Bisphosphonate (YM529) delays the repair of cortical bone defect after drill-hole injury by reducing terminal differentiation of osteoblasts in the mouse femur

Nagashima, Masato; Sakai, Akinori; Uchida, Soshi; Tanaka, Shinya; Tanaka, Masahiro; Nakamura, Toshio

doi:10.1016/j.bone.2004.11.013

Cited by 50 publications

(23 citation statements)

References 22 publications

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“…8 In a recent study of ours using a bisphosphonate for mice with a drill hole in the femur, osteocalcin mRNA expression and calls remodeling were suppressed from 14 to 28 days after operation. 9 In the present study, elcatonin suppressed increases in osteoclast surface both in the bone defects and in the noninjured bone. m-CT demonstrated that there was no delay of bone wound healing, filling-up bone defect, or lamellar bone formation.…”

Section: Discussionmentioning

confidence: 76%

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

Katae

Tanaka

Sakai

et al. 2009

Journal Orthopaedic Research

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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.

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Section: Discussionmentioning

confidence: 76%

“…At the same time, the strong suppression of the callus remodeling resulted in the persistent visibility of the original fracture line and lower content of the lamellar bone. 8,9 Thus, there are some difficulties in using a strong suppressor of bone resorption to manage osteoporotic patients during bone fracture healing.…”

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confidence: 99%

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

Katae

Tanaka

Sakai

et al. 2009

Journal Orthopaedic Research

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“…At 8 weeks postfracture when bone remodeling commenced, SR treatment further increased Since the imbalanced bone turnover with excessive bone resorption and impaired bone formation could produce destructive effect on fracture healing in osteoporotic subjects, anticatabolic drugs [such as bisphosphonates, estrogen, salmon calcitonin, 1α,25-Dihydroxy-2β(3-hydroxypropoxy)vitamin D3), et al] and anabolic agents (such as parathyroid hormone) have been applied on treatment of osteoporotic fracture. Anticatabolic drugs based on inhibition of bone resorption could lead to increased callus volume, BMD and biomechanical strength at the early healing period, and might delay callus remodeling to different extent afterwards [26,27]. Parathyroid hormone , the only FDA-approved anabolic agent, has been demonstrated to enhance cancellous bone healing at the site of osteotomy [24,28].…”

Section: Discussionmentioning

confidence: 98%

Systemic treatment with strontium ranelate promotes tibial fracture healing in ovariectomized rats

Luo

Feng

et al. 2009

Osteoporos Int

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“…Although bisphosphonates promote apoptosis of osteoclasts, they also reduce apoptosis of osteocytes and may inhibit osteoblast activity. [28][29][30] Mineral apposition rate on the periosteal surface of the femur and tibia was reduced with risedronate or alendronate treatment in growing rats. As this periosteal modeling should be independent of osteoclast activity, this may indicate a direct effect of bisphosphonates on osteoblast activity.…”

Section: Discussionmentioning

confidence: 99%

Bisphosphonate treatment delays stress fracture remodeling in the rat ulna

Kidd

Cowling

et al. 2011

Journal Orthopaedic Research

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Because bisphosphonates (BPs) are potent inhibitors of bone resorption, we hypothesized that they would retard direct remodeling of stress fractures. The aim of this study was to determine the effect of risedronate on direct remodeling and woven bone callus formation following stress fracture formation in the rat ulna. In 135 adult female Wistar rats, cyclic loading of the ulna created stress fractures. Rats were treated daily with oral saline, or risedronate at 0.1 or 1.0 mg/kg. From each bone, histomorphometry was performed on sections stained with toluidine blue at a standard level along the fracture. The high dose of risedronate caused a significant decrease in the percentage of repaired stress fracture and bone resorption along the stress fracture line at 6 and 10 weeks after loading (p < 0.05). At this dose, intracortical resorption was significantly reduced at 10 weeks after loading and intracortical new bone area was significantly reduced at 6 and 10 weeks. Woven bone formation and consolidation phases of stress fracture repair were not affected by low or high doses of risedronate. In conclusion, high dose bisphosphonate treatment impaired healing of a large stress fracture line by reducing the volume of bone resorbed and replaced during remodeling. We also confirmed that periosteal callus formation was not adversely affected by risedronate treatment. ß

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Bisphosphonate (YM529) delays the repair of cortical bone defect after drill-hole injury by reducing terminal differentiation of osteoblasts in the mouse femur

Cited by 50 publications

References 22 publications

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

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

Systemic treatment with strontium ranelate promotes tibial fracture healing in ovariectomized rats

Bisphosphonate treatment delays stress fracture remodeling in the rat ulna

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