The role of osteopontin and osteocyte-derived factors in secondary hyperparathyroidism-induced myopathy.
Eduardo Jorge DuqueShirley F CrispilhoIvone B OliveiraWagner V DominguezCleonice SilvaLuzia FurukawaAndré K TengCarla M AvesaniSamuel K ShinjoRosilene M EliasVanda JorgettiRosa M A MoysésPublished in: JBMR plus (2024)
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-β), 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-β (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)-1β, 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.
Keyphrases
- skeletal muscle
- transforming growth factor
- end stage renal disease
- chronic kidney disease
- bone mineral density
- gene expression
- patients undergoing
- ejection fraction
- soft tissue
- newly diagnosed
- oxidative stress
- rheumatoid arthritis
- peritoneal dialysis
- dna methylation
- epithelial mesenchymal transition
- diabetic rats
- type diabetes
- mental health
- bone loss
- adipose tissue
- drug induced
- metabolic syndrome
- high glucose
- patient reported
- signaling pathway
- resistance training
- heart rate
- pregnancy outcomes