Adjuvants Alter the Setting Behavior of a Ceramic Bone Graft Substitute: Implications for the Laboratory and Operating Room

Hydroxyapatite–calcium sulfate (HACaS) bone cements have been clinically established. Combining HACaS with an antiresorptive (zoledronic acid, ZA) and osteoanabolic agent (bone morphogenic protein 2; BMP-2) may enhance the performance of HACaS bone cements in challenging indications, but it must be ensured that this does not impair their setting and mechanical properties. This study established a Vicat/Gillmore-inspired indentation protocol to quantify force-based endpoints and the setting of HACaS with biological adjuvants. HACaS was mixed with or without ZA and/or BMP-2 at 0 min and after a 2 min pre-setting phase with reduced NaCl content (lower liquid-to-powder ratio). For each time point (3–90 min), three cylindrical pellets (Ø 4 mm, height 6 mm) underwent single indentation. Setting was defined as the maximum force at needle penetration, and endpoint hardness was defined as peak force at failure. For 24 h endpoints, specimens were incubated in blood at 37 °C. One-way ANOVA with Tukey’s H post hoc test was performed per time point (n = 3; 24 h endpoints n = 5). All 2 min protocols showed accelerated setting, consistent with the initial lower liquid-to-powder ratio. ZA significantly delayed setting and remained lowest at 90 min and after 24 h in blood. Mixing sequence and vehicle composition critically influenced early mechanical properties and should be considered in the further preclinical evaluation of HACaS with osteoanabolic or antiresorptive agents.