Summary Patients with pyogenic vertebral osteomyelitis (PVO) are at greater risk of bone loss. However, treatment guidelines for bone loss have been lacking. Early bisphosphonate treatment within 6 weeks after PVO diagnosis was significantly associated with superior outcome in femoral BMD at 2-year follow-up, compared to that with late treatment. Introduction Due to absence of concern and proper guidelines, management of bone loss or osteoporosis in PVO is often neglected or delayed. A retrospective cohort study was planned to investigate differences in bone mineral density (BMD) in PVO patients with osteoporosis according to the timing of osteoporosis treatment. Methods The PVO cohort consisted of 192 patients with osteoporosis who visited our institution between January 2003 and March 2015 and received bisphosphonate treatment for osteoporosis. According to the interval between PVO diagnosis and initiation of bisphosphonate, the patients were divided into three groups: group A (within 6 weeks after PVO diagnosis), group B (between 6 weeks and 3 months after diagnosis), and group C (more than 3 months after PVO diagnosis). Results The percent increase in total femoral BMD in group A was significantly larger than that in group B at 2-year follow-up ( p  = 0.036). Similarly, the percent increase in trochanteric ( p  = 0.008) and total femoral ( p  = 0009) BMD in group A was significantly larger than that in group C at 2-year follow-up. Even after multivariate adjustment, total femoral BMD changes were significantly associated with the treatment group. Group B (odds ratio = 2.824, p  = 0.013) and group C (odds ratio = 3.591, p  = 0.001) were more significantly associated with total femoral BMD decreases at 2-year follow-up compared with group A. Conclusions Early bisphosphonate treatment within 6 weeks after PVO diagnosis (group A) was significantly associated with superior outcome in femoral BMD at 2-year follow-up, compared to that with late treatment (groups B and C).