Management of osteoporosis in advanced chronic kidney disease: European Consensus Statement
The European Renal Osteodystrophy (EUROD) Working Group, bringing together expertise from the European Renal Association-European Dialysis and Transplant Association and International Osteoporosis Foundation (IOF) Committees of Scientific Advisors and National Societies, has published the 'European Consensus Statement on the diagnosis and management of osteoporosis in chronic kidney disease stages G4-G5D'. The Consensus provides a succinct review of current clinical practice and outlines practical recommendations for diagnosis, assessment of fracture risk, intervention thresholds, non-pharmacological and pharmacological intervention strategies, monitoring, and secondary fracture prevention through coordinator-based fracture liaison services.
Lead author, Dr Pieter Evenepoel, Department of Nephrology of the University Hospitals Leuven, Leuven, Belgium stated:
"Disturbances in mineral and bone metabolism occur early in the course of CKD and become almost universal in patients with advanced disease. Nevertheless, despite their very high risk of sustaining osteoporosis-related fractures, there is a vast osteoporosis care gap in these patients. Many clinicians are uncertain about the optimal diagnostic and therapeutic strategy and this may be fuelling inertia and a 'wait-and-see' approach in regard to osteoporosis care."
The Consensus recommendations are timely and important given that chronic kidney disease is a rapidly growing problem worldwide. It is estimated that as much as 10-15% of the adult population is affected. In 2010, 284 individuals per million population were estimated to be undergoing maintenance dialysis (CKD G5D) globally, and this is on the increase given the rapid increase in chronic cardiometabolic diseases worldwide.
Professor Serge Ferrari, co-author and Vice-Chair of the IOF Committee of Scientific Advisors, added:
"Recent studies suggest a similar efficacy of common osteoporosis drugs in patients with CKD G4-G5D as in the general patient population. We hope that the pragmatic consensus recommendations resulting from this successful collaboration between European societies, covering assessment, treatment and monitoring of bone health in renal disease, will serve to stimulate a proactive and cohesive approach to the management of osteoporosis in these high-risk patients."
The recommendations also highlight the importance of coordinator-based fracture liaison services in systematically identifying and guiding CKD patients with fragility fractures, in close collaboration with nephrologists as part of the multidisciplinary team.
Summary of Recommendations on diagnosis and management of Osteoporosis in Chronic kidney disease
Diagnosis of osteoporosis in chronic kidney disease
Osteoporosis is a condition characterized by low bone mass and microarchitectural and qualitative bone deterioration that leads to bone fragility and fracture susceptibility.
The operational definition of osteoporosis is based on an areal bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry (DXA) at the spine or hip <−2.5 standard deviation from the BMD in young female adults (T-score).
Risk factors for fragility fractures
Clinical risk factors for osteoporosis in chronic kidney disease (CKD) patients comprise traditional risk factors including older age, female sex, low body mass index, fragility fracture history, glucocorticoid treatment and CKD-specific risk factors such as long dialysis duration.
BMD as assessed by DXA predicts fractures in patients with CKD G4–G5D. However, DXA probably underestimates the actual fracture risk in patients with CKD G4–G5D, as it does not account for impaired bone quality. The consistency of the risk prediction across stages of disease and degree of parathyroid hormone (PTH) control remains to be documented.
Assessment of fracture risk
In patients with CKD G4–G5D, DXA may be considered in postmenopausal women, or men >50 years of age. Routine DXA testing (screening) in all CKD G4–G5D patients is not supported by current evidence.
The hip and the lumbar spine are the primary skeletal site to evaluate BMD by DXA.
The forearm may be included in the DXA evaluation of the skeletal site panel, but one should be aware of operator-dependent variability and potential bias by arteriovenous fistula.
Trabecular bone score and alternative imaging techniques need further clinical evaluation pending clinical implementation.
Vertebral fracture assessment (VFA) and/or lateral spine imaging is recommended in all patients undergoing DXA evaluation and in patients with a history of ≥4 cm height loss, kyphosis, or recent or current long-term oral glucocorticoid therapy. Imaging should include the abdominal aorta for determination of vascular calcification.
FRAX predicts fracture probability in all CKD stages. Additional evidence is required to define whether further arithmetic adjustments to conventional FRAX estimates have to be made with knowledge of advanced CKD.
Non-kidney-retained bone turnover markers (BTMs), especially bone-specific alkaline phosphatase, may be useful for fracture risk prediction in CKD G4–G5D, awaiting further confirmation.
Intervention thresholds for pharmacological therapy
CKD patients >50 years of age with a prior fragility fracture [(major osteoporotic fracture (MOF)] may be considered for treatment without the need for further BMD assessment.
In the absence of MOF, a DXA T-score threshold ≤−2.5 at the lumbar spine or hip is recommended, recognizing that a higher threshold of −2.0 or −1.5 may be more appropriate.
FRAX country-specific intervention thresholds are appropriate in CKD patients.
A sufficient supply of calcium should be guaranteed (800–1200 mg/day, preferentially through diet) and vitamin D stores should be repleted according to osteoporosis and CKD-MBD guidelines.
Regular weight-bearing exercise should be advised, tailored to the needs and abilities of the individual patient.
Thefalls risk needs to be evaluated regularly and acted upon.
CKD-MBD therapy should be optimized according to current guidelines before considering specific osteoporosis management.
Metabolic disturbances linked to bone fragility (acid–base, uraemic toxicity) should be controlled at all times.
Risks and benefits of available pharmacological interventions need to be balanced at the individual level and discussed with the patient. Formal informed consent may be required when considering off-label use.
Evolving evidence indicates that antiresorptive agents may be effective in advanced CKD and that vascular and skeletal risks are not excessively high.
Renal risks of bisphosphonates are poorly explored in patients with CKD G4–G5D, which calls for caution.
Denosumab confers no risk of kidney function decline, but the risk of severe hypocalcaemia with denosumab is increased in CKD and needs to be addressed by concomitant vitamin D and calcium supplementation.
Withdrawal of denosumab therapy may be associated with an increased risk of vertebral fracture.
Non-kidney-retained BTMs, such as bone-specific alkaline phosphatase, intact procollagen type I N-propeptide and tartrate-resistant acid phosphatase 5b, should be preferentially monitored in CKD patients.
Monitoring of BTMs may inform on the early therapeutic response.
Monitoring of BTMs after therapy withdrawal (offset of effect) may inform on the need for reintroduction.
Repeat DXA informs on the long-term treatment effect on BMD. The time interval when treatment effect can be detected may vary depending on the treatment modality and underlying type of renal osteodystrophy.
Systems of care
Coordinator-based fracture liaison services (FLSs) should be considered to systematically identify and guide CKD patients with fragility fractures, in close collaboration with nephrologists. The (cost-)effectiveness of FLSs has been established in the general population.