ObjectiveTo evaluate the efficacy of the glucosamine hydrochloride combined with risedronate in the treatment of knee osteoarthritis (KOA) associated with cold pain of knee. MethodsThe clinical data of 50 KOA patients including 25 with cold pain and 25 without cold pain, treated in the Department of Rheumatology between January and December 2015 were collected. The clinical symptoms, Western Ontario and McMater Universities (WOMAC) index of osteoarthritis score, knee cold pain score, knee joint therml texture maps (TTM) score, serum osteoprotegerin (OPG), Dickkopf-1 (DKK-1) , and sclerostin levels (SO) were recorded for comparison between patients with and without cold pain in order to investigate the correlation between these indicators and cold pain degree. Patients in the cold pain group were treated with glucosamine hydrochloride combined with risedronate. Follow-up lasted for six months, and the improvement of above indexes and the treatment safety were analyzed. ResultsThere were significant differences between the two groups in the disease course, TTM score of knee front and popliteal fossa, ΔTTM, DKK-1 and SO (P ＜ 0.05) . After 6 months of treatment, patients in the cold pain group improved significantly in WOMAC score, knee cold pain score, TTM score of knee front and popliteal fossa, ΔTTM, OPG, DKK-1 and SO (P ＜ 0.05) . ConclusionsAs one of the main complaints of patients with advanced OA, knee cold pain is associated with the metabolic activity of osteoclasts. It can be alleviated by the treatment with risedronate combined with glucosamine.