Changing bone patterns with progression of chronic kidney disease

Abstract

It is commonly held that osteitis fibrosa and mixed uremic osteodystrophy are the predominant forms of renal osteodystrophy in patients with chronic kidney disease. Osteitis fibrosa is a high-turnover bone disease resulting mainly from secondary hyperparathyroidism, and mixed uremic osteodystrophy is in addition characterized by a mineralization defect most often attributed to vitamin D deficiency. However, there is ancient and more recent evidence that in early chronic kidney disease stages adynamic bone disease characterized by low bone turnover occurs first, at least in a significant proportion of patients. This could be due to the initial predominance of bone turnover-inhibitory conditions such as resistance to the action of parathyroid hormone (PTH), reduced calcitriol levels, sex hormone deficiency, diabetes, and, last but not least, uremic toxins leading to repression of osteocyte Wnt/β-catenin signaling and increased expression of Wnt antagonists such as sclerostin, Dickkopf-1, and sFRP4. The development of high-turnover bone disease would occur only later on, when serum PTH levels are able to overcome peripheral PTH resistance and the other inhibitory factors of bone formation. Whether FGF23 and Klotho play a direct role in the transition from low- to high-turnover bone disease or participate only indirectly via regulating PTH secretion remains to be seen.

Fractures in patients with CKD—diagnosis, treatment, and prevention: a review by members of the European Calcified Tissue Society and the European Renal Association of Nephrology Dialysis and Transplantation

“…Recent studies showed changes from low to high bone turnover during CKD progression. 50 Unfortunately, we lack evidence of an association between fracture incidence and the histologic type of bone disease. Despite definitive proof, low or high bone turnover favors fractures as both increase bone fragility.…”

The Calcium/Phosphorus Homeostasis in Chronic Kidney Disease: From Clinical Epidemiology to Pathophysiology

“…19,20 There is evidence that this is associated with low levels of [25OHD] S , 21,22 impairment in the renal production of [1,25(…”

A patient with MEN1 and end‑stage chronic kidney disease due to Alport syndrome: Decision making on the eligibility of transplantation

“…Therefore an additional parathyroidectomy was not taken into consideration. In addition, post-surgical hypoparathyroidism usually worsens the adynamic bone state typical of uremic patients (11) and requires a strict adherence to medications to avoid hypocalcemia. We foresaw that a possible further rise in serum calcium would require a medical treatment in order to defer parathyroidectomy as long as possible.…”