High prevalence of low bone mineral density in pre-dialysis chronic kidney disease patients: bone histomorphometric analysis

Lobão, Rosélia Rs; Carvalho, Aluízio Barbosa de; Cuppari, Lílian; Ventura, R. T. P.; Lazaretti-Castro, Marise; Jorgetti, Vanda; Vieira, José Gilberto H.; Cendoroglo, Maysa Seabra; Draibe, S. A.

doi:10.5414/cnp62432

Cited by 53 publications

(37 citation statements)

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“…Skeletal Wnt inhibition and increased sclerostin are found in early CKD, 15 although remodeling rates may not be reduced in early CKD. The frequencies of decreased bone formation rates in early CKD stages 2-4 are controversial, ranging from 0% to 50%, [52][53][54] and may be age-related. In animal models of early CKD caused by polycystic kidney disease and Alport's disease, normal or elevated modeling rates were observed as osteodystrophy was detected, despite findings of decreased nuclear b-catenin in osteocytes and elevated sclerostin levels.…”

Section: Discussionmentioning

confidence: 99%

CKD-Induced Wingless/Integration1 Inhibitors and Phosphorus Cause the CKD–Mineral and Bone Disorder

Fang¹,

Ginsberg

Seifert

et al. 2014

Journal of the American Society of Nephrology

152

186

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In chronic kidney disease, vascular calcification, renal osteodystrophy, and phosphate contribute substantially to cardiovascular risk and are components of CKD-mineral and bone disorder (CKD-MBD). The cause of this syndrome is unknown. Additionally, no therapy addresses cardiovascular risk in CKD. In its inception, CKD-MBD is characterized by osteodystrophy, vascular calcification, and stimulation of osteocyte secretion. We tested the hypothesis that increased production of circulating factors by diseased kidneys causes the CKD-MBD in diabetic mice subjected to renal injury to induce stage 2 CKD (CKD-2 mice). Compared with non-CKD diabetic controls, CKD-2 mice showed increased renal production of Wnt inhibitor family members and higher levels of circulating Dickkopf-1 (Dkk1), sclerostin, and secreted klotho. Neutralization of Dkk1 in CKD-2 mice by administration of a monoclonal antibody after renal injury stimulated bone formation rates, corrected the osteodystrophy, and prevented CKD-stimulated vascular calcification. Mechanistically, neutralization of Dkk1 suppressed aortic expression of the osteoblastic transcription factor Runx2, increased expression of vascular smooth muscle protein 22-a, and restored aortic expression of klotho. Neutralization of Dkk1 did not affect the elevated plasma levels of osteocytic fibroblast growth factor 23 but decreased the elevated levels of sclerostin. Phosphate binder therapy restored plasma fibroblast growth factor 23 levels but had no effect on vascular calcification or osteodystrophy. The combination of the Dkk1 antibody and phosphate binder therapy completely treated the CKD-MBD. These results show that circulating Wnt inhibitors are involved in the pathogenesis of CKD-MBD and that the combination of Dkk1 neutralization and phosphate binding may have therapeutic potential for this disorder. CKD is a pandemic affecting 26 million Americans in its early stages. 1 CKD is associated with high rates of cardiovascular mortality, making it much more likely that affected individuals will sustain cardiovascular morbidity, including death, than reach end stage kidney disease that requires RRT.

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Section: Discussionmentioning

confidence: 99%

CKD-Induced Wingless/Integration1 Inhibitors and Phosphorus Cause the CKD–Mineral and Bone Disorder

Fang¹,

Ginsberg

Seifert

et al. 2014

Journal of the American Society of Nephrology

152

186

View full text Add to dashboard Cite

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“…The prevalence of fractures in patients with CKD stage 3-4 is higher than that in persons without CKD (40,41). Most studies also demonstrate an overall decline in calcium content of bone by dual-energy x-ray absorptiometry (DXA) with progression of CKD (42)(43)(44)(45). DXA is as predictive of fractures in CKD patients with estimated GFR , 60 ml/min per 1.73 m 2 as it is in persons without CKD (46).…”

Section: Efficacy Of Calcium Binders For Bone Health In the Ckd Populmentioning

confidence: 99%

Calcium Builds Strong Bones, and More Is Better—Correct? Well, Maybe Not

Jamal

Moe

2012

Clinical Journal of the American Society of Nephrology

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SummaryCalcium supplementation has been considered the gold standard therapy for osteoporosis in the general population. It is given in both the placebo and treatment groups of trials evaluating antifracture efficacy of new therapies. Similarly, calcium-based phosphate binders have been considered the gold standard comparator for all new phosphate binders. However, large randomized trials demonstrate conflicting data on the antifracture efficacy of calcium supplementation, particularly in high doses, in patients with osteoporosis without CKD. In addition, recent data suggest an increased risk for cardiovascular events. These new studies raise safety concerns for the general approach with calcium supplementation and binders. This review describes recent data on the adverse effects of calcium supplementation for osteoporosis and how these new data should affect the strategy for phosphate binder use in CKD.

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“…In a cohort of 50 patients with CKD stages II-V and low vertebral or femoral BMD, biopsies (n = 40 patients) revealed adynamic bone (n = 21), osteomalacia (n = 17), and mixed bone disease (n = 2). While the investigators found trabecular bone volume to be lower in the adynamic and osteomalacic patients, there was no correlation between trabecular volume and BMD [22] .…”

Section: Discussionmentioning

confidence: 84%

Bisphosphonate Use in Chronic Kidney Disease: Association with Adynamic Bone Disease in a Bone Histology Series

et al. 2010

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Dual X-ray absorptiometry is the standard diagnostic modality for identification of low bone mineral density, a finding which is in the general population usually indicative of osteopenia or osteoporosis. However, chronic kidney disease (CKD) patients diagnosed with osteopenia or osteoporosis may in actual fact have renal osteodystrophy with high or low bone turnover. While bisphosphonates are currently prescribed for the prevention of fractures in osteoporosis and high-risk osteopenic patients, the clinical utility of bisphosphonate therapy in CKD has not been established. Furthermore, bisphosphonates accumulate in bone, inhibit osteoclasts, and may cause or exacerbate low-turnover (adynamic) bone disease – particularly in patients presenting with low parathyroid hormone (PTH) levels or receiving treatment for secondary hyperparathyroidism. Bone biopsy with non-decalcified histopathology remains the gold standard for the identification and evaluation of bone disorders, including osteoporosis and renal osteodystrophy. Thirteen CKD patients (stage II–IV), referred to our clinic over a 12-month period, were identified as having taken bisphosphonates from 4 to >60 months after a diagnosis of osteopenia or osteoporosis. All patients underwent biopsies of trabecular bone from the iliac crest following oral administration of time-separated doses of doxycycline and tetracycline. Bone pathology was assessed after processing for mineralized histology. For all patients, clinical data collection included assessment of likely causes of kidney disease, MDRD glomerular filtration rate, calcium-phosphate product, intact PTH level, alkaline phosphatase, and bisphosphonate exposure. All 13 patients were diagnosed with adynamic bone on biopsy evaluation. Eleven biopsies revealed decreased cancellous bone mass; 8 showed decreased osteoid surface; 8 disclosed decreased osteoid thickness, and all 13 demonstrated low or low-normal osteoclast/osteoblast interface. Assessment of dynamic bone formation demonstrated decreased or absent single- or double-labeled osteoid in all 13 bone specimens. Based on these observations, the use of bisphosphonates in CKD cannot be recommended.

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High prevalence of low bone mineral density in pre-dialysis chronic kidney disease patients: bone histomorphometric analysis

Cited by 53 publications

References 0 publications

CKD-Induced Wingless/Integration1 Inhibitors and Phosphorus Cause the CKD–Mineral and Bone Disorder

CKD-Induced Wingless/Integration1 Inhibitors and Phosphorus Cause the CKD–Mineral and Bone Disorder

Calcium Builds Strong Bones, and More Is Better—Correct? Well, Maybe Not

Bisphosphonate Use in Chronic Kidney Disease: Association with Adynamic Bone Disease in a Bone Histology Series

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