*4.1.1 Biochemical abnormalities in CKD-MBD*

The biochemical abnormalities in CKD-MBD represent the laboratory aspect of the disorder. These include calcium level (ionized or total), phosphate level, PTH, alkaline phosphatase (total or bone specific), and VD status (25VD). Other indicators, such as 1,25VD and FGF-23 are not measured routinely. The earliest changes occur in PTH and VD metabolites—the abnormal values for PTH, 25VD and 1,25VD are detected in eGFR<60 ml/min/1.73 m2 , whereas abnormal calcium and phosphate levels are detected in eGFR below 40 and remain stable until eGFR<20 ml/min/1.73 m2 [18].

According to the current guidelines, testing for calcium, phosphate, PTH, and alkaline phosphatase should be initiated in eGFR<60 ml/min/1.73 m<sup>2</sup> ; the frequency of laboratory evaluation should be based on the rate of CKD progression, the magnitude of abnormalities, and the evaluation of treatment's effectivity. Similarly, 25VD should be tested in patients with eGFR<60 ml/min/1.73 m<sup>2</sup> and frequency of testing depends on baseline values and therapeutic interventions [17]. The timing and frequency suggested by Kidney Disease: Improving Global Outcomes (KDIGO) are summarized in **Table 2**.

## *4.1.2 Bone disorders in CKD-MBD*

Bone involvement in CKD [renal osteodystrophy (ROD)] is of pivotal importance, as it is associated with bone fractures (asymptomatic or symptomatic), bleeding, chronic disability, poorer life quality, and higher mortality in renal disease. In children with CKD, it leads to growth retardation and skeletal deformities [17].

Several types of bone histological changes can be detected in CKD, according to three major histological indicators: turnover, mineralization, and volume. Bone turnover (T) is a parameter, corresponding to bone formation rate. It can be abnormally low, normal, or very high and is best assessed via bone biopsy and tetracycline

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[17, 20].

*Vitamin D Deficiency in Renal Disease DOI: http://dx.doi.org/10.5772/intechopen.88928*

*CKD, chronic kidney disease; PTH, parathyroid hormone.*

**Table 2.**

low, normal, and high bone volume.

ROD categories are recognized [19]:

labeling. Mineralization (M) is the second parameter. Normally, the osteoblasts lay down new collagen and direct mineralization of the matrix. This process is impaired in CKD, leading to thickened osteoid. Mineralization is measured by osteoid maturation time and mineralization lag time. The osteoid maturation time is the osteoid width divided by the distance between labels per day. The mineralization lag time is the osteoid maturation time adjusted for the percentage of osteoid surface that has a tetracycline label. Mineralization is classified as normal and abnormal. Bone volume (V) sums up bone formation and resorption rates. It is generally accepted that bone volume is expressed as bone volume per tissue volume and is classified as

**Indicator CKD stage 3 CKD stage 4 CKD stage 5 and on dialysis** 

Calcium and phosphorus 6–12 months 3–6 months 1–3 months PTH and alkaline phosphatase Baseline 6–12 months 3–6 months 25-Hydroxyvitamin D Baseline Baseline Baseline

*Suggested testing for biochemical indicators of CKD-MBD according to CKD stage.*

**(CKD 5D)**

According to the TMV classification of bone histology in CKD, the following

1.Adynamic bone disease (AD)—low-turnover bone disease with normal mineralization. Volume can be low, but in some patients with normal mineralization and low turnover, it will be normal. AD is usually associated with PTH over-

2.Mild secondary hyperparathyroidism related bone disease (MHPTBD)—medi-

3.Osteitis fibrosa (OF)—represents a more advanced form of high-turnover disease, compared to MHPT, any bone volume and normal mineralization

4.Osteomalacia (OM)—low-turnover bone with abnormal mineralization. The bone volume may be low to medium, depending on the severity and duration

5.Mixed uremic osteodystrophy (MUO)—represents features of the above mentioned variants; for example, a combination of high-turnover, normal bone

. The current KDIGO guidelines

In addition, age related/postmenopausal osteoporosis can be detected. Measurement of bone mineral density [by using dual-energy X-ray absorptiometry (DXA)] is most informative in CKD stages 1–2; in these cases, low BMD is associated with osteoporosis and treatment is performed as in the general population. Patients with low BMD and CKD stages 3–5 are designated as having CKD-MBD with low BMD. Recent reports demonstrate that BMD testing can

broaden the indications for BMD testing in CKD stages 3–5D to assess fracture risk, if it will have effect on treatment. Finally, normal histology is also possible

um-to high bone turnover, any bone volume, normal mineralization

suppression, including overdose of VD analogs or calcitriol

of the process and other factors that affect bone health

volume, with abnormal mineralization

predict fracture risk in eGFR<60 ml/min/1.73 m<sup>2</sup>
