Pharmacological interventions versus placebo, no treatment or usual care for osteoporosis in people with chronic kidney disease stages 3-5D

Hara, Takashi; Hijikata, Yasukazu; Matsubara, Yukiko; Watanabe, Norio

doi:10.1002/14651858.cd013424.pub2

Cited by 14 publications

(7 citation statements)

References 122 publications

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“…Although it is now possible to use these treatment options in advanced CKD (licensed or off-licensed use) with BTM evidence supporting the drug mechanism, evidence on their fracture risk reduction in this population is limited ( 546 , 547 ). Large randomized controlled trials of denosumab and teriparatide have largely excluded advanced CKD patients with SHPT.…”

Section: Part 2 the Use Of Btm In Clinical Practice: Potential Proble...mentioning

confidence: 99%

Bone Turnover Markers: Basic Biology to Clinical Applications

et al. 2022

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Bone turnover markers (BTMs) are used widely, in both research and clinical practice. In the last 20 years, much experience has been gained in measurement and interpretation of these markers, which include commonly used bone formation markers bone alkaline phosphatase, osteocalcin, and procollagen I N-propeptide; and commonly used resorption markers serum C-telopeptides of type I collagen, urinary N-telopeptides of type I collagen and tartrate resistant acid phosphatase type 5b. BTMs are usually measured by enzyme-linked immunosorbent assay or automated immunoassay. Sources contributing to BTM variability include uncontrollable components (e.g., age, gender, ethnicity) and controllable components, particularly relating to collection conditions (e.g., fasting/feeding state, and timing relative to circadian rhythms, menstrual cycling, and exercise). Pregnancy, season, drugs, and recent fracture(s) can also affect BTMs. BTMs correlate with other methods of assessing bone turnover, such as bone biopsies and radiotracer kinetics; and can usefully contribute to diagnosis and management of several diseases such as osteoporosis, osteomalacia, Paget’s disease, fibrous dysplasia, hypophosphatasia, primary hyperparathyroidism, and chronic kidney disease-mineral bone disorder.

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Section: Part 2 the Use Of Btm In Clinical Practice: Potential Proble...mentioning

confidence: 99%

Bone Turnover Markers: Basic Biology to Clinical Applications

et al. 2022

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“…While determining the underlying bone pathophysiology in CKD patients with skeletal fragility could inform appropriate treatment strategies, bone biopsy is an invasive procedure available in only a few specialized centers and not routinely performed. Small studies have shown an improvement in bone mass in dialysis-dependent patients with CKD-MBD treated with antiresorptive drugs; however, the effectiveness of such treatment on reduction of fracture risk has not been established in this population …”

Section: Discussionmentioning

confidence: 99%

Severe Hypocalcemia With Denosumab Among Older Female Dialysis-Dependent Patients

Bird,

Smith,

Gelperin

et al. 2024

JAMA

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ImportanceDialysis-dependent patients experience high rates of morbidity from fractures, yet little evidence is available on optimal treatment strategies. Chronic kidney disease–mineral and bone disorder is nearly universal in dialysis-dependent patients, complicating diagnosis and treatment of skeletal fragility.ObjectiveTo examine the incidence and comparative risk of severe hypocalcemia with denosumab compared with oral bisphosphonates among dialysis-dependent patients treated for osteoporosis.Design, Setting, and ParticipantsRetrospective cohort study of female dialysis-dependent Medicare patients aged 65 years or older who initiated treatment with denosumab or oral bisphosphonates from 2013 to 2020. Clinical performance measures including monthly serum calcium were obtained through linkage to the Consolidated Renal Operations in a Web-Enabled Network database.ExposuresDenosumab, 60 mg, or oral bisphosphonates.Main Outcomes and MeasuresSevere hypocalcemia was defined as total albumin-corrected serum calcium below 7.5 mg/dL (1.88 mmol/L) or a primary hospital or emergency department hypocalcemia diagnosis (emergent care). Very severe hypocalcemia (serum calcium below 6.5 mg/dL [1.63 mmol/L] or emergent care) was also assessed. Inverse probability of treatment-weighted cumulative incidence, weighted risk differences, and weighted risk ratios were calculated during the first 12 treatment weeks.ResultsIn the unweighted cohorts, 607 of 1523 denosumab-treated patients and 23 of 1281 oral bisphosphonate–treated patients developed severe hypocalcemia. The 12-week weighted cumulative incidence of severe hypocalcemia was 41.1% with denosumab vs 2.0% with oral bisphosphonates (weighted risk difference, 39.1% [95% CI, 36.3%-41.9%]; weighted risk ratio, 20.7 [95% CI, 13.2-41.2]). The 12-week weighted cumulative incidence of very severe hypocalcemia was also increased with denosumab (10.9%) vs oral bisphosphonates (0.4%) (weighted risk difference, 10.5% [95% CI, 8.8%-12.0%]; weighted risk ratio, 26.4 [95% CI, 9.7-449.5]).Conclusions and RelevanceDenosumab was associated with a markedly higher incidence of severe and very severe hypocalcemia in female dialysis-dependent patients aged 65 years or older compared with oral bisphosphonates. Given the complexity of diagnosing the underlying bone pathophysiology in dialysis-dependent patients, the high risk posed by denosumab in this population, and the complex strategies required to monitor and treat severe hypocalcemia, denosumab should be administered after careful patient selection and with plans for frequent monitoring.

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“…A range of pharmacological agents have been developed for fracture prevention in osteoporosis, which are generally safe and effective in CKD stages 1–3 [ 2 , 3 , 14 ]. Despite a sparsity of large clinical trials, specifically targeting fracture risk in CKD stages 4–5D, evidence from post hoc analyses of randomized and controlled trials (RCTs), moderately sized prospective clinical trials and observational studies supports pharmacological fracture risk reduction in all stages of CKD, although some caveats and limitations need to be considered, and we advise to obtain informed consent when considering off-label use of osteoporosis medication in CKD.…”

Section: Treatment Optionsmentioning

confidence: 99%

“…Recent developments in diagnostic methodology and pathophysiologic understanding, and an increasing therapeutic armamentarium for the treatment and prevention of fragility fractures, open new possibilities for the clinician. Several systematic reviews of osteoporosis medication in CKD have been published recently, demonstrating an efficacy of different classes of bone-specific drugs for improvement of BMD and for fracture risk reduction [ 2 , 3 ]. Thus, it may be time for a re-evaluation of the diagnostic and therapeutic strategies for fracture prevention in CKD.…”

Section: Introductionmentioning

confidence: 99%

Management of fracture risk in CKD—traditional and novel approaches

Haarhaus

Aaltonen

Cejka

et al. 2022

Clinical Kidney Journal

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The coexistence of osteoporosis and chronic kidney disease (CKD) is an evolving health care challenge in the face of increasingly aging populations. Globally, accelerating fracture incidence causes disability, impaired quality of life, and increased mortality. Consequently, several novel diagnostic and therapeutic tools have been introduced for treatment and prevention of fragility fractures. Despite an especially high fracture risk in CKD, these patients are commonly excluded from interventional trials and clinical guidelines. While management of fracture risk in CKD has been discussed in recent opinion-based reviews and consensus papers in the nephrology literature, many patients with CKD stages 3–5D and osteoporosis are still underdiagnosed and untreated. The current review addresses this potential treatment nihilism by discussing established and novel approaches to diagnosis and prevention of fracture risk in patients with CKD stages 3–5D. Skeletal disorders are common in CKD. A wide variety of underlying pathophysiological processes have been identified, including premature aging, chronic wasting, and disturbances in vitamin D and mineral metabolism, which may impact bone fragility beyond established osteoporosis. We discuss current and emerging concepts of CKD—mineral and bone disorders (CKD-MBD) and integrate management of osteoporosis in CKD with current recommendations for management of CKD-MBD. While many diagnostic and therapeutic approaches to osteoporosis can be applied to patients with CKD, some limitations and caveats need to be considered. Consequently, clinical trials are needed that specifically study fracture prevention strategies in patients with CKD stages 3–5D.

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Pharmacological interventions versus placebo, no treatment or usual care for osteoporosis in people with chronic kidney disease stages 3-5D

Cited by 14 publications

References 122 publications

Bone Turnover Markers: Basic Biology to Clinical Applications

Bone Turnover Markers: Basic Biology to Clinical Applications

Severe Hypocalcemia With Denosumab Among Older Female Dialysis-Dependent Patients

Management of fracture risk in CKD—traditional and novel approaches

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