Type I collagen cross-links: specific markers of bone resorption. Type I collagen molecules in bone matrix are linked together by cross-linking molecules including pyridinoline (PYD) and deoxypyridinoline (DPD) in the region of N and C-telopeptides. DPD, which differs from PYD by the absence of an hydroxyl residue, is specific for bone tissue. During bone resorption, pyridinoline is released into the circulation and excreted in the urine in its free form or linked to C- (CTX) or N- (NTX) telopeptides. The different cross-link forms can be measured in serum and urine using specific immunoassays.

Combining imaging and biochemical markers to determine fracture risk. Based on a 2-year follow-up of 109 elderly women with hip fracture and 392 control subjects, DXA combined with biochemical markers of bone degradation was more predictive of fracture risk than either DXA or markers alone (Garnero, et al. J bone Miner Res, 1996).

Selecting the right molecular marker. Estrogen and bisphosphonate treatments show different effects on bone resorption markers, with only bisphosphonate treatment decreasing peptide cross-link excretion. This illustrates the importance of matching the marker to the type of treatment investigated (Garnero et al., 1994).

Effect of transdermal estrogen on biochemical markers of bone turnover in postmenopausal women. Estrogen treatment produces a rapid and dose dependent decrease in markers of bone turnover, with an earlier decrease in bone resorption (urinary CTX) than bone formation (serum osteocalcin and bone specific alkaline phosphatase) markers . Markers of bone turnover are very useful in phase II studies for dose selection. (Delmas and Garnero; 1999).

Short-term changes in bone markers predict long-term changes in bone mineral density in women treated with antiresorptive therapy. Note the correlation between decreased urinary NTX after 6 months and increased spine and hip BMD after 2 years of treatment with the bisphosphonate alendronate (Ravn and Christiansen; 1999).