Sixty-four post-menopausal women with osteoporosis scheduled for a unilateral total knee arthroplasty (TKA) were randomized to receive anti-osteoporosis treatment (alendronate; calcitriol; calcium carbonate) guided by bone turnover marker monitoring (n=32) or a standard 3 month anti-osteoporosis treatment (n=32). Outcomes of interest included duration of treatment, incidence of adverse reactions to treatment, maximum total point motion (MTPM), bone mineral density (BMD), pain on a Visual Analogue Scale (VAS), range of motion, and the Oxford Knee Score (OKS). Radiostereometric analysis for MTPM was performed at 6 and 12 months post-operation as well BMD analysis was performed at 1-3 days and 12 months post-operation. In addition, knee pain and functional scores were measured at 3, 6 and 12 months post-operation. Results revealed statistically significantly longer duration of alendronate, calcitriol and calcium treatment in the monitoring group compared to the control group (p<0.001 for all). No statistically significant difference was observed for the incidence of adverse reactions between the two groups (p=0.392).Moreover, MTPM was statistically significantly lower in the monitoring group compared to control at both 6 and 12 months post-operation (p=0.011; p=0.003, respectively). Moreover, the change in BMD from baseline at 12 months was statistically significantly greater in the monitoring group (p=0.002). VAS pain scores at 6 months were statistically significantly lower in the monitoring group (p=0.042), whilst OKS scores at 6 and 12 months were statistically significantly in favour of the control group (p=0.014; p=0.017, respectively). Finally, no statistical significant differences for range of motion were observed between the two groups at any time-point.