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Elcatonin injections suppress systemic bone resorption without affecting cortical bone regeneration after drill-hole injuries in mice

It is assumed that there are systemic changes in mineral metabolism during fracture healing that may cause a predisposition to sequential fractures in osteoporotic patients who suffered from previous fractures. Initial therapies for patients with osteoporotic fractures are important to prevent disab...

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Published in:Journal of orthopaedic research 2009-12, Vol.27 (12), p.1652-1658
Main Authors: Katae, Yuji, Tanaka, Shinya, Sakai, Akinori, Nagashima, Masato, Hirasawa, Hideyuki, Nakamura, Toshitaka
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description It is assumed that there are systemic changes in mineral metabolism during fracture healing that may cause a predisposition to sequential fractures in osteoporotic patients who suffered from previous fractures. Initial therapies for patients with osteoporotic fractures are important to prevent disabilities in daily life consequent to bone and muscle atrophies, and sequential fractures, although systemic and local bone metabolism during fracture healing have not been well understood. We evaluated the effects of bone injury and elcatonin injection as an initial therapy on systemic and local bone turnover and bone wound healing. Two drill holes were made in the diaphysis of the left femur and tibia of 12‐week‐old male C57BL/6J mice. They were treated with three doses of elcatonin or a vehicle thrice a week until the end of the 28‐day experiment. Urinary crosslinked C‐telopeptide of type I collagen (CTX) increased and the bone mineral densities (BMDs) in the lumbar vertebrae decreased in the vehicle‐treated mice. Elcatonin injection prevented increases in urinary CTX and reduction of the BMDs. In the noninjured femoral metaphysis, osteoclast surface increased until day 28, whereas elcatonin suppressed it. In the fracture site, elcatonin facilitated osteoblast proliferation and did not delay the healing of the bone defect. Bone injuries accelerated bone turnover systemically and locally, and the elcatonin injections suppressed the systemic acceleration of bone resorption without a delay of filling regenerated cortical bone in the bone defect. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1652–1658, 2009
doi_str_mv 10.1002/jor.20920
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Initial therapies for patients with osteoporotic fractures are important to prevent disabilities in daily life consequent to bone and muscle atrophies, and sequential fractures, although systemic and local bone metabolism during fracture healing have not been well understood. We evaluated the effects of bone injury and elcatonin injection as an initial therapy on systemic and local bone turnover and bone wound healing. Two drill holes were made in the diaphysis of the left femur and tibia of 12‐week‐old male C57BL/6J mice. They were treated with three doses of elcatonin or a vehicle thrice a week until the end of the 28‐day experiment. Urinary crosslinked C‐telopeptide of type I collagen (CTX) increased and the bone mineral densities (BMDs) in the lumbar vertebrae decreased in the vehicle‐treated mice. Elcatonin injection prevented increases in urinary CTX and reduction of the BMDs. In the noninjured femoral metaphysis, osteoclast surface increased until day 28, whereas elcatonin suppressed it. In the fracture site, elcatonin facilitated osteoblast proliferation and did not delay the healing of the bone defect. Bone injuries accelerated bone turnover systemically and locally, and the elcatonin injections suppressed the systemic acceleration of bone resorption without a delay of filling regenerated cortical bone in the bone defect. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. 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Orthop. Res</addtitle><description>It is assumed that there are systemic changes in mineral metabolism during fracture healing that may cause a predisposition to sequential fractures in osteoporotic patients who suffered from previous fractures. Initial therapies for patients with osteoporotic fractures are important to prevent disabilities in daily life consequent to bone and muscle atrophies, and sequential fractures, although systemic and local bone metabolism during fracture healing have not been well understood. We evaluated the effects of bone injury and elcatonin injection as an initial therapy on systemic and local bone turnover and bone wound healing. Two drill holes were made in the diaphysis of the left femur and tibia of 12‐week‐old male C57BL/6J mice. They were treated with three doses of elcatonin or a vehicle thrice a week until the end of the 28‐day experiment. Urinary crosslinked C‐telopeptide of type I collagen (CTX) increased and the bone mineral densities (BMDs) in the lumbar vertebrae decreased in the vehicle‐treated mice. Elcatonin injection prevented increases in urinary CTX and reduction of the BMDs. In the noninjured femoral metaphysis, osteoclast surface increased until day 28, whereas elcatonin suppressed it. In the fracture site, elcatonin facilitated osteoblast proliferation and did not delay the healing of the bone defect. Bone injuries accelerated bone turnover systemically and locally, and the elcatonin injections suppressed the systemic acceleration of bone resorption without a delay of filling regenerated cortical bone in the bone defect. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. 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They were treated with three doses of elcatonin or a vehicle thrice a week until the end of the 28‐day experiment. Urinary crosslinked C‐telopeptide of type I collagen (CTX) increased and the bone mineral densities (BMDs) in the lumbar vertebrae decreased in the vehicle‐treated mice. Elcatonin injection prevented increases in urinary CTX and reduction of the BMDs. In the noninjured femoral metaphysis, osteoclast surface increased until day 28, whereas elcatonin suppressed it. In the fracture site, elcatonin facilitated osteoblast proliferation and did not delay the healing of the bone defect. Bone injuries accelerated bone turnover systemically and locally, and the elcatonin injections suppressed the systemic acceleration of bone resorption without a delay of filling regenerated cortical bone in the bone defect. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. 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subjects Absorptiometry, Photon
Animals
Biomarkers - metabolism
Body Weight - drug effects
Bone Density Conservation Agents - pharmacology
Bone Regeneration - drug effects
Bone Regeneration - physiology
Bone Resorption - drug therapy
Bone Resorption - metabolism
calcitonin
Calcitonin - analogs & derivatives
Calcitonin - pharmacology
Collagen Type I - genetics
Collagen Type I - metabolism
Collagen Type I - urine
Disease Models, Animal
Femur - diagnostic imaging
Femur - drug effects
Femur - injuries
fracture
Lumbar Vertebrae - diagnostic imaging
Lumbar Vertebrae - drug effects
Lumbar Vertebrae - metabolism
Male
Mice
Mice, Inbred C57BL
microcomputed tomography (µ-CT)
Osteocalcin - genetics
Osteocalcin - metabolism
Peptides - urine
quantitative reverse transcription polymerase chain reaction (qRT-PCR)
RNA, Messenger - metabolism
urinary crosslinked C-telopeptide of type I collagen (CTX)
Wound Healing - drug effects
title Elcatonin injections suppress systemic bone resorption without affecting cortical bone regeneration after drill-hole injuries in mice
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