Adynamic Bone Disease: From Bone to Vessels in Chronic Kidney Disease☆,☆☆
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.
References (207)
- et al.
Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO)
Kidney Int
(2006) - et al.
Non-aluminic adynamic bone disease in non-dialyzed uremic patients: a new type of osteopathy due to overtreatment?
Bone
(1992) Hypokinetic azotemic osteodystrophy
Kidney Int
(1998)- et al.
Aplastic osteodystrophy without aluminum: the role of “suppressed” parathyroid function
Kidney Int
(1993) - et al.
Variant of adynamic bone disease in hemodialysis patients: fact or fiction?
Am J Kidney Dis
(2006) Adynamic bone in patients with chronic kidney disease
Kidney Int
(2008)- et al.
The spectrum of bone disease in end-stage renal failure--an evolving disorder
Kidney Int
(1993) - et al.
Bone disease in predialysis, hemodialysis, and CAPD patients: evidence of a better bone response to PTH
Kidney Int
(1995) - et al.
Different patterns of renal osteodystrophy in Iberoamerica
Am J Med Sci
(2000) - et al.
Mineral and bone disorders in chronic kidney disease and end-stage renal disease patients: new insights into vitamin D receptor activation
Kidney Int
(2011)
The calcemic response to PTH in the rat: effect of elevated PTH levels and uremia
Kidney Int
Dynamics of skeletal resistance to parathyroid hormone in the rat: effect of renal failure and dietary phosphorus
Bone
Intermittent versus continuous administration of 1,25-dihydroxyvitamin D3 in experimental renal hyperparathyroidism
Kidney Int
A novel mechanism for skeletal resistance in uremia
Kidney Int
The renal PTH/PTHrP receptor is down-regulated in rats with chronic renal failure
Kidney Int
Factors in the development of secondary hyperparathyroidism during graded renal failure in the rat
Kidney Int
Report on 2012 ISN Nexus symposium: ‘bone and the kidney’
Kidney Int
Early chronic kidney disease-mineral bone disorder stimulates vascular calcification
Kidney Int
Development of adynamic bone in patients with secondary hyperparathyroidism after intermittent calcitriol therapy
Kidney Int
Plasma insulin-like growth factors and bone formation in uremic hyperparathyroidism
Kidney Int
Association of changes in bone remodeling and coronary calcification in hemodialysis patients: a prospective study
Am J Kidney Dis
Identification of a low molecular weight inhibitor of osteoblast mitogenesis in uremic plasma
Kidney Int
Patterns of FGF-23, DMP1, and MEPE expression in patients with chronic kidney disease
Bone
Bone: a new endocrine organ at the heart of chronic kidney disease and mineral disorders
Lancet Diabetes Endocrinol
The uses and abuses of vitamin D compounds in chronic kidney disease-mineral bone disease (CKD-MBD)
Semin Nephrol
Development of secondary hyperparathyroidism and bone disease in diabetic rats with renal failure
Kidney Int
The impact of diabetes mellitus on vitamin D metabolism in predialysis patients
Bone
Role of advanced glycation end products in adynamic bone disease in patients with diabetic nephropathy
Am J Kidney Dis
Association of relatively low serum parathyroid hormone with malnutrition-inflammation complex and survival in maintenance hemodialysis patients
J Ren Nutr
KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD)
Kidney Int Suppl
Studies in calcium and phosphorus metabolism with special reference to pathogenesis and effects of dihydrotachysterol (A.T. 10) and iron
Medicine
Histomorphometric measurements of bone turnover, mineralization, and volume
Clin J Am Soc Nephrol
Is chronic kidney disease-mineral bone disorder (CKD-MBD) really a syndrome?
Nephrol Dial Transplant
Endorsement of the Kidney Disease Improving Global Outcomes (KDIGO) chronic kidney disease-mineral and bone disorder (CKD-MBD) guidelines: a European Renal Best Practice (ERBP) commentary statement
Nephrol Dial Transplant
Form of late rickets associated with albuminuria, rickets of adolescents
Lancet
Tumor of the parathyroid gland
John Hopkins Hosp Bull
Renal rickets associated with parathyroid hyperplasia
Arch Dis Child
Renal osteodystrophies
Osteoporosis and adynamic bone in chronic kidney disease
J Nephrol
The aplastic form of renal osteodystrophy
Nephrol Dial Transplant
Adynamic bone disease-bone and beyond
NDT Plus
Adynamic bone disease: clinical and therapeutic implications
Curr Opin Nephrol Hypertens
When, how, and why a bone biopsy should be performed in patients with chronic kidney disease (CKD)?
Semin Nephrol
Renal bone disease: a new conceptual framework for the interpretation of bone histomorphometry
Curr Opin Nephrol Hypertens
The link between bone and coronary calcifications in CKD-5 patients on haemodialysis
Nephrol Dial Transplant
Effects of sevelamer hydrochloride and calcium carbonate on renal osteodystrophy in hemodialysis patients
J Am Soc Nephrol
High prevalence of low bone mineral density in pre-dialysis chronic kidney disease patients: bone histomorphometric analysis
Clin Nephrol
Low turn-over bone disease in patients with chronic renal disease
Med Pregl
Spectrum of renal bone disease in end-stage renal failure patients not yet on dialysis
Nephrol Dial Transplant
The importance of bone health in end-stage renal disease: out of the frying pan, into the fire?
Nephrol Dial Transplant
Cited by (84)
Mechanistic insights into CKD-MBD-related vascular calcification and its clinical implications
2022, Life SciencesCitation Excerpt :Because secondary hyperparathyroidism is typically accompanied by hyperphosphatemia, a known cause of vascular calcification, or by the use of medications that may affect VC, such as calcium-based phosphate binders and calcitriol, secondary hyperparathyroidism has been found to make it more difficult to precisely determine the relationship between PTH and vascular calcification in human CKD clinical studies. On the other hand, people with kidney illness who also have adynamic bone disease (ABD), which is connected to vascular calcification, have low PTH levels [120,121]. ABD is distinguished by low bone turnover and a thin osteoid buildup without osteoid accumulation.
An optimized machine learning framework for predicting intradialytic hypotension using indexes of chronic kidney disease-mineral and bone disorders
2022, Computers in Biology and MedicineOsteoporosis in chronic kidney disease: A essential challenge
2022, Medicina ClinicaRenal hyperparathyroidism
2022, Vitamins and HormonesAdynamic bone disease: Revisited
2022, Nefrologia
- ☆
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.