In the past, considerable controversy on measurement and treatment of osteoporosis have done damage to the acceptance and comparability of the respective studies. It is one of the primary goals of the work to standardize and unify measurements, to enable the intercomparability of the various measuring procedures and to provide a standardized test bed for new procedures.
Research has been carried out to improve comparability of bone mass measurements between machines, measurement sites and centres, to establish normal European data, and to find out which techniques and regions are the most sensitive and specific for the diagnosis of osteoporosis. The main achievements were:
the establishment of a working relationship between basic researchers, clinicians and companies interested in quantitative assessment of bone mass and bone density;
the development of reference materials known as the European spine phantom (ESP) and the European forearm phantom (EFP);
the production and agreement of guidelines for standardization of measurements;
based on 823 ESP and EFP phantom measurement forms, it is now clear after statistical analysis that there are not only important differences in bone density values between instruments of the same type and brand from different manufacturers, and between different techniques, but that significant differences in precision, accuracy and stability have been found which could lead to important clincial misinterpretations;
the development of procedures and equations for interconverting the results of dual X-ray absorptiometry on the equipment of one manufacturer in conjunction with measurements made on the machines of another manufacturer;
the European phantoms and the European guidelines are at present used as a research tool in Japan and in the United States of America (USA);
manufacturers from the USA and Europe of dual energy X-ray absorptiometry equipment (DXA) and quantitative computer tomography (QCT) for the spine and for the forearm have given their collaboration and expressed their willingness to adapt their instrumentation along the lines of the research results which will come out of this project.
The development of new methods and procedures will require a continuous validation with patient data under standardized conditions. Accordingly work shall rest on three pillars.
1. Standardization of existing measurement procedures
-Recommendations for the use of calibration phantoms: In general each manufacturer provides a calibration phantom. These calibration phantoms may differ from installation. Recommendations in the use of these phantoms are to be worked out so that examinations performed by the participating centres can be unified.
-Creation of a material for quality control: To have a common basis for the inter-comparison of the various procedures, such as DPA, DXA, axial QCT and peripheral QCT humaniform phantoms will be devised with reference material (artificial bone of precisely known composition). This reference material has to be made in one single batch. Each participating centre will be provided with a phantom and is obliged to use this phantom in the work done for the concerted action.
-Exchange of samples: Most of the participating centres have access to only one or two of the measuring modalities. To make full use of the standardized procedures it will be advantageous to exchange samples.
Multicenter study - comparison of procedures
On a group of patients multiple examinations are to be performed to explore the sensitivity of various measuring sites and various procedures with standardized procedures. The patients are to be selected carefully using the same definitions for osteoporosis and normals. The definitions for osteoporosis and normals shall be worked out in collaboration with the COMAC-EPID project in osteoporosis and shall be in accordance with the recommendations of the European Foundation of Osteoporosis Research. The proposed standardization will enable to pool together data from all participating centres and hence allow a unique comparison of procedures and measuring sites with a statistically useful group size.
3. Improvements of procedures - towards a quantitation of bone quality
- Cortical bone density: Most existing measurement procedures are focussed on the evaluation of trabecular bone density. There is growing interest in a separate quantitation of cortical bone. Cortical bone and trabecular bone may be diminished in a different way dependent on the underlying disease. Cortical bone may also play an important role in the prediction of femur neck fractures.
-Structural analysis: In a collaborative effort axial QCT, peripheral QCT, ultrasound and histomorphometry will work out parameters describing bone structure. Bone structure may provide an important additional bone parameter for the prediction of fracture risk. By supplementing bone mass with bone structure it is hoped that the overlap between normals and osteoporotics can be reduced. This reduction in overlap may then also be the simplest criterion in the validation of this new parameter.
-Bone strength/fracture risk prediction: Mathematical modelling based on biomechanical considerations and using anatomical and structural information gathered with QCT will be used to improve fracture risk prediction. Bone strength in osteoporosis is also a topic of the COMAC-BME project II.2.5/6 'Monitoring of bone condition by vibration testing'. Therefore a collaboration between the centres doing vibrational testing will be established.