Denosumab Use in Chronic Kidney Disease Associated Osteoporosis: A Narrative Review

Abduelkarem, Abduelmula R; Guella, Adnane; Hamrouni, Amar M; Hassanein, Mohammed M; Nasr, Ahmed; Rana, Owais

doi:10.2147/rmhp.s426869

RMHP

2023

DOI: 10.2147/rmhp.s426869

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Denosumab Use in Chronic Kidney Disease Associated Osteoporosis: A Narrative Review

Abduelmula R Abduelkarem,

Adnane Guella,

Amar M Hamrouni

et al.

Abstract: Chronic kidney disease (CKD) and hemodialysis (HD) patients have a high incidence of bone disease and increased fracture risk, making effective management of their bone health a clinical challenge. Denosumab, a human monoclonal antibody, has been investigated as a therapeutic option in this patient population. In this review, we summarize the current evidence on the efficacy and safety of denosumab in CKD and HD patients. A comprehensive search of the relevant literature was conducted, including randomized con… Show more

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2024

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Cited by 4 publications

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Denosumab for osteoporosis in older adults in long‐term care: A randomized trial

Greenspan,

Perera,

Haeri

et al. 2024

J American Geriatrics Society

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BackgroundIn long‐term care (LTC), the incidence of hip or vertebral fractures are eight times that in the community. Despite the wide availability of osteoporosis therapy, LTC residents are omitted from pivotal trials and not treated. Denosumab is a relatively new, monoclonal antibody therapy for osteoporosis treatment. Via a randomized trial, we sought to determine the safety and efficacy of denosumab in LTC residents.MethodsWe conducted a 2‐year, double‐blind, placebo‐controlled, randomized clinical trial in 201 osteoporotic men and women aged ≥ 65 years, living in LTC communities. Participants with multimorbidity, dysmobility, and cognitive impairment were not excluded. The intervention was denosumab 60 mg subcutaneous every 6 months or placebo. Our primary outcome measures were hip and spine bone mineral density (BMD) improvement at 24 months. Secondary outcomes included BMD at other skeletal sites, function, and safety.ResultsWe included 123 women and 78 men with a mean ± standard error age of 81.5 ± 0.6. Overall, 83% and 71% completed 12 and 24 months, respectively. Compared with placebo, the women receiving denosumab had a greater 24‐month percent increase in spine (7.41 ± 0.93 vs. 2.15 + 0.56; p = 0.014), and total hip BMD (4.62 ± 0.62 vs. −0.19 ± 0.79; p = 0.007); and men in spine (7.91 ± 0.96 vs. 1.12 ± 1.13; p = 0.002) and total hip (3.74 ± 0.55 vs. 0.48 ± 0.74; p = 0.018). There were no significant differences in safety metrics.ConclusionsDenosumab was a safe and effective therapy for improving BMD in osteoporotic older men and women with multiple comorbidities in LTC.

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Denosumab for osteoporosis in older adults in long‐term care: A randomized trial

Greenspan,

Perera,

Haeri

et al. 2024

J American Geriatrics Society

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The Bone-Vascular Axis: A Key Player in Chronic Kidney Disease Associated Vascular Calcification

Shen,

2024

Kidney Dis

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Background: The bone-vascular axis plays a key role in the pathogenesis of vascular calcification (VC) in patients with chronic kidney disease (CKD). Understanding and managing the role of the bone-vascular axis in CKD-mineral and bone disorder (CKD-MBD) is critical for preventing and treating associated complications, including osteoporosis, arterial calcification, and cardiovascular diseases. This study aimed to comprehensively summarize the role of bone metabolism markers in uremic VC. Summary: The skeleton, as an endocrine organ, can regulate systemic metabolic processes by secreting various bioactive substances. These molecules can induce the transdifferentiation of vascular smooth muscle cells, promoting their transition to other functional states, thereby affecting vascular growth and remodeling. Key Messages: The prevalence of VC in individuals with CKD is notably high. CKD-associated VC is characterized by the widespread accumulation of hydroxyapatite within the arterial media, which occurs as a result of the transformation of smooth muscle cells into osteoblastic smooth muscle cells under the influence of uremic toxins. Osteoblasts and osteoclasts in bone tissue secrete mineral metabolic proteins, which can influence neighboring cells, primarily vascular smooth muscle cells, through paracrine signaling. Both circulating and osteocytic sclerostin can exert a protective effect by inhibiting wingless/integrated (WNT)-induced calcification. The therapeutic goal for CKD-MBD is to reduce production of sclerostin by decreasing the osteogenic transdifferentiation of vascular smooth muscle cells. Calciprotein particles act as a physiological agent for delivering calcium-phosphate the bone and inducing fibroblast growth factor-23 expression in osteoblasts.

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Renal Function Is Associated with Changes in Bone Mineral Density in Postmenopausal Osteoporotic Women Treated with Denosumab: Data From a Retrospective Cohort Study

Catalano,

Oliveri,

Natale

et al. 2024

JCM

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Background/Objectives: Renal function influences bone metabolism, as kidney failure can increase the risk of fractures. Denosumab is an approved osteoporosis treatment, but its efficacy in relation to renal function has not yet been studied in real-life scenarios. This study aimed to investigate the denosumab-induced change in bone mineral density (BMD) according to kidney function. Methods: A retrospective analysis was conducted at the outpatient clinic in postmenopausal women receiving denosumab (60 mg subcutaneously administered every 6 months). The glomerular filtration rate (eGFR) was measured by the 2021 CKD-EPI equation and patients were stratified for eGFR categories. BMD was measured by dual-energy X-ray absorptiometry. Results: 128 women (mean age 70.3 ± 9.4 years) were recruited. The mean denosumab treatment duration was 3.9 ± 1.4 years and all the participants had improved BMD values. In stepwise multiple regression analysis—after controlling for age, BMI, and treatment duration—the eGFR value (ß = −0.11, SE 0.04, p = 0.01) was independently associated with the lumbar spine BMD change. The same association remained when the eGFR categories were considered (ß = 3.564, SE 1.29, p = 0.007). In addition, after controlling for BMI and the duration of denosumab treatment, age (ß = −0.7915, SE 0.37, p = 0.03) and eGFR (ß = −0.3257, SE 0.1567, p = 0.04) were found to be associated with femoral neck BMD change. The association remained when considering eGFR categories (ß = 8.7339, SE 4.29, p = 0.04). Conclusions: This retrospective study suggests that eGFR is associated with denosumab efficacy in postmenopausal women treated for osteoporosis.

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Denosumab Use in Chronic Kidney Disease Associated Osteoporosis: A Narrative Review

Cited by 4 publications

References 39 publications

Denosumab for osteoporosis in older adults in long‐term care: A randomized trial

Denosumab for osteoporosis in older adults in long‐term care: A randomized trial

The Bone-Vascular Axis: A Key Player in Chronic Kidney Disease Associated Vascular Calcification

Renal Function Is Associated with Changes in Bone Mineral Density in Postmenopausal Osteoporotic Women Treated with Denosumab: Data From a Retrospective Cohort Study

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