Background: The process of bone remodelling is disturbed in the development of osteoporosis. Objective: To investigate if proteins in osteoporotic bone are modified by advanced glycation end products (AGEs), and whether these alterations are related to measures of bone remodelling based on histomorphometric findings. Methods: Bone specimens taken from the iliac crest by bone biopsy of eight osteoporotic patients were investigated by histomorphometry and by immunohistochemical staining with the AGEs imidazolone and N e -carboxymethyllysine. Results: Both AGEs were found in all bone specimens. The intensity of staining correlated with patient age. The percentage of bone surface covered with osteoblasts showed a significantly negative correlation with the staining intensity of both AGEs. Conclusions: It is known that AGEs can regulate proliferation and differentiation of osteoblastic cells and that AGE-specific binding sites are present in cultured osteoblast-like cells. Moreover, AGE induced biological effects in these cells might be mediated by RAGE (receptor of AGE) or by other AGE receptors in different stages of osteoblast development. The inverse relation between AGE staining intensity and the percentage of bone surface covered with osteoblasts in the trabecular bone may provide evidence that AGE modification of bone proteins disturbs bone remodelling. I t is currently known that bone is a permanently regenerating organ with a high number of removal sites at any time-the basic multicellular units. Physiological remodelling seems to be essential for preservation of bone quality. In this context questions arise as to what are the mechanisms behind the initiation of the remodelling in an enclosed bone site? What form of alterations intensifies the attraction of osteoclast precursors and triggers their maturation or disturbs osteoblast recruitment and/or function in the remodelling process?Advanced glycation end products (AGEs) are chemical modifications of proteins by carbohydrates, including metabolic intermediates formed during the Maillard reaction. The generation of AGEs is an inevitable process in vivo. AGEs constitute a heterogeneous class of structures. They are recognised by specific receptors on different cell types. The most well known receptor of AGEs is the RAGE. A remarkable feature of AGEs is their ability to mediate an additional cross linking of altered protein subunits, resulting in a high resistance to proteolytic digestion. The binding of an AGE on its cellular receptor (for example RAGE) activates the nuclear factor kB (NF-kB) in these cells, followed by an increased expression of, for example, cytokines such as interleukin 6, interleukin 1, and tumour necrosis factor a, as well as growth factors and adhesion molecules. [4][5][6] Among the well described and chemically identified AGEs are N e -carboxymethyllysine (CML), pentosidine, and imidazolone. Long living proteins such as collagen molecules in bone are particularly predestined to undergo such chemical modification. 7It seems probable th...

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Plasma PTH measurements using either the BI-PTH or I-PTH assay effectively identify patients with reduced bone turnover and serve to distinguish this subgroup from those with high turnover lesions of renal bone disease. Both assays provide better diagnostic discrimination for this purpose than calculated values for the ratio of PTH (1-84)/amino terminally truncated PTH fragments.

Objective. To evaluate digital x-ray radiogrammetry (DXR) and the Radiogrammetry Kit program as new diagnostic tools for quantifying disease-related periarticular osteoporosis and for measuring joint space narrowing according to the severity and duration of rheumatoid arthritis (RA).Methods. Using DXR, we performed computerized calculations of bone mineral density (BMD) and the metacarpal index (MCI) in 258 patients with active RA. Using the Radiogrammetry Kit program, we also performed semiautomated measurements of joint space width(JSW)atthesecondthroughthefifthmetacarpophalangeal (MCP) joints in these patients.Results. All correlations between the different parameters of both techniques (BMD and the MCI as measured by DXR and MCP JSW as measured by the Radiogrammetry Kit) were significant (0.36 < R < 0.63; P < 0.01). As expected, a significant negative association was shown between the different MCP JSW results and the results of all scoring methods (؊0.67 < R < ؊0.29). The BMD and the MCI measured by DXR both decreased significantly between Steinbrocker stage I and stage IV (by 32.7% and 36.6%, respectively; both P < 0.01). Reductions in the overall (mean) MCP JSW varied from 35.3% (Larsen score) to 52.9% (Steinbrocker stage). Over a period of 6 years, we observed relative decreases in BMD and the MCI as measured by DXR (32.1% and 33.3%, respectively), as well as in the overall (mean) MCP JSW (23.5%), and these were pronounced in early RA (duration <1 year). In addition, excellent reproducibility of DXR and Radiogrammetry Kit parameters was verified (coefficients of variation <1%).Conclusion. DXR with the integrated Radiogrammetry Kit program could be a promising, widely available diagnostic tool for supplementing the different RA scoring methods with quantitative data, thus allowing an earlier and improved diagnosis of RA and more precision in determining disease progression.

This case report of a 61-year-old woman suffering from Gorham-Stout syndrome shows osteolyses of the left pelvis, proximal femur and lumbar spine. The therapeutic regime has included two courses of percutaneous radiotherapy and also continuous application of bisphosphonates over 17 years. Despite this antiresorptive therapy, elevated urinary excretion of desoxypyridinoline has indicated the persistence of increased bone destruction. The radiological progression following bisphosphonate treatment was only moderate. However, physical disability is reduced, but without soaring handicaps suggesting that long-term bisphophonate therapy is a therapeutical option for this rare syndrome.