An open-label, prospective pilot clinical study of denosumab for severe hyperparathyroidism in patients with low bone mass undergoing dialysis

J Clin Endocrinol Metab. 2014 Jul;99(7):2426-32. doi: 10.1210/jc.2014-1154. Epub 2014 Mar 26.

Abstract

Context: Denosumab is widely used for bone diseases with increased bone resorption. Its effectiveness in patients with severe secondary hyperparathyroidism on dialysis is unclear.

Objective: This study aimed to evaluate the efficacy and safety of denosumab in patients with severe secondary hyperparathyroidism who are on dialysis.

Design: This 6-month prospective, open-labeled study evaluated 12 patients (five women, seven men; mean age 53.5 ± 3.8 y). All had intact PTH (iPTH; > 1000 pg/mL), low bone mass (T-score < -1.0 SD), and bone pain and were poor surgical candidates. Serum calcium, phosphorus, alkaline phosphatase (AP), and iPTH levels were assessed at baseline and every month thereafter. Vertebral spine x-rays and bone mineral densities (BMDs) (lumbar spine and femoral neck) were assessed at the start and end of the study. All patients received denosumab (60 mg), calcitriol, phosphate binders, and dialysate calcium that were adjusted according to the biochemistry data.

Results: The BMD increased in both the femoral neck (mean increase 23.7% ± 4.0%) and lumbar spine (17.1% ± 2.6%) after 6 months. In the first month, most patients had increased iPTH levels, which dramatically decreased from 1702.1 ± 181.9 to 518.8 ± 126.8 pg/mL by the end of the study after increasing the calcitriol dose. All patients had significant decreases in AP, calcium × phosphorus, and bone pain. Changes in femoral neck BMD correlated only with AP and iPTH levels.

Conclusions: Denosumab is effective in restoring bone mass and reducing bone pain in patients on dialysis with secondary hyperparathyroidism. It also allows for a more aggressive use of calcitriol to control hyperparathyroidism.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Bone Density / drug effects
  • Bone Diseases, Metabolic / drug therapy*
  • Bone Diseases, Metabolic / etiology
  • Denosumab
  • Female
  • Femur Neck
  • Humans
  • Hyperparathyroidism, Secondary / drug therapy*
  • Hyperparathyroidism, Secondary / etiology
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / therapy*
  • Lumbar Vertebrae
  • Male
  • Middle Aged
  • Pain / drug therapy
  • Pain / etiology
  • Pilot Projects
  • Renal Dialysis* / adverse effects
  • Severity of Illness Index

Substances

  • Antibodies, Monoclonal, Humanized
  • Denosumab