Renal osteodystrophy/adynamic bone disease is currently defined as an alteration of bone morphology in patients with

chronic kidney disease Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vo ...

(CKD). It is one measure of the skeletal component of the systemic disorder of

chronic kidney disease-mineral and bone disorder Chronic kidney disease–mineral and bone disorder (CKD-MBD) is one of the many complications associated with chronic kidney disease. It represents a systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combi ...

(CKD-MBD). The term "renal osteodystrophy" was coined in 1943, 60 years after an association was identified between bone disease and

kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

. The traditional types of renal osteodystrophy have been defined on the basis of turnover and mineralization as follows: 1) mild, slight increase in turnover and normal mineralization; 2) osteitis fibrosa, increased turnover and abnormal mineralization; 3)

osteomalacia Osteomalacia is a disease characterized by the softening of the bones caused by impaired bone metabolism primarily due to inadequate levels of available phosphate, calcium, and vitamin D, or because of resorption of calcium. The impairment of bon ...

, decreased turnover and abnormal mineralization; 4) adynamic, decreased turnover and acellularity; and, 5) mixed, increased turnover with abnormal mineralization. A Kidney Disease: Improving Global Outcomes report has suggested that bone biopsies in patients with CKD should be characterized by determining bone turnover, mineralization, and volume (TMV system). On the other hand, CKD-MBD is defined as a systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of the following: 1) abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism; 2) abnormalities in bone turnover, mineralization, volume, linear growth, or strength (renal osteodystrophy); and 3) vascular or other soft-tissue calcification.

Signs and symptoms

Renal osteodystrophy may exhibit no symptoms; if it does show symptoms, they include: *

Bone pain Bone pain (also known medically by several other names) is pain coming from a bone, and is caused by damaging stimuli. It occurs as a result of a wide range of diseases or physical conditions or both, and may severely impair the quality of life. ...

Joint pain Arthralgia (from Greek ''arthro-'', joint + ''-algos'', pain) literally means ''joint pain''. Specifically, arthralgia is a symptom of injury, infection, illness (in particular arthritis), or an allergic reaction to medication. According to MeSH, ...

* Bone deformation *

Bone fracture A bone fracture (abbreviated FRX or Fx, Fx, or #) is a medical condition in which there is a partial or complete break in the continuity of any bone in the body. In more severe cases, the bone may be broken into several fragments, known as a '' ...

* The broader concept of chronic kidney disease-mineral and bone disorder (CKD-MBD) is not only associated with

fractures Fracture is the separation of an object or material into two or more pieces under the action of stress. The fracture of a solid usually occurs due to the development of certain displacement discontinuity surfaces within the solid. If a displa ...

but also with cardiovascular

calcification Calcification is the accumulation of calcium salts in a body tissue. It normally occurs in the formation of bone, but calcium can be deposited abnormally in soft tissue,Miller, J. D. Cardiovascular calcification: Orbicular origins. ''Nature Mat ...

, poor quality of life and increased morbidity and mortality in CKD patients (the so-called bone-vascular axis). These clinical consequences are acquiring such an importance that scientific working groups (such as the ERA-EDTA CKD-MBD Working Group) or international initiatives are trying to promote research in the field including basic, translational and clinical research.

Pathogenesis

Renal osteodystrophy has been classically described to be the result of

hyperparathyroidism Hyperparathyroidism is an increase in parathyroid hormone (PTH) levels in the blood. This occurs from a disorder either within the parathyroid glands (primary hyperparathyroidism) or as response to external stimuli (secondary hyperparathyroidism). ...

secondary to

hyperphosphatemia Hyperphosphatemia is an electrolyte disorder in which there is an elevated level of phosphate in the blood. Most people have no symptoms while others develop calcium deposits in the soft tissue. Often there is also low calcium levels which can ...

combined with

hypocalcemia Hypocalcemia is a medical condition characterized by low calcium levels in the blood serum. The normal range of blood calcium is typically between 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L) while levels less than 2.1 mm ...

, both of which are due to decreased excretion of phosphate by the damaged kidney. Low activated vitamin D₃ levels are a result of the damaged kidneys' inability to convert vitamin D₃ into its active form,

calcitriol Calcitriol is the active form of vitamin D, normally made in the kidney. It is also known as 1,25-dihydroxycholecalciferol. It is a hormone which binds to and activates the vitamin D receptor in the nucleus of the cell, which then increases the ...

, and result in further

. High levels of

fibroblast growth factor 23 Fibroblast growth factor 23 (FGF23) is a protein and member of the fibroblast growth factor (FGF) family which participates in the regulation of phosphate in plasma and vitamin D metabolism. In humans it is encoded by the gene. FGF23 decreases rea ...

seem now to be the most important cause of decreased calcitriol levels in CKD patients. In CKD, the excessive production of

parathyroid hormone Parathyroid hormone (PTH), also called parathormone or parathyrin, is a peptide hormone secreted by the parathyroid glands that regulates the serum calcium concentration through its effects on bone, kidney, and intestine. PTH influences bone ...

increases the bone resorption rate and leads to histologic bone signs of secondary hyperparathyroidism. However, in other situations, the initial increase in parathyroid hormone and bone remodeling may be slowed excessively by a multitude of factors, including age, ethnic origin, sex, and treatments such as vitamin D, calcium salts,

calcimimetic A calcimimetic is a pharmaceutical drug that mimics the action of calcium on tissues, by allosteric activation of the calcium-sensing receptor that is expressed in various human organ tissues. Calcimimetics are used to treat secondary hyperparathyro ...

s, steroids, and so forth, leading to low bone turnover or adynamic bone disease. Both high and low bone turnover diseases are currently observed equally in CKD patients treated by dialysis, and all types of renal osteodystrophy are associated with an increased risk of skeletal fractures, reduced quality of life, and poor clinical outcomes.

Diagnosis

Renal osteodystrophy is usually diagnosed after treatment for

end-stage kidney disease Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vo ...

begins; however the CKD-MBD starts early in the course of CKD. In advanced stages, blood tests will indicate decreased

calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...

and

(vitamin D) and increased

phosphate In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid . The phosphate or orthophosphate ion is derived from phospho ...

, and

levels. In earlier stages, serum calcium, phosphate levels are normal at the expense of high parathyroid hormone and fibroblast growth factor-23 levels. X-rays will also show bone features of renal osteodystrophy (subperiostic bone resorption,

chondrocalcinosis Chondrocalcinosis or cartilage calcification is calcification (accumulation of calcium salts) in hyaline cartilage and/or fibrocartilage.Rothschild, Bruce M It can be seen on radiography. Causes Buildup of calcium phosphate in the ankle joints h ...

at the knees and

pubic symphysis The pubic symphysis is a secondary cartilaginous joint between the left and right superior rami of the pubis of the hip bones. It is in front of and below the urinary bladder. In males, the suspensory ligament of the penis attaches to the pubic ...

osteopenia Osteopenia, known as "low bone mass" or "low bone density", is a condition in which bone mineral density is low. Because their bones are weaker, people with osteopenia may have a higher risk of fractures, and some people may go on to develop osteop ...

and bone fractures) but may be difficult to differentiate from other conditions. Since the diagnosis of these bone abnormalities cannot be obtained correctly by current clinical, biochemical, and imaging methods (including measurement of bone-mineral density), bone biopsy has been, and still remains, the gold standard analysis for assessing the exact type of renal osteodystrophy. File:X-ray of periosteal reaction in renal osteodystrophy.jpg,

Projectional radiography Projectional radiography, also known as conventional radiography, is a form of radiography and medical imaging that produces two-dimensional images by x-ray radiation. The image acquisition is generally performed by radiographers, and the images ...

("X-ray") of

periosteal reaction A periosteal reaction is the formation of new bone in response to injury or other stimuli of the periosteum surrounding the bone. It is most often identified on X-ray films of the bones. Cause A periosteal reaction can result from a large number ...

. File:X-ray of ground glass density of the skull by renal osteodystrophy.jpg, Ground glass density of the skull. File:CT of sclerotic lesions in the skull in renal osteodystrophy.jpg, CT shows focal areas of osteosclerosis. File:X-ray of brown tumors in the pelvis and a hip fracture in renal osteodystrophy.jpg, Brown tumors in the pelvis and a hip fracture. File:CT of subchondral resorption in the SI joint in renal osteodystrophy.jpg, Subchondral resorption in the

sacroiliac joint The sacroiliac joint or SI joint (SIJ) is the joint between the sacrum and the ilium bones of the pelvis, which are connected by strong ligaments. In humans, the sacrum supports the spine and is supported in turn by an ilium on each side. The ...

. File:X-ray of rugger-jersey spine of renal osteodystrophy.jpg, X-ray of a subtle "rugger jersey spine" due to sclerotic bands adjacent to the vertebral endplates. File:CT of rugger-jersey spine of renal osteodystrophy.jpg, CT scan of the same case.

Differential diagnosis

To confirm the diagnosis, renal osteodystrophy must be characterized by determining bone turnover, mineralization, and volume (TMV system) (bone biopsy). All forms of renal osteodystrophy should also be distinguished from other bone diseases which may equally result in decreased bone density (related or unrelated to CKD): *

osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone ...

brown tumor The brown tumor is a bone lesion that arises in settings of excess osteoclast activity, such as hyperparathyroidism. They are a form of osteitis fibrosa cystica. It is not a neoplasm, but rather simply a mass. It most commonly affects the maxilla a ...

should be considered as the top-line diagnosis if a mass-forming lesion is present.

Treatment

Treatment for renal osteodystrophy includes the following: * calcium and/or native

vitamin D Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 (c ...

supplementation * restriction of dietary phosphate (especially inorganic phosphate contained in additives) *

phosphate binders Phosphate binders are medications used to reduce the absorption of dietary phosphate; they are taken along with meals and snacks. They are frequently used in people with chronic kidney failure (CKF), who are less able to excrete phosphate, resulting ...

such as calcium carbonate,

calcium acetate Calcium acetate is a chemical compound which is a calcium salt of acetic acid. It has the formula Ca(C2H3O2)2. Its standard name is calcium acetate, while calcium ethanoate is the systematic name. An older name is acetate of lime. The anhydrous ...

sevelamer Sevelamer (rINN) is a phosphate binding medication used to treat hyperphosphatemia in patients with chronic kidney disease. When taken with meals, it binds to dietary phosphate and prevents its absorption. Sevelamer was invented and developed by ...

hydrochloride or carbonate,

lanthanum carbonate Lanthanum carbonate, La( C O3)3, is the salt formed by lanthanum(III) cations and carbonate anions. It is an ore of lanthanum metal (bastnäsite), along with monazite. Chemistry Lanthanum carbonate is used as a starting material in lanthanum c ...

, sucroferric oxyhydroxide, ferric citrate among others * active forms of vitamin D (

alfacalcidol Alfacalcidol (or 1-hydroxycholecalciferol) is an analogue of vitamin D used for supplementation in humans and as a poultry feed additive. Alfacalcidol has a weaker impact on calcium metabolism and parathyroid hormone levels than calcitriol, howev ...

paricalcitol Paricalcitol (chemically it is 19-nor-1,25-(OH)2-vitamin D2. Marketed by Abbott Laboratories under the trade name Zemplar) is a drug used for the prevention and treatment of secondary hyperparathyroidism (excessive secretion of parathyroid horm ...

, maxacalcitol,

doxercalciferol Doxercalciferol (or 1-hydroxyergocalciferol, trade name Hectorol) is drug for secondary hyperparathyroidism and metabolic bone disease. It is a synthetic analog of ergocalciferol (vitamin D2). It suppresses parathyroid synthesis and secretion. ...

, among others) *

cinacalcet Cinacalcet, sold under the brand name Sensipar among others, is a medication used to treat tertiary hyperparathyroidism, parathyroid carcinoma, and primary hyperparathyroidism. Text was copied from this source which is © European Medicines Agenc ...

renal transplantation Kidney transplant or renal transplant is the organ transplant of a kidney into a patient with end-stage kidney disease (ESRD). Kidney transplant is typically classified as deceased-donor (formerly known as cadaveric) or living-donor transplantat ...

haemodialysis Hemodialysis, also spelled haemodialysis, or simply dialysis, is a process of purifying the blood of a person whose kidneys are not working normally. This type of dialysis achieves the extracorporeal removal of waste products such as creatinin ...

five times a week is thought to be of benefit *

parathyroidectomy Parathyroidectomy is the surgical removal of one or more of the (usually) four parathyroid glands. This procedure is used to remove an adenoma or hyperplasia of these glands when they are producing excessive parathyroid hormone (PTH): hyperparathy ...

for symptomatic medication refractive end stage disease

Prognosis

Recovery from renal osteodystrophy has been observed following kidney transplantation. Renal osteodystrophy is a chronic condition with a conventional hemodialysis schedule. Nevertheless, it is important to consider that the broader concept of CKD-MBD, which includes renal osteodystrophy, is not only associated with bone disease and increased risk of fractures but also with cardiovascular calcification, poor quality of life and increased morbidity and mortality in CKD patients (the so-called bone-vascular axis). Actually, bone may now be considered a new endocrine organ at the heart of CKD-MBD.

References

External links

Renal Osteodystrophy
- NKUDIC, NIH {{Nephrology Kidney diseases Histopathology 1940s neologisms