Osteoporosis is a major health problem in terms of fracture probability and disability. The aim of this ecological study is to identify the temporal trends in osteoporosis mortality in Spain from 1999 to 2015. Data on the Spanish population and number of deaths due to osteoporosis were obtained from the Spanish National Institute for Statistics. Age-adjusted mortality rates were estimated. Join point regression was used to identify the years when changes in mortality s and annual percentage change in mortality rates took place. Women presented a greater mortality rate decrease (p < 0.001), though this mortality difference by sex was reduced by half at the end of the period. The higher the age, the faster the mortality rate declined in women, while no clear pattern could be identified in men. In women, significant changes in trends were identified in three age groups (50–54, 60–64 and 80–84 years old). A sustained decrease in osteoporosis-associated mortality was found in women aged 75–79 and ≥85 years and men aged 60–64. In conclusion, mortality caused by osteoporosis in Spain is decreasing faster in the older age ranges especially in women.