Effect of denosumab, a human monoclonal antibody of receptor activator of nuclear factor kappa-B ligand (RANKL), upon glycemic and metabolic parameters

Abstract

Osteoporosis is a complication of type 2 diabetes mellitus (T2DM). Blockade of receptor activator of nuclear factor kappa-B ligand (RANKL) improves osteoporosis, but might also improve glucose tolerance through reduction of hepatic insulin resistance. However, the effect of denosumab (a human monoclonal antibody of RANKL) upon glycemic and metabolic parameters is controversial. We revealed the effect of denosumab upon glycemic and metabolic parameters for 52 weeks. We evaluated 20 individuals diagnosed with both osteoporosis (male and female: postmenopausal) and T2DM. We measured glycemic and metabolic parameters before and 26/52 weeks after administration of denosumab (60 mg per 26 weeks) without changing any other medication each patient was taking. All patients completed the study without complications and the T-score (lumbar spine and femoral neck) improved significantly from baseline to 52 weeks after denosumab administration (P < .001, .001, respectively). None of the glycemic parameters changed significantly from baseline to 26 weeks after denosumab administration, but levels of glycated hemoglobin and homeostasis model assessment of insulin resistance improved significantly from baseline to 52 weeks after administration (P = .019, .008, respectively). The levels of liver enzymes did not change significantly from baseline to 26 weeks after denosumab administration, but levels of aspartate transaminase and alanine aminotransferase improved significantly from baseline to 52 weeks after administration (P = .014, .004, respectively). None of the markers of lipid metabolism and body mass index changed significantly from baseline to 26/52 weeks after denosumab administration. These data demonstrated that denosumab is useful for T2DM patients with osteoporosis for glycemic control via improvement of insulin resistance. Also, the effect of denosumab might be due to improvement of hepatic function.

Effect of Denosumab on Glucose Homeostasis in Postmenopausal Women with Breast Cancer Treated with Aromatase Inhibitors: A Pilot Study

“…Schwartz et al [ 28 ] did not detect any significant effect of Dmab on metabolic parameters of osteoporotic women enrolled in the FREEDOM study, while in a further post hoc analysis of the same trial, Napoli et al [ 29 ] found that treatment with Dmab was associated with a reduction of FPG in drug-free diabetic women. More recently, Abe et al [ 30 ] reported a positive effect of one-year Dmab treatment on insulin resistance and HbA1c in a cohort of osteoporotic patients affected by T2DM. These observations suggest that RANKL blockade may be clinically relevant in the presence of abnormalities of glucose homeostasis, as suggested by previous animal and clinical studies [ 45 ].…”

“…Nonetheless, in a further post hoc analysis considering diabetic patients [ 29 ], treatment with Dmab was associated with a significant reduction in FPG in antihyperglicemic drug-free diabetic women. Abe et al [ 30 ] recently reported a reduction of HbA1c levels in a cohort of osteoporotic patients with T2DM after one year of Dmab treatment, strengthening the hypothesis that the impact of RANKL blockade may be more relevant in presence of overt abnormalities of glucose homeostasis.…”

Denosumab improves glucose parameters in patients with impaired glucose tolerance: a systematic review and meta-analysis

“…However, multiple studies, randomized controlled trials and observational studies, have assessed the effect of Denosumab on insulin sensitivity and FPG with contradictory results. In a few studies, the authors demonstrate a beneficial effect, in which Denosumab decreased FPG [4,19]; however, Schwartz et al demonstrate that Denosumab clearly increased FPG [20]. To address this conflict, a systematic review was conducted, aimed to evaluate the effects of Denosumab on different glycemic parameters.…”

Diabetes mellitus and osteoporosis: pathogenetic relationship and current principles of treatment

“…M. Rubin et al собираются определить, как применение антител к RANKL в течение 1 года повлияет на МПК, микроархитектонику, качество костного матрикса и количество AGEs в его составе [24]. Некоторые исследователи также отмечают положительное влияние деносумаба на гликемический контроль у пациентов с СД 2-го типа и ОП [25,26]. Точные механизмы этого эффекта пока не выяснены, но предполагается, что антитела к RANKL способны снижать печеночную инсулинорезистентность [26].…”

“…Некоторые исследователи также отмечают положительное влияние деносумаба на гликемический контроль у пациентов с СД 2-го типа и ОП [25,26]. Точные механизмы этого эффекта пока не выяснены, но предполагается, что антитела к RANKL способны снижать печеночную инсулинорезистентность [26]. Влияние деносумаба на гликемию и другие метаболические параметры у пациентов с СД 2-го типа на сегодняшний день остаются спорным вопросом, который требует проведения дальнейших исследований.…”