Denosumab Inhibition of RANKL and Insulin Resistance in Postmenopausal Women with Osteoporosis.
The tumor necrosis factor-related cytokine receptor activator of nuclear factor kappa B ligand (RANKL) has been proposed as predictor of incident type 2 diabetes mellitus, and experimental blockade of RANKL resulted in a marked improvement of glucose tolerance. Denosumab is a fully human monoclonal antibody that binds to RANKL and prevents osteoclast formation, function and survival, leading to fracture risk reduction. The aim of our study was to investigate glucometabolic parameters, insulin resistance, and lipid profile in non-diabetic women receiving denosumab. Forty-eight women with postmenopausal osteoporosis were enrolled and treated with a subcutaneous dose (60 mg) of denosumab. At baseline and after 4, 12, ad 24 weeks, insulin resistance was computed by homeostasis model assessment of insulin resistance (HOMA-IR) and total cholesterol, triglycerides and HDL cholesterol were also measured. At baseline and after 24 weeks, bone turn-over markers were also evaluated. After denosumab administration, with the exception of a slight reduction of insulin and HOMA-IR values after 4 weeks (p < 0.05), neither fasting plasma glucose nor insulin and insulin resistance were significantly changed. Lipid parameters remained unchanged at each time-points of this study. A reduction of C-telopeptide of type 1 collagen (-63%, p < 0.0001) and osteocalcin (-45%, p < 0.0001), as bone resorption and formation markers, respectively, were observed after 24 weeks. Baseline levels of bone biomarkers were not predictive of HOMA-IR, and changes of osteocalcin were not associated to markers of glucose control. In osteoporotic otherwise healthy postmenopausal women, denosumab was not associated with relevant modification of insulin resistance and lipid profile.
Department of Clinical and Experimental Medicine, University Hospital of Messina, A.O.U. Policlinico "G. Martino", Via C. Valeria, 98125, Messina, Italy.
Antonino
A
Lasco
Department of Clinical and Experimental Medicine, University Hospital of Messina, A.O.U. Policlinico "G. Martino", Via C. Valeria, 98125, Messina, Italy.
Nunziata
N
Morabito
Department of Clinical and Experimental Medicine, University Hospital of Messina, A.O.U. Policlinico "G. Martino", Via C. Valeria, 98125, Messina, Italy.
Giorgio
G
Basile
Department of Clinical and Experimental Medicine, University Hospital of Messina, A.O.U. Policlinico "G. Martino", Via C. Valeria, 98125, Messina, Italy.
Marco
M
Atteritano
Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.
Agostino
A
Gaudio
Services Department, University Hospital Messina, Messina, Italy.
Grazia Maria
GM
Giorgianni
Department of Clinical and Experimental Medicine, University Hospital of Messina, A.O.U. Policlinico "G. Martino", Via C. Valeria, 98125, Messina, Italy.
Elisabetta
E
Morini
Department of Clinical and Experimental Medicine, University Hospital of Messina, A.O.U. Policlinico "G. Martino", Via C. Valeria, 98125, Messina, Italy.
Bianca
B
Faraci
Department of Clinical and Experimental Medicine, University Hospital of Messina, A.O.U. Policlinico "G. Martino", Via C. Valeria, 98125, Messina, Italy.
Federica
F
Bellone
Department of Clinical and Experimental Medicine, University Hospital of Messina, A.O.U. Policlinico "G. Martino", Via C. Valeria, 98125, Messina, Italy. catalanoa@unime.it.
Antonino
A
Catalano
D000368:Aged; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D000069448:Denosumab / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000453:epidemiology; D053245:RANK Ligand / Q000037:antagonists & inhibitors*
D050071:Bone Density Conservation Agents; D008055:Lipids; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D000069448:Denosumab
Denosumab; Glucose; HOMA-IR; Insulin; Osteoporosis; Postmenopausal