Biochemical markers bone resorption

A. Paget s disease is often asymptomatic and picked up on plain bone films. Patients with Paget s disease should have their serum calcium level determined to make sure that they are not hypercalcemic from excessive bone resorption, their serum alkaline phosphatase measured as a marker of new bone formation, a bone scan to determine whether other bones are involved, and a 24-hour urinary hy-droxyproUne measurement to assess bone resorption. The patient who has minimal involvement and is biochemically normal does not need pharmacological therapy. No studies indicate that early treatment slows progression in individuals with the more severe form of this disorder. 

Treatment with beclomethasone dipropionate 1500 micrograms/day for 6 weeks significantly reduced markers of bone formation (osteocalcin and PICP), whereas fluticasone propionate 750 micrograms/day had no effect. Neither drug affected biochemical markers of bone resorption. There was no significant change in bone density (SEDA-22,183). 

The laboratory also measured biochemical markers of bone metabolism. The urinary excretion of deoxypyrolidone, a marker of bone resorption, was elevated (128 nmol/mmol creatinine normal is 31-110 nmol/mmol creatinine). Bone-specific alkaline phosphatase, a marker of bone synthesis, was also elevated at 400 U/L (normal is 70-139 U/L for girls between 3 and 8 years of age) (Tsai et al., 1999). The concentration of another marker of bone resorption, NTx (N-teleopeptide), in the patient s serum was elevated (110 nmol BCE/L normal is 20-68 nmol BCE/L [bone collagen equivalents]). 

P8. Popp-Snijders, C., Lips, P., and Netelenbos, J. C., Intra-individual variation in bone resorption markers in urine. Ann. Clin. Biochem. 33, 347-348 (1996). 

Osteoclasts are multinucleated cells found on the endosteal surface of bone, in Haversian systems and periosteal surfaces. PTH activates osteoclasts (indirectly via osteoblasts that possess PTH receptors). Calcitonin is a potent inhibitor of osteoclast activity. Local cytokine factors, including interleukin-1 (IL-1), tumour-necrosis factor (TNF), TGF- 0 and interferon-y (INF-y), are important regulators. Osteoclast resorption of bone releases collagen peptides, pyridinoline cross-links and calcium from the bone matrix, through the action of lysosomal enzymes (collagenases and cathepsins). The collagen breakdown products in serum and urine (e.g. hydroxyproline) can be used as biochemical markers. 

Biochemical markers of bone resorption and. formation have a number of potential uses" including (1) monitoring the effectiveness of therapy, (2) selection of patients for therapy, (3) prediction of bone loss, and (4) prediction of fracture risk. Of these, bone markers are currently most used for monitoring the effectiveness of therapy. Effective anti-resorptive therapy is followed by a significant reduction in resorption markers within few weeks, normally reaching a plateau within 3 to 6 months. Markers of bone formation respond more slowly, usually reaching a plateau at 6 to 12 months. Depending on the antiresorptive therapy and the bone marker, effective therapy is associated with a bone marker reduction of 20% to 80%. 

Blumsohn A, Naylor KE, Assiri AMA, Eastell R. Different responses of biochemical markers of bone resorption to bisphosphonate therapy in Paget s disease. Chn Chem 1995 42 1592-8. 

Kraenzlin ME, Seibel MJ. Measurement of biochemical markers of bone resorption. In Seibel MJ, Robins SP, Bilezikian, eds. Dynamics of bone and cartilage metabolism. San Diego Academic Press, 1999 411-26. 

Woitge HW, Seibel MJ. Risk assessment for osteoporosis II biochemical markers of bone turnover bone resorption indices. CUn Lab Med 2000 503-25. 

An estimated 75 million people are affected by osteoporosis to some degree in the United States, Europe, and Japan. Osteoporosis is a systematic skeletal disease characterized by bone mass and microarchitectural deterioration with a consequent increase in bone fragility and susceptibility to fracture. Operationally, osteoporosis can be defined as a certain level of bone mineral density. The definition of osteoporosis is somewhat arbitrary and is based on epidemiological data relating fracture incidence to bone mass. Uncertainty also is introduced due to variability in bone densitometry measurements. Other clinical measures to assess the skeleton include collagen cross-links (measure of bone resorption) and levels of bone-specific alkaline phosphatase and osteocalcin (bone formation). A list of biochemical markers of bone remodeling is provided in Table 37-3. Measurement of total serum alkaline phosphatase level and urinary hydroxyproline or calcium levels is of limited value. 

Biochemical Markers of Bone Formation and Bone Resorption... 

Some Biochemical Markers of Bone Resorption, Formation, and Turnover... 

Paget s disease (Table 35.6) is characterized by excessive bone resorption, followed by replacement of the normally mineralized bone with soft, poorly mineralized tissue (20). It has been determined that the osteoclasts have an abnormal structure, are hyperactive, and are present at elevated levels (20). Patients afflicted with this painful condition often suffer from multiple compression fractures. Administration of calcitonin and oral calcium and phosphate supplements had been the treatment of choice until the bisphosphonate risedronate was approved by the U.S. Food and Drug Administration (FDA). Daily administration of risedronate results in a decreased rate of bone turnover and a decrease in the levels of serum alkaline phosphatase and urinary hydroxyproline, two biochemical markers of bone turnover (4,20). A significant advantage to treatment with the bisphosphonates is long-term suppression of the disease (20). Calcium supplementation, which often is necessary in these patients, must be dosed separately from risedronate, because calcium- and aluminum- or... 

Strontium ranelate is an orally active agent that can be classified as both an antiresorptive agent and a bone-forming agent (42,43). It is able not only to stimulate replication of preosteoblastic cells to promote bone formation but also is able to decrease osteoclastic activity to prevent bone resorption. Biochemical markers for bone formation (e g., bone-specific alkaline phosphatase), which normally decrease in the presence of antiresorptive therapy, are elevated in the presence of strontium ranelate (44). Lumbar spine BMD increased 11.4% in patients treated with this new agent. 

Weaver, C.M., Peacock, M., Martin, B.R., McCabe, G.P., Zhao,)., Smith, D.L, and Wastney, M.E. (1997) Quantification of biochemical markers of bone turnover by kinetic measures of bone formation and resorption in young healthy females. J. Bone Miner. Res., 12, 1714-1720. 

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