Biochemical markers bone alkaline phosphatase

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. 

Glucocorticoids can even cause osteoporosis when they are used for long-term replacement therapy in the Addison s disease, as has been shown by a study of 91 patients who had taken glucocorticoids for a mean of 10.6 years, in whom bone mineral density was reduced by 32% compared with age-matched controls (SEDA-19, 377 198). However, these results contrasted with the results of a Spanish study in patients with Addison s disease, in which no direct relation was found between replacement therapy and either bone density or biochemical markers of bone turnover of calcium metabolism (alkaline phosphatase, osteocalcin, procollagen I type, parathormone, and 1,25-dihydroxycolecalciferol) (SEDA-19, 377 199). 

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]). 

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. 

The characteristic biochemical marker of Paget s disease is a grossiy increased alkaline phosphatase activity, as a consequence of increased bone 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. 

---