Effects of postmenopausal osteoporosis on renal osteodystrophy

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17754
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Tokai University
• Principal Investigator: TANAKA Hisae 東海大学, 医学部, 助教 (60803327)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 副甲状腺機能亢進症 / 慢性腎不全 / 閉経 / エストロゲン / 骨粗鬆症

Outline of Final Research Achievements

We induced secondary hyperparathyroidism (SHPT) by feeding high phosphorus diet after 5/6 nephrectomy, estrogen deficiency by ovariectomy (OVX), and combination of both in rats. Bone turnover and bone strength was evaluated with mRNA expression in bones and 3-point bend test for femurs, respectively. Rats with SHPT showed enhanced mRNA expression associated with both bone resorption and bone formation compared to sham operated rats. Additional OVX to SHPT led to increased RANKL/OPG ratio, which reflects bone resorption, and attenuated expression of mRNA associated with bone formation.Regarding mechanical properties of femur, yield force was lower in SHPT rats than sham rats, while higher force was required to break femurs of SHPT + OVX rats than CKD rats. This study suggests that OVX attenutates bone formation and exacerbate bone resorption caused by SHPT. Further studies are needed to elucidate the impact of OVX on bone strength in SHPT setting.

Free Research Field

CKD-MBD

Academic Significance and Societal Importance of the Research Achievements

エストロゲン欠乏と二次性副甲状腺機能亢進症を合併したときに，各々，またその組み合わせが骨代謝に与える影響を検討した研究は乏しく，慢性腎不全を有する女性の骨代謝におけるエストロゲンの重要性を示唆した．臨床的に慢性腎不全を伴う女性は男性よりも骨折リスクが高いことが分かっている．慢性腎不全を有する閉経後女性の骨粗鬆症や病的骨折に対する治療として，骨吸収抑制薬だけでは不十分で，エストロゲン補充や骨形成促進薬を用いて骨形成を促す必要性を示唆する研究である．