Biochemical markers bone formation

J.C. Gallagher, I. Pavo, J. Wang, and E.F. Eriksen. 2005. Early changes in biochemical markers ofbone formation correlate with improvements in bone structure during teriparatide therapy. J. Clin. Endocrinol. Metab. 90 3970-3977. 

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). 

P10. Price, P. A., Parthemore, J. G., and Deftos, L. J., New biochemical marker for bone formation Measurement by radioimmunoassay for GLA protein in the plasma of normal subjects and patients with bone disease. J. Clin. Invest. 66, 878-883 (1980). 

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%. 

ALP determined by usual biochemical panels reflects total serum concentrations and does not distinguish the source of the isoenzyme (i.e., liver, bone, or some other source). Clinicians must therefore rely on other markers of liver or other organ function or a more tissue-specific determination of ALP to assess the source of ALP. In normal individuals, ALP originates primarily from liver and bone. The bone isoenzyme is the marker of bone formation and is found in osteoblasts. 

Naylor KE, Eastell R. Measurement of biochemical markers of bone formation. In Seibel MJ, Robins SP, Bilezikian, eds. Dynamics of bone and cartilage metabohsm. San Diego Academic Press, 1999 401-10. 

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... 

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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