Teriparatide and Abaloparatide Have a Similar Effect on Bone in Mice

Abstract

Three bone anabolic pharmaceuticals are currently approved for treatment of osteoporosis, teriparatide (PTH (1-34)), the parathyroid hormone-related protein analog abaloparatide (ABL), and romosozumab. The present study compared the effect of intermittent PTH (1-34) and ABL on bone tissue directly mole-to-mole in female mice. Forty-seven C57BL/6 mice were randomly allocated to the following groups: Baseline (n = 11), Control (Ctrl) (n = 12), PTH (n = 12), and ABL (n = 12). The mice were injected s.c. with PTH (100 µg/kg), ABL (96 µg/kg), or saline (Ctrl) five days a week for three weeks. To assess the effect of PTH and ABL, the hindlimb bones were analyzed with DXA, µCT, mechanical testing, dynamic bone histomorphometry, and histological quantification of bone cells. In addition, serum calcium concentration was determined. PTH and ABL significantly increased femoral areal bone mineral density (aBMD) (borderline significant p = 0.06 for PTH), femoral mid-diaphyseal bone strength, femoral metaphyseal and epiphyseal and vertebral bone volume fraction (BV/TV), connectivity density, volumetric bone mineral density (vBMD), and bone formation rate (BFR/BS) compared to Ctrl. In addition, ABL also significantly increased mid-diaphyseal cortical thickness and bone area compared to Ctrl. Neither PTH nor ABL significantly increased bone strength at the femoral neck. In conclusion, abaloparatide and PTH have similar bone anabolic properties when compared directly mole-to-mole in mice.

Keywords: PTH; abaloparatide; bone formation; bone strength; μCT.

Figure 1

Micro-computed tomography (μCT) scan of a mouse femur and vertebra L4. (A) The magenta area represents the analyzed volume of interest (VOI) of the distal femoral metaphysis and (B) the yellow area represents the VOI of the distal femoral epiphysis consisting of trabecular bone only. (C) The blue areas represent the VOI consisting of cortical bone only at the femoral mid-diaphysis. (D) The green area represents the VOI containing trabecular bone only at vertebra L4. Dimensions are not to scale.

Figure 2

(A) 3D reconstructions of 105-μm-thick representative frontal slices through the distal femoral metaphyseal and epiphyseal. (B, C) Bone volume fraction (BV/TV) at the distal femoral metaphysis and epiphysis determined by μCT. Data are presented as mean ± SD. *p < 0.05 vs. Ctrl.