage. VFs may occur early in the natural disease history [ 25 ] and therefore normalization of biochemical activity should be mandatorily achieved as quickly as possible after the diagnosis, although this may not be enough to avoid fractures due to the known issue of diagnostic delay [ 24 , 82 ]. Additionally, concomitant diabetes mellitus, another common comorbidity of acromegaly [ 83 ], as well as a cause of bone fragility per se [ 84 ], was reported to increase the risk of fracture in active disease [ 85 ].…”

“…Recently, we showed that prevalence of radiological thoracic VFs was associated with elevated presurgical random GH levels in patients recently diagnosed with acromegaly [ 25 ]. Moreover, another recent study suggested that a diagnostic delay >10 years may be a quite strong predictor of incident VFs [ 24 ].…”

“…Therefore, in acromegaly an increase in fracture risk, particularly at the vertebral level [ 20 ], has been progressively and consistently reported in the last 15 years [ 21 , 22 ], and this now represents one of the most relevant systemic complications of the disease [ 23 ]. In fact, since the first report of excess morphometric fractures in postmenopausal women with acromegaly [ 21 ], many subsequent papers—including several from our group [ 24 , 25 ]—have confirmed, extended, analyzed the underlying mechanism(s) and possible protective effect of treatment, making this one of the hottest topics in the area of acromegaly management [ 26 ]. Due to the current clinical impact of bone involvement in acromegaly and its increasingly wide literature coverage, it was felt necessary to critically review and update the emerging evidence on the pathophysiology, clinical history and presentation, diagnosis and treatment of acromegaly-related osteopathy through this paper.…”

Early Predictors of Remission in Acromegaly Patients after Pure Endoscopic Endonasal Transsphenoidal Surgery

“…1 It is characterized by excessive growth hormone (GH) secretion by a pituitary neuroendocrine tumor (Pit-NET) causing bony and soft tissue enlargement and a series of life-threatening comorbidities such as cardiovascular, metabolic, and systemic diseases. 2,3 Oversecretion of the GH acting as a fertilizer for all the diseases and malignancies all over the body doubles the mortality rates in acromegaly patients compared with the general population. 4,5 Cardiovascular diseases, respiratory complications, and malignancies are theleading causes of death in 60, 25, and 15% of acromegaly patients, respectively.…”