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Abstract: FR-OR05

Parathyroidectomy Decreases Muscle Expression of TGF-β1 and Improves Muscle Function

Session Information

Category: Bone and Mineral Metabolism

  • 402 Bone and Mineral Metabolism: Clinical

Authors

  • Duque, Eduardo J., Universidade de Sao Paulo Hospital das Clinicas, Sao Paulo, São Paulo, Brazil
  • Crispilho, Shirley Ferraz, Universidade Nove de Julho, Sao Paulo, SP, Brazil
  • Kakinoki Teng, Andre, Universidade de Sao Paulo Hospital das Clinicas, Sao Paulo, São Paulo, Brazil
  • Oliveira, Ivone Braga de, Universidade de Sao Paulo Hospital das Clinicas, Sao Paulo, São Paulo, Brazil
  • Furukawa, Luzia Naoko Shinohara, Universidade de Sao Paulo Hospital das Clinicas, Sao Paulo, São Paulo, Brazil
  • Jorgetti, Vanda, Universidade de Sao Paulo Hospital das Clinicas, Sao Paulo, São Paulo, Brazil
  • Shinjo, Samuel Katsuyuki, Universidade de Sao Paulo Hospital das Clinicas, Sao Paulo, São Paulo, Brazil
  • Avesani, Carla Maria, Karolinska Institutet, Stockholm, Stockholm, Sweden
  • Elias, Rosilene M., Universidade de Sao Paulo Hospital das Clinicas, Sao Paulo, São Paulo, Brazil
  • Moyses, Rosa M.A., Universidade de Sao Paulo Hospital das Clinicas, Sao Paulo, São Paulo, Brazil
Background

Secondary hyperparathyroidism (SHPT) is commonly associated with muscle dysfunction in patients with chronic kidney disease (CKD). PTH and TGF-β are known to operate together to exert their biological activities, and pathological TGF-β release from bones was shown to mediate muscle weakness. We sought to investigate the relationship between changes in mineral and bone metabolism (MBD) in patients with SHPT pre- and post-parathyroidectomy (PTX), and muscle expression of TGF-β, FNDC5 (the irisin precursor), and RANKL, which has been recently recognized as an inductor of sarcopenia.

Methods

We prospectively enrolled 29 patients on dialysis (39 ys, 62% female) referred for PTX. Muscle phenotyping involved histological analysis by immunohistochemistry and gene expression; body composition by DXA; functional and strength tests analysis by using Actigraph GT3X accelerometer, handgrip (HGS), supine (SP) and leg press (LP). 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 and physical evaluation parameters are shown in Table 1. TGF-β1 expression decreased (21 vs 7%, p < 0.01) and vitamin-D receptor increased (31 vs. 68 +cells/mm2, p<0.01) after PTX. At baseline, muscle RANKL and FGF21 genes were upregulated (16-fold, p=0.002; and 6-fold, p=0.06, respectively), when compared to controls, with no effect of PTX. Conversely, FNDC5 was downregulated (3.2-fold, p=0.034), and PTX led to its increase (2-fold, p <0.01).

Conclusion

Patients with SHPT on dialysis submitted to PTX experienced a marked improvement in bone mass and muscular function, but not in muscle mass. Our findings suggest that muscle TGF-β1 and RANKL might play a role in CKD-associated sarcopenia. We also propose that SHPT impairs muscular strength through changes in Irisin and TGF-β synthesis, which were reverted by PTX.

Funding

  • Government Support – Non-U.S.