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

Abstract

Osteoporotic bones heal more slowly and ineffectively than normal bones. Acombination of antibodies against sclerosing protein (Scl-Ab), and parathyroid hormone 1-34 (PTH 1-34) may improve healing. Astandard osteoporotic rat model was established 12weeks after bilateral ovarian resection (OVX). Bone defects were created in the right femora of 80rats, 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 aweek) and PTH plus Scl-Ab. After 12weeks 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 typeI 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 asynergistic effect.