New Bone Formation Induced by Injection of Native Reindeer Bone Morphogenetic Protein Extract

Pekkarinen, Tarmo; Ts, Lindholm; Hietala, Oili A.; Jalovaara, P.

doi:10.1177/145749690309200312

Cited by 9 publications

(12 citation statements)

References 28 publications

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“…The 10 mg of bone extract group had significantly higher mean stiffness than the collagen group [9]. Our results confirm previous results, which showed that reindeer bone extract has good osteoconductivity both in [5,6,9]. It is known that the animal and fracture models, delivery systems and route of administration influence the dose response in bone healing studies [16].…”

Section: Discussionsupporting

confidence: 81%

“…We have shown previously that bone extract purified from reindeer bones effectively induces ectopic new bone formation (BF) in vivo [5,6]. The native reindeer bone extract has proved to possess better osteoinductivity than bovine or ostrich bone extracts, and it has been suggested that this is due to the fact that reindeers renew their antlers annually [7,8].…”

Section: Introductionmentioning

confidence: 99%

“…The collagen sponge was soaked in 200 μl sterile water and the sponge with extract was bundled up to form an implant. The doses were chosen according to our previous studies [5,6,9]. The InductOs™ kit (Wyeth Europa, Maidenhead/Berkshire, UK) for the implant contained 12 mg of rhBMP-2 and solvent.…”

Section: Reconstitution Of Implantsmentioning

confidence: 99%

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Reindeer bone extract can heal the critical-size rat femur defect

Tölli

Kujala

Jämsä

et al. 2010

International Orthopaedics (SICOT)

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Bone extract from reindeer induces new ectopic bone formation (BF) in muscle pouches, but its feasibility in experimental bone lesions has not been evaluated. We investigated the effects of implants, containing 2, 5, 15, 20 or 50 mg of reindeer bone extract in a collagen carrier, on the healing of 8-mm femur defects in 78 rats. We used 30 µg of recombinant human bone morphogenetic protein-2 (rhBMP-2) in a collagen carrier, collagen and untreated defects as controls. Bone healing was evaluated with radiographs, peripheral quantitative computed tomography (pQCT), biomechanics and histology. In comparison with empty defects, the groups receiving bone extracts showed more BF at three weeks and had better bone union (BU), larger mean cross-sectional bone area at the defect site in groups receiving higher doses of extract, showed greater torsional stiffness of the bones and higher maximum breaking load of bones at six weeks. In comparison to all other groups, in the rhBMP-2 group, BF and BU were best at the three-and six-week follow-up, bone area was largest and mechanical test results were best. Although rhBMP-2 is superior for new bone regeneration, native reindeer bone extract is also effective in the six-week follow-up period.

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Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

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Reindeer bone extract can heal the critical-size rat femur defect

Tölli

Kujala

Jämsä

et al. 2010

International Orthopaedics (SICOT)

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“…Thus, studies aiming at safe and effective products from native BMPs are still needed. We have shown previously that reindeer BMP extracts effectively induce ectopic new bone formation in vivo (Pekkarinen et al 2003(Pekkarinen et al , 2004(Pekkarinen et al , 2005a. However, the bone healing properties of reindeer BMP extract have not yet been evaluated.…”

mentioning

confidence: 99%

“…Bone morphogenetic proteins (BMPs) stimulate regeneration of bone and cartilage (Jortikka et al 1993a,b, Cook 1999, Govender et al 2002, Wozney 2002, Cheng et al 2003, Pekkarinen et al 2003. The bone-healing properties of different recombinant and extracted BMPs have been studied using long bone defect models in rabbits (Hollinger et al 1998, Kokubo et al 2003, dogs Johnson 2000, Tuominen et al 2000), rats (Takagi and Urist 1982, Chen et al 2002, Matsuo et al 2003 and sheep (Gao et al , 1997.…”

mentioning

confidence: 99%

Reindeer BMP extract in the healing of critical-size bone defects in the radius of the rabbit

Pekkarinen¹,

Jämsä

Määttä

et al. 2006

Acta Orthopaedica

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Background Native BMP extracts from reindeer effectively induce ectopic new bone formation in vivo, but their bone healing properties have not yet been evaluated. We investigated the effect of reindeer BMP extracts on the healing of long bone defects.Methods The implants tested contained 5 mg or 10 mg of unsterilized BMP extract from reindeer and 10 mg of gamma-sterilized BMP extract administered with collagen carrier (Lyostypt, B. Braun, Germany). 70 µg of rhBMP-2 with collagen carrier (InductOs; Wyeth Europa) served as positive control, and collagen implants (Lyostypt) and untreated defects served as negative controls. New Zealand White rabbits with 1.5 cm of critical-size radius bone defects were used, with 8 weeks of follow-up.Results Radiographic analysis showed bone formation (BF) to be higher in all groups containing BMPs than in the untreated controls. BF was also higher in the rhBMP-2 group, and marginally higher in the group treated with 10 mg of unsterilized reindeer BMP extract (p = 0.06) as compared to the collagen controls. Bone union (BU) was better in the unsterilized BMP extract groups and rhBMP-2 group than in the untreated controls. BU was also better in the implants with 10 mg of unsterilized reindeer BMP extract and rhBMP-2 than in the collagen-treated implants. The mean area of new bone at the site of the defect proved to be higher in all implants containing BMP than in the untreated defects. It was also higher in the groups with 10 mg of unsterilized reindeer BMP extract and rhBMP-2 than in the collagen-treated controls. Mechanical tests showed torsional stiffness of the bones to be higher in the group with 10 mg of unsterilized BMP extract than in the collagen

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A calcified chronic total occlusion preclinical model

Osherov

Qiang

Butany

et al. 2020

Cathet Cardio Intervent

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Objective To create an experimental chronic total occlusion (CTO) model with calcification by dietary modification (cholesterol, calcium carbonate, vitamin D) and local injection of pro‐calcification factors (dipotassium phosphate, calcium chloride, and bone morphogenetic protein‐2 [BMP‐2]). Background Percutaneous revascularization of CTOs frequently fails in heavily calcified occlusions. Development of novel approaches requires a reproducible preclinical model of calcified CTO. Methods CTOs were created in 18 femoral arteries of 9 New Zealand White rabbits using the thrombin injection model. Dietary interventions included a high cholesterol diet (0.5% or 0.25%), calcium carbonate (150 mg × 3–5 days/week), and vitamin D (50,000 U × 3–5 days/week). In selected animals, BMP‐2 (1–4 μg), dipotassium phosphate, and calcium chloride were injected locally at the time of CTO creation. Animals were sacrificed at 2 weeks (n = 4 arteries), 6 weeks (n = 4 arteries), and 10–12 weeks (n = 14 arteries). Results CTOs showed evidence of chronic lipid feeding (foam cells) and chronic inflammation (intimal/medial fibrosis and microvessels, inflammatory cells, internal elastic lamina disruption). In calcium/vitamin D supplemented rabbits, mineralization (calcification and/or ossification) was evident as early as 2 weeks post CTO creation, and in 78% of the overall arteries. Mineralization changes were not present in the absence of calcium/vitamin D dietary supplements. Mineralization occurred in 85% of BMP‐treated arteries and 60% of arteries without BMP. Conclusions Complex mineralization occurs in preclinical CTO models with dietary supplementation of cholesterol with vitamin D and calcium.

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New Bone Formation Induced by Injection of Native Reindeer Bone Morphogenetic Protein Extract

Abstract: Our results suggest that BMP can be administered percutaneously, and that collagen and physiological saline are equally good carriers of injectable implants of native reindeer BMP.

Cited by 9 publications

References 28 publications

Reindeer bone extract can heal the critical-size rat femur defect

Reindeer bone extract can heal the critical-size rat femur defect

Reindeer BMP extract in the healing of critical-size bone defects in the radius of the rabbit

A calcified chronic total occlusion preclinical model

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