Quantitative assessment of trabecular bone microarchitecture in extremity cone-beam CT (CBCT) would benefit from the high spatial resolution, low electronic noise, and fast scan time provided by complementary metal-oxide semiconductor (CMOS) x-ray detectors. We investigate the performance of CMOS sensors in extremity CBCT, in particular with respect to potential advantages of thin (<0.7mm) scintillators offering higher spatial resolution. A cascaded systems model of a CMOS x-ray detector incorporating the effects of CsI:Tl scintillator thickness was developed. Simulation studies were performed using nominal extremity CBCT acquisition protocols (90kVp, 0.126mAs/projection). A range of scintillator thickness (0.35-0.75mm), pixel size (0.05-0.4mm), focal spot size (0.05-0.7mm), magnification (1.1-2.1), and dose (15-40mGy) was considered. The detectability index was evaluated for both CMOS and a-Si:H flat-panel detector (FPD) configurations for a range of imaging tasks emphasizing spatial frequencies associated with feature size aobj. Experimental validation was performed on a CBCT test bench in the geometry of a compact orthopedic CBCT system (SAD=43.1cm, SDD=56.0cm, matching that of the Carestream OnSight 3D system). The test-bench studies involved a 0.3mm focal spot x-ray source and two CMOS detectors (Dalsa Xineos-3030HR, 0.099mm pixel pitch) - one with the standard CsI:Tl thickness of 0.7mm (C700) and one with a custom 0.4mm thick scintillator (C400). Measurements of modulation transfer function (MTF), detective quantum efficiency (DQE), and CBCT scans of a cadaveric knee (15mGy) were obtained for each detector. Optimal detectability for high-frequency tasks (feature size of ~0.06mm, consistent with the size of trabeculae) was ~4× for the C700 CMOS detector compared to the a-Si:H FPD at nominal system geometry of extremity CBCT. This is due to ~5× lower electronic noise of a CMOS sensor, which enables input quantum-limited imaging at smaller pixel size. Optimal pixel size for high-frequency tasks was <0.1mm for a CMOS, compared to ~0.14mm for an a-Si:H FPD. For this fine pixel pitch, detectability of fine features could be improved by using a thinner scintillator to reduce light spread blur. A 22% increase in detectability of 0.06mm features was found for the C400 configuration compared to C700. An improvement in the frequency at 50% modulation (f50 ) of MTF was measured, increasing from 1.8lp/mm for C700 to 2.5lp/mm for C400. The C400 configuration also achieved equivalent or better DQE as C700 for frequencies above ~2mm-1 . Images of cadaver specimens confirmed improved visualization of trabeculae with the C400 sensor. The small pixel size of CMOS detectors yields improved performance in high-resolution extremity CBCT compared to a-Si:H FPDs, particularly when coupled with a custom 0.4mm thick scintillator. The results indicate that adoption of a CMOS detector in extremity CBCT can benefit applications in quantitative imaging of trabecular microstructure in humans.