Markers bone alkaline phosphatase

Recent studies have suggested that MK-4, in particular, has a transcriptional regulatory function, for example, in osteosarcoma cell cultures, in which it binds to and activates the SXR steroid and xenobiotic receptor. This in turn increases mRNA levels for osteoblast markers bone alkaline phosphatase, osteoprotogerin, osteopontin, and MGP. MK-4 and its isolated geranyl-geraniol side chain was also able to suppress the synthesis of prostaglandin Ei, which is a potent bone resorption catalyst. These observations have led to speculation (i) that some of the menaqui-nones may possess some functions that are not shared by phylloquinone, and (ii) that there may be implications for cell proliferation and for cancer risk from variations in the supply of vitamin K and in its speciation. 

A study in 500 Australian women (aged 40 to 80 years) has shown that higher isoflavone intakes are associated with higher concentrations of bone alkaline phosphatase, a short-term marker of bone formation and turnover. 

Bouman AA, Scheffer PG, Ooms ME, Lips P, Netelenbos C. Two bone alkaline phosphatase assays compared with osteocalcin as a marker of bone formation in healtliy elderly individuals. Clin Chem 1995 41 196-9. 

Once stem cells are committed to the osteoblast lineage, proliferating osteoprogenitors become preosteoblasts, cell growth declines, and there is a progressive expression of differentiation markers by osteoblasts (Stein et al. 1996). Osteoblastic differentiation is characterized by the sequential expression of alkaline phosphatase (ALP), an early marker of osteoblastic phenotype, followed by the synthesis and deposition of collagen type I, bone matrix proteins, and glycosaminoglycans and an increased expression of os-... 

The most important organic components of bone are collagens (mainly type 1 see p.344) and proteoglycans (see p. 346). These form the extracellular matrix into which the apatite crystals are deposited (biomineralization). Various proteins are involved in this not yet fully understood process of bone formation, including collagens and phosphatases. Alkaline phosphatase is found in osteoblasts and add phosphatase in osteoclasts. Both of these enzymes serve as marker enzymes for bone cells. 

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]). 

Markers of bone resorption can be measured in serum or urine, whereas bone formation markers, such as bone-specific alkaline phosphatase, are usually measured in serum. Measurement of bone markers allows for real-time assessment of bone resorption or formation and can be used to monitor therapy (Ravn et al., 2003). The pyridonolines (deoxypyridinoline and pyridinoline) and the N- and C-teleopep-tides are the most frequently measured markers of bone resorption. Pyridinoline and teleopep-tides (NTx and CTx) are increased in individuals with metabolic bone diseases associated... 

The effects on bone metabohsm of carbamazepine, valproate, or phenobarbital as monotherapy have been analysed in a case-control study in 118 ambulatory children with epilepsy and corresponding controls (120). Patients taking carbamazepine or phenobarbital had significantly raised alkaline phosphatase and bone and liver isoenzyme activities compared with controls. Although the authors concluded that children who take anticonvulsants may have their bone metabolism affected, this conclusion was based on abnormal values of a surrogate marker for bone disease. 

There are five enzymes that are commonly used in diagnosis of liver disease Aspartate aminotransferase (AST EC 2.6.1.1), alanine aminotransferase (ALT EC 2.6.1.2), alkaline phosphatase (ALP 3.1.3.1), and y-glutamyl transferase (GGT EC 2.3.2.2), are commonly used to detect liver injury, and lactate dehydrogenase (LD EC 1.1.1.27) is occasionaEy used. ALT and GGT are present in several tissues, but plasma activities primarily reflect liver injury. AST is found in liver, muscle (cardiac and skeletal), and to a liipited extent iti fed cells. LD has wide tissue distribution, and is thus relatively nonspecific. ALP is found in a number of tissues, but in normal individuals primarEy reflects bone and liver sources. Thus based on tissue distribution, ALT and GGT would seem to be the most specific markers for liver injury. 

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. 

Elevated levels of serum alkaline phosphatase and osteocalcin are markers of bone formation and are elevated in all bone diseases that result in increased bone turnover. 

The activity of the enzyme alkaline phosphatase has traditionally been used as an indicator of bone turnover. The osteoblasts which lay down the collagen framework and the mineral matrix of bone have high activity of this enzyme. Increased osteoblastic activity is seen as an elevated alkaline phosphatase activity in a scnim specimen. Indeed, children who have active bone growth compared with adults have higher normal alktiline phosphatase activity iti semm. However alkaline phosphatase is also produced by the ceils lining the bilecanaliculi and is a marker for cholestasis. The botie isoenzyme of alkaline phosphatase may be measured, but there is need for a more specific and more sensitive marker. 

Alkaline phosphatase is a marker for bone formation. Urinary hydroxyproline is a marker for bone resorption. Better markers for bone turnover are being evaiuated. Osteomaiacia due to vitamin D deficiency can be confirmed by finding a iow... 

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

Plasma alkaline phosphatase also changes during growth periods, but it is not a useful marker of bone metabolism in rats or nonhuman primates (see Chapter 2). 

The AHRQ Report summarized numerous studies that evaluated the effects of soy products, including both protein and isoflavones, on various markers of bone health, such as bone mineral density (BMD) and biomarkers related to bone formation (bone-specific alkaline phosphatase and osteocalcin) and resorption (urinary hydroxyproline, urinary pyridinoline, and urinary deoxypyridinoline). In general, no effect of soy consumption on BMD or on biomarkers of bone formation resulted. Although a number of studies observed reductions in markers of bone resorption, these were restricted to only two biomarkers urinary pyridinoline and deoxypyridinoline. Moreover, the effects were not consistent across studies. The AHRQ report found no consistent evidence of dose-response effects for either soy isoflavones or soy protein on markers of bone turnover (Balk et al., 2005). 

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