The Utility of Digital X-ray Radiogrammetry in Osteoporosis Assessments and its Association with Distal Radius Fracture and Fracture Severity
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Background and objectives: Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue leading to an increase in bone fragility and susceptibility to fracture. The operational WHO definition of osteoporosis is based on a bone mineral density (BMD) cut-off of T-score ≤ -2.5 SD assessed by central Dual X-ray absorptiometry (DXA). However, a large proportion of individuals with fragility fracture do not fulfill the WHO criteria for osteoporosis, some even have normal BMD levels. This highlights the limitation of the WHO osteoporosis definition. Further, due to costs, lack of DXA equipment and lack of interest from the society and health care system, many people at risk for fragility fracture are not assessed for osteoporosis. Thus there is a need for more feasible methods to identify patients at high risk of fractures, and for methods which also measure bone properties related to bone strength that go beyond BMD. The objective of this thesis was to evaluate the utility of a digital X-ray radiogrammetry (DXR) method which uses plain X-rays of the hand. We examined the ability of DXR to identify women with osteoporosis according to femoral neck DXA; its association with fragility fracture at the distal radius and fracture severity, and its reliability for long-term follow-up of bone density. Further we also wanted to explore the long-term precision for the DXR method. Methods: In a cohort including both women with a current fragility fracture at distal radius and women from the general population, DXR was used to assess porosity, cortical thickness, bone width and BMD. We also measured BMD by DXA at lumbar spine and hip. This thesis consists of four papers; paper I compares DXR-BMD with the gold standard DXA, paper II explores DXR-porosity and its association to fracture, paper III explores the association between DXA and DXR-BMD and severity of fracture, and paper IV investigates the long-term precision for DXR-BMD. Results: Paper I included 311 women. By using a triage approach, setting two thresholds for DXR, we could identify with 90% certainty approximately 70% of the women who had or did not have DXA femoral neck T-score ≤-2.5 SD. About 30% of the women would require a DXA measurement in order to determine if osteoporosis is present or not. Paper II was a case control study including 123 women with low-energy fracture at the distal radius and 170 controls randomly selected from the background population. We found a significant association between porosity measured by DXR and distal radius fracture, further there was a trend for an association between increased porosity and increased number of any fractures in women with normal BMD. Paper III included 110 women with current distal radius fragility fracture. We did not find any association between DXR-BMD or DXA-BMD and the AO classification for fracture severity. There was a small but significant correlation between hand DXR and ulnar variance of the fracture and also between hand DXR and dorsal angle of the fracture, but no other associations between other radiographic parameters of fracture severity and BMD. Paper IV evaluated long-term precision for DXR-BMD. We found that the long-term precision for DXR-BMD was comparable with the known excellent short-time precision for the method. The longterm CV% ranged from 0.22 to 0.43% dependent on the radiographic system. Conclusion: We conclude that the digital DXR method has a satisfactory ability to discriminate between individuals with or without DXA-diagnosed osteoporosis. Thus DXR can be a tool to identify individuals at high risk for osteoporosis and thereby reduce the number of referrals for DXA where there is limited access to DXA. Increased cortical bone porosity measured by DXR is an independent risk factor for distal radius fracture risk in elderly women. Despite the evidence that low BMD is a strong risk factor for fracture, reduced BMD does not seem to influence the severity of the distal radius fracture. We also found that the DXR method has an excellent long-term precision for BMD which is of particular importance when exploring changes in BMD over time.