Current treatment protocols in acute lymphoblastic leukemia (ALL) are associated with high remission rates and long life expectancy, enhancing the importance of quality of life and prevention of treatment-related complications in patient care. As osteoporosis is a frequent complication in patients under chemotherapy, we investigated the effect of vitamin K2 (100 mcg menaquinone-7) and vitamin D3 (10 mcg calcitriol) on bone metabolism in children with ALL. Twenty-nine consecutive patients recently diagnosed with B precursor ALL (B-ALL) and treated according to the Turkish Acute Lymphoblastic Leukemia Berlin Frankfurt Münster 2000 protocol were randomly assigned into study and control groups. The study group (n=15, M/F: 8/7, age 1-14.5years, mean 6.5years) received vitamin K2 and vitamin D3 with their chemotherapy, while the control group (n=14, M/F 9/5, age 2-17years, mean 7.1years) received chemotherapy only. Serum calcium, phosphorus, magnesium, alkaline phosphatase, bone-specific alkaline phosphatase, uncarboxylated osteocalcin (ucOC), tartrate resistant acid phosphatase 5b, carboxyl terminal procollagen propeptide (PICP), osteoprotegerin (OPG), and receptor activator nuclear kappa B ligand (RANKL) were measured and bone mineral density (BMD) was determined at baseline and first, second, third and sixth months. The study group had higher serum OPG/RANKL ratio and lower ucOC levels compared to the control group at the first month; PICP levels were higher in the study group at second and third months. These results suggest an early beneficial effect of the combination of vitamin K2 and vitamin D3 on BMD in ALL patients especially during the period of intensive steroid therapy in the first months.