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Iron Lactate-Induced Osteomalacia in Association with Osteoblast Dynamics

Pathology Section, Drug Safety Evaluation, Developmental Research Laboratories, Shionogi & Co, Ltd, Toyonaka, Osaka 561-0825, Japan, shuuichi.matsushima{at}shionogi.co.jp, Research Institute of Drug Safety, Setsunan University, Hirakata, Osaka 573-0101, Japan

Mikinori Tor

Pathology Section, Drug Safety Evaluation, Developmental Research Laboratories, Shionogi & Co, Ltd, Toyonaka, Osaka 561-0825, Japan

Kiyokazu Ozaki

Research Institute of Drug Safety, Setsunan University, Hirakata, Osaka 573-0101, Japan

Isao Narama

Research Institute of Drug Safety, Setsunan University, Hirakata, Osaka 573-0101, Japan

Osteomalacia was induced in rats fed a diet containing 50,000 ppm (5%) iron lactate for 13 weeks. The histopathology and histomorphometrical dynamics of osteoblasts under this condition were examined. Bone histomorphometry of the proximal tibial metaphysis revealed that the osteoblast surface, osteoid volume, osteoid surface and labeled surface ratio, which are the parameters of bone formation had increased. The blood chemistry revealed the greatest elevation in the osteocalcin level; however, the parathyroid hormone (PTH) secretion and inorganic phosphorus level were very low. From the serum biochemical, histopathological and histomorphometrical findings, the bone lesion in iron lactate-overloaded rats was considered to be similar to low turnover osteomalacia showing decreased trabeculae in secondary spongiosa and increased lamellar osteoid. Furthermore, an iron-positive reaction was detected at the interface between osteoid and mineralized bone. In the bone lesions induced by chronic iron overload, osteoblast recruitment exceeded that of mineralization or, alternatively, the iron within osteoblasts along the trabecular bone suppressed the remodeling and led to an increase in osteoid thickness.

Key Words: Iron lactate • osteomalacia • parathyroid hormone • hypophoshatemia • osteoclast • osteoblast.

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Toxicologic Pathology, Vol. 31, No. 6, 646-654 (2003)
DOI: 10.1080/01926230390241990


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