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Mineral bone disease (MBD) is best described as a syndrome that encompasses altered bone morphology and vascular calcification, as well as abnormalities in serum markers of bone activity. The older term of “renal osteodystrophy” specifically refers to pathological variants noted on bone biopsy in patients with chronic kidney disease (CKD); however, bone biopsies are rarely performed in a clinical setting and are used now primarily for research purposes. Typically, the incidence of MBD rises as CKD progresses to end-stage kidney disease (ESKD); however, the disease may not be clinically apparent until the patient is approaching imminent need for dialysis.

It appears that the inciting event in the development of secondary hyperparathyroidism (HPT) is phosphate retention, usually due to a combination of kidney disease (resulting in nephron loss) and high dietary phosphorus ingestion. In an effort to maintain phosphorus homeostasis, proximal tubule reabsorption of phosphorus drops, leading to increased phosphaturia. Rising serum phosphorus levels result in the following actions:

  1. Reduction in serum calcium

  2. Decreased calcitriol production via suppression of 1-alpha-hydroxylase

  3. Transformation of vascular smooth muscle cells to osteochondrogenic smooth muscle cells

  4. Increased fibroblast growth factor-23 (FGF-23), which leads to lowered calcitriol levels (also via suppression of 1-alpha-hydroxylase) and a negative feedback effect on PTH production

Increases in FGF-23 (a peptide) and loss of both alpha-Klotho (a protein cofactor in FGF-23 binding) and calcitriol are relatively early events in CKD, and often correlate with early and abnormal changes in bone morphometry. However, the beneficial effect of FGF-23 in stimulating phosphaturia and decreasing intestinal phosphorus absorption is counterbalanced by its inhibitory effect on calcitriol with resultant hypocalcemia and HPT. The net effect of persistent hypocalcemia is a negative influence on bone morphometry, and has been associated with cardiovascular mortality in patients with kidney disease. Probably not coincidentally, rising FGF-23 levels have also been correlated with mortality in CKD patients; the exact mechanism by which this occurs is incompletely understood. Hypercalcemia, which may be iatrogenic, has likewise been shown to contribute to both vascular and extraskeletal calcification. Changes in serum calcium, phosphorus, and parathyroid hormone (PTH) have implications for both the density and sensitivity of vitamin D receptors (VDRs) and calcium-sensing receptors (CaSRs). This may be one of the pathways by which serum biomarkers of bone activity also influence cardiovascular mortality.1

MBD in CKD is generally divided into three major categories:

  1. Osteitis fibrosa cystica, characterized by high bone turnover with increased PTH levels

  2. Adynamic bone disease, with low bone turnover and low PTH levels; incidence appears to be increasing in ESKD, likely due to increasing use of vitamin D analogues and calcimimetics

  3. Osteomalacia, characterized by low bone turnover and abnormal mineralization (less common with declining use of aluminum-based phosphate binders)

These three types of bone disease can coexist, and the presence of any raises the risk of bone fracture. Unfortunately, PTH and ...

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