A preliminary study for non-invasive quantification of manganese in human hand bones.

Manganese (Mn) is a nutrient essential for regulating neurological and skeletal functions in the human body, but it is also toxic when humans are excessively exposed to Mn. Blood (or serum/plasma) and other body fluids reflect only the most recent exposure and rapidly return to within normal ranges, even when there has been a temporary excursion in response to exposure. In this context, we have been developing a non-invasive measurement of Mn stored in bone, using in vivo neutron activation analysis. Following feasibility studies, a first pilot study, using neutron activation analysis to measure Mn in the bones of the hand of ten healthy male human subjects, was conducted with the approval of the concerned research ethics boards. The participants of this study had no known history of exposure to Mn. Two volunteers were excluded from this study due to technical problems with their measurements. The inverse variance weighted mean value of Mn/Ca for the participants of this study is 0.12+/-0.68 microg Mn/g Ca which is comparable within uncertainties with the estimated range of 0.16-0.78 microg Mn/g Ca and mean value of 0.63+/-0.30 microg Mn/g Ca derived from cadaver data. It is recommended to investigate the use of the diagnostic technique for in vivo measurements of workers exposed occupationally to excessive amounts of Mn who could develop many-fold increased levels of Mn in bones as demonstrated through various animal studies. The technique needs further development to improve the precision of in vivo measurements in the non-exposed population.

Changes in cross-sectional geometry of the distal femoral metaphysis associated with inflammatory arthritis are reduced by a bisphosphonate (zoledronate).

An increased risk of fracture is a feature of rheumatoid arthritis and of animal models of inflammatory arthritis. We examined geometrical changes in the metaphyseal cortex of the distal femur in an animal model of inflammatory arthritis. Additionally, we examined the effect of a bisphosphonate in preventing these changes. Five groups of rabbits were studied: normal controls, those with inflammatory arthritis, and three groups with arthritis treated with bisphosphonate. To determine geometrical properties, image analysis was performed on digitized cross sections of the femoral metaphyseal cortices. The results demonstrated that the posterior cortical wall was significantly less thick in rabbits with arthritis than in normal rabbits and in the rabbits in the three bisphosphonate treatment groups (p < 0.05). Moment of inertia about the lateral-medial axis was reduced in rabbits with arthritis compared with normal rabbits (p < 0.05). Cross-sectional area was not significantly different between groups. The changes suggest a mechanism of weakening of bone in arthritis; when the results are coupled with results of previous porosity studies, severe directional weakness is apparent. Bisphosphonate was effective in preserving bone integrity in inflammatory arthritis.

Theoretical relationship between maximum pore size and toughness in experimental inflammatory arthritis.

Rheumatoid arthritis increases the risk of fracture. In an animal model of inflammatory arthritis, femoral diaphysis had a decreased toughness as well as increased cortical porosity, when compared to normal bone. Based on the hypothesis that stress concentration from the large porous defects reduces the ability of the cortical bone to resist failure, this work determined if the changes observed in porosity could explain the changes observed in toughness. Using theoretical relationships of the stress concentration and stress states, a model of the observed conditions was considered. A relationship was developed that indicated the relative difference in toughness between normal and arthritic specimens as a function of pore size. Results indicated that the increase in cortical pore size could theoretically reduce toughness by 55%. This decrease compares with the experimentally observed drop in toughness of 61%. Furthermore, the critical parameter for fracture in this situation is the ratio of pore diameter to cortical thickness. Efforts to reduce cortical porosity seen in inflammatory arthritis would be effective in enhancing the toughness of bone and may reduce morbidity in a human population.

Zoledronate (CGP 42'446), a bisphosphonate, protects against metaphyseal intracortical defects in experimental inflammatory arthritis.

This study investigated zoledronate (CGP 42'446), a bisphosphonate, as a potential prophylactic and therapeutic agent against intracortical defects in metaphyseal bone in an experimental model of inflammatory arthritis. Inflammatory arthritis was induced in the right tibiofemoral joint of rabbits by the repeated injection of carrageenan. Three groups of animals were treated with the bisphosphonate daily, beginning at different points after the induction of arthritis. Cross sections of the right distal femoral metaphysis were prepared, and intracortical defects were examined by computerized image analysis. The percentage of total bone area with defects (the ratio of void area to total bone area) was greatly increased in the arthritic group compared with that in the normal group (p < 0.001). In all groups treated with the bisphosphonate, there was a significantly lower percentage of total bone area with defects compared with that in the arthritic group (p < 0.001). Treatment was likewise effective in reducing the zonal (anterior and posterior) predilection for the formation of defects observed in arthritis. Although inflammatory arthritis has a substantial effect in producing intracortical defects in metaphyseal bone, a bisphosphonate, zoledronate, was considerably effective in preventing these changes from occurring.