Studies on inorganic pyrophosphate in pyrophosphate arthropathy

Hamilton, EB, 1994. Studies on inorganic pyrophosphate in pyrophosphate arthropathy. PhD, Nottingham Trent University.

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Abstract

Age, metabolic disease and familial tendency all predispose to CPPD crystal deposition. However, the effects of these predisposing factors on articular PPi metabolism have not been investigated.

The activities of the synovial fluid enzymes, NTPP, 5NT and ALP have previously been implicated in the pathogenesis of pyrophosphate arthropathy and CPPD crystal deposition. Normal controls, however, are lacking in previous studies. Whether a true relationship exists between these synovial fluid enzymes and crystal deposition, therefore, is unclear.

Reduced synovial fluid PPi concentrations have been reported in acute pseudogout compared to chronic pyrophosphate arthropathy, suggesting an association between inflammation and PPi concentrations. Few studies, however, have characterised joints according to inflammatory state. The effects of the inflammatory state of the joint on PPi metabolism, including effects on the activities of the enzymes NTPP, ALP and 5NT, are therefore, of interest in their putative association with CPPD crystal deposition.

In familial pyrophosphate arthropathy a systemic disorder of PPi metabolism has been proposed. In the sporadic form of pyrophosphate arthropathy, however, whether altered PPi metabolism reflects a generalised abnormality of cartilage in predisposed individuals, or a localised response to joint damage has not been investigated.

In this study articular PPi metabolism was studied in conditions that predispose to CPPD deposition, by the measurement of synovial fluid PPi and the activities of the enzymes NTPP, ALP and 5NT, which could be responsible for an aberration in articular PPi metabolism leading to CPPD crystal deposition. In addition knees were classified according to their clinical inflammatory state preceding aspiration to assess the effects of disease activity on articular PPi metabolism.

Knee synovial fluid PPi levels and NTPP activity were elevated in pyrophosphate arthropathy compared to osteoarthritis, rheumatoid arthritis and normal, implicating an error in PPi metabolism promoting CPPD crystal deposition. Knee synovial fluid PPi levels showed a positive correlation with NTPP activity in all disease groups, implicating NTPP as a major source of synovial fluid PPi. No correlation was apparent between age and synovial fluid PPi levels or NTPP activity in normals, despite the strong association between ageing and CPPD crystal deposition.

The effects of clinical inflammation varied between the disease groups studied, affecting PPi metabolism in pyrophosphate arthropathy and rheumatoid arthritis but not in osteoarthritis, suggesting the existence of different inflammatory mechanisms between diseases.

The enzymes ALP and 5NT, which have been implicated in the promotion of CPPD crystal deposition, via effects on PPi metabolism, showed no such association in this study, but did relate to the inflammatory state of the joint.

A defect in articular PPi metabolism was evident in several of the metabolic diseases studied which are known to predispose to CPPD crystal deposition. In haemochromatosis, hypomagnesaemia and hyperparathyroidism, increased synovial fluid PPi was evident. Synovial fluid NTPP activity was similarly increased in haemochromatosis and hypomagnesaemia.

Studies on articular PPi metabolism in familial pyrophosphate arthropathy did not reveal any abberation in PPi metabolism compared to the sporadic form of the disease. Factors promoting CPPD crystal deposition, in addition to those affecting PPi metabolism may be under genetic influence.

Item Type:	Thesis
Creators:	Hamilton, E.B.
Date:	1994
ISBN:	9781369325515
Identifiers:	Number Type PQ10290302 Other
Divisions:	Schools > School of Science and Technology
Record created by:	Linda Sullivan
Date Added:	05 Jul 2021 15:41
Last Modified:	20 Mar 2024 15:52
URI:	https://irep.ntu.ac.uk/id/eprint/43328

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