Osteoporosis is diagnosed based on an assessment of bone density. However, the results only provide a past history rather than a snapshot of what is happening today. It is much like a house remodeling project. You can't judge what activity is going to happen on the job site today by looking at the building. You can only measure progress in the work completed so far.
The bone cells—osteoclasts and osteoblasts—are constantly remodeling bone. The speed of their activity is called bone turnover. To see how fast or slow they are working, markers of bone turnover can be measured in the urine or blood. There are bone turnover markers that measure osteoclast function (bone breakdown) and different markers that measure osteoblasts function (bone formation).
Bone turnover markers do not establish a diagnosis; rather, they reflect the activity of bone remodeling. High marker levels predict bone loss and fracture risk. A high level of a turnover marker indicates a risk of fracture similar to that of a bone density score in the osteoporosis range (T-score lower than -2.5). Therapies that slow down bone breakdown make these marker levels decrease. Medicines that stimulate bone formation do the opposite.
Low bone density in the hip and high levels of markers of bone breakdown together are more predictive of fracture than either measure alone. Bone markers used in combination with bone density may be helpful to provide an overall picture of your bone health status. For example, at the menopausal transition and into early menopause, bone loss is accelerated with the loss of estrogen. Markers may be useful in the prediction of bone loss at menopause and may help in making a decision about whether to take preventive medicines or not.
However, these markers have not been used widely. They are more likely to be checked if you see a specialist. Most of the time, the reason you are seeing a specialist is for an in-depth investigation of your bone status. High levels of these markers indicate that additional assessment is needed to find any underlying causes of the high bone turnover.
Some doctors are promoting the use of bone turnover markers for assessing the risk of side effects from certain medicines used to treat osteoporosis. However, there is no convincing data showing a link between levels of bone turnover and occurrence of side effects. For instance, in the case of jaw problems related to the use of some bone medicines, individuals who develop the problem may not have extremely low bone turnover or so-called oversuppression.
Markers may be helpful in monitoring therapy. In contrast to waiting two years to get a follow-up bone density scan or, if indicated, one year, the differences in markers are almost immediate. For most medicines, the markers show the maximal level of effect from the prescribed treatment within three months of beginning treatment. For someone who may be at risk for fast bone loss, such as with high-dose steroid therapy, markers may help in evaluating the effect of osteoporosis medicines in counteracting the bone loss much sooner than a follow-up bone density scan. The failure of bone marker values to respond appropriately means that further evaluation is needed to find out if the medicine is not working and, if it is not working, why.
After long-term treatment with bisphosphonate medicines like Fosamax®, sometimes treatment is temporarily stopped. Bone turnover continues to be decreased for some years after stopping the medicine with a slow increase of markers. Therefore, the markers may help decide when to restart therapy. Once the bone turnover markers increase toward a pretreatment level, therapy should be restarted, if indicated.
MARKERS OF BONE BREAKDOWN
Bone tissue resembles reinforced concrete. The osteoclasts drill a hole into the hard concrete tissue, which is a hard bone matrix that is made up of inflexible calcium and phosphate minerals. It is reinforced by flexible fibers of collagen, a protein substance that plays a role similar to steel rebar. Fragments of collagen are released during bone breakdown.
The markers of bone breakdown measure parts of these collagen fragments in the urine or blood. The tests that your doctor might order include N-telopeptide (NTx), C-telopeptide (CTx), or deoxypyridinoline (DPD). You may be asked to collect a urine specimen in the morning the second time you urinate while still fasting. This urine sample gives a snapshot of the bone turnover during the time of highest activity. The analysis can also be done on a full day's collection of urine (twenty-four-hour urine) or a blood sample.
MARKERS OF BONE FORMATION
Bone is formed by the osteoblasts. The bone formation markers are the direct or indirect products of this type of bone cell. Some of these products are enzymes or other proteins that are secreted by osteoblasts. Others are byproducts of new collagen being deposited. All bone formation markers are measured from a blood sample. The ones most commonly measured are bone-specific alkaline phosphatase (BSAP), osteocalcin, and procollagen type 1 propeptides, referred to as P1NP.
Alkaline phosphatase is an enzyme that originates in other tissues in addition to bone. About half of total alkaline phosphatase is from the bone and the other half is produced by the liver. Measurement of alkaline phosphatase is part of your liver function tests on routine laboratory chemistries. A separate analysis called bone-specific alkaline phosphatase differentiates the bone-origin enzyme from the liver-origin enzyme.
Osteocalcin is a small protein synthesized by osteoblasts. Osteocalcin correlates with bone formation. However, the exact function of osteocalcin in bone is unknown.
P1NP is a measure of newly formed collagen in the bone. P1NP is a sensitive marker of bone formation rate. This test is the bone formation marker of choice when evaluating response to treatment.
Bone remodeling activity does not occur at the same rate throughout the day or from day to day. The workers need some down time. Levels of bone turnover markers are highest in the early morning and lowest in the afternoon and evening. Levels of urinary markers can vary 20 to 30 percent from the highest to the lowest values of the day. The challenge to checking these markers is the inherent biologic variability of activity of the osteoclasts and osteoblasts. The markers of bone formation appear to vary less from day to day than they do during any one day.
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The Bare Bones
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