Combined antisclerostin antibody and parathyroid hormone (1–34) synergistically enhance the healing of bone defects in ovariectomized rats

Kombinierter Antisklerostin-Antikörper und Parathormon (1–34) verbessern synergistisch die Heilung von Knochendefekten bei ovariektomierten Ratten

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Osteoporotic bones heal more slowly and ineffectively than normal bones. A combination of antibodies against sclerosing protein (Scl-Ab), and parathyroid hormone 1–34 (PTH 1–34) may improve healing. A standard osteoporotic rat model was established 12 weeks after bilateral ovarian resection (OVX). Bone defects were created in the right femora of 80 rats, which were randomly divided into 4 groups: control, Scl-Ab (25 mg/kg twice weekly), PTH (60 μg/kg of PTH 1–34 three times a week) and PTH plus Scl-Ab. After 12 weeks of treatment the rats were sacrificed and blood and the distal femora were harvested for biochemical evaluation, histology, microcomputed tomography and biomechanical testing. Compared to the control group, monotherapy and combination therapy with PTH and/or Scl-Ab promoted the formation of new bone, enhanced maximum femoral loading and increased the levels of procollagen type I N‑terminal propeptide (PINP) and osteocalcin. The administration of PTH + Scl-Ab maximally enhanced bone defect healing. Combination treatment was better than either treatment alone, indicating a synergistic effect.


Osteoporotische Knochen heilen langsamer und unwirksamer als normale Knochen. Eine Kombination von Antikörpern gegen Sklerosierungsprotein (Scl-Ab) und Parathormon 1‑34 (PTH 1‑34) kann die Heilung verbessern. Ein standardisiertes osteoporotisches Rattenmodell wurde 12 Wochen nach der bilateralen Ovarialresektion (OVX) etabliert. Knochendefekte wurden in den rechten Oberschenkelknochen von 80 Ratten erzeugt, die nach dem Zufallsprinzip in 4 Gruppen eingeteilt wurden: Kontrolle, Scl-Ab (25mg/kg zweimal pro Woche), PTH (60μg/kg PTH 1–34 dreimal pro Woche) und PTH plus Scl-Ab. Nach 12 Wochen Behandlung wurden die Ratten geopfert und Blut sowie die distalen Femora für biochemische Untersuchungen, Histologie, Mikrocomputertomographie und biomechanische Untersuchungen entnommen. Im Vergleich zur Kontrollgruppe förderten die Mono- und Kombinationstherapie mit PTH und/oder Scl-Ab die Bildung von neuem Knochen, eine erhöhte maximale Oberschenkellast und die Erhöhung der Konzentration von Gesamt-Prokollagen Typ I N‑Propeptid (PINP) und Osteocalcin. Die Verabreichung von PTH + Scl-Ab brachte eine maximale Verbesserung der Heilung von Knochendefekten. Die Kombinationsbehandlung war besser als jede der beiden Behandlungen allein, was auf einen synergistischen Effekt hinweist.

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This study was supported by the Zhejiang Provincial Medicine and Health Technology Project (grant no. 2017KY472 to Kailiang Zhou); Wenzhou Science and Technology Bureau Foundation (no. Y2017044 to Xiaolong Shui).

Author information

Correspondence to Kailiang Zhou M.D. or Xiaolong Shui M.D..

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Conflict of interest

J. Lin, J. Wu, S. Sun, K. Chen, H. Wu, R. Lin, C. Zhou, J. Kong, K. Zhou and X. Shui declare that they have no competing interests.

Ethical standards

This institution has agreed to publication of the manuscript. All authors gave their consent to publication of the animal experimental data; the ethics committee has given the required permission. All procedures performed were in accordance with the ethical standards of the institutional and/or national research committee and with the 1975 Helsinki declaration and its later amendments or comparable ethical standards. All animal experiments met all international standards on animal welfare and those of the Animal Research Committee of the Wenzhou Medical University.

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The authors Jinti Lin, Jun Wu and Shuaibo Sun contributed equally to the manuscript.

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Lin, J., Wu, J., Sun, S. et al. Combined antisclerostin antibody and parathyroid hormone (1–34) synergistically enhance the healing of bone defects in ovariectomized rats. Z Gerontol Geriat (2020).

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  • Antisclerostin antibody
  • Parathyroid hormone
  • Bone defect
  • Osteoporosis
  • Experimental animal model


  • Antisklerostin-Antikörper
  • Parathormon
  • Knochendefekt
  • Osteoporose
  • Experimentelles Tiermodell