OBJECTIVES: Osteoporosis is a condition consisting in reduced bone mass and density, thus resulting in an increased risk of fragility fractures. Considering the aforementioned, and in conjunction with the complications that osteoporosis engenders, a considerable economic burden is imposed on industrialized countries. The purpose of this study was to determine the thresholds at which treatment initiation becomes cost-effective in Greece, using the fracture risk assessment algorithm (FRAX^®) developed by WHO and recently adjusted for Greece.  METHODS: A previously developed state transition Markov model was populated employing epidemiological and economic data from Greece. The analysis calculated the cost-effective intervention thresholds using the Greek FRAX^® model, which estimates the 10-year probability of a major osteoporotic fracture in subjects with a fracture risk equivalent to that of a woman with a prior fragility fracture and no other risk fracture. The analysis was undertaken from a third-party payer perspective, assuming a willingness to pay of 30,000€ per QALY gained.  RESULTS: In Greece, the drug intervention aiming at reducing the fracture risk, was found to be cost-effective with a 10-year probability for a major osteoporotic fracture at/or above 12.3% (range:7.8%-20.4%) for women and 18.2% (range:9.6%-34.2%) for men aged from 50 to 59 years old.  When considering women and men aged between 60 and 74 years, the threshold was estimated ≥8.9% (range:8.5%-9.2%) and ≥9.4% respectively (range:8.9%-10.0%), whereas for women and men over 75 years old, the cost-effective thresholds were calculated to be ≥15.0% (range:13.0% to 16.0%) and ≥11.0% (range:10.6%-11.2%) accordingly. Significant age-variations were generally not noticed, some exceptions apart, especially for the age-range of 50-55.  CONCLUSIONS: As expected, the cost-effective thresholds obtained via FRAX^® were age-dependent in both sexes. Therefore, considering these thresholds should lead to cost-effective access to therapy of patients with high fracture probability, and ipso facto significantly reduce the economic burden of osteoporotic fractures in Greece.