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Emerging treatments for postmenopausal osteoporosis - focus on denosumab.

Geusens P - Clin Interv Aging (2009)

Bottom Line: The pathway of the receptor activator of the nuclear factor kappaB ligand (RANKL), RANK and osteoprotegerin (OPG) plays a central role in coupling bone formation and resorption during normal bone turnover and in a wide spectrum of diseases characterized by disturbed bone remodeling, increased bone resorption and bone destruction (osteoporosis, Paget's disease of bone, rheumatoid arthritis [RA], metastatic bone disease).The effects on fracture reduction in postmenopausal osteoporosis are awaited from the recently finished FREEDOM study.In clinical trials with denosumab, overall adverse events were similar to placebo or comparators, indicating a favorable safety profile in these diseases, which until now have been available up to 4 years, but data on long-term safety will be needed.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Subdivision of Rheumatology, Maastricht University Medical Center, Maastricht, The Netherlands. piet.geusens@scarlet.be

ABSTRACT
The pathway of the receptor activator of the nuclear factor kappaB ligand (RANKL), RANK and osteoprotegerin (OPG) plays a central role in coupling bone formation and resorption during normal bone turnover and in a wide spectrum of diseases characterized by disturbed bone remodeling, increased bone resorption and bone destruction (osteoporosis, Paget's disease of bone, rheumatoid arthritis [RA], metastatic bone disease). Clinical trials indicate that denosumab, a RANKL-specific recombinant humanized monoclonal antibody, is effective in suppressing bone resorption, resulting in increase in bone mineral density (BMD) in post-menopausal women with low BMD, and has the potential to prevent progression of erosions in RA and of skeletal-related events in metastatic bone disease. The effects on fracture reduction in postmenopausal osteoporosis are awaited from the recently finished FREEDOM study. In clinical trials with denosumab, overall adverse events were similar to placebo or comparators, indicating a favorable safety profile in these diseases, which until now have been available up to 4 years, but data on long-term safety will be needed.

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Related in: MedlinePlus

Effect of 4 years of denosumab every 6 months on lumbar spine (LS) bone mineral density. Adapted from J Bone Miner Res. 2007;22:1832–1841,30 with permission of the American Society for Bone and Mineral Research.
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f3-cia-4-241: Effect of 4 years of denosumab every 6 months on lumbar spine (LS) bone mineral density. Adapted from J Bone Miner Res. 2007;22:1832–1841,30 with permission of the American Society for Bone and Mineral Research.

Mentions: Efficacy and safety of denosumab were evaluated in a randomized, placebo-controlled, dose-ranging phase 2 study in 412 postmenopausal women with low BMD in the spine or femur and included a group of patients treated with open-label alendronate 70 mg/week.29 Denosumab (at a dose of 6, 14 or 30 mg every 3 months or 14, 60, 100 or 210 mg every 6 months over a period of 12 months) resulted in a rapid and sustained effect on BTM and a rapid increase in BMD in the spine, hip and distal radius, which was superior to placebo and similar or greater (for changes in BMD in the total hip and in the distal radius and in markers of bone resorption) than with weekly 70 mg of alendronate (Figure 2). These changes were sustained in an extension study over 24 months (Figure 3).30 Adverse events (AE) and serious AE (SAEs) were similar in character and percentage with denosumab compared with placebo. In terms of increase in BMD, the dose of 30 mg/3 months and 60 mg/6 months appeared optimal.


Emerging treatments for postmenopausal osteoporosis - focus on denosumab.

Geusens P - Clin Interv Aging (2009)

Effect of 4 years of denosumab every 6 months on lumbar spine (LS) bone mineral density. Adapted from J Bone Miner Res. 2007;22:1832–1841,30 with permission of the American Society for Bone and Mineral Research.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2697589&req=5

f3-cia-4-241: Effect of 4 years of denosumab every 6 months on lumbar spine (LS) bone mineral density. Adapted from J Bone Miner Res. 2007;22:1832–1841,30 with permission of the American Society for Bone and Mineral Research.
Mentions: Efficacy and safety of denosumab were evaluated in a randomized, placebo-controlled, dose-ranging phase 2 study in 412 postmenopausal women with low BMD in the spine or femur and included a group of patients treated with open-label alendronate 70 mg/week.29 Denosumab (at a dose of 6, 14 or 30 mg every 3 months or 14, 60, 100 or 210 mg every 6 months over a period of 12 months) resulted in a rapid and sustained effect on BTM and a rapid increase in BMD in the spine, hip and distal radius, which was superior to placebo and similar or greater (for changes in BMD in the total hip and in the distal radius and in markers of bone resorption) than with weekly 70 mg of alendronate (Figure 2). These changes were sustained in an extension study over 24 months (Figure 3).30 Adverse events (AE) and serious AE (SAEs) were similar in character and percentage with denosumab compared with placebo. In terms of increase in BMD, the dose of 30 mg/3 months and 60 mg/6 months appeared optimal.

Bottom Line: The pathway of the receptor activator of the nuclear factor kappaB ligand (RANKL), RANK and osteoprotegerin (OPG) plays a central role in coupling bone formation and resorption during normal bone turnover and in a wide spectrum of diseases characterized by disturbed bone remodeling, increased bone resorption and bone destruction (osteoporosis, Paget's disease of bone, rheumatoid arthritis [RA], metastatic bone disease).The effects on fracture reduction in postmenopausal osteoporosis are awaited from the recently finished FREEDOM study.In clinical trials with denosumab, overall adverse events were similar to placebo or comparators, indicating a favorable safety profile in these diseases, which until now have been available up to 4 years, but data on long-term safety will be needed.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Subdivision of Rheumatology, Maastricht University Medical Center, Maastricht, The Netherlands. piet.geusens@scarlet.be

ABSTRACT
The pathway of the receptor activator of the nuclear factor kappaB ligand (RANKL), RANK and osteoprotegerin (OPG) plays a central role in coupling bone formation and resorption during normal bone turnover and in a wide spectrum of diseases characterized by disturbed bone remodeling, increased bone resorption and bone destruction (osteoporosis, Paget's disease of bone, rheumatoid arthritis [RA], metastatic bone disease). Clinical trials indicate that denosumab, a RANKL-specific recombinant humanized monoclonal antibody, is effective in suppressing bone resorption, resulting in increase in bone mineral density (BMD) in post-menopausal women with low BMD, and has the potential to prevent progression of erosions in RA and of skeletal-related events in metastatic bone disease. The effects on fracture reduction in postmenopausal osteoporosis are awaited from the recently finished FREEDOM study. In clinical trials with denosumab, overall adverse events were similar to placebo or comparators, indicating a favorable safety profile in these diseases, which until now have been available up to 4 years, but data on long-term safety will be needed.

Show MeSH
Related in: MedlinePlus