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Abaloparatide versus teriparatide: a head to head comparison of effects on fracture healing in mouse models
Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
2018 (English)In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 89, no 6, p. 674-677Article in journal (Refereed) Published
Abstract [en]

Background and purpose - Teriparatide accelerates fracture healing in animals and probably in man. Abaloparatide is a new drug with similar although not identical effects on the teriparatide receptor. Given at 4 times the teriparatide dose in a human osteoporosis trial, abaloparatide increased bone density more than teriparatide, and both reduced fracture risk. We investigated in mice whether abaloparatide stimulates fracture healing, and if it does so with the suggested dose effect relation (4:1). Patients and methods - In a validated mouse model for metaphyseal healing (burr hole with screw pull-out), 96 mice were randomly allocated to 11 groups: control (saline), teriparatide or abaloparatide, where teriparatide and abaloparatide were given at 5 different doses each. In a femoral shaft osteotomy model, 24 mice were randomly allocated to 3 groups: control (saline), teriparatide (15 mu g/kg) or abaloparatide (60 mu g/kg). Each treatment was given daily via subcutaneous injections. Results were evaluated by mechanical testing and microCT. Results - In the metaphyseal model, a dose-dependent increase in screw pull-out force could be seen. In a linear regression analysis (r = 0.78) each increase in ln(dose) by 1 (regardless of drug type) was associated with an increase in pull-out force by 1.50 N (SE 0.18) (p amp;lt; 0.001). Changing drug from teriparatide to abaloparatide increased the force by 1.41 N (SE 0.60; p = 0.02). In the diaphyseal model, the callus density was 23% (SD 10), 38% (SD 10), and 47% (SD 2) for control, for teriparatide and abaloparatide respectively. Both drugs were significantly different from controls (p = 0.001 and p = 0.008), but not from each other. Interpretation - Both drugs improve fracture healing, but in these mouse models, the potency per mu g of abaloparatide seems only 2.5 times that of teriparatide, rather than the 4:1 relation chosen in the clinical abaloparatide-teriparatide comparison trial.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD , 2018. Vol. 89, no 6, p. 674-677
National Category
Orthopaedics
Identifiers
URN: urn:nbn:se:liu:diva-153697DOI: 10.1080/17453674.2018.1523771ISI: 000453932600015PubMedID: 30334479OAI: oai:DiVA.org:liu-153697DiVA, id: diva2:1276205
Available from: 2019-01-07 Created: 2019-01-07 Last updated: 2019-05-02

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Bernhardsson, Magnus

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Division of Surgery, Orthopedics and OncologyFaculty of Medicine and Health SciencesDepartment of Orthopaedics in Linköping
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