Peripheral quantitative computed tomography (pQCT) is a non-invasive, low radiation tool for measuring volumetric bone mineral density. It has potential for use in fracture healing applications, however the unknown attenuation effects of cast material on peripheral quantitative computed tomography have contributed to its limited use in this area. The effect of two common cast materials, polyester and Plaster of Paris was investigated by performing both in vitro and in vivo studies. The in vitro study tested the effect of increasing layers of cast material on bone density measurements performed on a hydroxyapatite phantom. Cast thickness was directly associated with a reduction in bone mineral density, with twelve layers of polyester and Plaster of Paris resulting in a 0.55% and 2.21% decrease in bone density measurements. Precision error in situ with polyester cast material was 0.71%, and 2.31% with Plaster of Paris cast material. The in vivo study comprised a prospective trial with 28 healthy adult participants to evaluate the effect of the two cast materials. Trabecular bone mineral density was increased by 0.5% in the presence of a polyester cast, and decreased 4.22% in the presence of a Plaster of Paris cast. Cortical bone mineral density was decreased 3.46% and 5.54% for polyester and Plaster of Paris respectively. This study quantified the effects of orthopaedic casts on pQCT derived bone parameters. The results suggest applicability of commonly utilised cast materials in combination with pQCT to assess fracture healing.