Clodronate increases the calcium content in fracture callus

Nyman, Markku; Paavolainen, Pekka; Ts, Lindholm

doi:10.1007/bf00451880

Cited by 42 publications

(37 citation statements)

References 9 publications

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“…A plethora of animal studies exist into the effects that bisphosphonates have on fracture healing in situations where the subject is already undergoing bisphosphonate therapy. The studies investigating bisphosphonates in fracture healing showed that continuous administration has an effect on callus size [ 1, 8,11,18,19,23]. This has been attributed to inhibition of remodeling during the healing process.…”

Section: Discussionmentioning

confidence: 99%

“…However, as these patients still sustain fractures, investigations have been conducted to assess fracture healing in the climate of continuous bisphosphonate dosing. Such studies usually showed an increase in callus size due to inhibition of remodeling, but not always an increase in callus strength [1,8,11,18,19,23]. Current opinion is that it is probably safe to continue bisphosphonate dosing during fracture repair [6].…”

Section: Introductionmentioning

confidence: 99%

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A single systemic dose of pamidronate improves bone mineral content and accelerates restoration of strength in a rat model of fracture repair

Amanat

Brown

Bilston

et al. 2005

Journal Orthopaedic Research

118

103

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Complications in fracture repair that lead to a delay in union remain clinically problematic. We believe that unwanted pre-mature catabolism of the healing callus, for example, in stress shielded situations, diminishes the rate at which strength is restored in bone repair and possibly leads to delayed union. We hypothesized that a single systemic dose of a nitrogen-containing bisphosphonate (N-BP) would increase bone mineral content (BMC), volume, and mechanical strength of union in fracture repair. We also set out to investigate local delivery to assess whether systemic exposure could be eliminated, due to concerns of bisphosphonate dosing of nontarget organs. After an open osteotomy fixed with a K wire, 40 12-week old Wistar male rats were divided into four groups of 10: saline control, bolus systemic subcutaneous injection of pamidronate (3 mg/kg), local low dose of pamidronate (0.1 mg), and a local high dose of pamidronate (1.0 mg). Rats were sacrificed 6 weeks post-operatively. Operated and non-operated femora underwent radiographic evaluation, quantitative computer tomography, and biomechanical testing in torsion. The growth plates and metaphyses of the tibia of the non-operated side were assessed for evidence of systemic exposure in the local groups. Significant increases in callus BMC and volume of the bolus systemic dose group were found compared to the saline control (p < 0.05). Further, the strength of the systemic dose callus was increased by 60% from 0.35 Nm (f0.11) for the saline control callus to 0.56 Nm (f0.25) for the systemic group (p = 0.05). Local treatment did not result in increased strength. The contralateral tibia1 growth plates of the local groups showed evidence of systemic exposure by the presence of retained primary spongiosa. This study confirms that a single perioperative systemic dose of pamidronate leads to significant increases in the BMC, volume, and strength of healing fractures in rats, making single dose N-BP therapy an appealing candidate for further examination in fracture repair.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A single systemic dose of pamidronate improves bone mineral content and accelerates restoration of strength in a rat model of fracture repair

Amanat

Brown

Bilston

et al. 2005

Journal Orthopaedic Research

118

103

View full text Add to dashboard Cite

show abstract

“…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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“…Studies on the effects of clodronate treatment on fracture healing are few and provide conflicting results. An increase in the calcium content in fracture callus during fracture healing in clodronate-treated rats has been shown (Nyman et al 1993) and the amount of callus may increase during clodronate treatment after fracture (Nyman et al 1993, Tarvainen et al 1994. The mechanical strength of the healing fractures may be unaffected when clodronate is administered after fracture induction (Nyman et al 1993, but it has also been impaired in nonosteoporotic rats, using therapeutic doses (Tarvainen et al 1994).…”

Section: Lars Nordsletten'mentioning

confidence: 99%