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Hypercalcemia Bone Pain


What Is It? Hypercalcemia is an increase in the blood levels of calcium due to excess calcium being leeched from the bones, causing bone pain.  Hypercalcemia is not a disease, but is a laboratory finding that has many causes including hyperactivity of the parathyroid gland (hyperparathyroidism), cancer (especially lung and breast or metastatic), tuberculosis, sarcoidosis, immobility due to disease or condition, medications such as lithium, and hereditary factors (rare).  Other causes of hypercalcemia (but rarely cause bone pain) include excessive calcium dietary intake, excessive vitamin D supplements, and dehydration.  Of all these causes, more than 90% are due to primary hyperparathyroidism and malignancy. Hypercalcemia may be transient (19%) or sustained (81%).  Approximately 3 times as many cases are due to malignancy compared to primary hyperparathyroidism.

Incidence: 0.6% of the population overall

Location: Long bones, global bone pain

Anatomy: -Malignancy causes hypercalcemia usually through metastatic disease (tumors growing in the bone far removed from the primary cancer source).  The metastatic disease causes a dysruption in the normal turnover process of the bone being made and remodeled.  This causes lytic (punched out appearance on x-ray) lesions, sclerotic appearance (hardening of the bone), and progressive growthleading to microfractures, and stretching of the periosteum causing pain in the bones.

-Primary hyperparathyroidism refers to an overactivity of the parathyroid glands (usually 4-6) lying in the neck, adjacent to the thyroid gland.  The parathyroid glands function is to monitor and adjust calcium levels in the blood within a narrow range.  They do this by varying the amount of parathyroid hormone they produce.  A low calcium level causes an increase in parathyroid hormone (a small protein) production that causes bones to release their calcium into the bloodstream to provide a constant level of calcium for the brain, nervous system, and muscles to work properly.  The parathyroids also stimulate the gut to absorb more calcium in cases where blood calcium levels are low.  Primary hyperparathyroidism is a disconnect in this feedback mechanism between the calcium levels in the blood and the parathyroid hormone output- ie. the parathyroid glands continue to make more parathyroid hormone in spite of the calcium levels being too high. Virtually 100% of the time, this is due to a tumor (usually not malignant) of the parathyroid glands.  Bone pain may result from too much calcium being removed from the bones causing osteopenia, osteoporosis, and fractures.  

-Sarcoidosis may have bone pain that occurs due to cystic lesions, punched out lesions, osteolysis, or defects in the cortex with granulomas in the medullary cavity (center of the long bones) in severe cases of sarcoidosis.  These lesions are seen mainly in the bones of the hands and feet but may be also found in the skull, nasal bones, and vertebrae.  Most of these lesions do not cause pain, but uncommonly sarcoidosis will manifest as bone pain.

-Tuberculosis of the bones may lead to bone pain, especially in the spine (Pott's Disease) and in the joints when TB invades these structures. TB can cause joint pain also or may cause osteomyelitis, a painful infection of the bone.

Onset: Gradual in most

Character: Severe aching deep in the bones

Intensity: Severe

Worsens: Nighttime (malignancy)

Relieved by: NSAIDS, treatment of the cause

Causes: see above

Diagnosis: Serum calcium levels above 10.2 are abnormal and deserve investigation; x-rays and history are important

Outcome: Depends on the cause

Associated with: Kidney stones (too much calcium in the blood can cause kidney stones), kidney failure (severe hypercalcemia can damage the kidneys), confusion, coma, heart arrhythmias, osteoporosis

Treatment: For primary hyperparathyroidism, surgical excision of the parathyroid glands is necessary.  For metastatic disease, NSAIDs and possible radiation treatment or cryo/radiofrequency may be useful.  

Differential Diagnosis: Excess oral calcium or vitamin D (these usually do not cause bone pain)

Complications: Bone fractures, other symptoms of hypercalcemia (excessive thirst, frequent urination, GI upset and nausea, vomiting and constipation, bone pain, confusion, lethargy, fatigue, kidney stones, kidney failure, gastric ulcer, arrhythmias)