Clinical effects of switching from minodronate to denosumab treatment in patients with postmenopausal osteoporosis: a retrospective study – BMC Blogs…

Postmenopausal osteoporosis is the most common bone disease. It is characterized by reduced bone mass and microscopic changes in the architecture resulting in impaired strength of bones, with consequent increased susceptibility to fracture, which results in high medical expenditures and substantial morbidity with a decrease in quality of life [1, 2]. The bone mineral density (BMD) reduces with age in the entire population, and women are particularly at higher risk since they rapidly lose bone in the peri- and post- menopausal periods [2]. Age, sex, family history, low baseline weight, weight loss, and alcohol use in women, and smoking in men are generally associated with low BMD [2]. Owing to an increasing life expectancy, the number of patients has been progressively increasing worldwide [3]. One of the most debilitating complications of osteoporosis is hip fracture, which has an estimated probability of 3.5% in men and 14.6% in women around the age of 50years old. Approximately 2050% patients with hip fracture suffer from a decreased quality of life, depression, loss of self-esteem, and social isolation, which leads to the drastic elevation of one-year mortality rate, up to 1460% [4,5,6,7]. Vertebral fractures are extremely common complications of osteoporosis and often asymptomatic. However, multiple vertebral thoracic fractures may induce restrictive lung disease and secondary heart problems. Lumbar fractures may cause gastrointestinal complaints, back pain (both, acute and chronic), depression, and positional restriction, resulting in increased mortality [7, 8]. In view of these numerous complications, the main objective of treating postmenopausal osteoporosis is the prevention of future fractures.

The two types of treatment options for osteoporosis include anti-resorptive and anabolic agents. Anti-resorptive drugs include bisphosphonates (e.g. alendronate, minodronate (MIN), etidronate, risedronate, pamidronate, and zoledronate), selective estrogen-receptor modulators (raloxifene and bazedoxifene), active vitamin D3 derivatives (alfacalcidol and eldecalcitol), a fully human monoclonal antibody to receptor activator of nuclear factor -B ligand (RANKL; denosumab), and thyroid hormone (calcitonin). Anabolic agents include parathyroid hormone (teriparatide), parathyroid-related peptide synthetic analogs (abaloparatide), and a sclerostin inhibitor (romosozumab) [9]. Among these treatment options, bisphosphonates are the most widely used all over the world. MIN is a third-generation bisphosphonate and the strongest inhibitor of bone resorption among the currently available oral bisphosphonates. In terms of bone resorption inhibition, MIN is 1000-fold more effective than etidronate and 10100-fold more effective than alendronate [10]. Large randomized, placebo-controlled, double-blind clinical trials revealed a significant increase in bone mineral density (BMD) of both, the lumbar spine and femoral neck over 3years of MIN therapy and a risk reduction in vertebral fractures in Japanese women with postmenopausal osteoporosis [11]. Therefore, MIN continues to be one of the most widely used bisphosphonates in Japan.

Denosumab is a fully human monoclonal anti-RANKL IgG2 antibody that inhibits the binding of RANKL to its receptor on osteoclasts, thereby decreasing the bone-resorption activity of mature osteoclasts [12]. In the phase 3 Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6Months (FREEDOM) trial, denosumab treatment significantly reduces the incidence of new vertebral, nonvertebral, and hip fractures compared with placebo treatment [13]. Furthermore, in the FREEDOM Extension trial, 10-year treatment with denosumab increases the BMD of patients progressively with a significantly lower incidence of fracture [14]. In Japan, denosumab is currently one of the first treatment options, as evidenced by the report that sales of denosumab exceed that of each bisphosphonate [15]. Lyu et al. performed a meta-analysis of 10 eligible trials including 5361 participants comparing denosumab and bisphosphonates [16]. Denosumab increases BMD more than bisphosphonates at the lumbar spine, total hip, and femoral neck. Furthermore, one study showed that denosumab has a lower osteoporotic fracture incidence than alendronate at 24months (risk ratio, 0.51; 95% confidence interval, 0.27 to 0.97) [17]. Based on this clinical evidence, both denosumab and bisphosphonates are widely prescribed for osteoporosis in Japan. However, since denosumab is more easily administered by two annual injections with less complication, which may possibly increase the compliance rate, it appears to be the better choice between the two drugs. Therefore, we assumed that it can be considered as a reasonable treatment option to switch from bisphosphonates to denosumab in the clinical setting. However, only a few studies have reported the efficacy of switching from bisphosphonates to denosumab; therefore, the evidence level remains low.

In view of these findings, we advised patients treated with MIN for more than 2years to switch to denosumab if they agreed after the detailed explanation of each drug from treating physicians. In this study, we aimed to retrospectively evaluate the treatment effects of patients who switched to denosumab and compared with those of patients who continued MIN treatment.

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Clinical effects of switching from minodronate to denosumab treatment in patients with postmenopausal osteoporosis: a retrospective study - BMC Blogs...