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Abstract: TH-OR36

The Role of Osteopontin and Osteocyte-Derived Factors in Secondary Hyperparathyroidism-Induced Muscle Dystrophy

Session Information

Category: Bone and Mineral Metabolism

  • 502 Bone and Mineral Metabolism: Clinical

Authors

  • Duque, Eduardo Jorge, Universidade de Sao Paulo, Sao Paulo, Brazil
  • Crispilho, Shirley Ferraz, Universidade Nove de Julho, Sao Paulo, SP, Brazil
  • Kakinoki Teng, Andre, Universidade de Sao Paulo, Sao Paulo, Brazil
  • Oliveira, Ivone Braga de, Universidade de Sao Paulo, Sao Paulo, Brazil
  • Furukawa, Luzia Naoko Shinohara, Universidade de Sao Paulo, Sao Paulo, Brazil
  • Elias, Rosilene M., Universidade de Sao Paulo, Sao Paulo, Brazil
  • Jorgetti, Vanda, Universidade de Sao Paulo, Sao Paulo, Brazil
  • Moyses, Rosa M.A., Universidade de Sao Paulo, Sao Paulo, Brazil
Background

Secondary hyperparathyroidism (SHPT) leads to harmful effects, including muscle dystrophy. We have previously shown that parathyroidectomy (PTX) improves muscle function, but not muscle mass. We hypothesized that this improvement is related to muscle inflammatory modulation. Osteopontin (OPN), a bone matrix protein, is stimulated by PTH and phosphate, and regulates the immune system at different levels. In this study, we sought to investigate the relationship between changes in mineral and bone metabolism (MBD) in patients with SHPT pre- and post-PTX, muscle expression of osteocyte-derived factors and inflammatory markers.

Methods

We prospectively enrolled 30 patients on dialysis (39 ys, 62% female) referred for PTX. Muscle phenotyping involved tissue analysis by immunohistochemistry, multiplex protein quantification, and gene expression; DXA for body composition; physical evaluation by accelerometer. Muscle biopsies were obtained from the vastus lateralis at baseline and 6 months after PTX, and from healthy controls. Biochemical parameters were also collected.

Results

MBD, DXA, physical evaluation, and tissue analysis are shown in Table1. We found a significant decrease in systemic and muscle OPN concentrations. Higher muscle OPN expression was noted at baseline compared to controls (11vs 2.9%*) and PTX led to a marked reduction (11vs 3%*). Systemic and muscle cytokines concentrations also decreased. Muscle, but not systemic, RANKL and sclerostin concentrations decreased after PTX. *p<0.01

Conclusion

Our findings suggest that muscle OPN and osteocyte-derived factors might play a role in CKD-associated sarcopenia. In addition to its role in mineralization, OPN may foster muscle tissue inflammation, which is blunted after PTX. Based on these results, new pathways are revealed as therapeutic targets for uremic sarcopenia

Funding

  • Government Support – Non-U.S.