Bone Fragility Fractures in CKD Patients

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Abstract

Chronic kidney diseases (CKD) are associated with mineral and bone diseases (MBD), including pain, bone loss, and fractures. Bone fragility related to CKD includes the risk factors observed in osteoporosis in addition to those related to CKD, resulting in a higher risk of mortality related to fractures. Unawareness of such complications led to a poor management of fractures and a lack of preventive approaches. The current guidelines of the Kidney Disease Improving Global Outcomes (KDIGO) recommend the assessment of bone mineral density if results will impact treatment decision. In addition to bone density, circulating biomarkers of mineral, serum bone turnover markers, and imaging techniques are currently available to evaluate the fracture risk. The purpose of this review is to provide an overview of the epidemiology and pathogenesis of CKD-associated bone loss. The contribution of the current tools and other techniques in development are discussed. We here propose a current view of how to better predict bone fragility and the therapeutic options in CKD.

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Romosozumab Treatment in Postmenopausal Women with Osteoporosis.

Felicia Cosman, Daria Crittenden, Jonathan D. Adachi … (2016)

Background Romosozumab, a monoclonal antibody that binds sclerostin, increases bone formation and decreases bone resorption. Methods We enrolled 7180 postmenopausal women who had a T score of -2.5 to -3.5 at the total hip or femoral neck. Patients were randomly assigned to receive subcutaneous injections of romosozumab (at a dose of 210 mg) or placebo monthly for 12 months; thereafter, patients in each group received denosumab for 12 months, at a dose of 60 mg, administered subcutaneously every 6 months. The coprimary end points were the cumulative incidences of new vertebral fractures at 12 months and 24 months. Secondary end points included clinical (a composite of nonvertebral and symptomatic vertebral) and nonvertebral fractures. Results At 12 months, new vertebral fractures had occurred in 16 of 3321 patients (0.5%) in the romosozumab group, as compared with 59 of 3322 (1.8%) in the placebo group (representing a 73% lower risk with romosozumab; P<0.001). Clinical fractures had occurred in 58 of 3589 patients (1.6%) in the romosozumab group, as compared with 90 of 3591 (2.5%) in the placebo group (a 36% lower risk with romosozumab; P=0.008). Nonvertebral fractures had occurred in 56 of 3589 patients (1.6%) in the romosozumab group and in 75 of 3591 (2.1%) in the placebo group (P=0.10). At 24 months, the rates of vertebral fractures were significantly lower in the romosozumab group than in the placebo group after each group made the transition to denosumab (0.6% [21 of 3325 patients] in the romosozumab group vs. 2.5% [84 of 3327] in the placebo group, a 75% lower risk with romosozumab; P<0.001). Adverse events, including instances of hyperostosis, cardiovascular events, osteoarthritis, and cancer, appeared to be balanced between the groups. One atypical femoral fracture and two cases of osteonecrosis of the jaw were observed in the romosozumab group. Conclusions In postmenopausal women with osteoporosis, romosozumab was associated with a lower risk of vertebral fracture than placebo at 12 months and, after the transition to denosumab, at 24 months. The lower risk of clinical fracture that was seen with romosozumab was evident at 1 year. (Funded by Amgen and UCB Pharma; FRAME ClinicalTrials.gov number, NCT01575834 .).

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Incidence and mortality of hip fractures in the United States.

Carmen Brauer, Marcelo Coca-Perraillon, David Cutler … (2009)

Understanding the incidence and subsequent mortality following hip fracture is essential to measuring population health and the value of improvements in health care. To examine trends in hip fracture incidence and resulting mortality over 20 years in the US Medicare population. Observational study using data from a 20% sample of Medicare claims from 1985-2005. In patients 65 years or older, we identified 786,717 hip fractures for analysis. Medication data were obtained from 109,805 respondents to the Medicare Current Beneficiary Survey between 1992 and 2005. Age- and sex-specific incidence of hip fracture and age- and risk-adjusted mortality rates. Between 1986 and 2005, the annual mean number of hip fractures was 957.3 per 100,000 (95% confidence interval [CI], 921.7-992.9) for women and 414.4 per 100,000 (95% CI, 401.6-427.3) for men. The age-adjusted incidence of hip fracture increased from 1986 to 1995 and then steadily declined from 1995 to 2005. In women, incidence increased 9.0%, from 964.2 per 100,000 (95% CI, 958.3-970.1) in 1986 to 1050.9 (95% CI, 1045.2-1056.7) in 1995, with a subsequent decline of 24.5% to 793.5 (95% CI, 788.7-798.3) in 2005. In men, the increase in incidence from 1986 to 1995 was 16.4%, from 392.4 (95% CI, 387.8-397.0) to 456.6 (95% CI, 452.0-461.3), and the subsequent decrease to 2005 was 19.2%, to 369.0 (95% CI, 365.1-372.8). Age- and risk-adjusted mortality in women declined by 11.9%, 14.9%, and 8.8% for 30-, 180-, and 360-day mortality, respectively. For men, age- and risk-adjusted mortality decreased by 21.8%, 25.4%, and 20.0% for 30-, 180-, and 360-day mortality, respectively. Over time, patients with hip fracture have had an increase in all comorbidities recorded except paralysis. The incidence decrease is coincident with increased use of bisphosphonates. In the United States, hip fracture rates and subsequent mortality among persons 65 years and older are declining, and comorbidities among patients with hip fractures have increased.

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Executive summary of the 2017 KDIGO Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD) Guideline Update: what’s changed and why it matters

Linda McCann, Sharon Moe, Rukshana Shroff … (2017)

The KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of CKD-MBD represents a selective update of the prior CKD-MBD Guideline published in 2009. This update, along with the 2009 publication, is intended to assist the practitioner caring for adults and children with chronic kidney disease (CKD), those on chronic dialysis therapy, or individuals with a kidney transplant. This review highlights key aspects of the 2017 CKD-MBD Guideline Update, with an emphasis on the rationale for the changes made to the original guideline document. Topic areas encompassing updated recommendations include diagnosis of bone abnormalities in CKD-mineral and bone disorder (MBD), treatment of CKD-MBD by targeting phosphate lowering and calcium maintenance, treatment of abnormalities in parathyroid hormone in CKD-MBD, treatment of bone abnormalities by antiresorptives and other osteoporosis therapies, and evaluation and treatment of kidney transplant bone disease.

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Author and article information

Contributors

Martine Cohen-Solal:

ORCID: http://orcid.org/0000-0002-8582-8258

martine.cohen-solal@inserm.fr

Journal

Journal ID (nlm-ta): Calcif Tissue Int

Journal ID (iso-abbrev): Calcif Tissue Int

Title: Calcified Tissue International

Publisher: Springer US (New York )

ISSN (Print): 0171-967X

ISSN (Electronic): 1432-0827

Publication date (Electronic): 21 November 2020

Publication date PMC-release: 21 November 2020

Publication date (Print): 2021

Volume: 108

Issue: 4

Pages: 539-550

Affiliations

[1 ]AURA Paris-Nord, Saint-Ouen, France

[2 ]Necker Hospital, University of Paris Descartes, Department of Renal Physiology, Paris, France

[3 ]GRID grid.411129.e, ISNI 0000 0000 8836 0780, Fundació Puigvert, Universitat Autònoma, IIB Sant Pau, REDinREN, , Nephrology Department, ; Barcelona, Catalonia Spain

[4 ]Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), REDinREN del ISCIII, Hospital Universitario Central de Asturias. Universidad de Oviedo, Bone and Mineral Research Unit, Oviedo, Asturias Spain

[5 ]GRID grid.411296.9, ISNI 0000 0000 9725 279X, INSERM U1132 & Université de Paris, Hôpital Lariboisière, , Department of Rheumatology, ; Paris, France

Author information

Martine Cohen-Solal http://orcid.org/0000-0002-8582-8258

Article

Publisher ID: 779

DOI: 10.1007/s00223-020-00779-z

PMC ID: 8052229

PubMed ID: 33219822

SO-VID: c7341e77-a81f-4184-aca4-aed4a026f519

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Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 8 October 2020

Date accepted : 4 November 2020

Custom metadata

ScienceOpen disciplines: Human biology

Keywords: bone,fracture,bone mineral density,ckd-mbd,phosphate,calcium,parathyroid hormone,imaging

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ScienceOpen disciplines: Human biology

Keywords: bone, fracture, bone mineral density, ckd-mbd, phosphate, calcium, parathyroid hormone, imaging

Bone Fragility Fractures in CKD Patients

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Most cited references 97

Romosozumab Treatment in Postmenopausal Women with Osteoporosis.

Incidence and mortality of hip fractures in the United States.

Executive summary of the 2017 KDIGO Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD) Guideline Update: what’s changed and why it matters

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