Bone growth and remodelling are normal physiological events that occur at a high rate throughout childhood and adolescence, and to a much lesser extent during adult years. It is the net result of the activity of two types of bone cell which have opposing actions: those that synthesise new bone material, mainly, osteoblasts, and cells called osteoclasts, which are responsible for resorbing or breaking down existing bone material.
An exaggerated rate of bone resorption underlies the pathophysiology of many human diseases—for example, Paget's disease, malignant hypercalcaemia, renal osteodystrophy, hyperthyroidism, hyperparathyroidism, and postmenopausal osteoporosis.22,30–32
The outcome is a progressive thinning of the bones and an increased risk of fractures.
Evidence shows that a pathological increase in bone resorption arises when osteoclasts are stimulated into resorption activity at an increased rate. This upsets the normal balance between bone resorption and bone synthesis.10
The increase in osteoclast activity is accompanied by an increase in the synthesis and secretion of type 5b AP. This enzyme is resistant to the inhibitory influence that L(+) tartrate has on the catalytic function of other APs. It is therefore commonly called tartrate resistant acid phosphatase (TRAP).10
Evidence indicates that TRAP is involved in the bone resorption process. Furthermore, resorption events are marked by a corresponding rise in the total amount of TRAP in the serum.33
An association between osteoclasts and the enzyme TRAP is nothing new. Osteoclasts are well known for containing a large amount of TRAP activity,33
and this phenomenon has been used for many years to identify osteoclasts in tissue samples using histochemical techniques.34
Further evidence of this association is abundant. For example, (1) osteoclasts cultured in the laboratory on cortical bone slices or dentine show a progressive accumulation of TRAP in the culture medium. This corresponds to the development of resorption lacunae on the bone surface.34
(2) Antibodies directed to the active site of TRAP prevent the enzyme carrying out its normal catalytic role. This triggers a decrease in bone resorption.35
(3) TRAP “knockout” mice, which do not carry the gene for synthesising TRAP, develop mild osteopetrosis (excessive bone growth) when the balance in bone remodelling is allowed to tilt towards osteoblast activity.36
(4) TRAP occurs in much higher concentrations in the serum of people with skeletal disease than in normal control subject.37–39
Furthermore, it increases with the rate of resorption taking place.40
There is a direct relation between excessive osteoclast facilitated bone resorption and the arrival of increased amounts of TRAP in the circulation. Therefore, serum TRAP has been indicated as a disease associated marker for the clinical diagnosis of excessive bone resorption and for quantitatively monitoring the rate and progression of metabolic bone disorders.33,41
“Hormones—for example, oestrogen and parathyroid hormone—undoubtedly influence the consequent resorption activity of osteoclasts”
Measuring the amounts of specific enzymes in the serum has for a long time provided a bedrock for the diagnosis of many commonly encountered clinical conditions. For example, PAP has been used to diagnose cancer of the prostate. Alanine aminotransferase and aspartate aminotransferase are released into the serum from the liver and provide a signal that hepatic cells have been damaged or ruptured. Isotypes of creatine kinase and lactate dehydrogenase are liberated from cardiac cells as a result of cell damage during myocardial infarction. Likewise, TRAP has the potential to be regarded as a diagnostic enzyme and thereby provide valuable information in the routine investigation of pathological bone resorption.
TRAP seeps into the serum after being released from osteoclasts that are actively resorbing bone tissue. The osteoclasts retain their cellular integrity as the enzyme is continually released. Therefore, its raised concentration in the plasma during episodes of pathological bone resorption is not the result of its liberation from damaged cells, as is the case with aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and creatine kinase, as previously mentioned. To trace the route by which TRAP passes before its arrival in the serum, and to unravel the physiological role of TRAP, it is important to appreciate current opinions on how osteoclasts go about resorbing bone tissue.