Abstract: TH-PO775

Effects of Denosumab in Osteoporotic Hemodialysis (HD) Patients with Secondary Hyperparathyroidism (SHPT)

Session Information

Category: Dialysis

  • 607 Dialysis: Epidemiology, Outcomes, Clinical Trials - Non-Cardiovascular

Authors

  • Funakoshi, Satoshi, Nagasaki Kidney Center, Nagasaski, Japan
  • Nishino, Tomoya, Nagasaki University School of Medicine, Nagasaki, Nagasaki, Japan
  • Harada, Takashi, Nagasaki Kidney Center, Nagasaski, Japan
  • Taguchi, Naoto, Nagasaki Kidney Center, Nagasaski, Japan
  • Hashiguchi, Jyunichiro, Nagasaki Kidney Center, Nagasaski, Japan
  • Yamashita, Makiko, Nagasaki Kidney Center, Nagasaski, Japan
  • Kawazu, Tayo, Nagasaki Kidney Center, Nagasaski, Japan
  • Sasaki, Osamu, Nagasaki Kidney Center, Nagasaski, Japan
  • Ichinose, Hiroshi, Nagasaki Kidney Center, Nagasaski, Japan
  • Sawase, Kenji, Nagasaki Kidney Center, Nagasaski, Japan
  • Obata, Yoko, Nagasaki University School of Medicine, Nagasaki, Nagasaki, Japan
Background

Denosumab, a human monoclonal antibody which binds to RANKL, inhibits osteoclast differentiation/activation and exerts primarily anti-resorptive action. Denosumab also inhibits bone formation and hence may correct high bone turnover observed in HD patients. Meanwhile serum markers for bone metabolism are reported to correlate with PTH but not with circulating fibroblast growth factor 23 (FGF23), which decreases bone mineralization and is markedly increased in HD patients.

Methods

Among HD patients with secondary hyperparathyroidism (SHPT) who received intravenous pulse therapy with vitamin D (VD) analogues, those with bone mineral density < 70% YAM were enrolled in this study after their informed consent was obtained. Serum calcium, phosphate, PTH, bone metabolism markers and FGF23 were measured before and 4 weeks after subcutaneous administration of 60mg of denosumab.

Results

A steep decline in serum calcium levels was observed in all 16 subjects (5 males and 11 females; mean age, 66.7±7.4 years old; mean HD duration, 11.4±7.6 years), and calcium-based phosphate binders and VD analogues were started to adjust their calcium levels. After 4 weeks of denosumab administration, significant decreases were seen in the bone resorption markers TRCP-5B and NTX, and the bone formation markers BAP and P1NP as well as in PTH; furthermore, FGF23 was significantly decreased (table).

Conclusion

Study results suggest that denosumab may potentially correct bone turnover in osteoporotic HD patients with SHPT. A possible explanations for decreased FGF 23 could be that the addition of calcium-based phosphate binders lowered the phosphate burden in HD patients and that VD signaling resulted in a negative feedback loop within FGF family.

Change of Serum Bone Metabolism Markers and FGF 23 after Denosumab Administration
 baseline (mean±SD)week 4 (mean±SD)p-value
calcium (mg/dL)9.4±0.58.3±1.4p<0.001
phosphorus (mg/dL)5.6±0.74.1±1.3p<0.001
i PTH (pg/mL)118.6±87.1375.6±332.6p<0.001
TRACP-5b (mU/dL)672.6±306.2132.5±68.6p<0.001
NTX (nM BCE/L)171.0±96.020.7±4.0p<0.001
BAP ( μ g/L)16.6±6.414.4±6.70.007
PINP (ng/mL)333.0±168.0205.3±125.30.002
FGF 23 (pg/mL)12954.6±16395.07646.4±14726.00.029

Funding

  • Private Foundation Support