Low-energy trauma and fragility fractures represent a major public health problem. The societal cost of the fragility fractures that occurred in Sweden 2010 has been estimated at €4 billion. In rheumatoid arthritis (RA), patient outcomes have improved greatly in recent years. However, the therapeutic decision making is still hampered by a lack of effective validated biomarkers. The cost of RA in Sweden 2010 has been estimated at €600 million, of which biologic drugs was €180 million. Digital X-ray radiogrammetry (DXR) is a method to measure bone mineral density (BMD) in the metacarpals of the hand. It can be applied opportunistically in several workflows where a person is already at an X-ray machine, including fracture repositioning follow up, mammography screening and hand imaging in RA. This thesis explored DXR-BMD as a marker to identify individuals who would benefit from anti-osteoporotic treatment, change rate of DXR-BMD as a biomarker in RA and under what conditions historical X-ray images can be used to estimate DXR-BMD. An automated method for measurement of joint space width in metacarpophalangeal and interphalangeal joints was also developed and evaluated as a biomarker in RA. Low DXR-BMD was predictive for hip fractures and predicted fragility fractures to a comparable degree as other BMD measurement sites. Rapid decrease of DXR-BMD was a strong and independent predictor for progression of radiographic damage in RA when manual radiographic progression scores were not available. Change of metacarpal joint space width was a statistically significant but weak predictor of joint space narrowing score progression. Guidelines and considerations for use of historical X-ray radiographs for DXR-BMD measurements in clinical trials have been developed and published.