Minodronate treatment improves low bone mass and reduces progressive thoracic scoliosis in a mouse model of adolescent idiopathic scoliosis

: Recent studies have shown an association between osteopenia and adolescent idiopathic scoliosis (AIS) and implied that osteopenia plays a causative role in AIS development. This study aimed to determine if minodronate (MIN) treatment could prevent curve progression by increasing bone mass in a thoracic restraint (TR) mouse model, which develops causes the development of thoracic scoliosis similar to human AIS. A total of 100 young female C57BL6J mice were divided into four groups: (1) control with vehicle (CON/VEH; n = 20), (2) control with MIN (CON/MIN; n = 20), (3) TR with vehicle (TR/VEH; n = 30), or (4) TR with MIN (TR/MIN; n = 30). MIN (0.01 mg/kg/week) and vehicle were administered intraperitoneally to their respective groups. TR was performed at age 4 weeks, and the mice were sacrificed at age 9 weeks. Body weights, spine radiographs, femoral bone mineral density (BMD), serum bone marker levels, and histomorphometry of the cancellous bone of the thoracic vertebrae were analyzed. TR significantly reduced weight gain in the TR/VEH group relative to the CON/VEH group. TR also induced osteoporosis with accelerated bone resorption, as indicated by decreases in femoral BMDs and thoracic cancellous bone volume and increases in serum bone resorption marker levels and histomorphometric resorption parameters in the TR/VEH group. MIN partially improved body weight gain and improved poor bone structure relative to the TR/VEH group by suppressing high bone resorption in the TR/MIN mice. MIN significantly reduced the curve magnitudes, as indicated by a 43% lower curve magnitude in the TR/MIN mice than in the TR/VEH mice (17.9 ± 8.9° vs. 31.5 ± 13.1°; p< 0.001). The administration of MIN increased bone mass and reduced the severity of scoliosis in the TR mice. MIN was suggested as a possible inhibitor of scoliosis development.