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Osteoporosis
Published in Jason Liebowitz, Philip Seo, David Hellmann, Michael Zeide, Clinical Innovation in Rheumatology, 2023
Mazen Nasrallah, Marcy B. Bolster
Denosumab is a fully human monoclonal antibody to the receptor activator of nuclear factor k-B ligand (RANKL), which binds to its receptor RANK on the surface of osteoclasts. By antagonizing the binding of RANKL to RANK, denosumab inhibits the activation and maturation of osteoclasts, and it likely reduces osteoclast survival.5 Denosumab was approved by the FDA in 2010 for the treatment of postmenopausal women at high risk of osteoporotic fractures, as well as those who are intolerant of or have failed other therapies, and it represented a milestone in bone health therapy by being the first approved monoclonal antibody therapy in osteoporosis.6 Denosumab is also approved for other indications, including men with high risk of fracture7 and glucocorticoid-induced osteoporosis.8
Bones and fractures
Published in Henry J. Woodford, Essential Geriatrics, 2022
Potential adverse effects of denosumab include hypocalcaemia (greater risk in people with renal impairment). Serum 25OHD should be tested prior to commencement and vitamin D supplementation given if low. Serum calcium should be checked two weeks prior to each dose. Use of this medication is also associated with the rare adverse effects of bisphosphonates – atypical fractures and osteonecrosis of the jaw. Denosumab prescription can be considered for people intolerant of oral therapy or when adherence with oral therapy is likely to be limited.21 It can be given for periods of up to five, possibly ten, years.
Osteoporosis and vitamin D deficiency
Published in Nadia Barghouthi, Jessica Perini, Endocrine Diseases in Pregnancy and the Postpartum Period, 2021
Denosumab crosses the placenta and causes an osteopetrotic phenotype in monkeys in utero.4 A few cases of denosumab therapy for postpartum PLO have been reported with resultant increase in trabecular volume and thickness of the radius and tibia but delaying conception for 6 months after the last dose was suggested.7
Treatment of fibrous dysplasia: focus on denosumab
Published in Expert Opinion on Biological Therapy, 2022
Bogdan Huzum, Sabina Antoniu, Raluca Dragomir
More recent studies have analyzed small cohorts for both the efficacy and safety of denosumab. One study involved a cohort of 12 patients with ‘uncontrolled’ or ‘suboptimally controlled’ FD/MAS after long-term therapy with bisphosphonates. Markers of disease activity included persistent pain and increased levels of biomarkers of bone turnover, such as ALP and propeptide of type 1 procollagen. Denosumab (60 mg) was administered at 3 or 6 month intervals. Patients were followed up for at least 12 months. The 3-month dosing regimen, but not the 6-month dosing regimen, was associated with sustained reduction in pain intensity and with a significant reduction in bone turnover. A median period of 15 months of denosumab therapy was associated with a reduction in serum ALP from 212 UI/l at baseline to 79 UI/l (p = 0.004) and propeptide levels from 346 to 55 ng/mL (p = 0.023). Pain was reported to be absent in six patients and was reduced in intensity in the others [38].
Medical treatment of osteoporosis
Published in Climacteric, 2022
Clinical trials have shown that the subcutaneous administration of denosumab 60 mg every 6 months reduces the risk of new vertebral fractures by 68%, and the incidence of clinical vertebral fractures, non-vertebral fractures and hip fractures by 69%, 20% and 40%, respectively, after 3 years of treatment in postmenopausal osteoporotic women. In addition, during the extension phase of these studies, up to 10 years of total follow-up, the protective effect on the risk of fractures remained over time. Of note, denosumab significantly reduces not only the risk of new vertebral fractures, but also the risk of new clinical vertebral fractures, multiple new vertebral fractures, new or worsening vertebral fractures, clinical osteoporotic fractures and primary or secondary fragility fractures. The efficacy of denosumab in reducing the risk of fractures is similar to that of the bisphosphonates [2,5,44–48]. Unfortunately, denosumab discontinuation is closely associated with a rebound effect, with an increase in bone turnover marker levels and a higher risk of rebound-associated vertebral fractures [2,5,44,49–52]. With regard to the risk of adverse events, the administration of denosumab is safe, with a low risk of side effects that include bacterial cellulitis, bone pain, cardiovascular disorders, hot flushes, hypertension, hypocalcemia, infection, nervous system disorders, pain in extremities and osteoarthritis. Remarkably, therapy discontinuation due to severe adverse events is rare [44–48].
Denosumab improves glucose parameters in patients with impaired glucose tolerance: a systematic review and meta-analysis
Published in Journal of Drug Assessment, 2021
Blanca T. Pacheco-Soto, Rebeca Garazi Elguezabal-Rodelo, Leonardo M. Porchia, Enrique Torres-Rasgado, Ricardo Pérez-Fuentes, M. Elba Gonzalez-Mejia
In the RANKL pathway, osteoprotegerin (OPG) is an inhibitor of RANKL, which enhances osteoclasts apoptosis [1]. Interestingly, elevated OPG serum levels are correlated with IGT [14] and that could be due to insulin levels decreasing over the years in patients with IGT [15] as well as the similar roles between OPG and insulin in blocking osteoclastogenesis [16]. Based on OPG’s function, Denosumab, a monoclonal antibody for human RANKL [17], could improve glucose entry into the muscle through increasing insulin sensitivity [2]. Furthermore, Denosumab was also proven to decrease DPP4 serum concentrations and increase glucagon-like peptide-1 (GLP-1) in subjects with IGT, demonstrating a crucial role in glucose and insulin metabolism [4]. Typically, Denosumab inhibits the maturation of osteoclasts and their precursors [18], as well as it is the current treatment for osteoporosis and other bone diseases. 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.