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Article

Hyperparathyroidism Is Augmented by Ovariectomy in Nagase Analbuminemic Rats

Masaaki Inaba¹, Hirotoshi Morii, Takashi Katsumata^*, Hitoshi Goto, Eiji Ishimura, Takahiko Kawagishi, Maya Kamao, Toshio Okano and Yoshiki Nishizawa

Second Department of Internal Medicine, Osaka City University Medical School, 1–4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan; ^* Institute of Sumitomo Pharmaceutical Company, Osaka, Japan; and Kobe Pharmaceutical College, 4–19-1, Motoyama-Kitamachi, Higashinada-ku, Kobe 658, Japan

¹To whom correspondence should be addressed.

The role of albumin in bone metabolism was studied in Nagase analbuminemic (NA) rats. Serum calcium (Ca), inorganic phosphate (Pi) and magnesium (Mg) concentrations did not differ between female NA and control Sprague-Dawley (SD) rats at the time of ovariectomy (ovx), although serum ionized Ca was significantly lower in NA rats than in SD rats. Serum parathyroid hormone (PTH) and osteocalcin (OC) concentrations and urinary Ca excretion were significantly greater in NA rats than in SD rats, suggesting hyperparathyroidism and the resultant enhanced bone turnover in NA rats. Paradoxically, ovx increased serum PTH and OC in NA rats but not in SD rats. Ovx-induced exacerbation of hyperparathyroidism was confirmed by significantly greater conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D in ovx NA rats even after normalization to vitamin D–binding protein. Bone mineral density (BMD) in proximal tibia increased similarly in a time-dependent manner in sham-operated NA and SD rats. However, ovx ablated the time-dependent increase of BMD in SD rats and significantly decreased BMD in NA rats by 2 wk after ovx, resulting in a significantly lower BMD in ovx NA rats than in ovx SD rats. In summary, NA rats, which are analbuminemic with compensatory increases in lipid and protein synthesis, developed hyperparathyroidism, possibly due to an increase in serum Pi and a reduction of ionized Ca, and ovx induced a greater BMD reduction in NA rats than in SD rats, probably by exacerbating hyperparathyroidism.

KEY WORDS: • albumin • protein deficiency • hyperparathyroidism • osteocalcin • 1,25-dihydroxyvitamin D • rats

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