Background: The application of a bioresorbable calcium sulfate/hydroxyapatite (CaS/HA) ceramic at the interface of fenestrated screws and osteoporotic bone significantly enhances the immediate mechanical anchorage compared with non-augmented controls. However, the anchoring effectiveness of different screw augmentation techniques in spines with varying vertebral bone mineral density (BMD) remains uncertain. Purpose: The aim of this study was to investigate the immediate anchoring effectiveness of CaS/HA augmentation with two different application techniques for pedicle screw fixation in spines with varying BMD levels. Methods: Two techniques were applied for pedicle screw augmentation: injecting CaS/HA through a cannulated pre-inserted fenestrated screw (injecting technique) or delivering the material through a partly inserted screw to the predrilled bone canal before the screw was fully inserted (pre-filling technique). All thoracic and lumbar vertebrae from fresh-frozen cadaveric spine specimens of a non-osteoporotic elderly male and an osteoporotic elderly female were collected. The injecting and pre-filling techniques were applied to the left and right sides of each individual vertebra, with 1 mL and 2 mL of CaS/HA paste per unilateral thoracic and lumbar screw, respectively. X-rays and CT scans were applied to monitor the procedures and the cement distribution of the augmented screws. Finally, all vertebrae were subjected to uniaxial pull-out testing. Results: The CaS/HA was effectively distributed around the screws in all vertebrae. The maximum pull-out force was comparable between the techniques in both non-osteoporotic and osteoporotic spines, while the pull-out force was significantly higher in the non-osteoporotic spine compared with the osteoporotic spine, regardless of the augmentation technique applied. Conclusion: The application of CaS/HA augmented cannulated or fenestrated pedicle screws, regardless of the augmentation technique employed, resulted in similar initial anchorage strength in both non-osteoporotic and osteoporotic spine. The vertebral BMD will determine the absolute maximum pull-out strength of the augmented screws.