Strontium Ranelate Enhances Callus Strength More Than PTH 1-34 in an Osteoporotic Rat Model of Fracture Healing

Abstract

Treatment of an underlying disease is often initiated after the occurrence of an osteoporotic fracture. Our aim was to investigate whether teriparatide (PTH 1-34) and strontium ranelate affect fracture healing in ovariectomized (OVX) rats when provided for the first time after the occurrence of an osteoporotic fracture. We combined the model of an OVX rat with a closed diaphyseal fracture. Sixty Sprague Dawley rats were randomly assigned to four groups. Fracture healing in OVX rats after treatment with pharmacological doses of strontium ranelate and PTH 1-34 was compared with OVX and sham-treated control groups. After 28 days, the femur was excised and scanned by micro computed tomography and the callus evaluated, after which biomechanical torsional testing was performed and torque and toughness until reaching the yield point were analyzed. Only treatment with strontium ranelate led to a significant increase in callus resistance compared to the OVX control rats, whereas both PTH 1-34 and strontium ranelate increased the bone volume/tissue volume ratio of the callus. The PTH 1-34-increased trabecular bone volume within the callus was even higher compared to sham. As for the callus tissue volume, the increase induced by strontium ranelate was significant, contrary to the changes induced by PTH. Callus in strontium ranelate-treated animals is more resistant to torsion compared with OVX control rats. To our knowledge, this is the first report of the enhancement of fracture healing by strontium ranelate. Because both treatments enhance bone and tissue volume within the callus, there may be a qualitative difference between the calluses of PTH 1-34- and strontium ranelate-treated OVX rats. The superior results obtained with strontium ranelate compared to PTH in terms of callus resistance could be the consequence of a better quality of the new bone formed within the callus.

Strontium ranelate improves delayed healing of osteolytic lesions of the jaw in a man with chronic osteomyelitis. Case report

“…SrRan seemed to represent a plausible solution in the setting of bone healing for our patient, since it could be speculated, based mainly on preclinical models (7)(8)(9)(10), that it would decrease further bone resorption locally by affecting the osteoclasts and possibly promote differentiation of prodromal cells of the osteoblastic lineage that would populate the bone lesions to osteoblasts. Indeed, in the setting of fracture healing, which is quite different than that of postmenopausal osteoporosis, data in animals suggest that SrRan may be beneficial as it is associated with improved bone microstructure, callus volume and biomechanical properties (21)(22)(23). Few case-reports in humans have also shown a positive effect of SrRan on fracture-healing either on atypical subtrochanteric fractures or fractures of the wrist or femur (15)(16)(17).…”

Sequential treatment with teriparatide and strontium ranelate in a postmenopausal woman with atypical femoral fractures after long-term bisphosphonate administration

“…17 Recent evidence indicates that under conditions of impaired fracture healing, such as ovariectomy induced bone loss, SR exerts beneficial effects on the healing process, including increasing bone strength at the fracture site. 18 Although there are no animal studies concerning the effect of SR on stress fracture healing, a recent study reported a favourable outcome in two patients with AFF treated with SR. 5 Moreover, SR has some additional advantages such as post-hoc based evidence of hip fracture risk reduction in patients with high risk. 19 Thus, in patients with AFF treated in the past with TRP, having other contraindications to TRP, or even displaying significant future risk for hip fracture, SR treatment seems the most rational option.…”

Pathogenetic treatment with strontium ranelate in women with postmenopausal osteoporosis

“…Уникальное действие Бивалоса на костный метаболизм подтверждено у больных в ходе клинических исследований III фазы на основании измерения уровней костных марке-ров [18]. Оказалось, что использование Бивалоса приводит к значительному повышению уровня маркеров образования кости и уменьшает уровень маркеров костной резорбции начиная с 3-го месяца лечения.…”