What Is Osteodystrophy?

Osteodystrophy is a medical term used to describe abnormal changes in the growth and formation of bone. It is most commonly the result of chronic kidney disease. In children, osteodystrophy can cause bone malformation and short stature, while adults may experience brittle bones and fractures.

Because the disease is the result of the malabsorption of calcium, osteodystrophy is most commonly treated with calcium supplements.

Types of Osteodystrophy

Osteodystrophy is most often the result of chronic kidney disease (CKD), a condition in which the gradual loss of renal (kidney) function causes wastes to accumulate in the body as the kidneys start to fail.

Osteodystrophy is part of a larger spectrum of disorders referred to as chronic kidney disease mineral and bone disorder (CKD-MBD). This refers specifically to the effect that mineral imbalances caused by CKD have on the body as a whole, including the heart and blood vessels.

Osteodystrophy doesn't manifest in the same way in everyone. There are variations based on abnormalities in two biological processes:

• Bone turnover—the resorption of minerals as old bone is broken down to form new bones.
• Bone mineralization—the manner in which minerals are placed in the bone matrix.

How each of these processes occurs with the other can determine if bones are brittle, underdeveloped, or malformed.

Classification

Based on the dynamic of bone turnover and bone mineralization, renal osteodystrophy can be classified into one of the following five types.

• Mild osteodystrophy: Characterized by a slight increase in bone turnover with normal mineralization
• Osteitis fibrosa: Characterized by increased bone turnover and normal mineralization, resulting in the formation of weak and deformed bones
• Osteomalacia: Characterized by decreased bone turnover and abnormal mineralization, resulting in the formation of "soft" bones than can bow and break
• Atypical osteodystrophy: Characterized by decreased bone turnover and acellularity ("true bone")
• Mixed osteodystrophy: Characterized by increased bone turnover with abnormal mineralization

A less common cause of osteodystrophy is severe primary hyperparathyroidism (overactive parathyroid glands). The parathyroid glands help regulate calcium levels by releasing hormones into the blood. When these hormones are overproduced, they can speed bone resorption, leading to bone mineral loss, pain, and deformity.

Osteodystrophy Symptoms

The symptoms of osteodystrophy vary by the timing of the onset of disease and other factors. The disease in children is very different from that in adults.

In early disease, there may be no notable signs or symptoms. It is only when bone turnover and/or mineralization are significantly impaired that the cumulative effect becomes more apparent. When symptoms do appear, they can manifest with:

• Bone pain
• Joint pain
• Bone deformity
• Pathologic fracture

In adults, symptoms of renal osteodystrophy aren't usually seen until people have been on dialysis for several years. Over time, the bones can become thin and weak, leading to the classic triad of bone pain, joint pain, and fractures.

Complications

As a facet of CKD-MBD, osteodystrophy can co-occur with cardiovascular disease. Due to mineral imbalances caused by kidney failure, excessive calcium in the bloodstream can begin to accumulate in the heart and blood vessels, causing them to harden (referred to as calcification) and structurally change (referred to as tissue remodeling).

Changes like these can impair blood flow and trigger an array of cardiovascular symptoms, including:

• Shortness of breath
• Persistent fatigue
• Lightheadedness, dizziness, or fainting
• Heart murmur
• Angina (chest pains)
• Heart palpitations
• Arrhythmia (irregular heartbeat)
• Bradycardia (slowed heartbeat)

If not treated appropriately, the cardiovascular symptoms of CKD-MBD can lead to heart failure and sudden cardiac death.

Adults with osteodystrophy are also vulnerable to avascular necrosis (a.k.a. osteonecrosis). This occurs when tiny breaks in a bone cause it to collapse and cut off blood circulation. The loss of oxygen and nutrients can cause permanent and irreversible bone death, manifesting with pain, limping, and a reduced range of motion.

Causes

The pathogenesis (manner of development) of osteodystrophy is complex. When the kidneys are damaged, they are less able to filter waste from the blood. Among the consequences of this: a mineral known as phosphorus can start to accumulate in the bloodstream, resulting in hyperphosphatemia (high blood phosphorus).

This can set off a chain reaction of events that can lead to bone damage:

1. When phosphorus levels rise in the bloodstream, calcium levels drop, because phosphorus combines with calcium to form calcium phosphate.
2. When calcium levels drop, the parathyroid glands release parathyroid hormone (PTH) in an effort to restore the balance between phosphorus and calcium levels.
3. In order to do this, however, PTH removes calcium from bones and places it into the bloodstream, causing bone mineral loss and/or the impairment of bone remodeling.

The kidneys are also responsible for converting vitamin D into its active form, called calcitriol. Calcitriol, under the direction of PTH, helps normalize calcium levels by increasing the absorption of calcium in the gut. If the kidneys are damaged, they are less able to synthesize calcitriol, leading to hypocalcemia (low blood calcium).

Primary vs. Secondary Causes

When osteodystrophy occurs as a result of CKD, it is said to be the result of secondary hyperparathyroidism leading to hyperphosphatemia and hypocalcemia.

However, if osteodystrophy occurs as a result of the parathyroid glands (with no kidney involvement), it said to be the result of primary hyperparathyroidism.

Primary hyperparathyroidism is most often caused by a noncancerous growth on the gland (called an adenoma) or the abnormal enlargement of two or more of the four parathyroid glands (referred to as parathyroid hyperplasia).

Regardless of whether osteodystrophy is caused by primary or secondary hyperparathyroidism, the outcomes remain more or less the same.

Risk Factors

Renal osteodystrophy is the result of CKD and the onset of acute kidney failure. In the end, if your kidneys start to fail, you are at risk of osteodystrophy.

With that said, there are certain predisposing factors that can increase your risk of osteodystrophy, including the following.

• Congenital kidney diseases: Examples include polycystic kidney disease (PKD), Alport syndrome, Goodpasture syndrome, and congenital hypoplasia.
• Glomerular diseases: A group of diseases that directly damage the filters of the kidneys, called glomeruli.
• Tubulointerstitial nephritis: The inflammation and injury of the renal tubules of the kidney that are responsible for reabsorbing calcium.
• Renal arteriosclerosis: The scarring of the kidneys commonly associated with chronic hypertension and atherosclerosis.
• Urinary tract obstruction: Possible causes include chronic prostate disease and recurrent renal calculus (kidney stones).

Diagnosis

Renal osteodystrophy is most often diagnosed when a person is already being treated for end-stage renal disease, although the condition can develop well before then.

If osteodystrophy is suspected, it can be diagnosed with a combination of a physical examination, blood tests, imaging studies, and a bone biopsy. Even so, osteodystrophy can be difficult to diagnose in the early stages, especially in children, and may require an experienced nephrologist to interpret findings.

Physical Examination

Osteodystrophy is often recognized in adults when a fracture occurs with advancing CKD. A history of bone and joint pain are also common complaints. Upon examination, there may be a significant restriction in the range of motion of weight-bearing joints, including the hip, knee, or ankle.

The findings can differ significantly in children. Because bone fractures are not a characteristic feature, healthcare providers will look for other common manifestations associated with impaired growth and skeletal deformities, including:

• The squaring of the skull and the flattening of the back of the skull, especially in babies and younger children
• The deformity of weight-bearing bones, including the bowing of the legs
• Scoliosis, the abnormal curvature of the spine, especially in older children

Children with CKD are commonly monitored for growth due to the risk of osteodystrophy. Those that fall below the 30th percentile for their age (meaning that 70% of children will be taller than them) are considered to be of short stature and at increased likelihood of osteodystrophy even if no other abnormalities are found.

Blood Tests

As part of an initial work-up, the healthcare provider will order a blood test called a comprehensive metabolic panel, which evaluates your blood chemistry, including calcium levels. If osteodystrophy is suspected, additional blood tests will be ordered to measure phosphorus, PTH, and calcitriol levels.

The stage of osteodystrophy can often be suggested by the results of these blood tests.

In early-stage disease, there will typically be an elevation of PTH and FGF-23 levels but otherwise normal calcium and phosphorus levels. With the onset of symptomatic disease, calcium and calcitriol levels will plummet as PTH and phosphorus levels rise.

Imaging Studies

Standard X-rays or computed tomography (CT) scans are typically used in the diagnosis of osteodystrophy. They can detect characteristic features of the disease, including calcification, osteomalacia, and areas of abnormal bone resorption.

Some of the common signs of osteodystrophy on X-ray or CT scan include:

• Thinning of the cortical (outer dense) and trabecular (inner porous) bone
• "Salt and pepper skull" (caused by patches of thinning bone on the skull)
• "Rugby jersey spine" (caused by alternating bands of abnormal dense and abnormally porous bones in the spine)
• Insufficiency fractures (a type of stress fracture caused by weakened bones)
• Joint erosion, especially the larger joints
• Joint cartilage calcification, which appears on X-ray as crystal-like deposits, particularly in the hip and knee
• Soft-tissue calcification, including calcium deposits in muscles, tendons, ligaments, and vertebral discs

Magnetic resonance imaging (MRI), while useful, may not provide any additional information compared to an X-ray or CT scan. Similarly, bone scans (bone scintigraphy) have limited used in early-stage disease and only offer significant insights when osteodystrophy is severe and advanced.

Bone Biopsy

A bone biopsy remains the gold standard tool for the diagnosis of osteodystrophy. By obtaining a sample of bone, medical pathologists can examine the cells under the microscope to look for characteristic abnormalities in their structure, porosity, or thickness.

Stains are important to the process. People with advanced CKD often have excessive amounts of aluminum and iron in their bodies. With osteodystrophy, these minerals will be found in high concentrations in bone and confirmed with special reactive stains.

Another test, called double tetracycline labeling, can detect abnormalities in bone turnover. It involves the consumption of oral tetracycline, an antibiotic. This binds to the newly formed bone. Then, 14 days later, a second dose of tetracycline is given, which will also bind to the bone. Next, the bone is examined, and the distance between the lines formed by the two doses is measured. If the distance is less than expected, it indicates either too little bone formation or too much bone resorption. Based on microscopic examination of the sample, a pathologist can calculate the rate of turnover and determine which type of osteodystrophy is involved.

A bone biopsy can either be performed with a needle biopsy performed in an office or an open biopsy performed in an operating room.

Differential Diagnoses

Because osteodystrophy can be tricky to diagnose, particularly in the early stages, healthcare providers will explore alternate explanations for the symptoms as part of the differential diagnosis. The exclusion of these conditions can help support the diagnosis.

The differential diagnosis of renal osteodystrophy varies depending on the sites of involvement. The conditions commonly explored include:

• Autoimmune disorders like rheumatoid arthritis, lupus, and Crohn's disease
• Ankylosing spondylitis
• Congenital disorders like Prader-Willi syndrome and Seckel syndrome in children
• Cushing syndrome
• Multiple myeloma
• Osteoporosis (including juvenile osteoporosis)

Treatment

Osteodystrophy is treated with a combination of medications, nutritional supplements, diet, and exercise. Given that renal osteodystrophy most often occurs in people with kidney failure, hemodialysis is typically involved.

Lifestyle

Renal osteodystrophy requires a lifestyle change to prevent further bone loss and damage. This includes the restriction of dietary phosphorus, especially inorganic phosphates found in food additives.

Phosphorus-rich foods to limit include:

• Bacon
• Beer
• Cheese
• Cola
• Cocoa and chocolate
• Custard and ice cream
• Organ meats
• Oysters
• Sardines
• Sausage

Routine exercise is also important, since it can improve your bone strength and range of motion. This typically involves low-impact resistance training and walking. By exercising outdoors, you are also getting sun exposure, which helps promote vitamin D synthesis in the body.

Over-the-Counter Therapies

Calcium and vitamin D supplements are also sometimes prescribed in people with hyperparathyroidism. Vitamin D is especially useful in those with primary hyperparathyroidism and is generally prescribed at a daily dose of 2,800 international units (IU).

Your healthcare provider may also recommend over-the-counter phosphate binders. These work by binding to phosphorus in the bloodstream and increasing its excretion from the body. Most are calcium-based medications like PhosLo (calcium acetate) and Tums (calcium carbonate) that are taken with meals and snacks.

Prescriptions

The drug Sensipar (cinacalcet hydrochloride) has been approved for the treatment of secondary hyperparathyroidism by the U.S. Food and Drug Administration. The drug works by imitating calcium, and, by doing so, lowers PTH levels in the blood. Taken twice daily by mouth, Sensipar can cause nausea, diarrhea, and vomiting in some people.

Rocaltrol (calcitriol) and One-Alpha (alfacalcidol) are prescription forms of vitamin D that help lower PTH levels when the kidneys are unable to produce ample quantities of calcitriol on their own. The drugs may be taken anywhere from once-daily to thrice-weekly and are not known to cause notable side effects.

There is also an injectable form of calcitriol called Calcijex.

Surgeries

If Sensipar and calcitriol supplementation are unable to slow the progression of osteodystrophy, healthcare providers may recommend a surgical procedure known as parathyroidectomy. The procedure, which removes the parathyroid glands, is generally reserved for people with refractory (treatment-resistant) end-stage renal disease.

Depending on the person's age and general health, a parathyroidectomy may be performed as either inpatient or outpatient surgery. Parathyroidectomies are minimally invasive, requiring a 2.5-centimeter (roughly 1-inch) incision. Recovery generally takes between one and two weeks.

A kidney transplant is also an option if other treatments fail. Candidates for a transplant are generally those who have not responded to other medical or surgical treatments, are either on dialysis or require dialysis in the near future, and are able to tolerate major surgery.

A Word From Verywell

Osteodystrophy can be a difficult disease to diagnose and a complex one to treat. It requires patience on your part to ensure the correct diagnosis and the appropriate treatment.

Given that osteodystrophy is a relatively strong indicator of CKD progression, it is important to take steps to prevent further loss of kidney function. This includes being adherent to your diet regimen, exercising appropriately, and taking your medications as prescribed.

If you suspect your child has osteodystrophy, ask your healthcare provider to investigate. Given that severe growth impairment in children with CKD is linked to an increased risk of death, it is best to err on the side of caution and seek a second opinion if needed.