Long-Term Oral Toxicity and Anti-osteoporotic Effect of Sintered Dicalcium Pyrophosphate in Rat Model of Postmenopausal
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ORIGINAL ARTICLE
Long-Term Oral Toxicity and Anti-osteoporotic Effect of Sintered Dicalcium Pyrophosphate in Rat Model of Postmenopausal Osteoporosis Yuh-Feng Tsai1,2 • Li-Ho Hsu3,4 • Chang-Chin Wu3,4,5 • Wei-Hua Cai6 Kai-Chiang Yang6 • Fang-Yu Fan6
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Received: 12 August 2015 / Accepted: 7 April 2016 Taiwanese Society of Biomedical Engineering 2017
Abstract Sintered dicalcium pyrophosphate (SDCP), a synthetic pyrophosphate analog, has shown potential for the management of osteoporosis. The long-term oral toxicity and anti-osteoporotic effect of SDCP in a postmenopausal osteoporosis rat model were evaluated in this study. SDCP was orally administered to bilateral ovariectomized (OVX) Wistar rats at a dose of 0.75 mg/kg daily for 24 weeks following by 2 weeks of observation. There were no abnormal findings in clinical signs of toxicity, food consumption, body weight, blood examination, necropsy, and histological inspection attributable to the ingestion of SDCP. The serum level of type I collagen fragments, a bone resorption marker, decreased in SDCP-treated rats, and the bone formation markers alkaline phosphatase, osteocalcin, and osteopontin significantly decreased. These
& Kai-Chiang Yang [email protected] & Fang-Yu Fan [email protected] 1
Department of Diagnostic Radiology, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei City 111, Taiwan
2
School of Medicine, Fu-Jen Catholic University, New Taipei City 24205, Taiwan
3
Department of Orthopedics, En Chu Kong Hospital, New Taipei City 23702, Taiwan
4
Department of Orthopedics, College of Medicine, National Taiwan University Hospital, National Taiwan University, Taipei City 10002, Taiwan
5
Department of Biomedical Engineering, Yuanpei University of Medical Technology, Hsinchu 30015, Taiwan
6
School of Dental Technology, College of Oral Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei City 11031, Taiwan
findings indicate that the bone turnover rate decreased in SDCP-treated animals. Relative to OVX rats, the increase in serum tartrate-resistant acid phosphatase 5b level represents an increase in bony tissues in the SDCP-treated rats. Histological examinations of distal femoral metaphyses further revealed that the ingestion of SDCP improved the trabecular bone architecture and decreased bone porosity. Analysis of limb bone ashes showed a significant increase in bone mineral content. Our results show that SDCP inhibits bone resorption to restore bone mass in OVX rats without deleterious effects, and therefore that SDCP has potential in the management of osteoporosis. Keywords Osteoporosis Pyrophosphate analog Sintered dicalcium pyrophosphate Oral toxicity Bone turnover markers
1 Introduction Osteoporosis, frequently found in the elderly and postmenopausal women, is characterized by low bone mass, deteriorated bone architecture, and alterations in bone quality [1]. Bone loss results from bone resorption by osteoclasts exceeding bone formation by osteoblasts, and is generally accompanied by an increased bone turnover rate [2].
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