Osteoporosis drugs including oral bisphosphonates show efficacy and safety in the treatment of bone loss in patients with chronic kidney disease (CKD) in several observational studies. However, caution is still urged, particularly with oral bisphosphonates, say the authors of the research, presented here at the American Society of Bone and Mineral Research (ASBMR) 2017 Annual Meeting.
“The take-home message…is that oral bisphosphonates seem to be safe and effective, at least in terms of bone-density improvement, in patients with chronic kidney disease,” coauthor Daniel Prieto-Alhambra, MD, an associate professor at the University of Oxford, in the United Kingdom, told Medscape Medical News.
But he advised that “these data are…observational, and we must replicate these analyses in external data before we can recommend any changes to existing clinical practice and/or recommendations.
“In the meantime, oral bisphosphonates continue to be contraindicated in patients with severe chronic kidney failure.”
Bone loss and resulting fractures are highly common in CKD, presenting a clinical challenge in terms of pharmacological treatment, particularly with oral bisphosphonates, which are eliminated through the kidneys and therefore are of concern in the setting of renal insufficiency.
However, evidence detailing drug effects is lacking because patients with severe CKD are often excluded from clinical trials.
In commenting on the research, Michael Econs, MD, a professor in the Indiana University School of Medicine, in Indianapolis, and incoming ASBMR president, said this work offers important insight to add to knowledge of osteoporosis drugs in CKD.
“The most notable finding…is that these drugs work in people with impaired kidney function,” he told Medscape Medical News.
Bisphosphonates Effective in CKD
In an effort to better understand the effects, Dr Prieto-Alhambra and his colleagues conducted several analyses looking at mortality, adverse events, and bone improvement among moderate- to severe-CKD patients treated with oral bisphosphonates.
In the first of three abstracts presented at the meeting, they evaluated the efficacy of bisphosphonate in patients with moderate or severe CKD [estimated glomerular filtration rate [eGFR] of <45 mL/min), looking at bone-mineral density (BMD) changes in a Danish population between 1999 and 2016. The study excluded patients who had previously used oral bisphosphonates
The review included data from a regional database of all DXA-based routine measurements in Funen, Denmark, in which the use of oral bisphosphonates in moderate to severe CKD was expectedly rare, with only 81 patients identified.
However, compared with 282 bisphosphonate nonusers, also with stage 3B CKD, the bisphosphonate users showed gains of an average of 0.59% total hip BMD per year, whereas the nonusers lost an average of 1.98% annually.
After adjustment for factors including age, sex, body mass index (BMI), baseline eGFR, fracture history, and other comorbidities, the mean difference was +1.81% and in the propensity score–adjusted analysis, the difference was +2.44 in favor of oral bisphosphonate use.
“The finding of an improved BMD is good news, as this suggests these drugs could be effective at improving bone strength,” Dr Prieto-Alhambra said.
The research team will also report on additional findings including rates of acute kidney injury (AKI), gastrointestinal events, and hypocalcemia, as well as all-cause mortality in patients in UK primary-care records with stage 3B or higher CKD (eGFR < 45) who were treated with oral bisphosphonates, compared with those who were not.
And another abstract to be presented at the meeting will detail the effects of the osteoporosis drug denosumab in patients with mild to moderate CKD. Unlike bisphosphonates, denosumab is not contraindicated in patients with severe CKD; however, research is nevertheless lacking on the drugs’ effects on renal insufficiency.
For that study, the researchers analyzed data on patients who were enrolled in the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every Six Months (FREEDOM) Extension study, which was the extension of the phase 3 FREEDOM trial, evaluating denosumab treatment for up to 10 years.
Patients included those who received long-term denosumab treatment for up to 10 years, as well as those in a crossover arm with up to 7 years of treatment.
Coauthor of this work, Paul D Miller, MD, a metabolic bone disease specialist with the Colorado Center for Bone Research at Panorama Orthopedics & Spine Center, in Golden, noted that an important limitation was the lack of patients with more serious CKD. “We did not study stage 4–5 CKD [GFR less than 30 or 15 mL/min], where hypocalcemia is more prevalent, though still rare.”
This story will be updated with the additional findings.
Dr Prieto-Alhambra’s studies were funded by National Institute for Health Research (NIHR) Health Technology Assessment, United Kingdom. His research group has received funding from Amgen, Servier, and UCB Pharma. Dr Econs is on the data safety and monitoring board for Amgen’s studies with denosumab and romozosomab.
American Society of Bone and Mineral Research 2017 Annual Meeting. September 8–11, 2017, Denver, Colorado. Abstract FR0242.
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