Efficacy of a Sclerostin Antibody Compared to a Low Dose of PTH on Metaphyseal Bone Healing

Agholme, FredrikLinköpings universitet,Avdelningen för inflammationsmedicin,Hälsouniversitetet (författare)

We compared the effect of a sclerostin antibody to that of a clinically relevant dose of parathyroid hormone (PTH) in a rat model for metaphyseal bone healing. Screws of steel or poly methyl methacrylate (PMMA) were inserted bilaterally into the proximal tibia of young male rats. During 4 weeks the animals then received injections of either phosphate buffered saline (control), sclerostin antibody (25mg/kg, twice weekly) or PTH (5 mu g/kg, daily). The healing response around the screws was then assessed by mechanical testing and X-ray microtomography (mu CT). To distinguish between effects on healing and general effects on the skeleton, other untraumatized bone sites and serum biomarkers were also assessed. After 4 weeks of treatment, PTH yielded a 48% increase in screw pull-out force compared to control (p=0.03), while the antibody had no significant effect. In contrast, the antibody increased femoral cortical and vertebral strength where PTH had no significant effect. mu CT showed only slight changes that were statistically significant for the antibody mainly at cortical sites. The results suggest that a relatively low dose of PTH stimulates metaphyseal repair (screw fixation) specifically, whereas the sclerostin antibody has wide-spread effects, mainly on cortical bone, with less influence on metaphyseal healing.

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Ortopedi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Orthopaedics hsv//eng
implant fixation; bone healing; mechanical testing; bone formation; Wnt-signaling
MEDICINE
MEDICIN

Macias, BrandonLinköpings universitet,Avdelningen för inflammationsmedicin,Hälsouniversitetet (författare)
Hamang, MattLilly Research Labs, IN USA (författare)
Lucchesi, JonathanLilly Research Labs, IN USA (författare)
Adrian, Mary D.Lilly Research Labs, IN USA (författare)
Kuhstoss, StuartLilly Research Labs, IN USA (författare)
Harvey, AnitaLilly Research Labs, IN USA (författare)
Sato, MasahikoLilly Research Labs, IN USA (författare)
Aspenberg, PerÖstergötlands Läns Landsting,Linköpings universitet,Avdelningen för inflammationsmedicin,Hälsouniversitetet,Ortopedkliniken i Linköping(Swepub:liu)peras36 (författare)
Linköpings universitetAvdelningen för inflammationsmedicin (creator_code:org_t)

Ingår i:Journal of Orthopaedic Research: Wiley-Blackwell32:3, s. 471-4760736-02661554-527X

Av författaren/redakt...: Agholme, Fredrik; Macias, Brandon; Hamang, Matt; Lucchesi, Jonath ...; Adrian, Mary D.; Kuhstoss, Stuart; visa fler...; Harvey, Anita; Sato, Masahiko; Aspenberg, Per; visa färre...

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Ortopedi

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