Abstract
PurposeBone health is compromised in acromegaly resulting in vertebral fractures (VFs), regardless of biochemical remission. Sclerostin is a negative inhibitor of bone formation and is associated with increased fracture risk in the general population. Therefore, we compared sclerostin concentrations between well-controlled acromegaly patients and healthy controls, and assessed its relationship with bone mineral density (BMD), and VFs in acromegaly.MethodsSeventy-nine patients (mean age 58.9 ± 11.4 years, 49% women) with controlled acromegaly, and 91 healthy controls (mean age 51.1 ± 16.9 years, 59% women) were included. Plasma sclerostin levels (pg/mL) in patients were measured with an ELISA assay, whereas in controls, serum levels were converted to plasma levels by multiplication with 3.6. In patients, VFs were radiographically assessed, and BMD was assessed using dual X-ray absorptiometry.ResultsMedian sclerostin concentration in controlled acromegaly patients was significantly lower than in healthy controls (104.5 pg/mL (range 45.7–234.7 pg/mL) vs 140.0 pg/mL (range 44.8–401.6 pg/mL), p < 0.001). Plasma sclerostin levels were not related to age, current growth hormone (GH) or insulin-like factor-1 (IGF-1) levels, gonadal state, treatment modality, remission duration, or BMD, VF presence, severity or progression.ConclusionPatients with long-term controlled acromegaly have lower plasma sclerostin levels than healthy controls, as a reflection of decreased osteocyte activity. Further longitudinal studies are needed to establish the course of sclerostin during different phases of disease and its exact effects in acromegalic osteopathy.
Highlights
Vertebral fractures (VFs) are a common complication of acromegaly, and contribute to the frequently observed thoracic kyphosis and high prevalence of back pain in these patients [1,2,3]
This study demonstrated significantly lower plasma sclerostin levels in patients with long-term well-controlled acromegaly compared to healthy controls
BMI correlated to sclerostin levels in controls, but not in acromegalic patients, and there was no significant correlation with age
Summary
Vertebral fractures (VFs) are a common complication of acromegaly, and contribute to the frequently observed thoracic kyphosis and high prevalence of back pain in these patients [1,2,3]. Prevalence of radiographic VFs is up to 40% during active disease, with even higher numbers after longterm follow-up in controlled patients (~60%) [4]. Supraphysiological growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels increase endocortical bone turnover in favor of bone formation, as reflected by biochemical bone markers and bone histomorphometry, leading to higher cortical BMD in the presence of stable trabecular bone mass [4, 7,8,9,10,11]. Despite a decrease in bone turnover, the GH-induced anabolic effects on bone mass sustain after prolonged remission in a large subset of patients [4, 12,13,14]. The increased GH-induced bone remodeling is considered to be harmful because of persistent structural changes in trabecular bone with loss of trabecular connectivity
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