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Iron Lactate-Induced Osteopenia in Male Sprague-Dawley Rats

Pathology Section, Drug Safety Evaluation, Developmental Research Laboratories, Shionogi & Co, Ltd, Toyonaka, Osaka, Japan, shuuichi.matsushima{at}shionogi.co.jp, Research Institute of Drug Safety, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka, 573-0101, Japan

Mariko Hoshimoto

Pathology Section, Drug Safety Evaluation, Developmental Research Laboratories, Shionogi & Co, Ltd, Toyonaka, Osaka, Japan

Mikinori Torii

Pathology Section, Drug Safety Evaluation, Developmental Research Laboratories, Shionogi & Co, Ltd, Toyonaka, Osaka, Japan

Kiyokazu Ozaki

Research Institute of Drug Safety, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka, 573-0101, Japan

Isao Narama

Research Institute of Drug Safety, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka, 573-0101, Japan

Osteopenia was induced in rats fed a diet containing 50,000 ppm (5%) iron lactate for 2 or 4 weeks. Blood chemistry, urinalysis, and bone histomorphometry of the proximal tibial metaphysis were performed. Urinary pyridinoline and deoxypyridinolin e and the osteoclast number per bone surface were selected for the measurement of dynamic resorption. The osteoclast surface, eroded surface, and osteoblast surface increased at both ends of the exposure periods, and bone resorption and formation both increased. The bone volume, trabecular thickness, and trabecular number decreased, and the secondary spongiosa of proximal metaphysis showed a marked bone loss. However, no mineralization defect was observed. At the end of the 2-week exposure period, biomarkers of osteoclasts and osteoblasts had increased the most, and the osteoblast surface, osteoclast surface, and osteoclast number per bone surface increased with prolonged exposure. The pathological changes of the bone lesion in iron lactate-overloaded rats were similar to those in rats of the osteoporotic model, because they consisted of changes reflecting the increase of bone resorption and formation without an osteomalacic change. However, the decline of serum parathyroid hormone (PTH) levels was different from that of the osteoporosi s model rat.

We concluded iron-induced bone lesions probably differ from those of low turnover bone diseases.

Key Words: Iron lactate • osteopenia • PTH • osteoclast • osteoblast.

Toxicologic Pathology, Vol. 29, No. 6, 623-629 (2001)
DOI: 10.1080/019262301753385951


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