Abstract
This study investigated bone regeneration in the femoral neck canal of osteoporotic rats using a novel animal model. A calcium sulphate (CS)/hydroxyapatite (HA) carrier was used to deliver a bisphosphonate, zoledronic acid (ZA), locally, with or without added recombinant human bone morphogenic protein-2 (rhBMP-2). Twenty-eight-week-old ovariectomized Sprague–Dawley rats were used. A 1 mm diameter and 8 mm long defect was created in the femoral neck by drilling from the lateral cortex in the axis of the femoral neck, leaving the surrounding cortex intact. Three treatment groups and one control group were used: (1) CS/HA alone, (2) CS/HA + ZA (10 μg) (3) CS/HA + ZA (10 μg) + rhBMP-2 (4 μg), and (4) empty defect (control). The bone formation was assessed at 4 weeks post surgery using in vivo micro computed tomography (micro-CT). At 8 weeks post surgery, the animals were sacrificed, and both defect and contralateral femurs were subjected to micro-CT, mechanical testing, and histology. Micro-CT results showed that the combination of CS/HA with ZA or ZA + rhBMP-2 increased the bone formation in the defect when compared to the other groups and to the contralateral hips. Evidence of new dense bone formation in CS/HA + ZA and CS/HA + ZA + rhBMP-2 groups was seen histologically. Mechanical testing results showed no differences in the load to fracture between the treatments in either of the treated or contralateral legs. The CS/HA biomaterial can be used as a carrier for ZA and rhBMP-2 to regenerate bone in the femoral neck canal of osteoporotic rats.
Highlights
Osteoporosis and fragility fractures are increasing with the increase in age and are only partly halted by primary and secondary national prevention programs.[1]
One sample from the calcium sulphate (CS)/HA + Zoledronic acid (ZA) group was excluded from the 4-week micro-CT analysis due to movement artifacts during the in vivo scans
N = 9/group were used for mechanical testing, but one sample in each of the empty, calcium sulphate/hydroxyapatite (CS/HA), and CS/HA + ZA + recombinant human bone morphogenic protein-2 (rhBMP-2) groups had to be excluded due to fractures occurring in the femoral neck canal during the adjustment of the compression device
Summary
Osteoporosis and fragility fractures are increasing with the increase in age and are only partly halted by primary and secondary national prevention programs.[1] More than 8.9 million osteoporotic fractures occur annually worldwide, with approximately one-third in Europe.[2] The direct cost of managing osteoporosis was estimated at e37 billion, but if quality-adjusted life-years lost were considered, the overall cost amounted to e98 billion in Europe in 2010.2 Due to the aging population, fragility fractures are predicted to increase further in the decade.[2] The life expectancy in hip fracture patients decreases by nearly 25%. The interest in osteoporosis therapy is declining, in particular for secondary
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