Progression of acromegalic arthropathy despite long-term biochemical control: a prospective, radiological study

Abstract

Objective: Arthropathy is an invalidating complication of acromegaly, of which the prognosis and determinants are currently unknown in treated acromegaly. Therefore, the objective of the present study was to investigate the radiographic progression of arthropathy over a mean follow-up period of 2.6 years and determinants of outcome in patients with long-term, well-controlled acromegaly. Design: Prospective follow-up study. Methods: In a prospective cohort study we studied 58 patients (mean age 62, women 41%) with controlled acromegaly for a mean of 17.6 years. Radiographic progression of joint disease was defined by the Osteoarthritis Research Society International classification as a 1-point increase in joint space narrowing (JSN) or osteophyte scores on radiographs of the hands, knees, and hips obtained at the first study visit and after 2.6 years. Potential risk factors for progression were assessed. Results: Progression of osteophytes and JSN was observed in 72 and 74% of patients respectively. Higher age predisposed for osteophyte progression. Patients with biochemical control by somatostatin (SMS) analogs had more progression of osteophytosis than surgically cured patients (odds ratioZ18.9, PZ0.025), independent of age, sex, BMI, baseline IGF1 SDS and exon 3 deletion of the GHR. This was also evident for JSN progression, as were higher age and higher baseline IGF1 SDS. Conclusions: Acromegalic patients have progressive JSN and osteophytosis, despite long-term biochemical control. Parameters reflecting GH/IGF1 activity were associated with progressive joint disease. Remarkably, biochemical control by SMS analogs was associated with more progression than surgical cure. Although the present study is not a randomized controlled trial, this may indicate insufficient GH control according to current criteria and the need for more aggressive therapy.

Bone and Joint Disorders in Acromegaly

“…Recently, it has been reported that despite long-term biochemically controlled disease, more than 70% of patients have progressive osteophytosis and/or JSN [85]. The highest radiographic progression rate was seen in older patients and in patients with higher GH/IGF-1 activity.…”

“…The highest radiographic progression rate was seen in older patients and in patients with higher GH/IGF-1 activity. Interestingly, the highest progression rate of joint disease was reported in medically treated patients compared to surgically cured patients [85]. Since GH secretion does not normalize during SMS treatment [86], subtle ongoing GH overproduction, despite normal IGF-1 levels, may explain the increased progression rate in these patients.…”

Exosomal hsa-miR-21-5p derived from growth hormone-secreting pituitary adenoma promotes abnormal bone formation in acromegaly

“…4 However, current therapies focusing on the GH/IGF-1 axis are only effective in approximately 28% of acromegalic patients, while the remaining 72% of patients have continuing excessive bone growth or abnormal bone metabolism even after GHPA shrinkage or GH/IGF-1 level normalization. [5][6][7][8] These facts strongly suggest that another pathogenic mechanism is essential in the majority of acromegaly cases. In this study, the relationship between GHPA and osteoblasts was explored by studying GHPA exosomes, with the goal of providing a new perspective for evaluating acromegaly mechanisms.…”

Three-dimensional soft tissue analysis of the hand: a novel method to investigate effects of acromegaly

“…Musculoskeletal-related disorders account for the main functional disability in patients with acromegaly [3]. Following successful treatment of acromegaly, some features of the disease may show partial reversibility [4], but results are conflicting [5]. Concerning the hands of patients in long-term remission of acromegaly, the late effects of the disease have not been fully characterized [6].…”