Bone Mass and Microarchitecture in CKD Patients with Fracture

Abstract

Patients with predialysis chronic kidney disease (CKD) have increased risk for fracture, but the structural mechanisms underlying this increased skeletal fragility are unknown. We measured areal bone mineral density (aBMD) by dual-energy x-ray absorptiometry at the spine, hip, and radius, and we measured volumetric BMD (vBMD), geometry, and microarchitecture by high-resolution peripheral quantitative computed tomography (HR-pQCT) at the radius and tibia in patients with CKD: 32 with fracture and 59 without fracture. Patients with fracture had lower aBMD at the spine, total hip, femoral neck, and the ultradistal radius, the last having the strongest association with fracture. By HR-pQCT of the radius, patients with fracture had lower cortical area and thickness, total and trabecular vBMD, and trabecular number and greater trabecular separation and network heterogeneity. At the tibia, patients with fracture had significantly lower cortical area, thickness, and total and cortical density. Total vBMD at both radius and tibia most strongly associated with fracture. By receiver operator characteristic curve analysis, patients with longer duration of CKD had area under the curve of Ͼ0.75 for aBMD at both hip sites and the ultradistal radius, vBMD and geometry at the radius and tibia, and microarchitecture at the tibia. In summary, patients with predialysis CKD and fractures have lower aBMD by dual-energy x-ray absorptiometry and lower vBMD, thinner cortices, and trabecular loss by HR-pQCT. These density and structural differences may underlie the increased susceptibility to fracture among patients with CKD. Fracture rates in patients with ESRD are elevated, 1 as high as individuals who have normal kidney function and are older by 10 to 20 years. 2 Recently, there has been increasing recognition that patients with predialysis chronic kidney disease (CKD) also experience an increased fracture burden. [2][3][4][5] In 2006, we reported that participants who were older than 50 years in the Third National Health and Nutrition Examination Survey (NHANES III) and had an estimated GFR (eGFR) between 15 and 59 ml/ min (stages 3 and 4 CKD) had a two-fold higher risk for hip fracture than individuals without CKD. 6 Subsequent studies confirmed our findings and also demonstrated that fracture risk increases as kidney function declines. [3][4][5] In one study, hip fracture risk was as high in patients with stage 4 CKD as in patients with ESRD. 4 Given the rapid expansion of the population of individuals who are older than 65 years worldwide and the high prevalence of CKD in the elderly, 7 it is highly important to improve our understanding of the structural and biologic mechanisms that contribute to increased fracture rates in patients with CKD so that we can develop strategies to identify those who are at risk for fracture.In patients with ESRD, relationships between areal

Discriminants of Prevalent Fractures in Chronic Kidney Disease

“…Consistent with our previous report, 14 measures of aBMD by DXA and of vBMD, size, and microarchitecture by HRpQCT were associated with fracture (Table 1). Fracture patients had significantly lower aBMD at the lumbar spine (LS), total hip (TH), femoral neck (FN), and 1/3 and ultradistal radius (1/3R and UDR, respectively).…”

“…Interestingly, whether BTMs were renally excreted did not affect fracture discrimination. In terms of pathogenesis, high iPTH and BTM levels were associated with low bone mass, smaller bone size, and a disrupted trabecular network, abnormalities we 14,19 and others 20 -23 have found to be associated with fracture.…”

“…14,55,[63][64][65][66] In brief, all imaging was performed in our laboratory by a dedicated research densitometrist. HRpQCT of the dominant limb was performed only if there was previous fracture or an arteriovenous fistula or graft in the nondominant limb.…”

Bone Microarchitecture in Hemodialysis Patients Assessed by HR-pQCT

“…The authors described a distinct difference in HR-pQCT and DXA parameters between patients with a history of fracture and those without fracture, but the discriminatory power was low. Overall, the ROC-AUC were below 0.75 for all parameters, but increased from 0.50 to 0.60 for patients with a disease duration Ͻ2.7 years to 0.60 to 0.80 for a CKD duration Ͼ6.9 years (18). Because all patients in the study presented here had end-stage renal disease, the duration of CKD was considerably longer and the discriminatory power of HR-pQCT and DXA therefore accordingly better.…”

“…A recent study investigated fracture status in patients with predialysis CKD with DXA and HR-pQCT (18). The authors described a distinct difference in HR-pQCT and DXA parameters between patients with a history of fracture and those without fracture, but the discriminatory power was low.…”