Women with Parkinson’s disease (PD) have increased fracture risk, yet the contribution of central dopaminergic dysfunction to skeletal deterioration remains poorly defined. Pathology and motor symptoms typically begin asymmetrically before progressing bilaterally, but it is unclear whether bone loss follows a similar pattern. This study examined whether unilateral dopaminergic injury produces side-specific skeletal changes and how oestrogen deficiency modifies this response. Adult female mice received a unilateral dopaminergic lesion to the right midbrain. A separate cohort underwent ovariectomy (OVX) prior to lesion to model postmenopausal hormone status. Spontaneous locomotion was assessed three weeks post-lesion, and animals were euthanised at five weeks. Left and right femurs were analysed by ex vivo microcomputed tomography across trabecular regions. Unilateral dopaminergic lesion produced asymmetrical skeletal effects. Motor deficits occurred contralaterally (left), while the ipsilateral (right) limb exhibited altered loading consistent with compensatory gait. Trabecular number was reduced in the right femur (1.02 ± 0.14 vs left, p <  0.05), and fractal dimension was similarly decreased (2.09 ± 0.06, p <  0.01), demonstrating side-specific structural deterioration. In contrast, bone volume fraction (BV/TV) was reduced bilaterally following dopaminergic injury (left: 5.71 ± 0.80; right: 5.07 ± 0.73 vs sham, left p = 0.02; right p = 0.04), indicating a concurrent systemic component. OVX induced widespread, symmetrical deficits, including reduced BV/TV (4.35 ± 1.28 vs sham, p <  0.01), trabecular number (0.88 ± 0.26, p <  0.01), and fractal dimension (2.05 ± 0.09, p <  0.01), and increased trabecular separation (0.39 ± 0.07, p <  0.05) in both femurs. Importantly, OVX abolished lesion-induced asymmetry across all measures and exacerbated deterioration in the left femur compared with sham controls (4.47 ± 1.52, p < 0.001). These findings demonstrate that unilateral dopaminergic dysfunction drives both localised and systemic skeletal changes, with oestrogen deficiency accelerating and generalising bone loss. The data support a role for central nervous system regulation of bone beyond mechanical unloading alone and suggest that early, asymmetrical skeletal deterioration may occur in PD before overt bilateral disease. This has implications for the timing and targeting of interventions to reduce fracture risk in vulnerable populations.