title: Effects of denosumab on fracture and bone mineral density by level of kidney function.
abstract: The incidences of osteoporosis and chronic kidney disease (CKD) both increase with increasing age, yet there is a paucity of data on treatments for osteoporosis in the setting of impaired kidney function. We examined the efficacy and safety of denosumab (DMAb) among subjects participating in the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) Study. We estimated creatinine clearance (eGFR) using Cockcroft-Gault and classified levels of kidney function using the modified National Kidney Foundation classification of CKD. We examined incident fracture rates; changes in bone mineral density (BMD), serum calcium, and creatinine; and the incidence of adverse events after 36 months of follow-up in subjects receiving DMAb or placebo, stratified by level of kidney function. We used a subgroup interaction term to determine if there were differences in treatment effect by eGFR. Most (93%) women were white, and the mean age was 72.3 ± 5.2 years; 73 women had an eGFR of 15 to 29 mL/min; 2817, between 30 to 59 mL/min; 4069, between 60 to 89 mL/min, and 842 had an eGFR of 90 mL/min or greater. None had stage 5 CKD. Fracture risk reduction and changes in BMD at all sites were in favor of DMAb. The test for treatment by subgroup interaction was not statistically significant, indicating that treatment efficacy did not differ by kidney function. Changes in creatinine and calcium and the incidence of adverse events were similar between groups and did not differ by level of kidney function. It is concluded that DMAb is effective at reducing fracture risk and is not associated with an increase in adverse events among patients with impaired kidney function.
authors.affiliation: Department of Medicine, University of Toronto, Ontario, Canada. sophie.jamal@utoronto.ca
authors.forename: Sophie A
authors.initials: SA
authors.lastname: Jamal
authors.forename: Osten
authors.initials: O
authors.lastname: Ljunggren
authors.forename: Catherine
authors.initials: C
authors.lastname: Stehman-Breen
authors.forename: Steven Ron
authors.initials: SR
authors.lastname: Cummings
authors.forename: Michael R
authors.initials: MR
authors.lastname: McClung
authors.forename: Stefan
authors.initials: S
authors.lastname: Goemaere
authors.forename: Peter R
authors.initials: PR
authors.lastname: Ebeling
authors.forename: Edward
authors.initials: E
authors.lastname: Franek
authors.forename: Yu-Ching
authors.initials: YC
authors.lastname: Yang
authors.forename: Ogo I
authors.initials: OI
authors.lastname: Egbuna
authors.forename: Steven
authors.initials: S
authors.lastname: Boonen
authors.forename: Paul D
authors.initials: PD
authors.lastname: Miller
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015519:Bone Density / Q000187:drug effects / Q000502:physiology*; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood; D000069448:Denosumab; D005260:Female; D050723:Fractures, Bone / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D005919:Glomerular Filtration Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000503:physiopathology; D007677:Kidney Function Tests; D008875:Middle Aged; D016017:Odds Ratio; D010919:Placebos; D053245:RANK Ligand / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D010919:Placebos; D053245:RANK Ligand; D000069448:Denosumab; D003404:Creatinine