Effects of denosumab on bone density, mass and strength in women with postmenopausal osteoporosis

Abstract

Denosumab is a human monoclonal antibody which specifically blocks receptor activator of nuclear factor κB ligand and is a very potent antiresorptive drug. Its efficacy in reducing the risk of vertebral, hip and nonskeletal fracture has been proven in a large prospective, randomized multicenter study of 7808 postmenopausal women with osteoporosis [Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) trial]. Denosumab causes somewhat greater increases in bone mineral density (BMD) than the class of bisphosphonate antiresorptives. Denosumab also causes an increase in bone mass and bone strength in the spine, ultradistal and diaphysis of the radius, proximal tibia and the hip. Recently long-term treatment with denosumab has been shown to cause a continued almost linear increase in total hip and femoral neck BMD beyond 3 years up to 8 years. In this respect, denosumab seems to differ from the bisphosphonate group in which the rate of improvement of BMD diminishes and for some drugs becomes negative after 3-4 years when the process of secondary mineralization flattens out. This unique property of an antiresorptive drug points towards mechanisms of action which differ from the bisphosphonate group. Both types of antiresorptives decrease cortical porosity but contrary to bisphosphonates the reduction in cortical porosity continues with denosumab which, in addition, also seems to cause a slight continuous modeling-based formation of new bone despite suppression of bone remodeling. The net effect is an increase in cortical thickening and bone mass, and increased strength of cortical bone. This may contribute substantially to the significant further reduction of the nonvertebral fracture risk which was found in the long-term denosumab arm of the FREEDOM extension trial during years 4-7.

A Remarkable Increase in Bone Mineral Density in Celiac Disease

“…In another study, Zanchetta et al showed significant improvement in BMD and bone microarchitecture as detected by high-resolution peripheral quantitative computed tomography after one year of GFD with concomitant calcium and vitamin D supplementation [6]. Overall, the gain in BMD seen in our patient at both the lumbar spine and total hip is more than the average gain reported with oral bisphosphonates over three years [12].…”

Denosumab: targeting the RANKL pathway to treat rheumatoid arthritis

“…DMab treatment for up to 8 years significantly decreased bone turnover (6), increased bone mineral density (BMD)(7), improved bone microstructure of both cortical and trabecular bone (7, 8), and reduces the risk of bone fracture and osteoporosis (3, 5, 9-12). Bone biopsies confirmed potent and sustained effects of DMab on bone quality with continuous DMab treatment for 5-8 years (3, 4). The beneficial effects of DMab, however, can be fully reversed at the tissue level within 2 years of discontinuation, indicating that the skeletal effects of DMab are directed towards regulation of bone turnover to inhibit resorption and maintain bone mineral density (BMD).…”

“…However, DMab, but not bisphosphonates, significantly suppressed bone metabolism in a cohort of Japanese RA patients not previously treated for osteoporosis. These findings suggest distinct cellular mechanisms underlying DMab- and bisphosphonate-based RA therapy (4, 58). DMab exerts its protective effects likely through the WNT/β-catenin signaling pathway via regulating DKK-1 (25, 59).…”

Marine Natural Products: New Avenue in Treatment of Osteoporosis

“…Kostenuik et al have stated that administration of high doses of Denosumab in adult ovariectomized cynomolgus monkeys (up to 16 months) significantly improved the structural bone strength and bone mass (Kostenuik et al, 2011). In a randomized placebo-controlled and FREEDOM trial, Denosumab treatment to postmenopausal women with osteoporosis, caused significant reduction in risk of non-vertebral, vertebral, and hip fractures by 20, 68, and 40% (P < 0.001), respectively, however it increased the risk of cellulitis (Cummings et al, 2009;Bell and Bell, 2011;Törring, 2015). According to the literature, Denosumab worked better than risedronate, raloxifene, and alendronate, at diminishing the occurrence of vertebral fractures (Freemantle et al, 2013).…”