Diagnosis of osteoporosis in osteoarthritis

Improvement in recent years of specific and sensitive biochemical markers, reflecting the overall rate of bone formation and resorption, significantly improved the noninvasive assessment of bone metabolism in various metabolic bone diseases. As is known, biochemical markers are divided into markers of bone formation and bone resorption.

The most promising markers of bone resorption include pyridinoline (Pir) and deoxypyridinoline (D-Pyr) , two indivisible pyridine compounds formed as a result of post-translational modification of collagen molecules present in native collagen and not participating in its resynthesis. In rheumatic joint diseases, these markers are considered as sensitive and specific laboratory indicators not only of bone resorption, but also of joint destruction. Thus, according to experimental data, in rats with adjuvant arthritis, an increase in urinary excretion of pyridinoline is observed within the first 2 weeks after the induction of the disease, which correlates with the clinical signs of inflammation. The level of deoxypyridinoline in the urine rises later and is more closely associated with a decrease in bone mineral density. It is noteworthy that the introduction of collagenase inhibitors is associated with a decrease in the excretion of pyridinoline and deoxypyridinoline.

The levels of pyridinoline and deoxypyridinoline in urine are significantly higher in children than in adults; characterized by an increase of 50-100% during menopause. In patients with osteoporosis, their concentrations in the urine (especially deoxypyridinoline) correlate with the rate of bone metabolism measured by the kinetics of calcium and the histomorphometry of bone tissue.

In patients with osteoarthrosis, the increase in urinary excretion of pyridinoline and deoxypyridinoline is less pronounced than in rheumatoid arthritis, and is weaker correlated with the severity of clinical manifestations. He noted the relationship between the severity of X-ray changes (Kellgren-Lawrence scale) and the levels of these markers.

Of the bone formation markers, mention should be made of osteocalcin. R. Emkey and co-authors (1996) found that intraarticular administration of corticosteroids leads to a significant decrease in the concentration of osteocalcin in the blood the day after the injection, followed by normalization for 2 weeks (the clinical effect persists for 4 weeks), with significant changes in concentration pyridinoline in urine was not observed. These results suggest that intraarticular administration of corticosteroids causes only transient inhibition of bone formation and does not affect the resorption process.

The determination of laboratory markers of bone metabolism increases the effectiveness of instrumental risk assessment for the development of osteoporosis (primarily densitometric methods). Repeated measurements of bone markers during treatment can improve the quality of monitoring of patients with osteoporosis.

Practical recommendations on the use of biochemical markers of bone metabolism for diagnosis of osteopenic conditions:

• Serum osteocalcin and bone isoenzyme of alkaline phosphatase are currently the most sensitive markers of bone formation in osteoporosis.
• The most sensitive markers of bone resorption are urinary excretion of pyridinoline compounds and terminal fragments of type I collagen by immunoassay or high-pressure liquid chromatography.
• Before the conclusion about the clinical significance of the laboratory markers of bone metabolism being studied, a thorough evaluation of each clinical situation and the peculiarities of the therapy should be made.
• An increased level of bone metabolism is associated with a high rate of bone loss. Laboratory markers of bone formation and / or resorption can help to identify among patients with osteoarthritis individuals with baseline normal bone mass who have an increased risk of osteopenia (especially in the early stages of the disease).
• Elevated levels of markers of bone resorption are associated with an increased risk of vertebral and femoral fractures, regardless of bone mass. Thus, a combined assessment of bone mass and bone metabolism markers is useful for selecting "targets" for the treatment of patients with osteoarthritis with the highest risk of fractures (taking into account other risk factors).
• Bone markers are useful for assessing the effectiveness of antiresorptive therapy for rapid (3-6 months) screening of patients who do not respond to treatment, since the effect of therapy on bone metabolism is detected earlier than changes in bone mass detected by densitometry.

The main drawback of currently used laboratory techniques is that they reflect only the state of bone tissue metabolism at the time of the study, without giving immediate information about the quantitative parameters of the bone tissue state (that is, on the basis of using only laboratory indicators it is impossible to establish a diagnosis of osteoporosis or osteopenia). It should also be noted that, in contrast to certain metabolic bone diseases (Paget's disease, renal osteodystrophy), which are characterized by a significant change in bone metabolism, in osteoporosis with osteoarthritis, often minor changes in bone remodeling over a prolonged period can lead to a significant loss of bone mass. This may explain the fact that the data obtained with standard markers (activity of total alkaline phosphatase, hydroxyproline level, etc.) in patients with osteoporosis are within normal limits in most time intervals. Therefore, it is necessary to develop more specific and sensitive markers of bone metabolism. Thus, the requirements for an ideal marker of bone resorption are as follows: it must be a degradation product of bone matrix components that is not found in other tissues, is not absorbed by the body during the new bone formation, and is also not influenced by endocrine factors when determining its level in the blood.

[1], [2], [3], [4], [5], [6], [7], [8]