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

Christopher L. Newman, Nannan Tian, Max A. Hammond, Joseph M. Wallace, Drew M. Brown, Xuening (Neal) Chen, Sharon Moe, Matthew Allen

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)20-31
Number of pages12
JournalAmerican Journal of Nephrology
DOIs
StateAccepted/In press - Feb 17 2016

Fingerprint

Calcitriol
Parathyroid Hormone
Chronic Renal Insufficiency
Animal Models
Bone and Bones
Skeleton
X-Ray Microtomography
Secondary Hyperparathyroidism
Bone Remodeling
Kidney Diseases
Osteoclasts
Standard of Care
Mechanics
Minerals
Histology
Population

Keywords

  • Animal models
  • Bone disease
  • Calcitriol#
  • Chronic kidney disease
  • Treatment

ASJC Scopus subject areas

  • Nephrology

Cite this

Calcitriol Suppression of Parathyroid Hormone Fails to Improve Skeletal Properties in an Animal Model of Chronic Kidney Disease. / Newman, Christopher L.; Tian, Nannan; Hammond, Max A.; Wallace, Joseph M.; Brown, Drew M.; Chen, Xuening (Neal); Moe, Sharon; Allen, Matthew.

In: American Journal of Nephrology, 17.02.2016, p. 20-31.

Research output: Contribution to journalArticle

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