Elsevier

Seminars in Nephrology

Volume 34, Issue 6, November 2014, Pages 626-640
Seminars in Nephrology

Adynamic Bone Disease: From Bone to Vessels in Chronic Kidney Disease,☆☆

https://doi.org/10.1016/j.semnephrol.2014.09.008Get rights and content

Summary

Adynamic bone disease (ABD) is a well-recognized clinical entity in the complex chronic kidney disease (CKD)–mineral and bone disorder. Although the combination of low intact parathyroid hormone (PTH) and low bone alkaline phosphatase levels may be suggestive of ABD, the gold standard for precise diagnosis is histomorphometric analysis of tetracycline double-labeled bone biopsies. ABD essentially is characterized by low bone turnover, low bone volume, normal mineralization, and markedly decreased cellularity with minimal or no fibrosis. ABD is increasing in prevalence relative to other forms of renal osteodystrophy, and is becoming the most frequent type of bone lesion in some series. ABD develops in situations with reduced osteoanabolic stimulation caused by oversuppression of PTH, multifactorial skeletal resistance to PTH actions in uremia, and/or dysregulation of Wnt signaling. All may contribute not only to bone disease but also to the early vascular calcification processes observed in CKD. Various risk factors have been linked to ABD, including calcium loading, ageing, diabetes, hypogonadism, parathyroidectomy, peritoneal dialysis, and antiresorptive therapies, among others. The relationship between low PTH level, ABD, increased risk fracture, and vascular calcifications may at least partially explain the association of ABD with increased mortality rates. To achieve optimal bone and cardiovascular health, attention should be focused not only on classic control of secondary hyperparathyroidism but also on prevention of ABD, especially in the steadily growing proportions of diabetic, white, and elderly patients. Overcoming the insufficient osteoanabolic stimulation in ABD is the ultimate treatment goal.

Section snippets

Definition Of Adynamic Bone Disease And Epidemiology

After the first descriptions of “late rickets associated with albuminuria” by Lucas7 in 1883 and “tumor of the parathyroid gland” by MacCallum8 in 1905, it was not until 1933 that Langmead and Orr9 suggested that parathyroid hyperplasia occurs secondary to advanced CKD. During the following decades, the development of secondary hyperparathyroidism and high turnover bone disease in CKD was the focus of research in this field,10 and it was not until the early 1980s that the term “aplastic bone

Aluminum

In the past, aluminum overload was the predominant cause of low-turnover bone disease in dialysis patients. A chronic low-dose exposure with concomitant high doses of vitamin D, probably favoring mineralization, was said to lead preferentially to ABD rather than to osteomalacia.12 As mentioned previously, mineralization defects in adults now are seen much more rarely than in previous decades,34, 35, 36 probably owing to decreasing aluminum exposure and more frequent use of active vitamin D

Risk Factors

A number of conditions decrease bone turnover and bone remodeling activity, and they are much more frequent than cases resulting from aluminum overload in current clinical practice. Thus, Ca loading (via Ca-based P binders or Ca content in the dialysate), excessive vitamin D or calcimimetic treatment, increasing age, diabetes, peritoneal dialysis, and bisphosphonates all have been described as risk factors for ABD, some of them independently of CKD.15, 16, 21, 25, 56, 97, 98, 99 Other possible

Diagnosis

As mentioned earlier, a bone biopsy is the gold standard for the diagnosis of ABD, but it is an invasive method and cannot be performed easily.12, 15, 21, 109 Radiographs and bone densitometry are not helpful for the diagnosis of ABD or ROD; curiously, however, important conceptual misunderstandings in this regard seem to be common among nephrologists according to a recent European Dialysis and Transplant Association-EDTA survey on the subject.110 Many other imaging techniques (from

Consequences Of Adynamic Bone Disease

Although some patients may develop persistent bone pain (the presence of aluminum should be especially suspected in this case), most patients with ABD are clinically asymptomatic.127, 128, 129 Consequently, we separate the main consequences of ABD into 3 categories: (1) laboratory abnormalities, (2) bone abnormalities, and (3) vascular calcifications, according to the concept of CKD-MBD. We also emphasize how all 3 are associated directly or indirectly with reduced survival and why ABD

Clinical Management

It must be taken into account that bone turnover is quite a slow process, which can take a few weeks to reverse in cases of high bone turnover, but a few months or even years in cases of ABD, whereas secretion of PTH is a very quick process (minutes) in response to variations in plasma Ca levels.59 As mentioned previously, little attention has been devoted to potential restimulation of bone metabolism when ABD is suspected or diagnosed, although it is known that ABD can be reversed in a

Acknowledgments

The authors would like to thank Dr. Martine Cohen-Solal for sharing the pathology pictures.

Jordi Bover belongs to the Spanish National Network of Kidney Research RedinRen (RD06/0016/0001 and RD12/0021/0033), the Spanish National Biobank network RD09/0076/00064, and to the Catalan Nephrology Research Group AGAUR 2009 SGR-1116, and collaborates with the Spanish Fundación Iñigo Alvarez de Toledo.

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    Financial support: none.

    ☆☆

    Conflict of interest statement: Jordi Bover has given lectures sponsored by Abbvie, Amgen, Genzyme, and Shire, has participated in national and international advisory boards for Abbvie, Amgen, Vifor, and Genzyme, and benefits from a joint-venture grant with other groups from Abbvie; Pablo Ureña has received personal fees and grants from Amgen, AbbVie, Genzyme-Sanofi, Hemotech, and Fresenius; and Vincent Brandenburg has received honoraria from Amgen, Sanofi, Astra-Zeneca, Fresenius, Synlab, Bayer, and Shire, and participated in advisory boards for Amgen, Sanofi, and Fresenius.

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