Editor’s note: EULAR 2020, the annual European congress of rheumatology, which was originally scheduled to be held in Frankfurt, Germany, starting June 3, was moved to a virtual format due to the COVID-19 pandemic.
EULAR 2020 e-CONGRESS—The knowledge that chronic kidney disease (CKD) patients are at increased risk of bone disorders and a lack of data to guide clinicians on how to treat them can leave clinicians in a state of renalism—nihilism in renal care, an expert said at the European e-congress of rheumatology.
There is a sense, said Pieter Evenepoel, MD, PhD, adjunct head of nephrology, University Hospitals Leuven, Belgium, that there is nothing much to be done to help patients in this regard. That is often a mistake.
“Doing nothing is a treatment, and not always the best treatment,” Dr. Evenepoel said. “An increased awareness, from nihilism to pragmatism, may help control the fracture burden in CKD.”
A working group recently unveiled suggestions on how to manage bone issues in chronic kidney disease patients, urging clinicians to assess risk and advising how to proceed based on what they find.
Dr. Evenepoel said the need for better care is clear: Studies have shown the risk of fracture increases according to the stage of CKD, with those on hemodialysis having three to four times the number of fractures as the general population.
One study found that those 65–74 years old in the general population suffer about four hip fractures per 1,000 patient-years, while those on dialysis had almost 20.1 The research group, a collaboration of the European Renal Association and the European Dialysis and Treatment Association, did not have hard evidence to use, but offers a scheme for approaching osteoporosis risk in patients with CKD, said Dr. Evenepoel, who helps lead the group.
Here is an outline of the recommended approach, which has been submitted for publication:
Identify patients at risk, using risk scores and bone mineral density data. The FRAX (Fracture Risk Assessment Tool) score, the most widely used test for determining the risk of fractures, is just as useful in predicting fracture in CKD patients as it is in the general population, Dr. Evenepoel said. It is not as good at predicting the number of fractures—giving overestimates as often as underestimates—but that doesn’t diminish its value in predicting fractures overall.
For measuring bone mineral density (BMD), dual-energy X-ray absorptiometry (DXA) used to be viewed skeptically, because there was no evidence it could be used to predict fractures in patients with CKD. According to Dr. Evenepoel, that began to change after 2009, and it’s now known that DXA-measured bone mineral density is as good at predicting fractures in CKD patients as it is in patients generally.2
“Among nephrologists, we are less reluctant to perform DXA now,” Dr. Evenepoel said. “There will be many more DXA scans being performed. So there will be many more patients referred for advice on what to do with a low DXA BMD result.”
The lumbar spine and hip are the first areas where BMD should be measured, according to Dr. Evenepoel. But the distal forearm is also a good measurement site, because it’s almost purely cortical bone, and could help better define a patient’s fracture risk.
Get information on bone turnover when an elevated risk is identified. Clinicians need insight into whether a patient has high, normal or low bone turnover (i.e., the process of resorption followed by new bone replacement with little change in shape). Low turnover can lead to decreased bone toughness, and high turnover can lead to more porosity in the cortical part of the bone, as well as other abnormalities that can lower bone quality and boost the risk of fracture.
The usual markers of bone turnover are not very reliable in patients with CKD, and those that work best—such as bone alkaline phosphatase, a protein on bone-forming cells, and trimeric P1MP, a peptide originating from bone-forming cells—are not typically used in daily practice, according to Dr. Evenepoel. So clinicians will often need to look at total alkaline phosphatase, which typically correlates well with the bone-specific form and can offer insight into bone turnover. They should also refer patients for a bone biopsy when appropriate.
Tailor treatments according to bone turnover results. For patients with a high total alkaline phosphatase level, clinicians should look for an increasing trend, together with a high parathyroid hormone (PTH) level and high calcium. Those factors will point to high bone turnover. These patients should be treated to control the high turnover; suppress PTH with calcimimetics to better control phosphate levels.
For patients with low bone turnover, clinicians could use a non-calcium phosphate binder, lowering calcium and allowing PTH to increase and normalizing bone turnover, said Dr. Evenepoel.
Patients with frank osteoporosis—with very low BMD scores—should be advised to exercise, quit smoking, take vitamin D and get enough calcium. If there’s a suspicion of low bone turnover, clinicians should consider anti-osteoporosis therapy—an anabolic therapy—and an anti-resorptive agent if turnover seems to be normal.
Final Thoughts
Dr. Evenepoel drew attention to the counterintuitive nature of PTH in chronic kidney disease patients. Although PTH is almost universally elevated in these patients, its usual effect of high bone turnover isn’t seen in this population. Instead, Dr. Evenepoel said, the majority of CKD patients actually have low or normal bone turnover because of a hypo-responsiveness to PTH. This is due to downregulation of PTH receptors, the presence of dysfunctional PTH receptors and other phenomena.
“CKD is not only a state of high PTH levels, but also a state of low PTH response,” he said. “It’s always the balance between [these states] that will, in the end, determine the bone phenotype—normal bone turnover, high or low bone turnover.”
Thomas R. Collins is a freelance writer living in South Florida.
References
- Moe SM, Nickolas T. Fractures in patients with CKD: Time for action. Clin J Am Soc Nephrol. 2016 Nov 7;11(11):1929–1931.
- Iimori S, Mori Y, Akita W, et al. Diagnostic usefulness of bone mineral density and biochemical markers of bone turnover in predicting fracture in CKD stage 5D patients—A single-center cohort study. Nephrol Dial Transplant. 2012 Jan;27(1):345–351.
