The role of osteopontin and osteocyte-derived factors in secondary hyperparathyroidism-induced myopathy

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Duque, Eduardo J. ; Crispilho, Shirley F. ; Oliveira, Ivone B. ; Dominguez, Wagner, V ; Silva, Cleonice ; Furukawa, Luzia ; Teng, Andre K. ; Avesani, Carla M. ; Shinjo, Samuel K. ; Elias, Rosilene M. ; Jorgetti, Vanda ; Moyses, Rosa M. A.

• Document type: Journal article
• Source: JBMR PLUS; v. 8, n. 8, p. 12-pg., 2024-06-28.

Abstract

Muscle weakness is a common symptom in CKD patients, and the pathway by which secondary hyperparathyroidism (SHPT) affects muscle function is unknown. Osteopontin (OPN), a bone matrix protein stimulated by PTH and phosphate, has been associated with inflammatory muscle diseases. In this observational and prospective cohort study, we evaluated 30 patients with severe SHPT (39 +/- 12 yr; 18 women), before and 6 mo after parathyroidectomy (PTx). We examined the relationships among CKD-mineral and bone disorder parameters; myokine and inflammatory cytokine levels; and changes in resting energy expenditure (REE), muscle function, BMD, and muscle-related proteins. At baseline, the patients showed low gene expression of muscle turnover markers and irisin, as well as high protein expression of OPN, transforming growth factor beta (TGF-beta), and fibroblast growth factor 21. Six months after PTx, REE and muscle mass had not changed, but physical performance, muscle strength, and bone mass improved, more so in patients undergoing total PTx. Also, there were reductions in the protein expression of OPN (11 vs 3%, p=.01) and TGF-beta (21 vs 7%, p=.002) in muscle, together with a significant increase in irisin muscular levels (30 vs 35 pg/mg, p=.02). The gain in bone mass and the increase in irisin levels correlated with a reduction in PTH. The levels of interleukin (IL)-1 beta, tumor necrosis factor alpha, and IL-17 (markers of myositis) were also lower after PTx. Our data suggest that SHPT plays a role in CKD-induced muscle dysfunction, indirectly, via release of bone-specific proteins, which is partially reverted with PTx. How secondary hyperparathyroidism (SHPT) affects muscle quality in CKD patients is unclear. This observational, prospective study performed muscle phenotyping by performance evaluation, body composition analysis, and muscle biopsies of 30 patients on dialysis with SHPT, before and after parathyroidectomy (PTx). The main findings include evidence of local tissue inflammation and blunting of muscle turnover in patients compared to healthy individuals. Despite no changes to muscle mass or energy expenditure, PTx improved functionality, bone mass, and influenced the molecular phenotyping of muscle tissue by altering the expression of bone-specific proteins and reducing inflammation. These findings suggest that SHPT plays a role in CKD-induced muscle dysfunction and that PTx has a beneficial effect on uremic myopathy. Graphical Abstract (AU)

• FAPESP's process: 19/14583-4 - Impact of parathyroidectomy on sarcopenia and energy metabolism in patients with chronic kidney disease on dialysis and with secondary hyperparathyroidism
• Grantee: Rosa Maria Affonso Moysés
• Support Opportunities: Regular Research Grants