Diagnosis, assessment, and treatment of bone turnover abnormalities in renal osteodystrophy

Martin, Kévin; Ølgaard, Klaus; Coburn, Jack W.; Coen, G; Fukagawa, Masafumi; Langman, Craig B.; Malluche, Hartmut H.; McCarthy, James T.; Massry, Shaul G.; Mehls, Otto; Salusky, Isidro B.; Silver, Justin; Smogorzewski, M; Slatopolsky, Eduardo M; McCann, Linda

doi:10.1053/j.ajkd.2003.12.003

Cited by 148 publications

(106 citation statements)

References 46 publications

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“…It is well accepted that elevations in PTH are primarily responsible for the high bone turnover in the majority of individuals with late-stage CKD, and PTH measurements are used to predict HTO renal osteodystrophy. (58,(60)(61)(62)(63)(64) Although we cannot exclude the possibility that assay sensitivity may have limited our ability to detect the earliest rise in PTH, several recent clinical observations support our preclinical result because PTH levels do not uniformly predict bone turnover when diagnosed via a bone biopsy. (65)(66)(67) These findings raise the possibility that PTH may not be the sole determinant of elevated bone turnover.…”

Section: Discussionmentioning

confidence: 66%

“…These data are consistent with previously published data, in which bone disease has been observed in both rat and human bones even in the presence of significant residual renal function. (52,53,58) 1,25(OH) 2 D 3 is an important physiological activator of osteoclast activity. (59) We therefore tested whether the difference in basal 1,25(OH) 2 D 3 levels found in jck and WT mice was responsible for increased osteoclast activity by performing bone histomorphometry on WT and jck bones fed either diet.…”

Section: Discussionmentioning

confidence: 99%

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Repression of osteocyte Wnt/β-catenin signaling is an early event in the progression of renal osteodystrophy

Sabbagh

Graciolli

O’Brien

et al. 2012

Journal of Bone and Mineral Research

236

224

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Chronic kidney disease–mineral bone disorder (CKD‐MBD) is defined by abnormalities in mineral and hormone metabolism, bone histomorphometric changes, and/or the presence of soft‐tissue calcification. Emerging evidence suggests that features of CKD‐MBD may occur early in disease progression and are associated with changes in osteocyte function. To identify early changes in bone, we utilized the jck mouse, a genetic model of polycystic kidney disease that exhibits progressive renal disease. At 6 weeks of age, jck mice have normal renal function and no evidence of bone disease but exhibit continual decline in renal function and death by 20 weeks of age, when approximately 40% to 60% of them have vascular calcification. Temporal changes in serum parameters were identified in jck relative to wild‐type mice from 6 through 18 weeks of age and were subsequently shown to largely mirror serum changes commonly associated with clinical CKD‐MBD. Bone histomorphometry revealed progressive changes associated with increased osteoclast activity and elevated bone formation relative to wild‐type mice. To capture the early molecular and cellular events in the progression of CKD‐MBD we examined cell‐specific pathways associated with bone remodeling at the protein and/or gene expression level. Importantly, a steady increase in the number of cells expressing phosphor‐Ser33/37‐β‐catenin was observed both in mouse and human bones. Overall repression of Wnt/β‐catenin signaling within osteocytes occurred in conjunction with increased expression of Wnt antagonists (SOST and sFRP4) and genes associated with osteoclast activity, including receptor activator of NF‐κB ligand (RANKL). The resulting increase in the RANKL/osteoprotegerin (OPG) ratio correlated with increased osteoclast activity. In late‐stage disease, an apparent repression of genes associated with osteoblast function was observed. These data confirm that jck mice develop progressive biochemical changes in CKD‐MBD and suggest that repression of the Wnt/β‐catenin pathway is involved in the pathogenesis of renal osteodystrophy. © 2012 American Society for Bone and Mineral Research.

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Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Repression of osteocyte Wnt/β-catenin signaling is an early event in the progression of renal osteodystrophy

Sabbagh

Graciolli

O’Brien

et al. 2012

Journal of Bone and Mineral Research

236

224

View full text Add to dashboard Cite

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“…The laboratory findings of both patients revealed a serum PTH level slightly elevated, but when it is compared to the levels before the removal of the parathyroid glands, the considerable improvement in the HPT-II status became evidently unmistakable. Especially in patient 1, this fact was supported by the demonstrated normal levels of calcium, phosphorus, and alkaline phosphatase, the latter being a biochemical marker and, together with the PTH, commonly used in the diagnosis of different forms of bone disease associated with CKD [12].…”

Section: Discussionmentioning

confidence: 69%

Severe maxillofacial renal osteodystrophy in two patients with chronic kidney disease

Lopes

Albuquerque

Germano

et al. 2015

Oral Maxillofac Surg

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Renal osteodystrophy (ROD) is the bone pathology that occurs as an uncommon complication related to the several alterations in mineral metabolism present in patients with chronic kidney disease (CKD). This paper describes two cases of severe ROD affecting the maxilla and mandible and causing facial disfigurement of a young and a middle-aged female patient with CKD. Both patients had a history of secondary hyperparathyroidism, previously treated by surgery. The pathogenesis of the disease, as well as its clinical, imaging, and histopathological features, and management of the patient are discussed.

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“…7,9,10 Bone biopsy is the recognized gold standard for the diagnosis and evaluation of renal bone disease. [11][12][13] Previous reports assessing changes in vertebral bone with phosphate binders by electron-beam tomography (EBT) did not assess changes in bone histology. 9,10 Thus, a study using bone biopsies was conducted to compare the effects of sevelamer hydrochloride and calcium carbonate on bone histology.…”

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confidence: 99%

Effects of Sevelamer Hydrochloride and Calcium Carbonate on Renal Osteodystrophy in Hemodialysis Patients

Ferreira¹,

Frazão²,

Monier-Faugere³

et al. 2008

Journal of the American Society of Nephrology

153

130

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Disturbances in mineral metabolism play a central role in the development of renal bone disease. In a 54-wk, randomized, open-label study, 119 hemodialysis patients were enrolled to compare the effects of sevelamer hydrochloride and calcium carbonate on bone. Biopsy-proven adynamic bone disease was the most frequent bone abnormality at baseline (59%). Serum phosphorus, calcium, and intact parathyroid hormone were well controlled in both groups, although calcium was consistently lower and intact parathyroid hormone higher among patients who were randomly assigned to sevelamer. Compared with baseline values, there were no changes in mineralization lag time or measures of bone turnover (e.g., activation frequency) after 1 yr in either group. Osteoid thickness significantly increased in both groups, but there was no significant difference between them. Bone formation rate per bone surface, however, significantly increased from baseline only in the sevelamer group (P ϭ 0.019). In addition, of those with abnormal microarchitecture at baseline (i.e., trabecular separation), seven of 10 in the sevelamer group normalized after 1 yr compared with zero of three in the calcium group. In summary, sevelamer resulted in no statistically significant changes in bone turnover or mineralization compared with calcium carbonate, but bone formation increased and trabecular architecture improved with sevelamer. Further studies are required to assess whether these changes affect clinical outcomes, such as rates of fracture. 19: 405-412, 200819: 405-412, . doi: 10.1681 Patients with chronic kidney disease (CKD) typically have abnormal bone histology. Alterations in bone turnover, mineralization, and volume in renal patients depend on several factors. In particular, disturbances in calcium-phosphate, parathyroid hormone (PTH), and vitamin D metabolism are important in the development of renal osteodystrophy (ROD). J Am Soc NephrolThe pattern of ROD observed in patients with stage 5 CKD has changed in recent years. Previously, observed bone conditions in renal patients in order of prevalence were mixed uremic osteodystrophy (MUO), predominant hyperparathyroid bone disease (HPBD), and aluminum-related os-

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Diagnosis, assessment, and treatment of bone turnover abnormalities in renal osteodystrophy

Cited by 148 publications

References 46 publications

Repression of osteocyte Wnt/β-catenin signaling is an early event in the progression of renal osteodystrophy

Repression of osteocyte Wnt/β-catenin signaling is an early event in the progression of renal osteodystrophy

Severe maxillofacial renal osteodystrophy in two patients with chronic kidney disease

Effects of Sevelamer Hydrochloride and Calcium Carbonate on Renal Osteodystrophy in Hemodialysis Patients

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