Abstract: Objective To explore the effect of zoledronic acid combined with hyaluronic acid in the treatment of postmenopausal osteoporotic(PMOP)patients complicated with osteoarthritis(OA). Methods One hundred and five patients of PMOP complicated with OA volunteering in May 2009 to April 2014 in our hospital were enrolled into this study and were randomly divided into two groups:the zoledronic acid group and the control group.They all received hyaluronic acid intra-articular injection for a cycle.The control group was given salmon calcitonin,calcium,alendronate and calcitriol and other traditional anti-osteoporosis therapy on the basis of those.The zoledronic acid group received intravenous 5mg zoledronic acid injections with 0.9% saline or 5% glucose solution once a year on the basis of the control group.The Western Ontario and McMaster American Universities Osteoarthritis Index score(WOMAC score),Lysholm knee score,VAS pain score,BMD and serum levels of β-CTX,BGP,B-ALP were recorded before and after the treatment. Results The WOMAC score,Lysholm knee score,VAS pain score and BMD of zoledronic acid group were superior than the control group(P<0.05).The WOMAC score,Lysholm knee score,VAS pain score and BMD of two groups were superior to those before the treatment(P<0.05).The serum levels of β-CTX,BGP,B-ALP after 12 months of treatment were lower than those before the treatment in zoledronic acid group(P<0.05) but had no significance in the control group(P>0.05).The serum levels of β-CTX,BGP,B-ALP in zoledronic acid group were lower than those in the control group after 12 months of treatment(P<0.05). Conclusion Zoledronic acid combined with hyaluronic acid in PMOP patients complicated with OA can significantly improve the bone metabolism,inhibit bone desorption,increase BMD and knee function,reduce knee pain and improve the quality of life of patients which deserved a clinical promotion.