HOUSTON – Intravenous pamidronate for management of bone hyperresorption in ventilator-dependent patients doesn’t adversely affect renal function, even in those with chronic kidney disease, according to a single-center retrospective study.
"This stands in contrast to prevailing concerns about bisphosphonate therapy to manage bone hyperresorption in chronically critically ill patients, many of whom have chronic kidney disease," Dr. Rifka C. Schulman reported at the annual meeting of the Endocrine Society.
"It is hoped that these results will remove barriers to more aggressive management of metabolic bone disease in chronic critical illness, which may have salutary downstream effects on morbidity and mortality," declared Dr. Schulman of the Mount Sinai School of Medicine in New York.
She presented a retrospective observational study of 315 patients admitted to the Mount Sinai Hospital respiratory care unit with ventilator-dependent chronic critical illness after surviving a bout of acute critical illness. In all, 115 received 30-90 mg of intravenous pamidronate (Aredia) infused over 4 hours, with dosing based on body weight. The other 200 patients did not receive pamidronate. All participants got calcitriol, calcium carbonate, and ergocalciferol to help protect their bones.
The study population consisted of 204 patients with either no or stage 1-2 chronic kidney disease, 41 with stage 3 CKD, 33 with stage 4 disease, and 37 with stage 5 CKD who were on hemodialysis.
The primary study end points were change in glomerular filtration rate and creatinine level following pamidronate administration. Importantly, none of the pamidronate-treated patients showed a 25% or greater reduction in GFR immediately after or at 7 or 14 days post infusion, regardless of their CKD status or dose received.
The group with no or only mild CKD showed no change in median GFR between baseline and day 7 post infusion. Those with stage 3 CKD had a median 4% drop in GFR. So did those with stage 4 disease. Patients with stage 5 CKD had a median 9% reduction in GFR on day 7. Among controls, those with stage 0-3 CKD had no change in median GFR, while those with stage 4 or stage 5 disease averaged a 6% increase in GFR during 7 days. These small fluctuations in renal function aren’t clinically meaningful, according to Dr. Schulman.
Creatinine levels rose between baseline and day 7 in lockstep with CKD status, but to the same extent in pamidronate-treated patients and controls. For example, creatinine climbed by 6.7% and 18.2%, respectively, in pamidronate-treated patients with stage 4 and stage 5 CKD, and by 8.8% and 20.8% in stage 4 and 5 controls.
She observed that metabolic bone disease involving bone hyperresorption with elevated levels of the bone turnover biomarker N-telopeptide is present in more than 90% of patients with chronic critical illness. Contributing factors include immobilization, inflammation, neuroendocrine abnormalities, low vitamin D levels and secondary hyperparathyroidism, and the use of high-dose corticosteroids and other medications with an adverse impact on bone.
Bone loss during critical illness is challenging to reverse. It predisposes to osteoporosis, fractures, and poor quality of life in patients who recover from chronic critical illness. That’s why Dr. Schulman and her coinvestigators favor turning to pamidronate when patients have a 24-hour urine N-telopeptide of 70 nmol BCE/mmol creatinine or a serum level in excess of 40 nmol BCE/L.
The study was supported by a grant from Select Medical. Dr. Schulman reported having no financial conflicts.