The extracellular matrix in bone and cartilage is stabilised by the formation of covalent cross-links between adjacent collagen chains. These cross-links are amino acid derivatives and can be divided into two main groups: labile cross-links that are abundant in newly formed collagen; and stable cross-links that are found only in mature collagen. Pyridinoline (PYD) and Deoxypyridinoline (DPD) are the major stable cross-links. These cross-links, primarily in bone and cartilage, have been found in all the connective tissues except the skin. PYD is the major component of these tissues, whereas DPD has only been detected in bone and dentine.
PYD and DPD are normally excreted in the urine, and larger quantities are excreted when bone resorption is increased. In contrast, when bone resorption is inhibited by bisphosphonates, oestrogen, or calcitonin therapy, the excretion of PYD and DPD is decreased. All available data indicate that PYD and DPD derive only from bone matrix degradation and thus are markers of bone resorption, not bone formation. The assay for pyridinoline collagen cross-links is useful as a sensitive and specific marker in the diagnosis and management of bone loss in osteoporosis. The cross-links assay is also useful in measuring bone resorption in other metabolic bone diseases such as primary hyperparathyroidism and Paget’s disease.
There is a significant circadian rhythm with higher levels of excretion at night (as much as 50%). There is also a day to day variation in excretion of deoxypyridinoline (as much as 20%). Whilst this may be due to inadequacies in the urine collection the variation may also be due to variation in renal handling and in the conversation of complexed to free deoxypyridinoline. It is therefore recommended that a carefully monitored second void collection is made; patients should be asked to empty their bladders on waking and discard the urine. Then they should collect the next specimen (the second morning void) in the container (plain container, no additives). To minimise the influence of day to day variability it is important to maintain the same collection protocol.
DPD and PYD are released from Type I collagen, which is mainly in bone, as a result of osteoclast resorption. They are increased above the reference range in conditions resulting in increased osteoclast activity and are therefore not diagnostic for a single bone pathology. The highest increases (>4 times upper limit of normal) are seen in immobilisation, Paget’s disease of bone and metastatic cancer. Increases between 2-3 time upper limits of normal are seen in osteoporosis, primary hyperparathyroidism, osteomalacia, thyrotoxicosis and several inflammatory conditions.
The main application for DPD and PYD is in assessing and monitoring response to osteoclast inhibitory treatment (mainly bisphosphonates) in osteoporosis and Paget’s disease of bone. A decrease >30% in value obtained pretreatment is indicative of a good response in osteoporosis. Normalisation of DPD and PYD is the ultimate goal when treating Paget’s disease of bone
Sample requirements: Urine
Sample volume: 10 mL
Specimen Requirements: There is a significant circadian rhythm with higher levels of excretion at night (as much as 50%). It is therefore recommended that a carefully monitored second void urine is collected. A baseline pre-treatment measurement is required if assessing response to antiresorption therapy
SAS Centres providing free urine deoxypyridinolines: