Abstract
BackgroundDelay in fracture healing or non-union can be devastating complication. Recent studies have reported that teriparatide (TP) demonstrated effectively on callus formation and mechanical strength and zoledronate (ZA) increased the callus size and resistance at the fracture site in rat fracture model. In this study, the effects of combination therapy with low dose TP and ZA on fracture healing was evaluated.MethodsFrom 1 week post-operation, TP (5 times a week administration) and ZA (0.1 mg/kg single administration) were administered by dividing the rats into the following five groups: TP 1 μg group {T(1): TP 1 μg/kg}, ZA group (ZA:0.1 mg/kg), TP1 μg+ZA group {T(1)+ZA: TP 1 μg/kg+ZA}, TP 10 μg+ZA group {T(10)+ZA: TP 10 μg/kg + ZA}, and control group (C: administered saline). Rt femurs were excised 7 weeks after the surgery; bone fusions were evaluated with soft X-ray images on a 4-point scale. And the histopathological examination was performed in demineralized and non-demineralized specimens. Furthermore, the Radiographic Union Scale was conducted in all specimens.ResultsAbout the bone fusions rates, C, T(1), ZA, T(1)+ZA, and T(10)+ZA groups demonstrated 20.0%, 55.6%, 70.0%, 70.0%, and 80.0%, respectively, and with 4-point scale, each group was 0.50, 1.56, 2.00, 2.60, and 2.80 points, respectively. The callus volume was significantly increased to 16.66 mm2 and 17.75 mm2 in the T(1)+ZA and T(10)+ZA groups, respectively, while 10.65 mm2 (p < 0.05) in the C group. Furthermore, the callus area in the T(10)+ZA group was also observed to have significantly increased to 78.78%, compared with 54.63% and 44.11% in the C and T(1)+ZA groups, respectively (p < 0.01). Histopathologically, cartilage tissue and immature callus formation were observed at the bone junction in the C group; however, the osseous bridge formation of mature callus was observed in the ZA, T(1)+ZA, and T(10)+ZA groups.ConclusionIt is suggested that administration of low dose TP and ZA in combination may lead to the treatment of delayed union of fracture. We hope the combination treatment may become one of new therapeutic strategy.
Highlights
Delay in fracture healing or non-union can be devastating complication
Since 2010, TP has been widely used as a therapeutic drug for osteoporosis in Japan; it is expected to be clinically applied in the future as a therapeutic agent that promotes fracture healing because of its intense osteogenesis-promoting effect
Several studies have investigated the administration of low-dose rhPTH (1–34; 10 μg/kg) in a rat femoral fracture model, in which treatment increased callus bone mineral content (BMC) and bone density, as well as dynamic strength and was found to be effective [4, 5]
Summary
Recent studies have reported that teriparatide (TP) demonstrated effectively on callus formation and mechanical strength and zoledronate (ZA) increased the callus size and resistance at the fracture site in rat fracture model. Improvements in surgical methods for fractures of the femoral shaft have resulted in delayed fracture healing and nonunion in up to 5–10% of patients, subsequent treatment upon the occurrence of nonunion is challenging. In a rat femoral fracture model, Andreassen et al administered a post-fracture subcutaneous injection of parathyroid hormone 1–34 (PTH 1–34) for consecutive days at two doses (60 and 200 μg/kg) and reported greater callus formation and strong callus in the group administered 200 μg/kg PTH [3]. Several studies have investigated the administration of low-dose rhPTH (1–34; 10 μg/kg) in a rat femoral fracture model, in which treatment increased callus bone mineral content (BMC) and bone density, as well as dynamic strength and was found to be effective [4, 5]
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