The literature is replete with reports of osteoporosis in rheumatoid arthritis, but the mechanism of bone loss remains obscure. This is probably due to the overlap with bone loss of aging and the menopause, whose exact mechanisms are also poorly understood. Against this background, a study was designed to evaluate generalised bone loss in young, premenopausal (if female), patients with rheumatoid arthritis. The protocol was designed to record demographic data, as well as information pertaining to the disease. Cortical bone mass was measured at the metacarpals and left femur, using an automated, computer-controlled technique. Trabecular bone was evaluated at the left femur (Singh index) as well as at the 3rd lumbar vertebra (Saville index). Bone kinetics were studied by the measurement of urinary excretion of calcium, phosphate and hydroxy-praline (resorption) and serum alkaline phosphatase (formation). Disease activity was measured clinically and with laboratory indices. Physical activity was indirectly measured by quantitating the disability, using the Keitel function test as well as a modified health assessment questionnaire (HAQ). The radiograph of the right wrist was scored by the Larsen index. The carpometacarpal ratio was also calculated from the radiograph. Numerous statistical techniques were applied in the analysis of the data. Healthy volunteers were used as controls. Patients with SLE were also studied, in order to compare the 2 inflammatory diseases. Patients with RA had generalised cortical bone loss (metacarpal and femur) (p < 0.001). Trabecular bone measurements were not significantly different from normals, using the crude radiographic techniques. Duration of disease was the most important clinical determinant of this bone loss. The relative contributions of disease activity and lack of physical activity to the loss of bone could not be adequately separated using conventional statistical techniques. Corticosteroid therapy did not promote metacarpal bone loss in these subjects, but may have contributed to thinning of the femoral cortex. Nonsteroidal anti-inflammatory drugs and disease modifying agents did not seem to influence the extent of the bone loss. Nutritional status and skinfold thickness did not correlate with bone mass. Dietary factors played no role in the genesis of bone loss, but may have had some effect on disease activity. Metacarpal measurements showed a sensitivity of 80% and specificity of 85% in discriminating between osteopaenic and normopaenic groups with RA. Osteopaenia could not be adequately predicted in the absence of metacarpal measurements. Metacarpal bone loss in RA was due to endosteal resorption, while in SLE it was due to periosteal resorption. The semi-automatic technique for measurement of metacarpal bone mass showed good reproducibility among 5 observers and at 2 different centres. The pathogenesis of bone loss in RA was multifactorial, the largest contribution probably coming from a humoral factor in the circulation, closely related to disease activity. Ionised calcium was elevated in 55% of RA patients, but only 5% of SLE patients. Serum PTH levels were normal in 99% of the RA subjects. Elevations in alkaline phosphatase. (25%) probably reflected disease activity rather than increased bone formation. Factor analysis of 27 variables showed that disease activity was central to the development of OP in RA. CS therapy tended to be used in the presence of active disease. Disability was not an important determinant of bone loss in RA, but may be a useful measure of activity of the disease. This study did not evaluate the relationships with sex hormonal status or vitamin D metabolism. Future research should aim at cohort analysis at 2 different periods, in order to improve our understanding of the pathogenesis of bone loss in RA.

by Chan Kwai Foon May. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (leaves 103-114). / Abstracts in English and Chinese. / Declaration --- p.2 / Abstract --- p.3 / Abstract in Chinese --- p.6 / Acknowledgements --- p.8 / Chapter Chapter 1. --- Introduction --- p.15 / Chapter Chapter 2. --- Osteoporosis : The relationship between aging and skeletal organization between men and women --- p.17 / Chapter 2.1. --- Skeletal organization --- p.17 / Chapter 2.1.1. --- Bone structure --- p.17 / Chapter 2.1.2. --- Bone metabolism --- p.17 / Chapter 2.1.3. --- Peak bone mass --- p.18 / Chapter 2.2. --- Bone loss between men and women --- p.20 / Chapter 2.2.1. --- Aging and bone loss --- p.20 / Chapter 2.2.2. --- Clinical aspects of bone loss in men and women --- p.21 / Chapter Chapter 3. --- Vertebral deformity : Bone Mineral Density and Body Composition --- p.23 / Chapter 3.1. --- Bone mineral density --- p.23 / Chapter 3.1.1. --- Types of vertebral deformity --- p.23 / Chapter 3.1.2. --- Clinical diagnosis in vertebral deformity --- p.24 / Chapter 3.1.3. --- Bone mineral density measurements --- p.25 / Chapter 3.1.4. --- Vertebral deformity and bone mineral density --- p.28 / Chapter 3.2. --- Bone composition --- p.33 / Chapter Chapter 4. --- Literature Review on Health Consequences of Vertebral Deformity --- p.36 / Chapter 4.1. --- Back pain --- p.36 / Chapter 4.1.1. --- Back pain and vertebral deformity --- p.36 / Chapter 4.1.2. --- Back pain in men and women with vertebral deformity --- p.38 / Chapter 4.2. --- Morale and functional limitation and vertebral deformities --- p.39 / Chapter 4.2.1. --- Function evaluation : The Barthel Index --- p.40 / Chapter 4.2.2. --- Philadelphia Geriatric Morale Scale --- p.41 / Chapter Chapter 5. --- Objectives --- p.43 / Chapter Chapter 6. --- "Subjects and methods for phase I: anthropometric measurement, body composition and bone mineral density measurement in vertebral deformity patients and controls" --- p.44 / Chapter 6.1. --- Study subjects --- p.44 / Chapter 6.2. --- Radiology and digitization protocol for diagnosis vertebral deformity --- p.46 / Chapter 6.3. --- Diagnosis of vertebral deformity --- p.48 / Chapter 6.4. --- Body composition and bone mineral density measurements --- p.54 / Chapter 6.4.1. --- Body composition analysis --- p.54 / Chapter 6.4.2. --- Lumbar spine and hip bone mineral analysis --- p.54 / Chapter 6.5. --- Quality control --- p.56 / Chapter 6.5.1. --- Routine quality control of measurements --- p.56 / Chapter 6.5.2. --- Precision on patient repositioning --- p.56 / Chapter Chapter 7. --- Subjects and methods for phase II: health consequences of vertebral deformity patients and controls --- p.57 / Chapter 7.1. --- Questionnaire on health consequences --- p.57 / Chapter 7.1.1 --- Back pain and disability --- p.57 / Chapter 7.1.2 --- Activities of daily living --- p.59 / Chapter 7.1.3 --- Morale --- p.59 / Chapter 7.2. --- Statistical methods --- p.60 / Chapter 7.2.1. --- Bone mineral density and body composition --- p.60 / Chapter 7.2.2. --- Back pain and disability --- p.60 / Chapter 7.2.3. --- Activities of daily living and morale --- p.61 / Chapter Chapter 8. --- "Results for phase I: anthropometric measurement, body composition and bone mineral density measurement in vertebral deformity patients and controls" --- p.62 / Chapter 8.1. --- Demographic characteristics of study population --- p.62 / Chapter 8.2. --- Anthropometric measurements : Body composition and bone mineral density --- p.64 / Chapter Chapter 9. --- Results for phase II: Health Consequences of vertebral deformity patients and control --- p.76 / Chapter 9.1. --- Back pain --- p.76 / Chapter 9.2. --- Disability --- p.78 / Chapter 9.3. --- Activities of daily living --- p.81 / Chapter 9.4. --- Morale --- p.82 / Chapter Chapter 10. --- Discussion I --- p.83 / Chapter 10.1. --- Study Sample --- p.83 / Chapter 10.2. --- Digitization method and definition of vertebral deformity --- p.84 / Chapter 10.3. --- Methods for bone mineral density measurement --- p.87 / Chapter 10.4. --- Questionnaire validity --- p.88 / Chapter 10.4.1. --- Back pain and disability --- p.88 / Chapter 10.4.2. --- Barthel Index --- p.88 / Chapter 10.4.3. --- Philadelphia Geriatric Morale Scale --- p.89 / Chapter Chapter 11. --- Discussion II --- p.92 / Chapter 11.1 . --- Body composition and bone mineral density --- p.92 / Chapter 11.2. --- Differences of vertebral deformity between Chinese men and Caucasian men --- p.93 / Chapter 11.3. --- Health consequences in Chinese men --- p.96 / Chapter 11.4. --- Comparison of health consequences between Chinese men and Caucasian men --- p.98 / Chapter 11.5. --- Variation of health consequences between Chinese men and Chinese women --- p.101 / Chapter 11.5.1. --- Back pain and disability --- p.101 / Chapter 11.5.2. --- Morale --- p.102 / Chapter Chapter 12. --- Conclusion --- p.103 / Reference --- p.104 / Appendix I --- p.115 / Appendix II Publication