Biological or Clinical Significance:
Approximately 90% of the organic matrix of bone is type I collagen, a triple helical protein. Type I collagen of bone is crosslinked by specific molecules which provide rigidity and strength. Crosslinks of mature type I collagen in bone are the pyridinium crosslinks, pyridinoline (PYD) and deoxypyridinoline (DPD). DPD is formed by the enzymatic action of lysyl oxidase on the amino acid lysine. DPD is released into the circulation during the bone resorption process. DPD is excreted unmetabolized in urine and is unaffected by diet, making it suitable for assessing resorption.
Bone is constantly undergoing a metabolic process called remodeling. This includes a degradation process, bone resorption, mediated by the action of osteoclasts, and a building process, bone formation, mediated by the action of osteoblasts. Remodeling is required for the maintenance and overall health of bone and is tightly coupled; that is resorption and formation is in balance. In abnormal states of bone metabolism this process becomes uncoupled and, when resorption exceeds formation, this results in a net loss of bone. The measurement of specific degradation products of bone matrix provides analytical data of the rate of bone metabolism.
Osteoporosis is a metabolic bone disease characterized by abnormal bone remodeling. It is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in susceptibility to fractures. The most common type of osteoporosis occurs in postmenopausal women as a result of the estrogen deficiency produced by the cessation of ovarian function. Restoration of premenopausal estrogen levels by replacement therapy prevents bone loss and osteoporosis. Estrogens and a class of compounds known as bisphosphonates are anti-resorptive therapies which can be used to prevent bone loss or treat osteoporosis. Osteoporosis can also result from attaining an inadequate peak bone mass during the growing years, an age-related imbalance of bone remodeling with a net excess of resorption, and a number of clinical conditions and therapies which induce bone loss or bone remodeling imbalances. These include endocrine diseases such as hypo-gonadism, hyperthyroidism, hyperparathyroidism, and hypercortisolism; gastrointestinal diseases related to nutrition and mineral metabolism; connective tissue diseases; multiple myeloma; chronic immobilization, alcoholism, or tobacco use; and chronic therapy with heparin or corticosteroids. Other diseases characterized by abnormal bone remodeling include Paget’s disease and cancers metastatic to bone.
Principle of Test Method:
The DPD assay is a competitive enzyme immunoassay. DPD is reported as a normalized ratio to urinary creatinine in order to account for variations in urine flow rate. Therefore DPD and urine creatinine are preferably tested from the same aliquot.