Healing of a tibial double osteotomy is modified by clodronate administration

Nyman, Markku; Gao, Tian; Ts, Lindholm

doi:10.1007/bf00573453

Cited by 28 publications

(34 citation statements)

References 13 publications

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“…Animal studies have indicated that bisphosphonates may be of benefit in the clinical situation where increased strength of fractured or distracted bone is required (6–13) . In our previous rabbit study of distraction osteogenesis, ZA increased regenerate bone volume, BMC, and strength, while also preventing osteopenia at the 6‐week time‐point evaluated (16) .…”

Section: Discussionmentioning

confidence: 98%

Transient Retention of Endochondral Cartilaginous Matrix With Bisphosphonate Treatment in a Long-Term Rabbit Model of Distraction Osteogenesis

Smith

McEvoy

Little

et al. 2004

Journal of Bone and Mineral Research

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Bisphosphonates induce major increases in strength of callus in distraction osteogenesis in the short term. Poor understanding of the underlying mechanism, however, raises concerns about long-term consequences. In this long-term study in 32 rabbits, zoledronic acid transiently increased trabeculae by delayed temporal progression of endochondral bone remodeling but did not prevent radiographic completion of bone repair. Introduction:We hypothesized that bisphosphonate inhibition of osteoclast-mediated resorption would retain bone during repair, producing a larger callus in the short term. However, if remodeling was not restored, completion of the bone repair process in the long term could be jeopardized. Materials and Methods: Juvenile rabbits underwent right tibial osteotomy and 2 weeks of distraction, followed by a period of consolidation. Animals received saline (controls) or zoledronic acid (ZA; 0.1 mg/kg at surgery and again 2 weeks later), and distracted tibias were examined by radiograph, DXA, histology, and histomorphometry at 2, 4, 6, 18, and 44 weeks after surgery. Results: Regenerated bone in ZA-treated animals was denser than controls on radiographs at 6 weeks and had more distinct radiodense trabeculae and retention of original cortices at 18 weeks. By 44 weeks, controls and ZA-treated animals were radiographically healed and indistinguishable. Regenerate BMD and BMC increased between 2 and 4 weeks in all animals, with a greater effect in ZA. At 6 weeks, BMD and BMC in ZA-treated animals were 1.6-and 2-fold greater, respectively, than controls (p Ͻ 0.01). From 6 to 44 weeks, the control values gradually increased and approached the ZA-treated values. Regenerate bone volume and trabecular number by histomorphometry were from 1.6-to 2-fold greater in ZA-treated animals at 6 and 18 weeks (p Ͻ 0.05). Endochondral cartilaginous matrix volume was up to 2.4-fold greater in ZA-treated animals at 2 and 4 weeks (p Ͻ 0.05). TRACP ϩ cells in ZA-treated animals were larger with more nuclei. Mineral apposition rate and osteoblast number and surface were lower in ZA-treated animals at 6 weeks (p Ͻ 0.01) but not at later times. Conclusions: Disruption of TRACPϩ cell function by ZA during bone regeneration seems to lead to an accretion of cancellous bone built on a larger endochondral cartilaginous matrix and increased bone mass, consistent with reported increases in short-term callus strength. This increase in bone mass, caused by a delay in remodeling, provided a transient advantage without preventing radiographic completion of the bone repair process in the long term. Noncontinuous treatment with nitrogen-containing bisphosphonates thus can have short-term beneficial effects without preventing long-term bone repair.

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Section: Discussionmentioning

confidence: 98%

Transient Retention of Endochondral Cartilaginous Matrix With Bisphosphonate Treatment in a Long-Term Rabbit Model of Distraction Osteogenesis

Smith

McEvoy

Little

et al. 2004

Journal of Bone and Mineral Research

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“…It was concluded from previous studies using an array of earlier bisphosphonates in fracture models that there was neither a detrimental nor a net negative effect on healing, but in all there was delay in remodelling because osteoclastic inhibition was found. [16][17][18][19][20][21] In one previous study, using pamidronate and a distraction model, the dose of pamidronate was only 0.6 mg/kg. The BMD in the surrounding bone was preserved, but this wore off after 15 days and there was no significant change in the regenerate.…”

Section: Discussionmentioning

confidence: 99%

Intravenous pamidronate reduces osteoporosis and improves formation of the regenerate during distraction osteogenesis

Little

Cornell²,

Briody³

et al. 2001

The Journal of Bone and Joint Surgery. British volume

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W e examined the effect on bone mineral density (BMD) of a single dose of 3 mg/kg of the bisphosphonate, pamidronate (Novartis) in distraction osteogenesis in immature rabbits.Seventeen rabbits (9 control, 8 given pamidronate) were examined by dual-energy x-ray absorptiometry. There was a significant increase in the BMD in the pamidronate group compared with the control animals. The mean areal BMD (g/cm 2 ) in the bone proximal and distal to the regenerate was increased by 40% and 39%, respectively, compared with the control group (p < 0.05). The BMD of the regenerate bone was increased by a mean of 43% (p < 0.05). There was an increase of 22% in the mean area of regenerate formed in the pamidronate group (p < 0.05).Histological examination of bone in nine rabbits (5 control, 4 pamidronate) showed an increase in osteoblastic rimming and mineralisation of the regenerate, increased formation of bone around the pin sites and an increase in the cortical width of the bone adjacent to the regenerate in the rabbits given pamidronate.Pamidronate had a markedly positive effect. It reduced the disuse osteoporosis normally associated with lengthening using an external fixator and increased the amount and density of the regenerate bone. Further study is required to examine the mechanical properties of the regenerate after the administration of pamidronate.

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“…The effects of various bisphosphonates on fracture healing in different animal models have been studied in a number of studies which collectively report an augmented callus size (473)(474)(475)(476)(477)(478)(479)(480)(481)(482). The increased callus dimension has been shown to persist in rat fractures even after 49 weeks of healing (480).…”

Section: Gene Therapy Resultsmentioning

confidence: 96%

Gene therapy methods in bone and joint disorders

Ulrich-Vinther

2007

Acta Orthopaedica

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Healing of a tibial double osteotomy is modified by clodronate administration

Cited by 28 publications

References 13 publications

Transient Retention of Endochondral Cartilaginous Matrix With Bisphosphonate Treatment in a Long-Term Rabbit Model of Distraction Osteogenesis

Transient Retention of Endochondral Cartilaginous Matrix With Bisphosphonate Treatment in a Long-Term Rabbit Model of Distraction Osteogenesis

Intravenous pamidronate reduces osteoporosis and improves formation of the regenerate during distraction osteogenesis

Gene therapy methods in bone and joint disorders

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