Calcitriol Suppression of Parathyroid Hormone Fails to Improve Skeletal Properties in an Animal Model of Chronic Kidney Disease

Abstract

Background: Chronic kidney disease (CKD) leads to complex metabolic changes and an increased risk of fracture. Currently, calcitriol is the standard of care as it effectively suppresses parathyroid hormone (PTH) levels in CKD patients. While calcitriol and its analogs improve BMD and reduce fractures in the general population, the extension of these benefits to patients with advanced kidney disease is unclear. Here, the impact of calcitriol on the skeleton was examined in the setting of reduction in PTH. Methods: Male Cy/+ rats, a PKD-like CKD model, were treated with either vehicle or calcitriol for 5 weeks. Their normal littermates served as controls. Animals were assessed for changes in mineral metabolism and skeletal parameters (microCT, histology, whole bone mechanics and bone quality). Results: PTH levels were significantly higher (12-fold) in animals with CKD compared to normal controls. CKD animals also exhibited negative changes in bone structural and mechanical properties. Calcitriol treatment resulted in a 60% suppression of PTH levels in animals with CKD. Despite these changes, it had no impact on bone volume (cortical or cancellous), bone turnover, osteoclast number or whole bone mechanical properties. Conclusions: These data indicate that while calcitriol effectively lowered PTH in rats with CKD, it did little to prevent the negative effects of secondary hyperparathyroidism on the skeleton.

Vitamin K and D Supplementation and Bone Health in Chronic Kidney Disease—Apart or Together?

“…Newman et al [ 152 ] used a rat model of progressive CKD (Cy/+), which is characterized by autosomal dominant cystic disease. Starting at 25 weeks of age, Cy/+ male rats were treated with 10 ng/kg BW of calcitriol, intraperitoneally, 3× weekly for 5 weeks.…”

“…Summarizing, the recently performed studies showed that the treatment of CKD animals with 1,25D may not improve bone quality [ 152 ], or even can be associated with mineralization defects [ 153 , 154 ]. These observations are consistent with the results of studies performed on non-CKD animals [ 155 , 156 , 157 ], which reported that treatment with calcitriol led to growth plate defects, an accumulation of osteoid and prolongation of mineralization lag time, reduction of cortical thickness, and suppression of bone matrix mineralization.…”

N-acetylcysteine (NAC), an anti-oxidant, does not improve bone mechanical properties in a rat model of progressive chronic kidney disease-mineral bone disorder

“…Structural mechanical properties of the left femur were determined by four-point bending as previously described [35]. The anterior surface was placed on two lower supports located ±9 mm from the mid-diaphysis (18 mm span length) with an upper span length of 6 mm.…”

Renal Osteodystrophy in End Stage Renal Disease Patients in a Center in South East of Iran: A Cross-Sectional Study

“…Serum calcium, phosphorus, albumin, creatinine, alkaline phosphatase, parathyroid hormone, blood sugar, vitamin D, hemoglobin, ferritin and ESR were measured in each patient [28][29][30][31].…”