Addressing acromegaly and its musculoskeletal complications through new treatment strategies: Focus on growth hormone antagonists

Acromegaly is a rare but severe multi-organ disease that negatively affects the quality and duration of patients’ lives. This is exacerbated by the formation of a pathological complex of progressive hormonal, metabolic, and systemic disorders, each of which is an independent risk factor for early disability and premature death. In acromegaly, damage to the musculoskeletal system occurs due to the hyperproduction of growth hormone and insulin-like growth factor-1, leading to increased regeneration of bone tissue with changes in the cortical and trabecular structures of the bones. The activity of osteoclasts exceeds that of osteoblasts, resulting in specific microarchitectural changes in trabecular bone and loss of bone mass. Characteristic musculoskeletal disorders in patients with acromegaly include hypertrophic arthropathies of the peripheral and axial skeleton, temporomandibular joint diseases, and carpal tunnel syndrome, which diminish the quality of life for patients even after normalization of hormone secretion. The issue of therapy selection for patients with acromegaly and osteoarthropathy has been insufficiently studied. Medical therapy for acromegaly is an important stage both for the preoperative preparation of patients and for subsequent treatment. In cases of partial or complete resistance to monotherapy with somatostatin analogs or their intolerance, the use of a growth hormone receptor antagonist, specifically pegvisomant, is advisable as a recommended therapy. This drug suppresses the action of excess growth hormone, reduces the concentration of insulin-like growth factor-1 in the serum, as well as serum proteins sensitive to growth hormone, including free insulin-like growth factor-1; it modulates the proliferation, differentiation, and mineralization of osteoblast cells; it exhibits high selectivity for growth hormone receptors and does not interact with the receptors of other hormones, including prolactin. This type of therapy is highly effective, neutralizes the adverse effects of somatostatin analogs on carbohydrate metabolism, and stabilizes tumor growth. A distinctive feature of pegvisomant’s action is its ability to influence the proliferation, differentiation, and mineralization of osteoblast cells, which reduces the frequency of spinal fractures in patients with acromegaly.