Renal osteodystrophy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: nazia fuadSynonyms and keywords:↓↑

Overview

Renal osteodystrophy is the term used to describe the complex metabolic bone disorders that occur as a complication of chronic renal insufficiency.secondary hyperparathyroidism and 1a,25-dihydroxycholecalciferol (1a,25-dihydroxyvitamin D3) deficiency are major contributors to renal osteodystrophy .

Historical Perspective

International work group convened in 2006 by Kidney Disease: Improving Global Outcomes (KDIGO) recommended that the term, renal osteodystrophy, be exclusively used to define bone pathology associated with CKD,chronic kidney disease.

During the 1970s and 1980s, it was discovered that an accumulation of aluminum from water used for dialysis and aluminum salts used as phosphate binders caused osteomalacia and an adynamic bone disease .The identification of these disorders broadened the spectrum of renal osteodystrophy and led to changes in the composition of dialysis fluids and the substitution of calcium carbonate for aluminum salts. As a result, the frequency of aluminum-related bone disease is waning.

Classification

Table 1. Histologic Classification of Renal Osteodystrophy

Histologic Classification of Renal Osteodystrophy
Disorder	Description	Pathogenesis	frequency(%)
Osteitis fibrosa	Peritrabecular fibrosis, increased remodeling — resorption and formation.	Secondary hyperparathyroidism, secondary role of cytokines and growth factors	50
Osteomalacia	Increased osteoid, defective mineralization	Aluminum deposition, plus unknown factors	7
mixed disease	Features of both osteitis fibrosa and osteomalacia	Secondary hyperparathyroidism and aluminum deposition, plus unknown factors	13
mild disease	Slightly increased remodeling	Early or treated secondary hyperparathyroidism	3
adynamic renal bone disease	Hypocellular bone surfaces, no remodeling	Aluminum deposition, parathyroid hormone suppression, and other factors (deficiency of bone growth factors or increased suppressors of bone remodeling)	27

Table 2 .TMV Classification:

It is done on the basis of interpretation of bone biopsy,and uses three histologic descriptors- bone turnover, mineralization

and volume. it provides a clinically relevant description of the bone pathology as assessed by histomorphometry, which in turn define the pathophysiology and thereby guide therapy.

Turnover	Mineralization	Volume
Low		Low
	Normal
Normal		Normal
	Abnormal
High		High

Pathophysiology :

The factors that contribute to pathophysiology of Renal osteodystrophy in chronic kidney disease are:

• Hyperphosphatemia , due to impaired renal phosphorus excretion with GFR below 60ml/min in chronic Kidney disease.
•  Hypocalcemia, 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, and result in further hypocalcaemia.
•  Hyperphosphatemia combined with hypocalcemia leads to hyperparathyroidism
• Elevated level of Hyperparathyroid leads to Osteitis fibrosa .
• High levels of fibroblast growth factor 23

Factors in the pathogenesis of hyperparathyroidism in chronic renal disease
	phosphorus retention	hypocalcemia	low calciterol	skeletal resistance	altered parathyroid function
↓Renal mass	+		+
↑phosphorus		+	+	+	?
↓calcium					+
↓calciterol		+		+	+
skeletal resistance	+
desensitization to PTH		+
↓vit D recepters					+
altered cell growth					+
Acidosis			+

• ==

Causes

The common causes of renal osteodystrophy are:

• Disorder of bone and mineral metabolism associated with chronic renal disease.
• Skeletal disorders associated with renal dysfunction.
• Hypocalcemia,
• Hyperphosphotemia
• 1,25D defeciency
• Parathyroid gland hyperplasia.
• Systemic acidosis
• Aluminum retention,(in dialysis patients)
• Accumulation of β2M in bone and joints.

Differentiating Renal Osteodystrophy from Other Diseases

Renal osteodystrophy must be differentiated from other diseases that cause abnormal bone mineralization, unexplained bone fractures and bone pain,it include

• Primary Hyperparathyroidism,which typically presents with hypercalcemia, hyperparathyroidism, and normal-to-low phosphate in patients with normal or minimally-reduced renal function
• Tertiary Hyperparathyroidism typically presents as hypercalcemia, hyperparathyroidism, and normal-to-elevated phosphate in patients with longstanding CKD-MBD.

• Osteoporosis and
• Vitamin D deficiency will have normal or minimally reduced renal function.

Epidemiology and Demographics

• Approximately 8% of the adult population in the US has a glomular filtration rate (GFR) less than 60 mL/min and is at risk of developing renal osteodystrophy and other manifestations of CKD-MBD.
• prevelence in developing countries:

• .the prevelance of renal osteodystrophy in developing countries 24.4% to 63%.

• Aluminium related bone disease is a common cause. High strontium levels and iron overload in developing countries play a major role in the development of renal bone disease among dialysis patients.

Risk Factors

Common risk factors in the development of Renal Osteodystrophy are:

• Chronic Renal Disease
• Secondry Hyperparathyroidism
• Aluminium intoxication(mainly in dialysis patients)
• Vit D deficiency

Natural History, Complications, and Prognosis

Common complications of Renal osteodystrophy include

• Bone fractures,
• Vascular calcifications leading to atheroscelorosis, coronary artery calcification, hypertension, left ventricular hypertrophy, and congestive heart failure.
• Extraskeletal calcification can also affect the heart valves and the cardiac conduction system.
• Calcification of skin arterioles may lead to a condition of ischemia and necrosis of the skin known as calciphylaxis.

Prognosis is generally good after Renal Transplant, otherwise it is associated with increase risk of bone fractures , cardiovascular calcifications ,poor quality of life and increased morbidity and mortality in patients with Chronic Kidney disease.

Diagnostic Study of Choice

Bone biopsy

A definitive diagnosis of renal osteodystrophy and the identification of histologic subtype are made by bone biopsy .

however bone biopsy are infrequently performed because of invasive and expensive procedure. 

indication for bone biopsy:

according to KDIGO 2017 guidelines a bone biopsy is indicated if knowledge of the type of renal osteodystrophy will affect treatment decisions

Serum biomarkers: 

• serum calcium, levels are typically low.
• serum phosphorous,,elevated depending on the stage of CKD, adherence to dietary phosphorous restriction, and use of phosphate binders.
• alkaline phosphatase (total or bone-specific)
• Parathyroid hormone(PTH) .

PTH levels are the best noninvasive option for assessment of bone turnover. ==

the following parameters are used to define the risk for specific subtypes of renal osteodystrophy :

 ●PTH <100 pg/mL suggests adynamic bone disease and a decreased risk of osteitis fibrosa cystica and or MUO.

●PTH >450 pg/mL suggests osteitis fibrosa cystica and/or MUO.

●Intermediate PTH levels between 100 and 450 pg/mL are not useful to predict the type of renal osteodystrophy. Intermediate values may be associated with normal or increased turnover or even reduced turnover. .   

History and Symptoms

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

• Bone pain
• Joint pain
• chest pain due to atherosclerotic disease
• Dyspnea, due to CHF
• palpitation or slow pulse due to conduction heart defects.

Physical Examination

Patients with Renal osteodystrophy usually appear sick. Physical examination of patients with Renal Osteodystrophy may include

• Bone deformity
• Bone fracture
• Hypertension
• Congestive heart failure
• Heart murmur
• Increase Pulse Pressure( due to aortic calcification)
• Ischemia and Necrosis of skin called calciphylaxix.

Laboratory Findings

•  Measurement of bone turnover on a bone biopsy is assessed by labeling the bone with tetracycline at two separate times approximately 2 weeks apart. The distance between the two areas of tetracycline deposition can be used to calculate bone growth.

• serum calcium, levels are typically low.
• serum phosphorous,,elevated depending on the stage of CKD, adherence to dietary phosphorous restriction, and use of phosphate binders.
• alkaline phosphatase (total or bone-specific)
• Parathyroid hormone(PTH) .

PTH levels are the best noninvasive option for assessment of bone turnover. === the following parameters are used to define the risk for specific subtypes of renal osteodystrophy :

 ●PTH <100 pg/mL suggests adynamic bone disease and a decreased risk of osteitis fibrosa cystica and or MUO.

●PTH >450 pg/mL suggests osteitis fibrosa cystica and/or MUO.

●Intermediate PTH levels between 100 and 450 pg/mL are not useful to predict the type of renal osteodystrophy. Intermediate values may be associated with normal or increased turnover or even reduced turnover. .   

Electrocardiogram

ECG findings associated with Renal Osteodystrophy may include

• Heart block
• Non ST elevation MI

X-ray

•  routine radiographic screening are not performed for bone disease in patients with end-stage renal disease (ESRD).

• Radiographic findings are less sensitive for diagnosis than PTH levels and do not establish the type of bone disease.

• Imaging may be done for patients with unexplained bone pain or fractures.
• Characteristic radiographic findings of osteitis fibrosa cystica include subperiosteal resorption and new bone formation, particularly at the radial aspect of the middle phalanges.
• Resorptive loss of bone may be also observed at the terminal phalanges, distal ends of the clavicles, and in the skull.

• Radiographs may also reveal soft tissue calcification, particularly including the vasculature,

Echocardiography or Ultrasound

echocardiography will show

• Diastolic dysfunction,
• Left Ventricular Hypertrophy,
• valvular calcifications

CT scan

CT scan findings associated with Renal Osteodystrophy are the same that r related to chronic kidney disease .

MRI

There are no MRI findings .

Other Imaging Findings

There are no other imaging findings associated with Renal Osteodystrophy

Other Diagnostic Studies

 DEXA bone densitometry may reveal low bone density.

Treatment

Medical Therapy:

The mainstays of the prevention and treatment of renal osteodystrophy continue to be phosphate binders and supplemental calcium.

Control of Serum Phosphate

• A low-phosphate diet is integral to the management of end-stage renal disease, to maintain a normal serum phosphate concentration.
• A phosphate binder, either calcium carbonate68 or calcium acetate,69 taken with each meal in proportion to the phosphate content of the meal, is usually also required;
• aluminum-containing phosphate binders should be avoided. Reducing dialysate magnesium concentrations and adding magnesium-containing binders to decrease the calcium salts may allow both the control of serum phosphate concentrations and higher doses of calcitriol70 .
• Control of Serum CalciumCalcium malabsorption is very common in end-stage renal disease because of deficient 1a,25-dihydroxycholecalciferol.
• Serum calcium concentrations need to be maintained at the high end of the normal range in order to prevent or suppress oversecretion of parathyroid hormone.
• 71 A dialysate calcium concentration of 7 mg per deciliter (1.75 mmol per liter) provides an influx of approximately 800 mg per treatment.
• . When calcium salts are required to control hyperphosphatemia, the increased dialysate calcium concentration may cause hypercalcemia. The dialysate calcium concentration should be reduced to 5 mg per deciliter (1.25 mmol per liter), a level that will not affect the calcium balance and will allow for sufficient oral intake of calcium salts to maintain normal serum phosphate concentrations.73 The timing of oral calcium intake is important; calcium taken between meals is more a calcium supplement than a phosphate binder.
• use of Vit D analogue

.Surgery

• The mainstay of treatment for Renal Osteodystrophy is medical therapy. Surgery is usually reserved for patients with hyperparathroid

bone disease,these patients need subtotal parathyroidectomy

• Renal Transplant

Primary Prevention

• Timely recognition and treatment of hyperparathyroid patients.
• Early recognition and treatment of renal diseases to prevent chronic renal failure and consequently Renal osteodystrophy

Secondary Prevention

• Vit D administration with every session of dialysis
• Use of aluminium free phosphate binders.

Related Chapters

• osteoporosis
• osteopenia
• osteomalacia
• hyperparathyroidism
• multiple myeloma
• soft tissue calcification including collagen vascular disease
• hydroxyapatite crystal deposition disease
• hypervitaminosis

External links

Renal Osteodystrophy

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