Little is known about the contextual variability in osteoporosis medication utilization. Our aims were 1) to describe variations in utilization and spending on osteoporotic medication between the Primary Care Health Zones (PHZ) of the Valencia region, Spain, 2) to analyze observed variations using Small Area Variation Analysis methods, and 3) to quantify the influence of the specialized care level on variations in utilization. We conducted a population-based cross-sectional ecological study of expenditure and utilization of five therapeutic groups marketed as osteoporosis treatments in Spain in 2009. The unit of analysis was the PHZ (in total 240) nested in the 23 Hospital Healthcare Departments (HHD) of the region of Valencia, covering a population of about 4.9 million inhabitants. Drug utilization was measured by dispensed Defined Daily Dose per 1000 women aged 50 years old and over and day (DID) per PHZ and cost was measured by the annual osteoporosis drug cost per woman aged 50 and older as well as the average price of DDD (Defined Daily Dose) in each PHZ. We calculated Indirect Standardized Drug Utilization Ratios (ISR) and we used Spearman’s correlation to analyze associations between the ISRs of the different therapies. The average osteoporosis drug consumption was 119.1 DID, ranging from 77.6 to 171.3 DID (2.2 times higher) between PHZs in the 5th and 95th percentiles. Annual expenditure also showed a two-fold variation among PHZs. Average prices of the DDD by therapeutic group showed very low or no variation, although they differed substantially among therapeutic groups. Regarding the standardized consumption of osteoporotic drugs, HHDs explained a substantial part (39%) of the variance among PHZs. In conclusion, there is considerable variability in the volume and choice of anti-osteoporotic treatments between PHZs. with HHDs explaining an important proportion of the variation in utilization. Interventions aimed at reducing variation to improve appropriate care should take into account both the PHZ and HHD levels of care.